Women's Health

Vaginal neoplasm -Rare, usually secondary to other cancers; 50s, 80-90% squamous cell; Typically asymptomatic; abn vaginal bleeding b/w periods; MC in upper vagina -dxs: Pap smear, Vaginal Biopsy -TX: RT

Vulvar neoplasm -70yo; 90% squamous cell -sxs: Pruritus, red/white ulcerative crusted lesions on vulva, Unifocal, vulvar plaque/mass on labia -RFs: HPV -DX: Biopsy -TX: SX excision, RT, chemo

HPV: Cervical Cancer is a sexually transmitted disease; HPV 16 (highest) & 18 (2nd) are most high risk & lead to cervical cancer (b/c non-enveloped double stranded DNA); low risk goes to genital warts -Known cofactors that incr likelihood of persistent HPV infection include cigarette smoking, a compromised immune system, and HIV; Most young W have an effective immune response that clears infection in avg of 8mos/decrs viral load to undetectable levels in 8-24mos; Only a small fraction of infections are persistent, but persistent infection at 1 & 2yrs after initial infection strongly predicts risk of (CIN) 3/cancer regardless of age Cervical Cancer -typically squamous cell carcinoma -Early cervical cancer is freq asymptomatic: usually discovered as result of screening/visual lesion on pelvic exam -MC sxs: Irregular/heavy vaginal/postcoital bleeding; Vaginal Discharge (non specific, may be mistaken for vaginitis/cervicitis) -sxs in advanced disease: Pelvic/low back pain, may radiate along posterior side of LEs; Bowel/urinary sxs (hematuria, hematochezia, vaginal passage of urine or stool) -Most Serious Factor Contributing to Cervical Cancer: LACK OF SCREENING Screening: Papanicolaou (Pap) Test (cytology) and HPV testing used alone/in combo -<21yo: none -21-29: Pap q3yrs -30-65: Pap & HPV q5yrs; Pap q3yrs ->65: none if previously neg -ppl who had total hysterectomy don't need cytology screening & HPV test unless >=CIN 2 or if supra-cervical hysterectomy -Rationale for Screening: Invasive squamous cell cancer of cervix is end result of progressive intraepithelial dysplastic atypia occurring w/in epi of cervical transformation zone; Studies have identified persistent infection w/high risk HPV as cause of virtually all cases of cervical cancer Screening in HIGH-RISK W (annual screen): Immunocompromised (eg, HIV/on immunosuppressive therapy) have decr rates of clearance of HPV infection and incr rates of cervical dysplasia and cancer. Also W exposed to diethylstilbestrol in utero or previously txed for CIN 2, 3, cancer. -HIV+: Should undergo cervical cancer screening 2x in 1st YR after dx of HIV; Then ANNUALLY if test results nl; Exam to include thorough visual inspection of anus, vulva, vagina, and cervix (at risk for other cancers too); Colposcopy at initial evaluation Dysplasia: lesion in which part of epi is replaced by cells show varying degrees of atypia CIN: Cervical Intraepithelial Neoplasia; CIN 1: fairly recent HPV infection; CIN 2: large inter-observer variability; CIN 3: considered a strong predictor of progression to cervical cancer Initiation & intervals of cervical cancer screening -In evaluating appropriate screening intervals, it is important to consider time required for disease progression. Most HPV-related types of cervical neoplasia progress very slowly & cervical cancer is rare <20yo -Cervical cancer screening should begin at 21yo. W/exception of W who are infected w/HIV, W <21yo should not be screened regardless of age of sexual initiation or presence of other behavior-related risk factors -Earlier onset of screening than recommended may incr anxiety, morbidity, and expense and lead to overuse of follow-up procedures ; Important to distinguish for the pt that she needs STD screening <21 if sexual RF exist RFs: Young Age at first coitus, Multiple sexual partners, Sexual partner w/multiple sexual partners, Young age at 1st pregnancy, Low SES, Smoking, PLEASE NOTE: Fhx is not a risk factor

ASCUS: Atypical Squamous Cells of Undetermined Significance; can rpt cervical cytology Pap test at 6mo; resume regular screening if cleared after a yr b/c will go back to nl cells -Case: 28 yr old woman has a pap that returns as ASC-US. She has never had an abnormal pap. What is the next step? HPV 16 & 18 test will say how high risk is HSIL: High-grade Squamous Intraepithelial lesions; more likely to result in neoplasia/cervical cancer, so immediate colposcopy -A visible lesion needs a diagnostic procedure (biopsy), not a screening procedure (pap) Colposcopy: irregular surface (erosion/ulceration), dense aceto-white change, mosaic; abn vessels Staging: 1: confined to cervix II: beyond cervix but not to pelvic wall/vagina III: dz to pelvic wall/lower 1/3rd vagina IV: bladder, rectum, metastasis SX -CIN2-3: Cryotherapy (not great), LEEP (Loop Electrical Excisional Procedure), Cold Knife Cone (CKC; cut cone in cervix to get full depth removal of cancer) -Invasive Cervical Cancer: Simple Hysterectomy; Radical Hysterectomy & pelvic LN dissection (Removal of entire uterus, surrounding tissue, upper part of the vagina, and LNs) -RT -Chemo: Extrapelvic metastasis, recurrence -Vaccination and regular screening can prevent almost all cervical cancers. HPV Vaccine: 9-Valent (Gardasil): 3 dose series (0, 2, 6mos) -27-45yo is FDA approved to receive vaccine; can reverse effects cervical cancer -2 dose: <15yo; 0, 6-12mos; if 1st & 2nd dose <5mos, 3rd dose neeeded -3 dose: >15yo, immunocompromised -C/I: allergic rxn to gardasil; wait until mod/severe acute illness improved; pregnant W (delay until after delivery) -bivalent & quadrivalent HPV vaccines immunize against only HPV-16 & 18; nearly 100% protection against CIN caused by these 2 in previously uninfected W; 30% of cases of cervical cancer from other HPV genotypes not included in the vaccine are expected to continue to occur -9-valent HPV vaccine immunizes against 5 add high-risk subtypes but still does not cover all subtypes -vaccination can be through 26yo, a time when many W may already have acquired the virus, which sig decrs efficacy of vaccine; Still recommended after initiation of sexual activity though not thought to be as effective

Menopause -nl natural event, defined as final menstrual period (FMP), confirmed after 1yr of no menstrual bleeding; permanent cessation of menses resulting from loss of ovarian follicular fxn, usually due to aging -When? Naturally (spontaneously) 51yo; Prematurely from medical intervention; At any time from impaired ovarian fxn -Stages of Reproductive aging +10 staging system for reproductive aging in W: no reason to get labs if no periods & sxs -Perimenopause: The time around menopause, also called "menopause transition"; most symptomatic phase for W -Induced (iatrogenic) menopause: Cessation of menstruation that follows BL oophorectomy (w/w/o hysterectomy)/chemo/pelvic RT -Premature menopause: Any menopause that occurs <40yo -Primary ovarian insufficiency: continuum of impaired ovarian fxn leading to amenorrhea in W <40yo -Postmenopause: yrs after FMP; 1/3-1/2 of lifespan of most US W -Changes in both menstrual flow and freq are common and usually nl Sxs: Change in menstrual cycle pattern (early) -Vasomotor sxs: Recurrent, transient episodes of flushing w/sensation of warmth/intense heat on upper body/face; Triggered by small incrs in core body temp acting w/in decr thermoneutral zone -Vaginal sxs: vaginal dryness, vulvovaginal irritation/itching, and dyspareunia (painful intercourse; ask pts); Unlike vasomotor sxs, which abate over time, vaginal atrophy is typically progressive and unlikely to resolve on own; txs=regular sex, lubricants & moisturizers, and local vaginal estrogen Sleep disturbances: sleep less, more freq insomnia, more likely to use rx sleeping aids; from general aging effects (eg, nocturnal urination), Sleep-related disorders (eg, apnea), other illness (eg, chronic pain, depression), Stress, negative mood, Ovarian hormone changes -Hot flashes (night sweats) can trigger awakenings in first half of night, but REM in 2nd half suppresses thermoregulation thus hot flashes -Decisions on whether and how to tx (behavioral/drug therapy/both) depend on: Context/Severity of sleep disturbance, (eg, distressing hot flashes or life stress), Severity of daytime consequences Cognitive concerns: Midlife W should be counseled that memory and conc problems are probably not related to menopause but rather to nl aging/mood/stress/other life circumstances Mood disorders: Feelings of upset, loss of control, irritability, fatigue, and blue moods (dysphoria) at midlife may be caused by fluctuating hormone levels that perturb neural systems transiently; W w/hx of premenstrual syndrome, sig stress, sexual dysfunction, physical inactivity, or hot flashes are more vulnerable to depressive sxs -most predictive factor for depression is prior hx of clinical depression -TX: Relaxation and stress reduction techniques, antidepressants, and counseling/psychotherapy Urinary sxs: no link to menopause-related estrogen loss has been identified; >50% W w/urinary incontinence also report sxs of overactive bladder (OAB); Mild incontinence in early perimenopause tends to decline in first 5yrs after menopause -TX: wt loss for overweight; Kegel exercises cure >50% cases of stress incontinence when performed regularly; Several meds for OAB Osteoporosis: compromised bone strength; Serious health threat for aging postmenopausal W by incr risk of fx; Lower estrogen levels account for 2/3 of bone loss during 5-7yrs around menopause -BMD results: Nl: T-score >=-1.0; Low bone mass (osteopenia): b/w -1.0 & -2.5; Osteoporosis: T-score <=-2.5 -BMD testing: For ≥67yo w/nl BMD/mild osteopenia, one could wait 17yrs; w/mod osteopenia, 5yrs -In addition to lifestyle changes, osteoporosis drug therapy is recommended for: Postmenopausal w/vertebral/hip fx; Postmenopausal w/T-scores ≤−2.5 at lumbar spine, femoral neck, or total hip; Postmenopausal w/T-scores from −1.0-−2.5 and 10yr FRAX risk of major osteoporotic fx of 20%/hip fx of 3% CVD (CHD and stroke)=leading cause of death for W ≥65yo -aim for: Total cholesterol <200 mg/dL: HDL-C >50 mg/dL, LDL-C <100 mg/dL; BP <120/80; Fasting blood glucose <100; BMI <25; No smoking; Physical activity: ≥150 min/wk mod, ≥75 min/wk vigorous, or both; Healthy (DASH-like) diet Cancer: Menopause not associated w/incr cancer risk, But b/c cancer rates incr w/age and cancer is 2nd leading cause of death in women, screen for following cancers regularly: -Breast: mammogram q2yrs, 50-74yo -Colorectal: colonoscopy (q10y) or FOBT, sigmoidoscopy, or barium enema (q5y) beginning 50yo -Endometrial cancer: eval any postmenopausal bleeding w/pelvic US/endometrial biopsy -Ovarian cancer: no satisfactory screening tests, but timely eval needed if presenting w/bloating, pelvic pain, or urinary urgency -Cervical cancer: refer above

Abn uterine bleeding (AUB): excessive/erratic bleeding: -Heavy menstrual bleeding (>80 mL) esp w/clots -Menstrual bleeding lasting >7ds or ≥2ds longer than usual -Intervals <21ds from onset of 1 menstrual period to onset of next one -Any spotting/bleeding b/w periods -Bleeding after sex Sexual health -Sexual issues generally incr w/aging; distressing sexual complaints peak during midlife (45-64) and are lowest from 65 onward -decr estrogen causes decline in vaginal lubrication and elasticity; decr testosterone may contribute to a decline in sexual desire and sensation -An active sex life, lubricants and moisturizers, and local vaginal estrogen help maintain vaginal health -Clinicians should not assume that peri/postmenopausal W are not at risk for STIs; Vaginal atrophy incr risk for contracting an STI; Older W may not be as knowledgeable about risks Hormone therapy (HT): only pharmacologic therapy government approved in US and Canada for tx menopausal sxs. -Estrogen therapy (ET): Unopposed estrogen is prescribed both a) systemically for no uterus and b) locally in very low doses for any vaginal sxs -Estrogen-progestogen therapy (EPT): Progestogen is added to ET to protect W w/uterus against endometrial cancer, which can be caused by estrogen alone -Bioidentical hormone therapy (BHT): hormones chemically identical those made in body. 2 sources: 1) FDA approved and tested; 2) unapproved and untested from compounding pharmacies; conventional FDA approved HT is preferred -Absolute risks for HT use in healthy 50-59yo are low, but can include thrombosis, stroke, and CV events -HT initiation in older W carries greater risks: Breast cancer risk incr w/EPT beyond 3-5yrs; ET can be considered for longer duration of use b/c lower risk for breast cancer -Premarin: used most; start w/lowest dose -17b estradiol=Estrace (can also use patch) -Bazedoxefine: SERM, newer product Alternatives to hormone therapy -Nonhormonal rx drugs (off-label use; don't get as much benefit): Antidepressant (SSRIs: fluoxetine, paroxetine, escitalopram; SNRIs: venlafaxine and desvenlafaxine), Hypnotic: Eszopiclone; Anticonvulsant Gabapentin: Antihypertensive Clonidine: Neuropathic pain drug Pregabalin -alternatives: soy, Chinese medicine, herbs=not too effective -lifestyle: relaxation, avoid hot flash triggers, vaginal moisturizer (Replens)

Mother: mono-like illness (probably asymptomatic) child: Usually asymptomatic; 10% of neonatal pts at time of birth; sensorineural hearing loss (rub), chorioretinitis (toxo), retinal scars, strabismus, ascites, cardiomyopathy, enterocarditis, hepatosplenomegaly, jaundice, microcephaly -CMV has emerged as MC congenital viral infection; Maternal CMV infection during pregnancy MC from close contact w/young children, esp children attending daycare centers Clinical suspicion in newborn: -S/S consistent w/congenital CMV dz -abn neuroimaging consistent w/CMV -documented SNHL -born to mothers w/CMV infection during pregnancy -Immune-compromised

Cytomegalovirus/Congenital Cytomegalovirus (CMV) -molecular detection of CMV: urine/saliva samples IV ganciclovir

-MC ovarian neoplasm; germ cell tumor; 10-15% teratomas are BL;. Composed primarily of ectodermal tissue, sweat and sebaceous glands, hair follicles, teeth; Slow-growing tumors; 25-50yo; Most are <10 cm in diameter. Case: A 25 y/o Go complains of a painful full sensation in her RLQ. She has had regular periods since menarche. She has no hx of STDs. On PE you find a mobile mass in her R adenxae about 8 cm x 8 cm. This mass is mobile. Her urine pregnancy test is negative. You order a TVS=8 cm right adnexal mass that is described as composed of mixed and solid components, some of which are calcified. There is no evidence of ascites and the left adnexa appears unremarkable.

