1. Female Reproductive Diseases

A) Congenital (Developmental) Disorders

Embryological Basis

Classification of Uterine Anomalies

Key Clinical Points

• Septate uterus: women carry up to 60% risk of spontaneous miscarriage; embryos that implant on the poorly vascularized septum suffer abnormal placentation. Hysteroscopic metroplasty significantly reduces pregnancy loss.
• DES exposure in utero: diethylstilbestrol (banned 1971) causes T-shaped uterus, cervical abnormalities, vaginal adenosis, and associated obstetric complications. Women whose mothers took DES have higher malformation rates.
• Vaginal anomalies: imperforate hymen, transverse vaginal septum, and vaginal agenesis (in Müllerian agenesis) present with primary amenorrhea ± cyclical pain.
• Cervical anomalies: incompetent cervix associated with DES exposure and uterine hypoplasia → second-trimester loss and premature labor.

B) Inflammatory Diseases (Infections)

Vulvovaginal Infections

Pelvic Inflammatory Disease (PID)

• Neisseria gonorrhoeae — mucosal route of spread; acute suppurative salpingitis with intraluminal pus (pyosalpinx)
• Chlamydia trachomatis — causes cervicitis → salpingitis, endometritis; major cause of PID
• Post-abortion/postpartum polymicrobial: staphylococci, streptococci, coliforms, Clostridium perfringens — spread via lymphatics/veins → deeper tissue involvement

• Acute: peritonitis, bacteremia → endocarditis, meningitis, septic arthritis
• Chronic: infertility/tubal obstruction, ectopic pregnancy, chronic pelvic pain, intestinal adhesions

Bartholin Gland Infection

C) Hormonal / Functional Disorders

Polycystic Ovary Syndrome (PCOS)

• Most common endocrine disorder of reproductive-age women
• Features: anovulation/oligomenorrhea, hyperandrogenism, insulin resistance, ovarian radiologic appearance of multiple small follicles
• Elevated LH → premature oocyte aging and dyssynchronous endometrial maturation
• Linked to recurrent pregnancy loss (found in 40–80% of recurrent miscarriage patients)
• Insulin resistance and elevated androgens adversely affect uterine receptivity

Luteal Phase Insufficiency

• Inadequate progesterone production by the corpus luteum
• Impaired decidualization of the endometrium → natural selection of embryos → pregnancy loss
• Normal pregnancy depends on the corpus luteum from ovulation to 7–9 weeks, after which the trophoblast assumes progesterone production (luteal-placental shift)

Thyroid Disease

• Hypothyroidism associated with ovulatory dysfunction, luteal phase defects, and recurrent miscarriage
• Recommended TSH threshold during pregnancy: <2.5 mIU/mL
• Even euthyroid patients with anti-thyroid antibodies have elevated miscarriage rates; thyroid hormone supplementation reduces pregnancy loss in these patients undergoing IVF

Hyperprolactinemia

• Elevated prolactin → hypothalamic-pituitary-ovarian axis disruption → impaired folliculogenesis and luteal dysfunction → miscarriage
• Normalizing prolactin with dopamine agonists improves live birth rates in recurrent pregnancy loss patients

Diminished Ovarian Reserve (DOR)

• Associated with higher proportion of aneuploid embryos → increased first-trimester miscarriage
• Assessed by FSH, estradiol, and anti-Müllerian hormone (AMH) in early follicular phase

Endometriosis

• Ectopic endometrial glands and stroma outside the uterus (ovaries, peritoneum, fallopian tubes)
• Causes dysmenorrhea, dyspareunia, chronic pelvic pain, and infertility
• Mechanism of infertility: altered uterine contractility, peritoneal inflammation, adhesions, impaired tubal function

2. Gestational and Placental Disorders

a) Implantation and Early Pregnancy Disorders

Spontaneous Abortion (Miscarriage)

• 60%: sporadic chromosomal aneuploidy (most common cause of 1st trimester loss)
• Remaining 40%: chronic maternal illness (diabetes, connective tissue disorders), uterine structural malformations, infections, inadequate progesterone, immunologic factors

Ectopic Pregnancy

• Implantation outside the uterine cavity, most commonly in the fallopian tube (especially ampullary region)
• Risk factors: prior PID/salpingitis (tubal scarring), prior ectopic, IUD use, assisted reproduction
• Presentation: amenorrhea, unilateral pelvic pain, vaginal bleeding; rising but subnormal hCG
• Diagnosis: transvaginal ultrasound (empty uterus + adnexal mass/ring)
• Life-threatening if tubal rupture occurs → hemoperitoneum
• Treatment: methotrexate (unruptured, stable) or surgical salpingostomy/salpingectomy

Molar Pregnancy (Gestational Trophoblastic Disease)

b) Hypertensive Disorders of Pregnancy

Classification

1. Gestational hypertension: new-onset BP ≥140/90 mmHg after 20 weeks without proteinuria
2. Preeclampsia: hypertension + proteinuria (>0.3 g/24 hrs) after 20 weeks
3. Severe preeclampsia: BP >160/110 + significant proteinuria (>5 g/24 hrs) + end-organ damage
4. Eclampsia: preeclampsia + seizures (one or more convulsions)
5. Chronic hypertension with superimposed preeclampsia: accounts for 15–30% of hypertensive disease in pregnancy

