Reproductive

other changes in pregnancy

-all patients are prescribed vitamins plus extra iron -25-35 weight gain in normal; too little weight will cause intrauterine growth restriction; gain too much weight which will increase morbidity and likelihood of needing a C section

uterine landmarks

-at *pelvic brim at 12 weeks* -at *umbilicus at 20 weeks* -beyond one centimeter from pubic bone is one week of gestation

qualifications of a teratogen

-must have characteristic set of malformations -must exert effects at a particular stage of fetal development -show dose-dependent incidence

ovarian menstrual cycle

-*follicular phase (days 1-14)*: also known as the proliferative phase; this is stage in which the oocyte matures within an ovarian follicle; *key features*: zona pellucida, granulosa cells, and theca cells; increased estrogen in this phase drives the proliferation of the uterine lining -*ovulation (day 14)*: positive feedback of estrogen triggers the release of *LH* from the anterior pituitary; this leads to the rupture of follicle and release of the ovum -*luteal phase (days 14-28)*: associated with the formation of the corpus luteum which produces *estrogen, progesterone, inhibin, and activin*; its role is to maintain the lining of the uterus until implantation; the corpus luteum regresses after 10 days if no fertilization occurs

mechanism of action of testosterone

-*genomic effects*: testosterone cross membrane and *converted to DHT via 5alpha-reductase* and binds to androgen receptor (AR); the AR-DHT complex is transported to the nucleus to bind to androgen-response site to initiate RNA transcription -*non-genomic effects*: T of DHT binds to sex hormone globulin g-protein couple receptor that acts via cAMP which leads to phosphorylation, increase in lipid mediators and increase in intracellular Ca

mechanisms of action of estrogen

-*genomic effects*: the hormone is membrane permeable so within the cytoplasm it binds to a nuclear receptor (ERalpha or ERbeta)--> the estrogen/receptor complex is transported to the nucleus to bind to the hormone response element on the DNA--> it initiates RNA transcription to increase protein synthesis -*non-genomic effects*: estrogen binds to membrane estrogen receptors (mERs) to increase the production of cyclic nucleotides, protein phosphorylation, lipid mediators, and intracellular Ca

prescription drug labeling

-8.1 pregnancy (includes labor and delivery) -8.2 labor and delivery OR lactation -8.3 nursing mothers/females and males of reproductive potential

FDA pregnancy categories

-A: adequate studies have not demonstrated a risk to the fetus during the 1st trimester -B: animal studies have not demonstrated a risk to the fetus but there are no adequate studies in pregnancy women suggesting risk to fetus during 1st trimester -C: animal studies have shown an adverse effect on fetus but no adequate studies in humans -D: evidence of human fetal risk but potential benefits from use of drug may be acceptable for the risk -X: studies have demonstrated fetal abnormalities or adverse reactions; risk of use in pregnant woman clearly outweighs any potential benefit

infectious diseases that are routinely screened for?

-Hepatitis B, syphilis, chlamydia, gonorrhea, HIV, Hepatitis C -varicella can cause major morbidity in the mother if she is pregnant but it is not screened

male sex hormone synthesis

-again *cholesterol desmolosase* (activated by *LH*) and *17beta-hydroxysteroid dehydrogenase* (converts androstenedione into testosterone) are the key regulator enzymes -DHT (dihydrotesterone) is an active metabolite of testosterone and produced in prostate and all other androgen-responsive organs; it is produced by *5alpha-reductase*

spermatogenesis

-begins at puberty and continues throughout life -begins as spermatogonia--> undergoes mitosis and differentiation to become *primary spermatocytes* present at birth--> undergoes 1st meiotic division to become *secondary spermatocytes*(this process occurs continuously after puberty)--> another round of meiosis occurs to give rise to *spermatids*--> these cells undergo maturation and differentiation to become *mature spermatozoa*

function of human placenta

-brings nutrients and oxygen to the fetus -remove harmful waste: exchange of gases, nutrients, and elecrolytes between maternal fetal circulation -provide immune protection -hormone production: support fetal development (hCG, progesterone, estrogen (mainly E3), inhibin, and hPL

