Combo with "Development of the genital system" and 22 others

diagnosis of adenocarcinoma rule of 2's and cell types

"2" many; 2 crowded; 2 small; 2 simple; 2 *large nucleoli* the cell that duplicates is the *luminal cell*, not the basal cell - *NO BASAL CELLS IN THE CANCER GLANDS, JUST LUMINAL CELLS*

prostate nodular hyperplasia (BPH) treatment

"Watch and see" Medical (alpha blockers, DHT inhibitor-*finasteride*) - alpha blocker to relax the SM and open urethra TURP: take out pieces of prostate with a catheter Surgery

placenta previa

"low lying placenta" *Painless* 3rd trimester bleeding Association with placenta accreta

pregnancy and thrombosis

*Coagulation factors and venous thromboembolic disease increase*

genetic changes in breast cancer

- Overexpression of the HER2/NEU proto-oncogene - undergoes amplification in 30% of invasive breast cancers, member of epidermal growth factor receptor family, associated with poor prognosis - Amplification of RAS and MYC genes - Mutations in tumor suppressor genes RB and TP53

breast cancer stats

1 in 8 women 20% mortality

Lymphogranuloma Venereum (LGV): strain of chlymedia

1 vesicle or ulcer -> 2ry regional adenopathy, fever -> 3ry suppurative adenitis (*abscess*) -> *bubo* -> fibrosis *groove sign: inguinal ligament transecting the abscess* diagnosis: Aspirate for culture treat: doxycycline x 21 days *is a strain of chlymedia*

Undescended testis (Cryptorchidism)

1% of 1 year old boys Failure of the intraabdominal testis to descend into the scrotal sac *Despite control by hormonal factors - not due to hormonal disorders* Unilateral in 75% of cases *Risk of trauma, infertility and 5-10 x increase in risk of tumor development* = have to remove

edometriosis pathogenesis theories

1. Regurgitation theory -retrograde menstruation through the fallopian tubes 2. Metaplastic theory - mesothelium could give rise to the endometrium 3. Vascular or lymphatic dissemination theory - would explain the presence of endometriosis in the lymph nodes and lungs 4. Implantation at the time of surgery

role of the placenta

1. serves as a maternal-fetal barrier 2. transports nutrients & waste products 3. provides protective immunity 4. is a major endocrine organ 5. initiates parturition (birth)

fertiliztion is usually ____ of the way down the tube

1/3rd

what percentage of ovarian cancer is metastatic?

15% mostly coming from breat, GI, endometrium

how many new STD's a year

19 million in US but many many more that go unreported

follicular phase of menstrual cycle

1st part of cycle (day 0-14) aka proliferative phase (the endometrium is growing) FSH tells follicle to make estrogen and to mature this also causes proliferation of the endometrium

PCO Diagnostic Criteria

2003 Rotterdam criteria 2/3 of the following: - Oligo- or anovulation - Clinical or biochemical signs of hyperandrogenism - Polycystic ovaries (≥12 follicles 2-9mm) EXCLUSION OF OTHER CAUSES

MORPHOLOGY OF NONPROLIFERATIVE FIBROCYSTIC CHANGES IN BREAST

3 patterns: - cysts: filled with protein fluid - fibrosis - cyst ruptures, inflammatory reactin in stroma makes it become fibrotic - adenosis: just an increase in the number of lobules

breast cancer morphology

4% bilateral or multifocal 50% in upper oter quadrant (UOQ) non-invasive 15-30% *invasive 70-85% (mostly ductal)* can be inflammatory carcinoma

length of pregnancy

40 weeks (+/- 2w) Expected date of confinement (EDC)-280 days from the beginning of last menstrual period, 266 from the ovulation three trimesters

enzyme responsible for converting testosteron to DHT

5 alpha reductase

what % of population is exposed to HPV? what about high risk HPV?

75% to HPV 50% to high risk HPV Persistent HPV and High grade dysplasia: 10% Invasive carcinoma: 1.3%

time it takes from 1ry to 2ry follicle

>120 days

syndromes

A series of congenital malformations in different structures that results from an underlying defect in a single molecular gene or process

ovarian carcinoma pap smear & histo

A.Psammoma bodies B.Cells shed into fallopian tube to uterus to cervix can appear in Pap smear

deformation

Abnormal form, shape or position of part of the body caused by mechanical forces—usually intrauterine constraint

neuroblastoma bad prognotic factors

Age (> 1 year) Stage (II-IV) *N-myc amplification* *bcl-2 expression* Diploid

personal breast cancer risk factors

Age > 55 Prior Breast Cancer Early menstruation < age 12 Age of first term pregnancy ( > age 30) No pregnancies - nulliparity Age of menopause (later is worse) Dense Breast Tissue Obesity Alcohol intake Family history of breast cancer

Eugonadotrpic amenorrhea due to Receptor Abnormalities and Enzyme Deficiencies

Androgen insensitivity syndrome—absent androgen receptors—male genotype, Female Phenotype—High Testosterone levels Reifenstein's syndrome 5a-reductase deficiency 17-b-OH-steroid dehydrogenase deficiency Genetic mutations in the genes for the androgen receptor or in the genes for enzymes active in androgen biosynthesis

sex-chord stromal tumors

Benign Thecoma Fibroma Malignant Granulosa cell tumor Sertoli and Leydig cell tumors

benign epithelial lesions of the breast

Benign alterations of ducts and lobules Nonproliferative fibrocystic changes (no cancer risk) Proliferative fibrocystic changes (intermediate cancer risk) Atypical hyperplasia (more cancer risk than the others)

Fibroma

Benign, solid, well circumscribed *Perimenopausal women* Can be mixed with theca cells (fibrothecoma) and produce estrogen *Often associated with ascites*

example of insulin sensitizers

Biguanides and Thiazolidinediones

Basal cell nevus syndrome

Bilateral fibrothecomas, basal cell carcinoma, odontogenic cysts of jaw

POP: Side Effects

Bleeding irregularities - Estrogen, NSAIDs to control Amenorrhea Other side effects similar to COC, but less common

Signs and Symptoms of Ovarian tumors

Bloating, Increased abdominal girth, Pelvic or abdominal pain, Urinary symptoms, Early satiety Malignant tumors may present with anorexia and significant weight loss Symptoms in general are mild Most malignant tumors are diagnosed at stage III or above leading to a disproportionately high mortality rate for ovarian cancer

COC's side effects

Breakthrough bleeding (have to increase estrogen) Nausea (E) Breast tenderness (E/P) Headaches (E/P) Hypertension Weight gain

POC: Contraindications

Breast cancer Cirrhosis/ liver tumors/ active liver disease Unexplained vaginal bleeding Diabetic nephropathy* Active thrombotic disorder Ischemic heart disease* Stroke* * - applies to the longer acting methods

chlymidia

C. trachomatis is most common bacterial STI in U.S.

conditions for exclusion of PCOS

CAH (congenital adrenal hyperplasia), androgen-secreting tumors, Exogenous Androgens, Cushing's syndrome, thyroid disease, primary ovarian insufficiency, prolactin disorders, Acromegaly

stains to recognize that it is Ewing sarcoma?

CD99 stain FLI 1 stain however, Ewing sarcoma must me diagnosed molecularly (genetics)

tripe test for breast cancer

CLINICAL RADIOLOGIC PATHOLOGIC

carcinoma of the penis

Carcinoma in situ: *Bowen's disease*, erythroplasia of Queyrat, Bowenoid papulosis thought to be associated with HPV is a squamous carcinoma Spread (inguinal nodes)

hydrops placenta pathophysiology

Cardiac failure Tissue hypoxia in the fetus and placenta Edema in the fetus and placenta

congenital malformations associated with diabetes (pre-gestational) during pregnancy

Caudal agenesis syndrome - "Mermaid syndrome" Congenital heart disease Neural tube defects

acute Prostatitis

Cause: UTI bacteria (E. Coli / Gram Neg) Neutrophils (occ microabscesses) Symptoms: dysuria, urinary frequency, *lower back pain* Diagnosis: fractionated urine - micro + culture Treatment: Antibiotics

chronic prostatis

Cause: bacterial (gram Neg) (chlamydia/ ureaplasma)and abacterial/prostatodynia Clinical: asymptomatic, no pain Treatment: antibiotics - longer duration , alpha-adrenergic blockers, NSAIDs

Diabetic Embryopathy

Causes unknown but presumably due to intermittent hyperglycemia in fetus Fetuses usually large (macrosomia) Intestinal malformations, cystic kidneys Cardiac: TGA, VSD, TOF, ASD, PDA, cardiomyopathies skeletal and CNS defects

lymph node involvement of each cancer (cervix, vaginal, vulva)

Cervical Carcinoma: Pelvic Lymph Nodes Vulvar Carcinoma: Inguinal Lymph Nodes Vaginal Carcinoma: Upper half: Pelvic Lymph Nodes Lower half: Inguinal Lymph Nodes

unintended pregnancies

Chance of pregnancy in one year of unprotected sex: 85% 3 million unintended pregnancies each year in the US - 47% of these end in abortion

causes of chronic anovulation with a normal functioning ovary

Chronic anovulation due to increased androgens - Cushing's syndrome - Congenital adrenal hyperplasia - Polycystic ovarian syndrome

chronic salpingitis

Chronic inflammation, fibrosis and fusion of plicae if fellopian tubes, scarring leading to: Tubo-ovarian adhesions Tubo-ovarian abscess Pyosalpinx Hydrosalpinx Ectopic Pregnancy Infertility

clear cell histology

Clear Cell : Secretory type glands with cytoplasmic clearing looks like endometrial epithelium in secretory phase glands filled with glycogen - washed out during preparation -> clear cell

Combined Hormonal Contraception methods

Combined Oral Contraceptive (COC) Transdermal (Ortho-Evra®) patch Vaginal ring (Nuvaring®) Differences: - compliance, ease of use, preference

Mucinous Cystadenocarcinoma

Complicated epithelial architecture: *cribriform/solid patterns*, Nuclear atypia, Stromal Invasion Differential diagnosis for mucinous ovarian tumors *should always include metastatic mucinous tumors from gastrointestinal tract*. Appendix and colon are the most common primary sites for metastatic mucinous tumor in ovary.

Neonatal morbidity due to diabetes during pregnancy

Complications of prematurity Complications of Intrauterine growth restriction (IUGR) Erythrocytosis Hyperbilirubinemia Cardiomyopathy Hypoglycemia and other metabolic abnormalities Respiratory problems Congenital anomalies and their management

Causes of Amenorrhea Outflow tract level

Congenital obstruction Mullerian agenesis Recurrent endometrial infections Intra uterine Adhesions (Asherman's)

major actions of progesterone

Controls: *Breast development, endometrial gland maturation, maintaining uterus during pregnancy, inhibits lactation during pregnancy* Contributes to insulin resistance Increases: Body temperature, minute ventilation

non-neoplastic cysts of the ovary

Corpus Luteum Follicular Cysts Theca Lutein Cysts Surface inclusion Cysts Endometriosis

Management of patient at increased risk of preterm delivery <34 weeks

Corticosteroid administration (dexamethasone or betamethasone) to reduce the risk of and severity of Respiratory distress syndrome Also reduces risk of intraventricular hemmorrage prior to 32 weeks Tocolysis: goal of therapy to delay delivery for 48 hours

Criteria for PE

Criteria - Ejaculation occurs with minimal stimulation - Ejaculation occurs before the man wishes - The condition causes distress to the man or his partner Additional qualifications - Lifelong vs acquired - Generalized vs situational

managements for dysplasia

Cryosurgery: LSIL Cone biopsy: HSIL - includes the transormation zone if positive margins on cone: Repeat cone biopsy/follow up with paps Hysterectomy

other causes of androgen excess other than PCOS

Cushings (DST or 24 hr urine) Congenital adrenal hyperplasia Hyperprolactinemia (Prolactin) Acromegaly (IGF-1) Drugs (dilantin,steroids,progestins,diazoxide) Ovarian or adrenal tumors

side benefits of the contraceptives

Cycle control: shorter, more regular menses 60-90% reduction in dysmenorrhea Menorrhagia: 38-50% reduction in blood loss , improvement in anemia Endometriosis suppression Prevention of functional ovarian cysts

malignant Ovarian Surface Epithelial Tumors

Cystic with large solid areas Age group: 50s and older, most patients are 65 or older

Borderline Ovarian Surface Epithelial Tumors (Tumors of Low Malignant Potential)

Cystic with small solid areas Age group: 40s and 50s

Rh antigens

D-antigen - "Rh positive" or "Rh negative" Other Rh antigens: C,c,E,e Anti-D, anti-c and anti-E are considered to be high risk antibodies Other common of "minor" red cell antigens causing hemolytic anemia: Kell (K) Rhogam only protects against developing Abs to D

what leads to vaginal adenocarcinoma

DES used to be used to prevent abortion, no longer used caused adenosis in 1/3rd of the women, adenocarcinoma in 0.1%

maturation phase of spermiogenesis

DNA condenses mitochondria start moving into the mid piece alot of the cytoplasm in shed into a *residual body* = sertoli cell chews that up

Hypothalamic Amenorrhea

Decreased hypothalamic gonadotropin-releasing hormone (GnRH) secretion Decreased pulses of gonadotropins, absent midcycle surges in luteinizing hormone (LH) secretion, absence of normal follicular development, anovulation, and low serum estradiol concentrations . Hypogonadotropic hypogonadism

Hormonal Changes with Age - Males

Decreased levels of total and free testosterone *Increased levels of SHBG* *Increased FSH and LH*

MHT benefits

Decreases in: - Flushes - Vaginal atrophy - Sexual dysfunction - Insulin resistance - Cataracts - Colon cancer - Hip fracture - Other fracture - Skin wrinkling

Why is placenta previa more frequently associated with placenta accreta ?

Deficiency of decidua in that part of the uterus

Endometriosis

Definition: Presence of endometrial glands and stroma outside of uterine corpus; benign 30's-40's - *Infertility, dysmenorrhea, pelvic pain* most common sites: ovaries, ligaments, fallopian tubes, rectovaginal septum, wall of rectum, even *lymph nodes* problems bc they break down like regular EM -> inflammation

Evaluation of the Infertile Couple

Detailed history Initial testing Diagnose likely cause Logical approach to treatment Sensitivity

Diabetes in pregnancy : gestational diabetes

Diabetes with onset/first recognition during pregnancy Screening tests between 24-28 weeks A1: euglycemic with diet & nutrition A2: euglycemic with insulin & oral medication cause by HPL

Chlamydia: Diagnosis & Rx

Diagnosis: NAAT Treatment: - Azithromycin 1gm X 1 (94.4% effective) - Doxycycline (7d) (97.5% effective) (compliance problem) Repeat screening in 6 months for Chlamydia and GC

adenocarcinoma of the prostate

Diagnosis: by biopsy, MRI arise in the periphery of the gland (unlike BPH) macro: difficult to see, firmer area usually, but prostate is a firm organ micro: simple glands, crowded

treatment for amenorrhead due to hyperprolactenemia:

Dopamine agonist Bromocriptine Cabergoline

diseases with decreased AFP

Down Syndrome Trisomy 18 Turner Syndrome Intrauterine death

what part of the HPV virus function as oncoproteins?

E6 and E7 E7 binds to retinoblastoma (Rb) gene E6 binds to P53

what is continually expressed when there is dysplasia?

EGFR

what to think about when thinking about infertility

Egg Sperm Fallopian Tubes Uterus Cervix Vagina Timing

EC: Ulipristal Acetate

Ella®, 30 mg - Within 120 hours (5 days) - Selective Progestin Receptor Modulator (SPRM) - Partial agonistic as well as antagonistic effects on the progesterone receptor - Need a Rx

Kisspeptin

Encoded by KISS 1 *Gatekeeper of puberty* Modulating GnRH sectretion

criteria for diagnosis of hypertensive pregnancy disorders: end-organ damage

End-organ damage (often associated with severe disease) - Platelet count <100,000/ul - Serum creatinine >1.1 mg/dL or doubling of serum creatinine in the absence of other renal disease - Liver transaminases at least twice the normal - Pulmonary edema - Symptoms: headache, visual changes, epigastric pain Oliguria - Fetal growth restriction, oligohydramnios

physiology of pregnancy

Endocrine-Thyroid demands, increase in diabetes Cardiac -CO 30-50% Renal (Creatinine clearance increases by 50%) Pulmonary tidal volume (30-50%) Estrogen is a profound vasodilator Physiologic anemia *Coagulation factors and venous thromboembolic disease increase*

PCOS: MORBIDITY

Endometrial hyperplasia, Endometrial cancer Infertility Obesity/metabolic syndrome, Increase in nonalcoholic fatty liver Increased risk of cardiovascular disease Increased risk of diabetes (2-5X)

choriocarcinoma

Epithelial malignancy Rapidly invasive, widely metastatic preceded by: Hydatidiform mole in 50%, Previous abortion in 25%, Normal pregnancy in 22% Ectopic pregnancy and gonadal/extragonadal teratomas

Hypogonadism - Background

Estimated to affect almost half of middle aged American males 40% of 40 year olds Not always seen or treated - estimated that less than 10% of patients seek eval

Nexplanon as compared to DMPA

Estradiol levels do not decrease as seen w/DMPA Insert: Days 1-5 of menses Typical Use = Perfect Use (efficacy = effectiveness)

the efferent tubules connect to the excretory ducts:

Excretory Ducts - Epididymis: by the time sperm reaches tail of epididymus they can now fertilize an egg; takes 14 days to get through; *lined by pseudostratified columnar epithelium with stereocilia* sperm stored after the epi.. if there is a "call to action" sperm passes to: - Vas Defrens: same epithelium, *3 layer of SM under sympathetic innervation* to propel the sperm - Penile Urethra

cytologic methods

Exfoliative Cytology: examination of cells that are spontaneously shed into body fluids or secretions, i.e. sputum, urine, effusions, cerebrospinal fluid, lavage specimens. Abrasive Cytology: mechanical dislodgement of cells from body surfaces, i.e. endoscopic brushings of gastrointestinal tract, scrapings of oral lesions. Aspiration Cytology: Thin needle (22-27 gauge) is used to obtain cells. Palpable lesions of breast, thyroid, skin, lymph nodes, salivary gland or deep organs such as pancreas, liver, kidneys, adrenal gland through the use of radiologic guidance.

AMH

Expressed in the *granulosa cells of the recruited primordial follicles* Proposed to be a good indirect marker of ovarian reserve

risk factors for breast cancer

FAMILY HISTORY H/O PROLIFERATIVE BREAST DISEASE (1.5-2X) (5X FOR ATYPICAL DUCTAL HYPERPLASIA) GEOGRAPHIC INFLUENCE: US AND NORTHERN EUROPE LENGTH OF REPRODUCTIVE LIFE: INCREASES WITH EARLY MENARCHE AND LATE MENOPAUSE PARITY: MORE FREQUENT IN NULLIPAROUS AGE AT FIRST CHILD: RISK INCREASED IN WOMEN OLDER THAN 30 POSTMENOPAUSAL HORMONE REPLACEMENT THERAPY WITH COMBINED ESTROGEN AND PROGESTIN HORMONE THERAPY IS ASSOCIATED WITH INCREASED RISK

birth defects due to advanced paternal age

FGFR mutations that are autosomal dominant: e.g: achondroplasia (70% dwarfism) Apert's syndrome also been linked to: autism spectrum disorders, schizophrenia

key gene for POI

FMR-1

what is commonly done for breast massess?

FNA

if lump is found: histologic diagnosis types

FNA biopsy core needle biopsy surgical excision biopsy

what are the limitations of FNA in terms of breast cancer

FNA cannot distinguish invasive from in situ carcinoma

what happens once no ore eggs available in ovaries

FSH and LH will remain elevated will remain elevated unless exogenous estrogen is supplied

causes of post partum bleeding

Failed placental separation (placenta accreta) Retained placental tissue Uterine rupture or tear Atonic uterus Uterine pathology

Causes of Amenorrhea Hypothalamic Level

Failure to attain/maintain critical levels of body fat Severe stress Severe systemic illness Syndrome of anosmia and GnRH deficiency

chosen pattern in development

Female

important factors when taking history (male)

Fertility in other relationships Alcohol, marijuana use, cigarette smoking *Environmental exposure (heat [eg, saunas, hot tubs], chemical, radiation exposures)*

endocrinology of pregnancy: compartments

Fetal Maternal Placental These "compartments" work together as a unit

future of prenatal testing

Fetal DNA (cfDNA) in maternal blood permits noninvasive prenatal diagnostic testing for mutations, deletions, Y chromosome, and trisomies!! Determination of Sex and Trisomies with nearly 100% accuracy by 10-14 weeks and few false positives for now its expensive

treatment for sex-chord tumors

Fibroma, Thecoma: Removal of the tumor Granulosa/Sertoli Cell Tumor: Unilateral salpingo-oophorectomy if confined to the ovary, plus chemotherapy if beyond ovary.

what happens after the LH surge (mature corpus luteum)

First meiotic division/ovulation Basement membran dissolution thecal cells invade, proliferate and contract --> vascularize hypertrophy of granulosa cells -> alot of progesteron internal part makes a fibrin clot

FSH stands for

Follicle stimulating hormone

non-structural cause of amenorrhea (non-ovulation) leading to infertility

Follicle-stimulating hormone (FSH) elevation >40 μg/L indicates premature ovarian insufficiency Decreases ovarian reserve

breast cancer in the US

For women in the U.S., BC death rates are higher than those for any other cancer, besides lung cancer.

meaning of G and P in wome

G - times pregnant P - times she gave birth

Prevention and Counseling

GC & chlamydia screening yearly for high risk women High risk males: HIV, syphilis, chlamydia, GC testing at least yearly

other major hormone related to puberty other than FSH and LH

GH Pulsatile release More than 70% of total daily *GH secretion occurs at night* Specifically during the first few hours of sleep-slow wave sleep *Peak levels can be 100X low levels*

what is the best indicator of prognosis for prostate cancer

GRADE not stage

Genetics in Hypothalamic Amenorrhea

Genetic mutations identified in 7 /55 patients with hypothalamic amenorrhea KAL1, FGFR1 (KAL2 gene), FGF8, Prokineticin 2 (PROK2) and prokineticin receptor 2 (PROKR2) mutations (KAL3 and KAL4), Kisspeptin 1 receptor, GnRH receptor mutations, GnRH1 mutations, Tachykinin 3 (TAC3) and tachykinin 3 receptor (TAC3R) mutations.