Dermoid Cyst (benign cystic teratoma) -SX tx (cystectomy vs oophectomy) IF SYMPTOMATIC/LARGE CYST; During SX, CL ovary must be examined since 10-15% are BL; Laparotomy vs Laparoscopic procedure (depending on size of cyst) -It is acceptable to do expectant management if cyst is small (<5 cm) and no sxs; Ok to observe as long as no sxs/pain

Pustules/papules, erythematous; Pruritus -Inflammation/infection of hair follicle -S aureus, P aeruginosa (hot-tub folliculitis)

Folliculitis -DX: Hx, PE -Spontaneously resolves in 2wks; Avoid shaving, warm compresses -Topical abx (mupirocin/clinda) -PO abx (dicloxacillin)

3 D's (Cyclical): Dysmenorrhea (painful periods), Dyschezia (pain w/defecation), Dyspareunia (pain w/ sex) esp w/deep-thrust due to implant in uterosacral ligaments; amt of dz does not correlate w/sxs** (tiny implant can cause lots of pain) -chocolate cyst=endometrioma; pt has endometriosis for sure -benign condition in which endometrial glands and stroma are present outside uterine cavity and walls. -no single theory for cause -retrograde menstruation (sampson's theory): Menstrual fluid spill out of tube and implants in peritoneum; common in patent fallopian tubes; Clinical observation of retrograde menstrual flow during laparoscopy in humans -implants of tissue outside uterus act just like the tissue lining uterus; During menstrual cycle, they get thicker, then break down and bleed, but blood cannot flow out of body & implants can get irritated and painful. -RFs: freq/prolonged menses, W>B/asian; infertility, pelvic pain, fhx; 20-30's; cervical/vaginal atresia, other outflow obstruction, early menarche; decr risk w/low estrogen levels -Can be in teens but more likely Primary Dysmenorrhea, ovarian pathology, abuse, STD's. -Onset in 40's - think Fibroids, Ovarian Neoplasm, Infections, Adenomyosis Case: A 25 y/o nulligravida female presents to our clinic complaining of severe pelvic pain during her periods. Her pain is severe enough that she sometimes needs to be absent from her work. She reports that her periods are not heavy and last 4-5 days. She currently is sexually active with only one partner. She is in good state of health and does not take any medications. She reports pain with intercourse for the past 6mos. The patient also reports pain with defecation. She is planning to have a baby in the next 2 years. On examination she has significant cervical motion tenderness and thickening of uterosacral ligaments. A transvaginal ultrasound was done and showed no abnormalities. -offer meds, not SX b/c wanting to have baby Case: 21yo W, return to you after 3 months on OCPS. She tells you her symptoms are not improved. Next step? do laparoscopic -pt taken to OR and dx of endometriosis is made. She does not desire pregnancy at this moment. You placed her on GnRH agonist; S/E=hot flashes, mood swings; duration tx=6mos, then reeval; at 6mos, happy=can continue but need estrogen/progesterone Case: 48 y/o female comes to you with 1 year history of pelvic pain. She was diagnosed with endometriosis at age 25 and had 3 children after infertility treatment. She had a tubal ligation at age 38. She desires to know your recs for tx. -You can still offer her meds, but she will be a good candidate for definitive tx (TAH/BSO) Case: RR is a 31 yr old G0 with 2 years of infertility and longstanding dyspareunia

Endometriosis -Direct visualization w/laparoscopy/laparotomy -can initiate medical tx if suspect endometriosis; pt F/U (in about 3-6mos) to assess response; If no response, consider dx laparoscopy -NSAIDS, OCPs (prevent ovulation), Levonorgestrel-containing IUD (Mirena), Progestin, Danazol -GnRH agonists (Depolupron): chemical menopause (same sxs as menopause so counsel pts); Short duration tx (6mos); If pt is satisfied w/tx & sxs under control, then she may continue w/tx for >6mos provided that she is placed on "add-back" therapy -Endometriosis "Add-Back" Therapy: preventing bone loss & hot flashes sx relief; gives estrogen & progesterone SX: Remove implants and prevent progression, Relieve pain, Enhance fertility, Prevent recurrence; The desire for future fertility guides SX -conservative, wants pregnant: Lysis of adhesions (laser laparoscopy): destroy all endometriotic implants and remove all adhesive disease; Large endometriomas (>3 cm) are amenable only to SX resection; Repair tubal damage, Presacral neurectomy, Uterosacral n ablation -non-conservative: TAH, BSO w/destruction of all peritoneal implants, and dissection all adhesions

abn vaginal bleeding*, postmenopausal bleeding, abn discharge -MC GYN malignancy -Type I (80%): Endometrioid histology (grade 1 & 2), Favorable px, Arise from estrogen stimulation, Preceded by an intraepithelial neoplasm (atypical and/or complex hyperplasia) -Type II (10-20%): Grade 3 endometrioid, and non-endometrioid histology: serous, clear cell; High grade, poor px; Not associated w/estrogen stimulation; No precursor lesion (very sudden onset, more aggressive) -RFs mainly for type I: incr age, prolonged estrogen stimulation, Tamoxifen therapy, early menarche/late menopause (more estrogen), PCOS, obesity, DM, estrogen secreting tumor, nulliparity (not being pregnant), lynch & cowden syndrome, fhx endometrial/ovarian/breast/colon Ca

ENDOMETRIAL CA -Endometrial Biopsy DOC; Post-menopausal/Perimenopausal intermenstrual bleeding; Postmenopausal w/endometrial cells on pap; Thickened endometrial stripe on U/S -Transvaginal U/S: Checking endometrial thickness; Endometrial stripe thickness <4 mm=low risk; >4 mm high risk, proceed w/biopsy -Fractional curettage +/- hysteroscopy is diagnostic GS -Pap Test: very low sensitivity, but necessary to r/o cervical cancer as cause of PMB Staging is SX: Total Abd Hysterectomy (uterus & cervix) TOC; BL Salpingo-Oophorectomy if appropriate age; Pelvic and para-aortic LN dissection TX based on initial clinical presentation. -Stage 1: TAH, BSO, Pelvic & Para-aortic LND -Stage II: ^ + Pelvic RT, brachytherapy -Stage III, IV: Chemo +/- RT/SX

Maternal Physiology Cardiac Anatomical Alterations: Rotates up w/axis deviated to L on EKG; Systolic flow murmur CO antepartum -incr HR by 30-50% by 10 weeks; Maximum by 20-24wks -decr peripheral resistance: progesterone induced vasodilation; placenta is like a arterial venous fistula (sucks up blood); baroreceptors reset; angiotensin II relative resistence -Supine Hypotension Syndrome: hypotension, tachy, diaphoresis, decr CO CO Intrapartum -incr by at least 30%; 300-500 ml of blood expressed w/each contraction; Valsalva maneuver; Pain and anxiety CO Postpartum -incr by 50% at 1hr; Blood infusion from contracting uterus; Release of caval compression; Mobilization of extravascular fluid Intravascular vol Changes: -40% blood vol expansion (has to fill placenta & uterus); plasma vol/RBC mass incr (RBC not as much so anemic) Venous Pressure Changes: -incr venous capacity; Venous pressure above umbilicus is nl; Venous pressure below umbilicus is increased Respiratory Changes: Anatomical changes given elevated diaphragm; incr in tidal vol (take deeper breaths), Slight hyperventilation w/incr pH -ph slightly alkalotic, pCO2 decr, pO2 incr GI: Delayed emptying of stomach, duodenum and gallbladder; C; incr risk of cholestasis; Hepatic=incr hormone-binding globulins & decr albumin Metabolic Changes: incr basal metabolic rate (baby steals energy); decr albumin fxn, incr lipids; incr insulin production, but decr effect (Relative IR b/c of Human Placental Lactogen hPL=insulin antagonizer); pregnancy is diabetogenic Carbohydrate Metabolism In fasting state: decr insulin; glucose crosses placenta by facilitated diffusion; hPL promotes lipolysis to free FAs; AAs freely cross placenta Skin Changes: Hyperpigmentation, Chloasma (tanning of cheek), Vascular spiders, Palmar erythema, Striae gravidarum Musculoskeletal: Pubic symphysis relaxation; incr lordosis (jts more limber) Renal Changes: incr renal plasma flow; incr GFR by 50%; decr BUN/Cr (kidneys working overdrive & filtering like crazy); Effected by posture; Hydronephrosis & hydroureters; incr GFR (exceeds tubular reabsorption :glycosuria; proteinuria; loss of water soluble vits and AAs) Cervix: incr vascularity, edema → softer connective tissue; Hypertrophy and hyperplasia of cervical glands; Mucus plug Ovary: Ovarian fxn ceases; Single corpus luteum (Progesterone production 6-7wks; Relaxin), Decidual rxn (red flush areas on ovary, common) Uterus -Growth: 10-->5,000cc pot vol -Hypertrophy of existing m cells; incr fibrous tissue •Contractility is maintained •Blood flow incr to 500 cc/min at term Early Pregnancy Maintenance -Dominant follicle converts to corpus luteum after ovulation -hCG rescue of corpus luteum if pregnancy occurs -hcG: Similar to LH, FSH, TSH; 2 non-identical subunits (α & β subunits); Common α subunit; β subunit confers biologic activity; Pregnancy test = hCG; Rapid incr in hCG levels 3-9wks; Doubling q48hrs; Failure to observe this doubling=suspicious for ectopic pregnancy -Corpus Luteum: SX removal of ovary before 6-8wks can result in pregnancy loss; Supplemental progesterone needed to maintain pregnancy until approximately 10-12wks

Estrogens: incr uterine blood flow; Regulation of steroidogenesis; Parturition -estrone & estradiol small incr -Estriol high incr: Exclusively produced from placenta Progesterones: Antagonize estrogen effects; decr uterine blood flow; Facilitate fertilization/conception via tubal relaxation (anticontraction, antipartuition to keep pt pregnant); Inhibition of T-lymphocyte mediated tissue rejection; Generalized smooth m relaxation; Uterine relaxation -Predominantly produced by corpus luteum <6wks; Beyond 12wks placenta is predominant source; Produced from maternal LDL and cholesterol (that's why don't use meds that affect cholesterol in preg) Cortisol/Cortisone/CRH: incr levels throughout pregnancy; Maintains pregnancy and maternal/fetal steroidogenesis Thyroid: incr levels of TBG; Compensatory incr in free T4 and T3 w/doubling of total levels (hcG weakly thyrotropic); Serum T4 levels return to nl after 1st trimester -TSH levels relatively unchanged -Hyperemesis gravidarum (excessive NV): mild transient suppression of TSH can be seen Human Somatomammotropin (hPL): Antagonizes insulin action inducing glucose intolerance, lipolysis, and proteolysis; Protects transfer of glucose and AAs to fetus; Levels incr beginning at about 5wks and rises throughout gestation; Highest levels 3rd trimester; Glucose tolerance testing Alpha-fetoprotein (AFP): Produced by fetus (yolk sac, liver, GI tract); Osmoregulator/Immunomodulator; Clinically used for detecting fetal anomalies/aneuploidy -High AFP: Spina bifida, abdominal wall defects, fetal tumors -Low AFP: Aneuploidy -AFP is part of maternal serum multiple marker screening test for aneuploidy (Down syndrome, Trisomy 18, ect); Test includes: AFP, hCG, estriol +/- inhibin Lactation -Estrogen: Growth of ductal tissue and alveolar budding -Progesterone: Maturation of mammary glands (brakes for lactation ntoo) -Lactogenesis: promoted by prolactin; Placental sex steroid hormones inhibit secretory activity of glandular epi -Prolactin: made in ant pit; Levels rise in maternal serum and amniotic fluid throughout gestation; Release inhibited by dopamine; Important role for milk production; Release stimulated by infant suckling -Oxytocin: post pit; Release stimulated by infant suckling; Responsible for milk ejection; Promoted uterine contractions -Suckling Reflex: Infant suckling stimulates neurofibrils of breast; Signals pituitary to release prolactin and oxytocin -Engorgement occurs 2-4ds postpartum -Colostrum (initial milk from breast): Secreted from breast for first 2-3ds after birth; High levels of secretory IgA=Conveys high level of passive immune protection -breast feeding Advantages: Improved digestion, Promotes bonding, Immune protective, Provides contraception, decr blood loss, Neonatal/Maternal health benefits -Infant Benefits, decr risk for: Otitis media, Allergies, DV, Menignitis, Lower respiratory infections, UTI, NEC -Maternal benefits: Enhanced caloric expenditure, decr risk for breast and ovarian ca, incr bone strength, Delay menses (prolonged interpregnancy interval) -C/I: Active tb, HIV, HSV (involving the breast) -Amenorrhea: Ovulation ensues 6-12wks after delivery in absence of breast feeding; Exclusive breast feeding: Amenorrhea - up to 6mos (birth control) -Contraceptive Issues: Use of estrogen containing OCP can decr milk production; Reliable birth control options: Sterilization, IUDs, barrier, progestin only contraceptives

Intimate Partner Violence: Assaultive & coercive behavior that may include physical, sexual or psychological abuse, stalking, deprivation, intimidation and reproductive coercion; Perpetrator is someone who is, was, or wishes to be involved in an intimate/dating relationship; W are more likely to be victims; IPV may be as common in same sex relationships as in heterosexual relationships -Physical Abuse: Pushing, kicking, slapping, beating, biting, strangling, use of a weapon -Psychological Abuse: Name calling, degradation, threats, stalking, isolation -Sexual Abuse: Unwanted kissing, touching, or fondling, sexual coercion, rape -Reproductive Coercion: Sabotage contraceptive efforts, intentionally expose a partner to an STD, control outcome of a pregnancy, control access to reproductive health services RFs: <24yo, Divorced/separated, alcohol/substance/childhood abuse, Pregnancy, Low SES, Recent restraining order Characteristics of an Abuser: May be of any race, age or SES; Feelings of inadequacy; Minimize their abusive behavior; diff private and public personalities; Witness to a victim of abuse in childhood; socialize and interact w/other abusive/aggressive men Cycle of abuse: 1) tension building, 2) incident (abuse), 3) reconciliation, 4) calm -Each cycle incr in freq and intensity -Results in worsening violence and shorter honeymoon phase -Self worth/esteem decr w/each cycle -Results in incr isolation and dependence on abuser; Violence freq associated w/alcohol use Coordination of care: Medicine, Law, Social Work, Police ID of Victims of Intimate Partner Violence -Hx: Inconsistent explanation of injuries/delay in tx; Chronic somatic complaints: HA, GI sxs, fatigue, eating disorders, depression; Late prenatal care; freq ER visits; Noncompliance; pt's demeanor-flat affect, avoids eye contact, anxious; Partner refuses to leave room/answers questions -PE: Areas of injury are central body (Breasts, abd, genitals); Defensive wounds to forearms; Injury to head and neck (Bruising, attempted strangulation); Bruises in varying stages of healing -Silence Hides Violence: Listen to your instincts; Don't be afraid to ask pt about abuse -SAFE: S-Does pt feel safe? A-Has pt felt abused by her partner? F-Are friends/family available for support? E-Is there a plan in case of emergency? -RADAR: R-Routinely ask, A-Ask directly, D- Document findings; A-Assess safety; R-Review options and refer -Routinely Ask: Universal screening, Screening must occur in a safe and confidential environment & alone, Healthcare provider must have ability to listen to pt; Reasons that screening may not occur: Lack of training, Socioeconomic/cultural prejudice, Time, Frustration by healthcare provider, Fear, Personal hx of abuse -Ask Directly: Use words pt understands like Do you feel safe with your partner? Has your partner ever slapped, kicked, hit or otherwise physically hurt you? -Document Findings: Describe details of abuse and use pt's words; Be specific (Weapon used, time, date, number of attacks); Photographs if possible/body map; Documentation is crucial if legal proceedings will occur -Assess Safety: Are there children in home? Are there guns/other weapons in home? Is pt afraid to go home? -Review Options and Refer: Provide resources, Hotline phone numbers, Shelter numbers, Referral to social work and counseling, Positive reinforcement - the abuse is not her fault, Review exit plan -Exit Plan: Savings account/credit card; Money, keys, documents, clothes on hand; Someone to stay w/; Shelter/hotline phone #s available; Cell phone or calling card available; FREQUENTLY REVIEW EXIT PLAN

