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Benefit of Delayed Fertility Therapy With Preconception Weight Loss Over Immediate Therapy in Obese Women With PCOS
Richard S Legro1, William C Dodson1, Allen R Kunselman1
1Department of Obstetrics and Gynecology (R.S.L., W.C.D., C.L.G., S.J.E.), Penn State College of Medicine, Hershey, Pennsylvania; Department of Public Health Sciences (R.S.L., A.R.K., C.M.S.), Penn State College of Medicine, Hershey, Pennsylvania; Department of Nutritional Sciences (P.M.K.-E.), Penn State College of Health and Human Development, University Park, Pennsylvania; Department of Kinesiology (N.W.), Penn State College of Health and Human Development, University Park, Pennsylvania; Departments of Psychiatry (K.C.A., D.B.S.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; Department of Surgery (D.B.S.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; Department of Obstetrics and Gynecology (M.P.D.), Wayne State University, Detroit, Michigan; Department of Obstetrics and Gynecology (W.D.S.), University of Colorado, Denver, Colorado; Department of Obstetrics and Gynecology (P.R.C.), University of Vermont, Burlington, Vermont; Department of Obstetrics and Gynecology (G.M.C.), University of Michigan, Ann Arbor, Michigan; Department of Obstetrics and Gynecology (K.T.B., C.C., A.D.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; Department of Obstetrics and Gynecology (W.B.), University of Alabama Birmingham, Birmingham, Alabama; Carolinas Medical Center (R.U.), Charlotte, North Carolina; Department of Obstetrics and Gynecology (S.L.), Virginia Commonwealth University, Richmond, Virginia; Department of Obstetrics and Gynecology (V.B.), Stanford University Medical Center, Stanford, California; Department of Biostatistics (H.H.), Yale University School of Public Health, New Haven, Connecticut; Fertility and Infertility Branch (E.E.), Eunice Kennedy Shriver NICHD, Rockville, Maryland.
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, And Participants:
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.
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