Hereditary Non-Polyposis Colon Cancer Syndrome/HNPCC/Lynch syndrome`

Germ line mutations of mismatch repair genes MLH-1, MSH-2 and less commonly of PMS1, PMS2 and MSH6 Increased risk of colon, uterine and ovarian, breast , liver pancreas and other cancers Usually Low grade and low stage tumors

Hypertensive disorders of pregnancy

Gestational HTN Preeclampsia Eclampsia

progesterone withdrawal test

Give someone progesterone and then withdraw it bc: - Estrogen alone increases the endometrium - Estrogen + Progesterone, withdrawal results in bleed - Tests Estrogen status and Outflow tract

examples of hormones that the placenta secretes

GnRH, TRH, CRH, Placental lactogen, HCG, chorionic thyrotropin, TSH, ACTH notice hCG curve

types of precocious puberty

Gonadotropin-dependent-- central or true precocious puberty is caused by early maturation of the hypothalamic-pituitary-gonadal axis. (isosexual). Gonadotropin-independent precocious puberty is independent of GnRH and gonadotropin is caused by excess secretion of sex hormones (estrogens or androgens) derived either from the gonads or adrenal glands. (isosexual) or (contrasexual). happens 5 x more in girls than boys

grading and ovarian tumor

Grades I/II/III (well/moderately/poorly differentiated) Higher the grade, more aggressive is the tumor Serous carcinoma is graded only as low and high grade

what do you always do when you get someone with an STD

HIV test treat partner

the bad thing about HPL

HPL is thought to contribute to the increase in maternal insulin resistance that occurs as pregnancy progresses

the MOST common STD

HPV worldwide

Evaluation of Tubal Patency

HSG Laparoscopy

Vaccines, Pre-exposure Prophylaxis, and Treatment

Hepatitis B Hepatitis B Meningococcal vaccinations HIV: Post exposure prophylaxis PREP can decrease infection

Emerging Issues: Hepatitis C

Hepatitis C: sexually transmitted - Especially among MSM with HIV infection Annual Screening

risks of testosterone therapy

Hepatotoxicity (prolonged use of high doses of oral androgens, eg, methyltestosterone) INFERTILITY!! Edema in patients with preexisting cardiac, renal, or hepatic disease: *bryproduct of the polycythemia* Gynecomastia Sleep apnea CVD?

physical findings for PCOS

Hirsuitism Acne Acanthosis nigricans (some) Increased waist-hip ratio Thinning scalp hair

Erectile Dysfunction (ED) - Diagnostic Workup

History and Physical Exam Laboratory Workup - Testosterone Free and Total, FSH, LH, prolactin, DHEA, Estradiol - checked in AM Imaging - Penile doppler ultrasound (blood vessels)

PCOS treatment: drugs

Hormonal contraceptives Insulin sensitizers (Biguanides and Thiazolidinediones) Androgen receptor blockers Ovulation induction (If fertility is desired) Hair removal

Non- Estrogen Options

Hot flushes- Paroxetine 7.5mg-Brisdelle Osteopenia, Osteoperosis- Bisphosphonates, Tamoxifen, Roloxifen Vulvovaginal atrophy- Ospemifene(Osphena), vaginal moisurizers, coconut oil, Laser

gestational trophoblastic diseases

Hydatidiform mole - Complete - Partial Invasive mole Choriocarcinoma Placental site trophoblastic tumor

Primary Amenorrhea Classification

Hypergonadotropic hypogonadism---FSH > 20 IU/L, Primary gonadal insufficiency Hypogonadotropic hypogonadism---FSH <5 IU/L, Primary hypothalamic-pituitary dysfunction Eugonadotrpic---FSH 5-20 IU/L, Normal HPO axis, Anatomic, Ovulatory dysfunction

invasive ductal carcinoma (IDC) of the breast

INCLUDES 70-80% OF CARCINOMAS IRREGULAR, SPICULATE MASSES STONY HARD ON CUT SECTION, GRITTY

Human Papillomavirus: The Most Common STD

Immune system clears 90% most HPV w/in 2 yrs Associated with anogenital malignancies in MSM and head/neck cancer in men Routine vaccination of females and males Anal PAP smears for HIV+ patients at risk

pathogenesis of preeclampsia

Impaired trophoblast differentiation and invasion Abnormal remodeling of the spiral arterioles Increased sensitivity to angiotensin II Exposure to paternal/fetal antigens appears to be protective genetic factors: family history ups risk Hypoperfusion, hypoxia, and ischemia can lead to it

Chlamydia Genital Infection

In women leads to *ectopic pregnancy, infertility, PID* Chlamydia Cervicitis and Perihepatitis: chlamydias at its worse - perihep: inflamm of liver capsule and adjacent periteneum

Why is toxemia associated with infarcts ?

Inadequate maternal vessels remodeling Ischemia of placenta

PCOS: BIOCHEMICAL FEATURES

Increased LH/FSH ratio Increased testosterone or free testosterone, DHEAS, Decreased SHBG (sex hormone binding globullin) Increased AMH * Normal cortisol, prolactin (may be mildly elevated), 17 OH P, TSH, IGF-1

MHT risks & contraindications

Increases in: - Venous clotting CI's: - Chronic liver disease - Pregnancy - Estrogen dependent malignancy (breast) - History of thromboembolic event (CVA, VTE, PE)

diagnosis of Rh alloimmunization

Indirect Coombs: most accurate technique Direct Coombs: used for neonate's RBCs

type 1 ovarian cancer

Indolent and Present as stage I Develop from well established precursors such as - Borderline tumors - Endometriosis the incesant ovulation theory works here

Prolactin inhibition and stimulation

Inhibited by dopamine and stimulated by TRH Levels rise during pregnancy and help to (a) prepare the breast for lactation (b) stimulate fetal lung surfactant (c) modulate uterine contractility, and (d) enhance a variety of immune functions

Prostate Gland

Inner periurethral zone = Transition zone (TZ): enlarges w age Outer zone = Peripheral zone (PZ) central zone = CZ Cancer = PZ Hyperplasia = TZ

mutations that lead to type1 ovarian cancer

KRAS, BRAF, PIK3CA, ERB2, PTEN, Beta Catenin

what hormone induces Leydig cells to make testosterone

LH

good predictor of ovulation? used in the sticks

LH levels

Parturition

Labor- rhythmic forceful contractions Delivery Immediate Hormonal Changes

Pituitary Causes of Amenorrhea

Lactotroph adenoma-prolactinoma (90%) Other - Mass lesion in the Sella - Pituitary surgery - Pituitary radiation - Infiltrative lesions - Hereditary hemochromatosis - Lymphcytic hypophysitis - Pituitary infarction - Sheehan's syndrome (post partum hemorrhage) - Genetic diseases - Infection

Causes of Amenorrhea pituitary level

Large pituitary tumors Hyperprolactinemia Postpartum necrosis

chorionic villi 1st trimester

Large with double layer of trophoblast (cyto- inner, syncytio-outer) Loose stroma Few blood vessels (nucleated red blood cells)

Phyllodes tumor histo

Leaf-like pattern stromal hypercellularity

Myometrial Lesions

Leiomyomata (Fibroids) - most common (30-40% of women have them), can cause infertility, bleeding, and other problems Adenomyosis

umbilical cord length

Length: mean 60 cm - Long knots, prolapse, strangulation - Short abruption, uterine inversion, umbilical hernia psychomotor impairment

what are some colposcopy findings with dysplasia

Leukoplakia (white patch) (30%) mosaic (20%) punctate (20%) warty (15%) normal (15%)

hypogonadotropic hypogonadism with normal MRI (meaning no pituitary tumor or craniopharyngioma) can be due to

Low body fat (athletes) Physical stress Psychologic stress (athletes, ballerinas, figure skate) Genetic (GnRHr, FSH, LH) Unexplained Infiltrative lesions Systemic illness-Celiac disease Hypothyroidism Adrenal hypoplasia

New Hormonal Option

Low dose CEE combined with a SERM provides new entity: Tissue Selective Estrogen Complex(TSEC)

Ovarain Germ cell tumors

MATURE CYSTIC TERATOMA (95%) IMMATURE TERATOMA DYSGERMINOMA YOLK SAC TUMOR (ENDODERMAL SINUS TUMOR) EMBRYONAL CARCINOMA CHORIOCARCINOMA

a few days after birth, what can be seen in the milk

MFG - milk fat globules have lipids and proteins

Management of patient at increased risk of preterm delivery <32 weeks

Magnesium sulfate infusion to reduce the risk of cerebral palsy Tocolysis: goal of therapy to delay delivery for 48 hours

Carcinosarcoma (MMMT) of the endometrium

Malignant *epithelial* + malignant *mesenchymal* elements Homologous - recapitulates normal elements of the uterus Heterologous - contains elements not normally found in the uterus, e.g. cartilage, bone, skeletal muscle differentiation Prognosis: poor (25% 5-year survival)

leiomyosarcoma

Malignant neoplasm with smooth muscle differentiation Pathologic criteria: - *Cellular atypia* - *Necrosis* - *Mitotic count: ≥10 per 10 high power fields* Prognosis: 50% 5-year survival, 51% recurrence, 78% distant mets

Treponema pallidum: syphilis

Man is the only host protean manifestations: can cause disease in many different organ systems - 1/3 of exposed become infected

what is the endocrine definition of puberty

Marks the transition from a non-cyclic to a cyclic reproductive endocrine system Growth and development of primary sexual characteristics (genitalia and gonads) Development of secondary sexual characteristics Results in complete sexual maturation

examples of what can cause hypoperfusion, hypoxia, or ischemia leading to preeclampsia

Maternal vascular insufficiency (eg, hypertension, diabetes, systemic lupus erythematosus, renal disease, acquired and inherited thrombophilias) Increase placental mass without correspondingly increasing placental blood flow (eg, hydatidiform mole, hydrops fetalis, diabetes mellitus, twin gestation) Increased prevalence among women who live at high altitudes (>3100 meters)

treatment for germ cell tumors

Mature cystic Teratoma: Cystectomy or unilateral oophorectomy Malignant: Unilateral salpingo-oophorectomy plus chemotherapy

2ry Amenorrhea-Ovary

Measure FSH, LH, Estrogen levels Polycystic ovarian syndrome - normal Estradiol, Low FSH, High LH, High Androgens Premature ovarian insuffiency - Low Estradiol, High FSH, LH

Meckel-Gruber syndrome

Microcephaly Occipital encephalocele Cleft lip/palate Polydactyly Cystic kidneys (ADPKD type) is autosomal recessive, usual on MKS1 gene - MKS is involved in microtubule and cilia formation

incomplete hydatidiform mole

Mixture of: - Edematous villi - Normal-sized villi Irregular villous outline (trophoblastic inclusions) Very rare reported cases of choriocarcinoma *has fetal parts*

breast cancer Targeted Therapy Options

Monoclonal Antibodies Tyrosine Kinase Inhibitors Antibody/chemotherapy conjugates Radiolabelled antibodies Novel agents

twin gestation

Monozygotic ("identical") - division of ONE fertilized OVUM Dizygotic ("fraternal")- fertilization of TWO OVA

Inflammation of Testis: orchitis

More common for retrograde spread: 1st epididymitis, then secondary orchitis Primary orchitis: *mumps, TB, syphilis* Idiopathic granulomatous orchitis (autoimmune orchitis): release of spermatozoa - elicits granuloma in epididymis, + lymphoplasmacytic inflamm

Malformation

Morphologic abnormality of an organ or larger region of the body resulting from an intrinsically abnormal developmental process If not structure forms at all - aplasia or atresia If structure is smaller than normal -- hypoplasia If defects in histiogenesis or cytogenesis, often called dysplasia

disruption

Morphologic defect of an organ or larger region of the body resulting from an extrinsic breakdown of, or interference with, an originally normal developmental process. usually related to amniotic bands

difference between high and low grade serous carcinomas

Morphologically the main difference is the degree of nuclear atypia (mild in low grade, severe in high grade) Low grade serous carcinoma is often seen in association with borderline serous tumors, shows KRAS and BRAF mutations and is relatively chemoresistant High grade serous carcinoma is often seen in association with fallopian tube STIC lesions, shows p53 mutation and is relatively chemosensitive

Endometrial Carcinoma

Most common malignant tumor of the female genital tract 55-65 yrs old there are two types

mucinous epithelium (endocervical) histo

Mucinous epithelium: Columnar cells with basal nuclei and pale blue cytoplasm

what are the type 1 ovarian cancers

Mucinous, Clear cell, Malignant Brenner Low grade serous Low grade endometrioid

what are the problems with IVF

Multiple Gestation Preterm Delivery Miscarriage Ectopic Pregnancy Ovarian Hyperstimulation Syndrome (OHSS) Cost Medical Risk

Hereditary Breast - Ovarian Cancer Syndrome

Multiple cases of breast or ovarian cancer on the same side of the family Germ line mutations of BRCA1 or BRCA2 Increased risk of breast cancer, but also of ovarian and fallopian tube cancer

non - gonococcal urethritis

Mycoplasma genitalium (MG) Known cause of acute or persistent NGU (18-46%) Newly recognized cause of cervicitis and PID Evidence that MG activates cytokines inflammation and HIV genital shedding in infected women!!!

diseases with elevated AFP

NTDs (neural tube defects) - Anencephaly, Spina Bifida Body Wall Defects - Gastroschisis, Omphalocele Multiple fetuses (blood only)

defenition of menopause

Natural: The permanent cessation of menses from loss of ovarian follicular function Surgical: Cessation of menstruation produced by artificial means (ie, surgical removal of ovaries) Result is a gradual (natural) or sudden (surgical) condition of estrogen deficiency.

Eclampsia

New onset grand mal seizures in a woman with preeclampsia that cannot be attributed to other causes

Gestational HTN

New onset hypertension in pregnancy without other findings after 20 weeks gestation

Preeclampsia

New onset of hypertension and proteinuria or end-organ dysfunction, occurring after 20 weeks of gestation in a previously normotensive woman Multisystem, progressive disorder Ranges from mild to severe Progression to severe disease may be gradual or rapid

PDE5 Inhibitor big contraindication

Nitrate Contraindication - can have too much lowering of bp

What is the pathophysiologic mechanism of annovulatory cycle

No CL→ No Progesterone → Unopposed Estrogen

Contraceptive Transdermal Patch

Norelgestromin (150mcg) and ethinyl estradiol (20 mcg) daily Labeling: Wear new patch each week for 3 weeks, then one week off

Defining norms: birth weight

Normal Weight at Term: 3300 +/- 600 grams Low Birth Weight (LBW) <2500 grams Extremely Low Birth Weight (ELBW) < 1000 grams Large for Gestational Age (LGA) >90%ile - Macrosomia >4000 grams

serous carcinoma of the endometrium

Not associated with hyperestrogenism *Arises in a background of endometrial atrophy* Post-menopausal age group Poorer prognosis and higher stage at diagnosis

cervical SQCC on pap smear

Notice the pink background of kerating, most importantly the SPINDLE CELLS = SQCC keratin pearls on histo

Progestin-Only Oral Contraceptives (POP) ("Minipill")

Often recommended for breastfeeding women May be less effective than COC's - Need for strict compliance - "27-hour rule" - hormone levels drop Similar non-contraceptive benefits No "pill-free interval" - taken daily

example of a sequence

Oligohydramnios - usually caused by a defect in renal development system results in little amniotic fluid -> increased pressure -> malformations

Assessing Ovarian Reserve

Patient's Age Day 3 FSH and Estradiol - both low is good Antral Follicle Count on ultrasound AMH- reflects the size of the primordial follicle pool *

Treatment Options for ED

Pills (PDE5 inhibitors) Suppositories (MUSE) Injections (Trimix, Bimix) Mechanical (vacuum erection device) Surgical (penile prosthesis surgery, revasc, stenting?) Hormonal (testosterone, clomiphene)

causes of third trimester bleeding

Placenta previa Placental abruption

endocrinology of pregnancy:

Placenta steroid synthesis requires cholesterol precursors from the maternal compartment. Placenta estrogen synthesis requires processing by the fetal adrenal and fetal liver. The placenta lacks 17-hydroxylase and 17, 20-desmolase and is thus unable to convert progesterone to estrogen

Penile Injection Therapy: Disadvantages

Poor long-term tolerability (dropout rate >60%) Bruising, prolonged erection, cavernosal fibrosis, pain at injection site, penile deformity (rare) Cumbersome, especially for patients with poor manual dexterity/vision or severe obesity Requires training, follow-up, and dosing adjustments

progesterone functions

Prepare the endometrium for implantation Suppress maternal immune system *Act as a substrate for fetal adrenal glucocorticoids and mineralocorticoids* Maintain pregnancy Regulate Growth Factors

types of amenorrhea

Primary No menses by age 13-14 in the absence of secondary sex characteristics No menses by age 15-16 regardless of development No menses 5 years after breast development Secondary Absence of menses after menses has begun (usually >3months)

Tubal carcinoma

Primary Tumors: Very rare Most primary malignancies are serous adenocarcinomas that may present as ovarian masses due to early involvement of Ovary Metastatic Tumors Ovary, endometrium, breast, cervix

criteria for diagnosis of hypertensive pregnancy disorders: proteinuria

Proteinuria: - ≥0.3 grams in a 24-hour urine specimen - protein (mg/dL)/creatinine (mg/dL) ratio ≥0.3 - Dipstick 1+ if a quantitative measurement is unavailable

what is acute salpingitis

Purulent infection of the fellopian tube, usually sexually transmitted -Neisseria gonorrhae, Chlamydia trachomatis, Mycoplasma, E.coli, H. influenzii, grp A streptococci

therapy for baby with hemolytics anemia (so Rh + with a mom with ab's)

RBC transfusion through fetal blood sampling When to transfuse: Hct <30% Transfuse up to a Hct of 40-50%

management for Rh risks

Recommendations depend on history No history of affected infant: - First trimester titer <1:16 or 1:32 - Titer ≥ 1:16 or 1:32: further evaluation necessary History of affected fetus: - Maternal titers are not helpful in predicting degree of anemia - Subsequent pregnancies likely to involve greater severity of hemolytic disease - Initiate testing (amnio or MCA Dopplers) at 18 weeks

importance of breast cancer screening

Regular screening lowers breast cancer mortality by - 15%-20% in women aged 40-49 - 25%-30% in women aged 50-69 Limited evidence for effectiveness in women optimal interval unknown - Reductions in mortality have occurred at intervals ranging from 12-33 months

Cervical Factor of infertility

Responsible for 5% of infertility Mullerian duct abnormalities during development Cervical stenosis or infection Suggested by *history of cone biopsy, cautery, cervicitis, obstetrical trauma, DES exposure in utero* - Postcoital test to confirm - If history is clear, not necessary

how to recognize efferent ductules

SCALLOPED APPERANCE

medullary carcinoma of the breast: histo

SOLID SYNCYTIAL SHEETS OF LARGE CELLS, VESICULAR, PLEOMORPHIC NUCLEI WITH PROMINENT NUCLEOLI AND FREQUENT MITOSES (many mitotic figures) LYMPHOPLASMACYTIC INFILTRATE SURROUNDING AND WITHIN THE TUMOR PUSHING BORDERS

in terms of cell shape and size, what type of cancer usually shows spindled cells?

SQCC when become malignant start showing spindle cells also show a pink background (keratin) which is from the squamous cells

meds for PE

SSRI's: - clomipramine - fluoxetine - paroxetine - sertraline Side effects: drowsiness, tremor, dizziness, insomnia, asthenia, nausea, sexual dysfunction

yolk sac tumor histo

Schiller Duval body ( arrow) and hyaline globules is a capillary lined by tumor cells in an empty space that is also lined by tumor cells

accessory glands of the male repro tract

Seminal Vesicles: lie lateral to the prostate, *produce about 70% of the volume of an ejaculate*, high in fructose Prostate: rish in SM and elastic fibers Bulbourethral (Cowper's) Glands: provides lubrication to the membranous urethra

Testis Tumor Classification

Seminoma non-seminoma: - Embryonal carcinoma - Teratoma - Yolk sac tumor - Choriocarcinoma

Orgasm: centrally controlled

Sensory experience Can occur *independently of erection, emission, and ejection*

Endometrial Carcinoma type II

Serous Carcinomas - less common, -type II Older age group High-grade

Nomenclature of ovarian epithelial tumors

Serous cystadenoma/cystadenocarcinoma Serous borderline tumors (same as above for mucinous and endometrioid) Clear cell carcinoma (Benigns vs malig not well stablished) Benign Brenner Tumor ( Benign transitional cell Tumor) Transitional cell carcinoma Borderline /Atypical proliferative transitional cell tumor

serous epithelium (fellopian tube) histo

Serous epithelium : Cuboidal to columnar cells with central nucleus and cilia

tumors derived from surface epithelium can be:

Serous type (resemble fallopian tube epithelium) Mucinous type (resemble endocervical epithelium) Endometrioid type (resemble endometrial epithelium) Clear cell type (resemble secretory endometrial epithelium) Transitional type (resemble urinary epithelium)

Hypogonadism - Symptoms

Sexual Dysfunction - Poor libido, erectile dysfunction, anejaculation Constitutional Complaints - Poor energy - Poor workplace concentration - Decreased strength or endurance - Decreased mood

tuner syndrome phenotype

Short stature (<58inch) Low posterior hairline High-arched palate Webbed neck Shield-shaped chest Coarctation of the aorta Hyperconvex fingernails Short metacarpal Edema of hands and feet

Progesterone Level

Should be taken d 21 or calculated 7 d after ovulation should have occurred *used to confirm ovulation* <2 ng/mL indicates anovulation >3 ng/mL confirms ovulation >15 ng/mL associated with successful pregnancies

PDE5i Failure

Significant percentage of men (70% discontinuation within 1 yr) Occurs at significant financial and emotional cost Necessitates other treatments

Hypogonadism - Definitions

Signs and symptoms consistent with hypogonadism Total Testosterone checked in the AM *less than 350 ng/dl* or in the lower limit of the laboratory in question

umbilical cord blood vessel abnormalities

Single umbilical artery - 1% of placentas - Neonatal mortality and fetal malformation

Chorionic Villi - 2nd Trimester

Smaller Stroma more cellular Increased number of blood vessels Discontinuous layer of cytotrophoblast`

Chorionic Villi - 3rd Trimester

Smallest CV Increased in number Cytotrophoblast not apparent *Syncytiotrophoblastic knots* - the syncytiotrophoblasts move to the side,stain darker Syncytiovascular membranes

Nonprescription menopause remedies

Some alternative therapies may provide relief of mild vasomotor symptoms for some women - black cohosh - relizen - vitamin E - phytoestrogen/isoflavone

fertilization overview

Sperm penetrates ovum Zona pellucida-Block to polyspermy -2nd polar body is extruded Fertilized ovum begins to divide Fertilization occurs in the fallopian tube within 48 hours of ovulation

complications of diabetes during pregnancy FOR PRE-GESTATIONAL DIABETICS

Spontaneous abortion/Intrauterine demise Congenital malformations (up to 25% risk if A1c>10) Macrosomia (birth weight > 4000gm; 90th percentile) Preeclampsia Polyhydramnios

Emergency Contraceptive Pills: Progestin

Start within 120 hours (5 days) of unprotected intercourse Not an "abortion pill" - will NOT interrupt an established pregnancy WHO Contraindications: NONE

uterine fibroids (myomas) can be

Subserosal Sumucousal: these are the ones that interfere with pregnancy intrmural

placental architecture anomalies

Succenturiate (accessory) lobe: vessels going to this lobe are prone to mechanical damage Extrachorial placenta: the edge of the placenta is not covered by the fetal membrane (the chorion)

gonorrhea symptoms in women

Symptoms: vaginal discharge, lower abdominal pain, dysuria, dyspareunia Signs: Mucopurulent cervical discharge Sequelae: chronic pelvic pain, infertility, ectopic pregnancy

syphillis

Syphilis: *↑ over last 7 yrs especially in AAM and in MSM* - african american men, men sex with men Treponema pallidum

what makes the tuboalverolar glands stop producing once mother is not longer feeding

TGF-beta

Tachyphylaxis (drug resistance)

Tachphylaxis does not make physiologic sense in a drug taken so episodically Failure to respond to therapy in time most likely signifies progression of disease state, a symptom to be taken very seriously!

