Ovulatory Disorders

Ovulatory Disorders: Basics & WHO - Ovulation Off-Kilter

• Definition: Disruption in the normal, cyclical release of an oocyte from the ovary; a primary cause of female infertility.
• Key Signs: Irregular menstrual cycles (oligomenorrhea: >35 days or <8 cycles/year) or absent menses (amenorrhea).
• WHO Classification (Anovulation):
  • Group I: Hypothalamic-pituitary failure (↓FSH, ↓Estradiol). E.g., Hypothalamic amenorrhea, Kallmann syndrome.
  • Group II: Hypothalamic-pituitary dysfunction (Normoestrogenic, often normal gonadotropins or ↑LH:FSH ratio). E.g., PCOS (most common), mild hyperprolactinemia.
  • Group III: Ovarian failure (↑FSH, ↓Estradiol). E.g., Premature Ovarian Insufficiency (POI), gonadal dysgenesis.

⭐ PCOS, a WHO Group II disorder, is the most common cause of anovulatory infertility, affecting 6-15% of reproductive-aged women globally.

Etiology Deep Dive - Why No Egg-citement?

• WHO Group I: Hypothalamic-Pituitary Failure (↓GnRH, ↓FSH/LH, ↓E₂)
  • Functional Hypothalamic Amenorrhea (FHA): Stress, ↓weight, ↑exercise (Female Athlete Triad).
  • Kallmann Syndrome: Anosmia, GnRH deficiency.
  • Pituitary: Sheehan's, tumors, infiltrative disease.
• WHO Group II: H-P Dysfunction (Dysregulation; often normal E₂)
  • Polycystic Ovary Syndrome (PCOS): Most common. Hyperandrogenism, oligo/anovulation, PCOM.
  • Hyperprolactinemia: Prolactinoma, drugs, hypothyroidism (↑TRH).
  • Thyroid disorders (hypo/hyper).
• WHO Group III: Ovarian Failure (↑FSH/LH, ↓E₂, ↓AMH)
  • Premature Ovarian Insufficiency (POI): Failure < 40 yrs.
    • Genetic (Turner's, FMR1), autoimmune, iatrogenic (chemo/radio, surgery).
  • Gonadal dysgenesis.
• WHO Group IV: Other
  • Congenital Adrenal Hyperplasia (CAH) - late-onset.
  • Androgen-secreting tumors.
  • Cushing's.

⭐ PCOS is the most common cause of anovulatory infertility, affecting 6-10% of reproductive-age women.

Clinical Clues & Diagnosis - Spotting Ovulation Snooze

• Clinical Presentation:
  • Menstrual dysfunction: Oligomenorrhea (<9 menses/yr or cycle >35 days), amenorrhea (>3-6 months).
  • Symptoms of cause:
    • PCOS: Hirsutism, acne, obesity.
    • Hyperprolactinemia: Galactorrhea, headaches.
    • Thyroid disease: Weight changes, fatigue.
• Diagnostic Toolkit:
  • Basal Body Temperature (BBT): Sustained ↑0.5°F post-ovulation (biphasic). 📌 BBT: Basal Body Temp ↑ post-ovulation.
  • Urinary LH Kits (OPKs): Detect LH surge 24-36 hrs pre-ovulation.
  • Mid-luteal Serum Progesterone (Day 21): >3 ng/mL suggests ovulation; >10 ng/mL optimal.
  • Transvaginal Ultrasound (TVS): Follicular tracking, corpus luteum, endometrial thickness (≥7 mm).
  • Hormonal Assays: FSH, LH, estradiol, prolactin, TSH, AMH.

⭐ A mid-luteal serum progesterone level >3 ng/mL is the most commonly accepted biochemical evidence of recent ovulation.

Management Strategies - Ovulation Re-Boot Camp

• Goal: Unifollicular ovulation & conception.
• General Approach:

• Pharmacological Agents:
  • Clomiphene Citrate (CC): 50-150mg/day x 5 days. SERM. 📌 CC: Clomiphene Cheers Ovaries.
  • Letrozole: 2.5-7.5mg/day x 5 days. Aromatase inhibitor. Preferred in PCOS.
  • Gonadotropins (FSH, hMG): For CC/Letrozole failure. Monitor (USG, E2). Risks: OHSS, multiples.
  • Metformin: Adjunct in PCOS with insulin resistance.
  • Dopamine Agonists (Cabergoline): For hyperprolactinemia.
• Surgical: Laparoscopic Ovarian Drilling (LOD) for CC-resistant PCOS.

⭐ Letrozole: first-line for OI in PCOS; ↑ live birth, ↓ multiple pregnancy vs CC.

High‑Yield Points - ⚡ Biggest Takeaways

• Ovulatory disorders are a leading cause of female infertility.
• WHO classification is key: Group I (hypothalamic failure), Group II (PCOS), Group III (ovarian failure).
• PCOS (WHO Group II) is most common cause of anovulatory infertility.
• Clomiphene citrate & letrozole: first-line for PCOS anovulation.
• Hyperprolactinemia can cause anovulation; treat with dopamine agonists.
• Premature Ovarian Insufficiency (WHO III) often requires oocyte donation.
• Confirm ovulation with mid-luteal serum progesterone.