OB/GYN
High-yield obstetrics and gynecology for USMLE Step 2/3 — teratogens, fetal heart rate tracings, hypertensive disorders of pregnancy, postpartum hemorrhage, amenorrhea workup, contraception, AIS vs Müllerian agenesis, and cervical cancer screening, extracted from Divine Intervention and organized for exam performance.
- Isotretinoin (Accutane): Disrupts HOX genes → limb placement anomalies, craniofacial defects. Requires two forms of contraception + iPLEDGE registration before prescribing
- Warfarin: Crosses placenta → fetal hemorrhage, stippling of epiphyseal plates, CNS defects. Use heparin or LMWH in pregnancy (do not cross placenta)
- ACE inhibitors / ARBs: Renal agenesis → fetal anuria → oligohydramnios (amniotic fluid index <5 cm) → Potter sequence (limb deformities, pulmonary hypoplasia, abnormal facies)
- Fetal alcohol syndrome: Smooth/hypoplastic philtrum + thin upper lip + short palpebral fissures + microcephaly. VSD is the most common cardiac defect. #1 preventable cause of intellectual disability in the US
- Valproic acid: Neural tube defects (never use in pregnancy — even if stopping it causes seizures, the rule stands); also hepatotoxic. Safe AED in pregnancy: lamotrigine
- Cocaine: Sympathomimetic vasoconstriction of placental vessels → placental abruption (painful bright-red third-trimester bleeding) + asymmetric IUGR (head spared, body small)
Master Teratogen Table
| Drug / Agent | Mechanism | Fetal / Neonatal Effect | HY Integration |
|---|---|---|---|
| Isotretinoin | HOX gene disruption | Craniofacial, limb, cardiac defects | Must have 2 contraceptives + iPLEDGE; stop before pregnancy |
| Warfarin | Vitamin K antagonist — crosses placenta | Fetal hemorrhage, epiphyseal stippling, CNS defects | Switch to heparin/LMWH in pregnancy (prosthetic valves: heparin bridge) |
| ACE inhibitors / ARBs | Block renal development → oliguria | Renal agenesis, oligohydramnios, Potter sequence | Clue: AFI <5 cm in woman on lisinopril/losartan |
| Statins (HMG-CoA inhibitors) | Block cholesterol synthesis necessary for fetal development | Multiple congenital anomalies | Hold statins in all pregnant women, even with high CV risk |
| Methotrexate | Dihydrofolate reductase inhibitor → blocks DNA synthesis | Neural tube defects, abortifacient | Used to treat ectopic pregnancy — stop before trying to conceive |
| Alcohol (FAS) | Neuronal apoptosis, midline disruption | Smooth philtrum, thin lip, short palpebral fissures, microcephaly, VSD | Philtrum abnormality on exam = FAS until proven otherwise |
| Valproic acid | Folate antagonism | Neural tube defects (most severe of AEDs) | NEVER use in pregnancy, regardless of seizure control |
| Danazol | Pro-androgenic | Virilization of female fetus, precocious puberty in males | Used for endometriosis — stop before pregnancy |
| Thalidomide | Anti-angiogenic | Phocomelia (proximal limb absent; distal extremities attach to shoulder/hip) | Rare in modern practice but classic NBME vignette |
| Aminoglycosides | Ototoxic — ablates CN8 | Sensorineural hearing loss → language delay | Newborn doesn't turn toward sound or respond = audiometry |
| Tetracyclines | Bind calcium in bones and teeth | Tooth discoloration, bone growth suppression | Avoid <8 years old. Exception: Rocky Mountain Spotted Fever at ANY age (including pregnancy) |
| Lithium | Cardiac teratogen (mechanism unclear) | Ebstein's anomaly (downward displacement of tricuspid valve, "atrialization" of RV) | Bipolar disorder in pregnancy: switch to antipsychotic |
| Paroxetine (SSRI) | Serotonin disruption in pulmonary vasculature | Persistent pulmonary hypertension of newborn | Only SSRI contraindicated in pregnancy; sertraline is safest SSRI |
| Cocaine | Vasoconstriction of placental arteries | Placental abruption, asymmetric IUGR (head normal, body small) | Painful third-trimester bleeding in IV drug user = abruption |
| DES (diethylstilbestrol) | Hormonal disruption of Müllerian development | Clear cell adenocarcinoma of vagina/cervix, T-shaped uterus, recurrent pregnancy loss | Vaginal adenocarcinoma (not SCC) in young woman = DES exposure |
| Cyclophosphamide | Alkylating agent — cross-links DNA | Limb defects, cleft palate, neural tube defects | Used for GPA (Wegener's) — must stop before/during pregnancy |
| Chloramphenicol | Impairs mitochondrial 70S ribosomes → overwhelms neonatal glucuronidation | Gray baby syndrome: ashen color, cardiovascular collapse | Common in developing world; immigrant mother vignette |
| TMP-SMX / Pyrimethamine | Folate synthesis inhibitors | Neural tube defects | Toxoplasmosis in pregnancy: use spiramycin (not pyrimethamine/sulfadiazine) |
| Ergotamine | Vasoconstrictive + uterotonic | IUGR, premature labor, fetal demise | Migraine med — avoid in pregnancy; safe chronic prophylaxis = propranolol, topiramate |
| Gestational diabetes (IDM) | Fetal hyperinsulinemia from maternal hyperglycemia | VSD, TGA, caudal regression syndrome (sirenomelia), neonatal RDS (insulin inhibits surfactant), hypoglycemia/hypocalcemia seizures, small left colon | Term baby with RDS = think gestational DM, not prematurity |
Never use: Valproic acid (any seizure severity), warfarin (switch to heparin), ACE inhibitors / ARBs, statins, methotrexate, isotretinoin (also requires 2 contraceptives), live attenuated vaccines (varicella, MMR, intranasal influenza — except rotavirus in infants under 1 year).