Hypogonadism - Diurnal Variation

Testosterone levels best checked in *AM when Testosterone is highest* Explains AM erection phenomenon Diurnal rhythm lost in poor sleepers, nightshift workers, so on

menstrual cycle side notes

The corpus luteum will undergo spontaneous regression starting 9-11 days after ovulation unless "rescued" by hCG produced by an implanting trophoblast. Involution of the corpus luteum is accompanied by dramatic fall in the production of estrogen, progesterone, and inhibin. This removes the negative feedback suppression of the hypothalamus followed by an increase in GnRH pulse frequency. Because inhibin selectively inhibits FSH release to a greater extent than LH, the decline in inhibin production leads to a greater release of FSH than LH just prior to menstruation. This selective rise in FSH allows a new cohort of follicles to escape atresia and initiates the selection of a new dominant follicle.

what does the fall in progesterone cause

The fall in progesterone destabilizes lysosomal membranes resulting in the release of potent lytic enzymes in the endometrium which bring about the release of prostaglandins and endometrial autolysis. The release of prostaglandin F2a induces rhythmic vasodilation and vasoconstriction of the spiral arteries leading to endometrial ischemia, vascular thrombosis, and myometrial contractions (experienced clinically as menstrual cramps).

birth defects are

The major cause of infant mortality in the first year of life and the 2nd highest cause in first 5 years also A major cause of prenatal mortality

Chorionic Villi changes

The morphology of the placenta changes progressively with the trimester of pregnancy, and the changes as it matures are directed toward facilitating maternal-fetal exchange. Well-formed and easily recognizable vessels are formed at the 5th week.

Clinical Cervical Signs of Ovulation

The rise in estrogen increases production and causes *thinning of cervical mucus*, which allows sperm to penetrate the cervix more easily The ability of cervical mucus to stretch is referred to as *spinnbarkeit* Ferning activity: presence of estrogen in cervical mucus

Alveolar rhabdomyosarcoma immunohistochem

These tumors unlike embryonal rhabdomyosarcoma are going to express skeletal muscle marker stains - *myogenin and myoD1 are going to be diffusely and strongly positive*

external breast cancer risk factor

Toxins Exogenous Hormones - OCP ? - IVF (in vetro fertilization?) - HRT (hormone replacement therapy) Radiation Exposure - (< age 30) treatment for lymphoma or other conditions - Environmental radiation

Disseminated Gonococcal Infection

Triad of tenosynovitis, dermatitis, and polyarthralgias

IVF indications

Tubal factor Severe endometriosis Unexplained infertility Male factor Decreased ovarian reserve

Torsion of the testis

Twisting of vascular supply Infarction Swollen dusky scrotum - extremely painful Predisposing causes: incomplete descent, atrophy, trauma, abnormal attachment of epididymis

Alveolar rhabdomyosarcoma

Typically occur in deep muscles of extremities, axial muscles or perineum Rapidly growing, aggressive tumor Poor overall prognosis

prenatal testing

Ultrasonography First Trimester Screen - Ultrasound + Blood Tests Triple & Quad Screen (2nd trimester) Tests Chorionic Villus Sampling - Chromosome Amniocentesis - Chromosome, Protein Detection Fetal DNA tests - Sequencing of cfDNA or SNP detection

endometrium factor of infertility tests:

Ultrasound Hysteroscopy HSG to evaluate for anything messing with the endometrium (Submucous myoma, Bicornate uterus, Uterine Anomalies, Endometrial Polyp)

Placental Sulfatase Deficiency

Unable to hydrolyse DHEAS Low estriol levels Failure of cervical dilation or effacement Rare X-linked

Uterine Sarcomas

Uncommon neoplasms (5%) Two most common types: - Leiomyosarcoma - Endometrial Stromal Sarcoma

mucinus tumors of the ovary

Unilateral Large in size Multiloculated, Smooth cyst walls - Mucinous cystadenoma (80-85%) - Borderline Mucinous tumor (5-10%) - Mucinous Adenocarcinoma (10%)

Gonorrhea in Men

Urethritis causes dysuria, discharge, testicular pain Proctitis causes tenesmus, constipation, discharge Other sites: epididymitis, pharyngitis

Fetal/neonatal complications of Rh

Varying degrees of anemia due to alloimmune hemolytic anemia Severity depends on antibody concentration Severe anemia --> high output cardiac failure, hydrops fetalis, death

Erectile Dysfunction (ED) - Causes

Vascular Neurogenic Hormonal Psychogenic Often in combination to some degree

clinical symptoms of menopause

Vasomotor symptoms (hot flashes) - key feature people complain of Mood changes, memory problems(*nouns*) Irregular menses amenorrhea Urogenital atrophy, low libido: dry vagina, dificult intercourse Sequelae, not symptoms: - Cardiovascular disease - Osteoporosis - insomnia

Semen Analysis

Volume Concentration Motility (%, age of motile sperm) Morphology (% of normal shapes)

syndromes associated with wilm's tumor

WAGR: WT + Aniridia + Genital anomaly + Retardation - due to deletion in WT1 Denys-Drash: Mesangial sclerosis + pseudo-hermaphroditism - due to WT1 mutation Overgrowth syndromes including: - *Beckwith-Weideman* : WT2 mutation - Idiopathic hemihypertrophy

Kleinfelter sydrome

XXY karyotype male characteristics gynecomastia

Reifenstein syndrome

XY karyotype, but partial androgen insensitivity variable external genitalia

what is a krukenberg tumor

a *metastatic adenocarcinoma* in the ovary with *signet ring morphology* shows mucin filled signet ring cells with eccentric nucleus embedded in fibrous stroma *Most common primary source for Krukenberg tumor is stomach cancer (70%).* Bilateral mucinous ovarian tumors are likely to be metastatic from other site

what clogs up the penile opening during male development

a bundle of epithelial cells cells derived from ectoderm migrate down to the gland (tip) and go in, chew out the epithelial that plugs it

invasive mole

a complete mole invading into maternal wall Molar tissue penetrates or perforates myometrium Persistent GTD, hCG remains elevated ->can figure out tx via checking HCG lvls If there is increase in HCG, will probably be recurrence of mole -> usually excellent tx w/ chemo Treatment: - Chemotherapy (methotrexate) - Hysterectomy (for excessive bleeding or perforation)

for many BCs, doing a segmental excision with radition therapy is equivalent to

a mastectomy

what causes the LH surge during menstruation?

a peak in estrogen, switching to positive feedback instead of negative

what is CVS (chorionic villus sampling)

a small sample of cells (called chorionic villi) is taken from the placenta where it attaches to the wall of the uterus. risks mixing of blood between mom and embryo

what is a choriocarcinoma

a tumor where germ cells differentiate towards extraembryonic tissue (placental). It secretes *beta hCG*. Responsive to chemotherapy has both *syncytrophoplastic and cytotrophoplastic* cells (multinucleated) have alot of hemorrage

what is hydrops fetalis

abnormal accumulation of fluid in 2 or more fetal compartments

what is hydatidiform mole

abnormal form of pregnancy in which a non-viable fertilized egg implants in the uterus and will fail to come to term

when does the 2nd meiotic division happen?

after fertilization

main reason for lost of baby

aneuploidy which goes up with age

what is rhoGAM

anti-D immunoglobulin 16% of Rh negative women become sensitized after 2 deliveries of Rh positive infants; rhogan reduces it to 0.1% if given antepartum and postpartum

what main drugs are used for patients with atypical hyperplasia?

anti-estrogen drugs like tamoxifen lowers risk of breast cancer goes down by 86%

what is the schiller test

application of iodine solution to the cervix normal epithelium - brown abnormal epithelium - white

metastatic prostate cancer more often presents....

as back pain, bc it like to metastasize to bone bone looks brighter on MRI, but is really just weaker

what groups have a lower risk of breast cancer

asian, hispanic, and native american women

Intrauterine Contraception: Insertion

at any time in cycle as long as no pregnancy Can also insert after 1st trimester abortion (immediate)

what is important about the fact that hCG has thyrotropic activity

at the beginning of pregnancy women may present with a bit of hyperthyroid like activity

amniocentesis vs chorionic villus sampling

both allow to test Rh, Karyotype, and genetics only amniocentesis allows for AFP testing

PDE 2,3,4

break down cAMP to AMP

role of PDE5

breaks down cGMP into GMP turns off the signaling for an erection

why is hPL so important

by being anti-insulin, it slows glucose clearance giving more time for glucose to be taken up by the baby

when do women develop oocytes

by the fifth month of life

umbilical cord marginal insertion

can also lead to hemorraghe bc vessels are not protected

granulomatous endometritis

can be due to TB or any other granulomatous disease can be necrotizing granuloma or non-necrotizing

anything that causes 2ry amenorrhea....

can present as primary amenorrhea not vice versa

Chronic Endometritis (inflammation) histo

characterized by presence of plasma cells

where are the embryonic blood vessels? (plate wise) and where are the mom's blood vessels

chorionic plate decidual plate

what are most pregnancy lossess due to?

chromosomal errors

example of a SERM

clomifen

norepinephrine to the penis SM

comes through sympathetics increases intracellular Ca

progesterone levels throughout pregnancy

continually increases

on the mothers side, the placenta is separated into smaller units called

cotyledons 15-20 per placenta

endometrium during proliferative stage

cuboidal to low columnar epithelium (if right after, not much epithelium) has glands that goes down to the basalis stromal cells and blood vessels

in absence of SRY, the mesonephric duct will

degenerate

treatment for preeclampsia

deliver the baby Plan for delivery at 37 weeks in the absence of severe features Anti-hypertensive medications are generally avoided if pressure is below 160/110 Medical termination is offered <24 weeks gestation

Dysfunctional Uterine Bleeding

diagnosis by exclusion Bleeding not attributable to any organic pathologic condition. Most common cause is Anovulatory Cycle Other causes: Luteal Phase Defect Persistent Corpus Luteum (Irregular Shedding)

what happens when baby suckles? crying baby?

direct stimulus into the brain to allow for oxytocin and prolactin increase

treatment for Her2-new breast cancers

directed monoclonal antibodies (herceptin) can be used for treatment (trastuzumab)

immature breast histo

ducts have simple columnar epithelium

important to remember about fetal development

each part of the organism develops at a different time, most important period is the 1st 8 weeks so same teratogenic agent can cause different anomalies depending on what time it was exposed

what went down with frozen-thawed IVF

ectopic pregnancies, miscarriages went down implantation rates go higher

where is ovarian surface epithelium derived from

embryonic coelemic epithelium

hydrops placenta

end stage condition very variable etiology

parts of the uterus

endometrium myometrium (most of it) perimetrium

what is usually the main type of estrogen? which one is the highest during pregnancy?

estradiol (E1) - normal estriol (E2) - pregnant

retrograde ejaculation

experience orgasm, but most ejaculate end in bladder anatomic issues

what particular feature can be found in the ovarian medulla

fat droplets

type of stroma in neuroblastomas

fine fibrillary type stroma that interdigitate the tumor: *called neuropil*

HSV first vs other flares

first flare is the worst they dont look so horrible after

first step in 2ry amenorrhea workup

focused physical: check for high androgen levels and TSH - Life style changes-Stress-Death, moving, school - Weight loss - Symptoms-heat or cold intolerance, constipation, lethargy, nipple discharge - Increases in acne or hirsuitism Then: - Family history - Medications

what eggs are better? fresh or frozen

frozen

gentics and teratogens

genetic factors have a role in how detrimental a teratogen can be fraternal twins can show different levels of malformation

rubella is aka

german measles is a minor illness but a known teratogen

Botryoid rhabdomyosarcoma histo

has squamous cell lining basement membrane layer *condensed hyperellular mesenchymal proliferation: cambium layer*

Stein-Leventhal Syndrome: Polycystic Ovary Disease

have 2/3: *androgen excess, ovulary dysfunction (amenorrhea, oligomenorrhea), polycystic ovaries* High risk of type II diabetes and CVD 50% of patients are obese runs in families

how does a trophoblast look in histo?

huge cell with hundreds of nuclei surrounding the placental villi

in terms of repro, what does the hypothalamus/pituitary make?

hypo - GnRH in pulsatile pattern Pituitary - FSH, LH = tell the ovary to make estrogen and other molecules

what can be wrong (area wise) with amenorrhea?

hypothalamus pituitary ovaries outflow tracts

when do we see peau d'orange

in breast cancer, due to lymphedema

where do the sperm and the egg meet

in the ampulla of the fallopian tube

where does the first division happen? (once the egg is fertilized)

in the fallopian tube

incidence of breast cancer

increases with age steady decrease in mortality 12% lifetime risk of developing BC for women (1/8)

erection generating CNS signals

injury above T12 - can get reflex erection with like a catheter change injury below S3 - incapable of erection

what does insulin do to theca cells?

insulin increases theca cell production of testosterone so for PCOS, you have alot of testosterone plus hyperinsulinemia-- even more testosterone

almost the entire urogenital system develops from

intermediate mesoderm

where does the mesonephric duct originally drain?

into the primitive bladder (urogential sinus)

Corpus Luteum Follicular Cysts can cause..

irregular menses due to continued progesterone or estrogen production

prostate gland

is a *tubular alveolar gland* very rich in SM as men get older, has precipitates called *concretions* - look like pink pearls

Phyllodes tumor

is a stromal tumor irregular borders *solid and cystic* ranges from benign to malignant

seeing pink on the cytoplasm of a cell on a pap smear shows that:

it is a squamous cell, the pink is keratin

where does the vas deference go

it joins with the seminal vesicle to form the *common ejaculatory duct* make its way through the prostate and comes out the *prostatic urethra*

oxytocin effects on the myometrim

it leads to contractions and when oxytocin is being released, the myometrium actually makes more oxytocin receptors

prolactin effect on GnRH

it lowers GnRH levels

what usually gets anorexics to stop

knowing that they are not menstruating and realizing they could loose reproductive health also low levels of estrogen: Lanugo, Bradycardia, Constipation, Low blood pressure, Hypothermia, low bone density lanugo: increased body hair

seminal vesicles

lined by pseudostratified columnar epithelium has anastamosin group of channels with seminal fluid inside

most common malignancy in children

liquid types - leukemias (15x more common than other ped tumors) - lymphomas - CNS tumos - Soft tissue sarcomas - Germ cell tumors - Bone tumors - Neuroblastoma - Wilms tumor - Retinoblastoma - Liver tumors

effect of testicuar testosterone is....

local

what part of the menstrual cycle is usually invariable?

luteal part is usually 14 days and not very variable

Meconium staining of the fetal membrane

meconium (baby poop) in the amniotic sack (happens when baby is stressed) is an irritant for the amniotic membranes: can induce hyperplasia of the amnion epithelium

correctable causes for delayed ejaculation

medication, hormonal

what are oocytes stuck in?

meiosis I

demographic that goes to the doctor the least

men 18-35

estrogen and the brain

menopausal women on estrogen: better cognition debate on whether it acutally helps to prevent dementia

struma ovarii is an example of

monodermal teratoma *More than 50% of the tumor tissue should be thyroid tissue* to be classified as Struma ovarii 5-10% patients may have hyperthyroidism clinically 20-30% patients *may have thyroid cancer arising in struma ovarii* (commonly Papillary type, occasionally follicular type)

Hydatidiform mole

more common in Asia than Western contries Present with *vaginal bleeding in 1st trimester* Uterus larger than expected HTN in 1st trimester (25% in Complete Mole) *Elevated Human Chorionic Gonadotropin*

Kallman's syndrome

more common in XY males: deficiency of GnRH presents with Hypogonadotropic hypogonadism + no smell (anosmia) Genetic - heterogeneity with x-linked and autosomal Anosmia- aplasia of olfactory bulb and sulci, failed migration of GnRH neurons from the olfactory placode to the medial basal hypothalmus

thalidomide

morning sickness drug caused unusual malformations in other Europe and Asia

breast fibroadenoma

most common *benign* tumor usually presents as a *mobile* mass that is well-circumscribed on ultrasound is *always wider than it is tall* arises from the *intralobular stroma*

what is MIF

mularian inhibitory factor - causes degeneration of the paramesonephric duct

McCune-Albright syndrome

mutation of G protein - *constant activation of Gn receptors in granulosa cells* leading to estrogen production Triad: *precocious puberty, polyostotic fibrous dysplasia of bone, and café au lait spots (skin pigmentation)*

what is in the theca externa

myofibroblasts help propel the oocyte out eventually

is there positive or negative feedback in the luteal face?

negative its only positive when the mature oocyte releases alot of estrogen to turn on the LH surge

clinical features of dysplasia

none

Does Time Lapse Microscopy and Morphology Predict Euploidy?

nope

medullary carcinoma of the breast

occurs in younger patients BRCA1 accounts for 13% of cases well circumscribed, they just push tissue slightly better prognosis

non-seminoma tumors

often *advanced beyond testes* early mets radioresistant serum markers: AFP, HCG good prognosis

seminoma tumors

often *localized to testes* late mets radiosensitive no markers excellent prognosis

where does fetal blood sampling sample blood?

on the umbilical vein of the placenta

what happens to an antral follicle

once a month, one will become the Graafian/preovulatory follicle undergoes ovulation

most common neuroblastoma presentation?

persistent fever Physical examination reveals a palpable abdominal mass Radiological imaging localizes mass to the adrenal gland

gonorrhea

plateaued over the last 3 years *increasing drug resistance*

what happens if the cytotrophoblasts don't remodel the blood vessels properly?

pre-eclampsia

breast Nonproliferative fibrocystic changes

present in most women lumpy bumpy changes on exam 20-40 years of age, peaks peri or premenopausal no risk of breast cancer

what do syncytioblasts do (in terms of barrier)

prevents proteins and pathogens from crossing placenta exceptions include Infectious agents (Toxoplasma, gondii, Rubella, Cytomegalovirus, herpes, syphilis, measles, varicella)

embryonal carcinoma

primitive embryonic tissue undifferentiated totipotential cells. Responds well to chemotherapy.

what is the key for normal GnRH, FSH, LH secretion?

pulsatile patterns

brenner tumors

rarely seen, completely bening made of transitional epithelium are solid (not cystic) but small have *OVAL NUCLEI WITH GROOVES*

what happens to the cell surrounding the oocyte that undergoes ovulation

remains to become the corpus luteum - make the steroid hormones just like the follicles remains around for 10 days - then degenerates

treatment for testicular tumor

remove the tumor, then base treatment of off what kind of tumor it was Seminoma: radiate non semi: take out retroperitoneal lymph nodes to avoid later metastasis all tumors stage II and III: chemo

what does the release of prostaglandin F2a induce

rhythmic vasodilation and vasoconstriction of the spiral arteries leading to endometrial ischemia, vascular thrombosis, and myometrial contractions (experienced clinically as menstrual cramps).

most fatal ovarian tumors

sadly, surface epithelial tumors

histo with efferent ductules and epididymis

scalloped: efferents epi: notice the amount of muscle, and can kind of see the stereocilia inside the lumen

what happens to the endometrium glands durig the menstrual phase of ovulatory cycle

see pools of blood

spectrum of endometrial hyperplasia

simple without atypia: crowded glands with reduced amount of stroma btwn them; cystic dilation of glands complex with atypia: very crowded glands; *can still outline each gland* (unlike adenocarcinoma) - leads to adenocarcinoma

what kind of cells are are seen in breast cancer FNA?

single cells look PLASMACYTOID: the nucleus moved to the side like a plasma cell

what can cause disrupted puberties (as in in times of war)?

sleep depravation, because of lack of REM nightime LH surges

Vaginal cancer

squamous carcinoma (most common, but infrequent) adenosis and clear cell carcinoma (very rare disease) embryonal rhabdomyosarcoma

continued GnRH administration

suppression of FSH and LH

where does the testicular artery come from

the abdominal aorta so have to cool it before reaching testes: the *pampiniform plexus of veins wraps around the artery, and by countercurrent action the arterial blood cools*

IVF and embryo time outside of the mom

the longer it is out, the better rates i guess knocks out the ones that werent going to survive

so the heat flashes are due to....

the low estrogen so patients who we lower estrogen by giving GnRH -> can get hot flashes

reason for the variability in a woman's cycle

the proliferative phase Duration is variable (10-20d) Stromal and Glandular Proliferation Stimulation of the endometrium by Estrogen

what part of the male genitalis isn't made from mesoderm?

the prostate

histology of ovary

there is a cortex and a medulla there is a hilus where blood vessels nerves and lymphatics enter and leave covered by germinal epithelium (continuous with peritoneal cavity covering) - is cuboidal

since sertoli cells create a barrier, what else do they have to do

they also have to nourish the developing sperm

what does GnRH bind to

to G protein-linked GnRH receptors on the surface of the gonadotrophs on the pituitary

main function of STEREOCILIA in male repro tract

to begin resorbing fluid as sperm passes

sertoli cell histo

triangular nucleus prominent nucleolus

neuroblastomas histo

typically solid, well circumscribed lesions in adrenal gland small round blue cell tumors that are showing a little bit of a nested appearance high N/C ratio "salt and pepper" chromatin type distribution thin fibrous stromal tissue between nests

complete Hydatidiform mole

ultrasound "snowstorm pattern" Villous edema and cisterns (grape-like vesicles) Trophoblastic proliferation Prognosis - 80-90% benign - 10% invasive mole - 2.5% choriocarcinoma

lateral plate mesoderm

underlies either ectoderm (Parietal or somatic) or endoderm (visceral)

candida on papa smear

vulva itching with white cheesy discharge white patches on vulva on P.E see spores and pseudohyphae on pap

do women who are alive and adult still have premordial follicles?

yes

Why is toxemia associated with placental abruption ?

