Examining Effects of Metformin on Live Birth Rate in PCOS-Induced Mice: A Research Protocol

Abstract

Introduction: Polycystic Ovary Syndrome (PCOS) is the prevailing endocrinopathy of women of reproductive age. With insulin resistance as a key feature of the disorder, metformin has been observed to improve ovulation induction, anovulatory infertility, and hyperandrogenic symptoms. Some hesitancy to prescribe this medication can be attributed to its possible contribution to pregnancy loss. This research protocol investigates the effect of metformin therapy on live birth rates (LBRs) to deduce its efficacy extending beyond fertility for pregnancy success. Congenital anomalies and birth weights are also evaluated. Methods: A transgenic C57BL/6 mouse model is adopted using the bovine luteinizing hormone beta subunit (LHβ) gene to induce a high expression of LH and subsequently lead to PCOS-like symptoms. At first anovulation detection, metformin therapy is administered to the experimental mice. At 26 days, artificial insemination is conducted to induce pregnancy. The experimental mice are divided into three sections: the first terminating metformin treatment at fertilization (MetF), the second at the end of the first trimester (MetT1), and the last extending throughout pregnancy (MetT2). Results: It is hypothesized that MetT2 mice will yield a higher LBR than those without continuous metformin treatment, with the MetF group producing the lowest rate of all mice provided with the drug. Furthermore, the control group should noticeably differ in LBR compared to the experimental group. Congenital anomalies and birth weights are expected to remain unchanged regardless of treatment. Discussion: The currently available information regarding metformin’s influence on LBR is inconsistent, but it is reasonable to conclude that there will be some improvement. Fetal outcomes have been less explored. Conclusion: By comparing LBRs, congenital anomalies, and birth weights, this experiment can expose the most advantageous duration of metformin administration. Future directions should include combining with other pharmacological therapies and investigating metformin effects on LBR using different animal models.