Give to all newborns of HBsAg-positive mothers: HBIg + HBV vaccine immediately at delivery (passive + active immunization).
HIV-positive mother's newborn: Give zidovudine (AZT) prophylaxis.
Symmetric vs Asymmetric IUGR
| Type | Head vs Body | Causes | Timing |
|---|---|---|---|
| Symmetric IUGR | Head and body both small | TORCH infections, chromosomal abnormalities (trisomies), early teratogen exposure | Early pregnancy (first trimester) |
| Asymmetric IUGR | Head normal, body small (brain-sparing) | Placental insufficiency, cocaine, late teratogen exposure | Late pregnancy (second/third trimester) |
Polyhydramnios (too much fluid): Fetus cannot swallow — anencephaly, tracheoesophageal fistula, duodenal atresia ("double bubble"), neuromuscular disorders. AFI >24 cm.
Oligohydramnios (too little fluid): Fetus cannot urinate — renal agenesis (Potter sequence), bilateral renal agenesis, ACE inhibitor exposure. AFI <5 cm. Leads to pulmonary hypoplasia + limb deformities from uterine wall compression.
Safe Drugs in Pregnancy (High-Yield)
- Antihypertensives: Labetalol (first-line), hydralazine, nifedipine, methyldopa. Avoid ACE/ARB. Avoid atenolol (less fetal bradycardia data than labetalol)
- Antiepileptics: Lamotrigine is preferred. If patient is seizure-controlled on phenytoin and stable, do not abruptly discontinue (risk of status epilepticus > teratogen risk) — except valproic acid, which must be stopped regardless
- Antibiotics: Penicillins, cephalosporins, azithromycin, clindamycin, nitrofurantoin (avoid third trimester). Avoid tetracyclines, fluoroquinolones, aminoglycosides, TMP-SMX
- Antidepressants: Sertraline (safest SSRI). Avoid paroxetine
- Anticoagulation: Heparin (unfractionated or LMWH) — does not cross placenta. Warfarin and DOACs are contraindicated
- Normal FHR: 110–160 bpm. Tachycardia (>160) = maternal fever, fetal anemia, maternal hypotension, fetal hypoxia. Bradycardia (<110) = maternal beta-blocker use, neonatal lupus (anti-Ro/La antibodies → complete heart block)
- Reactive non-stress test: At least 2 accelerations (>15 bpm above baseline for ≥15 seconds) within 20 minutes
- Variable decelerations: Umbilical cord compression. Abrupt drop/return (<30 sec nadir). First step: left lateral decubitus position. If persistent: amnioinfusion or reduce oxytocin
- Early decelerations: Head compression → Cushing's reflex bradycardia. Nadir coincides with contraction peak. Gradual (>30 sec). Benign — no intervention needed
- Late decelerations: Uteroplacental insufficiency. Nadir comes AFTER contraction peak. Gradual (>30 sec). First step: left lateral decubitus. Repetitive late decels → urgent delivery (C-section)
- Sinusoidal pattern: Sine-wave FHR = severe fetal anemia (Rh isoimmunization, fetal-maternal hemorrhage)
VEAL-CHOP Mnemonic
| FHR Finding | Cause | Mechanism | Management |
|---|---|---|---|
| Variable decelerations | Cord compression | Umbilical cord compressed → ↑ SVR → baroreceptor → parasympathetic → ↓ HR. Abrupt: nadir in <30 seconds | Left lateral decubitus (first) → amnioinfusion (second) → reduce oxytocin |
| Early decelerations | Head compression | ↑ ICP from head compression → Cushing's reflex → vagal bradycardia. Gradual: nadir in >30 seconds, coincides with contraction peak | None — benign, physiologic |
| Accelerations | Okay | Fetal movement → sympathetic response → ↑ HR. Sign of fetal well-being | None — reassuring |
| Late decelerations | Placental insufficiency | Uteroplacental blood flow inadequate → fetal hypoxia. Gradual: nadir in >30 seconds, comes AFTER contraction peak | Left lateral decubitus → supplemental O₂ → stop oxytocin → if repetitive: urgent delivery |
Early: nadir = same time as contraction peak. Think: mirror image of contraction (symmetrical). Benign.
Late: nadir comes AFTER contraction peak. The delay = time it takes for placental insufficiency to register. Ominous — requires intervention.
Both are gradual (>30 sec from onset to nadir). Variable decelerations are abrupt (<30 sec).
Causes of Fetal Tachycardia vs Bradycardia
| Fetal Tachycardia (>160) | Fetal Bradycardia (<110) |
|---|---|
| Maternal fever (↑ metabolic rate) | Maternal beta-blocker (labetalol for preeclampsia) |
| Fetal anemia (↑ cardiac output to compensate) | Neonatal lupus (anti-Ro/anti-La → complete heart block) |
| Maternal hypotension (fetal compensatory ↑ HR) | Prolonged cord compression (late-stage variable decel) |
| Fetal hypoxia (compensatory early; becomes bradycardia if severe) | Fetal hypothyroidism (rare) |
Sinusoidal Pattern
A sine-wave FHR pattern (smooth, regular undulations, no variability, no accelerations) indicates severe fetal anemia. Causes: Rh isoimmunization (anti-D antibodies), massive fetal-maternal hemorrhage, fetal hydrops, severe fetal infection. Management: urgent delivery or intrauterine transfusion.