↑Placental vasoconstrictors and maternal hypertension Damage of maternal vessels

tubular carcinoma of the breast

♦ usually detected as spiculated masses on mammography ♦ well formed tubules with absent myoepithelial layer and apocrine snouts ♦ axillary metastases uncommon ♦ excellent prognosis

Diabetes in pregnancy : pre-gestational diabetes

(13%) Type I or II diabetes diagnosed before pregnancy

the dominant follicle

(a) has the highest concentration of FSH receptors (b) has the highest level of aromatase activity, and (c )has the greatest estradiol production

Evans staging of neuroblastoma: stage IV-S

(special) - stage I or II with remote disease in liver, skin, bone marrow (with no bony destruction)

DMPA: Noncontraceptive Health Benefits

** Reduction in frequency of epileptic seizures ** Reduction in sickle crises Reduction in symptoms of endometriosis No known drug interactions

benign Ovarian Surface Epithelial Tumors

*4 times more common than malignant tumors* Usually entirely cystic, can be massive in size Age group: 20s to 40s

Proposed Organic Factors in PE

*5-hydroxytryptamine (5-HT) type 1& 2 (5HT-1 & 5HT-2)* receptors are concentrated in brain centers that integrate sexual responses - 5HT-1 enhances sexual responses - 5HT-2 inhibits sexual responses PE may be caused by - Hypersensitivity of central 5-HT1a receptors - Hyposensitivity of 5-HT2c receptors

management for diabetes in pregnancy

*Achieving and maintaining excellent glycemic control* - FBS < 95, 1h PP < 140 - HbA1c <6.0 mg/dL; Random glucose <95 mg/dL Screening, monitoring, and intervention for maternal medical complications Monitoring of, and intervention for, fetal and obstetrical complications

granulosa cell tumor

*Adult form: after menopause* *Juvenile form: before puberty* Secretes *Estrogen and inhibin* : Precocious puberty, endometrial hyperplasia/carcinoma Low Malignant Prognosis better in Juvenile form

Prostatic Intraepithelial Neoplasia (PIN)

*Benign glands (stratified epithelium) containing atypical cells [nucleoli]* - remember: prostate cancer -> luminal cells and nulceoli! Precursor lesion Increased risk for development of prostate cancer

granulos cell tumor histo

*Call-exener bodies* ( arrow) - are follicles filled with protenacious material *coffee bean nuclei*

endometriosis gross pathology

*Chocolate cyst*, thick-walled, adherent to adjacent structures, occasionally confused with malignancy

Endometrial Stromal Sarcoma

*Low grade sarcoma* *Morphologically similar to endometrial stroma in proliferative phase* Prognosis: 40% local recurrence, up to 20 years after Dx, rare lung mets low mitotic count, look almost benign HAVE ESTROGEN AND PROGESTERONE RECEPTORS - RESPOND TO PROGESTERONE TREATMENT

Luteal Phase Support

*Luteal supplementation with either human chorionic gonadotropin (HCG) or progesterone significantly improved fertility outcomes* Intramuscular (IM) progesterone was better than vaginal or oral Hyperstimulation occurred with HCG but not with IM progesterone

most important areas for sexual stimulation

*Medial preoptic area (MPOA)* paraventricular nucleus (PVN) Multiple regulatory neurotransmitters - *Serotonin*: *reuptake of seratonin out of the synaptic* *space is involved in normal ejaculation* - Dopamine - Oxytocin - Gamma-aminobutyric acid (GABA)

Prostate Cancer

*Most common cancer in males* 2nd Leading cause of cancer death in males (lung 1) Rapid increase in incidence in early 90s Decreased to plateau level: better at detecting it more common in western countries

hypogonadism - signs

*Osteopenia/osteoporosis* *Decreased insulin sensitivity* Truncal obesity Metabolic syndrome - DM, truncal obesity, hyperlipidemia NOT SO VAGUE; VERY IMPORTANT

dysgerminoma

*Ovarian counterpart of testicular seminoma* Most common malignant germ cell tumor of ovary *Undifferentiated germ cells* *May produce hCG leading to elevated serum hCG levels* Radiosensitive, excellent prognosis looks lobulated

sertoli-leydig cell tumor histo

*Reinke crystals* ( arrow) in Leydig cells notice the primitive testes on the left pic

testing for testosterone

*bioavailable testosterone* = albumin bound + free

Endometriotic cysts are aka ____ because they contain

*chocolate cysts* they contain old clotted blood that look really dark Cyst wall is formed by endometrial epithelium and stroma considered *precursors of endometrioid and clear cell types of ovarian cancer*

polycystic ovary disease pathogenesis

*increase in LH production* (continuous instead of surge) - theca cell overproduction--> androgen overproduction - estrogen levels also raised due to androgen stimulating estrogen secretion decrease in FSH: follicle arrest --> annovulation

Bacterial Vaginosis

*is a vaginal microbiome change: loss of lactobacilli* Risk: multiple or new sexual partner(s) DX: pH, clue cells, *DNA probes & POC tests* - Point Of Care test Can lead to pre-term delivery, higher risk of *HIV, HSV-2, GC & Chlamydia* Treatment: - Metronidazole - Recurrences: metronidazole gel for x 4-6 mos

endometrial atrophy

*most common cause of bleeding in post menopausal pts* due to Lack cyclical changes of estrogen and progesterone *so can also be seen in pts taking OCP* endometrium becomes thin, few glands Stroma is fibrotic Occasional cystic dilatation

choriocarcinoma microscoph

*no formation of chorionic villi* Sheets of malignant cells recapitulating primitive cyto-/syncytiotrophoblast Elevated hCG Extremely responsive to chemotherapy

Adenomyosis (macroscopic and microscopic)

*painful*, dificult to manage but *benign condition* thickened wall uterine wall with endometrial glands in it (tissue that shouldn't be there) - results in muscle hyperplasia around it the endometrial part sheds like regular EM tissue, but since trapped -> inflammation -> painful

Embryonal Rhabdomyosarcoma immunohistochemistry

*patchy MyoD-1, myogenin*

VICTERL syndrome acronym

*v*ertebral anomalies *a*nal atresia *c*ardiac *t*racheo - *e*sophagial fistula *r*enal anomalies *l*imb

spermatogenesis: spermatogonia to spermatozoa

1) Spermatocytogenesis: spermatogonia to primary spermatocytes 2) Meiosis: primary spermatocytes to spermatids 3)Spermiogenesis: spermatids to spermatozoa (3 phases can be distinguished) a. Golgi Phase b. Acrosomal Phase c. Maturation Phase 4)Spermiation: release of spermatozoa

role of magnesium sulfate in pregnancy:

1) decrease cerebral palsy 2) for seizure prophylaxis given intrapartum and for 24h postpartum for moms with preeclampsia

uterus endometrial changes during ovulatory cycle

1) menstrual phase - shedding of endometrium 2) proliferative phase - FSH, estrogen, endometrial regeneration 3) Secretory luteal - LH, progesterone, estrogen - endometrium grows, gets vascularized and ready for implantation 4) ischemia - hormone levels fall, no implantation, spiral arteries contract, endomtrium starts to shed again

cell types critical for testes development

1) within the tubules: sertoli cells - secrete factor MIF 2) in connective tissue btwn tubules: Leydig cells - make testosterone

conclusions of IVF

1. A euploid baby is the desired outcome of IVF 2. Many embryos created from IVF are aneuploid 3. Frozen-embryo transfer has distinct advantages over fresh embryo transfer 4. Embryo culture selects for and enriches euploid embryos 5. Aneuploid embryos cause most miscarriages 6. Aneuploid embryos account for the age-related decline in fertility 7. Single-Thawed Euploid Embryo Transfer (STEET) offers a way of performing single embryo transfer and maximizes outcome

Morphologic Parameters in Cytologic Evaluation: cell size and shape

1. Variable size depending on the neoplasm: i.e. small uniform cells in chronic lymphocytic lymphoma, large anaplastic cells in giant cell carcinoma of the pancreas 2.Nucleus: shape, alteration in chromatin and nucleolar prominence. Malignant cells are usually abnormally shaped with irregular nuclear membranes, hyperchromatic cells and large nucleoli. 3.Cytoplasm: color (keratin is orange on Pap stain), vacuoles (mucin, lipid), pigments (melanin, lipofuscin, bile).

Abnormal findings in Squamous cells on a pap smear

1.Infections: Candida albicans, Trichomonas vaginalis, Neisseria gonorrhea, Herpes, Actinomyces, Tuberculosis 2.Contaminants: Talc from gloves, sperm, lubricating creams 3.Squamous abnormalities

Nomenclature

1.Negative for malignant cells 2.Atypical: The cells are not normal in appearance but the changes do not signify cancer (reactive atypia in inflammatory conditions) 3.Suspicious: changes most likely represent malignancy however the evidence is scanty 4.Positive for malignant cells

Morphologic Parameters in Cytologic Evaluation: cellular arrangements

1.Sheets: honeycomb pattern, usually signifies benign epithelium 2.Three dimensional clusters A.Papillary B.Glandular or Tubular: e.g colorectal adenocarcinoma C.Pearls D.Rosettes 3.Single cells: E.g breast cancer

INHERITED genetic factors in breast cancer

10% of breast cancer related to inherited mutations. Approximately 1/3 of females with hereditary breast cancer have mutations in BRCA1 or BRCA2- tumor suppressor genes, cancer arises only when both allelles are inactivated or defective

mammary glands

10-100 alveoli/lobule 20-40 lobuli / lobe Each lobe drained by a lactiferous duct 15-20 ducts / breast Ducts drain to sinuses to nipple

what is ovulation

10-12 hours after LH surge 34-36 hours after LH onset one oocyte completes meiosis I Granulosa cells luteinized, progesteron secretion begins

Progestin-only ECP Effectiveness: Single Use

100 women have unprotected sex in the 2nd or 3rd week of their cycle 8 will become pregnant without emergency contraception 1 will become pregnant using progestin ECPs (88% reduction)

% of deaths of 1-14 year olds due to cancer

11% yet cancer is rare in childredn

menopause

12 months of amenorrhea after the final menstrual period Average age in US - 51 yr Range 45-55 POI= onset before age 40 Diagnosis usually made by history and confirmed with FSH level

hyperprolactenemia is responsible for ____ of 2ry amenorrhea cases

13%

in situ (non-invasive) ductal carcinoma of the breast

15-30% of cases picked up by mammography - 50% of those found are DCIS (ductal carc. in situ) this type of cancer *cannot invade through the basement membrane of the ducts and therefore cannot metastasize* can spread through the ductal system and involve large segments *see calcifications on mammograms that look like ducts*

what is the most common type of HPV?

16 18 they are also high risk HPV with 20% progressin to dysplasia

what is usually considered the BMI at which the hypothalamus-pituitary-ovary (HPO) axis gets messed up?

17%

layes of muscle in the oviduct

2 - circular and longitudinal

embryo initial stages:

2 cell 4 cell 8 cell morula blastocyst (implantation)

prevalence of HPV

2 to 5% based on screening diagnosis of cervical dysplasia and HPV changes 5 to 10% based on Southern Blotting

rule of 20's for PCOS

20% of people with polycystic ovaries don't have PCOS 20% of people with PCOS dont have polycystic ovaries

family history of breast cancer

20-30% of women with breast cancer have a family history of the disease. One first-degree relative (parent, sibling, child) doubles the risk. Two first-degree relatives lead to a 5-fold increase in risk. Men with breast cancer are an important aspect of family history.

treatment for gonorrhea

2007: Fluoroquinolones No Longer indicated for Treatment of Gonococcal Infections 2013: Strains with lowered cephalosporin susceptibility CDC Recommended Regimens - *Ceftriaxone 250 mg IM PLUS azithromycin 1 gram po* Retreat suspected failures with 2nd dose of ceftriaxone + azithromycin Evaluate sexual partners within 60 d *for GC/Chlamydia and treat*

peak age for IVF

25

when to give rhoGAM

28 weeks pregnant (all Rh - women, unless know partner is Rh - ) post delivery if fetus is Rh pos After invasive procedures: amnio, CVS, PUBS, multifetal reduction Antepartum bleeding Blunt trauma to abdomen intrauterine fetal death (IUFD) Hydatidiform mole

Ewing sarcoma (PNET)

2nd most common bone malignancy in children diffuse sheets of small round blue cells Rare in Africans and African-Americans Typically occurs in diaphysis of long bones, pelvis, ribs

neuroblastoma facts

2nd most common malignancy in childhood Median age at diagnosis: 22 months - the older the worse prognosis Most common site: adrenal gland but *can from anywhere along the sympathetic chain* 90% produce catecholamines - Elevated serum catecholamines, but dont cause things like high Bp; so we look for: - Elevated urine metabolites (vanillylmandelic acid [VMA] and homovanillic acid [HVA])

seminomas

30-40% of all testicular tumors 2 Types: Classic (90%) & Spermatocytic (<10%) Macro: Solid, pale, homogeneous Micro: Lobules of uniform round clear cells surrounded by fibrous septa *containing lymphocytes*

standard rhogam dose

300 mcg IM - protects against 30mL whole blood (15mL RBC)

which are the intermediate risk HPV's

31/33/35 5% progress to dysplasia

infertility factors

40% "male" factor 40% "female" factor 10% combined 10% unexplained

turner syndrome as related to maternal/paternal age

45 X0 Est. 1% survive to birth (18% of aborted fetuses) Not assoc with maternal age No mental impairment but learning issues Streak gonads, Short stature, Web neck, Shield chest Many other defects (CHD, renal)

congenital adrenal hyperplasia

45 XX, female but very high levels of testosterone - congenital adrenal hyperplasia (is this 21-beta-hydroxylase deficiency?)

spontaneous abortion and implantation

45% of fertilized embryos abort 30% of implanted embryos abort Most pregnancy losses are due to abnormal chromosome

testicular feminization syndrome (CAI)

46 XY, female phenotype widely spaced nipples, broad shoulders, vagina is short and blind ended, bilateral bulges in pelvic area (testes) *has seminiferous tubules with sertoli cells (MIF), DHT levels normal, working 5 alpha reductase* problem is *Complete androgen insensitivity (CAI)*

Nexplanon: Single rod etonorgestrel implant

4cm long implant, 68 mg etonorgestrel Provides 3 years of contraception Releases ~60 mcg/day etonorgestrel initially ("burst" effect), then slowly decreases

5ARI Effect on Prostate

5 alpha reductase inhibitor - prevents the conversion of testosterone into DHT good for the prostate: remember DHT's relationship to the prostate

invasive lobular carcinoma (ILC) of the breast

5-10% OF CANCERS BILATERAL IN 20% MULTICENTRIC IN SAME BREAST DIFFUSELY INFILTRATIVE PATTERN: meaning that its hard to get along the edges of a lobular tumor

normal levels of FSH?

5-20 IU/L

causes of congenital malformation

50% idiopathic 25% due to genetics and teratogenic factors

cancer risk factors

50-75% of cancer deaths : related to modifiable personal behaviors > 30% of all cancer deaths: related to cigarette smoking 30% of all cancer deaths in the U.S. are related to poor nutrition & inactivity leading to obesity Risk may be reduced by increasing consumption of fruits & vegetables and limiting high-fat foods

OVARIAN CARCINOMA: Epidemiology

5th commonest fatal malignancy in women after breast, lung, colon and pancreas White women have a higher risk than Blacks and Asians Jewish women have a much higher risk than non-Jewish

which are low risk HPV's

6 and 11

retinoblastoma facts

60% sporadic, 40% familial (autosomal dominant) develops on 80% of those with with mutant Rb gene bilateral in 30% of cases tends to invade optic nerve 6-20% risk of having a 2ry primary tumor 10-20 years after removal

time it takes form 2ry follicle to graafian

70-85 days

what percentage a breast microcalcifications are benign?

85%

genetics of Ewing sarcoma/ PNET (REQUIREMENT FOR DIAGNOSIS

85% have t(11;22) the EWS/FLI1 - is a translocation of FLI1 - from chromosome 11 to chromosome 22 - cuases overexpression of ETS 5-10% have t(21;22)(q22;q12) the EWS/ERG

testis tumor origins

95% Germ cell tumors 5% Sex-cord / Gonadal stroma (Leydig / Sertoli cell tumors) Others: Lymphoma

Pathogenesis of Surface epithelium ovarian tumors: Surface Inclusion Cysts

A part of the epithelium invaginates and gets trapped due to some injury - inclusion cyst Over time, some under go metaplasia and become mucinous or serous --> rise to cysts/tumors correlates with the theory of incessant ovulation

sequence

A pattern of multiple anomalies derived from a single known or presumed prior anomaly or mechanical factor, leading to secondary effects in developmentally unrelated structures

Limitations of Cytopathology

A.Cannot assess invasiveness (vascular invasion, depth or extent of invasion) B.Specificity is practically 100% however sensitivity is 80-90% due to inadequate sampling

Advantages of Cytopathology

A.Less invasive with fewer complications B.Samples larger surface area C.Rapid diagnosis D.Can evaluate organ sites that cannot be biopsied, i.e. pancreas E.Cost containment

what is elevated in serum when there is a yolk sac tumor

AFP

non-seminoma tumor serummarkers

AFP, HCG

placental abruption as a clinical syndrome

Abdominal *pain* Vaginal/concealed *bleeding* (uterine tetany) Rapid delivery of the fetus and *fetal distress* Marginal / retroplacental *hematoma* 1/3 of patients with clinical abruption will have hematoma and vice versa

causes of First trimester bleeding

Abortion (spontaneous, induced) Hydatidiform mole Ectopic gestation

Treatment for Prostate Cancer

Active surveillance: Gleason 6 Therapy for Gleason 7 and higher: Surgery: Radical Prostatectomy: Gleason 7 or higher Radiation: Brachytherapy - pellets in prostate; External Beam Hormonal then chemo- therapy: If cancer no longer localized (metastatic)

Clinical Approach: breast cancer Local Control - Radiation Therapy

Adjunctive therapy to primary surgery "Standard Technique" Complications/Side effects New Approaches - Shorter duration ( 3wks vs. 6 wks) - Prone vs. Supine - Limited field - Brachytherapy

phases of puberty

Adrenarche is the activation of the adrenal medulla for the production of adrenal androgens Gonadarche is the activation of the gonads by the pituitary hormones FSH and LH. Pubarche is the appearance of pubic hair. *Thelarche is the appearance of breast tissue* Menarche is the age of onset of the first menstrual period.