Reporting Abuse: Most states DO NOT have mandatory reporting (TX); Mandatory reporting is controversial; diff than child and elder abuse IPV and Pregnancy: Violence may begin/worsen during pregnancy; Pregnancy is followed closely for complications; Low birth wt, preterm labor, trauma, abruption, incr risk of attempted homicide; Screen at initial visit, each trimester and at postpartum visit LT Consequences for Victim -Physical: trauma, somatization -Socioeconomic: limited resources & income -Psychological: depression, anxiety, PTSD, substance abuse, multiple personalities -Death LT Consequences for Children: Psychological effects. Poor social skills, Poor academic performance, rpt pattern of abuse (Girls identify w/mom and learn to accept violence; Boys identify w/father/partner and learn that violence and bullying is acceptable) Why Doesn't Victim Leave? Fear, Isolation, Financial, Lack of social support, Inability of law enforcement to protect her, Fear of legal proceedings Sexual Assault: Use of violence and aggression; Sexual act that is performed on a person w/o consent; Encompasses a spectrum of activity from coercion to contact abuse to rape -Who performs exam? ER physician, OB/GYN, SANE (Sexual Assault Nurse Evaluation); Preferably a provider trained to care for sexual assault victims -Benefits of SANE: Improved quality of forensic evidence, Protection of chain of evidence, Expedite eval & referral to community services, Improved sensitivity to psychological trauma -HX: Be specific w/documentation; Circumstances (date, time, location or weapons), Loss of consciousness/memory; Specifics of penetration and type of contact - oral, anal, vaginal, ejaculation or condoms; Bleeding from victim/assailant; Recent consensual sex & site of contact; Has victim brushed teeth, changed clothes or showered -PE: pt's emotional state; Evidence of trauma-photos; Special attention to extragenital trauma; Bruises and abrasions on thighs, upper arms, face, neck, breasts; Common areas of anogenital trauma are labia minora and posterior vagina; Colposcopy can aid in evaluation; UV light can be used to check skin for semen -Forensic Evaluation: May be collected up to 1wk (96hrs in TX) after assault; Varies by state; Clothing; Swabs of buccal mucosa, vagina, rectum, areas highlighted by UV light; Combed specimen from scalp and pubic hair; Control samples of hair; Blood and saliva samples; FOLLOW STEPS CAREFULLY AND EXACTLY -Laboratory Testing: Offer STD screening, NOT MANDATORY FOR PT (Gonorrhea, Chlamydia, Trichomoniasis, Syphilis, Hepatitis B, HIV, Pregnancy, Drug screen as indicated) -TX: Physical injuries, STD prophylaxis, Emergency contraception, Psychosocial care -F/U: 1-2wks in clinic w/PCP; rpt HIV at 72hrs, 6wks, 3mos and 6mos -LT Consequences: PTSD, Depression, Somatization, Sexual Dysfunction, Cervical Cancer, Unwanted Pregnancy, Rape Trauma Syndrome Rape Trauma Syndrome Acute Phase: Disorganization Phase=Shock, Confusion, Cognitive dysfunction, Anxiety, Fear, Sleep disturbance, Humiliation Delayed phase: Reorganization phase= Rationalization of event, Reality of victimization, Changes in lifestyle, daily habits, social life, Somatization, Insomnia, Shame and guilt

TORCH Toxoplasmosis Other (syphilis, Zika, enteroviruses, varicella zoster virus, parvovirus B19, etc.) Rubella Cytomegalovirus (CMV) Herpes simplex virus (HSV) -Infections acquired in utero/during birth process are a sig cause of fetal and neonatal mortality and an important contributor to childhood morbidity; Requires high index of suspicion -Screening pregnant women: U.S.=syphilis, rubella, and varicella at first prenatal visit; Other countries=some add toxoplasmosis -No TORCH titer in infants; Test for specific pathogen based on clinical presentation

-Intrauterine infection may be suspected on basis of labs obtained during pregnancy=+ syphilis serology w/incr titers -Intrauterine infection may be suspected in newborns w/certain clinical manifestations (but not limited to): Hydrops fetalis, Microcephaly, Seizures, Cataract, Hearing loss, Congenital heart dz, Hepatosplenomegaly, Jaundice, Rash, Thrombocytopenia The evaluation of a newborn w/clinical findings compatible w/intrauterine infection may include: -Review maternal hx for evidence of rubella immunity, syphilis serology, hx HSV, exposure to cats -Assessment of physical stigmata consistent w/various intrauterine infections -CBC & platelet count -Liver fxn tests -Radiographs of long bones -Ophthalmologic evaluation -Audiologic evaluation -Neuroimaging -Lumbar puncture

Anovulatory AUB (AUB-O; AUB related to ovulatory dysfxn): Unpredictable, Irregular, Heavy, Prolonged, abn levels of PGs exacerbate blood loss -Bleeding characteristics and pathophysiology differ from ovulatory AUB; Typically, is result of endocrinopathy (PCOS) -Mechanism: unopposed estrogen; Bleeding characteristics: ranges from amenorrhea to irregular heavy cycles; Unpredictable; Endometrium that develops under these conditions is fragile, vascular and lacks stromal support -Causes: Adolescence, Perimenopause, Lactation, Pregnancy, Hyperandrogenism: PCOS, Hypothalamic dysfunction -Nl=Luteal phase: marked incr in tissue levels of PG F2α, (powerful vasoconstrictor) leading to endometrial ischemia. This allows for a complete sloughing of outer 2/3rds of endometrium and avoids prolonged menstruation. -Anovulatory cycles: chronic proliferative endometrium, less PG F2α, less likely to initiate an efficient menstrual period of short duration. -Endometrial loss during continuous estrogen stimulation is irregular. -As one area of bleeding begins to heal, another area begins to slough, resulting in irregular and prolonged menstrual flow Case ex: Over last 2yrs, cycles are irregular. She bleeds 14/30ds of month, amt varies b/w spotting->requiring pads; Has "accidents": bleeding through protection; "I always have to wear a pad" -problem: AUB -Mrs. Jones has nl TSH, Prolactin, CBC and is NOT pregnant; Her EMB is benign and TVUS shows nl GYN anatomy; best first line? OCP fastest; Provera takes longer

AUB in general -clinical evidence of hyperandrogenism: acne, hirsutism -TSH*, Prolactin, Preg test first=bhCG (if reproductive age, pregnancy test also #1), CBC; Consider GC/Chl if at risk -Pelvic U/S -Consider SIS* (Saline Infusion Sonohysterography) /hysteroscopy if suspect myoma, polyps -Endometrial biopsy** (>45yo, younger w/RF, failed medical mgmt, persistent AUB) TX: Based on etiology (PALM COEIN) -Structural etiology-SX, occasionally meds -nonstructural: tx cause -Meds: Provera*, OCP (esp in chronic anovulation, PCOS)*, NSAID, Tranexamic acid (lysteda) -Procedures: Levonorgestrel containing IUD -SX: Hysteroscopy D&C** -If no longer interested in childbearing: Endometrial ablation** -Hysterectomy -F/U: If anemic, place on Fe; Recheck hct after 8wks of therapy; Sometimes bleeding gets a little worse before it gets better; PATIENCE; Improvement seen after 2-3mos -Emergency Situations: OCP taper; IV estrogen; Transfusion; Emergent D&C

heavy periods & severe dysmenorrhea (painful periods) -extension of endometrial glands and stroma into uterine musculature >2.5 mm beneath basalis layer (build up & can't bleed out) -Contrary to picture in a uterine myoma, no distinct capsular margin can be detected on cut section b/w adenomyoma & surrounding myometrium -Uterus is generally symmetrically enlarged and somewhat boggy and tender if exam is conducted premenstrually Case: pt is a 45 yr old G2P2002 w/hx of progressively worsening painful and heavy periods. She has tried birth control pills without improvement. She is examined and has a boggy tender uterus. You repeats exam 2wks later and finds uterus to be smaller and not as tender. What is likely dx?

Adenomyosis (AUB-A) -US & MRI -Official dx only w/SX pathology (generally after a hysterectomy) -if still childbearing goals: manage w/hormones; when done, move towards hysterectomy

Consent to Medical Care -Parents have right to consent to minor child's medical/dental care -Minors can consent if: Active duty w/armed services; 16yo/older and residing apart from parents, managing conservator/guardian and managing his/her own financial affairs; Unmarried and pregnant and consenting to tx related to pregnancy other than abortion (judicial bypass for minors to get abortions); Unmarried & parent of a child and has actual custody of that child and consents for tx of child; dx/tx of an infectious, contagious, or communicable dz; tx for chemical addiction, dependency; Suicide prevention; sexual, physical, or emotional abuse.

Adolescent Clinic Visit -Assess current office practices -Train & prepare staff -Create an appealing office environment -Provide on-site educational materials -Appropriate supplies & equipment -Tailor visit to adolescents: more layman's terms -Schedule a F/U visit -Greeting pt: first name & ask about their lives -Gather info w/pt & her family; Gather info w/adolescent in private: sexual activity, abuse, depression, drugs, self harm -Engage adolescent and her parent/caregiver in education; Provide straightforward explanations; Use diagrams and pictures whenever possible -Develop a plan together: Discuss alternatives, possible outcomes, and how adolescent feels about issue

Vulvovaginal dryness, decr vaginal lubrication w/intercourse, dyspareunia, bleeding, vulvovaginal burning/irritation, vaginal discharge; incr susceptibility to infection & trauma-->bleeding, petechiae, ulceration -Hypoestrogenic changes to vulvovaginal area; Natural/SX menopause

Atrophic Vaginitis PE: labia minora resorption/fusion, loss of hymenal remnants, prominence of urethral meatus, vulvovaginal pallor/erythema, loss of rugae, thinning of epi cells, loss of elasticity of vaginal epi, narrowing of vaginal canal, decr vaginal secretions, scarce pubic hair -Vaginal moisturizers/lubricants (w/intercourse) -Vaginal estrogen

-50-75% asymptomatic -Vaginal Discharge: off-white/gray, thin, homogeneous -Odor- "fishy smell"; worse after intercourse and with menses -Shift in vaginal flora from Lactobacillus to facultative anaerobes (Gardnerella) - Vaginal pH >4.5 (nl 4.0-4.5); NOT a STI -RFs: sex, STIs, minority population, douching, smoking Case: 34yo G2P2 presents with 2 days of vaginal discharge with vaginal odor. She is in a monogamous relationship and has no new sexual partners. On exam, the vulva appears normal. You swab the vaginal discharge and perform a wet mount and see this under the microscope: clue cells

Bacterial Vaginosis (AMSEL IN BACTERIAL DISTRESS) -Amsel criteria (at least 3): characteristic vaginal discharge, incr pH, clue cells on wet mount**, positive whiff-amine test (fishy odor with 10% KOH) -Commercial tests: Affirm (DNA probe assay) -Metronidazole PO (don't drink alcohol)/vaginal gel (when breastfeeding) -Clindamycin if allergic

Contraception -abstinence: only 100% effective -Gold: implants, IUD, female/male sterilization -Silver: injectable, pills, patch, ring -Bronze: M/W condom, diaphragm, fertility awareness based -Participation: spermicides & sponges -Not recommended: w/drawal & no contraception -stop sign: emergency Abstinence: not having intercourse; 100% protection against all STD's; 100% protection against pregnancy; Free; No S/Es Implant (Nexplanon): Progestin-containing implant that is placed subdermally in upper arm; Lasts for 3yrs; MOA: suppresses ovulation, incr cervical mucus viscosity, endometrial atrophy; Not studied in W who weighed >130% of ideal body wt; S/E abn bleeding IUD: Progesterone-releasing; Mirena (5yrs), Liletta (6yrs), Kyleena (5yrs), Skyla (3yrs) -MOA: atrophic endometrium, thickens cervical mucus, decr tubal motility -C/Is: pregnancy, uterine anomaly, PID, uterine infection in past 3mos, uterine/ cervical neoplasia, uterine bleeding of unknown etiology, untxed acute cervicitis/vaginitis, acute liver disease/tumor, incr susceptibility to pelvic infection, allergy to device, breast ca or other progestin-sensitive ca Copper IUD (Paragard): 10yrs; MOA: inflammatory response against sperm, blastocyst; inhospitable endometrium for implantation -C/I: pregnancy, uterine anomaly, PID, uterine infection in last 3 months, uterine/cervical malignancy, uterine bleeding of unknown etiology, mucopurulent cervicitis, Wilson's disease, allergy -Can be used for emergency contraception up to 5ds after unprotected intercourse -can make periods worse, but Mirena can make amenorrheic -IUD's and implant should be offered routinely as safe and effective contraception options for nulliparous women and adolescents. Female Sterilization (risk of regret esp <30): -Hysteroscopic office procedure: Essure-now removed from market -SX: Postpartum BL tubal ligation or during c-section; Laparoscopic BL tubal ligation - Laparoscopic BL salpingectomy Male Sterilization=Vasectomy: Safer, less expensive, more effective! ** Depo-Provera Injection: IM injection q12wks; MOA: incr cervical mucus viscosity, thin endometrium, may suppress ovulation -C/I: pregnancy, unexplained uterine bleeding, liver dz, cerebrovascular dz, thromboembolic disease

Birth Control Pills (OCPs): Contain estrogen and/or progesterone; 1 pill at same time each d (if on estrogen pill & miss pill by 3hrs, need backup birth control for 2ds); MOA: inhibit ovulation, thicken cervical mucus, thin endometrium -C/I: pregnancy, uncontrolled HTN, DM, CAD, migraines w/ aura, DVT/PE, thrombophilias, cardiac defects/arrhythmias, breast/endometrial ca, liver problems Patch: Estrogen & progesterone; MOA and C/Is similar to OCPs; Place 1 patch, 1x/wk for 3wks; Then remove for 1wk; Can place anywhere except breast; wt >90 kg are at incr risk of pregnancy. Ring: Estrogen and progesterone; Insert vaginally for 3wks then remove for 1wk;. Must be refrigerated. Shelf life is 4 months. Can remove for intercourse but must replace w/in 3hrs. Male Condom -Prevent semen from entering vagina/cervix; Must be placed prior to intercourse every time; Does prevent against STD's; Perfect use failure: 2/100; Typical use failure: 18/100; High failure rate; Even higher in teens! Female Condom: Placed inside vagina to prevent semen from reaching cervix; Do not use w/a male condom Cervical Cap and Diaphragm: Placed over the cervix; Must be fitted by a healthcare professional; Not commonly used Fertility Awareness-based Methods: ID of fertile days based on menstrual cycle & observational methods and avoid intercourse during those days; Takes education, persistence, and motivation from both partners Spermicide: Creams, gels, foam, film; If used w/o other forms of contraception, they are not very effective; Not effective at preventing STD's and may incr rate of HIV transmission. Emergency Contraception: -"Plan B": one dose w/in 72hrs (up to 120) and a second dose 12hrs later; Prevents 75% of pregnancies; S/Es: NV, cramping; MOA: delay/inhibit ovulation, prevent implantation; Does not disrupt an existing pregnancy. It is not the abortion pill. No clinical exam is necessary -Copper IUD; Inserted up to 5 days after unprotected intercourse; Most effective method Lactation: 20% of breast-feeding W will ovulate by 3 months postpartum; Ovulation often precedes menstruation; OCPs may begin at 6wks postpartum if breastfeeding is well established. Other methods can be started right after delivery Immediate Postpartum LARC -Benefits: convenient, effective at preventing pregnancy and lengthening interpregnancy intervals -Risks=IUD: incr risk of expulsion/loss of IUD strings; Implant: theoretical interference w/breastfeeding

