A couple of weeks ago, I wrote a piece on the possible impacts of metformin on sperm, highlighting what I thought was an excellent paper raising concerns about the link between this diabetes treatment in men and birth defects. In response, a number of people asked about metformin in women. One reason is its use in treating diabetes, as it is used in men. But beyond diabetes, metformin is also often prescribed for infertility.
So today, a quick follow-up on this question. The TL;DR is that we do not see this same set of birth defect concerns, although the evidence on the efficacy of metformin for treating infertility is also fairly weak.
Metformin is a commonly used drug to treat diabetes. This is its only on-label usage. However: it has been used for many years off-label to treat polycystic ovary syndrome (PCOS) and infertility. It is not atypical for it to be incorporated into IVF treatment, in the hopes of improving outcomes.
Digging into the data on this, I found reassurance and also caution, though around different questions.
On the reassurance side: although it would be good to have larger sample sizes, a review of studies from 2014 shows no increased risk of birth defects from maternal use of metformin. Moreover, in looking at papers that study the efficacy of this treatment in terms of fertility, we do not see concerns raised about these issues.
One other thing to note, related to the paper on fathers: it focused on taking metformin during the period of spermatogenesis (i.e. when the sperm is made). This occurs in the several months before conception. For women, our eggs are already produced before birth, which means this particular mechanism could not operate in the same way.
Bottom line for the first concern: if you are prescribed metformin, the evidence doesn’t suggest an elevated birth defect risk. It is worth noting that most women who have diabetes pre-pregnancy are switched to insulin during pregnancy for better control.
On the other hand, there is a lot of caution raised in the literature about whether metformin is a useful addition to fertility treatments. A well-cited paper from 2007 in the New England Journal of Medicine used a randomized trial to compare metformin and clomiphene citrate (another medication) in fertility treatments. It found that clomiphene citrate was significantly more successful than metformin, and adding metformin to the clomiphene citrate didn’t significantly increase pregnancy rates.
A 2020 Cochrane Review that focused on IVF in women with PCOS found “no conclusive evidence that metformin improves live birth rates.” This echoed the conclusions of a 2013 review. These studies do find metformin useful in lowering the risk of ovarian hyperstimulation (i.e. this review), although there are arguments that perhaps there are better approaches.
The science of infertility is vast, and treatments are enormously complicated and individual-specific. So none of this is to suggest at all that metformin might not be appropriate in particular situations. The data doesn’t suggest prescription as a general rule for everyone.
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