Erectile Dysfunction (ED) - Background

Affects 40% of 40 year old men 70% of 70 year olds

breast cancer Screening Guidelines Healthy Women

Age 20 - 39 - Monthly Self Breast Exam - Clinical Breast Exam q 3 yrs Age > 40 - Annual Mammogram - Annual Clinical Breast Exam - Monthly Self Breast Exam High Risk - Imaging and clinical exam starting at age 35 or younger - Additional imaging modalities: ultrasound, MRI

causes of testicular failure

Aging Anorchia Cryptorchidism Genetic disorders - Klinefelter's syndrome Idiopathic Malnutrition Neurodegenerative illnesses Respiratory disorders Trauma Viral orchitis

hCG structure

Alpha unit: - Identical to TSH, FSH, LH - Encoded by a single gene on chromosome 6 Beta unit: - Unique, encoded by several genes on chromosome 19

Triple and Quad Screen Tests (15-20 weeks)

Alpha-fetoprotein Estriol is a placental hormone. Estriol is decreased in the Down syndrome pregnancy. hCG -- placental hormone increased in Down syndrome pregnancies Inhibin A is a protein secreted by the ovary, and is designed to inhibit the production of the hormone FSH by the pituitary gland. The level of inhibin A is increased in the blood of mothers of fetuses with Down syndrome (Quad Screen Test)

prostaglandin E1

Alprostadil produces corporal smooth muscle relaxation by increasing the concentration of cAMP via modulation of adenylate cyclase. This in turn stimulates protein kinase A and ultimately inhibits the activity of voltage-dependent calcium ion channels. Problem: *after using PGE1, patients often complaint about pain in the penis*

yolk sack tumor

Also called as *endodermal sinus tumor* 2nd most common malignant germ cell tumor Most patients *under 20 yrs of age* Differentiation towards extraembryonic tissue *Elevated serum AFP* Early metastasis Conservative surgery and combination chemo = complete cure in 80% cases at all stages

Trichomonas Vaginalis

Always sexually transmitted, 30-40% of male sexual partners infected but asymptomatic *Facilitates HIV transmission & associated with PID* diagnosis: , new DNA probes and monoclonal Abys metronidazole *treat sex partners simultaneously* - can ping pong back

Treatment Options: Hypothalamic Amenorrhea

Anovulatory: normal estradiol = clomiphene Amenorrhea: low estradiol, low weight, high stress = gonadotropins

what goes into placenta through receptor mediated endocytosis

Antibodies including IgG Fe, Cu, Folate

checking TSH in amenorrhea

Approximately 5% of adult women with secondary amenorrhea will have abnormal TSH or Prolactin levels

placental infarct

Area of ischemic necrosis due to obstruction of blood supply (spiral arteries-thrombus, outside compression) Peripheral or marginal no clinically significant usually - clinical if >3 cm, central portion (the primary site of gas and nutrient exchange) Associated with diabetes, HTN, lupus, toxemia

Amnion nodosum

Associated with oligohydramnios and fetal urinary tract abnormalities must be excluded caused by the baby moving around and hitting the placenta and the amnion

thecoma

Benign, solid, well circumscribed Unilateral Occur in *postmenopausal women* Appears yellow grossly *Produce estrogen: Abnormal uterine bleeding, breast enlargement, endometrial hyperplasia or carcinoma*

treatment for ovarian surface epithelial tumors (benign and borderline)

Benign: Cystectomy or Unilateral Oophorectomy Borderline: Young patient: Cystectomy/ unilateral Oophorectomy Older patient: Bilateral salpingo-oophorectomy with hysterectomy and staging

breakdown of hCG curve by its units

Beta unit - has the curve, increases alot then decrese alpha unit - continuously increases

clinical presentation of a breast inflammatory carcinoma

CLINICAL PRESENTATION DUE TO INVOLVED DERMAL LYMPHATICS RESULTING IN AN ERYTHEMATOUS BREAST usually a stage 4 cancer

Nonpharmacologic Treatment/Prevention of Osteoporosis

Calcium intake 1200 mg/d-1500 mg/d Vitamin D 600-800 IU/d Regular weight-bearing, muscle-strengthening exercises Avoid smoking Identify and remove factors contributing to bone loss

histology of the breast

Ductules are lined by inner layer of epithelial cells and outer layer of myoepithelial cells Flattened layer of myoepithelial cells contain myofilaments Basement membrane follows contour of ducts and ductules Lobules are enclosed by a hormonally responsive loose myxomatous stroma (intralobular stroma)

Failed placental separation

Due to abnormal adherence of placenta to uterine muscle without intervening decidua types: Accreata/increata/percreata = diff stages - accreta: villi attach to myometrium - increta: villi penetrate myometrium - percreta: villi perforate serosa Associated with: placenta previa, uterine scar (C-section, curettage), submucous leiomyoma

Perinatal mortality: Fetal + neonatal mortality

EMBRYONIC: ≤10 weeks FETAL: between 10 weeks gestation and birth Statistically, fetal death is defined as intrauterine demise between 20 weeks and birth NEONATAL: first 28 days of life (4 weeks) INFANT: first year of life

abnormal uterine bleeding Organic abnormalities

ENDOMETRIUM: - Endometritis - Atrophy of the EM - EM polyps - Endometrial Hyperplasia / Carcinoma MYOMETRIUM: - Leiomyomata

2ry Outflow obstruction: Asherman's Syndrome

Endometrial lining scarred by surgery or infection The most common clinical antecedents are a curettage performed for pregnancy related hemorrhage (post partum or spontaneous abortion) or Endometritis due to tuberculosis or schistosomiasis are rare in the U.S Normal Hormonal Evaluation!!

endometrial epithelium histo

Endometrial: Proliferative type glands with columnar cells

Endometrial Carcinoma type I

Endometrioid Adenocarcinoma (80%)-type I Associated with *unopposed and prolonged estrogen exposure* *Obesity, Diabetes, Infertility, Hypertension (positive correlation)* Low-grade, usually presents with vaginal bleeding

estrogen effects on the circulatory system

Estrogen is a profound vasodilator

which treatment showed better outcomes in terms of CHD?

Estrogen only also better in breast cancer risk

Targeted/Biologic Therapy for breast cancer

Estrogen receptor as first biologic target Her 2 neu Many other new targets being identified Understand the signal Target the signal ? Clinical effect

Combined Hormonal Contraceptives: Mechanism of Action

Estrogenic: - Suppress FSH, LH Suppress ovulation - Endometrial changes at cellular level Progestin: - Suppress LH - Thicken cervical mucus - Inhibit capacitation of sperm - Endometrial changes

important placental hormones

Estrogens (from adrenal DHEA-S), Progesterone Chorionic Gonadotropin (hCG) Placental Lactogen (hPL)- anti-insulin, induces IGF in fetus --important for growth and other developmental processes

Combined Oral Contraceptives (COCs)

Ethinyl estradiol (20-35 mcg per pill) - All OCPs with <35 mcg - considered SAFE Progestin component varies can be Monophasic, biphasic, triphasic: referring to changing progestin amounts throughout the cycle

Contraceptive Vaginal Ring

Etonorgestrel (120mcg) and ethinyl estradiol (15mcg) daily 3 weeks in, one week off (labeling) Can remove for up to 3 hours - If ring is removed or expelled for 3 hrs, back-up contraception is necessary for 7 days *low first year failure rate* Cumulative monthly dose of estrogen lower than with OC or patch

limitations of MRI screening for breast cancer

Expensive, Long exam (30 minutes) Hormone dependent Claustrophobia Incompatible devices such as pacemakers and aneurysm clips Interpretation of another institution's MRI is difficult Repeat exam may be required High false positive rate

hormones of ovulatory cycle

FSH causes 2ry follicles (antral) to develop and proliferate and make estrogen once a Graafian follicle is chosen - alot of LH is released IGF-1 is also needed in the process - binds to insulin like receptors

explanation of glucose and insulin levels during pregnancy

Fasting glucose levels decrease because glucose is transported across the placenta to the fetus by facilitated diffusion, and amino acids actively transported to the fetus are not available for maternal gluconeogenesis. Lipolysis and ketogenesis increase, and fasting ketone and free fatty acid levels are higher. Fatty acids do not cross the placenta. Maternal insulin is bound and degraded by the placenta and does not cross into the fetal compartment. The fetus depends on its own insulin for glucose disposal; fetal insulin is produced by 12 weeks gestation.

when to do fetal testing for Rh

Fetal testing if father is heterozygous or unknown do amniocentesis or Chorionic villus sampling (CVS): Amnio preferred due to less FMH, avoid transplacental passage Fetal blood sampling: consider if amnio negative yet titers rise Cell-free fetal DNA: widely used in UK and Europe - testing the mom's blood

secretory phase of menstrual cycle

Fixed Day 14 to Day 28 (2 weeks) - always 14 days after ovulation Progesterone and Estrogen *Morphologic features in the secretory phase of the EM permit dating*

Ovarian carcinoma

Florid cellular proliferation giving rise to solid areas Nuclear atypia High mitotic activity Areas of necrosis Stromal infiltration = Metastatic potential

Requirements for Lactation

Fully developed mammary gland Prolactin Glucocorticoids Insulin Thyroid hormones ?Growth hormone *Estrogen withdrawal: estrogen has to be low*

Human Placental Lactogen (HPL)

GH and hPL gene family - regulation of maternal and fetal metabolism and the growth and development of the fetus. hPL: - is produced by the *syncytiotrophoblast*. - stimulates the production of IGFs, insulin, adrenocortical hormones, and pulmonary surfactant - *increases throughout pregnancy* - stimulates maternal lipolysis, making more fatty acids available for fuel during periods of fasting - *Is an Insulin antagonist: Increases glucose to the fetus*

what particular histo feature can be seen in neuroblastomas? aside from the stroma

HOMER-WRIGHT psudeorosettes the "lumen" in the rosettes is filled with neuropil

an evidence that HPV causes cervical caner?

HPV genome was found in cancer cells

HSV

HSV is the most common cause of genital ulcers

syphilis diagnosis

Have to do *2 tests*: Serology: non-treponemal tests: *RPR* or VDRL: - non-specific for screening = false + common - *titer falls with Rx, so RPR is good to see response to Rx* - if positive: do specific test Treponemal: - Specific, confirmatory: *stays positive after therapy* *after 1st infection, RPR is the only way to check for re-infection*

what is gonadal dysgenesis (turner syndrome)

Having 45 X0 karyotype - most have a webbed neck, low estrogen germ cells don't migrate to the gonadal ridge on time (either to early or too late) - leads to person having the genitals, but follicles (or tubes) are degenerated and therefore no estrogen and no period, breasts, etc give pts estrogen

benign causes of scrotal masses

Hernia Hydrocele - enlarged with fluid varicocele - enlarged veins spermatocele - cystic dilatation of the epididymis

hypogonasidsm - abnormalities that point to certain issues

High T, low FSH, low LH - exogenous Low T, high FSH, high LH - testis failure All low + high prolactin - pituitary adenoma or other CNS lesion (MRI brain!!!) Other abnormalities can point to certain solutions - *low T, high E2 - weight loss, Arimidex*

what are the type 2 ovarian cancers

High grade Serous High grade Endometrioid MMMT ( carcinosarcoma) Undifferentiated carcinoma

Major Maternal Hormonal and Metabolic Changes during Pregnancy

Higher estrogen and progesterone Low LH and FSH Increasing prolactin *High total T4, normal free T4 and TSH* Increased total and free cortisol *Lower fasting glucose, increased post-prandial glucose* *Higher postprandial insulin; increased insulin resistance*

Penile Injection Therapy: Advantages

Highly effective 80% even after PDE-5 failure Mimics natural physiology of erection No effect on sensation, ejaculation, fertility Higher level of discretion, thus spontaneity

1st step in amenorrhea evaluation:

Hx including: Age, onset, family history, diet, health, medication, exercise, cyclic pain?, Symptoms? Followed by P.E: Height/weight, Galactorrhea, Growth curve, Secondary sexual characteristics, Hirsuitism, acne, Tanner staging Labwork: hCG, FSH, LH, Estradiol, Prolactin, TSH

criteria for diagnosis of hypertensive pregnancy disorders: HTN

Hypertension: - Systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg

amenorrhea due to Hypogonadotropic Hypogonadism

Hypothalamic Level - Failure to attain/maintain critical levels of body fat - Severe stress - Severe systemic illness - Syndrome of anosmia and GnRH deficiency - Constitutional delay - Tumor Pituitary Level - Large pituitary tumors - Hyperprolactinemia

what phyllodes tumor features suggest it is a malignant one

INCREASED STROMAL CELLULARITY, MITOTIC FIGURES AND NUCLEAR PLEOMORPHISM RAPID INCREASE IN SIZE

drug use and cigarrette smoking cause

IUGR - intra uterine growth restriction

precocious puberty can be caused by

Idiopathic Estrogen, Androgen or HCG producing neoplasm CNS lesions McCune-Albright syndrome Hypothyroidism

Eugonadotrpic amenorrhea due to anatomic features

Imperferate Hymen-Failure of the hymen to canalize -Accumulation of blood in vagina, uterus -Surgical correction Tranverse Septum- Failure of Mullerian derived upper vagina to fuse with UG sinus derived lower vagina - Surgical correction Meyer-Rotansky-Kuster-Houser Syndrome -Mullerian agenesis- Can be complete or partial. - Missing upper 2/3 of the vagina and Uterus-

placental development

Implantation - day 7 (2nd week) Chorionic villi - Primary CV (trophoblast), day 12 - 14 (2nd week) - Secondary CV (mesenchymal core), day 16 - Tertiary CV (blood vessels), day 21 (3rd - 5th week)

what did testing for euploidy in IVF lead to (discovery wise)

Implantation Rate of Euploid Embryos is Independent of Age: Aneuploidy is the cause of the age-related decline in fertility

infertility definition

Inability to conceive within 1 y of unprotected intercourse Affects 10%-15% of reproductive-age couples in the US 50% of healthy couples under the age of 40 will be pregnant after 6 mo Often seen as "life crisis": up stress - bad for HPO axis

adrenarche

Increase in adrenal androgen production *(DHEA, DHEAS)* Clinical development of pubic and axillary hair Begins at about six years of age in both girls and boys *Unrelated to the pubertal maturation of the neuroendocrine-gonadotropin-gonadal axis*

Osteoporosis - Risk Factors

Increased risk - female, advanced age, previous fracture, estrogen deficiency, cigarette smoking, cortisone use, sedentary lifestyle Decreased risk - African-American race, obesity (BMI >30 kg/m2), current or past use of estrogen, regular exercise

Effects of Increased Estrogen During Pregnancy

Increased: - Hepatic protein synthesis, heart rate, stroke volume, cardiac output, uterine blood flow, blood volume, coagulation factors, renal perfusion, creatinine clearance Causes: - Peripheral vasodilation - *Physiologic anemia*

Effects of Increased Progesterone during Pregnancy

Increased: - Minute ventilation Decreased: - Intestinal motility, uterine contractions Causes: - Compensated respiratory alkalosis, smooth muscle relaxation, lower sphincter relaxation, urinary collecting system stasis

effects of estrogen on blood and fat distribution

Increases: Blood clotting factors, blood coagulation, HDL cholesterol, triglyceride turnover, hepatic-binding protein synthesis, renin substrate Decreases: Bone resorption

placental circulation abnormalities

Infarct Toxemia of pregnancy Hydrops placenta

maternal complications of PTL

Infection related to prolonged cervical dilation or ruptured membranes Chorioamnionitis - bacterial, usually polymicrobial Hemorrhage Morbidity related to operative delivery

the umbilical cord

Insertion - Eccentric (80%) - Central (5%) - 2 arteries and 1 vein

Other means to transfuse a baby other than fetal blood sampling

Intrahepatic vein Intracardiac: loss rate of 8%, LAST RESORT

Injectable Contraception: Depo MedroxyProgesterone Acetate (DMPA)

Intramuscular (IM) injection or Subcutaneous injection: 104 mg every 3 months, *not great one year continuation rates* (25-53%) When to start: - Within 5 days of menses - Every 11-13 weeks thereafter

other (than PDE5i) treatment options

Intraurethral agents - MUSE (alprostadil) prostaglandin E1 Intracavernosal agents - Caverject, Edex (injectable prostaglandin E1) - Bimix - compounded mixture of papaverine and phentolamine - Trimix - same + prostaglandin

Treatment Options for infertile

Intrauterine insemination Ovulation induction Clomiphene citrate Gonadotropins In vitro fertilization (IVF)

nexplanon side effects

Irregular bleeding likely - can vary over time in same woman Pain at insertion site Progestin side effects

Ovarian Cystadenoma

Lining epithelium of the inclusion cyst undergoes metaplasia to become serous or mucinous Single layer of epithelium lines the cyst cavity Tumors can become massive, usually filled with serous or mucinous fluid depending on the type of lining epithelium or with blood in case of endometrioma 5 year survival: 100%

manifestations of CMV baby

Manifestations: hepatosplenomegaly, loss of vision, hearing loss, seizures, mental retardation, thrombocytopenia, hepatitis, DIC presentation: Diffuse jaundice Non-blanching petechial and purpuric skin rash Hepatosplenomegaly

Penile Implant Surgery

Mechanical Malfunction - Failure rate of 5%/year; avg lifespan of just under ten years Infection - down to 1-2% in large series Poor patient satisfaction - Complaints typically include size

POC's: Mechanism of Action/Benefits

Mechanism of Action - Suppress ovulation (some methods) - Thicken and decrease cervical mucus - Endometrial changes/ atrophy Benefits - Few contraindications - Breastfeeding: no inhibition - Control of menorrhagia

PCOS HPI shows as

Menstrual irregularity/annovulatory bleeding--rarely presents as primary amenorrhea 50-90% oligoamenorrheic (<9 periods/yr) Hirsuitism Weight gain symptoms usually begin at puberty and are slowly progressive--if acute, R/O tumor

Testis Tumors

Most common cancer in men: 25-40 yrs old Presents with *painless enlargement of testis* or with metastasis Wide spectrum of cellular differentiation - complex classification *very susceptible to chemotherapy, so even if metastasize outcome could be good*

Congenital Cytomegalovirus Infection

Most common hematogenous infection of the fetus Most mothers are asymptomatic Most infants asymptomatic biggest risk: primary maternal infection

Embryonal Rhabdomyosarcoma

Most common rhabdomyosarcoma subtype (65%) Children ages 3-10 years - affects hollow cavities nasal and oral cavities, orbit, middle ear, prostate, paratesticular region intermediate prognosis

genital herpes simplex

Most infections undiagnosed 2° mild illness Many cases transmitted by persons unaware they are infected or when asymptomatic risk of sexual & perinatal transmission Link between HSV and HIV 70% of transmission during *known*asymptomatic periods

immature teratoma

Most patients *under 20 yrs of age* Mature and immature elements from three germinal layers. *Immature neural tissue common*. Grows rapidly, can rupture in peritoneal cavity or metastasize to lymph nodes, lung, liver. Treatment: Surgery + chemotherapy.

preventive factors for ovarian cancer

Oral contraceptive pills: 5 year intake is supposed to reduce the risk of ovarian cancer by 50% Hysterectomy and tubal ligation: Possibly by reducing pelvic inflammation by eliminating access to genital flora or other environmental factors.

Testosterone Replacement Therapy: Adverse Events

Oral tablets - Effects on liver and cholesterol (methyltestosterone) - Associated with myocardial infarction and stroke Pellet implants: requires surgery *Intramuscular injections* - Fluctuation in mood or libido - *Polycythemia (especially in older patients)* Gel: can transfer to partner, children

Hypogonadism

Oral treatments - not available in US (consider clomid) - *increases FSH, LH* Transdermals - patches, gels (Testim, Androgel) Injectable - Testosterone cypionate, Aveed Long term - Testopel Monitor - free and total testosterone, LH, CBC, PSA, Fasting Lipids, Hepatic Panel

abnormal uterine bleeding

Organic abnormalities DUB (Dysfunctional Uterine Bleeding): things that we cannot see & cause the woman to bleed in between normal cycles - usually due to hormonal inbalance

Serum markers for ovarian Tumors

Ovarian Carcinoma: CA-125 - not very reliable Granulosa Cell Tumor: Estradiol, Inhibin and AMH Choriocarcinoma: HCG Yolk sac tumor: AFP

Causes of Amenorrhea ovary level

Ovarian dysgenesis (Turner's) Androgen insensitivity Syndromes Chemotherapy/Radiation damage Autoimmune disease Chronic Anovulation-PCO

Meig's syndrome:

Ovarian fibroma with ascites and pleural effusion

Alveolar rhabdomyosarcoma genetics

PAX-FKHR(FOX01) Translocation PAX3 fusion: 50% = bad prognosis PAX7 fusion 20% = better prognosis

ovulation induction is used for

PCOS Hypothalamic amenorrhea - Hyperprolactinemia - Hypopituitary Thyroid disorder - Adrenal disorder

PCOS:EPIDEMIOLOGY

PCOS is the most common endocrine problem in young women Occurs in 5-10% of reproductive age women in the US There is a familial link but is probably polygenic clear link between hyperinsulinemia and androgen excess.

marker in the blood that tells about prostate enlargement

PSA - prostate specific antigen not specific to cancer; can be high in BPH

when to use fine needle aspirations

Palpable lesions: breast, thyroid, salivary gland, soft tissue Deep lesions (CAT scan, ultrasound or MRI guidance): liver, pancreas, bone, lung, retroperitoneum, brain Mammographic guidance by stereotaxic aspiration

cervical cytology guidelines

Pap smear recommended every 3 years in women ages 21 to 65 High grade Squamous Intra-epithelial lesion (HGSIL): Colposcopy and Biopsy Low Grade Squamous Intra-epithelial lesion (LGSIL): HPV testing -High Risk HPV positive- Colposcopy and Biopsy -High Risk HPV negative- 3 monthly Paps until these return to normal for 2 years.

Embryonal Carcinoma

Peak age = 30 years Macro: Varied appearance, hemorrhage & necrosis Micro: *Sheets, papillary or glandular patterns, marked anaplasia (variation in nuclear size and shape)* *Keratin expression* + (immunohistochemistry) [neg in seminoma]

Postpartum Psychiatric Disorders

Postpartum Blues (40-80%) Postpartum Depression (4-9%) - if had it in one pregnancy, very likely will in another Postpartum Psychosis (.1-.2%)

Intrauterine Contraception: Insertion and candidate selection

Postpartum: Await uterine involution (At least 4 weeks) post placental: within 10 mins of placental delivery Candidates for use: - Women at low risk for STD (multip OR nullipara) - Long-term, reversible contraception - Co-existing medical conditions contraindicating systemic hormonal methods

placental abruption

Premature separation of placenta after 20 weeks, secondary to rupture of maternal vessels *Painful* 3rd trimester bleeding Marginal - vaginal bleeding Central - *retroplacental hematoma* Higher incidence of: toxemia, HTN

what is Precocious Puberty

Premature sexual development, which occurs at an age more than *2.5 SD below the mean age of puberty* Defined as the onset of pubertal development in *girls before age 8 and in boys before age 9*

PPROM is...

Preterm premature rupture of membranes water breaks early

syphilis treatment

Primary/Secondary: penicillin - *Benzathine 2.4 mu x 1 or tetracycline x 14 d (PCN- allergic)* tertiary - Benzathine PCN x 3 weekly doses Special considerations - *Jarisch-Herxheimer reaction* may occur w/in first 24 hrs: when spirochetes lyse from effective treatment -> cytokine storm: shaking chills, fever, headache

Low Testosterone (Hypogonadism): Types and Causes

Primary: testicular failure Secondary: hypothalamic or pituitary dysfunction Combined: decreased pulsatility of gonadotropins plus decreased Leydig cell response Congenital (eg, Kallman's syndrome) or acquired (eg, pituitary adenoma)

important factors when taking history (female)

Prior pregnancies, fertility in other relationships Gynecologic history (pelvic inflammatory disease [PID]; endometriosis; fibroids; cervical dysplasia; intrauterine device [IUD] use; previous pelvic or abdominal surgery) Menstrual history (age at menarche, cycle length and regularity); presence of hot flashes *Diethylstilbestrol (DES) exposure*, cigarette smoking frequency of intercourse

Progestin Only Contraceptives

Progestin only pill (POP) Depo MedroxyProgesterone Acetate (DMPA) Nexplanon Progestin IUS - Mirena - Skyla

Emergency Contraception types (4)

Progestin-only pills Combined pills Copper IUD: insert within 120 hours Selective Progesterone Receptor Modulator (SPRM)

causes of hyperprolactenemia

Prolactin secreting pituitary tumors -microadenoma (<10mm) macroadenoma (>10mm) Primary hypothyroidism Medications that affect dopamine Acromegaly

Borderline Tumor

Proliferation of epithelial lining gives rise to some solid areas Can shed epithelial cells from its surface No stromal infiltration Can not metastasize Recurs 5 year survival up to 90% even with peritoneal involvement: death due to non-malignant complications like bowel obstruction

What would be expected on the endometrial histo of annovulatory cycle?

