Review question: Cochrane authors examined the evidence about aromatase inhibitors (AIs) for subfertile women with polycystic ovary syndrome (PCOS).

Background: PCOS is the most common cause of infrequent or absent menstrual periods, and affects about 4% to 8% of women worldwide. It often causes anovulatory subfertility (subfertility related to failure to ovulate). AIs are used to make ovulation happen. Since about 2001 clinical trials have reached differing conclusions as to whether the AI letrozole is at least as effective for treating subfertility as the most commonly used treatment, clomiphene citrate (CC).

Study characteristics: The review includes clinical studies where participants were randomly assigned to the intervention or to the comparison group (randomised controlled trials, RCTs). Our review includes 42 RCTs with 7935 women. In all trials the aromatase inhibitor used was letrozole. Comparators included CC, which was used in 25 of the RCTs, and laparoscopic ovarian drilling (a surgical technique to puncture the membrane surrounding the ovary), which was used in five RCTs. Several studies included other treatments in one or both arms.

Key results: Letrozole appears to improve live birth and pregnancy rates compared to CC when used to cause ovulation and timed intercourse. The quality of this evidence was moderate and seems to be reliable. There appeared to be no difference for miscarriage rate or multiple pregnancy rate. There appeared to be no difference between letrozole and laparoscopic ovarian drilling for any observed outcomes, although there were few relevant studies. Ovarian hyperstimulation syndrome (OHSS), a serious adverse event of hormonal stimulation, was a very rare event and in most studies it did not occur. The evidence is current to January 2018.

Quality of the evidence: The overall quality of the evidence ranged from moderate to high. Some studies in favour of clomiphene citrate may never have been published. It appears that studies that reported live births report higher clinical pregnancy rates in the letrozole group than studies that failed to report live births. This suggests that results might be somewhat less favourable to letrozole if all studies reported live births.