For both variable and late decelerations, the first management step on NBME exams is left lateral decubitus position. This relieves aortocaval compression (IVC compression by the gravid uterus), increasing maternal cardiac preload → increased uteroplacental perfusion. If the question doesn't list this, then the next answer is amnioinfusion (for variable decels) or delivery (for repetitive late decels).
- Gestational hypertension: BP ≥140/90 after 20 weeks, no proteinuria, no end-organ damage. Normalizes by 12 weeks postpartum
- Preeclampsia: BP ≥140/90 after 20 weeks + proteinuria (≥300 mg/24h or protein:Cr ≥0.3) OR end-organ damage (thrombocytopenia, renal insufficiency, elevated liver enzymes, pulmonary edema, new-onset headache/visual changes)
- Severe features: BP ≥160/110, thrombocytopenia <100K, creatinine >1.1, transaminases 2× ULN, pulmonary edema, headache/visual symptoms. Deliver if ≥34 weeks; if <34 weeks consider steroids + magnesium then deliver
- HELLP syndrome: Hemolysis (↑ LDH, schistocytes) + Elevated Liver enzymes + Low Platelets. Definitive treatment: delivery (can occur before 20 weeks or postpartum)
- Eclampsia: Preeclampsia + seizures. Treatment: IV magnesium sulfate (first-line anticonvulsant) + antihypertensives. Delivery is curative
- Safe antihypertensives in pregnancy: Labetalol (IV acute), hydralazine (IV acute), nifedipine (oral). Never ACE inhibitors or ARBs
Hypertensive Disorders of Pregnancy — Classification
| Condition | BP Threshold | Proteinuria | End-Organ Damage | Management |
|---|---|---|---|---|
| Chronic HTN | ≥140/90 before 20 weeks or pre-existing | No (unless superimposed) | No | Labetalol or nifedipine; deliver at 37 weeks |
| Gestational HTN | ≥140/90 after 20 weeks | No | No | Monitor; deliver at 37 weeks |
| Preeclampsia (without severe features) | ≥140/90 after 20 weeks | Yes (≥300 mg/24h) | No | Deliver at 37 weeks; serial monitoring |
| Preeclampsia with severe features | ≥160/110 (or any BP with end-organ damage) | Yes or No (end-organ enough) | Yes | Deliver if ≥34 weeks; magnesium seizure prophylaxis; antihypertensives |
| HELLP | Variable | Variable | Yes (hemolysis, liver, platelets) | Deliver regardless of gestational age; platelets if <50K before delivery |
| Eclampsia | Variable | Variable | Yes + seizures | IV magnesium (first-line), secure airway, antihypertensives, then deliver |
Magnesium is the treatment for eclamptic seizures AND prophylaxis in severe preeclampsia. Signs of toxicity in order:
1. Loss of patellar reflexes (first sign, 7–10 mEq/L) → 2. Respiratory depression (10–13 mEq/L) → 3. Cardiac arrest (>15 mEq/L).
Antidote: calcium gluconate IV (not calcium chloride — gluconate is safer peripherally).
HELLP Syndrome — Diagnosis
- Hemolysis: ↑ LDH, ↑ indirect bilirubin, schistocytes on peripheral smear
- ELevated Liver enzymes: AST/ALT >2× ULN
- LP: Low Platelets <100,000/µL
- Can occur without classic hypertension/proteinuria — diagnose on labs
- Mimics: TTP, HUS, acute fatty liver of pregnancy (AFLP). AFLP = hypoglycemia + coagulopathy + liver failure
Placenta Previa vs Placental Abruption
| Placenta Previa | Placental Abruption | |
|---|---|---|
| Bleeding character | Painless, bright red | Painful, dark red; "woody" uterus |
| Onset | Third trimester (any time) | Acute (third trimester) |
| Cause | Placenta implanted over cervical os | Premature placental separation; cocaine, HTN, trauma |
| Next step | Transabdominal ultrasound (NO digital exam — can precipitate massive hemorrhage) | Clinical diagnosis + ultrasound; urgent delivery if severe |
| Delivery | C-section (placenta over os = cannot deliver vaginally) | Vaginal delivery if stable; C-section if fetal distress or severe bleeding |
| DIC risk | Low | High (placental thromboplastin release) |
Screening: 1-hour 50g glucose challenge at 24–28 weeks (threshold: ≥140 mg/dL for abnormal → proceed to diagnostic test).
Diagnosis: 3-hour 100g OGTT. Abnormal if ≥2 values exceed: fasting 95, 1-hr 180, 2-hr 155, 3-hr 140 mg/dL.
Management: Diet first → insulin if diet fails. Metformin and glyburide are used but not FDA-approved for GDM.
Fetal complications: Macrosomia, shoulder dystocia, neonatal hypoglycemia, neonatal RDS (insulin inhibits surfactant), caudal regression syndrome, VSD/TGA.
