Six weeks of structured exercise training and hypocaloric diet increases the probability of ovulation after clomiphene citrate in overweight and obese patients with polycystic ovary syndrome: a randomized controlled trial

S Palomba,F Giallauria,F Zullo,F Orio,M Rocca,A Falbo,T Russo,A Tolino

doi:10.1093/humrep/deq254

Abstract

Clomiphene citrate (CC) is the first-line therapy for the induction of ovulation in infertile women with polycystic ovary syndrome (PCOS), but ∼20% of patients are unresponsive. The aim of the current study was to test the hypothesis that a 6-week intervention that consisted of structured exercise training (SET) and hypocaloric diet increases the probability of ovulation after CC in overweight and obese CC-resistant PCOS patients. A cohort of 96 overweight and obese CC-resistant PCOS patients was enrolled consecutively in a three-arm randomized, parallel, controlled, assessor-blinded clinical trial. The three interventions were: SET plus hypocaloric diet for 6 weeks (Group A); 2 weeks of observation followed by one cycle of CC therapy (Group B); and SET plus hypocaloric diet for 6 weeks, with one cycle of CC after the first 2 weeks (Group C). The primary end-point was the ovulation rate. Other reproductive data, as well as anthropometric, hormonal and metabolic data, were also collected and considered as secondary end points. After 6 weeks of SET plus hypocaloric diet, the ovulation rate was significantly (P =0.008) higher in Group C [12/32 (37.5%)] than in Groups A [4/32 (12.5%)] and B [3/32 (9.4%)] with relative risks of 3.9 [95% confidence interval (CI) 1.1-8.3; P = 0.035] and 4.0 (95% CI 1.2-12.8; P = 0.020) compared with Groups A and B, respectively. Compared with baseline, in Groups A and C, a significant improvement in clinical and biochemical androgen and insulin sensitivity indexes was observed. In the same two groups, the insulin sensitivity index was significantly (P < 0.05) better than that in Group B. In overweight and obese CC-resistant PCOS patients, a 6-week intervention of SET and a hypocaloric diet was effective in increasing the probability of ovulation under CC treatment. The study was registered at Clinicaltrials.gov:NCT0100468.

Highlights

Clomiphene citrate (CC) was the first agent used to induce ovulation in oligomenorrheic women, and it is still considered the first therapeutic option for the management of anovulatory infertility related to polycystic ovary syndrome (PCOS; Palomba et al, 2004)
The aim of the present study was to test the hypothesis that a 6-week intervention that consisted of structured exercise training (SET) and a hypocaloric diet could increase the ovulation rate after CC administration in PCOS patients with known CC resistance
No randomized subject was excluded from the final analysis, the data analysed according to the per-protocol analysis were the same as those analysed by the ITT analysis

Summary

Introduction

Clomiphene citrate (CC) was the first agent used to induce ovulation in oligomenorrheic women, and it is still considered the first therapeutic option for the management of anovulatory infertility related to polycystic ovary syndrome (PCOS; Palomba et al, 2004). Notwithstanding the efficacy of CC, ovulation is not achieved in a proportion of patients, a maximum dosage is used. These patients are defined generally as CC-resistant (Kousta et al, 1997). 150 mg/day CC is considered the highest dose that should be administered (NICE, 2004). In this regard, the United States (US) Food and Drug Administration (FDA) has suggested that doses of CC should not exceed 750 mg per cycle (Dickey and Holtkamp, 1996)

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