Benefit of delayed fertility therapy with preconception weight loss over immediate therapy in obese women with PCOS

Richard S. Legro, William C. Dodson, Allen R. Kunselman, Christy M. Stetter, Penny M. Kris-Etherton, Nancy I. Williams, Carol L. Gnatuk, Stephanie J. Estes, Kelly C. Allison, David B. Sarwer, Michael P. Diamond, William D. Schlaff, Peter R. Casson, Gregory M. Christman, Kurt T. Barnhart, G. Wright Bates, Rebecca Usadi, Scott Lucidi, Valerie Baker, Heping ZhangEsther Eisenberg, Christos Coutifaris, Anuja Dokras

Research output: Contribution to journalArticlepeer-review

99 Scopus citations


Context: In overweight/obese women with polycystic ovary syndrome (PCOS), the relative benefit of delaying infertility treatment to lose weight vs seeking immediate treatment is unknown. Objective: We compared the results of two, multicenter, concurrent clinical trials treating infertility in women with PCOS. Design,Setting,andParticipants: This was a secondary analysis of two randomized trials conducted at academic health centers studying women 18-40 years of age who were overweight/obese and infertile with PCOS. Intervention: We compared immediate treatment with clomiphene from the Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) trial (N = 187) to delayed treatment with clomiphene after preconception treatment with continuous oral contraceptives, lifestyle modification (Lifestyle: including caloric restriction, antiobesity medication, behavioral modification, and exercise) or the combination of both (combined) from the Treatment of Hyperandrogenism Versus Insulin Resistance in Infertile Polycystic Ovary Syndrome (OWL PCOS) trial (N = 142). Main Outcome Measures: Live birth, pregnancy loss, and ovulation were measured. Results: In PPCOS II, after four cycles of clomiphene, the cumulative per-cycle ovulation rate was 44.7% (277/619) and the cumulative live birth rate was 10.2% (19/187), nearly identical to that after oral contraceptive pretreatment in the OWL PCOS trial (ovulation 45% [67/149] and live birth: 8.5% [4/47]). In comparison, deferred clomiphene treatment preceded by lifestyle and combined treatment in OWL PCOS offered a significantly better cumulative ovulation rate compared to immediate treatment with clomiphene. (Lifestyle: 62.0% [80/129]; risk ratio compared to PPCOS II = 1.4; 95% confidence interval [CI], 1.1-1.7; P =.003; combined: 64.3% [83/129]; risk ratio compared to PPCOS II = 1.4; 95% CI, 1.2-1.8; P <.001 and a significantly better live birth rate lifestyle: 25.0% [12/48]; risk ratio compared to PPCOS II = 2.5; 95% CI, 1.3-4.7; P =.01 and combined: 25.5% [12/47]; risk ratio compared to PPCOS II = 2.5; 95% CI, 1.3-4.8; P =.01). Conclusions: These data show the benefit of improved ovulation and live birth with delayed infertility treatment with clomiphene citrate when preceded by lifestyle modification with weight loss compared with immediate treatment. Pretreatment with oral contraceptives likely has little effect on the ovulation and live birth rate compared with immediate treatment.

Original languageEnglish (US)
Pages (from-to)2658-2666
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Issue number7
StatePublished - Jul 2016

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


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