- Definition: Blood loss >500 mL vaginal delivery or >1000 mL C-section. Most common cause: uterine atony (80%)
- Uterine atony risk factors: Multiple gestation (twins/triplets), prolonged labor, polyhydramnios, chorioamnionitis, high parity. Uterus has "run out of energy" to contract
- Management algorithm: Uterine massage (first, rarely an exam answer) → oxytocin (pitocin) → tranexamic acid (TXA) → misoprostol → carboprost → ergotamine → surgical (B-Lynch suture, uterine artery ligation, hysterectomy)
- Carboprost (15-methyl PGF2α): Prostaglandin → uterine contraction. Contraindicated in asthma (bronchospastic). Alternative: misoprostol (PGE1) — safe in asthma
- Tranexamic acid (TXA): Lysine analog → antifibrinolytic → prevents clot breakdown. Use early for hemorrhage
- The 4 T's of PPH causes: Tone (atony), Trauma (lacerations), Tissue (retained placenta), Thrombin (coagulopathy)
PPH Management Algorithm
| Step | Intervention | Mechanism | Key Contraindication |
|---|---|---|---|
| 1st | Bimanual uterine massage | Mechanical compression; stimulates contraction | None (rarely an NBME answer — usually they ask what's next) |
| 2nd | Oxytocin (Pitocin) IV | Uterotonic; compresses myometrial vessels to reduce bleeding | None in acute setting |
| 3rd | Tranexamic acid (TXA) | Antifibrinolytic (lysine analog); stabilizes clot | History of thromboembolic disease (relative) |
| 4th | Misoprostol (PGE1) | Prostaglandin → uterine contraction | Safe in asthma |
| 5th | Carboprost (15-methyl PGF2α) | Prostaglandin → uterine contraction (more potent) | Asthma (bronchospastic — do NOT use) |
| 6th | Methylergonovine (ergot) | Vasoconstrictive uterotonic | Hypertension, vascular disease, Raynaud's |
| Surgical | B-Lynch suture → uterine artery ligation → hysterectomy | Mechanical hemostasis | If all medical therapy fails |
Blood vessels run between the myometrial muscle fibers. When oxytocin causes myometrial contraction, it mechanically compresses ("ligates") these intramyometrial vessels. This is analogous to surgical ligation — stopping the bleeding source without cutting. This is why uterine massage works too: same principle, mechanical.
4 T's of PPH
| T | Cause | Diagnosis | Treatment |
|---|---|---|---|
| Tone | Uterine atony (80%) | Soft, boggy uterus on exam | Uterotonic drugs (oxytocin, carboprost, misoprostol) |
| Trauma | Cervical/vaginal/uterine lacerations | Firm uterus but ongoing bleeding; inspect carefully | Surgical repair |
| Tissue | Retained placenta or placental fragments | Incomplete placenta at delivery, uterus won't contract | Manual extraction or uterine curettage |
| Thrombin | Coagulopathy (DIC from abruption, AFLP, HELLP, amniotic fluid embolism) | ↑ PT/PTT, ↓ fibrinogen, schistocytes | FFP, cryoprecipitate, platelets; treat underlying cause |
Sudden cardiovascular collapse + hypoxia + DIC during or immediately after labor/delivery. Fetal cells and amniotic fluid enter maternal circulation → complement activation → massive inflammatory cascade. Management: supportive (ICU, FFP, platelets, oxygen). Very high maternal mortality (>50%). Differentiate from PE (no DVT history, onset during delivery) and sepsis (no fever prodrome).
- Category I FHR: Normal baseline (110–160), moderate variability, accelerations present, no late/variable decels. Routine monitoring only
- Category III FHR (ominous): Sinusoidal pattern OR absent baseline variability with recurrent late decels, recurrent variable decels, or bradycardia → immediate delivery or intrauterine resuscitation then delivery
- C-section indications: Category III FHR not responsive to resuscitation, placenta previa, prior classical (vertical) uterine incision, active HSV/HIV outbreak, cord prolapse, malpresentation (transverse lie)
- Cord prolapse management: Elevate presenting part manually (take pressure off cord) → emergency C-section. Do NOT push cord back in
- Shoulder dystocia: Head delivers but shoulders impacted behind pubic symphysis. First step: McRoberts maneuver (hyperflexion of maternal hips) + suprapubic pressure. If fails: Woods screw, Zavanelli, episiotomy
- Oxytocin (Pitocin) use in labor: Augment or induce contractions. Excess → uterine hyperstimulation (tachysystole) → placental insufficiency → late decelerations. Treat by stopping oxytocin + left lateral decubitus
Stages of Labor
| Stage | Definition | Substages | Key Facts |
|---|---|---|---|
| Stage 1 | Onset of labor → full dilation (10 cm) | Latent (0–6 cm, slow), Active (6–10 cm, faster) | Active phase: ≥1 cm/hr in nulliparous. Prolonged active phase = arrest → augment or C-section |
| Stage 2 | Full dilation → delivery of baby | — | Pushing phase. Prolonged (>3 hrs nulliparous, >2 hrs multiparous with epidural) → consider operative delivery |
| Stage 3 | Delivery of baby → delivery of placenta | — | Normal: <30 min. >30 min = retained placenta |
| Stage 4 | First 2 hours postpartum | — | Highest risk for PPH — monitor uterine tone and bleeding |
Shoulder Dystocia Management (HELPERR)
- Help — call for additional personnel immediately
- Episiotomy — consider (provides room but does not solve the bony impaction)
- Legs — McRoberts maneuver (hyperflex maternal thighs against abdomen → flattens lumbar lordosis → ↑ pelvic outlet)
- Pressure — suprapubic pressure (NOT fundal pressure — makes it worse)
- Enter — rotational maneuvers (Woods screw: push anterior shoulder toward fetal back; Rubin II: push anterior shoulder toward fetal chest)
- Remove posterior arm — manually deliver posterior arm first
- Roll — Gaskin (all-fours) position
Never apply fundal pressure — drives shoulder further into the pubic symphysis and worsens impaction. Suprapubic pressure (downward + lateral) is correct. Never pull on the fetal head — risks brachial plexus injury (Erb's palsy: C5-C6, "waiter's tip" position).
