Podcast: Aromatase inhibitors for subfertility treatment in women with polycystic ovary syndrome

The Cochrane Gynaecology and Fertility Group has prepared more than 200 reviews and in May 2018, a team from Germany, The Netherlands and New Zealand updated one of these reviews, looking at the use of letrozole for subfertile women with anovulatory polycystic ovary syndrome. Lead author, Sebastian Franik from the University of Münster in Germany describes the latest findings in this podcast.

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John: Hello, I'm John Hilton, editor in the Cochrane Editorial and Methods department. The Cochrane Gynaecology and Fertility Group has prepared more than 200 reviews and in May 2018, a team from Germany, The Netherlands and New Zealand updated one of these reviews, looking at the use of letrozole for subfertile women with anovulatory polycystic ovary syndrome. Lead author, Sebastian Franik from the University of Münster in Germany describes the latest findings in this podcast.

Sebastian: Polycystic ovary syndrome (PCOS) is the most common cause of infrequent, or absent, periods worldwide, affecting about one women in 15 and often leading to subfertility. Various drugs have been tested, with clomiphene citrate proving to be the most successful through the past four decades. However, in 2002, a new class of drugs called aromatase inhibitors were introduced for ovulation induction, and many clinical trials have reported that one of these, letrozole, might be at least as effective as clomiphene citrate. However, there have been fluctuating results and, so, we’ve been doing this Cochrane Review to evaluate the effectiveness and safety of aromatase inhibitors for subfertile women with anovulatory PCOS.
We searched for published and unpublished randomized trials in which an aromatase inhibitor had been used alone or in conjunction with other medical therapies for ovulation induction in anovulatory women with PCOS. We’ve added 16 trials as part of this update, bringing the total number of studies in the review to 42 and these had recruited nearly 8000 subfertile women with PCOS.
Our primary outcomes were live birth rate, which was reported in 16 studies, and ovarian hyperstimulation syndrome rate, for which we could use data from 21 studies.
26 studies compared letrozole to clomiphene citrate with or without additional treatment. 13 of these reported an increase in live birth rate, and when we combined them in a meta-analysis, it suggested that the odds of having a live baby were increased by 70% among women using letrozole rather than clomiphene citrate. Furthermore, we found high-quality evidence that ovarian hyperstimulation syndrome occurred with similar frequency with letrozole or clomiphene citrate. We were able to use data from 25 studies to investigate the proportion of women who became pregnant, and found a 60% increase with letrozole. Where data were available on unintended side effects, there was no evidence to distinguish between letrozole and clomiphene citrate on miscarriage rate or multiple pregnancies.
We also compared letrozole against laparoscopic ovarian drilling in women with clomiphene resistance and PCOS. There was low-quality evidence that live birth rates were similar, but there was insufficient data to show evidence of a difference between letrozole and laparoscopic ovarian drilling in ovarian hyperstimulation syndrome. There was also not enough data to show whether or not different doses of letrozole made a difference to the main outcomes.
To sum up, our updated results suggest that subfertile women with PCOS treated with letrozole have better pregnancy and live birth outcomes compared to women treated with clomiphene, while the rates of ovarian hyperstimulation syndrome are similar. However, unanswered questions remain, including uncertainty about the dosage effects of aromatase inhibitors, which need to be tackled in studies comparing different drugs and dosages and testing whether the use of multiple drugs is beneficial.

John: If you would like to explore the findings of the update in more detail, go online to Cochrane Library dot com and search 'aromatase inhibitors and PCOS'. That's also where you’ll find further updates of the review, as new evidence becomes available and the current uncertainties are tackled.

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