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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 <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> effects of metformin on oocyte development and ovulatory function.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We utilized metformin treatment in the transgenic <jats:italic>ob\/ob<\/jats:italic> and <jats:italic>db\/db<\/jats:italic> mutant murine models which demonstrate metabolic and reproductive characteristics similar to women with PCOS. Results: Metformin did not improve <jats:italic>in vitro<\/jats:italic> oocyte maturation nor did it have an appreciable effect on <jats:italic>in vitro<\/jats:italic> granulosa cell luteinization <jats:italic>(<\/jats:italic> progesterone production) in any genotype studied. Although both mutant strains have evidence of hyperandrogenemia, anovulation, and hyperinsulinemia, only <jats:italic>db\/db<\/jats:italic> 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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Our 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 <jats:italic>db\/db<\/jats:italic> 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.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1757-2215-4-8","type":"journal-article","created":{"date-parts":[[2011,5,24]],"date-time":"2011-05-24T06:38:43Z","timestamp":1306219123000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Metformin therapy in a hyperandrogenic anovulatory mutant murine model with polycystic ovarian syndrome characteristics improves oocyte maturity during superovulation"],"prefix":"10.1186","volume":"4","author":[{"given":"Mary E","family":"Sabatini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lankai","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen P","family":"Lynch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph O","family":"Doyle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HoJoon","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo R","family":"Rueda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron K","family":"Styer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2011,5,23]]},"reference":[{"key":"66_CR1","doi-asserted-by":"crossref","unstructured":"Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS) Hum Reprod 2004, 19: 41\u201347.","DOI":"10.1093\/humrep\/deh098"},{"key":"66_CR2","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.beem.2006.02.005","volume":"20","author":"MO Goodarzi","year":"2006","unstructured":"Goodarzi MO, Azziz R: Diagnosis, epidemiology, and genetics of the polycystic ovary syndrome. 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