Definition: failure to conceive after 1 year of regular sexual intercourse without the use of contraception in women <35 years of age or failure to conceive after 6 months of regular intercourse without contraception in women >35 years of age. Primary infertility: Couple has never been pregnant. Secondary infertility: Couple has been pregnant.


Incidence is the probability of achieving a pregnancy within 1 year. 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.


  • About 25% of couples experience infertility at some point in their reproductive lives.
  • ~9% of couples between ages 15 and 34 years, 25% between ages 35 and 39 years, ~30% couples between the ages of 40 and 44 years meet the criteria for being infertile, according to the National Survey of Family Growth.
  • May increase as more women delay childbearing.

Etiology and Pathophysiology

  • Most cases multifactorial: approximately 35% of cases due to female factors (of which 21% are due to ovulatory dysfunction and 14% due to tubal damage); ~26% due to male factors; 28% unknown etiology
  • Acquired: Most common cause of infertility in the United States is pelvic inflammatory disease (PID) secondary to sexually transmitted infections (STIs), endometriosis, polycystic ovary syndrome (PCOS), premature ovarian failure, and increased maternal age.
  • Diminished ovarian reserve (DOR): low fertility due to low quantity or functional quality of oocytes
  • Congenital: anatomic and genetic abnormalities


  • Higher incidence of genetic abnormalities among 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 oligozoospermia.
  • 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, prior pregnancy
    • 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: STI, prostatitis, medication use (i.e., β-blockers, calcium channel blocker, antiulcer medication), endocrinopathy, cancer
    • Surgical history: orchiopexy, hernia repair, vasectomy with/without reversal
    • Social: 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

General Prevention

Normal diet and exercise, avoid smoking and other substance abuse, prevention of STIs

Commonly Associated Conditions

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

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