Operative Vaginal Delivery
| Forceps | Vacuum | |
|---|---|---|
| Fetal risk | Facial nerve injury, cephalohematoma | Cephalohematoma, subgaleal hemorrhage, retinal hemorrhage |
| Maternal risk | Vaginal/perineal lacerations (3rd/4th degree) | Same but less |
| Indication | Prolonged second stage, fetal distress | Same |
| Contraindication | Fetal coagulopathy (hemophilia), <34 weeks | Fetal coagulopathy, <34 weeks (more fragile vessels) |
- Test indication: Amenorrhea workup (rule out pregnancy first). Always do progestin challenge first, then estrogen-progestin if needed
- Progestin challenge (positive = bleeds): Patient lacked progestin (did not ovulate → no corpus luteum → no progesterone). Diagnosis: anovulation (e.g., PCOS)
- Progestin challenge (negative = does not bleed) → do estrogen-progestin challenge: If bleeds = patient was hypo-estrogenic. Causes: Turner syndrome (45,XO), Kallmann syndrome (no GnRH), hypothalamic dysfunction, premature ovarian insufficiency
- Both challenges negative (no bleed): Outflow tract obstruction or uterine unresponsiveness. Diagnoses: Asherman syndrome (intrauterine adhesions from D&C), transverse vaginal septum, imperforate hymen
- Asherman syndrome: Multiple D&C → intrauterine adhesions → endometrium cannot respond to hormones AND physical outflow obstruction. No bleed on either challenge
- Kallmann syndrome: GnRH deficiency → low FSH/LH → low estrogen → primary amenorrhea + anosmia (inability to smell — olfactory bulb agenesis)
Challenge Test Decision Algorithm
| Challenge Performed | Result | Interpretation | Classic Diagnosis |
|---|---|---|---|
| Progestin alone | Bleeds (withdrawal bleed) | Progesterone was the missing piece → no ovulation occurred | Anovulation (PCOS, hypothyroidism, hyperprolactinemia) |
| Progestin alone | No bleed → proceed to E+P | Not just progesterone deficiency — something else is wrong | — |
| Estrogen + Progestin | Bleeds | Estrogen was deficient — once supplemented, endometrium responded | Hypoestrogen state: Turner syndrome, Kallmann syndrome, premature ovarian insufficiency, hypothalamic amenorrhea |
| Estrogen + Progestin | No bleed | Uterus/outflow cannot respond even with hormones | Asherman syndrome, imperforate hymen, transverse vaginal septum |
The normal menstrual cycle: follicular phase (estrogen builds endometrium) → LH surge → ovulation → corpus luteum forms → progesterone (converts endometrium to secretory) → corpus luteum dies → progesterone falls → withdrawal bleed.
In anovulation (e.g., PCOS): estrogen is made but no ovulation → no corpus luteum → no progesterone. The endometrium is primed with estrogen but has no progesterone withdrawal trigger. When you give exogenous progestin and then withdraw it — you simulate the end of the luteal phase → withdrawal bleed occurs. This confirms the endometrium was primed (estrogen was present) and the only missing piece was progesterone (anovulation).
Primary Amenorrhea — Differential by Karyotype and Anatomy
| Condition | Karyotype | Gonads | Uterus | Key Feature |
|---|---|---|---|---|
| Turner syndrome | 45,XO | Streak gonads (no estrogen) | Present (small) | Shield chest, webbed neck, bicuspid aortic valve, coarctation; ↑ FSH/LH; ↓ estrogen |
| Androgen Insensitivity (AIS) | 46,XY | Testes (intra-abdominal) | Absent (AMH destroys Müllerian ducts) | Phenotypically female, no pubic/axillary hair (Tanner 1-2), breast development intact; ↑ testosterone |
| Müllerian Agenesis (MRKH) | 46,XX | Ovaries (normal) | Absent (Müllerian ducts don't form) | Normal breast and pubic hair (all Tanner 5); normal testosterone; vaginal canal absent or blind |
| Kallmann Syndrome | 46,XX or 46,XY | Normal but non-functional | Present | Anosmia + primary amenorrhea; ↓ GnRH → ↓ FSH/LH → ↓ estrogen |
| Hypothalamic amenorrhea | 46,XX | Normal | Present | Low BMI, extreme exercise, stress; ↓ GnRH → low FSH/LH; reversible |
Both: Phenotypically female, primary amenorrhea, absent uterus.
AIS: 46,XY, testes present (intra-abdominal, malignant potential → gonadectomy after puberty), breast development good, pubic/axillary hair sparse (androgens don't work).
MRKH: 46,XX, ovaries present, breast development good, pubic/axillary hair good (ovaries make estrogen and testosterone normally).
The exam question tells you: If Tanner stage for pubic hair is 1-2 but breasts are Tanner 5 = AIS (androgen receptor defect). If both breasts and pubic hair are Tanner 5 = MRKH (ovaries work fine).
