Infertility in patients with PCOS
Editors: Julie Decesare, MD and Eduardo Lara-Torre, MD
Polycystic ovarian syndrome (PCOS) is the leading cause of infertility in reproductive age women. Anovulation is generally assumed to be the cause after other anatomic, hormonal, and male factor causes are ruled out. A semen analysis should be performed to rule out male factor, and a HSG should be considered in high risk patients (previous PID, ectopic history, endometriosis) prior to initiating ovulation induction.
Ovulatory function may be assessed by a mid-luteal phase serum progesterone level or urinary ovulation predictor kits. Patients with obvious patterns of anovulatory bleeding may not need further testing to confirm ovulatory dysfunction.
Prior to ovulation induction, preconception counseling should include recommended lifestyle changes such as weight reduction, increased exercise, and smoking cessation. 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.
Risks of ovulation induction include ovarian hyperstimulation syndrome and multiple pregnancies, which may be increased in women with PCOS. These medications should be started during the early follicular phase and continued for 5 days. Dosing may be increased if ovulation does not occur.
Letrozole, an aromatase inhibitor, is the first line treatment for women with PCOS. It has an increased live birth rate when compared to clomiphene citrate (27% vs 19%) and has lower ovarian hyperstimulation and multiple pregnancy rates. Metformin is an insulin-sensitizing agent that is used in some women with PCOS who have impaired glucose tolerance or difficulty with weight loss. In women already using metformin who also need ovulation induction, clomiphene citrate may be added to improve pregnancy rates. Its use as a single agent for ovulation induction is not indicated.
If ovulation induction does not occur after 3 to 6 cycles with letrozole or clomiphene citrate, second line treatments with gonadotropins may be initiated. Risks of injectable gonadotropins include multiple pregnancies and ovarian hyperstimulation syndrome. Up to 30% of gonadotropin-stimulated pregnancies are multiples, one third of them triplets or higher order.
Laparoscopic ovarian surgery including ovarian drilling or laser diathermy has unclear benefit on ovarian function. It can be used as a second line treatment and may provide temporary increase in fertility. It has not shown to be superior to gonadotropins in pregnancy rates, but may have a decreased risk of multiple births. The long term effects of these techniques are unknown.
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.
American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 738: Aromatase Inhibitors in Gynecologic Practice. Obstet Gynecol. 2018 Jun;131(6):e194-e199. doi: 10.1097/AOG.0000000000002640.
Initial approval July 2017. Revised January 2019
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