# Clinical Cases: Infertility ## Case 1: Polycystic Ovary Syndrome and Anovulatory Infertility ### Patient Demographics - **Age:** 28 years - **Sex:** Female - **Occupation:** Marketing manager ### Chief Complaint "My husband and I have been trying to get pregnant for 18 months without success." ### History of Present Illness The patient reports irregular menstrual cycles since menarche, occurring every 35 to 90 days. She has never been pregnant. She notes gradual weight gain over the past 5 years and increasing facial hair requiring weekly removal. Her last menstrual period was 8 weeks ago. She denies hot flashes, vaginal dryness, or galactorrhea. Her husband is 30 years old and healthy with no known fertility issues. They have been having unprotected intercourse 2-3 times weekly for 18 months. ### Past Medical History - Obesity (BMI 34 kg/m2) - Acne vulgaris treated with topical retinoids ### Physical Examination Findings - **Vital Signs:** BP 128/82 mmHg, HR 76 bpm, BMI 34 kg/m2 - **General:** Obese female, android body habitus - **Skin:** Hirsutism on upper lip, chin, and chest; acanthosis nigricans at posterior neck and axillae - **Thyroid:** Normal size, no nodules - **Breast:** No galactorrhea expressed - **Abdomen:** Soft, non-tender, obese - **Pelvic:** Normal external genitalia, cervix appears normal, uterus normal size, no adnexal masses palpable ### Diagnostic Workup - **Serum beta-hCG:** Negative - **Day 3 FSH:** 6.2 IU/L (normal) - **Day 3 Estradiol:** 42 pg/mL (normal) - **Anti-Mullerian Hormone (AMH):** 8.2 ng/mL (elevated, consistent with PCOS) - **Total Testosterone:** 68 ng/dL (elevated) - **Free Testosterone:** 2.1 ng/dL (elevated) - **DHEA-S:** 320 mcg/dL (upper normal) - **TSH:** 2.1 mIU/L (normal) - **Prolactin:** 12 ng/mL (normal) - **Fasting Glucose:** 102 mg/dL (impaired fasting glucose) - **Fasting Insulin:** 22 mIU/mL (elevated) - **HbA1c:** 5.8% - **Mid-luteal Progesterone:** 1.2 ng/mL (consistent with anovulation) - **Transvaginal Ultrasound:** Bilateral enlarged ovaries (12 mL and 14 mL) with more than 20 small peripheral follicles (2-9 mm) in each ovary; normal uterus with 8 mm endometrial thickness - **Hysterosalpingogram:** Normal uterine cavity; bilateral tubal patency with free peritoneal spill - **Semen Analysis (partner):** Volume 3.2 mL, concentration 45 million/mL, motility 58%, morphology 6% normal forms (all within WHO reference values) ### Diagnosis **Polycystic Ovary Syndrome (PCOS)** meeting Rotterdam criteria (2 of 3): 1. Oligo-ovulation/anovulation (irregular cycles, low luteal progesterone) 2. Clinical and biochemical hyperandrogenism (hirsutism, elevated testosterone) 3. Polycystic ovarian morphology on ultrasound **Associated findings:** Insulin resistance, impaired fasting glucose ### Management Plan **Lifestyle Modification (First-Line):** 1. Weight loss goal of 5-10% body weight (target loss of 15-20 lbs) 2. Mediterranean-style diet with reduced refined carbohydrates 3. Regular aerobic exercise 150 minutes per week 4. Referral to registered dietitian **Medical Treatment:** 1. **Letrozole** 2.5 mg daily for days 3-7 of menstrual cycle (first-line ovulation induction for PCOS per PPCOS II trial) 2. Ovulation monitoring with urinary LH kits starting cycle day 10 3. Timed intercourse every 1-2 days during fertile window 4. Consider metformin 500 mg twice daily as adjunct for insulin resistance **Follow-up:** 1. Mid-luteal progesterone to confirm ovulation 2. If no ovulation at 2.5 mg, increase letrozole to 5 mg then 7.5 mg in subsequent cycles 3. If no conception after 3-4 cycles of letrozole with confirmed ovulation, proceed to IUI 4. Reassess after 6 months; consider referral for IVF if unsuccessful **Counseling Points:** - 80% of women with PCOS will ovulate with ovulation induction agents - 30-40% conception rate expected within 6 ovulatory cycles - Weight loss of 5-10% can restore spontaneous ovulation in many patients - Multiple pregnancy risk approximately 5-7% with letrozole (lower than clomiphene) - Long-term health counseling regarding diabetes, cardiovascular disease, and endometrial cancer risk ### Clinical Image ![Polycystic Ovaries on Ultrasound](case_01_image.jpg) **Image Description:** Transvaginal ultrasound image demonstrating a polycystic ovary with characteristic peripheral arrangement of multiple small follicles (2-9 mm), creating the classic "string of pearls" appearance. The central ovarian stroma appears increased in echogenicity. The ovarian volume exceeds 10 mL. **Attribution:** Image from Wikimedia