ectopic pregnancy

-can be located in *ampulla of fallopian tube* (most common), isthmus, fimbria, interstitium, abdomen, ovary, cervix -most common cause of death in first trimester (often due to hemorrhage) -risk factors: chlamydia/GC, PID, tubal ligation, previous ectopic preg, IVF pregnancies, endometriosis, tubal reanastomisis -pathophys: most risk factors except IVF causes scarring and deter travel of embryo to the uterine cavity -symptoms: 7-8 weeks gestation the patient will complain of irregular bleeding and pain; an ultrasound will reveal an empty uterus; fallopian tube can rupture and cause severe hemorrhage (blood in abdomen, acute abdomen, tachycardia/hypotension, anemia) -draw quantitative hCG levels (should double in 48 hours) and progesterone (<5 suggests failed pregnancy) -treatment: surgery is standard (laparoscopy if patient is stable OR laparotmoy if patient is unstable); methotrexate if mass is <5 cm (must check if hCG levels go down)

premature birth

-complications: respiratory distress syndrome, bronchopulmonary dysplasia, apnea, PDA, intraventricular hemorrhage, periventricular leukomalacia, *necrotizing enterocolitis* (blood stools, abdominal distension and circulatory collapse), sepsis, anemia, retinopathy -hyaline membrane disease/RDS is causes by insufficient pulmonary surfactant that leads to failure of lungs to inflate after birth; pathology: hyaline membranes consisting of necrotic epithelial cells and plasma proteins

normal placenta histology

-cytotrophoblast: present in early gestation, differentiates into villous or extravillous trophoblast -synctiotrophoblast: form outer layer of villus trophoblastic mantle; secrete hCG and hPL; mutlinucleated giant cells with abundant eosinophilic or basophilic cytoplasm -Hofbauer cells: fetal macrophages located in villous stroma; round-to-ovoid cells with eccentric nuclei and granular cytoplasm

placental membranes

-decidua is on outside, hyalinzed villi and trophoblast is in the middle, and chorion (aminion) on the inside -fetal part of placenta develops from chorionic sac -maternal part is derived from endometrium, the mucous membrane comprising the inner layer of the uterine wall

risk factors for multiple gestations

-dizygotic: AA, maternal family history, young maternal age -monozygotic: sporadic and the only risk factor is IVF

paternal teratogenicity

-drug/toxicant exposure during spermatogenesis could lead to mutation in DNA or altered gene expression OR can come into direct contact with the fetus via seminal fluid -*boceprivir and telaprevir* are contraindicated; cytotoxic anticancer agents, mabs, and retinoids are strongly precautioned against

dating a pregnancy

-due date: count back 3 months + 7 days from LMP -*normal gestation is calculated based on first day of LMP*

cellular effects of estrogen in females

-during puberty estrogen promotes genital and breast development and influences female fat distribution -in ovary it stimulates follicle growth -in uterus it leads to maturation, endometrial proliferation, maintenance of pregnancy -in fallopian tubes it stimulates ciliary action -breast is stimulates growth of the glands -brain it has both negative and positive effects on GnRH, FSH, LH, and prolactin secretion -bones it regulates bone growth, preserves bone density, and prevents osteoporosis -increases sex-hormone-binding globulins -it regulates cholesterol production, decreases LDL cholesterol, and increases HDL cholesterol -has cardioprotective effects and anti-atherosclerotic effects and reduces plaque formation

estrogen

-estradiol (E2) is *mainly* from the ovaries but also is made in small amounts in the zona reticularis of the adrenal glands -estrone (E1): is a weak estrogen and E2 precursor made in adipose tissue -estriol (E3): is an E2 metabolite and the weakest estrogen made primarily in the placenta -potency: E2> E1> E3 -synthesis: key enzymes is *cholesterol desmolase* (activated by *LH*) in *theca cells* that produces pregnenolone, *17beta hydroxysteroid dehydrogenase* is within *granulosa cells* form tesosterone, *aromatase* within *granulosa cells* forms estradiol from testosterone and is *activated by FSH*; DHEA is another important precursor to estrogen production

