Effect of metformin taken in the ‘fresh’<i>in vitro</i>fertilization/intracytoplasmic sperm injection cycle upon subsequent frozen embryo replacement in women with polycystic ovary syndrome

Brewer, Christopher; Sk, Acharya; Thake, Fiona; Tang, Thomas; Balen, Adam

doi:10.3109/14647273.2010.504805

Cited by 10 publications

(1 citation statement)

References 56 publications

(58 reference statements)

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“…Despite widespread and continued use, the efficacy of metformin as a treatment for PCOS remains unproven and controversial. Metformin has been shown by some investigators to result in weight loss, normalization of menstrual cycles, and an improvement of conception rates following therapies such as ovulation induction and controlled ovarian hyperstimulation prior to in vitro fertilization (IVF) [ 16 - 19 ]. In contrast, other studies have demonstrated that metformin does not offer any clinical benefit [ 20 - 22 ].…”

Section: Introductionmentioning

confidence: 99%

Metformin therapy in a hyperandrogenic anovulatory mutant murine model with polycystic ovarian syndrome characteristics improves oocyte maturity during superovulation

et al. 2011

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BackgroundMetformin, an oral biguanide traditionally used for the treatment of type 2 diabetes, is widely used for the management of polycystic ovary syndrome (PCOS)-related anovulation. Because of the significant prevalence of insulin resistance and glucose intolerance in PCOS patients, and their putative role in ovulatory dysfunction, the use of metformin was touted as a means to improve ovulatory function and reproductive outcomes in PCOS patients. To date, there has been inconsistent evidence to demonstrate a favorable effect of metformin on oocyte quality and competence in women with PCOS. Given the heterogeneous nature of this disorder, we hypothesized that metformin may be beneficial in mice with aberrant metabolic characteristics similar to a significant number of PCOS patients. The aim of this study was to gain insight into the in vitro and in vivo effects of metformin on oocyte development and ovulatory function.MethodsWe utilized metformin treatment in the transgenic ob/ob and db/db mutant murine models which demonstrate metabolic and reproductive characteristics similar to women with PCOS. Results: Metformin did not improve in vitro oocyte maturation nor did it have an appreciable effect on in vitro granulosa cell luteinization (progesterone production) in any genotype studied. Although both mutant strains have evidence of hyperandrogenemia, anovulation, and hyperinsulinemia, only db/db mice treated with metformin had a greater number of mature oocytes and total overall oocytes compared to control. There was no observed impact on body mass, or serum glucose and androgens in any genotype.ConclusionsOur data provide evidence to suggest that metformin may optimize ovulatory performance in mice with a specific reproductive and metabolic phenotype shared by women with PCOS. The only obvious difference between the mutant murine models is that the db/db mice have elevated leptin levels raising the questions of whether their response to metformin is related to elevated leptin levels and/or if a subset of PCOS women with hyperleptinemia may be responsive to metformin therapy. Further study is needed to better define a subset of women with PCOS that may be responsive to metformin.

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