Commons. Licensed under CC BY-SA 4.0. Source: https://commons.wikimedia.org/wiki/File:Polycystic_Ovaries.jpg --- ## Case 2: Male Factor Infertility with Varicocele ### Patient Demographics - **Age:** 32 years (female patient presenting for couple's infertility) - **Partner Age:** 35 years - **Occupation:** Elementary school teacher ### Chief Complaint "We've been trying to conceive for 14 months. My periods are regular, but something might be wrong with my husband's sperm." ### History of Present Illness The female patient has regular 28-day menstrual cycles with positive ovulation predictor kits at mid-cycle. She has no history of pelvic infections, prior surgeries, or endometriosis symptoms. Her partner reports no erectile dysfunction or ejaculatory problems. He has noticed a painless scrotal swelling on the left side for several years. They have been having intercourse every other day during her fertile window without lubricant use. ### Male Partner History and Examination - History of undescended left testicle corrected surgically at age 2 - No history of sexually transmitted infections - No medications; occasional alcohol use - No history of chemotherapy or radiation - Physical examination by urologist: Left-sided varicocele grade III (visible without Valsalva), normal testicular size bilaterally ### Female Evaluation - **Day 3 FSH:** 7.1 IU/L - **Day 3 Estradiol:** 38 pg/mL - **AMH:** 2.8 ng/mL (normal ovarian reserve) - **TSH:** 1.8 mIU/L - **Prolactin:** 14 ng/mL - **Mid-luteal Progesterone:** 14.2 ng/mL (confirming ovulation) - **Hysterosalpingogram:** Normal uterine cavity, bilateral tubal patency ### Male Partner Semen Analysis (Repeated x2) - **Volume:** 2.8 mL - **Concentration:** 8 million/mL (oligospermia; reference >15 million/mL) - **Total Motility:** 28% (asthenospermia; reference >40%) - **Progressive Motility:** 18% (reference >32%) - **Morphology:** 2% normal forms (teratospermia; reference >4%) - **Diagnosis:** Oligo-astheno-teratospermia (OAT syndrome) ### Male Partner Additional Workup - **FSH:** 9.8 IU/L (upper normal, suggesting impaired spermatogenesis) - **LH:** 5.2 IU/L (normal) - **Total Testosterone:** 380 ng/dL (normal) - **Scrotal Ultrasound:** Left varicocele with dilated pampiniform plexus vessels >3 mm; normal testicular parenchyma bilaterally ### Diagnosis 1. **Male Factor Infertility** - Oligo-astheno-teratospermia (OAT syndrome) 2. **Left Varicocele Grade III** - most common correctable cause of male infertility 3. History of cryptorchidism (additional risk factor for impaired spermatogenesis) ### Management Plan **Option 1: Varicocele Repair** 1. Urology consultation for microsurgical varicocelectomy 2. Improvement in semen parameters expected in 60-70% of men 3. Timeline: 3-6 months for spermatogenesis cycle to complete after repair 4. Natural conception may become possible if parameters improve sufficiently **Option 2: Assisted Reproductive Technology** 1. Given the severity of OAT, IVF with ICSI (intracytoplasmic sperm injection) offers the highest per-cycle pregnancy rate 2. ICSI overcomes sperm motility and morphology defects by direct injection of single sperm into oocyte 3. Fertilization and pregnancy rates with ICSI are comparable to conventional IVF when oocyte quality is normal **Recommended Approach:** 1. Discuss both options with couple; decision based on patient preference, timeline, and financial considerations 2. If couple prefers to try varicocele repair first: proceed with surgery, repeat semen analysis at 3-4 months, attempt natural conception or IUI if improvement adequate 3. If rapid conception desired or severe oligospermia persists: proceed directly to IVF with ICSI **Genetic Counseling:** - Karyotype analysis recommended for men with sperm concentration <5 million/mL (patient at 8 million) - Y-chromosome microdeletion testing if severe oligospermia or azoospermia - If genetic abnormality found, implications for offspring to be discussed before proceeding with ART **Counseling Points:** - Male factor contributes to infertility in approximately 35% of couples - Varicocele repair improves semen parameters in majority but does not guarantee conception - IVF/ICSI success rates 40-50% per cycle for female partner's age - Consider cryopreservation of sperm before any treatment ### Prognosis With IVF/ICSI, expected per-cycle live birth rate of approximately 45% given female age of 32 with normal ovarian reserve. If varicocele repair pursued and semen parameters improve to allow IUI, per-cycle pregnancy rate of 10-15%.