estrogen production in males

-estrogen is produced from testosterone by *aromatase* in liver, testes, muscle, brain, and adipose tissue; estrogen receptors are expressed in males and is necessary for male fertility ; its production is increased in obese men; has neuroprotection, cardioprotection, immune function -estrogen imbalance: xenoestrogens include food, plastic containers, pesticides, herbicides, and personal care products; symptoms: enlarged prostate, prostate cancer, low sex drive, impotence, urinary problems, breast development, depression, fatigue, heart disease, stroke, weight gain, loss of muscle tone

hormone production during menstrual cycle

-estrogen peaks during ovulation (has positive feedback mechanism on the anterior pituitary) and triggers the LH and FSH surge from the anterior pituitary; LH triggers ovulation: progesterone peaks right after ovulation in the luteal phase -in early follicular phase the *estrogen* produced at low concentrations (stimulated by LH and FSH) acts in a negative feedback mechanism to *inhibit both the anterior pituitary production of LH* and the hypothalamus; *inhibin* acts on anterior pituitary to *inhibit FSH* -immediately before ovulation estrogen reaches such a high concentration that it *switches to positive feedback mechanism* on hypothalamus and anterior pituitary to increase LH production which will trigger ovulation -in luteal phase, progesterone works in negative feedback mechanism on hypthalamus and anterior pituitary (inhibits LH and FSH) as well as inhibin

development of mammary glands

-estrogen, prolactin, progesterone, growth hormone, adrenal glucocorticoids, insulin -progesterone is required for final development of milk-secreting organs; causes additional growth of breast lobules and budding alveoli and development of secretory characteristics -prolactin: milk production of mammary gland; suckling promotes milk production via inhibition of dopamine secretion; inhibits GnRH and reduces LH and FSH; estrogen is inhibited and ovulation is inhibited--> *lactational amenorrhea* (temporary postnatal infertility) -oxytocin: important for milk ejection by stimulating myoepithelial cells; suckling promotes milk ejection via neural input to hypothalamus which will increase oxytocin secretion from post. pituitary

trimesters of pregnancy

-first: 0-14 weeks -second: 14-28 weeks -third: 28-40 weeks

how to document pregnancy history

-gravida (G): number of pregnancies -para (P): full-term births, preterm births, abortions, living children -twins: G1P1002 (pregnant once, delivered once, two living children)

testosterone transporting plasma proteins

-high affinity binding: sex steroid binding globulin -weak binding: albumin

hormones of pregnancy

-in first trimester, the corpus luteum produces estrogen and progesterone but in second and third trimesters the placenta is the major source of hormones -*human chorionic gonadotropin (hCG)*: comes from trophoblast/placenta; in very early states of pregnancy; alpha subunit (similar to FSH, LH, and TSH alpha subunits) and beta subunit (unique to hCG. . . picked up on pregnancy test); peaks at 16 weeks of pregnancy; purpose: rescue the corpus luteum from regression and prevents menstruation; an ovulator inducer used in in vitro fertilization -*estrogen*: gradually increases over pregnacy; made from trophoblast and placenta; the fetus produces E3 mainly (allow to check for the well-being of the fetus); important for breast development and preparation for milk production -*progesterone*: trophoblast/placenta at high levels; prevents spontaneous abortion and promotes endometrium development -*inhibin*: placenta -*human placental lactogen (hPL)*: made by placenta; starts at 5th week and peaks at 3rd trimester; promotes lactation; stimulates gluconeogensis from adipose fat; provides glucose/amino acid supply to fetus -*oxytocin*: important for uterine contraction during birth; made in paraventricular nucleus of hypothalamus and stored in posterior pituitary; triggered by stretching of uterine cervix; pitocin is used to induce or stimulate labor for difficult pregnancies -*prostaglandins*: F2alpha produced by uterus to induce labor and is stimulated by oxytocin; prevents progesterone via acting on corpus luteum

progesterone effects in females

-in uterus it prepares the uterus for implantation of fertilized ovum; maintenance of pregnancy; decreases spontaneous contractions of uterus -regulates development of the breast -negative feedback on hypothalamus and anterior pituitary -increases the basal body temperature by 05.-1 degrees Fahrenheit (the best time for fertilization is 12-24 hours of ovulation before the body temp increases)

