What is the most common cause of infertility?

Most Common Causes of Infertility

Polycystic Ovary Syndrome (PCOS) is the most common cause of infertility in women, affecting approximately 7% of reproductive-aged women and representing the leading cause of anovulatory infertility. 1

Female Factors (60-65% of cases)

Ovulatory Disorders (25% of all infertility cases)

• PCOS: The predominant cause, affecting 7-15% of reproductive-aged women 2
  • Characterized by hyperandrogenism and polycystic ovarian morphology (>25 small follicles in at least one ovary or ovarian volume >10 mL) 1
  • Accounts for approximately 70% of women with anovulation 3

Age-Related Factors

• Deterioration of oocyte quality with advancing maternal age 1, 4
• Significant decline in fertility begins in mid-30s, becoming more pronounced after age 35 4
• Women >35 years should be evaluated after 6 months of trying to conceive rather than the standard 12 months 4

Tubal and Uterine Factors

• History of salpingitis (such as from chlamydia infection) 1
• Tubal occlusion and peritubular adhesions from previous pelvic infections or surgery 1
• Intrauterine synechiae (adhesions) 1
• Uterine cavity abnormalities interfering with implantation 1

Endometriosis

• Affects at least one-third of women with infertility and up to 10% of reproductive-aged women 1
• Mechanism of infertility is unclear but confirmed association exists 1
• Requires laparoscopy for definitive diagnosis and staging 1

Male Factors (30-40% of cases)

Semen Abnormalities

• Abnormal parameters according to WHO reference limits 1:
  • Low sperm concentration (<16 million/mL)
  • Poor motility (<30% progressive motility)
  • Abnormal morphology (<4% normal forms)
  • Low semen volume (<1.4 mL)

Genetic Factors

• Karyotype abnormalities - most common known genetic cause of male infertility 1
  • Klinefelter syndrome (47, XXY) and other chromosomal numerical anomalies
  • Structural anomalies (deletions, duplications, inversions)
• Y-chromosome microdeletions - found in 5% of males with severe oligospermia 1

Obstructive Causes

• Congenital bilateral absence of vas deferens (CBAVD)
• Ejaculatory duct obstruction (EDO)
• Characterized by low volume, acidic pH, azoospermic ejaculate 1

Unexplained Infertility (15% of cases)

• Approximately 15% of infertile couples have no identifiable cause despite complete evaluation 3

Evaluation Algorithm

For Women:

1. Initial assessment: Menstrual history, signs of ovulation, and age-related risk assessment
2. Ovarian function: Transvaginal ultrasound for antral follicle count and ovarian volume
   • Diminished ovarian reserve suggested when ovarian volume <3 cm³ and <5 antral follicles 1
3. Tubal patency: Hysterosalpingography or other imaging when indicated
4. Uterine evaluation: Ultrasonography, hysteroscopy, or MRI when indicated for abnormalities

For Men:

1. Semen analysis: Assess concentration, motility, morphology, and volume
2. Genetic testing: Karyotype for males with azoospermia or sperm concentration <5 million/mL with elevated FSH or testicular atrophy 1
3. Hormonal evaluation: FSH, testosterone levels when indicated

Common Pitfalls in Diagnosis

• Failure to evaluate both partners simultaneously: ASRM recommends evaluation of both partners begin at the same time 1
• Delayed evaluation in women >35: Should be assessed after 6 months of trying rather than 12 months 4
• Overlooking PCOS: Remember that PCOM on imaging is not sufficient for diagnosis without clinical features 1
• Missing endometriosis: Small endometrial implants are not well detected on imaging; laparoscopy remains the diagnostic standard 1
• Neglecting lifestyle factors: Fertility rates are lower in women who are very thin or obese, and those with high caffeine intake 1

By understanding these common causes and following a systematic approach to evaluation, clinicians can effectively diagnose and address infertility in most couples.