Proliferative endometrium with breakdown

other treatments for PE

Promescent - topical lidocaine that numbs nerves, but not the ones involved in pleasure

signaling used by the parasympathetic nerve to start erection

Prostaglandin E1 Acetocholine NO

PCA3

Prostate CAncer gene 3 biomarker that measure RNA in urine: is a non coding RNA

Contraindications of Testosterone Therapy

Prostate cancer Breast cancer Advanced prostate obstruction with voiding disorder

Lactation

Protects fetus from infection Decreases fetal allergies Optimal development of vital organs Ideal "formula"

type 2 ovarian cancer

Rapidly growing and high stage at presentation Precursor not identified seems to start fellopian tube epithelium involved, not incesant ovulation theory. by the time the tumor reaches the ovary is already very malignant

pregnancy and the kidneys

Renal (Creatinine clearance increases by 50%)

hCG functions

Rescues the CL Secreted by syncytiotrophoblasts Maintains corpus luteum steroidogenesis until the placenta assumes this role (7-10.4 weeks) Appears to stimulate fetoplacenta unit steroidogenesis Has thyrotropic activity (.025% of TSH)

fetal/neontal complications of PTL: risk is inversely related to Gestational Age at delivery

Respiratory distress syndrome (hyaline membrane disease) Bronchopulmonary dysplasia Intraventricular hemorrhage (brain) Retinopathy of prematurity Hyperbilirubinemia Sepsis Adverse neurodevelopmental outcomes

what drugs cause retinopathies

Retinoic acid derivatives treatment for acne and psoriasis

Initial Assessment for infertility

Review couple's ages Review previous pregnancies Time attempting pregnancy Coital frequency History and physical

Rh alloimmunization

Rh (D) antigen generally elicits a strong immune response in Rh(D) neg, but it is variable The likelihood of mounting a response depends on: - VOLUME - TIME since exposure - FREQUENCY of exposure *Response develops slowly*

Embryopathies due to Maternal Factors

Rh disease/hemolytic disease of fetus and newborn - hydrops fetalis Autoimmune diseases - lupus, myasthenia gravis Maternal Diabetes

Birth Control & Antibiotics

Rifampin is the ONLY antibiotic ever shown to interfere with levels and effectiveness.

ED due to neurogenic factors

Risk factors - *Diabetes, Prior radical pelvic surgery (prostatectomy, cystectomy), concomitant neurological disorder* Prostatectomy - 80% chance of return of function after two years assuming: - Good erectile function prior to surgery - Nerve-sparing operation

ED due to vascular reasons

Risk factors - hypertension, hyperlipidemia, diabetes, coronary artery disease, peripheral vascular disease, smoking history ED is an important future predictor of CAD and/or stroke 2.5x higher risk (= to smoking or family history)

ED due to hormonal factors

Risk factors - obesity, *diabetes (metabolic syndrome)*, prior injury to testis Secondary causes important to recognize as well - thyroid abnormality, hyperprolactinemia, anabolic steroid use

endometrial hyperplasia (organic abnormality)

Significance: the early part of a spectrum of changes that *starts from simple hyperplasia and culminates in endometrioid adenocarcinoma* Perimenopausal age Associated with prolonged exposure to unoppposed estrogen (so strats with DUB) Definition: Increase proliferation of endometrial glands, which result in ↑ gland : stroma ratio

Intracavernosal Injection

Smooth muscle-relaxing medication injected directly into the penis (PGE1)

clinical features of invasive cervical carcinoma

Spotting or bleeding Post Coital bleeding Abnormal Pap Advanced case: Uremia

cytology of breast fibroadenoma

Staghorn cohesive clusters of epithelial cells (purple) stromal fragments (magenta) myoepithelial cells

placenta does:

Supportive- embryo implantation into the uterus and transporting nutrients and oxygen necessary for fetal growth Immune- suppressing the local immune system Endocrine- including hormone synthesis, transport, and metabolism to promote fetal growth and survival Inability of the placental unit to perform these functions leads to multiple complications of human pregnancy, including abortion, impaired fetal growth, and preeclampsia Healthy placenta=Healthy baby

PCOS Treatment: goals

Suppress the ovarian androgen Cycle control or pregnancy(as desired) Eliminate unwanted hair growth, hair loss, acne Weight control /regulate Metabolic needs Life-style modification: Diet, Exercise Protect the endometrium

Levonorgestrel IUS MOA

Suppresses endometrium, thickens cervical mucus *Does not reliably suppress ovulation* Pregnancy rate 0.1/ 100 women/year Reduces menstrual blood loss by 90% no long term effect on fertility

ovarian tumor types and incidence breakdown

Surface Epithelial tumors: 75% Germ Cell tumors: 15% Sex-Cord Stromal tumors: 10%

cytology vs biopsy

Surface cells have higher nuclear/cytoplasmic ratio in severe dysplasia than in mild dysplasia. This difference is relied upon in Pap smear evaluation. Pap smear finding of high grade SIL (Squamous Intraepithelial lesion) usually correlates with biopsy finding of CIN III. However, there are cases in which there is a lack of correlation between cytology and biopsy findings. A biopsy is therefore usually done in managing patients with low grade or high grade SIL.

treatment for ovarian surface epithelial tumors (carcinomas)

Surgery: Debulking and Staging (TAH - total abdominal hysterectomy) TAH/BSO, pelvic and peritoneal biopsies, omentectomy, para-aortic and pelvic lymph node dissection for staging Aspiration of ascites, pelvic wash, biopsies from paracolic gutters, surface of diaphragm for staging Adjuvant Chemotherapy: Combination of a platinum compound (carboplatin/cisplatin) and a taxane (paclitaxel/docetaxel)

how to remember infectious agents that get through the synctytophoblasts

TGRs Can Have Such Mean Varicella

vaginal cytology after menopause

The vaginal surface becomes thinner, less elastic, and more friable. Fewer vaginal secretions are produced, and production is delayed longer during sexual stimulation *loss of rugal folds*. The most common symptoms of vaginal atrophy are *vaginal dryness, itching, and burning but may include dyspareunia and leukorrhea (yellow malodorous discharge).* Thinning of the mucosal lining of the urethra and bladder may result in urethritis accompanied by frequency, urgency, and dysuria

toxemia of pregnancy: events

There are events of primary importance in this disorder: 1) placental ischemia → 2) HTN → 3) DIC (disseminated intravascular coagulation) The causes of the initial events in toxemia are unknown, but evidence points out to an abnormality of placentation. This may involve both an abnormality in both trophoblast invasion and the development of the physiologic alteration in the maternal vessels required to perfuse the placenta adequately. This results in placental ischemia, the basis of the toxemic placenta.

TORCH(ES) Infections

Toxoplasmosis Other: Parvovirus B19, Varicella zoster, Listeria Rubella Cytomegalovirus HErpes virus Syphilis

Morphologic Parameters in Cytologic Evaluation: cellularity

Transudate: accumulation of fluid due to increased hydrostatic or osmotic forces (low cellularity) - e.g - CHF edema Exudate: accumulation of fluid due to inflammation with increased capillary permeability (high cellularity)

menopausal hormone therapy (MHT) who to treat

Treatment of moderate-to-severe vasomotor symptoms associated with menopause Treatment of vulvar and vaginal atrophy Prevention of postmenopausal osteoporosis

partial (incomplete) mole genetics

Triploid (1materal +2 paternal haploid set) Dispermy Monospermy (1 sperm, unreduced paternal genome)

Mature cystic teratoma (dermoid cyst)

Tumor differentiation towards all three germ cell layers *Skin is the most common tissue seen* *46XX* Rarely malignancy may arise in one of the elements of tumor tissue ( in older women) *Squamous carcinoma is the most common type of carcinoma arising in dermoid cyst* (since skin is the most common tissue seen)

serous ovarian tumors

Very commonly bilateral - Serous cystadenoma (60%) - Borderline serous tumor (15%) - Serous adenocarcinoma (25%) Low Grade serous adenocarcinoma (Type I cancer) High grade serous adenocarcinoma (Type II cancer)

Sertoli-Leydig Cell Tumor

Very rare ( 1% of all ovarian tumors) Low malignant potential/ may metastasize *esemble embryonic testis* Secretes weak androgens : *Virilization with large tumors*

PDE5 Pharmacology

Viagra, Levitra, Stendra, and Cialis - Enable smooth muscle relaxation in the cells of the penis, but has to have already occured Similar side effects - - Headache, flushing, congestion, color vision change, muscle ache, priapism, hearing loss - most are due to effects on other PDE's in the body that affect other SM cells (e.g muscle aque bc of PDE11 with *cialis*, color vision due to PDE6 with *sildenafil*) cialis: 36 hours

Hypothalamic Amenorrhea: Weight

Weight loss below a certain target level (approximately 10 percent below ideal body weight) Exercise Marked interpatient variability in the degree of weight loss or exercise required to induce amenorrhea Nutritional deficiencies --Fat restrictions

Hypogonadism - besides testosterone, what else to check

What else do I check in symptomatic patients? - Follicle stimulating hormone (FSH) - Luteinizing hormone (LH) - *Estradiol* - Dihydroepiandrosterone (DHEA) - Prolactin What else might I check - *thyroid panel*

when its parasympathetic signal to penis

a cAMP and cGMP protein kinase drives all the Ca into the ER this then gets turned off by PDE5 (Phosphodiesterase type 5)

A very high HCG level may indicate

a trophoblastic tumor such as a hydatidiform mole or a choriocarcinoma.

errors of morphogenesis

abnormal formation of tissue abnormal forces on normal tissue destruction of normal tissue

any delivery before 20 weeks is considered...

abortion

adenocarcinoma of the cervix

about 10% of cervical carcinomas HPV 18 is frequently detected characterized by gland formation

in males, in relation to the mesonephric duct, where does the ureter attach to the bladder

above the duct

example of what can lead to PTL

activation of maternal-fetal HPA axis (like stress) inflammation (infections can do it) pathologic uterine distension (the more the uterus is stretched, the more likely it is to contract = plyhydramnios, multifetal pregnancies, uterine anomalies)

testosterone bound to SHBG

acts as a reservoir, only tapped into if the other two (albumin, free) are too low

toxemia can lead to

acute atherosis *there is no absolute correlation between the severity of eclampsia and the magnitude of the anatomic changes*

risk factors for ovarian cancer

advanced age, rare under 30 Early menarchy and late menopause Nulliparity HRT - hormone replacement therapy Endometriosis Weight, talc, smoking, radiation

cervical cancer highest mortality rate by race

african americans followed by hispanics

fall of hormones post partum

after 3 days, estrogen and progesterone levels go back to normal prolactin levels start to increase alot: & remember that prolactin inhibits estrogen and progestorone

prostate cancers are mainly dependent on

age and endocrine specially on testosterone

Gonadal dysgenesis (turner's syndrome)

aka: failure of ovarian production 45,X (50%) 45,X 46,XX or 46,XY or other Mosiac (25%)

known main teratogens

alcohol, cocaine androgens (high doses) diethystilbestrol isotretinoin, phenytoin (delantin) tetracyclin, thalidomide Valproic acid CMV, Rubella, Herpes

other than estrogen, what other drugs can we give to treat the osteoporosis

alendronate, tebolone tamoxifen, raloxifen (SERMS)

Alpha Fetoprotein (AFP) Levels in Amniotic Fluid and Maternal Blood

alpha fetoprotein is the fetal albumin. made in the fetal liver. A small amount gets into the mother's blood. In NTDs (neural tube defects) and other body integrity defects, larger amounts of AFP get into the amniotic fluid and are also measurable in maternal blood. In Down syndrome, AFP is decreased, presumably because the fetus is smaller than usual.

stimulation and cells of mammary glands

alveolar cells: stimulated by prolactin myoepithelial cells: stimulated by oxytocin

Alveolar rhabdomyosarcoma histo

alveolar or lepidic pattern of growth will typically have anaplasia, high mitotic activity and may have intratumoral necrosis

PCOS hormone levels

always high LH usually low FSH high estrogen and testosterone

DMPA: Side effects

amenorrhea in most cases (alot of people like this) Irregular bleeding Weight gain *Changes in bone mineral density (BMD)* - bounce back after quitting Delayed return to fertility (7-9 months avg) *Lipids: decreased HDL, increased LDL*

definition of amenorrhea

an abnormal absence of menstruation.

65% of people with primary amenorrhea will have ____

an abnormality that they are born with. Chromosomal mutation or absence of uterus compare to 3% on secondary

polycythemia wiki

an abnormally increased concentration of hemoglobin in the blood, through either reduction of plasma volume or increase in red cell numbers. It may be a primary disease of unknown cause, or a secondary condition linked to respiratory or circulatory disorder or cancer.

two cell theory

applies to when there is an LH surge leading to progesterone and estrogen secretion (luteal/ secretory phase) remember its secretory bc endometrium secretes

breast atypical ductal hyperplasia

architectural and cytologic atypia: cells become bigger, high N/C ratios, become more rounded cells fail to entirely fill the lumen usually calcified

the testis

are covered by the *tunica albugenia* everything that enters or leave happens in the *mediastinum of the testes* = the posterior surface - because the anterior surface is covered by the *tunica* *vaginalis* from the testes descent are devided into lobules, and each lobule contains the *seminiferous tubules* - each lobule = 1-4 seminiferous tubules

association syndromes

are due to contiguous gene deletions affecting unrelated things Williams syndrome: where elastin gene deletion leads to cardiovascular problems but many have hypertension, cocktail party personality and/or mild to moderate mental impairment due to other gene deletions.

liquid based pap smear cytologic methods (SUREPATH)

are liquid based wash off background debris can do HPV testing on vials can also test for gonorrhea and chlamydia

semineferous tubules

are sitting in very rich connective tissue where spermatogenesis occurs: - takes us from a *spermatogonia to a spermatozoa*

Embryonal Rhabdomyosarcoma histo

areas of hypo- and hypercellularity has "tadpole cells" - have a eosinophilic tail - this is from rhabdomyoblastic differentiation

at what stage does the embryo implant? usually..

at the blastocyst stage After fertilization, the early embryo spends 3 days in the ampulla of the fallopian tube and divides to reach the 8-cell stage (morula). An additional 2-4 days (so 7 after fertilization) are spent floating in the uterine cavity which allows for development of a secretory endometrium, the loss of the zona pellucida (hatching), and further cell division to reach the blastocyst stage

breast atypical hyperplasia types

atypical ductal hyperplasia atypical lobular hyperplasia 5X risk of breast cancer

besides the turning on of oncogenes, what else has been found in HPV infected cervical cells?

atypical mitosis, specially in HPV 16/18

NON-ARTERITIC ANTERIOR ISCHEMIC OPTIC NEUROPATHY (NAION)

bad side effect of PDE5 drugs the optic nerve looses blood flow - leads to blindness Characterized by sudden painless unilateral visual loss No proven effective treatment; prophylaxis also unproven

why elevated AMH in PCOS?

bc AMH is a sign of follicle maturing, these people have many of those, therefore elevated AMH

why is treating testicular infection difficult?

bc the sertoli cells dont allow the immune system to come in

why do we give progesterone too?

bc unopposed estrogen would cause too much endometrial proliferation

why is the pelvic exam so important for PCOS?

because if clitoromegaly is found, it means that most likely it isn't PCOS

why do you always see some blood right under the endometrium surface?

because of the spiral artery capillares draining into the lacunae

what happens to the paramesonephric duct remnants (male)

becomes the prostatic utricul and the appendix of the testes

age dependent feedback sensitivity for estrogen

before puberty the hypothal is very sensitive to estrogen; later it becomes less sensitive to the feedback and so more GnRH is released

molecular subtypes of breast cancer: best and worst prognosis

best: luminal subtype A worst: basal subtype (has no receptors, we dont really know how to attack) - triple negative (er,pr, Her2neu)

chorionic and decidual plate histo

between the anchors are "bushy villi", they are all part of the anchoring villi there is maternal blood in btwn them

role of E7

binds to Rb immortalized keratinocytes

effect of estrogen on celiated and Peg cells

both cell types hypertrophy, become taller, cilia get longer

what happens to the corpus luteum if no fertilzation

breakdown - Corpus Albican remmnants stay around for a while

order of female puberty changes

breasts --> pubarche -->growth spur --> menstruation

shortening of the cervix

called effacement, also by prostaglandins

Chronic Endometritis (inflammation)

can be part of Chronic Pelvic Inflammatory Disease can be due to Post-partal or post-abortal endometrium due to retained POC can happen in Patients with Intra-uterine device (IUD) Tx: Remove offending cause

what to use for er+ or er/pr+ breast cancers?

can be treated with tamoxifen (anti-estrogen that blocks estrogen receptor) or arimidex(aromatase inhibitors)

chorions in twin gestation

can be: - dichorionic diamniotic with fused placenta (early split) - dichorionic diamniotic (early split) - monochorionic diamniotic (split when blastocyst) - monochorionic monoamniotic (least common, dangerous)

Leiomyomas (degeneration, macroscopic and microscopic)

can get so big that outgrow blood supple - ischemic changes see areas of necrosis and hemorrhage

what can happen in areas of endometriosis?

can give rise to any malignancy that can happen to normal endometrium

possible complication of ovarian non-neoplastic cysts

can potentially cause intra-abdominal hemorrhage/peritonitis secondary to rupture or torsion

WHY CAN CYTOLOGIC STUDIES BE USED IN THE ASSESSMENT OF CANCER ?

cancer leads to unregulated cellular proliferation and nuclear dysfunction: - nuclear membrane irregularities - increased nuclear to cytoplasmic ratio - hyperchromasia and abnormal mitotic figures - disordered cell differentiation - Cancer cells are less adhesive than normal cells and therefore are preferentially shed so they are detected in cytologic samples

what goes into placenta through active transport

carbs, amino acids, vitamins, some ions

what happens with Rh? (2 babies)

case: mom is Rh -, baby Rh + : bloods mix mom makes antibodies to the Rh + mom has another baby who is Rh+, bloods mix mom's blood antibodies attack babies Rh + cells: no good

condyloma of the vulva

caused by low risk HPV (so 6/11)

dilatation of the cervix

caused by the contractions (oxytocin) and aided by prostaglandins

cells in the oviduct epithelium

celiated cells Peg cells - thin and inbtween celiated cells - secretory cells

Herpes on pap smear

cell nuclei get a molty look Ground glass appearance

1ry oocytes histo

cells become cuboidal can be multilaminated - more than one layer of cuboidal cells at this stage its making the zona pellucida

Hofbauer cells

cells in the placental villi that act like macrophages

invasive lobular carcinoma (ILC) of the breast histo

cells penetrate in a single file pattern have to do wide excisions around it strands of infiltrating tumor cells

what happens to the myometrium during gestation

cells proliferate, become much bigger used for contractions under control of prostaglandin and oxytocin

normal pap smear

cells with lots of cytoplasm pink cells are more superficial blue are more basal

histology of fibroadenoma

cellular fibroblastic stroma enclosing glandular cystic spaces lined by epithelium

what does CIN refer to

cervical intraepithelial neoplasia seen in BIOPSY ranges from I to III

toxemia of pregnancy

characterized by triad of symptoms. 6% of pregnant women, *in the last trimester and more commonly in primiparas than multiparas* preeclampsia (HTN, proteinuria, edema) eclampsia (preeclampsia plus convulsions) Associated with placental abruption and infarction

what is PID (pelvic inflammatory disease )

chronic salpingitis with involvement of surrounding structures including ovary and parametrium *characterized by exacerbations of acute episodes*

what is atonic uterus

closure of blood vessels contingent w/ uterus's ability to contract if no closure of blood vessels uterus unable to contract maternal blood vessels won't close -> lots of bleeding -> requires hysterectomy

what is an important effect of large levels of estrogen in puberty?

complete *epiphysial fusion* leading to *"capping" of growth* important bc people who develop to soon bc you may cap growth early

endometrial polyps

composed of variable sized glands, some cystically dilated usually have *thick walled blood vessels* and fibrotic stroma

Penis

composed of: Corpus cavernosum Corpus spongiosum: is also the transfer for the penile urethra

when it is just dysplasia (even high grade) treatment is usually:

cone biopsy

what can mimic the clinical presentation of PCOS?

congenital adrenal hyperplasia (21 hydroxylase deficiency)

what happens to the mesonephric kidney under the influence of testosterone

connect the testes to the mesonephric duct and then becomes the efferent ductual, epididymis, vas deference, seminal vesicles, and shared common ejaculatory duct

what is good about the basement membrane of the lobules? (in terms of breast tumors)

contains the tumors, until a tumor breaks the membrane it can't really go anywhere

in absence of MIF, the paramesonephric duct will

continue to develop as parts of the female repro system

PCOS:PATHOPHYSIOLOGY

cycle: start isnt known: hyperinsulinemia is associated with lower SHBG and higher free testosterone insulin may stimulate LH secretion Insulin may also have hypothalamic effects and direct appetite stimulation insulin has been shown to augment adrenal androgen production

facts about gonadotropin releasing hormone (GnRH)

decapeptide Pulsatile secretion "The pulse generator" for GnRH is located in the arcuate nucleus of the medial basal hypothalamus Half-life 2-4 min Secretion begins at gestational week 4 Levels remain low until puberty

what is the tunica albugenia (thin in the case of women) made of?

dense connective tissue

HSV: Diagnosis and Treatment

diagnose by *PCR* treat: - for 1ry disease: neucleoside analog (acyclovir) - Started within 72 hrs may duration & severity - Recurrent: nucleoside analogue for 5 d - Suppressive: daily for *> 6 recurrences/year* Counsel about asymptomatic shedding HIV may require increased doses

lichen sclerosus ET atrophicus

disease of old age atrophic and itchy valvular skin on histo: dense collagen below the epithelium

leukoplakia of vulva

disease of old age white patch in vulva biopsly to rule out dysplasia

how to asess estrogen status?

do they have breasts? then they have had estrogen labwork can show estrogen ultrasouns of uterus: thick endometrium - estrogen (proliferative)

Graafian (pre-ovulatory) follicle histo

dont see proteins in the antrum - yet there is plasminogen, glycosaminoglycans oocyte is in a stalk called cumulus oophorus and surrouned corona radiata

what interferes with GnRH pulses

dopamine, norepinephrine, endorphins leptin, neuropeptide-Y

what happens if both paramesonephric ducts dont fuse & both touch the urogenital sinus

double vagina

trisomy 21

down syndrome have simian crease and characteristic face Life expectancy 60 years 40-50% CHD Mental impairment (IQ 50) 75-80% spontaneously abort, 2/3rds electively aborted