maternal response to embryonic hCG

-increases gonadal steroids (estrogen and progesterone) which serve to stimulate growth of uterus and block contractions to sustain pregnancy -negative feedback on hypothalamus and pituitary to block ovulation and menstrual cycle

common teratogenic mechanisms

-interference with folate availability or activity (lamotrigine, cholestyramine, valproic acid) -interruption of transcription factors (bosentan, isoretinoin) -sex hormone disruption (diethylstilbrestrol, environmental agens) -generation of ROS (thalidomide) -placental obstruction/spasm: misoprostol, ergotamine -*renal bloodflow and development: ACEi and ARBs* -cholesterol depletion: statins

progesterone

-made in corpus luteum (theca cellls and granulosa cells as well) of ovaries, placenta, testes, adrenal glands -synthesis: the key enzyme is *cholesterol desmolase (CYP11A1)* in mitochondria and is under regulation by LH which activates the enzyme; cholesterol desmolasen converts cholesterol to pregnenolone and that is converted to progesterone via 3beta hydroxysteroid dehydrogenase

large for gestational age

-maternal diabetes: glucose moves across placenta, babies become macrosomic, babies at risk for birth injury (shoulder dystocia), neonatal comlications (hypoglycemia, polycythemia, hypocalcemia, hyperbilirubinemia) -Beckwith-Weideman syndrome

fetal growth restriction

-may result from fetal, maternal, or placental abnormalities -fetal abnormalities leads to symmetric growth restriction and can be caused by TORCH infections -placental abnormalities: asymmetric and spares the brain (restriction of growth in the latter half of gestation); vascular anomalies, placental abruption, placenta previa, placental thrombosis/infarction, placental infection, multiple gestations -maternal abnormalities: maternal conditions that result in decreased placental blood flow; vascular diseases such as preeclampsia and chronic hypertension

diagnosing pregnancy

-missed menses, nausea/vomiting, breast tenderness, perceived fetal movement -urine hCG (>25 mIU/ml at 5-6 weeks); serum hCG (>5 mIU/ml at 3 weeks); levels double every 48 hours in early pregnancy and peaks at 10-12 weeks -physical exam: uterus soft 6-7 weeks gestation, cervix is bluish, can tell it is enlarged at 7-8 weeks, can hear fetal heart tones at 10 weeks

pharmacokinetic changes after birth

-newborn has poor metabolic capacity that matures over 1st year or so -newborn's body composition is very different than that of an older child (very little body fat for lipophilic drugs to distribute to but much more total body water for hydrophilic drugs) -reduced capacity for plasma protein binding in neonate compared to older child -more gastric acidicity and bile acid secretion in neonate -neonate has immature renal function -skin of newborn is thin but has good perfusion (uncontrolled)

labor

-not sure what induces labor in humans (fetuses that don't produce cortisol are still born; estrogen/progesterone ratio may be involved; prostaglandins may be involved -*first stage*: onset of contractions changing the cervix to completely dilated; *latent phase* 0-4 cm dilated; *active phase*: from this phase to 4-5 cm -*second stage*: from completely dilated to delivery -*third stage*: delivery of baby to delivery of placenta -latent labor: 2 cm dilated -active labor: goes from 2-4, then 4-8, and levels out at 10 cm dilated -second stage: maxes out at 10 cm

monozygotic twins

-one egg and sperm and conception splits the zygote into two in early development; chorionicity depends on split happens -*morula*: dichorionic/diamniotic -*blastocyst*: monochorionic/diamniotic -*implanted blastocyst*: monochorionic/monoamniotic -*formed embryonic disk*: conjoined twins -complications: with monochorionic/monoamniotic twins cord entanglement and death can occur; monochorionic/diamniotic twin to twin transfusion; one dies in utero

human breast milk

-pH of 7 with high fat content (concentrates bases and lipophilic drugs); levels increase and decrease with maternal plasma levels -drugs that are problematic: chloramphenicol (bone marrow suppression), diazepam (causes sedation), heroin (can produce narcotic dependence), iodine (thyroid suppression), lithium (avoid unless levels quantitated), methadone (withdrawal if drug interrupted), propylthiouracil (thyroid suppression)

