Continuing Metformin in Early Pregnancy Linked to Lower Miscarriage Risk in PCOS: Meta-Analysis

The research team analyzed data from 12 randomized controlled trials involving a total of 1,708 women with PCOS. All included trials assessed the use of metformin initiated before conception and continued until at least a confirmed pregnancy, comparing outcomes against either placebo or no treatment.

The analysis revealed the following findings:

• Women who continued metformin through the first trimester had higher clinical pregnancy rates (OR 1.57).
• In this group, there was a trend toward fewer miscarriages (OR 0.64).
• A possible increase in live birth rates was also noted (OR 1.24), though not statistically conclusive.
• Women who stopped metformin after a confirmed pregnancy also showed higher clinical pregnancy rates (OR 1.35).
• However, this group had a potential increase in miscarriage risk (OR 1.46).
• Indirect comparisons favored continued metformin use over stopping it at pregnancy confirmation.
• Trends indicated a lower risk of miscarriage (OR 0.44) and better pregnancy outcomes when metformin was continued through the first trimester.

These findings challenge previous clinical guidance. The 2017 American Society for Reproductive Medicine (ASRM) guidelines stated there was insufficient evidence to support metformin use during pregnancy for miscarriage prevention. Similarly, current European Society for Human Reproduction and Embryology (ESHRE) guidelines recommend discontinuing metformin after conception during IVF or ICSI cycles.

Given these new insights, the authors suggest that international clinical recommendations may need to be reassessed. A large ongoing multicenter UK trial (LOCI trial) is expected to provide additional clarity. This trial examines metformin use in combination with ovulation induction agents, with treatment extended until 14 weeks of gestation.

The authors also emphasize the need for future research, particularly studies that explore the impact of metformin throughout the full course of pregnancy and its effects across different PCOS phenotypes. Tailoring treatment based on individual patient characteristics could optimize outcomes for women with PCOS planning pregnancy.

"Continuing metformin through the first trimester may help lower the risk of miscarriage and improve live birth rates in women with PCOS. Keeping the treatment going after a positive pregnancy test seems more beneficial than stopping it early. However, more high-quality studies are needed to confirm these findings," they concluded.

Reference:

CHESHIRE J, GARG A, SMITH P, DEVALL AJ, COOMARASAMY A, DHILLON-SMITH RK, Preconception and first trimester metformin on pregnancy outcomes in women with polycystic ovary syndrome: a systematic review and meta-analysis, American Journal of Obstetrics and Gynecology (2025), doi: https://doi.org/10.1016/j.ajog.2025.05.038.