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Review
July 6, 2021

Diagnosis and Management of Infertility: A Review

Author Affiliations
  • 1Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut
  • 2Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut
JAMA. 2021;326(1):65-76. doi:10.1001/jama.2021.4788
Abstract

Importance  In the US, approximately 12.7% of reproductive age women seek treatment for infertility each year. This review summarizes current evidence regarding diagnosis and treatment of infertility.

Observations  Infertility is defined as the failure to achieve pregnancy after 12 months of regular unprotected sexual intercourse. Approximately 85% of infertile couples have an identifiable cause. The most common causes of infertility are ovulatory dysfunction, male factor infertility, and tubal disease. The remaining 15% of infertile couples have “unexplained infertility.” Lifestyle and environmental factors, such as smoking and obesity, can adversely affect fertility. Ovulatory disorders account for approximately 25% of infertility diagnoses; 70% of women with anovulation have polycystic ovary syndrome. Infertility can also be a marker of an underlying chronic disease associated with infertility. Clomiphene citrate, aromatase inhibitors such as letrozole, and gonadotropins are used to induce ovulation or for ovarian stimulation during in vitro fertilization (IVF) cycles. Adverse effects of gonadotropins include multiple pregnancy (up to 36% of cycles, depending on specific therapy) and ovarian hyperstimulation syndrome (1%-5% of cycles), consisting of ascites, electrolyte imbalance, and hypercoagulability. For individuals presenting with anovulation, ovulation induction with timed intercourse is often the appropriate initial treatment choice. For couples with unexplained infertility, endometriosis, or mild male factor infertility, an initial 3 to 4 cycles of ovarian stimulation may be pursued; IVF should be considered if these approaches do not result in pregnancy. Because female fecundity declines with age, this factor should guide decision-making. Immediate IVF may be considered as a first-line treatment strategy in women older than 38 to 40 years. IVF is also indicated in cases of severe male factor infertility or untreated bilateral tubal factor.

Conclusions and Relevance  Approximately 1 in 8 women aged 15 to 49 years receive infertility services. Although success rates vary by age and diagnosis, accurate diagnosis and effective therapy along with shared decision-making can facilitate achievement of fertility goals in many couples treated for infertility.

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