blood changes in pregnancy

-plasma volumes increases 50-60% but red cell volume does not increase compensatorily such that you get a physiologic anemia (hematocrit decreases. . . percentage of blood volume that is attributed to blood cells); iron deficiency anemia is common as well; platelets do not change; WBC increase slightly -large intestines increases the absorption of water (estrogen slows gastric motility and delay gastric emptying); constipation, indigestion, and heartburn are common symptom -peripheral resistance decreases due to progesterone in order to accomodate extra blood volume; symptoms are dizziness, headache, pedal edema, and hypotension

maternal changes during pregnancy

-pregnancy sickness/morning sickness: hyperemesis gravidarum which is nausea, vomiting, and depression -preeclampsia: fluid retention, hypertension, proteinuria -breast changes, CV and respiratory changes; uterine growth; neurogenesis; reduced anxiety and increased aggression; metabolic demands; reduced fever response

testosterone

-production begins in fetal development and produce by Leydig cells -leads to differentiation of fetal genitourinary tract, gender formation, masculinization of internal and external genitalia in utero -there is a second surge of testosterone in early infancy that leads to a minipuberty and is thought to be important for brain development; third surge is during actual puberty

implantation

-secondary oocyte undergoes 2nd meiotic division after fertilization--> zygote formation with 46 chromosomes--> mitotic divisions forming a blastomere--> morula formation (up to 100 cells)--> blastocyst formation (200-300 cells) is when differentiation occurs--> implantation of the blastocyst occurs 14-21 days of the menstrual cycle--> the process of embryogenesis begins -trophoblasts: early placenta that is required for implantation, nutrition, and production of hCG; cells invade the decidua

routine labs during pregnancy

CBC (checking for anemia and thrombocytopenia), urine culture, blood group, infectious disease, Pap smear, genetic screening (Down Syndrome, sickle cell disease, cystic fibrosis, SMA type I, hemoglobinopathies); *at 28 weeks there is a screen for diabetes after giving a serum injection*, *at 28 weeks Rhogam is given*; *36 weeks repeat STI screening and culture for group B strep*

sperm transport in female tract

-sperm reaches the cervix--> transported in fallopian tubes (*capacitation* occurs: hyperactivation, increased flagellar movements. . . Ca and ATP, and acrosomal changes)--> meets the oocyte in the cumulus (the chance that this occurs is 1:200,000,000;needs chemoattractants such as progesterone, odorants, and ANP) -estrogen is important for sperm transport to enhace contractions of myometrium and reduce viscocity of mucus in the uterus; in fallopian tubules it induces proliferation of mucosal lining with increased ciliated epithelial cells

human sperm

-structure: there is an acrosome underneath the cell membrane that releases digestive enzymes (hyaluronidase, proteolytic enzymes) to enter the ovum and initiate fertilization; the nucleus contains densely packed DNA; mitochondria provides ATP for movement; the flagella contains the axoneme has 11 microtubules -24-48 hours outside of the body is the life expectancy but can last up to 5 days inside of a woman's body

Sertoli cells

-supporting cells that are the site of spermatogenesis and also produces androgen-binding protein -under positive control via *FSH* from anterior pituitary and the testosterone -provides nutrients for developing sperm;* maintains the blood-testis barrier*; *produces inhibin*; produces some level of testosterone; activates Leydig cells via production of growth factors; elimination of defective sperm via phagocytosis; *secretes Anti-Mullerian hormone* to regress embryonic female Mullerian ducts

preeclampsia

-systemic syndrome with maternal endothelial dysfunction resulting in HTN, proteinuria, and edema in the 3rd trimester; the placenta becomes ischemic and releases factors that effect the maternal endothelium; loss of blood supply of the fetus -*villous ischemia*: increased syncytial knots; maternal decidual vessels with fibrinoid necrosis of vessel wall

effects of testosterone and DHT in males

-testosterone: stimulates spermatogenesis; differentiation of epididymus, vas deferens, and seminal vesicles; increased muscle mass; pubertal growth spurt; cessation of pubertal growth spurt; growth of penis and seminal vesicles; deepening of voice; negative feedback on ant. pit., libido -DHT: differentiation of penis, scrotum, prostate in fetal development; *male hair pattern*; *male pattern baldness*; sebaceous gland activity; *growth of prostate* -5alpha-reducate inhibitors are used for many uses including baldness, prostate hyperplasia, and prostate cancer