Breast Mass Disorders Cyst: Arise from apocrine metaplasia of lobules, Soft, mobile and smooth, 40-50yo; dx=US; May be aspirated if painful -Simple: sonolucent on US (looks completely black, filled w/liquid); just observe -Complicated: internal echoes; Should be drained, not resolve then biopsy -Complex: septa/masses; Excision is recommended Fibroadenoma: Comprised of glandular and cystic epi structures surrounded a cellular stroma; MC of breast clinic visits; Adolescents and premenopausal W; Rubbery**, mobile, smooth w/distinct margins; May involute at menopause; differentiate from cyst is US; Followed w/o excision (triple test); If growing remove Galactocele: Cystic dilation of a duct; Painless mass palpable usually in central portion of breast; Breastfeeding pt, could get infected; Subsides on own Fat Necrosis: Breast mass that can develop after blunt trauma, breast SX, radiation or injection of foreign substance (fat, paraffin or silicone); Solitary, irregular, ill-defined* mass; Can be clinically difficult to distinguish from malignant mass; imaging & biopsy Phylloides Tumor: Histologically similar to fibroadenomas, Rare; 40yo; Benign, intermediate, malignant (diff from fibroadenoma is that can be malignant; based on cellular atypia); tends to grow rapidly so Wide local excision

Breast Cancer: 2nd MC cancer (skin), MC in W; 2nd leading cause of death from cancer (lung); Mortality has decr steadily since 1990=Earlier detection and improved tx; Lobular/Ductal Carcinoma insitu (cancer but hasn't invaded tissue; best px); Invasive breast Cancer (invading); Pagets dz; Inflammatory breast Cancer -staged by TNM -TX: SX, chemo, RT, Hormonal therapy -Screening: Breast Imaging (Mammogram; start around 40), Clinical Breast Exam, pt self examination or self awareness -Mammogram: Detection at early stage are small and confined to breast; Pot identify nonpalpable mass measuring 1mm-1cm (preclinical phase); Sojourn time (before it becomes palpable) -Breast Imaging Reporting and Database System (BI-RADS) from mammogram 1: Negative, no sig or noticeable abn 2: Benign finding 3 Probably benign, finding likely benign (6 mth FU) 4: Suspicious abn, may require biopsy 5: Highly sugg of malignancy, requires biopsy 6: Known biopsy proven malignancy 0: Need additional eval -U/S screening: Inconclusive mammographic findings; Young pts/dense breast tissue; Guiding tissue core needle biopsy; Differentiating cyst vs solid mass; Not rec as screening modality for W at avg risk -MRI: Adjunct to mammogram; Cost, duration, injection of contrast material; recommends MRI for >=20% lifetime risk of developing breast Ca; if BRCA1/2, 1st degree rel w/BRCA but no testing themselves, hx of radiation tx to chest b/w 10-30yo; Other genetic dz (Li Fraumeni, Cowden, Bannayan Riley Ruvalcaba)

-Primary: genital ulcer/mucosal inflammation at site of inoculation. Resolves w/in few ds. -Secondary: 2-6wks after primary. Infection extends to LNs. Inguinal syndrome-inflammatory rxn in inguinal LNs -->"groove sign"; can cause buboes and rupture; Anorectal sxs- inflammatory mass in rectum and peritoneum-->proctitis, rectal discharge, pain, C, tenesmus. -Late: fibrosis & strictures in anogenital tract; If severe, can cause destruction of external genitalia and infertility. -L1, L2, L3 serovars of Chlamydia trachomatis; STI

Lymphogranuloma Venereum -NAAT- swab lesion, FNA, rectal specimen -Serology: complement fixation titer >1:64 -+ chlamydia w/proctitis= presumptive dx -azithro/doxy; tx partner

Found on vulva, groin, perineum, anal skin; Flesh-colored, red, hyperpigmented; Single/multiple, cauliflower-like**; Asymptomatic -Anogenital warts; Sexually transmitted; HPV types 6, 11 -RFs: Immunosuppression: HIV, DM, smoking

Condyloma Acuminata (vulvar lesion) -PE; Biopsy if uncertain; Screening for other STIs Pt-administered: Imiquimod cream MC, Podofilox solution/gel, Sinecatechins ointment Provider-administered: Trichloroacetic acid (TCA) solution; Cryotherapy; SX removal

Perinatally Acquired Herpes Simplex -HSV is transmitted to an infant during birth, primarily through an infected maternal genital tract -risk of transmission is greater w/primary HSV infection acquired during pregnancy, compared w/reactivation of previous infection -Most newborns w/perinatally acquired HSV appear nl at birth Dz develops in 1/3 patterns: Localized to skin, eyes, and mouth (SEM); Localized CNS dz (seizures, tremors, poor feeding); Disseminated dz involving multiple organs (sxs may be non specific: Temperature instability, Respiratory distress, Poor feeding, Lethargy, Vesicular skin lesions may /not be present, Hypotension, Jaundice, DIC, Apnea and shock)

Congenital (in utero) Herpes Simplex Infection -Rare; Usually results from maternal viremia associated w/primary HSV infection during pregnancy -S/S in liveborn infant: Characteristic triad of skin vesicles, ulcerations, or scarring; Eye damage; Severe CNS manifestations; Microcephaly/hydranencephaly (kind of combined of all 3 perinatal patterns?) TX for both perinatally acquired and congenital herpes simplex: acyclovir

Mother: painless papule-->indurated ulcer Child: Consider how common it is in W of childbearing age; Seen in infants when mother received no prenatal care, no PCN tx, or inadequate tx before/during pregnancy; Most infants are asymptomatic at birth; Clinical manifestations are divided arbitrarily into early (≤2yo) and late (>2yo) MC: Placental & umbilical cord abns, Hepatomegaly, Syphilitic rhinitis ("snuffles"), Maculopapular Rash -late sxs: saddle nose, Hutchinson teeth

Congenital Syphilis Child -quantitative nontreponemal test on infant serum -PE for evidence of congenital syphilis/direct fluorescent ab (DFA) staining of suspicious lesions/body fluids -Pathologic examination of placenta/umbilical cord w/ specific fluorescent antitreponemal ab staining Parenteral PCN DOC

Erythematous papule(s)-->pustule(s)-->ulcer(s)=PAINFUL; Regional lymphadenopathy -Rare in US; H. ducreyi; Sexually transmitted

Chancroid -PE; Negative testing for syphilis; Negative HSV PCR or culture -Azithro/Ceftriaxone

Majority asymptomatic; Mucopurulent cervical discharge, friable cervix, intermenstrual vaginal bleeding, post-coital bleeding, DU -Chlamydia trachomatis; Sexually transmitted

Chlamydia -NAAT GS -Azithro/Doxy (not in pregnancy) -Poss complications: PID, infertility, ectopic pregnancy; Pregnancy: PROM, PTD, low birth wt Case: 19yo G1P0 (pregnant for 1st time) presents for initial OB visit in first trimester. She is asymptomatic. Her pelvic examination is benign. You perform a routine urine collection of gonorrhea and chlamydia as your standard prenatal labs. The test comes back positive for chlamydia. How will you treat her? Azithro (doxy not safe); do test of cure at next appt

Nl Pregnancy Pregnancy Duration -Trimesters: 14wks each; 1st=spontaneous abortions; 2nd=quickening, heart sounds; 3rd=neonatal viability, preeclampsia -Obstetricians use LMP; Mean = 280 ± 17ds (± 2SD); Naegle's rule for EDD: Add 7ds to LMP, Subtract 3mos Pregnancy Dating -Accurate assessment of GA: Establish an EDD=1st visit; Confirm EDD=Early is better; Critical in decision making: Preterm labor, Medical complications Rpt Prenatal Visits -Assess fetal and maternal wellbeing -Freq: q4wks until 28wks, 2wks 28-36wks, qwk >36wks -Every visit: wt, BP, edema, urine dip, fundal ht, fetal heart tones, fetal position Key Milestones -12wks: Fetal heart tones by Doppler -15: Triple Screen -18-20 Quickening -20 Fetal heart tones by fetoscope -24-28 Glucola -28 CBC, RPR, IDC, BCM, Rhogam -36 Cultures, Hemoglobin -41 Antepartum testing Miscarriage/Spontaneous Abortion: death of embryo/fetus w/hemorrhage into decidua basalis-->adjacent tissue necrosis; stimulates uterine contractions & expulsion; ovulation may resume as early as 2wks after early abortion -dx: lack of embryonic/fetal development w/o cardiac motion on U/S -TX: control bleeding, infection control -most in 1st trimester is from chromosomal anomalies; less in 2nd, and 3rd from other causes -other causes: infections (listeria), DM/thyroid dz, radiation, alcohol -missed abortion: lack of embyronic/fetal development w/o cardiac motion on US w/no cervical dilation; tx: wait on spontaneous evacuation; Misoprostol vs dilation & curettage -incomplete: lack of embyronic/fetal development w/o cardiac motion on US w/incomplete uterine emptying; need to intervene b/c high risk infection=Misoprostol vs dilation & curettage -complete: lack of embyronic/fetal development w/o cardiac motion & complete evacuation of uterus; tx: tissue testing, reassurance Gestational Diabetes: any degree of glucose intolerance during pregnancy -incr IR, decr suppression of hepatic gluconeogenesis -Diabetogenic hormones: hPL, prolactin, cortisol, somatomammotropin -Insulin release fails to keep pace w/ demands -screening all pregnant women -dx: 1 hr PO glucose challenge (screen), 3hr glucose tolerance test (dx) -if fair 3hr: glucose monitoring 5-7x/d; diet, exercise; tx

Chronic Hypertension: Onset <20wks gestation Gestational Hypertension: No proteinuria; Onset ≥ 20wks gestation Preeclampsia: onset >=20wks; HTN, proteinuria, edema; goes away after pregnancy -RFs: Nulliparity, Maternal ≥ 35yo, Obesity, AA, Multifetal gestations, Hx preeclampsia, HTN, etc -HTN: ≥ 140/90 -Proteinuria: >300 mg protein per 24hr urine collection; Protein/Cr ratio ≥ 0.3 -HTN w/o proteinuria: Thrombocytopenia; Renal insufficiency: Serum Cr > 1.1; incr liver transaminases, Pulmonary edema, cerebral/visual sxs -Preeclampsia w/severe features: >=160/110; thrombocytopenia; impaired liver fxn, severe RUQ pain, renal insuff, pulm edema, new onset cerebral/visual sxs -HELLP syndrome: Hemolysis, Elevated Liver enzymes, Low Platelets -TX: delivery; term-->deliver; preterm-->Await Severe Criteria Eclampsia -Tonic-clonic seizure as manifestation of preeclampsia -Prelude HA in 80% of cases -tx seizure (magnesium sulfate) and deliver Preterm Labor: Delivery <37wks gestation -very common & super expensive Vaginal Bleeding In Pregnancy -pot causes: sex, infection, preterm labor, abruption, placenta previa, ca Postpartum Blues 70% -Transient state of tearfulness, anxiety, irritation, restlessness -sxs occur in 1st wk and resolve by d10 -No therapy indicated except for reassurance Postpartum Depression 8-15% -RFs: Life situations, stresses; hx of depression -50-100% risk of recurrence -tx w/antidepressants and supportive care; Usually self-limiting by 1yr Postpartum Psychosis -Schizophrenia and bipolar rxns are more common postpartum -Feticide, homicide, suicide -hx of mood/thought disorders are RFs -Usually lasts 2-3mos -Hospitalization and tx

Benign Ovarian Tumors HX: potential for pregnancy should be evaluated in all W of reproductive age b/c ectopic pregnancy is ddx of adnexal mass in early pregnancy. -sxs of UL, intermittent, and then acutely worsening pelvic pain: ovarian torsion. -more indolent, progressive pelvic pain w/Fs chills, V, & vaginal discharge: infectious etiology such as a tubo-ovarian abscess. -acute/chronic dysmenorrhea/pain w/intercourse: endometrioma -Persistent bloating, generalized abd pain, and early satiety: malignancy -abn uterine/postmenopausal bleeding may be caused by estrogen produced by sex cord-stromal tumors -if adnexal mass, need pelvic exam & bimanual palpation w/rectovaginal exam as indicated Imaging -TVS MC for adnexal masses; abd ultrasonography is useful too -CT/MRI not for initial eval; CT for metastasis/cancer Ca-125: Tumor marker; May help to distinguish b/w benign & malignant masses (specially in postmenopausal pts) -CA 125 glycoprotein ag screens for ovarian ca; incr 50% w/early-stage dz and 80% advanced ovarian ca -Can be incr in: Pregnancy, Fibroids, Ovarian ca (Used to monitor tx response, in thousands), Endometriosis (in hundreds), Liver dz, PID

Functional Ovarian Cyst -follicle must reach diameter of 3 cm; may cause pelvic pain, a dull sensation, or heaviness in pelvis. -dx when 3-8cm cystic adnexal mass is noted on bimanual examination -confirmed when lesion regresses over course of next several cycles; In general, is mobile, UL, and not associated w/ascites. -Low-dose contraceptive agents may be given to suppress gonadotropin levels and prevent development of another cyst. (preventing ovulation prevents new cyst; OCPs can't dissolve cysts) -SIZE MATTERS! A cyst of 3cm vs 10cm will cause diff sxs and will require diff txs (observation vs SX) -When to refer to a Gynecologist? If cyst persists after >=6wks; symptomatic; large cyst (>10cm); if ovarian torsion can not be r/o Case: A 23 y/o G1P1 (1 baby, 1 pregnancy) presents to clinic w/new crampy pain in her right pelvic over last 3ds. Her LMP was 3wks ago and was nl. She uses condoms for contraception and her urine pregnancy test is negative. On pelvic examination, a 3-4 cm tender cystic mass is found in R adnexa. The remainder of her examination is negative. -next step: TVS (CT too expensive, Ca125 pt is still young, dx laparoscopy too aggressive) -TVS showed 3.1cm R ovarian cyst, no ascites: F/U in 6wks; she has a fxnal cyst -During F/U, pt feels better and pelvic exam is unremarkable. TVS showed no ovarian cyst BL; You offer her: OCPs