Preeclampsia

• Soluble Flt-1 (VEGF receptor-1)
• Endoglin
• Decorin

• Mild: bed rest, close surveillance; delay delivery until fetal maturity or complications
• Severe: delivery within 24 hours
• Seizure prophylaxis: IV magnesium sulfate — loading dose 4 g over 15–20 min, then 2 g/hr infusion; continued 12–24 hours postpartum
• BP control: IV hydralazine if diastolic persistently >110 mmHg

HELLP Syndrome

• Hemolysis
• Elevated Liver enzymes
• Low Platelets

Eclampsia

• One or more generalized convulsions in a woman with preeclampsia
• Pathology: extensive placental infarcts reduce uteroplacental circulation → fetal malnutrition, FGR, fetal death
• Treatment: magnesium sulfate (prevention and treatment of seizures), urgent delivery

c) Metabolic / Systemic Gestational Disorders

Gestational Diabetes Mellitus (GDM)

• Glucose intolerance first recognized during pregnancy; results from insulin resistance amplified by placental hormones (hCS/human placental lactogen)
• Human chorionic somatomammotropin (hCS) causes decreased glucose utilization and increased free fatty acids in the mother, contributing to the diabetogenic state
• Screening: 50 g oral glucose challenge test (GCT) at 24–28 weeks; confirmed by 100 g OGTT
• Complications: macrosomia, shoulder dystocia, neonatal hypoglycemia, polyhydramnios, increased risk of C-section, future type 2 DM in mother
• Maternal hyperglycemia is directly linked to embryonic damage and increased risk of spontaneous pregnancy loss in overt insulin-dependent diabetes

Preterm Labor

• Betamethasone 12 mg IM × 2 doses (24–34 weeks) to accelerate fetal lung maturity
• GBS prophylaxis
• Tocolysis: magnesium sulfate, nifedipine; terbutaline limited to 48–72 hours only (FDA restriction)

Intrahepatic Cholestasis of Pregnancy

• Pruritus (especially palms/soles), elevated bile acids and liver enzymes in third trimester
• Associated with increased fetal risk (stillbirth); managed with ursodeoxycholic acid and early delivery

Thyroid Disease in Pregnancy

• Hypothyroidism: TSH should be kept <2.5 mIU/mL; associated with fetal neurodevelopmental impairment
• Hyperthyroidism (most commonly Graves'): propylthiouracil preferred in 1st trimester; methimazole after 1st trimester

d) Fetal Growth and Development Disorders

Fetal Growth Restriction (FGR) / Intrauterine Growth Restriction (IUGR)

• Estimated fetal weight <10th percentile for gestational age
• Causes:
  • Placental: preeclampsia (most important), placental infarction, abruption, poor spiral artery remodeling
  • Fetal: chromosomal anomalies (trisomy 18, 13), congenital infections (TORCH), structural malformations
  • Maternal: malnutrition, smoking, substance abuse, chronic disease (hypertension, renal disease, SLE)
• Pathophysiology in preeclampsia: anti-angiogenic molecules (sFlt-1, endoglin) impair uteroplacental perfusion → fetal malnutrition
• Consequences: increased perinatal mortality; long-term risk of cardiovascular disease and type 2 diabetes in adulthood (Barker hypothesis — "fetal programming")
  • Low birth weight followed by rapid catch-up growth further increases the risk of metabolic syndrome
  • Child obesity in epidemic proportions is partly traceable to placental dysfunction

Polyhydramnios

• Amniotic fluid index (AFI) >24 cm or deepest pocket >8 cm
• Associated with: fetal swallowing impairment (esophageal atresia, anencephaly), maternal GDM (fetal polyuria), preeclampsia
• Risk: preterm labor, cord prolapse, malpresentation

Oligohydramnios

• AFI <5 cm
• Causes: renal agenesis/urinary tract obstruction (Potter sequence), PPROM, severe FGR with placental insufficiency, post-term pregnancy
• Risk: pulmonary hypoplasia, limb deformities (positional), umbilical cord compression

Rh Incompatibility / Hemolytic Disease of the Fetus and Newborn (HDFN)

• Rh(D)-negative mother sensitized by Rh(D)-positive fetal blood → anti-D IgG crosses placenta → fetal hemolysis
• Prevention: anti-D immunoglobulin (RhoGAM) at 28 weeks, at delivery, and after any sensitizing event
• Severe cases: hydrops fetalis, fetal death
• Management: intrauterine transfusion; neonatal phototherapy or exchange transfusion

The Barker Hypothesis (Developmental Origins of Health and Disease — DOHaD)

• Cardiovascular disease
• Type 2 diabetes
• Hypertension
• Obesity (especially with rapid postnatal catch-up growth)

• Berek & Novak's Gynecology
• Robbins, Cotran & Kumar — Pathologic Basis of Disease
• Textbook of Family Medicine, 9th Edition
• The Developing Human: Clinically Oriented Embryology