Male Factor Infertility

Male Factor Infertility: Introduction & Overview - The Seed Story

• Accounts for ~50% of all infertility cases, impacting couples worldwide.
• Infertility: inability to conceive after 1 year of regular, unprotected intercourse.
• Male factor involves issues with:
  • Sperm production (azoospermia, oligospermia)
  • Sperm function (asthenospermia, teratospermia)
  • Sperm delivery (e.g., ejaculatory duct obstruction)
• Semen analysis is the cornerstone of initial investigation.

⭐ Male factor is the sole cause in approximately 20-30% of infertile couples and a contributing factor in an additional 20-30%.

Male Factor Infertility: Etiology & Risk Factors - Sperm Saboteurs

• Pre-testicular (Endocrine):
  • Hypothalamic-pituitary dysfunction (e.g., Kallmann syndrome).
  • Hyperprolactinemia, thyroid disorders.
• Testicular (Primary Gonadal Failure):
  • Genetic: Klinefelter syndrome (47,XXY), Y-chromosome microdeletions (AZF).
  • Varicocele (most common correctable).
  • Cryptorchidism, mumps orchitis.
  • Gonadotoxins: Chemotherapy, radiation.
• Post-testicular (Ductal Obstruction / Ejaculatory Dysfunction):
  • Obstruction: CBAVD (CFTR gene), infections (epididymitis), vasectomy.
  • Ejaculatory dysfunction: Retrograde ejaculation, anejaculation.
• Sperm Function Defects:
  • Immotile cilia syndrome (Kartagener's), globozoospermia, antisperm antibodies.
• Idiopathic: ~30-40% of cases; no identifiable cause.
• Key Risk Factors:
  • Advanced paternal age (>40 years).
  • Lifestyle: Smoking, ↑alcohol, obesity, anabolic steroids.
  • Environmental: Heat exposure (e.g., saunas), toxins (pesticides).
  • Medical: STIs, diabetes, previous testicular surgery/trauma.

⭐ Varicocele is the most common surgically correctable cause of male infertility, found in approximately 40% of men presenting with infertility.

Male Factor Infertility: Clinical Evaluation & Semen Analysis - Sperm Sleuthing

• Clinical Evaluation:
  • History: Coital hx, developmental (cryptorchidism), infections (mumps), medications, lifestyle (smoking, alcohol, heat).
  • Exam: BMI, secondary sexual characteristics, gynecomastia. Genital exam: testicular size (orchidometer, normal >15 mL or >4 cm length), consistency, presence of vas deferens, varicocele (check with Valsalva maneuver).
• Semen Analysis (WHO 2021 Lower Reference Limits): 📌 Abstinence: 2-7 days.
  • Volume: ≥ 1.4 mL
  • Sperm Concentration: ≥ 16 million/mL
  • Total Sperm Count: ≥ 39 million/ejaculate
  • Total Motility (Progressive PR + Non-Progressive NP): ≥ 42%
  • Progressive Motility (PR): ≥ 30%
  • Morphology (Kruger's Strict Criteria): ≥ 4% normal forms
  • Vitality (live spermatozoa): ≥ 54%
  • Leukocytes (WBC): < 1 million/mL (Pyospermia if ≥ 1 million/mL)

⭐ At least two abnormal semen analyses, performed 1-3 months apart, are generally required to diagnose male factor infertility due to significant biological variability in semen parameters.

Male Factor Infertility: Advanced Investigations & Management - Fertility Fixers

• Advanced Investigations:
  • Hormonal Assay: FSH (↑ in primary testicular failure), LH, Testosterone, Prolactin.
  • Genetic Testing: Karyotype (e.g., Klinefelter 47,XXY), Y-chromosome microdeletions (AZF regions).
  • Imaging: Scrotal Ultrasound/Doppler (varicocele, testicular mass), Transrectal Ultrasound (TRUS) for Ejaculatory Duct Obstruction (EDO).
• Management Strategies:
  • Medical: Hormonal therapy (gonadotropins for hypogonadotropic hypogonadism), antioxidants.
  • Surgical: Varicocelectomy (for clinical varicocele & abnormal semen), vasectomy reversal, sperm retrieval (TESE/MESA).
  • Assisted Reproductive Technology (ART): IUI (mild factor), IVF, ICSI (severe factor).

    ⭐ ICSI is the cornerstone for severe male infertility, including azoospermia with surgically retrieved sperm (TESE/MESA).

High‑Yield Points - ⚡ Biggest Takeaways

• Idiopathic infertility is the most common diagnosis, affecting 30-40% of males.
• Varicocele is the most frequent correctable cause of male infertility.
• Semen analysis: Oligozoospermia (<15 million/mL), Asthenozoospermia (<40% motility), Teratozoospermia (<4% normal forms).
• Azoospermia: Obstructive (normal FSH, testis size) vs. Non-obstructive (↑FSH, small testes).
• Kallmann syndrome: Hypogonadotropic hypogonadism with anosmia.
• Klinefelter syndrome (47,XXY): Hypergonadotropic hypogonadism, often leading to azoospermia.
• Y-chromosome microdeletions (e.g., AZFc) cause severe spermatogenic failure.