Abd pain, Amenorrhea, Vaginal bleeding -nl pregnancy discomforts (breast tenderness, freq urination, N ,etc) -pelvic tenderness, cervical motion, enlarged uterus, adnexal mass/tenderness OR asymptomatic (small, unruptured) -implantation of fertilized egg in location outside of uterine cavity; fallopian tubes (MC 95%; 70% ampulla); uncommon types: Cervical, Ovarian, Interstitial, Abd, Intramural (pregnancy implanted w/in myometrium of uterus) -leading cause of maternal death due to hemorrhage in 1st trimester -High RFs: Previous ectopic pregnancy/tubal SX, Tubal ligation/pathology, In utero DES exposure, Current IUD use -Why?: (1) conditions that prevent passage of fertilized oocyte into uterine cavity or (2) factors inherent in embryo that result in premature implantation -pregnancy test; C/I: no uterus (hysterectomy), confirmed menopause, young girls before menarche, XY -pregnant W w/suspected ectopic gestation: BHCG & TVS -BHCG: Can be detected in serum/urine as early as 8ds after LH surge if pregnancy has occurred; 85% viable intrauterine pregnancies=BHCG rises by 66% q48hrs during 1st 40ds of pregnancy; BHCG rises much slower in most ectopic/nonviable intrauterine pregnancies -Discriminatory Zone: serum BhCG level above which a gestational sac should be visualized by US if an intrauterine pregnancy is present=1500 w/TVS & 6500 w/transabd US -TVS: detects presence/absence of gestational sac w/in/outside of uterus and establishes dx; US is most useful for identifying an intrauterine gestation. The earliest sonographic sign of an intrauterine pregnancy is presence of a true gestational sac -dx of ectopic pregnancy=Visualization of an extrauterine gestational sac containing a yolk sac/embryo; Fluid in pouch of Douglas (Cul-de-sac); complex adnexal mass, + pregnancy test & empty uterus=highly suggestive of extrauterine gestation & MC sonographic abn

Ectopic pregnancy Other dx but TVS & BHCG usually sufficient nlly -Progesterone concs lower in ectopic; <5 ng/mL: poss ectopic; >20 ng: not ectopic -Curettage: intrauterine location is dx w/certainty if trophoblastic tissue is obtained by uterine curettage -Doppler: Blood flow in a's of fallopian tube w/ectopic pregnancy is 20-45% higher than in opp tube; Color Doppler may demonstrate a ring of blood flow -laparoscopy -culdocentesis: Blood in cul-de-sac may be from bleeding from tubal pregnancy MTX: antimetabolite/folic acid antagonist that binds to catalytic site of dihydrofolate reductase, stopping synthesis of purine nucleotides and AAs serine and methionine, thus inhibiting DNA synthesis/repair & cell replication; affects actively proliferating tissues -dose of MTX used to tx ectopic pregnancy (50 mg/m2or 1 mg/kg) is relatively low -for: hemodynamically stable, willing and able to comply with posttx FU; BHCG ≤5000 mIU/mL; no fetal cardiac activity; ectopic mass size <3-4 cm -CI: Breastfeeding, immunodef; Alcoholism, alcoholic liver dz, or chronic liver dz; Preexisting blood dyscrasias such as BM hypoplasia, leukopenia, thrombocytopenia, or sig anemia; Known sensitivity to MTX; Active pulm dz; Peptic ulcer dz; Hepatic, renal or hematologic dysfxn SX for: Hemodynamic instability; rupture of ectopic mass; CI MTX; Coexisting intrauterine pregnancy; Lack of timely access to a medical institution for management of tubal rupture; Desire for permanent contraception; Known tubal disease w/planned invitro fertilization for future pregnancy; Failed meds -Laparoscopy: standard SX approach for ectopic -Salpingectomy: removal of a fallopian tube -Salpingostomy: SX incision into a fallopian tube; risk of persistent/recurrent ectopic pregnancy; weekly bhCG & TVS after until level undetectable -Exploratory Laparotomy: if hemodynamically unstable, active bleeding, inexperience w/laparoscopy, lack of laparoscopic equipment

-Most benign "tumors" of fallopian tubes are infectious/inflammatory: hydrosalpinx and pyosalpinx (pus, most likely from active infection); quite difficult to differentiate a tubal neoplasm from other adnexal masses on PE/bimanual exam and operative exploration is generally necessary to confirm dx Case: A 32 y/o patient comes in for her routine annual exam. She does not have any complaints. Her gynecological hx is remarkable for chlamydia infection* about 2 years ago. She was txed successfully for this infection. On pelvic examination, there is a 4cm x 4cm left adnexal fullness. Her pregnancy test is negative. An TVS is ordered=tubular structure adjacent to L ovary; L ovary appeared nl, no pelvic fluid===hydrosalpinx (water inside fallopian tube; most likely caused by infection that caused fluid to be retained)

Fallopian tube tumors -Salpingectomy

Infertility: failure of a reproductive age couple to conceive after ≥ 12mos of regular coitus w/o contraception; Not sterility, but subfertility -Expected Time Required for Conception: 3mos 57%, 6mos 72%, 12mos 85%, 24mos 93% -When to evaluate: <35yo=after 12mos of unprotected intercourse; 35-40yo=after 6mos; >40yo= immediate evaluation, prayer, counseling; any time for known/suspected pathology -causes: tubal/pelvic path & male infertility MC -hx: age W; Cystic Fibrosis, Sickle Cell DX 1. Nl semen analysis: vol >1.5, pH >7.2; Sperm conc >15 million/ml; Motility >40%; Morphology >30% & >4% strict morphology -Total motile (vol x ct x % motile) > 10million -Male Endocrine Evaluation (FSH, test): abn semen analysis (<10 mil total motile), Impaired sexual fxn, Other S/S; If test is low, check total & free test, LH, Prolactin -Male infertility: Post-ejaculatory U/A (retrograde); Ultrasonography; Antisperm abs; Chromosomal analysis -Chromosomal abns: Non-obstructive azoospermic (semen has no sperm); Inversely correlated w/ct (Azoospermic 10-15%; Oligospermic 5%; Nl <1%); 10-15% of azoospermic/severely oligospermic have Y-chromosome microdeletions; CBAVD (congenital BL absence vas deferens)= Cystic Fibrosis 2. Ovulation/Ovarian fxn: Evaluate for Hypothyroidism, Hyperprolactinemia, Adrenal hyperplasia late onset, Androgen excess; Consider ovarian reserve testing: AMH best -Methods used to assess ovulation: Basal body temp chart (not great; only retrospective), Midluteal phase serum progesterone best, Luteal phase endometrial biopsy, Detection of LH in urine MC (pee on stick), Cervical Mucous, Cyclic pain, US, REGULAR CYCLE/Moliminal sxs (if do, then ovulatory) -Ovulatory dysfxn: PCO MCC 70%; Hypothalamic & pit disorders 10% each; 5% ovarian failure; 10% pts w/unexplained infertility will have diminished ovarian reserve -If not PCOS: if incr Prolactin, obtain MRI, TSH, Assess Ovarian fxn when indicated by sxs (hot flashes, amenorrhea) or >35 yo; Strongly consider in unexplained infertility. -Nl Ovarian Reserve Values: D3 FSH <10 IU/L, E2 <80 pg/mL (estradiol); AMH: ≥1 ng/ml, grey zone (0.7-1.0) MC; AFC: nl >4 follicles in each ovary, abn <8 total. 3. Tubal Patency: hysterosalpingogram (HSG); pelvic pathology associated w/infertility: tubal dz, endometriosis, uterine abns 4. Uterine Abns: Congenital deformities of uterus, Leiomyomas, Asherman's syndrome, Intrauterine polyps 5. Peritoneal abns: After nl HSG consider dx laparoscopy and hysteroscopy if hx pelvic SX/infection/pain, 3-6mos of unsuccessful tx & IVF not an option, before ovulation induction/IUI in pt w/suspected endometriosis*

Fertility TX Options -Expectant -Timed Intercourse (TI): no pregnancies when intercourse occurred day after ovulation; highest is 2ds before ovulation -Clomiphene Citrate (CC)/TI: doubles pregnancy -Newer agents Femara/Metformin (PCOS) -CC/Intrauterine Insemination (IUI): doubles pregnancy -CC/gonadotropins (OI)/IUI -Gonadotropin/IUI -SX -In Vitro Fertilization (IVF): Most aggressive & expensive & risk for multiple gestations but highest success rates; Not first line but should be considered sooner in many circumstances: Age, known indications, unsuccessful basic fertility tx -if didn't get tx at 3yrs, can still conceive 25% Conclusions: Infertility evaluation and tx should be AGE sensitive and tailored to individual pt -Basic Eval: Semen Analysis, HSG, Ovulation Assessment, Consider Ovarian Reserve Testing -"High Tech" is not always required: Timing of intercourse prior to ovulation; wt loss; Maximize OI (ovulation induction) and IUI usage -Specific underlying disorders tx; Most couples who conceive do so in 1st 3mos of therapy. Progress tx or refer to REI; When in doubt, >35, or known indications don't delay......REFER!

Vulvar burning, itching, tingling-->painful genital ulcers/vesicles -Systemic sxs (primary infection): F, HA, malaise, myalgias, dysuria, tender inguinal lymphadenopathy; Duration: 10-19ds -HSV-1 & 2; Sexually transmitted -Incubation period: 2-12ds after exposure Case: 26yo G0 presents with a few "blisters" on her labia majora that she noticed 2ds ago. She has a new sexual partner and does not use condoms. The lesions are very painful and worse w/urination and direct pressure from clothing. She has also had a fever and m aches.

Genital Herpes Simplex Virus (viral vulvar lesions) -Virologic Tests (viral culture and PCR) -Type-specific Serologic Tests (HSV-1/2 Ab) -Tzanck smear: multinucleated giant cells** -Acyclovir/Valacyclovir -Pregnant: Suppressive therapy daily starting 36wks gestation to delivery-Acyclovir; C-section if active lesions/prodromal sxs at time of delivery

Majority asymptomatic; Vaginal pruritus, mucopurulent discharge, incr DU; Friable cervix -N gonorrhoeae (G- coccus); Sexually transmitted

Gonorrhea -NAAT GS -Ceftriaxone IM + azithro -Must tx partner -Poss complications: PID, infertility, ectopic pregnancy, and chronic pelvic pain -Pregnancy: chorioamnionitis, PROM, PTD (premie), low birth wt, spontaneous abortions; neonatal conjunctivitis, pharyngitis, arthritis, gonococcemia -Conjunctivitis, pharyngitis, disseminated gonococcal infection

Human Papillomavirus (HPV) -HPV is associated w/oropharyngeal and anogenital cancer; Includes cervical, vaginal, vulvar, penile, and anal cancer and genital warts ->150 HPV genotypes, 13 have been shown to cause cervical cancer; Most cases of HPV-associated cancer are caused by HPV genotypes 16 and 18=Account for 66% of cases of cervical cancer -90% of genital warts caused by genotypes 6 and 11

HPV Vaccine -routine HPV vaccination for girls and boys at target age of 11-12yo; may be given from 9yo (<15yo, only 2 shots) -Despite benefits of HPV vaccines, only 41.9% W and 28.1% M in recommended age group have received all recommended doses -Advisory Committee on Immunization Practices recommended 9-valent HPV vaccine (9vHPV) -Vaccines are administered in a 3-dose schedule typically: 2nd dose is given 1-2mos after 1st; 3rd dose 6mos after 1st; If vaccine schedule is interrupted, series does not need to be restarted -Compared w/many other countries, HPV vaccination rates in US are unacceptably low -Vaccination is recommended regardless of sexual activity/prior exposure to HPV -The vaccine may be less effective in previously infected individuals; However some benefit will be experienced b/c prior exposure to all 9 vaccine types is highly unlikely; no indication for a booster -vaccination not associated w/earlier onset of sexual activity or incr incidence of STIs -No data to suggest that there are any severe ADRs linked to vaccination -Assess pts for severe allergies, including but not limited to an allergy to yeast or prior HPV vaccine dose -An individual w/mod/severe febrile illness should wait until illness improves before receiving a vaccine -Do not give in pregnancy

simultaneous pregnancies at 2 diff implantation sites; MC combo of intrauterine & ectopic pregnancies

Heterotopic Pregnancy -US: complex adnexal mass/fluid in pelvis -laparoscopy for stable pts; laparotomy TX of ectopic pregnancy should be tailored to site of implantation; Should utilize least invasive therapy in order to preserve concomitant intrauterine pregnancy. -MTX C/I in presence of viable intrauterine gestation. -Salpingectomy is standard SX approach of a coexistent tubal pregnancy -Local injection into sac under sonographic guidance; KCL & Hyperosmolar glucose

Nipple Discharge Disorders Galactorrhea: spontaneous BL milky nipple discharge; Consider pathologic and need evaluation; Hyperprolactinemia; usually comes w/amenorrhea -Multiple causes: Physiologic conditions (Pregnancy, postpartum, stimulation w/bra/sex); meds/Herbs (antipsychotics, lots); Neoplastic processes (pituitary adenoma, renal adenocarcinoma, lymphoma); Systemic dz (hypothyroidism, cushing, RF, acromegaly); Chest wall irritation (zoster, burn, SX, dermatitis); Other (TB, sarcoidosis, MS) -TX directed to cause, Observation may be sufficient, If desires pregnancy (decr prolactin so pt. can have period): Bromocriptine/Carbegoline

Intraductal papilloma=Milk duct polyps: Ductography, poss mammary ductoscopy/US; Duct excision

Drugs in Pregnancy and Lactation -2/3 W use 4-5 drugs -W w/HTN, diabetes, epilepsy must continue therapy; Meds may need to be started, stopped or adjusted -w/a few notable exceptions, MC rxed drugs and meds can be used w/relative safety during pregnancy Maternal Physiology -Altered absorption, distribution, elimination; decr gastric emptying; incr intestinal transit time; incr pulmonary blood flow, hyperventilation; incr tidal volume incrs absorption of inhalation agents "Birth Defects" 3 % of all children born in U.S. have major structural malformation detectable at birth; drugs rarely cause birth defects -teratogen: agent which produces a congenital defect -Congenital Defect: Genesis during embryonic/fetal development; Major/minor deviation from nl morphology/fxn; id of a defect is not enough to prove causation -embryos (3-8wks) are way more sensitive to teratogenesis than fetus -Criteria for Teratogenicity: Proven exposure at critical time; Consistent findings by ≥2 epidemiologic studies; Careful delineation of cases (make sure comparing apples to apples); Rare exposure = rare defect (ex: zika); Teratogenicity in an animal; Biologically plausible -Old FDA Classifications: category A (controlled studies in humans: no risk; tylenol & prenatal vits), B (Animal studies show no risk & no controlled human studies OR Animal studies show incr risk but controlled human studies show no risk; ex: Penicillin/Methyldopa), C (Animal studies show incr risk and no controlled human studies OR No animal/human studies; Ex: Nifedipine/Acyclovir/Sumatriptan), D (Proven risk in humans; Benefits might outweigh risks; ex: Valproic acid/Gentamicin), X (Category X; Proven risk in humans, animals, or both; Risk outweighs benefits; Ex: Isotretinoin/Misoprostol/Warfarin) -Study Problems: Recall Bias; Reporting Bias; Hawthorne Effect (pop observed closely is more likely to report things) -Confounding Factors: Drug administered for condition which itself is teratogenic; Malformation causes sxs which then prompt tx w/a drug; Drug inhibits abortion of an already malformed fetus; Drug freq used w/a second drug which is teratogenic; Common RFs for drug use and anomalies (incr age) Preconception Counseling: The best time to prevent med effects on a pregnancy is before pregnancy; Review Medication and Drug Use; Provide Risk Assessment; Formulate Management Plan Bendectin: Antihistamine (doxylamine) and pyridoxine; Many lawsuits in 1970's, w/drawn from market in 1983; No evidence of teratogenicity; when drug went off market, NV rates incr; hurt W by poor science Thalidomide: Severe limb reduction defects; Ear, renal, and cardiac abns; affects 20-30% of fetuses exposed b/w 27-40th d after conception (27-30: arms only; 30-33: legs only) -lessons: Placenta is not a barrier; Extreme variability in species susceptibility (Mouse and rat insensitive; Rabbit, monkey, humans sensitive); Precise relationship b/w time of exposure and defect