Delantin (phenytoin)

drug for epilepsy causes Fetal Hydantoin Syndrome (Dilantin Embryopathy) challenge of treatment - bc you have to treat the epilepsy regardless

when do most preterm births happen?

during the late period: 34-36 weeks

how come, the dominant follicle has alot of FSH recptors yet makes the highest amount of estrogen? knowing that estrogen turns of the FSH produciton

during this part of the cycle, estrogen switches to positive feedback instead of negative feedback

what happens to the paramesonephric duct in females - in terms of migration and movement

each duct (one on each side) will come to the center and meet each other and touch on the urogenital sinus this induces the urogenital sinus to send a "bud" out into the parameso duct - hellps form the vagina

peaks in incidence of ped tumors

early on: 0-5 y.o - primitive derived tumors: neuroblastoma, wilms tumor, retinoblastoma, primitive neuroectodermal tumor (PNET) overlapping: 2-6 y.o - leukemias, non-hodhkins lymphoma adolescence - germ cell tumors, sarcomas, hodgkins disease, testicular and ovarian cancer

Williams syndrome

elastin gene deletion leads to cardiovascular problems but many have hypertension, cocktail party personality and/or mild to moderate mental impairment due to other gene deletions.

parts of the cervix histo

endocervix - continuation of the uterus lining: simple columnar epithelium ectocervix - vagina like portion: stratified squamous epithelium

causes of annovulation

endocrine disorders (e.g. thyroid disease) Primary ovarian disorder (e.g. polycystic ovaries) Generalized metabolic disturbance (e.g. severe malnutrition)

what could happen if someone is on constant estrogen without progesterone or without stopping?

endometrail growth without shedding which could lead to neoplasm

Endometriosis is the pprecursor for

endonetrioid and clear cell carcinoma

Nodular hyperplasia (BPH) - of the prostate

enlargement of TZ - all components of it, glandular and stromal hyperplasia In high proportion of men > 40 years Cause: *Estrogen increases DHT receptors - potentiating DHT* Gross: Diffuse and nodular enlargement,*compression of urethra* - incomplete bladder emptying Micro: glandular areas and stromal tissue increase

remnants of the mesonephric duct in females turns to

epoopheron and paroopheron in the mesovarium gargner cyst on later wall of vagina

Erection: a neurovascular event

erection is a parasympathetic event (flacid is symptathetic) - pudendal nerve gives erection, this is the nerve we are careful with if doing protectomy sympathetic chain constantly sends flacid signal through the NANC nerve - non andrenergic, non cholinergic - works through SM contraction - penis is baseline SM contracted

types of estrogen

estradiol - E1 estriol - E2 estrone - E3

why does pregnancy cause anemia?

estrogen = higher blood volume red cell numbers don't increase as much as the volume leading to physiologic anemia

what did the Womens health initiative find in terms of breast cancer?

estrogen alone decreased BC incidence estrogen + progesterone actually raised BC incidence *The researchers found a 23% reduction in the incidence of invasive breast cancer compared with placebo during an overall follow-up period of nearly 12 years, Women in the estrogen group who did develop breast cancer had a 63% reduction in deaths from the disease*

secretory (luteal) phase of menstrual cycle

estrogen and progesterone secretion by corpus luteum LH surge also when corpus luteum dies, the hormone levels fall and menstruation begins

what do 2ry sexual characteristics indicate:

estrogen levels

using suction we can now test embryos for....

euploidy

Papanicolaou smears

evaluates endo and exocervix, infections HPV dysplasia and carcinomas ovarian carcinoma

average euploidy by age

even in women <35, only half of the eggs were euploidy aneuploidy goes up with age we just notice how many bad eggs there are with IVF, in normal life we'd never know that there were bad eggs

in females, the paramesonephric duct gives rise to:

felopian tubes, uterus, and upper third of vaginal cannal the lower 2/3rds of the vagina (being an outpocketing of the urogenital sinus) is derived from endoderm

LARCS: Long-acting Reversible Contraceptives

few contraindications includes implants and IUD's its thought it should be first line

fingerlike projections at the end of the ovaduct

fimbriae

the corticla chords of the ovaries will become the

follicles

name of the area where there is intermediate mesoderm that will lead to genitals

genital ridge (where the gonads are going to form be it an ovary or a teste) very close to the mesonephric duct

6 weeks into development...

germ cells have migrated to the genital ridge indifferent stage. couldn't tell if it is a male or a female

what happens to the mesonephric duct (in terms of connection to bladder) when its a male?

gets resorbed by the primitve bladder and when that happens, the epithelium covering the area (trigones) get covered by mesoderm then the kidneys begin to ascend from the pelvis (where they originally developed) and pull the ureter with them (ureteric bud)

treatment for priopism after PDE5i

give norepinephrine to try to contract the SM if it has been too long, then have to drain bc blood clotted - might not have normal function after

if no bleed after progesteron withdrawal test?

give them progesterone + estrogen and withdraw: - no bleed = problem with tract - if bleed = problem with estrogen production?

gonadotropins

give to someone who is *hypothalamically supressed* - exercise, stress, BMI usually *combines with insemmination or IVF*

what happens to the endometrium glands during the secretory luteal phase of ovulatory cycle

glands become coiled and start to secrete

grading of prostate cancer

gleason's grading system strong correlation with prognosis and need for therapy Add commonest pattern to second most common pattern (add two values each out of 5 to get a score out of 10) Increasing values indicate worse prognosis

what is important that is secreted into the lumen of the glands during the secretory period

glycogen for the fetus to use for energy

hypergonodatropic hypogonadism:

gonadal dysgenesis - 45XO (Turner's syndrome) (50% of pts) - 46XX,45XO - 46XY(sawyer's syndrome)

fertility decreases with age

good chance at 30 decrease at 35 big decline at 40

what is a serous cyst adenofibroma

growth of the stroma into the cyst, yets still lined by a single serous epithelium

what do syncytiotrophoblasts secrete in terms of maintaining pregnancy

hCG keeps corpus luteum alive and making progesterone, until the placenta takes over and makes progesterone

a pregnancy test measures...

hCG beta unit

primordial oocyte histo

has a flat layer of follicular cells

2ry (antral) follicle histo

has a space that fills up with protein necessary for ovulation (somtimes called the liquor) the cells around it now called granulosa cells start making estrogen under the influence of FSH theca cell layer has separated into theca internal and theca externa bigger, accentric and with bigger antrum when late 2ry

sperm overview

has an alkaline pH, protects it from acidic vagina Sperm migrate through the cervix and uterus to the fallopian tube (5 min ) remember: Cervical mucous is hostile except during the ovulatory period

serous carcinoma of the endometrium histo

has papillary growth pattern: the malignant component lines papillary structures has "little cells coming off of the papilla" *hobnail cells* = the nucleus moves to the apical part of the cytoplasm

invasive lobular carcinoma (ILC) of the breast histo

have to do wide excisions around it strands of infiltrating tumor cells in a single file pattern without formation of tubules *lacks cell adhesion molecule: E-Cadherin*

FSH and estrogen levels:

high FSH is worrysome for the ovarian reserve low estrogen could be a hypothalamic problem, ovarian problem, and many other things so we look mainly at FSH; but like to see both low on day 3 which is a good thing

camedocarcinoma

high grade malignant cells with central necrosis in breast necrosis gets calcified an noted on mammograms clustered, linear, or branching calcifications usually a type of ductal carcinoma in situ

Pap smear with HGSIL (SIL=CIN)

high grade squamous intraepithelial lesions the nucleus is much larger and the cytoplasm barely there

why can hypothyroidism cause precocious puberty

high levels of TSH TSH can bind to FSH receptors

Theca Lutein cysts are associated with (as in formed by)

high serum beta-HCG or Leutinizing hormone (LH) levels, therefore seen in: Molar pregnancy, Choriocarcinoma, Polycystic ovary syndrome

Ewing sarcoma/ PNET poor prognosis factors

high stage direct extension into soft tissue aneuploidy metastases grossly viable tumor post chemo

Chancroid

highly infectious gram negative bacteria Cofactor for HIV; 10% co-infected HSV or syphilis Men: single, painful penile ulcers, inguinal suppuration Women: multiple painful ulcers, suppuration uncommon Treatment: Aspirate buboes (inflammed lymph), HIV test, *azithromycin 1gm x 1*

how to diagnose Embryonal Rhabdomyosarcoma

histological test followed by immunohisto to differentiate from the other types of rhabdomyosarcoma

contraceptive efficacy

how well can it work? Ideal/ perfect use: Method used exactly as prescribed Example: COC's have efficacy of >99%

contraceptive effectiveness

how well does it work? Typical use: What happens in the real world Actual effectiveness of COC is closer to 92%

lesions of the penis

hypospadias - common - *no full fusion of the urethral groove* epispadias phimosis: foreskin cannot retract Paraphimosis: obstruction of lymphatic drainage of penis Balanoposthitis STDs

reproductive health (female) is mainly under the control of the _____

hypothalamus pituitary ovarian axis

after chemo, what is an important prognosis factor in wilms tumor?

if alot of blastema is left behind - bad prognosis

when to consider fetal blood sampling for Rh status

if amniocentesis is negative yet titers rise

differentiating twins from the chorion

if dichorionic, dont know but if monochorionic, they have to be identical twins

estrogen and CVD

if estrogen given *in the 1st 9 years = 10% decline in heart disease* the more you wait, the more risk of heart disease

how can hCG show a healthy pregnancy?

if it doubles every two days however, doesn't rule out ectopic pregnancy

why is axillary node (sentinal node) so important in breast cancer?

if no metastasis in sentinal node, not metastasis anywhere else if postive, chance of metastasis

exam after prostate massage examination

if urine is richer in neutrophils after exam (pushing the prostate) we know that there is some inflammation in the prostate

is neuropil mature or immature tissue

immature nerve tissue

organs that have cyclic changes

in oviduct, uterus, cervix and vagina are regulated by steroid hormones

leydig cells are under the influence of/located in

in the connective tissue of the seminiferous tubules under control of LH: release testosterone testosterone drives spermatogenesis

where is the placenta usually attached to the decidua?

in the upper part of the uterus when it attaches lower - placenta previa - decidua is thinner here

where are the primordial germ cells?

in the yolk sack - have to migrate up to the genital ridge

first trimester screen

includes hCG and PAPP-A, nuchlar transparency hCG high and PAPP-A low in Trisomy 21 helps finds many trisomys, and turner's

epithelial hyperplasia in proliferative breast disease

increase in the layers of epithelial cells of the breast lobules due to increased proliferation or lack of apoptosis notice that it is *bound to the basement membrane* makes the lumen irregular

prostate adenocarcinoma

increase incidence with age majority of tumors are *endocrine dependent*

hormonal influences of breast cancer

increased exposure to estrogen unopposed by progesterone may be that estrogens stimulate growth factors

proliferative breast disease

increased risk of carcinoma associated with: (1.5-2X risk of cancer) - moderate or florid ductal epithelial hyperplasia - sclerosing adenosis - radial scar - Papillomas

gonorrhea again

increasing antibiotic resistnace increases risk of HIV diagnosis: *NAAT - nucleic acid amplification test*

Intrauterine insemination

indications: Mild male factor Minimal endometriosis Cervical factor Unexplained infertility *Adjunct to clomiphene*

what is pure gonadal dysgenesis

individual has 45 XY karyotype, are females presenting like turner syndrome (but no webbed neck) the cells never reach the gonadal ridge, no cells in the genital ridge (unlike degenerting in turners)

what role does oxytocin play in mamary glands?

induces the myoepithelial cells in the glands to contract expelling the milk

bartholin gland abscess

infection of the bartholin glands in the labia need to be drained: marsupialization

Morphologic Parameters in Cytologic Evaluation: Cellular Background

inflammatory cells, extracellular material (mucin, myxoid material), necrotic debris, microorganisms.

parts of the oviduct

infundibulum with fimbriae ampulla isthmus intramural portion

viagra MOA

inhibition of PDE5 keeep in minds that you still need the signaling for Parasympathetic nerve, this just makes sure it doesnt turn off

HELLP Syndrome:

intravascular Hemolysis + Elevated Liver enzymes + Low Platetets

types of breast invasive carcinoma

invasive ductal carcinoma - most common invasive lobular carcinoma medullary carcinoma colloid carcinoma - good prognosis tubular carcinoma - good prognosis

clomiphene citrate

is a SERM acts as a weak estrogen and estrogen receptor blocker makes pituitary think that there is no estrogen -> FSH increase so much so that it can lead to twins due to two eggs reaching maturity

condyloma

is aka HPV wiki: Approximately 90% of condyloma acuminata are related to HPV types 6 and 11.

acute Chorioamnionitis

is an ascending infection from the vagina into the uterus mother produces alot of neutrophils as a response can lead to preterm delivery

where does the prostate come from?

is an outpocketing of the urogenital sinus as a response to dihhydrotestosterone (DHT) - very potent androgen

mucosa of the oviduct

is infolded the more we approach the cervix, the less infolded

monochorionic twin gestation (common membrane)

is see through has 2 layers: - just the two layers of amnion, the babies share the chorion must be monozygotic twins

Acute funisitis

is the baby's response to an ascending infection the response travels through the umbilical chord and into whartons jelly can lead to preterm delivery increased perinatal mortality

artery that brings blood for erection

is the deep cavernous artery pressure during erection can reach 400 mmHg

dichorionic Twin Gestation (Common Membrane)

is very opaque has 4 layers: - two chorions fused - two aminios one on each baby

blastemal component of wilms tumor

is very varied

what is good about MRI for breast cancer

is very very sensitive, but it is not specific

effect of cigarrte smoking on ovaries

it decreases ovarian reserve

what usually happens to the mesonephric kidney

it degenerates (usually)

what happens to the corona radiata at the time of ovulation

it goes with the oocyte

what is a very important characteristic of adrenarche

it is Unrelated to the pubertal maturation of the neuroendocrine-gonadotropin-gonadal axis

what happens to basal body temperature during ovulation?

it raises

spermatognesis is synched?

its asynchronous spermatogenesis takes 64 days, so in order to ejaculate every time it has to be this way

mamary gland ducts are called

lactiferous ducts get more and more branched away from the nipple end in lobules

hersitism and lanugo

lanugo is like baby hair - anorexia hersitism is more manly hair so in the man places

prophase of the first meiotic division in spermatogenesis

lasts about 22 days so in histo, when see dividing cell in the tube, those are the primary spermatocytes

what do you worry about on a 46 XY gonadal dysplasia patient?

later malignancy, they have to get their gonads removed

LH stands for

letenizing hormone

retinoblastoma presentation

leukocoria: white in the retina, pretty much diagnostic tumor arises from the retina of the eye - grows backwards towards optic nerve and pulls the retina with it

AIDS and cervical carcinoma

life-style and impaired immune system contributes to increased risk of cervical cancer

what is a colposcopy

like a magnified view of the cervix

anatomy of the breast

lobule is the functional unit of the mammary gland, where alot of abnormalities happen Each terminal duct and its ductules compose the terminal duct lobular unit

PDE5i works by

looks like cGMP, so it binds to PDE5

choriocarcinoma

looks like malignant placenta, produces *HCG* micro: has *cytotrophoblasts and syncitiotrophoblasts* decreased response to chemo

what does HPV vaccine target

low and high risk HPV 6/11/16/18

effects of hypothyroidism on GnRH

low thyroid hormone leads to high TRH--> TSH TRH stimulates prolactin prolactin lowers GnRH

how are pediatric cancers different than adult cancers?

lower incidence better prognosis have special predispositions: - Chromosomal and genetic syndromes - Congenital immunodeficiency syndromes increased incidence of later effects of chemo

most important prognotic factor in breast cancer

lymph node metastasis

spontaneous abortion during first trimester

majority are due to chromosomal anomalies: trisomy more common Occurs in up to 1 in 5 recognized pregnancies increases with increased maternal age

Infertility Factors and Tests

male factor - semen analysis ovulatory factor - progesterone, TSH, prolacitn, Ov pelvic factor - Hysterosalpingogram,?Laparoscopy cervical factor - post coital testing age of ovary - Day 3 FSH, Estradiol, AMH, Antral follicle count

invasive ductal carcinoma (IDC) of the breast: histo

malignant cells in cords, solid cell nests or tubules stroma becomes very desmoplastic (fibrotic)

SQCC of vulva

mass, ulcer, or itching at presentation usually well differentiated (unlike cervical cancer which is usally poorly differentiated) shows keratin pearls

LIN28B (6q21 region)

may be important for mediating variation in *age at menarche*

what is MHT

menopausal hormone therapy The dose of estrogen required for vasomotor symptom relief and osteoporosis prevention is almost *six fold lower than the estrogen content in the lowest dose oral contraceptives* Circulating estrogen levels during menopausal hormone therapy (MHT) are similar to the lowest estrogen levels during a typical menstrual cycle

the two ducts that run down the embryo

mesonephric duct paramesonephric duct - responsible for female duct parts

how are POD patients treated

metformin, lifestyle changes to control sugar clomifen to induce ovulation antiandrogenic treatments

Development of oocytes

millions made in fetal life but only a few hundred survive to maturity and undergo ovulation

invasive cervical carcinoma histo features

mitotic activity large nuclei irregular outlines

wilm's tumor (nephroblastoma)

most common renal tumor in children (85% of cases) typically: solitary well circumscribed mass - if bilateral, horrible prognosis replaces the kidney parenchyma median age of presentation: 3-4 years 90% are sporadic 10% syndromic: (WT1 mutation)

Fetal Alcohol Syndrome

most common teratogen, not recognized until the 70s Distinctive facial features - flat midface with low nasal bridge, short upturned nose, long and indistinct philtrum, thin upper lip Microcephaly, mild holoprosencephaly Mental impairment, delayed development, learning difficulties Abnormal behavior -- short attention span, hyperactivity, poor impulse control, extreme nervousness and anxiety

circulation of testosterone

most of the testostosterone made by leydig is used i the testes, some of it goes out into the bloodstream - a small fraction is unbound = free = can bind androgen receptors - some of it bind to albumin (made by live) - SHBG (sex hormone binding globulin) - made by liver- binds most of the testosterone

what part of the breast stroma is responsive to hormones

myxomatous stroma (aka intralobular stroma) they can from some tumors bc of it

Preparation of Specimens

never use formalin -> bursts the cells most samples go to lab "fresh" Cytocentrifugation or membrane filtration involves centrifuging the specimen or passing it through a filter in order to concentrate the number of cells can also be prepared by smearing on glass slides and then fixing them rapidly in 95% ethanol Fine needle aspiration smears can be air dried and stained with Diff-quik stain (modified Giemsa stain) or fixed in 95% ethanol and stained with Papanicolaou stain or hematoxylin and eosin.

what does a complete mole mean?

no DNA from mom - 1 sperm w/ X chromosome fertilizes faulty egg + undergoes duplication - diploid DNA Looks like nml karyotype of girl, but actually abnml b/c everything comes from mom - Can have 2 sperm fertilization if both YY, baby will die (46YY is non-viable) *HAS NO FETAL PARTS, NO MOTHER'S X*

problems with LH receptor would lead to: (in an XY)

no testosterone, lack of male phenotype

what can cause vaginal atresia (3)

no touching of the ducts with the sinus or, the inducing factor isnt made, or the inducing factor attachement doesnt work

do FSH and LH become active together in puberty?

no, Large nocturnal *LH pulses come first* Begins during *REM sleep* Estrogen causes development of secondary sex characteristics

does maternal circulation touch fetal circulation?

no, the fetal arteries and veins are lined by trophoblasts its an exchange

diagnosis of prostate cancer

nodule on rectal exam: by the time nodule is found the cancer is pretty advanced elevated PSA metastasis: *has a great predisposition to go to bone*

in a trial, how many frozen-thawed eggs were aborted due to down syndrome? (in 40-43 year olds)

none 4 when compared to fresh

do umbilical cord knots interfere with blood supply

not really

do condoms protect agains HPV

not really, mixed studies

although it shows more benefit, can we give most people estrogen alone?

not unless they dont have a uterus (unoposed estrogen problem)

histo cross section of vas deference

notice amount of muscle and the lumen folds pseudostratified columnar epithelium; unlike the transitional epithelium of the urethra

prepubital testes histo

notice that although there are tubules, they are empty - no testosterone: no making of sperm

histo: inside the tubule

notice the basal lamina flush to it: spermatogonia large nucleus and dark nucleulus: sertoli the cells w/ chromosomes: 1ry spermatocytes solid pink ones: early spermatids late spermatids: look more like a spermatozoa

penis histo

notice the corpus spongiosum with the urethra see the corpus cavernosum with some arteries going through it

histo showing Rete testis

notice the cuboidal cells straight tubules are almost impossible to see

histo: tunica albugenia and many seminiferous tubules

notice the large *leydig cells* between the tubules

leydig cell making testosterone histo

notice the lipid droplets being used as precursors for the testosterone

histo showing some rete testis and efferent ductules

notice the retes on the bottom lined with cuboidal on top, see SM and an epithelium that looks dark and light = celiated and not celiated

characteristic marker or testicular cancer

oncogenes duplicated on short arm of *chromosome 12 (isochromosome 12p = i12p)*

what happens if the parmesonephric ducts join but dont fuse (touch thr urogenital sinus together)

one vagina, two cervix

where does estrogen come from in men?

only from testosterone by *aromatase*

types of sarcomas that affect adolescents

osteosarcoma Ewing sarcoma soft tissue sarcoma

main differential diagnosis for Ewing sarcoma

osteosarcoma desmoplastic small round blue cell tumor

mutations of type 2 ovarian cancer

p53

inhibin/activan

part of TGF family Inhibin = alpha+beta inhibits FSH Activan = beta+beta stimulates FSH

pre-term labor

parturition at less than 37 weeks (most spontaneous) Prematurity is the leading cause of death in infants without birth defects leading cause of hospitalization during pregnancy. threshold of viability is around 24 weeks

who does MUSE work for?

patients with spinal cord injury that barely have feeling in the penis and dont mind putting the catheter in with the prostaglandin E1

who do we mainly worry about with PDE5i drugs?

