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 journalArticle

35 Citations (Scopus)

Abstract

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
Volume101
Issue number7
DOIs
StatePublished - Jul 2016

Fingerprint

Clomiphene
Polycystic Ovary Syndrome
Fertility
Weight Loss
Oral Contraceptives
Live Birth
Ovulation
Life Style
Pregnancy
Birth Rate
Therapeutics
Odds Ratio
Confidence Intervals
Infertility
Health
Insulin
Hyperandrogenism
Caloric Restriction
Insulin Resistance

All Science Journal Classification (ASJC) codes

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

Cite this

Legro, Richard S. ; Dodson, William C. ; Kunselman, Allen R. ; Stetter, Christy M. ; Kris-Etherton, Penny M. ; Williams, Nancy I. ; Gnatuk, Carol L. ; Estes, Stephanie J. ; Allison, Kelly C. ; Sarwer, David B. ; Diamond, Michael P. ; Schlaff, William D. ; Casson, Peter R. ; Christman, Gregory M. ; Barnhart, Kurt T. ; Wright Bates, G. ; Usadi, Rebecca ; Lucidi, Scott ; Baker, Valerie ; Zhang, Heping ; Eisenberg, Esther ; Coutifaris, Christos ; Dokras, Anuja. / Benefit of delayed fertility therapy with preconception weight loss over immediate therapy in obese women with PCOS. In: Journal of Clinical Endocrinology and Metabolism. 2016 ; Vol. 101, No. 7. pp. 2658-2666.
@article{61913684588a43efb86fb3d1b2aa5b1a,
title = "Benefit of delayed fertility therapy with preconception weight loss over immediate therapy in obese women with PCOS",
abstract = "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.",
author = "Legro, {Richard S.} and Dodson, {William C.} and Kunselman, {Allen R.} and Stetter, {Christy M.} and Kris-Etherton, {Penny M.} and Williams, {Nancy I.} and Gnatuk, {Carol L.} and Estes, {Stephanie J.} and Allison, {Kelly C.} and Sarwer, {David B.} and Diamond, {Michael P.} and Schlaff, {William D.} and Casson, {Peter R.} and Christman, {Gregory M.} and Barnhart, {Kurt T.} and {Wright Bates}, G. and Rebecca Usadi and Scott Lucidi and Valerie Baker and Heping Zhang and Esther Eisenberg and Christos Coutifaris and Anuja Dokras",
year = "2016",
month = "7",
doi = "10.1210/jc.2016-1659",
language = "English (US)",
volume = "101",
pages = "2658--2666",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "7",

}

Legro, RS, Dodson, WC, Kunselman, AR, Stetter, CM, Kris-Etherton, PM, Williams, NI, Gnatuk, CL, Estes, SJ, Allison, KC, Sarwer, DB, Diamond, MP, Schlaff, WD, Casson, PR, Christman, GM, Barnhart, KT, Wright Bates, G, Usadi, R, Lucidi, S, Baker, V, Zhang, H, Eisenberg, E, Coutifaris, C & Dokras, A 2016, 'Benefit of delayed fertility therapy with preconception weight loss over immediate therapy in obese women with PCOS', Journal of Clinical Endocrinology and Metabolism, vol. 101, no. 7, pp. 2658-2666. https://doi.org/10.1210/jc.2016-1659

Benefit of delayed fertility therapy with preconception weight loss over immediate therapy in obese women with PCOS. / Legro, Richard S.; Dodson, William C.; Kunselman, Allen R.; Stetter, Christy M.; Kris-Etherton, Penny M.; Williams, Nancy I.; Gnatuk, Carol L.; Estes, Stephanie J.; Allison, Kelly C.; Sarwer, David B.; Diamond, Michael P.; Schlaff, William D.; Casson, Peter R.; Christman, Gregory M.; Barnhart, Kurt T.; Wright Bates, G.; Usadi, Rebecca; Lucidi, Scott; Baker, Valerie; Zhang, Heping; Eisenberg, Esther; Coutifaris, Christos; Dokras, Anuja.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 101, No. 7, 07.2016, p. 2658-2666.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Benefit of delayed fertility therapy with preconception weight loss over immediate therapy in obese women with PCOS

AU - Legro, Richard S.

AU - Dodson, William C.

AU - Kunselman, Allen R.

AU - Stetter, Christy M.

AU - Kris-Etherton, Penny M.

AU - Williams, Nancy I.

AU - Gnatuk, Carol L.

AU - Estes, Stephanie J.

AU - Allison, Kelly C.

AU - Sarwer, David B.

AU - Diamond, Michael P.

AU - Schlaff, William D.

AU - Casson, Peter R.

AU - Christman, Gregory M.

AU - Barnhart, Kurt T.

AU - Wright Bates, G.

AU - Usadi, Rebecca

AU - Lucidi, Scott

AU - Baker, Valerie

AU - Zhang, Heping

AU - Eisenberg, Esther

AU - Coutifaris, Christos

AU - Dokras, Anuja

PY - 2016/7

Y1 - 2016/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84978402780&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84978402780&partnerID=8YFLogxK

U2 - 10.1210/jc.2016-1659

DO - 10.1210/jc.2016-1659

M3 - Article

C2 - 27172435

AN - SCOPUS:84978402780

VL - 101

SP - 2658

EP - 2666

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 7

ER -