testes

-the site of spermatogenesis -seminiferous tubules: 250 m of tubules which is the site of sperm production; 30 million sperm/day -epididymus: 6 m tube and the site of sperm maturation and where they begin to be motile -vas deferens: stores mature sperm in the suppressed state (can be stored up to 1 month)

timing of organ development in utero

-this is important for thinking about drug exposures to teratogens -*CNS* develops all throughout the pregnancy -*heart* develops from 3-9 weeks -*arms*: 4-9 _*eyes*: 4-birth -*legs*: 4-9 -*teeth*: end of 6-16 -*palate*: end of 6-9 -*external genitalia*: 7-birth -*ear*: 4-16

placental implantation

-trophoblasts infiltrate the decidua and myometrium of placental site and then invades and replaces the spiral arteries of the basal plate to establish maternal-fetal circulation to keep vessels patent; forms the trophoblastic shell and secretes PTH-related protein -fertilized ovum normally implants in the uterine fundus -*placenta previa*: very low lying placenta that covers the os; can cause severe hemorrhage with cervical dilation; requires Cesarean delivery and can cause fetal anemia that may require transfusion -*placenta accreta*: lack of formation of normal decidual plate; chorionic villi extend into myometrium and placenta cannot separate normally following delivery; severe hemorrhage; *accreta is superficial. . .increta is deep into myometrium. . . percreta is through the myometrium* -*placental abruption*: premature separation of placenta prior to delivery with formation of retroplacental blood clot; prevents oxygenation to fetus; fetal distress will show on the EKG and *can lead to DIC* from large release of fibrinogen -*vaso previa*: rare condition in which the fetal blood vessels are located too close to the os of the cervix and can lead to severe fetal bleeding

hyperandrogenism/anabolic steroids

-used for steroid hormone deficiency; delayed puberty; diseases that result in loss of lean muscle mass -complications: reduced spermatogenesis and *testicular atrophy*, breast enlargement in men, masculinization in women, liver and kidney disease, heart problems, neuropsych effects

inflammation of placenta

-vasculitis: inflammation of umbilical vessels -funisits: inflammation of cord substances -phlebitis: inflammation of umbilical vein -arteritis: inflammation of umbilical arteries -necrotizing funisitis: long standing infections can cause tissue necrosis -peripheral funisits: inflammation located at peripher or surface of umbilical cord

fetal presentation at birth

-vertex 95% of the time -malpresentation occurs 5% of time (breech, foot, face, arm, cord, placenta)

theca cells

2-5 cell layer next to basal lamina that is required for oocyte maturation and ovulation; produces *androgens and progesterone*

drug abuse in pregnancy

5-10% of pregnancy women use illicit drugs and/or binge drink in first trimester; signs of withdrawal involve autonomic hyperactivity, irritability, excessive crying, poor feeding and abnormal reflexes (may mimic hypoglycemia, infection, hypocalcemia, hyperthyroidism, intracranial hemorrhage, hypoxic ischemic; you manage by re-exposing neonate to lower tapering doses

abortion

<20 weeks or less than 500 gm

preterm

<37 weeks gestation

viability

>23 weeks gestation

late term

>41 weeks gestation

postterm

>42 weeks gestation

antiepileptic drugs and pregnancy

one of most common teratogens prescribed in pregnancy; associated with increased risk of major congenital malformations; cognitive developmental delays; *valproate and carbamazepine* is associated with malformations and developmental delay

fetal hydrops

accumulation of edema fluid in the fetus during intrauterine growth; hemolytic anemia associated with Rh blood group incompatibility is associated with this; there is also nonimmune hydrops

hypertension drugs in pregnancy

alpha-methyldopa is DOC and labetalol is comparable; beta blockers cause fetal bradycardia, *calcium channel blockers are safe in pregnancy*, little data on alpha blockers

chorionic villus

arteries carry poorly oxygenated fetal blood and waste products from the fetus and the veins carry oxygenated blood and nutrients to fetus; the placental membrane separates the maternal blood in the intervillous space from the featl blood in the capillaries in the villi