Isotretinoin (Accutane): Spontaneous abortion in 40%; Major malformations (≥ 25%): CNS, CV, Craniofacial; Known to be teratogenic before used clinically; Explicit warning labels utilized; Many cases of retinoid embryopathy reported Diethylstilbesterol (DES): Mullerian Anomalies; Vaginal Clear Cell Carcinoma Anti-Seizure Drugs: 2-3x incr risk for NTD (neurotubal defects); Impaired folic acid metabolism -Phenytoin & carbamazepine: Hydantoin syndrome -Valproate: NTD's in 1 - 2% Trimethadione: Major defects in 66% Fetal Hydantoin Syndrome: Craniofacial/limb abns, Cleft lip/palate, Hypertelorism, Broad nose, Nail hypoplasia, IUGR, Mental retardation Alcohol Dose-dep Effects: ≥ 3 oz. EtOH/d: 50% abn; 1-2 oz EtOH/d: functional & growth disturbances; < 1 oz EtOH/d: usually no effect Warfarin (Coumadin) -1st Trimester: Fetal Warfarin Syndrome -2nd Trimester: Mental Retardation, Blindness -3rd Trimester: Hemorrhage, Stillbirth -Embryopathy: 15-25 % affected w/1st trimester exposure; Critical period 6-9wks; Likely results from tissue microhemorrhages; Microcephaly, Nasal Hypoplasia, Stippled vertebrae and femoral epiphyses ACEi: Fetal/Neonatal Renal Failure (renal tubular dysgenesis), Oligohydramnios, Pulmonary Hypoplasia, IUGR, Stillbirth Misoprostol: incr risk of miscarriage (40%); Use in first trimester w/Mobius syndrome: CN VI /VII palsy; Limb malformations; Craniofacial abns Lithium: cardiac defects Tetracycline: Readily crosses placenta; Staining of deciduous teeth (>16wks); Enamel hypoplasia; Inhibition of bone growth Pot Teratogens -Danazol: Weak androgen effect; Virilization of W fetuses exposed <13wks: Clitoromegaly, Labial Fusion -Metronidazole: Carcinogenic in rodents, Mutagenic in bacteria, No associated malformation in humans; Avoid 1st trimester -Aminoglycosides: pot for ototoxicity (1-2%); No associated malformations -Sulfonamides: Competes w/ bilirubin-binding sites; pot for hyperbilirubinemia; No known malformations -Quinolones: High affinity for bone/cartilage; Arthropathy in children; No known malformations -Unlikely Teratogens: Steroids. Tranquilizers, Antidepressants, Anti-inflammatory Drugs, Antibiotics, Antihistamines, Anesthetic agents Alcohol: MC preventable cause of mental retardation; Fetal Alcohol Syndrome (FAS); Absent Philtrum, Midface Hypoplasia, Low Nasal Bridge, Low Set Ears, Microcephaly, Shortened Palpebral Fissures Illicit Drugs -Cocaine: Vascular disruptions -LSD: No clinical effect -Marijuana: Dose-related IUGR -Amphetamines: IUGR, cardiac defects, facial clefts -Heroin/Methadone: Neonatal withdrawal Mercury: neuro abns, microcephaly Lead: dev delay, decr IQ, minor malformations Lactation: Consider dose, portion excreted in milk, amt absorbed by infant; wt corrected % of maternal dose ingested by 3 kg newborn and resulting neonatal blood level -Milk more acidic (7.1) than plasma -High liposolubility facilitates passage -High MW do not cross easily -High protein binding limits passage -C/I: methotrexate, lithium Conclusions: Before rx a drug, consider dose, timing, susceptibility; Although many drugs appear to be safe in pregnancy, no drug can be guaranteed harmless; Evaluate drug therapy before conception!

Pelvic Pain Dysmenorrhea: Painful periods; Primary= Have been present since onset of menses; Secondary=Developed later in life Dyspareunia: Pain w/sex Vulvadynia: Pain of vulva Dyschezia: Pain w/bowel movements Dysuria: Pain w/urination Chronic pelvic pain: Pelvic pain that has been present for >6mos Cyclical vs. Daily: Cyclic does not always mean GYN related, but daily pain usually is not GYN related; Cyclic pain make you think of thinks like fibroids, endometriosis, adenomyosis Associated symptoms -Urinary sxs: Interstitial cystitis, UTI, Kidney stone ? -Worse w/movement or certain positions - Back pain, musculoskeletal pain? -GI sxs - IBS, IBD? Appendicitis -Heavy irregular bleeding- Fibroids? -Fevers? Kidney infection, Appendicitis, PID, Diverticulitis ? -wt loss/incr abdominal girth: Ovarian Cancer, Cervical cancer, Uterine Cancer, GI cancer -Age of Onset -Could she be pregnant? Remember that tubals fail about 1/100; pts are correct about their last period only about 2/3 of the time so can't trust LMP; get pregnancy test Exam: All lower abd pain warrants a pelvic exam -Abdominal exam: rebound, guarding, point tenderness on a scar? (acute process) -Back: CVA tenderness, lbp can radiate to front and be reported as pelvic pain -Vaginal/vulvar pain: Herpes, abuse; if chronic pain, could be levator ms -Bladder pain: palpate it just anterior to uterus -Uterine pain, cervical motion tenderness: Infection, PID, endometritis, adenomyosis -Posterior to uterus: Nodularity may mean Endometriosis -Speculum exam: Cervicitis , do STD swab for most pts -Adnexa - Fullness, tenderness, Remember that bowel also lives in the adnexa

Labs: Pregnancy test; CBC if seems to be infection/heavy bleeding; Tumor markers like CA-125 are seldom helpful in premenopausal pt; Urine culture if urinary sxs Sonogram (vaginal US) often first test we use for evaluating pelvic pain; Can show us fibroids, infected (dilated) tubes, Adnexal masses, blood in the abdomen; Better at seeing adnexa than CT scan; Most adnexal masses in premenopausal pts will resolve in 2-3mos CT scan: Better is you suspect a GI etiology like diverticulitis, Appendicitis DX Laparoscopy may be indicated it suspect endometriosis; Cannot make dx of endometriosis w/o SX specimen BUT you CAN try tx w/hormones w/o pathologic dx if you suspect endometriosis; May also take to SX if dx unclear if Appendicitis vs. PID -Ovarian masses 6-10 cm can twist on themselves (Ovarian torsion) and is a SX emergency as they could lose ovary -Ectopic pregnancy may require SX

Breast Pain Disorders -Cyclic: usually BL, Proliferation of nl glandular breast tissue; Associated w/hormones & menstrual cycle, usually 1wk prior (put on OCP to tx pain, but can be OCP S/E); General measures: NSAIDs, mechanical support, diet, OCP -Non cyclic: Lesions of breast/chest wall; Large pendulous (hypertrophic) breast, Diet/ lifestyle (caffeine?, nicotine), HRT, Ductal ectasia, Mastitis, Inflammatory breast cancer, Hidradenitis Supurativa Extramammary Pain: Chest wall (MSK), Spinal and paraspinal disorders, Trauma

Mastitis Puerperal -Staph infection -Warm, tender, diffuse erythema -Systemic sx=F, myalgias, leukocytosis -Tx w/PO abx (dicloxacilin) -Continue to breastfeed to prevent stasis -Lanolin based lotion for cracked/excoriated nipple -Mass ? - r/o abscess (US) Non puerperal (mastitis not related to breast feeding) -Cellulitis; Uncommon, prompt imaging and biopsies to exclude inflammatory breast cancer

Clinic Visit=HX -usually never have to do pelvic exam; ask pt first -Reason for visit -Health status: medical, SX and menstrual hx, reproductive health -Fhx: coagulopathies -Dietary & nutrition assessment*: eating disorders=screening essential -Obesity: this is your wt today & your ht; this is how we calculate BMI; the healthy wt is this; this gap doesn't have to be addressed in a short amt of time; 2-5lbs/mo; set realistic & healthy expectations; applaud changes in food diary -Physical activity -Use of meds, including supplements -Tobacco, alcohol, other drug use -Emotional, physical, sexual abuse -Sexual practices: when was last time you had sex (oral sex, are you active w/bf?); important understand safe sex practices, RFs, and pregnancy; also that tx is available if exposed Clinic Visit=PE -Ht, wt, BMI, BP, Secondary sexual characteristics (Tanner staging=breast bud & areolar development gives gauge of estrogen), Pelvic exam When indicated-NO Pap smear <21yo, Abd exam Labs -Chlamydia & gonorrhea: If <=24yo and sexually active -HIV testing: If sexually active, be aware of state screening requirements -High-risk gps: Diabetes/Lipid screening (BMI >30), Genetic testing (known genetic disorder should be co-managed w/pediatrician; refer to genetic counselor if RFs), hg level (heavy bleeding), Hepatitis, Syphilis (trichomonas is vaginal swab), TB -Immunizations: Tdap, HPV, Meningococcal, Influenza Nl Menstrual Cycle -Menarche (median age): 12.43yo -Mean cycle interval: 32.2ds in 1st gynecologic year -Menstrual cycle interval: 21-45ds -Menstrual flow length: 7ds/less -Menstrual product use: 3-6 pads/tampons/d

Menstrual Abns That May Require Evaluation=Menstrual periods that: -Have not started w/in 3yrs of thelarche (breast development) -Have not started by 14yo + hirsutism (excessive hair growth) -Have not started by 14yo + excessive exercise/eating disorder -Have not started by 15yo -Occur more freq than q21ds or less freq than q45ds -Occur 90ds apart even for 1 cycle -Last >7ds -Require freq pad/tampon changes (soaking >1 q1-2hrs) -Are heavy and are associated w/hx of excessive bruising/bleeding or fhx of a bleeding disorder Dysmenorrhea* -Most adolescents experience primary dysmenorrhea (painful menstruation in absence of pelvic path) -MCC of secondary dysmenorrhea is endometriosis -NSAIDs should be mainstay of pain relief for adolescents w/endometriosis (NSAIDs wk before & throughout cycle); Adolescents should not be prescribed narcotics LT to manage endometriosis outside of a specialized PM team. Adolescent Pregnancy -In 2015, young adult birth rate reached a historic low; Largely b/c adolescents are becoming more effective contraceptive users; U.S. continues to have highest adolescent pregnancy rate among industrialized countries w/data -2 factors can affect pregnancy rate: Contraceptive use, Sexual activity; Nearly 80% W used a BC method the 1st time they had sex Contraception Counseling -Elicit pt's reproductive goals/values and support her ability to honor those w/her contraceptive decisions -Discuss contraceptive efficacy and failure rates -Fully explain potential adverse effects and risks -Describe ease of use and noncontraceptive benefits; Explain use of barrier methods to decr risk of STI transmission -"Quick Start" initiation: give BC that day (except IUD if concern of pregnancy) -The ideal contraceptive practice for adolescents is Dual method use; condoms in combo w/more effective contraceptive methods to protect against infections and unwanted pregnancy -ACOG and AAP endorse use of IUDs and implants as contraceptive options for adolescents

Small, shiny, firm, dome-shaped papules with central indentation -Poxvirus - Usually sexually transmitted in adults

Molluscum Contagiosum (viral vulvar lesions) -DX: PE -Usually resolve in 6-12mos, can take up to 4yrs -Physical removal: cryotherapy (liquid nitrogen), curettage, laser -Oral: cimetidine -Topical: podophyllotoxin cream [not recommended in pregnancy], cantharidin

A 45 y/o G3P3 woman presents at the outpatient clinic with gradually increasing abdominal swelling first noticed 2 years ago. Swelling was accompanied by vague pain all over the abdomen for 6 months and increasing in size from four months. Due to the huge mass she was unable to walk and had anorexia. There was no history of colicky pain, vomiting or other gastrointestinal disturbances. Her bowel and bladder habits were normal. There was history of generalized weakness. She had no serious illness or surgeries before. On abdominal examination, abdomen was grossly distended and she also exhibits abdominal girth at the level of the umbilicus was 42 inches. Pelvic examination showed a large mass. On CT Scan, the uterus was seen separate from the mass. Large cystic mass was seen occupying the whole abdomen and the abdominal organs were compressed by the mass. -The mucinous neoplasms of ovary can attain a huge size, often filling entire pelvis and abdomen; often multilocular, and benign mucinous tumors are BL in <10% of cases.

Mucionous Cystadenoma

Abd discomfort (50%)/distention, bloating; N, C, dyspepsia; Vaginal bleeding (15%); Early satiety; Urinary sxs -All typically indicative of metastatic dz -95% W report sxs of 1-12mos duration prior to dx -2nd MC GYN malignancy in U.S; Largest # in GYN deaths; Rises w/age, 54-64 -RFs: BRCA1/2 mutation, Lynch syndrome -red flags: breast ca <50yo or M any age; ovarian ca any age; 2 primary breast cas/both breast & ovarian ca any age; 2/more breast cas in family (1 <50yo), ashkenazi Jewish ancestry W w/breast/ovarian ca; BRCA mutation in family

OVARIAN CA -Transvaginal U/S first -CA-125 level:Sensitivity and specificity too low for screening tool alone -CT abdomen & pelvis -SX: Definitive staging procedure & TX; TAH, BSO, complete SX staging and tumor debulking -adjuvant chemo after: carboplatin & taxol -Key- early detection of cancer Findings Indicative of Malignancy Imaging -Solid component not hyperechoic and often nodular/papillary -Septations, if present, that are thick (> 2-3 mm) -Color/doppler demonstration of flow in solid component -ascites -Peritoneal masses, enlarged nodes, or matted bowl When to Refer to a GYN ONC Subspecialist -Postmenopausal w/pelvic mass and at least 1: CA-125 >nl; Ascites; Nodular/fixed mass; abd/distant mets; fhx of 1/more 1st * relatives w/ovarian/breast ca -Premenopausal: CA-125 >200; Ascites; abd/distant mets; fhx of 1/more 1st * relatives w/ovarian/breast ca

acute onset of mod-severe pelvic pain, often w/NV in W w/ovarian cyst; Guarding, rebound. -complete/partial rotation of ovary on ligamentous supports, often resulting in impedance of its blood supply; MC gynecologic emergency and may affect all ages; only tx is SX -When ovarian torsion occurs, ovary typically rotates around both infundibulopelvic & utero-ovarian ligament. -MC RF: ovarian functional cyst; As size of mass incr, risk of torsion incr, until mass becomes large enough to be fixed in place in pelvis; More likely to occur when cyst is >=5 cm -Complete occlusion of ovarian blood supply will ultimately result in loss of ovarian fxn and necrosis of torsed tissues. Add pot adverse effects are hemorrhage/peritonitis -SURGICAL EMERGENCY!

Ovarian Torsion -TVUS (often show lack of color blood flow=high index of suspicion), CT, MRI Case: A 32 y/o G1P1 comes to ER w/sudden onset of LLQ pain that started 2hrs ago. The pain is described as sharp and comes in "waves". The pain is associated w/NV. PE is remarkable for a left adnexal fullness and rebound and guarding. TVS showed a 5 cm ovarian cyst. There was no blood flow to left ovary. Pt was taken to OR and dx of ovarian torsion was made. A left salpingoophorectomy was done.

