Definition: failure to conceive after 12 months of regular sexual intercourse without contraception; evaluation for infertility should begin for failure to conceive after 6 months of regular intercourse without contraception in women >35 years of age. More immediate evaluation is recommended in women >40 years of age. Primary infertility: Couple has never been pregnant. Secondary infertility: Couple has been pregnant.


The incidence of infertility increases with age, with a decline in fertility in the early 30s, accelerating in the late 30s. ~85% of couples will conceive within 12 months of unprotected intercourse. ~95% of couples will conceive within 24 months of unprotected intercourse. In the United States, ~12.7% of women of reproductive age seek infertility treatment each year (1).


  • Infertility affects 8.8% of U.S. women between the ages of 15 and 49 (1).
  • ~9% of couples between the ages of 15 and 34 years, 25% of couples between the ages of 35 and 39 years, and ~30% of couples between the ages of 40 and 44 years meet the criteria for being infertile, according to the National Survey of Family Growth.
  • This may increase as more women delay childbearing.

Etiology and Pathophysiology

  • Most cases are multifactorial: Approximately 85% are due to identifiable causes such as tubal disease, ovulatory dysfunction, and male factor infertility (due to abnormal sperm production or delivery). The other 15% have unexplained causes of infertility.
  • Acquired: The most common cause of infertility in the United States is pelvic inflammatory disease (PID) secondary to sexually transmitted infections (STIs), followed by endometriosis, polycystic ovary syndrome (PCOS), premature ovarian failure, and increased maternal age. ~25% of infertility diagnoses are due to ovulatory disorders (such as PCOS, hyperprolactinemia, hypothyroidism or hyperthyroidism, primary ovarian insufficiency, ovarian dysgenesis/agenesis, exposure to chemo or radiotherapy, eating disorder, tumors, prior surgery). 70% of women with anovulation have PCOS.
  • Diminished ovarian reserve (DOR): low fertility due to insufficient quantity or functional quality of oocytes
  • Congenital abnormalities: anatomic (such as undescended testicles, bicornuate uterus, etc.) and genetic

There is a higher incidence of genetic abnormalities among the infertile population, including Klinefelter syndrome (47, XXY), Turner syndrome (45X or mosaic), and fragile X syndrome. Y chromosomal microdeletions are associated with isolated defects of spermatogenesis → found in 16% of men with azoospermia/severe oligospermia; cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation causing congenital bilateral absence of vas deferens (CBAVD)

Risk Factors

  • Female
    • Gynecologic history: irregular/abnormal menses, STIs, dysmenorrhea, fibroids
    • Medical history: advanced age, endocrinopathy, autoimmune disease, undiagnosed celiac disease, collagen vascular diseases, thrombophilia, obesity, and cancer
    • Surgical history: appendicitis, pelvic surgery, intrauterine surgery, tubal ligation
    • Social history: smoking, alcohol/substance abuse, eating disorders, exercise, advanced maternal age
  • Male
    • Medical history: STIs, prostatitis, medication use (i.e., β-blockers, calcium channel blockers, antiulcer medication), endocrinopathy, cancer
    • Surgical history: orchiopexy, hernia repair, vasectomy with/without reversal
    • Social history: smoking, alcohol/substance abuse, anabolic steroids, environmental exposures, occupations leading to increased scrotal temperature (frequent use of saunas, hot tubs, or tight underwear), prescription drugs that impair male potency

Commonly Associated Conditions

Pelvic pathology, endocrine dysfunction, and anovulation (hyperandrogenism, PCOS)

There's more to see -- the rest of this topic is available only to subscribers.