Potters sequence

clubbed feet, pulmonary hypoplasia, and cranial anomalies associated with oligohydramnios (decreased amniotic fluid volume); can be caused by bilateral renal agenesis, atresia of ureter, polycystic or multicystic kidney diseases, renal hypoplasia, amniotic rupture, uretorplacental insufficiency from maternal hypertension

granulosa cells

cell lining the ovarian follicle; primary function is to produce *estrogen, progesterone, inhibin, activin*

blood typing in pregnancy

D antigen on RBC is one of the most common blood cell antigens; gene is dominant (85% of population is RH is positive); the problem is when mother is Rh negative and the fetus is positive; check the antibody titer (*low titers. . . 1:4* are not as concerning as *high titers. . . 1:64*) if a transfusion occurs then the mother will mount an immune response which can lead to problems with the next pregnancy (hydrops fetalis. . . hemolytic disease, edema, tachycardia, impending demise); only give Rhogam to a woman that has not been sensitized

antidepressants and pregnancy

autism spectrum disorder is associated with antidepressant use during preconception period; intellectual disability is not associated with antidepressant use

Group B strep and pregnancy

bacteria that mother carries in vagina that causes no harm to her but a newborn delivering through vagina will have meningitis, pneumonia, sepsis, and death; culture vagina at 36 weeks and give penicillin G is given 4 hours before delivery

stages of oogenesis

begin as *oogonia* (2n-46) in fetal life of the female (2-4 million)--> undergoes mitosis and differentiation to become a *primary oocyte* (46) at birth--> during childhood the cells undergo meiosis I and are *arrested at prophase 1* and becomes *secondary oocyte*--> at puberty one egg is "released" and completes meiosis I and is *arrested at metaphse II* to become the *ovum*

the greatest teratogen risk

between 3 and 8 weeks after conception; anything before thin is embryocidal or can cause implantation failure

parvovirus B19 and pregnancy

causes *erythema infectiosum*: destroys early RBCs causing anemia and fetal hydrops with marked erythroid hypoplasia of bone marrow and occational giant erythroblasts; pathology will show *viral inclusions* in precursors

CMV in pregnancy

causes a chronic villitis; gross appearance of the placenta is large and edematous or small and fibrotic; microscopically it will look like a lymphocytic or plasmacytic villitis with hyalinezed villi and mineralization (hyperplasia intranuclear and cytoplasmic inclusions)

cardinal movements

descent--> flexion--> internal rotation--> extension--> external rotation

regulatory standards

drugs and pesticides must be evaluated in 2 species (1 rodent and 1 non-rodent). . . usually rats and rabbits

majority of first trimester spontaneous abortions is caused by

genetic anomalies in the fetus; nondisjunction

activin

has positive feedback on anterior pituitary to stimulate FSH secretion and has the effect of stimulating estrogen production

fertilization

highest chance of fertilization is within 24 hours of ovulation -occurs in ampulla of Fallopian tube -sperm binds to Zona Pellucida via glycoprotein receptors--> acrosome reaction occurs to digest proteins--> fusion of egg and sperm plasma membranes--> polyspermy block to change membrane potential and receptors on Z pellucida -the highest chance of fertilization is if intercourse occurs 1-2 days before ovulation -morula: mulberry-shaped embryo (a dozen of cells); when the morula cavitates that is when it becomes a blastocyst

molar pregnancy

hydatidiform mole; noncancerous tumor that develops in the uterus; egg is fertilized but the placenta develops into an abnormal mass of cysts -in *complete molar pregnancy* there is no embryo or normal placental tissue; fertilized ovum contains only paternal chromosomes *(46 XX)* -*partial molar pregnancy* there is abnormal embryo and some normal placental tissue (embryo begins to develop but is malformed and can't survive); *triploid (69 XXY)* -associated with *increased risk of choriocarcinoma* (composed of syncytiotrophoblastic giant cells and cytotrophoblast in a hemorrhagic background);can metastasize; marked villous enlargement, edema, and circumferential trophoblast proliferation hCG levels are extremely high