Nl bleeding: Menses that are cyclic, predictable and have relatively consistent menstrual blood loss; q28-35ds; Duration: 3-5d Abn Bleeding: -Menorrhagia: Prolonged/excessive bleeding at regular intervals; Loss of >=80 cc/cycle; Cycle lasting >7ds (too much blood) -Metrorrhagia: Irregular menstrual bleeding or b/w periods -Polymenorrhea: Menstrual bleeding occurring at intervals of <=q21ds (too freq) -Oligomenorrhea: Bleeding occurring <q35ds (rare cycles) Causes Abn Bleeding -Anatomic problem: polyp, fibroid, endometrial pathology (hyperplasia, malignancy, endometritis), cervicitis, vaginitis -Systemic dz: hypothyroid, hyperprolactinemia, primary pituitary dz, coagulopathy -Iatrogenic: chemo, meds -DON'T FORGET PREGNANCY PALM-COEIN: Universally accepted system of nomenclature; Applies to reproductive age W; Classifies abn bleeding by pattern and etiology -Starting Out: abn uterine bleeding (AUB) Paired w/descriptive terms: Heavy: AUB/HMB (instead of menorrhagia) or Intermenstrual bleeding : AUB/IMB (instead of metrorrhagia)

PALM=structural causes P - polyp A - adenomyosis (nl glandular tissue in endometrial cavity gets into m layer) L - leiomyomata (benign smooth m tumor) M - malignancy and hyperplasia; RFs: unopposed estrogen=Nulliparity, Late menopause, Tamoxifen, obesity MC; DOC Endometrial sampling; do in AUB in >45yo or w/hx of unopposed estrogen COEIN: Nonstructural Causes C - coagulopathy; inherited=von Willebrandt dz; acquired=warfarin, heparin, NSAID, clopidogrel, aspirin, hormonal contraceptives, ginkgo, ginseng, motherwart O - ovulatory dysfunction MCC of AUB E - endometrial I - iatrogenic N - not yet classified + Screen for underlying blood disorder: -HMB (heavy) since menarche + -1 of: Postpartum hemorrhage, SX related bleeding, Bleeding associated w/dental procedures -OR 2 of: Bruising/epistaxis 1-2x/mo, freq gum bleeding, fhx of bleeding sxs Usual causes abn bleeding by age -baby: estrogen w/drawal -pre pubertal W: abuse/trauma -menarche: anovulation, coagulopathies, infection, pregnancy-related -reproductive age: anovulation, hormonal, pregnancy, infections, endocrine disorders, polyps -perimenopausal: anovulation, polyps, endometrial hyperplasia, cervical cancer -postmenopausal: atrophy, hormones, endometrial cancer MCC abn bleeding? Ovulatory; Ovulatory AUB MC than AUB related to ovulatory dysfxn-->Hypothalamic Pituitary Axis is intact; Steroid hormone profiles are nl -Mechanisms: abn PG synthesis and rec upregulation; incr local fibrinolytic activity & tissue plasminogen activator activity

Acute onset pelvic pain during/shortly after menses, pain worse w/intercourse/jarring movement -Post-coital bleeding, intermenstrual bleeding, menorrhagia -Urinary freq, abn vaginal discharge, F -PE: Abd TTP; Uterine, adnexal and cervical motion tenderness** (chandelier sign); Purulent endocervical discharge -Complication: Fitz-Hugh Curtis Syndrome- perihepatitis in setting of PID w/RUQ tenderness Infection of upper genital tract (uterus, fallopian tubes, ovaries); MC by STIs (gonorrhea & chlamydia) -RFs: multiple sexual partners, <25, partner w/STI, prior PID/STI. An 18-year-old college freshman comes to your clinic, complaining of severe left-sided lower abdominal pain and a foul yellow discharge. The pain began last night while she was having intercourse. By this morning she had a fever of 101 degrees and walking makes the pain worse; lying very still makes the pain better. She denies any nausea, vomiting, diarrhea, or constipation. Her past medical history is unremarkable. She has had two past sexual partners. She uses the birth control patch instead of condoms. She smokes a half pack of cigarettes a day and drinks four to five beers per weekend night. She denies any illegal drug use. On examination, she has a temperature of 102 and appears ill. She is tender in the left lower quadrant but has no guarding or rebound. Speculum examination reveals yellow purulent drainage from the os. On palpation, there is cervical motion tenderness and the left adnexa is swollen and tender. A urine analysis is unremarkable and the urine pregnancy test is pending. What is the most likely cause of her acute pelvic pain?

PID -R/o pregnancy -High suspicion: young sexually active W, high risk STIs, w/pelvic pain and organ tenderness -Temp >101F, mucopurulent discharge/cervical friability, abundant WBCs on microscopy of vaginal secretions, + gonorrhea/chlamydia -U/S: thickened, fluid-filled tubes/free fluid -Laparoscopy -Endometritis on biopsy -Screen for HIV and syphilis Indications for hospitalization: High F, NV, severe abd pain; tubo-ovarian abscess; Unable to tolerate PO meds; Pregnancy; Pt noncompliant w/therapy Parenteral TX: Cefotetan/Cefoxitin IV + doxy; PO therapy after 24hrs sustained clinical improvement Outpatient TX: Ceftriaxone + Doxy +/- Metro; No intercourse until completed therapy, sxs resolved, and sexual partners txed for STIs

-Cystocele/Apical (top of vagina) sxs: Heaviness, sensation of bulge, or fullness in pelvis; Sensation of "something falling out"; sxs often worsen after prolonged standing and are relieved by lying down; +/- sxs UF, incontinence/retention -Enterocele: Most asymptomatic; Low back/sacral pain; Perineal pressure; Palpable bulge; Rapid progression typical -Rectocele: Perineal pressure, Obstructive defecation: digital reduction (poo getting stuck), Genital looseness, Palpable bulge -Pelvic facia, ligaments, and ms may become attenuated from pregnancy, labor and delivery; incr intra-abd pressure (from chronic cough (bronchitis), habitual straining, or heavy lifting) may predispose; Atrophy may play a role in initiating/worsening pelvic relaxation (post menopausal will have decr estrogen which thins out tissue & makes it weaker) -RFs: Age, Multiparity, esp W w/injuries secondary to childbirth, Smoking, Pulm dz (chronic cough), Obesity, Genetics, Connective tissue disorders, Prior SX Types of prolapse -Anterior: cystocele -Apical: uterine/vaginal vault -Posterior: rectocele, enterocele -Procidentia: complete uterine prolapse (worst form)

Pelvic Organ Prolapse -postmenopausal bleeding: U/S (>4mm is abn) or EMB (endometrial biopsy)=endometrial ca -Prolapse Staging/POPQ: Stage 0 is nothing; Stage 4 is all the way out -Observation, Estrogen tx, Kegels/pelvic floor therapy (more likely to prevent, rather than improve), Pessaries (silicone device to list things up), SX -Fitting Pessaries: Be prepared to try various sizes & shapes; Trial and error; Empty bladder and rectum; Fit snugly, not too tight; Should fit pt comfortably; Pt. should void prior to leaving; Examine standing after fitting and after voiding; Should be visible at introitus, & not descend beyond hymen SX -Vaginal apex - Level I: Sacrocolpopexy (ASC) GS -Anterior compartment Level II: Anterior colporrhaphy (AR) -Posterior level III: posterior colporrhaphy (PR) -Colpocleisis: Only in W who no longer desire sexual activity b/c vaginal vault is closed off; More durable and lower risk than other repairs -Vaginal Mesh: all mesh kits removed from market b/c complications

No universally accepted criteria for dx -Rotterdam criteria 2/3: irregular Menstrual cycles (oligomenorrhea/ amenorrhea; >6wks apart, <9cycles/yr), Polycystic ovaries by US, Hyperandrogenism (hirsutism, acne, incr blood test) -Oligomenorrhea: =<9 menstrual cycles/yr; >6wks from start of menses to start of next menses; Typically begins around onset of menarche which may itself be delayed -Amenorrhea: No menstrual cycles for 3/more consecutive mos -Irregular menses are generally result of anovulation (failed oocyte production); Ovulation is required to form a corpus luteum which secretes progesterone; Endometrial lining requires priming w/ progesterone to slough off in a predictable fashion Hyperandrogenism: dx can be clinical/biochemical -Clinical dx: acne, male pattern hair loss, Hirsutism=Dark coarse hairs in androgen-dep areas (Upper lip, Chin, Midsternum, Upper abdomen, Back and buttocks); other features (deepening voice, clitoromegaly) are unusual & may suggest androgen-secreting tumor -biochemical dx: free/total test/SHBG -MC endocrine disorder; leading cause of infertility in W; Collection of S/Ss in W related to menstrual irregularity and excess circulating androgens; Other causes for these S/S must be excluded to make dx; Despite name, ovarian cysts are not required for dx -pts have incr risk of getting: Impaired glucose tolerance (30-40% of PCOS W), T2D, Dyslipidemia, CHD, Fatty liver dz, Obstructive sleep apnea, Depression and anxiety -Monozygotic twin sisters are twice as likely as dizygotic twin sisters to have PCOS, suggesting strong genetic influence -Multiple physiologic derangements: IR (acanthosis nigricans), Altered gonadotropin behavior, incr estrogen & androgen production from ovaries

Polycystic Ovary Syndrome TVUS: Rotterdam criteria: 12/more follicles 2-9 mm in diameter in each ovary/incr ovarian volume -Polycystic ovaries are an extremely common finding in PCOS W; 92% pts w/hirsutism; 87% pts w/oligomenorrhea; If menstrual cycle irregularity and hyperandrogenism are present, an US is not necessary to establish PCOS dx -W w/polycystic ovaries on US & no irregular menstruation/hirsutism do not need further workup and do not appear to be at incr risk of PCOS later in life R/o: -pregnancy test -TSH: Thyroid dysfunction -Prolactin: Hyperprolactinemia -17-hydroxyprogesterone: Nonclassic (late onset) congenital adrenal hyperplasia -free/total test/SHBG: Androgen-secreting tumor & for evidence hyperandrogenism -salivary/urinary cortisol, or dexamethasone suppression test: Cushing's -Labs to check at-risk conditions: diabetes, fasting lipid, biopsy for endometrial hyperplasia (if obese & irregular menses) -Fasting glucose (110-125=impaired fasting glucose; >=126=DM); 2hr PO glucose tolerance test (140-199= impaired glucose tolerance; >=200=DM) -ask about desire for pregnancy -wt loss in obese pts is first line; Multiple improvements noted w/wt loss: Androgen levels, Hirsutism, Menstruation, Fertility, decr lipid and glucose levels, CV morbidity and mortality -Combined PO contraceptives -Insulin sensitizing agents=metformin; spironolactone 2nd line: Can improve PCOS sxs; Lifestyle mods and wt loss are often effective and have less risk

Normal Pregnancy and Prenatal Care If pt wants to be pregnant in next year: -start on Folic acid 400 mcg; Optimize medical comorbidities: HTN, DM, thyroid disorder, etc; Meds; Prior obstetric outcomes; fhx; Lifestyle mods; Immunizations up to date; Genetic Screening Carrier Screening -All pts: CF, Spinal Muscular Atrophy, hemoglobinopathies (CBC) -Tay-Sachs: Ashkenazi Jewish, French-Canadian, Cajun -Ashkenazi Jewish: Tay-Sachs, Canavan disease, Familial Dysautonomia -Sickle Cell Anemia: AA (1:10 carrier) First Visit: Risk assessment and pt education; Obtain pt's hx; Establish pt's dates; PE including pelvic exam and pap smear if indicated; Screening: Substance abuse, depression, intimate partner violence, In private w/ proper translation; Referrals to counseling, legal, social work, etc Counseling: Scope of care that is provided- schedule, L&D coverage; Expected course of pregnancy; Labs and their indications; S/S to be reported to healthcare team; Practices to promote health maintenance; Risk counseling; Psychosocial topics in pregnancy and postpartum period; Review of fhx and genetic testing options Substance Abuse -Tobacco=Risks to pregnancy: growth restriction, placenta previa, placental abruption, PPROM, low birth wt, maternal mortality, ectopic pregnancy; Risks to child: sudden infant death syndrome, asthma, colic, childhood obesity; Nicotine replacement systems not well studied in pregnancy -Alcohol: Teratogen; No known safe quantity, frequency, type, or timing; Risks to child: intellectual disability, psychomotor development, emotional/behavioral problems; Fetal alcohol syndrome: growth restriction, facial abns, CNS dysfxn Mood-altering drugs -Testing for STIs and infectious agents (HCV) and rpt in 3rd trimester -Hepatitis B vaccine -Screen for depression and abuse -Breast feeding guidance -Involve social work, nutrition, behavioral health -Medication-assisted tx (methadone/buprenorphine) Preferred to withdrawal-high relapse rates and poorer outcomes; Infants are at risk of neonatal abstinence syndrome Prior OB hx -Gravidity: # of pregnancies -Parity: number of births -TPAL: Term, Preterm, Abortions, Living children -ex: G1 P1001=1 pregnancy, 1 term delivery, 1 living child; G3 P2012: 3 pregnancies, 2 term deliveries, 1 abortion, 2 living children -Year of delivery, GA at delivery, type of delivery and indication for cesarean delivery, wt of infant, complications with pregnancy, delivery, or postpartum -Prior gestational diabetes: early screening for diabetes -Prior midtrimester loss w/cervical insufficiency: poss cerclage -Prior preeclampsia: daily aspirin 81 mg after 12wks may decr recurrence and is recommended in high risk pts Establishing Gestational Age -LMP= last menstrual period; EDC= estimated date of confinement (date pregnancy) -Naegle's Rule: LMP - 3 mo + 7 ds -make sure US correlates w/LMP; if discrepancy, sometimes use US Initial OB Labs: Blood type; ab testing; CBC; Urine culture; Rubella; HIV; Hepatitis B (HBsAg); Syphilis (RPR); Chlamydia; Gonorrhea; tb: high risk pts; +/- pap smear Diet and Exercise: Well-balanced, varied, nutritional diet; add 300 Kcal incr/d; Vit D: 600 IU/d; Ca 1000-1300 mg/d; Fe supplement: 27mg/d; Folic acid: 400mcg/d; Vit A: >10,000 IU/d incr risk of fetal anomalies; Excessive vitamin/mineral intake (>2x recommended) should be avoided -Fish: Eat 2-3 servings/wk of low mercury containing fish (shrimp, Pollock, tilapia, catfish, cod); Avoid high mercury containing fish (shark, swordfish, king mackerel, marlin, orange roughy, tilefish, tuna); Avoid all raw or undercooked seafood -Avoid listeria: avoid hot dogs and lunch meat (unless steaming hot), unpasteurized soft cheeses, refrigerated pate and meat spreads, undercooked eggs and meat, unwashed fresh fruits/veggies -Exercise: 30 min/d of moderate exercise is recommended; Avoid falling and abd trauma -nl wt gain: 25-35lb -Teratogens: decr Lead, XR, Avoid hot tubs, saunas -Dental care: Caries, poor dentition, periodontal dz may be associated w/ preterm delivery; Recommend dental care and tx during pregnancy! -Work: pt can work up to delivery -Air travel: up to 36wks NV: Nonpharmacologic: incr protein, powdered ginger capsules, BRAT diet, eat several small meals -First line: vit B6 and doxylamine •Other options: diphenhydramine, prochlorperazine, promethazine, ondansetron, metoclopramide, methylprednisolone

