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Infertility in patients with PCOS

Author: Loriana Soma, MD

Editor: Sangini Sheth, MD, MHP, FACOG

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Polycystic ovarian syndrome (PCOS) is the leading cause of infertility in reproductive-age women.  Anovulation is typically the cause of infertility in PCOS.  However, evaluating anatomic reasons using an HSG, assessing hormonal levels, and obtaining a semen analysis for male factor are essential to consider before initiating ovulation induction.

Mid-luteal phase serum progesterone level or urinary ovulation predictor kits indicate ovulatory function.  Anovulatory bleeding can predict ovulatory dysfunction, thus requiring no further testing. 

Before ovulation induction, preconception counseling should include recommended lifestyle changes such as weight reduction, increased exercise, and smoking cessation if indicated by patient history.  As insulin resistance and obesity may contribute to infertility, subsequent weight loss of as little as 7% of body weight can improve ovulatory function and pregnancy rates.

In general, ovulation induction increases the risk of ovarian hyperstimulation syndrome and multiple births with associated increased maternal and neonatal risks (preterm birth, hypertensive disorders).  The rates of these risks are possibly higher in women with PCOS.  Ovulation induction medications start during the early follicular phase and continue for five days, with monthly incremental increases in dosage until ovulation is achieved.

Letrozole, an aromatase inhibitor, is the first-line treatment for women with PCOS.  Letrozole has a higher live birth rate (27% vs. 19%) than clomiphene citrate.  In addition, letrozole has lower rates of ovarian hyperstimulation and multiple births.  Clomiphene citrate may also be used. Metformin is an insulin-sensitizing agent, which some women with PCOS use who have impaired glucose tolerance or difficulty with weight loss. Metformin alone is not a first-line infertility treatment, however there is some evidence to support an increase in pregnancy rates with use of clomiphene citrate with metformin in women with PCOS. Metformin is considered safe in pregnancy.  

After 3 to 6 cycles with letrozole or clomiphene citrate, if unsuccessful, initiation of gonadotropins is the second-line treatment.  Risks of injectable gonadotropins include multiple pregnancies and ovarian hyperstimulation syndrome.  Up to 30% of gonadotropin-stimulated pregnancies are multiples, and one-third are triplets or higher order.

Laparoscopic ovarian surgery, including ovarian drilling or laser diathermy, has an unclear benefit on ovarian function.  Fertility benefits are temporary. The long-term effects of these techniques are unknown.  Adjuvant therapy is often necessary after ovarian drilling.  Surgery is not superior to gonadotropins in pregnancy rates but may have a decreased risk of multiple births. These approaches are not considered first-line therapy for infertility as safer, more effective medical options have become standard.

Further reading:

American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 194: Polycystic Ovary Syndrome. Obstet Gynecol. 2018 Jun;131(6):e157-e171. doi: 10.1097/AOG.0000000000002656.

Cunha A, Póvoa AM. Infertility management in women with polycystic ovary syndrome: a review. Porto Biomed J. 2021 Jan 26;6(1):e116. doi: 10.1097/j.pbj.0000000000000116. PMID: 33532657; PMCID: PMC7846416.


Initial approval July 2017. Revised January 2019; Reaffirmed September 2020, Revised March 2022; Revised March 2024.


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