Continuing Metformin Reduces PCOS Pregnancy Risks
METHODOLOGY:
Researchers conducted a systematic review and meta-analysis of randomized controlled trials evaluating metformin started preconception and continued at least until positive pregnancy test compared with placebo or no treatment in women with PCOS.
The analysis included 12 trustworthy studies with 1708 participants, with trials conducted across 14 countries spanning five continents, all graded as low to moderate quality evidence.
The primary outcome measure focused on miscarriage rate, defined as pregnancy loss prior to 20 completed weeks of gestation, while secondary outcomes included clinical pregnancy and live birth rates.
Investigators performed indirect comparisons between treatment groups using the Bucher technique to evaluate clinical pregnancy, miscarriage, and live birth rates for metformin treatment continued throughout first trimester vs stopped at a positive pregnancy test.
TAKEAWAY:
Women receiving preconception metformin continued throughout the first trimester had higher clinical pregnancy rates (OR, 1.57; 95% CI, 1.11-2.23), potential reduction in miscarriage (OR, 0.64; 95% CI, 0.32-1.25), and possible increase in live birth (OR, 1.24; 95% CI, 0.59-2.61) compared with placebo or no treatment.
Participants who stopped metformin once pregnant showed an increased clinical pregnancy rate (OR, 1.35; 95% CI, 1.01-1.80) but suggested higher miscarriage risk (OR, 1.46; 95% CI, 0.73-2.90) compared with placebo or no treatment.
Indirect comparisons consistently favored continuing metformin through first trimester vs stopping at pregnancy confirmation for clinical pregnancy (OR, 1.16; 95% CI, 0.74-1.83), miscarriage (OR, 0.44; 95% CI, 0.17-1.16), and live birth (OR, 1.14; 95% CI, 0.41-3.13).
IN PRACTICE:
'Women with PCOS have been shown to have a fivefold increased risk per year of developing insulin resistance and subsequent type 2 diabetes. Insulin resistance has been shown to be independently associated with a higher risk of miscarriage. Metformin acts by decreasing gluconeogenesis, lipogenesis and enhancing glucose uptake, all of which in turn reduce insulin resistance,' wrote the authors of the study.
SOURCE:
The study was led by James Cheshire, PhD, Birmingham Women's and Children's NHS Foundation Trust in Birmingham, England. It was published online in American Journal of Obstetrics and Gynecology .
LIMITATIONS:
According to the authors, the main limitation was the inherent heterogeneous nature of the study population and the overall low quality of evidence. Women with PCOS have different phenotypes and varying degrees of hyperandrogenism and insulin resistance, which could not be accounted for in the analyses. Additionally, many studies did not subdivide pregnancy outcome data by body mass index (BMI), preventing meaningful analyses in BMI subgroups. The limited outcome data in spontaneously conceiving populations (only 30 women from two studies) make it difficult to extrapolate findings to this group.
DISCLOSURES:
The authors reported having no conflicts of interest. The study received no external funding.
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