Infertility — Overview & Causes (Male + Female)

Definition

• Primary infertility: Never achieved a pregnancy
• Secondary infertility: Infertility after at least one prior pregnancy
• ~85% of couples conceive within 12 months; ~95% within 24 months

Causes — Overview

A complete workup of both partners is always recommended since multiple causes are frequently identified simultaneously.

Female Causes

1. Ovulatory Dysfunction (~20–40% of female infertility)

• PCOS — most common cause of anovulation; hyperandrogenism, oligo/anovulation, polycystic-appearing ovaries
• Diminished ovarian reserve — age-related decline (fecundability drops 53% at age 40–41 vs. 30–31)
• Premature ovarian insufficiency (POI) — loss of ovarian function before age 40
• Endocrine causes: hypothyroidism, hyperprolactinemia

2. Tubal Factor (~14–35%)

• Pelvic inflammatory disease (PID) — most common cause of tubal damage; often Chlamydia or Gonorrhoea
• Endometriosis — can cause peritubal adhesions and obstruction
• Prior pelvic/tubal surgery
• Salpingitis isthmica nodosa

3. Uterine Factor

• Submucosal fibroids (leiomyomas)
• Congenital Müllerian anomalies (e.g., septate uterus)
• Intrauterine adhesions (Asherman's syndrome) — often post-D&C
• Endometrial polyps

4. Decreased Ovarian Reserve

• Assessed by day 2–3 serum FSH + estradiol, anti-Müllerian hormone (AMH), and antral follicle count (AFC) on ultrasound
• High FSH or low AMH signals reduced reserve

5. Pelvic/Peritoneal Factor

• Endometriosis causing periadnexal adhesions
• Other pelvic adhesive disease

Male Causes

1. Testicular/Spermatogenic Defects (~30–40% of male infertility)

• Klinefelter syndrome (47,XXY) — most common genetic cause; azoospermia or severe oligospermia
• Y chromosome microdeletions (AZF regions) — impair spermatogenesis
• Varicocele — most common reversible cause
• Prior orchitis (e.g., mumps orchitis)
• Cryptorchidism (undescended testes)
• Chemotherapy/radiation exposure

2. Anatomic/Obstructive

• Vasectomy
• Congenital bilateral absence of vas deferens (CBAVD) — associated with CFTR mutations (cystic fibrosis)
• Ejaculatory duct obstruction
• Prior inguinal/scrotal surgery

3. Endocrine

• Hypogonadotropic hypogonadism (low FSH/LH → low testosterone) — can be idiopathic (Kallmann syndrome) or secondary
• Hyperprolactinemia
• Hypothyroidism
• Morbid obesity (↑ estrogen from aromatization)
• Exogenous anabolic steroids/androgens (suppresses LH/FSH)

4. Sexual/Ejaculatory Dysfunction

• Erectile dysfunction
• Retrograde ejaculation (common in diabetes, post-prostatectomy)
• Anejaculation

5. Genetic

• Klinefelter's, Y-microdeletions (as above)

Key Investigations

Semen analysis (WHO reference values): Volume ≥1.4 mL; total sperm number ≥39 million per ejaculate; progressive motility ≥30%; normal morphology ≥4% (Tygerberg strict criteria). No single parameter predicts infertility — multiple abnormalities increase risk.

Age Effect on Female Fertility

High-Yield Exam Points

• Infertility = 12 months; >35 yrs → 6 months; >40 yrs → immediate
• Male factor is involved in up to 50% of cases (sole cause in ~20%)
• PCOS = most common cause of anovulatory infertility in women
• Varicocele = most common reversible cause in men
• Klinefelter (47,XXY) = most common genetic cause of male infertility
• CBAVD → always test for CFTR mutations
• Unexplained infertility = up to 30% after full workup
• Spontaneous conception less likely: age >42, infertility >4 years, severe endometriosis, severe tubal disease