Infertility — workup & treatment by cause

◆Definition & when to start workup

• •Infertility = inability to conceive after 12 months of regular unprotected intercourse
• •Woman ≥35 → workup at 6 months (ovarian reserve declines after 35)
• •Start IMMEDIATELY if known risk factor: amenorrhea, prior PID, chemo/radiation, age >40, known male factor (varicocele, post-vasectomy)
• •About 15% of couples affected
• •Causes by frequency: ovulatory 25%, male factor 25%, tubal/peritoneal 25%, uterine 10%, unexplained 15%

◆Initial workup (BOTH partners simultaneously)

• •Semen analysis (do FIRST — cheap, easy, identifies 25% of cases)
• •Ovulation: mid-luteal (day 21) progesterone (>3 = ovulating); ovulation predictor kits; BBT charts
• •Tubal patency: hysterosalpingogram (HSG) — also has mild therapeutic benefit (lipid-soluble contrast)
• •Ovarian reserve: AMH (best), day-3 FSH + estradiol, antral follicle count (AFC) on US
• •Endocrine: TSH, prolactin, FSH/LH/estradiol, total testosterone, DHEA-S
• •Pelvic ultrasound to assess uterus and ovaries

◆Female: ovulatory disorders (by cause)

• •PCOS (most common anovulation): irregular menses + hyperandrogenism + polycystic ovaries; weight loss + LETROZOLE 1st-line (replaces clomid per PPCOS II)
• •Hypothalamic amenorrhea: low BMI / excessive exercise / stress; LOW FSH + LOW LH + low estradiol; restore energy intake, then pulsatile GnRH or gonadotropins
• •Premature ovarian insufficiency (POI): age <40 + HIGH FSH (>30–40); donor egg IVF — get karyotype, fragile X premutation, adrenal autoantibodies
• •Hyperprolactinemia: prolactinoma, drugs (antipsychotics, metoclopramide, opiates), hypothyroidism; treat with CABERGOLINE (or bromocriptine in pregnancy)
• •Thyroid dysfunction: treat to TSH <2.5 in women trying to conceive

◆Female: tubal & uterine factors

• •Tubal disease: PID (most common cause), endometriosis, prior pelvic surgery, ectopic with salpingectomy
• •HSG bilateral occlusion → IVF; hydrosalpinx → SALPINGECTOMY before IVF (fluid is embryotoxic)
• •Uterine factors: fibroids (esp submucosal), endometrial polyps, Asherman (intrauterine adhesions), septate uterus
• •Hysteroscopy for diagnosis + treatment of intracavitary lesions
• •Endometriosis: laparoscopic confirmation; mild–moderate may benefit from surgical excision/ablation; severe → IVF

◆Male factor

• •Repeat abnormal semen analysis in 4–6 weeks (spermatogenesis cycle 72 days)
• •Varicocele is the most common surgically correctable cause
• •Klinefelter (47,XXY): small firm testes, azoospermia, ↑ FSH, ↑ LH, low T → donor sperm or microTESE + ICSI
• •Hypogonadotropic hypogonadism: ↓ FSH/LH/T → hCG + FSH stimulation
• •Exogenous testosterone SHUTS DOWN spermatogenesis — must STOP before any workup
• •Congenital bilateral absence of vas (CBAVD): test for CF mutations (both partners) → ICSI with TESE
• •Severe oligospermia / azoospermia → ICSI: a single viable sperm enables pregnancy

◆Treatment ladders by diagnosis

• •PCOS: weight loss → letrozole → letrozole + metformin → gonadotropins → IVF
• •Hypothalamic: restore weight/energy → pulsatile GnRH or gonadotropins
• •Hyperprolactinemia: cabergoline (treat the cause)
• •POI: donor oocyte IVF
• •Tubal blockage: IVF (salpingectomy first if hydrosalpinx)
• •Severe male factor: ICSI ± donor sperm
• •Unexplained: empiric letrozole/clomid + IUI × 3–6 cycles → IVF
• •Age >38 + unexplained: skip empiric IUI, go directly to IVF

◆Assisted reproductive technology (ART)

• •IUI (intrauterine insemination): processed sperm placed in uterus around ovulation; cycle success ~10–15%
• •IVF (in vitro fertilization): ovarian stimulation → oocyte retrieval → fertilization in lab → embryo transfer; per-cycle live birth ~30–50% depending on age
• •ICSI: single sperm injected into oocyte — for severe male factor
• •PGT (preimplantation genetic testing): aneuploidy screening (PGT-A) or single-gene (PGT-M); useful in advanced maternal age or known mutation
• •Single-embryo transfer recommended in good-prognosis patients to avoid multiples
• •Cryopreservation of embryos and oocytes available; egg freezing for fertility preservation (pre-chemo, age, social)

◆Complications & risks of treatment

• •Ovarian hyperstimulation syndrome (OHSS): abdominal pain, ascites, hemoconcentration, VTE; risk highest in PCOS phenotype; supportive, dopamine agonist (cabergoline) prophylaxis in high-risk cycles
• •Multiple gestation: highest with gonadotropins; lower with letrozole than clomid; IVF risk minimized with eSET (single embryo transfer)
• •Ectopic pregnancy risk slightly elevated post-IVF
• •Psychological burden — counseling and support groups
• •Cost: IUI ~$500–1500/cycle; IVF $12–20k/cycle — variable insurance coverage

Anovulation: pattern recognition

Initial test → action