female hypothalamic-pituitary-gonadal axis

hypothalamus releases GnRH which stimulates the gonadotrophs to produce luteinizing hormone and follicle stimulating hormone; these stimulate the formation of estrogen, progesterone, and inhibin and activin

thalidomide

in the 1950s it was originally used to treat morning sickness is pregnancy; later it became associated with having teratogenic effects; people affected with *phocomelia*; has greater toxicity in development of the upper limbs and other tissues derived from mesoderm

physiological changes with pregnancy

increased CV function, increased respiratory function, increased hepatic portal vein bloodflow, increased hepatic artery bloodflow, increased GFR, decreased serum creatinine, decreased function of CYP2C19, 1A2, and NAT2 but increased function in all other CYPs

renal changes in pregnancy

increased GFR; creatinine clearane increases (serum Cr is the same or lower)

Leydig cells

interstitial cells that produce *testosterone*; under positive control via *LH* from anterior pituitary

respiratory and pregnancy

lung capacity decreases due to pressure on diaphragm but minute ventilation increases to remain oxygenated; she will have a slight respiratory alkalosis with decreased bicarbonate

spontaneous abortion

miscarriage defined as pregnancy loss before 20 weeks of gestation; 50% are caused by fetal chromosomal anomalies; maternal endocrine factors (luteal-phase defect, poorly controlled diabetes); physical defects of uterus such as leiomyomas; disorders of maternal vasculature (antiphospholipid antibody syndrome)

estrogen transporting plasma proteins

most estrogen is in the bound form (98%) and it increases its stability; high affinity binding is to sex steroid binding globulin; low affinity binding is to albumin

listeria

necrotizing intervillositis leading to chorioamnionitis

twin-twin transfusion syndrome

occurs with *monochorionic twin pregnancies*; have vascular anastomoses that connect the circulation of the twins; sometimes the connections include one or more arteriovenous shunts that can preferentially increase blood flow to one twin at the expense of the second (one twin will be underperfused and the second will be overloaded)

placental drug metabolism

placenta is capable of *aromatic oxidation*; may decrease fetal exposure and toxicity; can increase exposure to carcinogens; 40-60% of placental blood enters fetal liver before circulating to remainder of fetus

placental abruption

placental separation occuring third trimester that prevents oxygenation to fetus; *risk factors*: previous abruption, hypertensive disorders, smoking, cocaine use; risk for development of DIC due to thrombocytopenia and increased fibrinogen and d-dimer

amnion nodosum

seen in placentas by oligohydramnios and may be associated with fetal renal agenesis and pulmonary hypoplasia; may be due to desqaumated skin or membrane injury; *gross appearance*: multiple yellow-tan superficial aminiotic lesions; *microscopically*: nodules of protuberant eosinophilic fibrinous material with entrapped squamous cells and associated with stratified squamous metaplasia

metabolic adaptation to pregnancy

substrate for fetus is glucose via facilitated passive diffusion; hPL prodced by placenta promotes lioplysis and promotes insulin resistance to elevate glucose concetrations in the mother to prevent hypoglycemia; in early pregnancy the insulin needs go down but in mid and late trimesters insulin needs go up (due to hPL)

zona pellucida

surrounds the oocyte and is formed of glycoproteins; plays key role in fertilization

trans-placental drug passage

the ability of a drug to cross the placental barrier is dependent upon its: lipid solubility, degree of ionization at physiologic pH, molecular weight (*<600*), *duration and timing of exposure is most important*, maternal plasma protein drug bindind, placental development and blood flow, energy dependent drug transporter proteins, maternal/placental/fetal pharmacogenomics

male hypothalamic-pituitary-gonadal axis

the usual stuff except testosterone stimulates sperm production in Sertoli cells; has negative feedback mechanism on anterior pituitary to *prevent LH production*; inhibin has negative feedback on anterior pituitary to *prevent FSH production*

pregnancy is thrombogenic state

to prevent mother from bleeding out after birth; estrogen effect increases production of factors VII, VIII, IX, X, XII, and fibrinogen; depressed fibrinolysis; this increases the risk of clotting (DVT and pulmonary emboli)

dizygotic twins

two eggs are fertilized by two different sperm; two separate placentas (anterior and posterior)