patients with unrecognized or unstable angina

PID

pelvic inflammatory disease

what is the McCune-Albright Triad

precocious puberty, polyostotic fibrous dysplasia of bone, and café au lait spots (skin pigmentation)

number 1 reason for 2ry amenorrhea

pregnancy

Hormonal BC RX Based on Menopausal Status

premeno - LH antagonist or SERMs post meno - same & can use aromatase inhibitors

syphilis timeline

primary syphilis (14-21 days): chancres - can disappear here, or disseminate to other organs secondary syphilis (3-8 weeks after chancres, if not cured): - salmon colored measles-like rash, split papule, *condyloma lata*, adenopathy, *alopecia* Latent syphilis: no symptoms, but RPR and specific test are positive then no recurrence usually, but if recurrence: - Tertiary syphili CNS, cardiac and gumma spread

type of follicles made in fetal life

primordial follicles develop into primary follicles --> 2ry follicle (aka antral follicle)

yolk sac tumor

produces AFP macro: sponge appearance micro: microcystic and papillary formations

what hormone is only made in the luteal (secretory) phase and therefore is a good marker that a female is in that stage

progesterone

what hormones lead to maturation of the tuboalveolar glands during pregnancy

progesterone

Endometrial Stromal Sarcoma good therapeutic option

progesterone bc they express estrogen and progesterone receptors

what makes the oviduct very active?

progesterone which is secreted by the GLC's (granulosa leutin cells)

what is challenging about progestin in pills?

progesterone is similar to testosterone and therefore it can have androgenic effects on the person taking the pill

what hormone leads to tuboalverolar maturation (further) after giving birth

prolactin

3 developmental nephron systems

pronephric mesonephric metanephric all connected to the mesonephric duct

Botryoid rhabdomyosarcoma

protrudes from a hollow area usually from the vagina or nasal cavity Classic gross appearance - looks like a bunch of grapes Polypoid very gelatinous lesion good prognosis

using own eggs vs young donor

proves that it is the age of the egg that is important for preventing loss as opposed to the age of the uterus so a 40 y.o with a 20 y.o egg has same chance of giving birth as the 20 y.o herself

what is seens in ALL serous tumors

psammomma bodies

the end of the penis

remember that at the end of penis during development there was an epithelium plug in histo, at the end the penis has stratified squamous epithelium

PCOS explained

remember usually FSH -> maturation of one follicle, LH-> androgens by theca cells that get aromatized by granulosa cells into estrogen under FSH influence in PCOS - multiple follicles at the same time making testosterone, but not enough aromatase to turn it into E2: we have estrogen but also alot of testosterone: hirsutism, acne

neuroblastoma is by definition ___ poor

schwannian stroma poor meaning that most of the tumor (over 50%) is immature neuropil, as opposed to mature nerves

another important role of sertli cells

secrete *androgen binding protein* - binds testosterone, keep concentration high in the semineferous tubules - leading to spermatogenesis

what do cervical glands secrete? what makes it change

secrete viscous mucous the viscocity is reduced mid cycle to allow sperm in

sertoli cells

secretes MIF at the beginning under influence of FSH - critical for spermatogenesis forms the *blood testes barrier*: the *adluminal compartment* from where the spermatogonia are *IMPORTANT BECAUSE THE BODY WOULDN'T RECOGNIZE SPERM AS SELF!* - other than spermatogonia

breast histo during pregnancy

see duct made bigger and proliferation (alveolar like growth) of the glands see plasma cells - making IgA

LGSIL on pap smear

see koilocytes: larger nuclei, hyperchromatic with a "halo"around them maybe white patches on colposcopy

embryonal rhabdomyosarcoma

seen in children, very rare is a muscle tumor vagina and rest of repro tract is removed

Granulomatous salpingitis

seen in: Tubercular salpingitis Crohn's disease Foreign body granulomata Parasitic salpingitis: Schistosomiasis, histoplasmosis, enterobiasis

DCIS (ductal carcinoma in situ) of breast treatment

segmental excision with radiation if extensive, mastectomy DOESN'T METASTASIZE SO NO NEED FOR LYMPH NODE DISSECTION THOUGHT THAT MOST CASES OF DCIS WILL PROGRESS TO INVASIVE CARCINOMA IF NOT TREATED

risk factors for cervical carcinoma

sexual activity: # of partners, age at first intercourse STD's: HSVII, HPV, male partner with a prior wife with cervical cancer

dygerminoma histo

sheets of germ cells interspursed by fibrotic septa and some lymphocytes

retinoblastoma histo

shows Flexner-Wintersteiner rosette - is a true lumen, not filled with neuropil

what part of sleep does estrogen have arole in

sleep latency: from when you put you head in pillow until you fall asleep menopausal women have problems mainly going back to sleep

Contraindications to Combined Hormonal Contraception

smoker over age of 35 Personal history of venous or arterial thrombotic events (DVT/PE, MI, CVA) Diabetes with vascular complications Migraine with focal neurologic symptoms ANY MIGRAINE if 35 or older Hypertension Coronary artery disease Unexplained vaginal bleeding

host factors leading to lower immune response and higher risk to advance to dysplasia

smoking, low folate or vitamin C levels pregancy, oral contraceptives concurrent chlamydia infection

spermiogenesis

spermatids to spermatozoa - golgi phase - acrosomal phase - maturation phase

the two cells in the seminiferous tubules

spermatogonia sertoli cells

spermatocytogenesis

spermatogonia go through mitosis - some stay some become *type b spermatogonia* - these will pass the sertoli barrier and become a *primary spermatocyte* -> meiosis -> spermatid

most important blood vessels in the endometrium

spiral arteries - become capillaries and end in lacunae at the end of the endometrium

example of androgen receptor blocker

spironolactone

causes of second semester bleeding

spont. abortions mainly due to structural abnormalities of the uterus (incompetent cervix, leiomyomas, EMP, maternal infections). missed abortion - - POC are retained after fetal death (POC - product of conception)

what is the most important predictor of ovarian tumor prognosis

stage Stage I: Limited to one or both ovaries. Five year survival 90% Stage II: Involvement of pelvic tissues. Five year survival 60% Stage III: Involvement of lymph nodes or extra-pelvic peritoneum. Five year survival 25% Stage IV: Distant metastasis. Five year survival 15%

wilms tumor staging

stage V - bilateral tumor if lower than stage III, straight to chemo, bc if biopsy - ->tumor "spillage" -> tumor automatically becomes stage III

type 2 ovarian cancer pathogenesis

starts with p53 mutations in fallopian tube fimbrial epithelium that gives rise to STIC (serous tubal intraepithelial carcinoma). STIC cells are possibly implanted on the ovulation injury site and grow rapidly to present as high stage ovarian cancers. Possible precursor of type II ovarian cancer is STIC.

type 1 ovarian cancer pathogenesis

starts with the formation of cortical inclusion cysts that undergo mullerian metaplasia (serous/mucinous/endometrioid). It follows a stepwise progression from adenoma to carcinoma through borderline tumors. K-ras mutations are most commonly seen in mucinous carcinoma, B-raf in low grade serous carcinoma and PTEN in endometrioid carcinoma of ovary.

testosterone chemical structure

steroid molecule 4 rings, 19 carbon feedsback negatively on the HP axis

what is in the theca interna of a graafian follicle

steroid secreting cells - testosterone, androstenedione they are clumps of cells with lipids in them (most steroid secreting cells have lipids around them - cholesterol) Do so under LH control

physiology of the penis

stimulus from pudendal NO gets released vascular SM relaxation cGMP formation influx of blood to the sinusoids the veins that let the blood out get sealed shut! blood gets trapped

what are amniotic bands?

strands of tissue that form in the amniotic sack, wrap around parts of the fetus leads to dirsuption

effective management of the treatable infections

strategic element in prevention of HIV

vagina histo

stratified squamous epithelium has alot of glycogen - looks empty

parts of the endometrium

stratum basalis - the part next to the myometrium stratum functionalis - the part that proliferates and shed

what keeps prolactin high?

sucking, mechanical suction keeps prolactin high

menopausal syptoms worse if natural or surgical?

surgical

mechanism of ejaculation: ejection

sympathetic (and somatic) S2-S4 *Bladder neck closure* - no closure = retrograde Relaxation of external (striated) urinary sphincter Rhythmic contraction of bulbospongiosus/pelvic floor muscles

mechanism of ejaculation: emission

sympathetic T10-L2 Contraction of seminal vesicles and prostate Expulsion of sperm/seminal fluid into posterior urethra

what is acanthosis nigricans

symptoms of insulin resistance: dark patches in the back of the neck and under armpits

PCOS: Polycystic ovarian syndrome

syndrome incuding pathologic ovarian findings and triad of amenorrhea, hirsitism, and obesity hirsitism: excess hair

testosterone and PSA

taking testosterone increases PSA

what lowers SHBG (sex hormone binding globulin)

testosterone, insulin

what did the Womens health initiative find in terms of CVD and osteoporosis?

that once you account for how long women spent without estrogen after menopause, you realize that the earlier they are given estrogen the healthier they will be later in life (in terms of bones and CVD's)

what does the gelason grade show

that the less differentiated the cancer cells are (aka the less they look like glands) the worse the cancer is

what does the ectoderm migration to the tip tell us?

that the tip of the penis is somatically innervated (will hurt) but the rest wont think of catherers

what leads to sexual differentiation after 6 weeks development

the SRY region of the Y chromosome coding for the SRY gene called the TDF (testes developing factor) is basically a transcription factor

myoepithilium is commonly seen in what kind of tumors?

the benign tumors

what major changes makes a more mature placenta better at oxygenating?

the blood vessels move from the middle of the villi to the side, coming into close contact with the synctyitrophoblasts there are much less cytotrophoblasts

hCG makes the ___ not degenerate

the corpus luteum - stays for about 5 months after

Carcinosarcoma (MMMT) of the endometrium histo

the epithelial component usually forms glandular structures mesenchymal part has a diffuse pattern of growth

breast fibroadenoms in terms of their response to hormones

the epithelium is hormonally responsive so: - SLIGHT INCREASE IN SIZE AT END OF MENSTRUAL CYCLE OR DURING PREGNANCY - REGRESSION OCCURS POSTMENOPAUSALLY LEADING TO HYALINIZATION AND CALCIFICATION

what is hydrosalpinx

the fellopian tubes become filled with fluid, becomes almost like a cystic mass

when will an insult most likely result in a spontaneous abortion?

the first 3 weeks

what makes estrogen?

the follicles

when the oocyte come out of the ovary - what holds it to make sure it doesnt fall into the peritoneal cavity

the glycosaminoglycans - are basically like glue

golgi phase of spermiogenesis followed by the acrosomal phase

the golgi makes vesicles that begin to form the acrosome this part of the sperm will move to the anterior portion of the cell *the one that faces the sertoli cell* at this point the *centrioles move to the back; the flagella begins to grow there*

what are stage 0 breast cancers?

the in situ ones

in mediastinum, the sminiferous tubules connect to

the intratesticular ducts: - Straight tubules: epithelium is sertoli w/some cuboidal - Rete testis: cuboidal cells - Efferent ductules: *lined by alternating cells that have and dont have celia; connect to the epididymis; phygocytose a bad cells the sertoli made; have some smooth muscle and a SCALLOPED LOOK* at this point, the sperm arent even motile, they move by peristaltic movement and the fluid movement

how to tell you are on the chorionic plate?

the membrane is smooth on the maternal side it is irregular due to the invasion

during male gential development what part of developmental nephron systems is retained?

the mesonephric duct is retained (the caudal most excretory tubules that attach to the duct) in female it will degenerate

what does the uroteric bud make?

the metanephric kidney originally empties into the mesonephric duct

what is the decidua/what does it do

the mucous endometrium that undergoes changes during pregnancy keeps the embryo separated from the actual muscle of the uterus

wilms tumor is thought to arrise from

the nephrogenic zone (primitive kidney) sits under the renal capsule supposed to be gone by time of birth, children with NZ remnants seem to develop wilms tumor

pap with HPV infection

the nuclei get bigger with perinuclear clearing (called koilocytosis) aka LGSIL - low grade squamous intraepithelial lesions

most trisomys are derived from

the ovum, over 90% higher risk with higher age (specially women >40) bc it depends on the length of time the follicle stays arrested in meiosis I. Decades of dormancy thought to increase nondisjunction

DHT effects on genitalia

the phallus begins to grow urethral groove fuses/closes scrotal swelling become the scrotum

what happens when decidua is thin?

the placenta can attach to the muscle and wont let go during delivery

what does the placenta have that the embryo lacks in order to make estriol (E2)?

the placenta has sulfatase, to take out the sulfate on DHEA the embryo uses its adrenal cortex to make DHEA-sulfate and the liver to add and OH group.

most important histo factor for wilms tumor

the presence of anaplasia: tripolar mitotic figures and nuclear pleomorphism (nuclei 3x bigger than neighbors' and hyperchromatic)

in the 6th week (undefferentiated) what happens in the abscence of SRY (TDF), no MIF etc

the primitive sex cords degenerate instead of turning into the seminiferous tubules, epithelium doesnt thicken 2nd wave of chords come from the epithelium - the cortical sex chords which get showered by the primordial germ cells: form the follicle

what is DHT responsible for

the prostate gland AND the external genitalia

spermiation

the release of a spermatozoa by a sertoli cell

nonproliferative fibrocystic cysts in breast & metaplasia

the secretory products within the cysts can calcify: shows up on mammogram *apocrine metaplasia*: - cysts becomes lined by polygonal cells with abundant granular eosinophilic cytoplasm

what does paraxial mesoderm give rise to

the somaties sleratomes, dermatomes, myotomes

what part of the fetus invades the blood vessels

the synctyiotrophoblasts

what separates ovarian (serous/mucinous) borderline tumor from cysts?

the the epithelium for borderline is more than a single row of cells, grossly then look like a cystic wall with some outgrowths

umbilical cord vilamentous insertion

the umbilical cord can insert into the fetal membranes instead of the fetal surface of the placenta: - if the veins cross the cervix, can have vasa previa - the vessels are more prone to mechanical damage since they arent really protected

IVF and maternal age

the younger the more viable, like regular pregnancy

what layer surrounds the basal membrane of a primary oocyte?

theca cells

mature corpus luteum histo

thecal cells become thecal leutin cells granulosa cells become granulosa leutin cells

effects of estrogen on the body

there are estrogen receptors almost everywhere in the body

what happens at the time of menopause follicle-wise

there are no follicles left

what always happens in twin gestation? vascular wise

there is always anastamosis between the two placental disks The presence of vascular anastomoses is the anatomic basis for twin to twin transfusion - when one baby has too much blood, the other not enough

annovulatory cycle simply

there is no ovulation -> no corpus leuteum -> no production of progesterone so only constant estrogen affecting the EM -> growth until it outgrows its blood supply and bleeds

characteristic complaint of a patient with Kallman's syndrome

they can't smell anything

what do granulosa cells do when body switches to more LH secretion than FSH?

they continue to produce estrogen, but now under the control of the steroid made by the theca interna

what happens during the process of development between the sperm?

they form cytoplasmic bridges so they are talking to each other while they develop

what do cytotrophoblasts do

they migrate all the way across the endometrium and form a layer next the maternal decidual cells is the layer that holds the embryo to the uterus - called the basal plate also remodels the blood vessels

problem with tamoxifen and roloxifen?

they still have the thrombotic effects that we try to avoid from estrogen

SRY leads to

thickening of epithelium around the genital ridge becoming - tunica albuginea primary cords detach from the epithelium (inside) and get populated by primordial germ cells - where the seminiferous tubules will form differentiation of sertoli and leydig cells

complications of prostate nodular hyperplasia

thickening of the muscle of bladder UTI's hydronephritis bladder diverticuli

giving a pt prostaglandin E1

this drug it doesnt matter what you are doing, even if spinal cord isnt working if given to the penis tissue it should relax and SM and allow an erection

where does testicular cancer metastasis go?

to where the testes came from, goes to the posterior abdomen

Surface inclusion cysts are formed by

trapped ovarian surface epithelium and play important role in the pathogenesis of ovarian cancer

Wilm's tumor histo

triphasic tumor 1) small round blue cell component: blastema 2)epithelial component-immature tubules (most often) and glomeruli 3)mesenchymal stromal component

what happens to the endometrium if there is implantation

trophoblasts in the ovary differentiate to make syncytiotrophoblast and cytotrophoblast lacuna get invaded, glands get invaded

what glands make milk

tubualveolar glands, drain into the lobules that lead to the lactiferous ducts

what carcinoma has apocrine snouts? what are they?

tubular carcinomas are small projections into the lumen of the cytoplasm

spermatogonia are inside a _____

tubule surrounded *loose connective tissue w/ many fibroblasts* as we get close to basal lamina fibroblasts assume properties of *smooth muscle cells: called myoid cells* on top of basal lamina - stratified epithelium sometimes called a *germinal epithelium* lying right on the basal lamina is the spermatogonia (adluminal compartment): turn to spermatocytes as they move towards the lumen

colloid carcinoma (mucionous carcinoma) of the breast

tumor cells "float" in white mucinous material older women, slow growing well circumscribed and soft excellent prognosis associated with hypermethylation of BRCA1 promoter in 55% of cases

Leiomyomas (macroscopic and microscopic)

tumor is well circumscribed composed of smooth muscle and connective tissue (sometimes the smooth muscle gets replaced by fibroblasts: *hyalinized leiommyomas*) *cigar shaped nuclei*

acute endometritis (inflammation0

uncommon, its usually combined with chronic endometritis Vaginal discharge, infertility, uterine tenderness, asymptomatic most commonly due to Retained placental tissue (Post-abortion / partum) can be due to an ascending infection from vagina Tx: Removal of retained tissue, antibiotics

non-invasive ways to assess hemolytic anemia of the baby?

use doppler ultrasound anemic babies will try to move the blood faster and therefore will show more flow in the doppler

applications of cytopathology

used to screen for the early detection of asymptomatic cancer, including organs such as the uterine cervix (the pap smear), bladder (urine cytology), lung (sputum cytology), and endometrium (endometrial brushings). for surveillance to detect recurrent cancer diagnosis of benign neoplasms, cysts, inflammatory conditions and infections

trisomy 13 and 18

usually not compatible with post natal life cleft lip and palate, clubbing, plydactyl, microopthamia

what happens to chromosomally abnormal embryos

usually they miscarry

what do E1 and E2 do in HPV?

usually they repress E6/7 when the virus integrates into the genome, E1/2 are lost in the process causing increased E 6/7

endometroid adenocarcinoma histo

very crowded glands see *cribriform glands*= small glands inside the bigger glands cannot trace individual glands *invasion of smooth muscle* of the endometrium

what do we use to stimulate eggs before IVF

we use gonadotropins to stimulate eggs to mature basically put a year worth of maturation into 1 cycle

Luteal Placental Shift During Pregnancy

when the corpus luteum stops making progesterone and the placenta takes over

Premature Ovarian Insufficiency

when the ovary no longer functions Chromosomal abnormalities Genetic (FMR-1) high FSH and LH Early oocyte depletion - severe infection, chemo, RT, or idiopathic

bone and estrogen

when there is no estrogen, there is more osteoclast activity

where in the cervix are most cases of squamous metaplasia

whenre endocervix meets the ectocervix (columnar to stratified squamous)

what part of the cervix is more prone to cervical dysplasia/cancer?

where it turns from columnar epithelium to stratified squamous

adluminal compartment

where the sperm lies not including the spermatogonia

GPR54 (KISS 1R)

which encodes a G-protein coupled receptor, appears to have an important role in the *initiation of puberty* via its effect on hypothalamic GnRH

explanation of enlargement/dysplasia/invasion

with HPV infection: see the koilocytes, basal cells ok dysplasia: basal cells become abnormal, some large some small invasion: going into stroma, dysplasia not a necessary precursor

why do they get hot flashes?

without estrogen the *thermoneutral zone* narrows so at lower temperature they begin to sweat and they might start shivering at a higher temperature as before

what would you find in SQCC of the lung when doing a Respiratory Tract smear: Sputum, Washings or Brushings

would find cells with pink cytoplasm - meaning squamous cells secreting keratin and therfore concluding that it is SQCC

are there genetic factore for the decrease in estrogen sensitivity of the hypo?

yes, proven by: Monozygotic twins-2.2mo between menses, Dizygotic twins-8.2 mo between also geographic area, stress, and body fat have a role

atretic follicle histo

zona becomes a solid pink band (bc its hard to digest)

Infertility Causes

■Male factor— 26 percent ■Ovulatory dysfunction — 21 percent ■Tubal damage — 14 percent ■Endometriosis — 6 percent ■Coital problems — 6 percent ■Cervical factor — 3 percent ■Uterine + Unexplained — 28

CARCINOMA IN MALE BREAST

♦ 1:100 ♦ strongly associated with brca2 in some families but not brca1 ♦ dcis and lcis are rare (so in situ is rare) ♦ same subtypes as female, more likely to have estrogen receptors ♦ due to scant amount of breast tissue rapidly infiltrates skin and thoracic wall ♦ men present at higher stages but when matched for stage prognosis is similar

ER, PR AND HER-2-NEU in breast cancer

♦ 2/3 of breast cancers are er+ or er/pr+. er+/pr+ have better prognosis. ♦ her-2-neu proto oncogene overexpression correlates with poor prognosis. overexpressed in 20-30% of breast cancer. human epidermal growth factor receptor

breast cancer clinical findings

♦ can cause retraction and dimpling of skin ♦ lymphatic involvement can cause lymphedema and skin thickening = peau d'orange ♦ involvement of lymphatics with redness and tenderness = inflammatory carcinoma, associated with high incidence of systemic metastases

male breast problems

♦ gynecomastia ♦ relative increase in adrenal estrogens ♦ cirrhosis of liver, drugs, alcohol, marijuana, heroin, anabolic steroids ♦ subareolar enlargement ♦ hyperplasia of the ductal lining with proliferation of hyaline collagenous connective tissue

breast cancer prognostic factors

♦ lymph node metastases: most important prognostic factor ♦ tumor size ♦ histologic subtype: tubular and colloid have best prognosis ♦ lymphovascular invasion ♦ tumor grade ♦ estrogen and progesterone receptors (bc we can just block the receptors) ♦ her-2-neu

spread of breast cancer

♦ spread by lymphohematogenous route ♦ outer quadrants = axillary nodes ♦ inner quadrants = internal mammary nodes ♦ supraclavicular ♦ 1/3 have metastasis at presentation ♦ distant metastases: lungs, bone, liver, adrenal, brain, meninges