ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Reproduction
This article is part of the Research TopicAdvancing Reproductive Outcomes: Integrating Molecular, Metabolic, and Endocrine Insights into Oocyte MaturationView all 5 articles
Metformin improves pregnancy outcomes in non-PCOS women with insulin resistance and recurrent implantation failure before frozen embryo transfer
Provisionally accepted
- 1Department of Reproductive Immunology, Shanghai First Maternity and Infant Hospital, Shanghai, China
- 2Shanghai First Materity and Infant Hospital, Shanghai, China
- 3Shanghai First Maternity and Infant Hospital, Shanghai, China
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Background: Recurrent implantation failure (RIF) leads to a significant waste of embryos and imposes substantial physical, emotional, and financial stress on patients. Given its complex and diverse etiology, identifying the underlying causes and developing effective interventions are crucial. Previous studies have shown that insulin resistance (IR) has negative effects on reproductive health, and metformin pretreatment helps improve the pregnancy outcomes in IR patients. However, its role in patients with RIF remains unclear, especially in those without polycystic ovary syndrome (PCOS). Methods: A retrospective cohort study was conducted. The FET cycles of RIF patients without PCOS were stratified based on the presence or absence of IR. We used the univariate and multivariate generalized estimating equations (GEE) analysis to compare pregnancy outcomes between patients with IR and without IR, as well as between metformin-exposed and metformin-unexposed groups of RIF patients with IR. Results: In a subgroup of 941 cycles without IR and 145 cycles with IR, we found that patients with IR had a lower live birth rate (10.34% vs 20.94%, P = 0.0039) and a higher early miscarriage rate (52.77% vs 27.52%, P = 0.0034). After adjusting for potential confounders, the IR group still had a lower live birth rate (aOR = 0.5, 95% CI: 0.28-0.89, P = 0.019). In the subgroup of IR patients (n=330 cycles), patients in the metformin-exposed group (n=185 cycles) had a higher clinical pregnancy rate (43.24% vs 24.83%, P < 0.001), implantation rate (33.22% vs 17.04%, P < 0.001) and live birth rate (33.51% vs 10.34%, P < 0.001), as well as a lower early miscarriage rate (12.50% vs 52.78%, P < 0.01), compared to the metformin-unexposed group (n=145 cycles). These differences remained significant after adjusting for potential confounders using GEE analysis. Conclusions: Our results demonstrated that IR may be a risk factor for a low live birth rate in RIF patients without PCOS. However, the negative impact of IR on the live birth rate can be alleviated by metformin pre-treatment before FET cycles.
Keywords: recurrent implantation failure, Insulin Resistance, Frozen embryo transfer, Metformin, pregnancy outcomes
Received: 23 Jul 2025; Accepted: 18 Nov 2025.
Copyright: © 2025 Peng, Yang, Du, Deng, Zhang, Qin and Bao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Shihua Bao, baoshihua@tongji.edu.cn
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