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Definition: failure of a couple to conceive after 1 year of normal sexual activity without contraceptives. Primary: Couple has never been pregnant. Secondary: Couple has been pregnant. Fecundability: the probability of achieving pregnancy in one menstrual cycle


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.

  • About 25% of couples experience infertility at some point in their reproductive lives.
  • ~11.5% couples between ages 15 and 34 years and 42% between ages 35 and 44 years meet the criteria for being infertile.
  • May increase as more women delay childbearing; 20% of women in the United States have their first child >35 years.
  • CDC National Survey of Family Growth noted 12% of U.S. women >15 to 44 years old have impaired fecundity.

Etiology and Pathophysiology

  • Most cases multifactorial: approximately 50% of cases due to female factors (of which 20% are due to ovulatory dysfunction and 30% due to tubal and pelvic pathology); ~40% due to male factors; 20% unknown etiology
  • Acquired: Most common cause of infertility in the United States is pelvic inflammatory disease (PID) secondary to chlamydia (1), 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 azoo-/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, sexually transmitted infections (STIs), dysmenorrhea, fibroids, prior pregnancy
    • Medical history: 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

  • Sexual behavior increasing risk for STIs
  • Pelvic pathology: endometriosis, ovarian cysts, endometrial polyps, and uterine fibroids
  • Endocrine dysfunction (thyroid, glucose metabolism, menstrual cycle abnormalities, prolactin)
  • Anovulation is commonly associated with hyperandrogenism and PCOS.

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