Harvey's Garden

Infertility

3 min read

  • Definition
    • Inability to conceive after 12 months of regular, unprotected intercourse in females <35 years old.
    • Inability to conceive after 6 months in females ≥35 years old.

Initial Workup

  • Male Partner:
    • Semen Analysis: Best initial test for the male partner; assesses sperm concentration, motility, and morphology.
  • Female Partner:
    • Ovulation Assessment: Check mid-luteal phase (Day 21) serum progesterone.
    • Ovarian Reserve: Day 3 FSH, LH, estradiol, and Anti-Müllerian Hormone (AMH).
    • Tubal Patency: Hysterosalpingogram (HSG) is an x-ray used to visualize the uterine cavity and fallopian tubes.
    • Uterine Anatomy: Transvaginal ultrasound (TVUS) to assess for structural abnormalities like fibroids or polyps.
    • Endocrine Labs: TSH and prolactin levels.

Female Infertility (~65%)

  • Ovulatory Disorders (~25%)
    • Patho: Failure to release a mature oocyte regularly.
    • Etiologies:
      • Polycystic Ovary Syndrome (PCOS): Most common cause of anovulatory infertility. Characterized by hyperandrogenism, ovulatory dysfunction, and/or polycystic ovaries on ultrasound. Associated with insulin resistance. Lab findings often show ↑LH/FSH ratio >2:1, ↑testosterone, and ↑estrogen.
      • Hypothalamic Amenorrhea: ↓GnRH from stress, excessive exercise, or low body weight → ↓FSH, ↓LH, ↓estrogen.
      • Primary Ovarian Insufficiency (POI): Depletion of oocytes before age 40. Presents with ↑FSH, ↑LH, and ↓estrogen.
      • Hyperprolactinemia: High prolactin levels suppress GnRH release.
      • Thyroid Disease: Both hypothyroidism and hyperthyroidism can disrupt ovulation.
  • Tubal & Pelvic Factors (~35%)
    • Patho: Structural blockage or damage preventing the union of sperm and egg or transport of the embryo.
    • Etiologies:
      • Pelvic Inflammatory Disease (PID): Major cause of tubal scarring and occlusion, often from N. gonorrhoeae or C. trachomatis infections.
      • Endometriosis: Ectopic endometrial tissue causes inflammation and adhesions, distorting pelvic anatomy.
      • Previous Pelvic/Abdominal Surgery: Can lead to adhesions.
  • Uterine Factors (~10%)
    • Patho: Anatomic abnormalities that impair embryo implantation or growth.
    • Etiologies:
      • Submucosal Leiomyomas (Fibroids): Protrude into the uterine cavity, distorting it.
      • Endometrial Polyps: Overgrowths of endometrial tissue.
      • Intrauterine Adhesions (Asherman Syndrome): Scarring of the endometrium, often after D&C.
      • Congenital Müllerian Anomalies: e.g., septate uterus.

Male Infertility (~35%)

  • Pre-testicular (Endocrine)
    • Patho: Inadequate hormonal stimulation of the testes.
    • Etiologies:
      • Hypogonadotropic Hypogonadism: Low GnRH, FSH, and LH. Can be congenital (e.g., Kallmann Syndrome - anosmia and GnRH deficiency) or acquired (e.g., pituitary tumor).
      • Exogenous Androgen Use: Suppresses the HPG axis, leading to ↓FSH and impaired spermatogenesis.
  • Testicular (Primary Gonadal Failure)
    • Patho: Intrinsic testicular failure leading to impaired sperm production.
    • Etiologies:
      • Varicocele: Most common correctable cause of male infertility. Dilated pampiniform plexus raises scrotal temperature, impairing spermatogenesis.
      • Genetic: Klinefelter Syndrome (47, XXY), Y-chromosome microdeletions.
      • Other: Cryptorchidism, orchitis (e.g., mumps), trauma, chemotherapy/radiation.
  • Post-testicular (Obstructive)
    • Patho: Blockage of the ductal system, preventing sperm transport.
    • Etiologies:
      • Congenital Bilateral Absence of the Vas Deferens (CBAVD): Strongly associated with CFTR gene mutations (Cystic Fibrosis).
      • Acquired Obstruction: Previous vasectomy, infections (e.g., epididymitis).

Management Highlights

  • Ovulation Induction:
    • Letrozole: Aromatase inhibitor that lowers systemic estrogen, reducing negative feedback and ↑FSH/LH. First-line for PCOS.
    • Clomiphene Citrate: Selective estrogen receptor modulator (SERM) that blocks estrogen receptors at the hypothalamus, ↑GnRH pulsatility and thus ↑FSH/LH.
  • Anatomic Issues:
    • Surgical Correction: Lysis of adhesions, hysteroscopic resection of fibroids/polyps.
  • Assisted Reproductive Technology (ART):
    • Intrauterine Insemination (IUI): Placement of concentrated sperm directly into the uterus.
    • In Vitro Fertilization (IVF): Ovarian stimulation, egg retrieval, fertilization in the lab, and embryo transfer. Used for tubal disease, severe male factor, or failed ovulation induction.
    • Intracytoplasmic Sperm Injection (ICSI): Single sperm injected directly into an egg; used for severe male factor infertility.

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