Most infertile couples have an identifiable cause, JAMA review reports
About 85% of infertile couples had an identifiable cause, according to a 2021 JAMA review by two Yale physicians. The review draws on 71 articles about couples trying to conceive. Ovulation problems, male factor, and blocked tubes were the most common causes. The other 15% were labeled unexplained.
Key Findings
A PubMed and Cochrane search identified 71 articles: 31 systematic reviews, 29 meta-analyses, 5 clinical trials, and 6 practice guidelines.
An identifiable abnormality or underlying disease explained infertility in 85% of couples. For the remaining 15%, the review uses the label "unexplained infertility."
Problems with ovulation make up approximately 25% of infertility diagnoses. Among women who do not ovulate, 70% have polycystic ovary syndrome (PCOS, now also called PMOS).
Endometriosis is present in 25% to 40% of women with infertility. A male factor occurs in 35% of infertile couples.
In women with PCOS, live birth occurred in 103 of 374 (27.5%) with letrozole and 72 of 376 (19.1%) with clomiphene.
Interpretation
The paper is a JAMA review of published studies. The authors searched PubMed and Cochrane for English-language studies from January 2015 to November 2020. It covers causes of infertility, evaluation, and treatment. The authors state that some content rests on guidelines, which can reflect expert opinion. They know of no high-quality randomized trials comparing tubal surgery with IVF, and note that IVF bypasses tubal blockage.
RRM Context
Most couples have a cause that can be found. That supports cause-based evaluation. Unexplained infertility means the workup found nothing, so the couple is undiagnosed. IVF bypasses the reproductive system and leaves the cause in place. Restorative reproductive medicine looks for causes in both partners.
Our editorial summary of this paper, not the article's abstract.
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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