Subsequent Visits Freq: q4wks until 28wks, q2wks until 36wks, weekly until delivery -Vital signs, Assessment of fetal movements, vaginal bleeding, loss of fluid, contractions; PE (uterine size/fundal ht (same as how many wks), fetal heart activity w/Doppler, fetal presentation; Urine dipstick (glucose, protein, nitrites, ketones); Education/anticipatory guidance U/S -1st trimester ultrasonography: Confirm intrauterine pregnancy, # fetuses, cardiac motion, and GA; r/o ectopic pregnancy/miscarriage -Single U/S for assessment of fetal anatomy b/w 18-22 wks; 2 types: Level I/II Routine Labs •DM screening: 24-28 wks •Ab testing: if Rh neg at 28 wks •CBC: Q trimester •HIV/Chlamydia/Gonorrhea: high risk in 3rd TM •Syphilis: high risk in 3rd TM and at delivery •Group B strep: 35-37 wks -1st trimester screen: US + lab; good for down syndrome; also quad screen & cell-free DNA DX Testing: W w/+ screening test should be offered further detailed counseling and dx testing -Chorionic villus sampling (rare): 10-13 wks; Obtain piece of placental tissue for testing •Amniocentesis: 15-20 wks; Obtain amniotic fluid sample for testing; Risks: bleeding, rupture of membranes, fetal loss, fetal limb abnormality, infection Rh -: Rhogam should be administered in an unsensitized pt w/: Ectopic, Abortion, Procedures w/poss fetal to maternal bleeding (CVS, amniocentesis); Conditions w/fetal-maternal hemorrhage (abd trauma or placental abruption); Vaginal bleeding; 28wks of gestation*; Delivery of a newborn who is Rh+* Gestational Diabetes Screening: 50g glucose challenge then 1hr assessment of glucose level (cutoff 130-140 mg/dL); If elevated, need dx testing w/100g 3 hr test Group B Hemolytic Strep: •Leading cause of infectious mortality and morbidity among newborns; Maternal risks: UTI, chorioamnionitis, endometritis, sepsis, meningitis (rarely); Fetal risks: sepsis, pneumonia, meningitis, death -if GBS+, will be given PCN during delivery Second/Third Trimester Issues •Childbirth education classes or hospital tour; Choosing a newborn provider; Signs of labor; Breast feeding; Intrapartum pain management options; Postpartum depression; Postpartum contraception Breast Feeding -Maternal benefits: decr risk of breast and ovarian ca, DM, HTN, heart dz -Infant benefits: decr risk of infections, SIDS, metabolic disease -C/I: infant w/galactosemia, mother w/HIV, active TB, varicella/HSV involving nipple, chemo, drug use Common Complaints: abd pain, Backaches/HAs, Breast tenderness, nipple discharge, CTS, Constipation, Edema, Fatigue, Heart burn, Hemorrhoids, Leukorrhea, Lightheadedness, Mask of pregnancy, Stretch marks, Varicose veins Antepartum Vaccinations •If indicated, administer: inactivated virus/bacterial vaccines/toxoids •Avoid: live vaccine; theoretical risk; CI: varicella, MMR •Flu vaccine: any gestation •Tdap: 27-36 wks •Others that are indicated: Hepatitis A/B, pneumococcal •HPV: not during pregnancy but safe w/breastfeeding Delivery Planning Issues •Uncomplicated pregnancy: await spontaneous labor until 41wks (induction at 41wks) •Fetal and/or maternal complications sometimes necessitate earlier delivery •Prior Cesarean Delivery; rpt Cesarean Delivery at 39wks; Trial of Labor After Cesarean (TOLAC) •Breech: External cephalic version Group Prenatal Care/ Centering: Begun after 1st prenatal visit; Composed of W w/similar due dates; 8-12 W and lasts 1-2hrs; Benefits: improve preparation for childbirth, decr incidence of preterm delivery, incr rates of breastfeeding initiation

Mom: mild, self-limited illness (F, rash); Maternal-fetal transmission occurs via hematogenous spread during maternal viremia -Congenital rubella infection (CRI): Encompasses all outcomes w/intrauterine rubella infection (miscarriage, stillbirth); Severity secondary to when Mom got rubella -Congenital rubella syndrome (CRS): Variable constellations of birth defects Majority of infants asymptomatic at birth -CRS presentation in the child: Devastating effects on developing fetus, Sensorineural deafness, Cataracts, Cardiac malformations (PDA, pulmonary artery hypoplasia), Growth retardation, Radiolucent bone dz, Purpuric skin lesions, Classically described as "blueberry muffin" lesions (RUBELLY MUFFIN), Hyperbilirubinemia

Rubella -Rare in developed countries w/established rubella immunization programs; no longer endemic in tUS -cases usually in infants whose mothers emigrated from countries w/o rubella immunization programs -Prevention is most important aspect of management of congenital rubella infection -Children w/CRS are considered to be contagious until at least 1yo

asymptomatic or sudden onset of sharp focal mod/severe UL lower abd pain, often after sex/exercise -low-grade F; Any signs of hemodynamic instability require that evaluation for bleeding/pot SX be expedited; healthy young pts may lose a sig amt of blood before a change in BP/pulse are seen. -The pain associated w/a ruptured ovarian cyst is thought to be due to an irritant effect, if there is blood from rupture site -release of sebaceous material/blood into abd may cause overt peritonitis w/rigidity of abd wall and rebound tenderness -Due to severity of pain, pts usually present to ED -R ovary is MC affected -pelvic exam: If cyst has not completely collapsed, an adnexal mass may be palpable on bimanual exam; poss Cervical motion tenderness -common occurrence in reproductive age (but can be in postm) -RFs: vaginal intercourse/likelihood of ovulation (incr w/ovulation induction and decr w/estrogen-progestin contraceptives) Case: A 28 y/o G0P0 woman presents to ER w/sudden onset of RLQ pain that started after having sex. Pt has hx of ovarian cysts. She is not using any contraceptive method. PE is remarkable for RLQ tenderness to palpation. TVUS showed pelvic fluid. Pregnancy test is negative.

Ruptured Ovarian Cyst -Serum/urine pregnancy testing: If hCG +, then pt must be evaluated for ectopic pregnancy w/pelvic U/S -CBC w/diff: poss low hematocrit from hemorrhage. -Blood type and crossmatch is indicated in pts w/peritoneal signs/hemodynamic instability. -Urine, cervical, or blood tests for STIs: if concomitant F +/- peritoneal sxs to r/o pelvic/UTI. -Pelvic U/S=cornerstone; adnexal mass & fluid in pelvis suggest ruptured ovarian cyst -If fluid has debris w/in it, then it is suspicious for blood or infection. -Rupture of cyst contents typically yields only a small pool of peritoneal fluid, but large amts of fluid may be present if rupture is accompanied by hemorrhage. -SX usually required for rupture of a dermoid cyst -Most can be managed w/observation, analgesics, and rest (if uncomplicated cyst) but some W require SX -no known methods to prevent rupture of an existing ovarian cyst, except SX drainage/removal of cyst. -sxs/suspicion of malignancy are indication for SX for an adnexal mass, but don't do SX for cyst rupture prevention -Hormonal txs that suppress ovulation may prevent development of new cysts -Signs of an infectious process: F, leukocytosis, and peritoneal signs suggest that there is an intraperitoneal infectious process, and require further evaluation. -Findings suggestive of malignancy: Postmenopausal w/an ovarian mass freqly have benign ovarian tumors, but malignancy must be excluded -Heavy/ongoing blood loss: inpatient observation/SX

-Treponema pallidum; Sexually transmitted (direct contact w/ infectious lesion) or congenital -Early: primary & secondary; late: tertiary Primary (chancre): Papule--> ulcerated lesion w/indurated margin; PAINLESS; Spontaneously resolves 3-6wks Secondary: wks-mos after primary; Systemic sxs F, HA, malaise, anorexia, sore throat, myalgias, wt loss; Adenopathy; Rash- generalized maculopapular rash, including palms and soles; Alopecia, hepatitis, osteitis, renal abns, meningitis, uveitis Tertiary: 1-30yrs after primary; Cardiovascular (aortitis); Gummatous syphilis- rare. Granulomatous, nodular lesions in skin and bones MC; CNS- neurosyphilis (general paresis and tabes dorsalis)

Syphilis -A nontreponemal test (VDRL/RPR) [screening] & a treponemal test (FTA-ABS) [confirmatory] -PCN G benzathine (early needs 1 dose; late needs 1q3wks) -Clinical eval & serologic testing at 6 & 12mos

Breast Development Disorders -Breast arises from basal layer of epidermis; UL/BL enlargement in 70% newborns -Newborn (witches milk) BL milky discharge, maternal hormones stimulation, transient several wks (nothing to worry about) -Thelarche, 8 and 13 yrs: growth of breast tissue -Younger pts have less fat (more dense). Older more fat (less dense) POLYTHELIA: accessory nipples POLYMASTIA: breast tissue (add mammary glands); Along embryonic milk line (axilla to groin); Usually asymptomatic, excision not required PREMATURE TELARCHE: breast development <8yo; r/o Precocious Puberty (other pubertal development); Benign, self limited; Most cases regress/stabilizes; Monitor body growth/Tanner stage (tells if pt goes into precocious puberty; if breast growth & pubic hair) BREAST ASYMMETRY: one breast bigger than other; r/o mass on bigger breast; Yearly exams; Not required, but SX augmentation/reduction after full breast growth BREAST HYPERTROPHY: Extremely large breast; Sx - Back pain, shoulder discomfort, kyphosis, psychosocial distress; reduction mammoplasty (until full growth)

TUBEROUS BREAST: Fascia adheres densely to underlying m, restricting peripheral expansion of base - growth directed forward; Exogenous hormone replacement (genetic, metabolic endocrine conditions), initiate w/small dose and gradually incr; SX modification LACK OF DEVELOPMENT: Congenital absence (Amastia) very rare; Constitutional delayed puberty; Chronic conditions, chemo, radiation, Genetic disorders (gonadal dysgenesis), Extreme physical activity (athletes); tx directed to cause

-may develop w/high levels of hCG in pts w/hydatidiform mole/ choriocarcinoma (ca/mass in uterus) or undergoing ovulation induction w/gonadotropins/clomiphene (Ovarian Hyperstimulation Syndrome (OHSS); pt undergoing infertility tx w/ovulation induction agents) -usually BL, may become quite large (>30 cm), and regress slowly after gonadotropin level falls -Only occur if pt has incr BHCG ("pregnancy hormone"); If pregnancy test -, r/o theca luthein cyst Case: A 35 y/o G2P1001 comes to office w/pelvic pain and pressure. She is 10wks pregnant. Serum quantitative pregnancy hormone is 250,000 IU. TVS=uterus w/heterogeneous material and BL 10 cm ovarian cysts. Based on TVS findings, you suspect molar pregnancy (non-viable fertilized egg implants in uterus and will fail to come to term. A molar pregnancy is a gestational trophoblastic dz which grows into a mass in uterus that has swollen chorionic villi.)

Theca-lutein cysts -discontinuation of meds as well as IV fluids and correction of electrolytes -IF PT HAS A MOLAR PREGNANCY, TX IS EVACUATION OF UTERINE CONTENTS W/D&C (DILATION AND CURETTAGE); ONCE SOURCE OF PREGNANCY HORMONE IS REMOVED, CYSTS WILL REGRESS

Mother: usually asymptomatic, maybe mono-like illness (F, chills, sweat, HA, rash) Child (4 types): 1) Subclinical infection: no sxs 2) Severe dz in neonatal period: symptomatic usually from primary maternal infection during 1st trimester 3) Mild/severe dz in 1st few mos of life 4) Sequelae/relapse (usually ocular) of undx infection later in infancy, childhood, or adolescence Failure to treat: Triad=chorioretinitis (MC late finding), hydrocephalus, and intracranial calcifications -Intellectual disability (mental retardation), deafness, seizures, and spasticity also can be seen in a minority of untxed children

Toxoplasmosis TOC Pyrimethamine + sulfadiazine

Green/yellow, frothy, thin, malodorous discharge; Vaginal burning, pruritus, DF, lower abd pain, dyspareunia; Punctate hemorrhages on vagina/cervix on PE ("Strawberry cervix") -Protozoan- Trichomonas vaginalis (flagellated); Sexually transmitted

Trichomoniasis -Wet mount- motile flagellated protozoan -NAAT [PCR] -Affirm (DNA hybridization probe) -Metronidazole

HX: most important PE: can actually see stress incontinence and urethral hypermobility=Q tip test >30* deflection -Stress: due to urethral hypermobility +/- intrinsic sphincter def (diff positions) -Urge: due to detrusor spasms (overactive) -Mixed: both stress & urge -Overflow: some element of urinary retention and urine simply drips out when the bladder is over full

Urinary Incontinence -U/A & cultures: r/o infection -Check PVR <150=nl -Urodynamics: watch how urethra & bladder react to filling and voiding; not needed if +CST (cough stress), nl PVR, neg UA Urge/Overactive Bladder -Bladder retraining, Biofeedback, Behavior mod, fluid management, Pelvic floor exercises -Antichols: relax bladder; Oxybutynin (worst S/Es), Tolterodine (does not cross BBB), Trospium (Does not cross BBB so minimal CNS S/Es; good for older pts dementia), darifenacin(C, GI upset), solifenacin (no effect on QTI/memory); if fail any, refer -Estrogen also works -Mirabegron: Activates β3 adrenergic rec in detrusor m in bladder-->m relaxation & incr in bladder capacity (don't use in uncontrolled BP) -Botox: Injected in bladder wall to eliminate involuntary m contractions -Sacral n stimulation: Sends electrical pulses to sacral n. to help w/urge -Percutaneous Tibial N Stimulation (PTNS) -Consider cystocele repair in W w/prolapse Stress -Biofeedback, Pelvic floor exercises, Pessary -Estrogen if post-menopausal -Imipramine TCA -Urethral bulking (inject to tighten urethra); Burch/MMK; Mid-urethral Sling (work well)

Most have no sxs; Large ones may have urinary sxs/back pain/dysmenorrhea b/c of size effect -Heavy/long periods are generally caused by submucosal (even if small) or multiple intramural fibroids, not generally caused by subserosal/pedunculated -Hormone dep so will often shrink after pt enters menopause (low estrogen state) -benign tumors derived from smooth m cells of myometrium; MC uterine neoplasia, but minimal chance for malignant transformation; Up to 70% in Caucasians and up to 80% in AA W Case: 42 yr old G2P2002 w/2 years of heavy painful periods and pelvic pressure. She has tried birth control pills with mild improvement of bleeding but still has pressure symptoms. On exam her uterus is at the level of the umbilicus with irregular shape. What is the most likely diagnosis?

Uterine leiomyomas (AUB-L) "fibroids" -vaginal U/S -Hormones (OCPs or progesterone) -GNRH Agonist (temporary solution because they return to previous size once you stop) -Myomectomy: Hysteroscopic if >50% in cavity;Open or robotic (generally only done if wants to preserve fertility) -Hysterectomy -Uterine Fibroid Embolization

Vulvar pruritus, burning, irritation; Dysuria, dyspareunia; Vulvar & vaginal erythema and vulvar edema; Vaginal discharge: thick, white, curd-like and adherent to vaginal walls -Candida albicans (MC);NOT a STI -RFs: DM, abx use, immunosuppression

Vulvovaginal Candidiasis -hx & PE -Wet mount w/10% KOH: budding yeast, pseudohyphae, hyphae -Vaginal culture (if recurrent infections/microscopy non-dx) -Fluconazole PO -Topical: clotrimazole, miconazole, terconazole (use for pregnant)