Secondary Amenorrhea Causes (Mnemonic: PIRATE)
- Pregnancy — always rule out first with β-hCG
- Iatrogenic — oral contraceptives, Depo-Provera (post-pill amenorrhea)
- Rax hypothyroidism / hyperprolactinemia — TSH and prolactin are first-line tests
- Asherman syndrome — prior D&C; no bleed on both challenge tests
- Tumors — prolactinoma (galactorrhea + amenorrhea), Cushing's
- Exercise / Eating disorders — hypothalamic dysfunction (low GnRH)
- First-line (no contraindications): LARC — Long-Acting Reversible Contraceptive. Includes IUDs (Mirena and copper) and Nexplanon (subdermal implant, 3 years). Most effective reversible methods
- Combined OCP contraindications (absolute): History of VTE/stroke/MI, age >35 + smoker, migraines with aura, uncontrolled HTN, breast cancer, liver failure/hepatic adenomas, pregnancy/postpartum breastfeeding, immobilization, hypercoagulable states (Factor V Leiden, protein C/S deficiency)
- Combined OCP benefits: Reduces ovarian cancer (↓ ovulations) + endometrial cancer. Treats acne, endometriosis, dysmenorrhea, PMS. Raises BP — biggest cause of HTN in reproductive-age women
- Progestin-only (safe postpartum): Mini-pill, Mirena IUD, Nexplanon, Depo-Provera. No estrogen → safe for breastfeeding. Depo: delayed fertility return (up to 2 years), reversible ↓ bone density → calcium/vitamin D supplementation
- Copper IUD: Non-hormonal LARC. Contraindicated: Wilson's disease, active STI within 6 months, distorted uterine anatomy, heavy bleeding/coagulopathy. Best emergency contraception (effective up to 7 days post-coitus)
- CYP450 inducers ↓ OCP efficacy: Rifampin (TB), phenytoin, carbamazepine, phenobarbital, griseofulvin, primidone, St. John's Wort
Contraceptive Methods — Organized by Type
| Method | Type | Duration / Notes | HY Feature |
|---|---|---|---|
| Nexplanon implant | Progestin LARC | 3 years; subdermal inner arm | No effect on bone density; rapid return to fertility after removal; LARC on USMLEs |
| Mirena IUD | Progestin LARC | 5 years | Also treats adenomyosis (heavy bleeding + boggy uterus); rapid return to fertility; safe postpartum |
| Copper IUD | Non-hormonal LARC | 10 years; emergency contraception ≤7 days | Contraindicated: Wilson's disease; causes heavier periods; foreign body reaction destroys sperm |
| Depo-Provera | Progestin injection | Every 3 months | Reversible ↓ bone density (supplement calcium/vit D); delayed fertility return (up to 2 years); not a LARC |
| Combined OCP | Estrogen + progestin oral | Daily; 21/7 or 28-day pack | Progestin thickens cervical mucus, inhibits LH surge; estrogen suppresses FSH/follicle development |
| NuvaRing | Combined vaginal ring | 3 weeks in, 1 week out | Risk: toxic shock syndrome (foreign body in vagina + high fever, desquamation, hypotension) |
| Transdermal patch | Combined | 1 patch/week × 3 weeks, 1 week off | Same contraindications as combined OCP |
| Progestin-only pill | Progestin oral | Daily at same time | Must take at SAME TIME every day (small progestin-only window); safe postpartum/breastfeeding |
| Levonorgestrel (Plan B) | Emergency OCP | Within 72 hours (↓ efficacy by 72h); less effective than copper IUD | Not effective after 72 hours; copper IUD superior up to 7 days |
| Ulipristal | Emergency (SPRM) | Within 120 hours | Progesterone receptor modulator; more effective than levonorgestrel 72–120 hrs |
Hypercoagulability states: History of VTE, DVT, PE, stroke, MI — estrogen raises clotting risk. Factor V Leiden, protein C/S deficiency, antithrombin III deficiency (also lost in nephrotic syndrome), antiphospholipid syndrome.
Vascular disease: Age >35 + active smoking, uncontrolled hypertension, migraines with aura (already elevated stroke risk).
Hormone-sensitive cancers: Breast cancer (estrogen/progestin receptor positive).
Liver: Cirrhosis, active hepatitis, hepatic adenoma (estrogen stimulates adenoma growth).
Breastfeeding/postpartum: Estrogen reduces milk quantity and quality — use progestin-only methods instead.
OCP Benefits — Beyond Contraception
- Reduces ovarian cancer risk (↓ lifetime ovulations → ↓ repetitive epithelial repair → ↓ cancer risk)
- Reduces endometrial cancer risk (progestin suppresses endometrial proliferation)
- Treats endometriosis (progestin suppresses ectopic endometrial tissue)
- Treats PCOS (suppresses androgens → improves acne and hirsutism)
- Reduces acne (consider as answer when OCP is asked in acne vignette)
- Treats primary dysmenorrhea and PMS
- Reduces menstrual blood loss (helpful in iron deficiency anemia)
CYP450 Inducers That Reduce OCP Efficacy
- Rifampin (TB treatment — classic vignette: starts TB meds, becomes pregnant)
- Phenytoin (epilepsy)
- Carbamazepine (epilepsy, trigeminal neuralgia, bipolar)
- Phenobarbital / Primidone (primidone used for restless leg syndrome — classic NBME vignette)
- Griseofulvin (onychomycosis / ringworm)
- St. John's Wort (depression supplement)
Complications: IUD Insertion
| Complication | Presentation | Management |
|---|---|---|
| Uterine perforation | Heavy bleeding + lower abdominal pain + foreign body on ultrasound outside uterine cavity | Conservative if stable; laparoscopy if symptomatic |
| Expulsion | IUD strings longer than expected on exam or IUD seen at cervical os | Confirm location with ultrasound; reinsert or choose alternate method |
| Infection / PID | Fever, pelvic pain, cervical motion tenderness within 3 weeks of insertion | Antibiotics; remove IUD if no improvement |
| Ectopic pregnancy | IUD does not prevent implantation 100% — if pregnancy occurs, high ectopic risk | Methotrexate (if stable) or salpingectomy |
- AIS (androgen insensitivity syndrome): Also called testicular feminization. Karyotype 46,XY but phenotypically female. Testosterone receptor defective → testosterone has no effect → wolfian ducts don't virilize → phenotypically female
- AIS presentation: Primary amenorrhea + Tanner stage 5 breasts + Tanner stage 1-2 pubic/axillary hair. No uterus (testes produce AMH → Müllerian duct destroyed). Elevated testosterone levels
- Müllerian agenesis (MRKH): 46,XX phenotypically female. Ovaries present (normal estrogen + testosterone). Müllerian ducts fail to develop → no uterus, fallopian tubes, cervix, upper vagina. Primary amenorrhea with normal secondary sexual characteristics
- Key differentiator: AIS = sparse pubic/axillary hair (androgens don't work). MRKH = normal pubic/axillary hair (ovaries produce androgens that work normally)
- AIS management: Gonadectomy after puberty (intra-abdominal testes have malignant potential → gonadoblastoma/dysgerminoma). Estrogen replacement after gonadectomy
- Müllerian duct derivatives: Fallopian tubes, uterus, cervix, upper 1/3 vagina (all absent in both AIS and MRKH)
AIS vs MRKH — Complete Comparison
| Feature | AIS (Androgen Insensitivity) | MRKH (Müllerian Agenesis) |
|---|---|---|
| Karyotype | 46,XY (genetically male) | 46,XX (genetically female) |
| Gonads | Testes (intra-abdominal — no scrotal descent) | Ovaries (normal, functional) |
| Uterus | Absent (AMH from testes destroys Müllerian ducts) | Absent (Müllerian ducts failed to develop) |
| Fallopian tubes | Absent | Absent |
| Vagina | Blind-ending vaginal pouch or absent | Blind-ending vaginal pouch or absent |
| Breast development | Tanner 5 (testosterone aromatized to estrogen by testes) | Tanner 5 (normal ovarian estrogen) |
| Pubic/axillary hair | Tanner 1-2 (androgens don't work — receptor defect) | Tanner 4-5 (androgens work normally from ovaries) |
| Testosterone level | High (normal male range — receptor absent) | Normal female range |
| FSH/LH | ↑ (testes do not suppress pituitary normally) | Normal |
| Cancer risk | Gonadoblastoma/dysgerminoma in intra-abdominal testes | None from ovaries |
| Management | Gonadectomy after puberty (allow estrogen-driven puberty first); then HRT | Vaginal dilators (progressive dilation to create functional vagina); uterus transplant being studied |
| Fertility potential | None (no uterus, no eggs) | Gestational surrogacy possible (own eggs + donor uterus) |
Wolffian (mesonephric) ducts → require testosterone → develop into: seminal vesicles, vas deferens, epididymis, ejaculatory duct. In AIS: testosterone is made but receptor is defective → Wolffian structures do NOT develop.
Müllerian (paramesonephric) ducts → require absence of AMH → develop into: fallopian tubes, uterus, cervix, upper vagina. AMH (from testes) destroys Müllerian ducts in males. In AIS: testes produce AMH → Müllerian ducts are destroyed → no uterus/fallopian tubes/upper vagina.
In MRKH (46,XX): No AMH produced (no testes) but Müllerian ducts simply fail to form — idiopathic agenesis.
- Presentation: Postcoital bleeding (most common symptom), pelvic pain, watery discharge. Most common cause of death = renal failure (ureter obstruction → obstructive uropathy → hydronephrosis)
- HPV pathogenesis: High-risk HPV 16, 18 (and 31, 33). E6 protein = ubiquitin ligase for p53; E7 protein = ubiquitin ligase for Rb. Both tumor suppressors degraded → unregulated cell growth
- Screening: Start at age 21 (regardless of sexual debut). Ages 21–29: Pap smear every 3 years. Ages 30–65: Pap smear every 3 years OR co-test (Pap + HPV) every 5 years. HIV patients: 2× in first year, then annually forever
- 5 indications for colposcopy: HSIL, atypical glandular cells, ASC-H, positive high-risk HPV (HPV 16/18), repeated positive ASC-US. If abnormal pap but none of these 5 → test for high-risk HPV
- CIN grading: CIN1 = lower 1/3 dysplasia. CIN2 = lower 2/3. CIN3 (HSIL) = full thickness → same as carcinoma in situ (cells have NOT broken basement membrane)
- LEEP / conization risk: Both increase risk of cervical incompetence → painless second-trimester pregnancy loss (fetal descent through incompetent cervix). Treat with cervical cerclage
HPV Pathogenesis — Molecular Mechanism
E6 protein: Ubiquitin ligase that polyubiquitinates p53 → targets p53 to proteasome for degradation → loss of tumor suppressor → uncontrolled cell cycle progression past G1.
E7 protein: Ubiquitin ligase that polyubiquitinates Rb (retinoblastoma protein) → Rb degradation → E2F transcription factor released → unrestrained S-phase entry → uncontrolled DNA synthesis.
Both p53 and Rb are tumor suppressor genes. HPV's one strategy (E6 + E7) eliminates both checkpoints simultaneously — explaining its potent oncogenic potential.
Cervical Cancer Screening Algorithm
| Age Group | Screening Test | Interval | Notes |
|---|---|---|---|
| <21 years | None | — | Do not screen regardless of sexual debut |
| 21–29 years | Pap smear alone | Every 3 years | No HPV co-testing (too many transient HPV infections in this age group) |
| 30–65 years | Pap smear alone OR Pap + HPV co-test | Every 3 years (Pap alone) or every 5 years (co-test) | Co-test is preferred; negative co-test allows 5-year interval |
| >65 years | Stop if adequate prior screening + low risk | — | Continue if: HIV, immunocompromised, DES exposure, prior CIN2+ history |
| HIV / immunocompromised | Pap smear | Twice in first year after HIV diagnosis → annually forever | No stopping age for HIV patients |
| After hysterectomy | Stop (for benign indication) | — | Continue if hysterectomy for malignant/premalignant lesion → annual vaginal cuff Pap |
Pap Smear Result → Management
| Pap Result | Next Step | Why |
|---|---|---|
| HSIL (CIN3) | Colposcopy | Full-thickness dysplasia — high risk of invasion; cannot wait |
| Atypical glandular cells (AGC) | Colposcopy + endocervical curettage + endometrial biopsy | May indicate endocervical or endometrial malignancy — must assess entire reproductive tract |
| ASC-H (cannot exclude HSIL) | Colposcopy | Suspicious for high-grade lesion |
| High-risk HPV 16 or 18 positive | Colposcopy | Highest-risk HPV types; immediate colposcopy regardless of cytology result |
| ASC-US (repeated positive) | Colposcopy | Multiple indeterminate results → pattern is enough to warrant direct visualization |
| ASC-US (single, first time) | High-risk HPV reflex testing | HPV testing trumps "repeat Pap in 6-12 months" if both options offered |
| LSIL (CIN1-2) | High-risk HPV testing or repeat Pap in 12 months | Low-grade lesions often regress spontaneously; monitor first |
AGC is the one pap result that requires evaluating the ENTIRE reproductive tract (not just the cervix), because it can indicate pathology anywhere from cervix to uterine corpus:
1. Colposcopy — ectocervix
2. Endocervical curettage (ECC) — endocervical canal
3. Endometrial biopsy (endometrial sampling) — uterine cavity
All three must be done. Missing any one is an incomplete workup.
CIN Grading — Histological Classification
| Grade | USMLE Synonym | What It Means | Basement Membrane |
|---|---|---|---|
| CIN1 | LSIL (part of) | Dysplasia in lower 1/3 of cervical epithelium | Intact |
| CIN2 | LSIL (part of) | Dysplasia in lower 2/3 of cervical epithelium | Intact |
| CIN3 | HSIL = Carcinoma in Situ | Dysplasia of FULL epithelial thickness; mitoses, nuclear atypia throughout | Intact (not yet invasive) |
| Invasive carcinoma | Cervical carcinoma | Cells break through basement membrane into stroma | Breached |
Treatment Options for CIN
| Procedure | Indication | Key Complication |
|---|---|---|
| LEEP (Loop Electrosurgical Excision Procedure) | CIN2-3; allows histology of specimen | Cervical incompetence → painless second-trimester loss; treat with cerclage in next pregnancy |
| Conization (cold-knife cone biopsy) | HSIL extending into endocervical canal; same risk as LEEP | Cervical incompetence; same risk |
| Cryotherapy | CIN1-2 (older approach) | Destroys biopsy specimen — cannot do histologic analysis; generally avoided |
| Hysterectomy | Invasive cervical cancer | Definitive for early stage; add radiation ± chemo for advanced |
Recommended ages: 9–26 years (routine at 11-12). Can extend to age 45 with shared decision-making.
Number of doses: 2 doses if starting before age 15; 3 doses if starting at 15 or older or immunocompromised.
Covers: HPV 6, 11 (condyloma), 16, 18, 31, 33, 45, 52, 58 (9-valent Gardasil).
Primary vs secondary prevention: Vaccination = primary (prevents HPV infection). Pap smear = secondary (detects precancerous lesions before invasive cancer).
Other Gynecologic Malignancies — High-Yield Summary
| Cancer | Most Common Type | Key Risk Factors | Tumor Marker | Screening |
|---|---|---|---|---|
| Endometrial cancer | Endometrioid adenocarcinoma (type 1) | Unopposed estrogen (obesity, PCOS, tamoxifen, exogenous estrogen without progestin, late menopause, nulliparity) | CA-125 (less specific) | No routine screening; biopsy triggered by abnormal uterine bleeding (AUB), especially postmenopausal |
| Ovarian cancer | Serous cystadenocarcinoma (epithelial) | BRCA1/2 mutation, family history, nulliparity, late menopause. OCP use is PROTECTIVE (↓ ovulations) | CA-125 (monitoring, not screening); HE4 | No routine population screening; TVUS + CA-125 in high-risk (BRCA1/2) |
| Cervical cancer | Squamous cell carcinoma (80%) | HPV 16/18, multiple sexual partners, early coitus, immunosuppression, DES exposure (clear cell type) | SCC antigen | Pap smear ± HPV (see above) |
| Vaginal cancer | Squamous cell carcinoma (primary); clear cell adenocarcinoma (DES exposure) | DES exposure → clear cell adenocarcinoma in young women (mother took DES during pregnancy) | None specific | None routine |
| Vulvar cancer | Squamous cell carcinoma | HPV (younger women), lichen sclerosus (older women) | None specific | None routine; biopsy persistent lesions |
| Gestational trophoblastic disease | Hydatidiform mole (complete > partial) | Extremes of age, prior mole, Asian ethnicity | β-hCG (markedly elevated; complete mole β-hCG >100,000) | Serial β-hCG after evacuation; methotrexate if persistent elevation (GTN) |
Complete mole: 46,XX (all paternal — 2 sperm + empty egg); no fetal parts; β-hCG markedly elevated; "snowstorm" appearance on ultrasound; theca-lutein cysts (from excess β-hCG); 2% risk of choriocarcinoma.
Partial mole: Triploid (69,XXX or 69,XXY — 2 sperm + 1 egg); fetal parts present; lower β-hCG; less malignant potential.
Management: Suction curettage → weekly serial β-hCG until undetectable × 3 → avoid pregnancy for 6–12 months. Rising or plateauing β-hCG after evacuation = gestational trophoblastic neoplasia (GTN) → methotrexate.