Effect of a lifestyle intervention in obese infertile women on cardiometabolic health and quality of life: A randomized controlled trial.

BACKGROUND: The prevalence of obesity, an important cardiometabolic risk factor, is rising in women. Lifestyle improvements are the first step in treatment of obesity, but the success depends on factors like timing and motivation. Women are especially receptive to advice about lifestyle before and during pregnancy. Therefore, we hypothesize that the pre-pregnancy period provides the perfect window of opportunity to improve cardiometabolic health and quality of life of obese infertile women, by means of a lifestyle intervention. METHODS AND FINDINGS: Between 2009-2012, 577 infertile women between 18 and 39 years of age, with a Body Mass Index of ≥ 29 kg/m2, were randomized to a six month lifestyle intervention preceding infertility treatment, or to direct infertility treatment. The goal of the intervention was 5-10% weight loss or a BMI < 29 kg/m2. Cardiometabolic outcomes included weight, waist- and hip circumference, body mass index, systolic and diastolic blood pressure, fasting glucose and insulin, HOMA-IR, hs-CRP, lipids and metabolic syndrome. All outcomes were measured by research nurses at randomization, 3 and 6 months. Self-reported quality of life was also measured at 12 months. Three participants withdrew their informed consent, and 63 participants discontinued the intervention program. Intention to treat analysis was conducted. Mixed effects regression models analyses were performed. Results are displayed as estimated mean differences between intervention and control group. Weight (-3.1 kg 95% CI: -4.0 to -2.2 kg; P < .001), waist circumference (-2.4 cm 95% CI: -3.6 to -1.1 cm; P < .001), hip circumference (-3.0 95% CI: -4.2 to -1.9 cm; P < .001), BMI (-1.2 kg/m2 95% CI: -1.5 to -0.8 kg/m2; P < .001), systolic blood pressure (-2.8 mmHg 95% CI: -5.0 to -0.7 mmHg; P = .01) and HOMA-IR (-0.5 95% CI: -0.8 to -0.1; P = .01) were lower in the intervention group compared to controls. Hs-CRP and lipids did not differ between groups. The odds ratio for metabolic syndrome in the intervention group was 0.53 (95% CI: 0.33 to 0.85; P < .01) compared to controls. Physical QoL scores were higher in the lifestyle intervention group (2.2 95% CI: 0.9 to 3.5; P = .001) while mental QoL scores did not differ. CONCLUSIONS: In obese infertile women, a lifestyle intervention prior to infertility treatment improves cardiometabolic health and self-reported physical quality of life (LIFEstyle study: Netherlands Trial Register: NTR1530).

Randomized Trial of a Lifestyle Program in Obese Infertile Women.

BACKGROUND: Small lifestyle-intervention studies suggest that modest weight loss increases the chance of conception and may improve perinatal outcomes, but large randomized, controlled trials are lacking. METHODS: We randomly assigned infertile women with a body-mass index (the weight in kilograms divided by the square of the height in meters) of 29 or higher to a 6-month lifestyle intervention preceding treatment for infertility or to prompt treatment for infertility. The primary outcome was the vaginal birth of a healthy singleton at term within 24 months after randomization. RESULTS: We assigned women who did not conceive naturally to one of two treatment strategies: 290 women were assigned to a 6-month lifestyle-intervention program preceding 18 months of infertility treatment (intervention group) and 287 were assigned to prompt infertility treatment for 24 months (control group). A total of 3 women withdrew consent, so 289 women in the intervention group and 285 women in the control group were included in the analysis. The discontinuation rate in the intervention group was 21.8%. In intention-to-treat analyses, the mean weight loss was 4.4 kg in the intervention group and 1.1 kg in the control group (P<0.001). The primary outcome occurred in 27.1% of the women in the intervention group and 35.2% of those in the control group (rate ratio in the intervention group, 0.77; 95% confidence interval, 0.60 to 0.99). CONCLUSIONS: In obese infertile women, a lifestyle intervention preceding infertility treatment, as compared with prompt infertility treatment, did not result in higher rates of a vaginal birth of a healthy singleton at term within 24 months after randomization. (Funded by the Netherlands Organization for Health Research and Development; Netherlands Trial Register number, NTR1530.).

Elevated early follicular progesterone levels and in vitro fertilization outcomes: a prospective intervention study and meta-analysis.

OBJECTIVE: To assess the impact of elevated early follicular progesterone (P) levels in gonadotropin-releasing hormone (GnRH) antagonist cycles on clinical outcome using prospective data in combination with a systematic review and meta-analysis. DESIGN: Nested study within a multicenter randomized controlled trial and a systematic review and meta-analysis. SETTING: Reproductive medicine center in an university hospital. PATIENT(S): 158 in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI) patients. INTERVENTION(S): Recombinant follicle-stimulating hormone (FSH) (150-225 IU) administered daily from cycle day 2 onward; GnRH antagonist treatment randomly started on cycle day 2 or 6; assignment into two groups according to P level on cycle day 2: normal or elevated (>4.77 nmol/L or >1.5 ng/mL, respectively). MAIN OUTCOME MEASURE(S): Ongoing pregnancy rate (OPR) per started cycle. RESULT(S): The incidence of elevated P was 13.3%. A non-statistically-significant difference in OPR was present between the normal and elevated P groups (27.0% vs. 19.0%). No differential impact of early or late GnRH antagonist initiation on the effect of elevated or normal P on OPR was observed. A systematic search of Medline and EMBASE from 1972-2013 was performed to identify studies analyzing elevated early P levels in GnRH antagonists. The meta-analysis (n=1,052) demonstrated that elevated P levels statistically significantly decreased the OPR with 15% (95% CI -23, -7 %). Heterogeneity across the studies, presumably based on varying protocols, may have modulated the effect of elevated P. CONCLUSION(S): From the present meta-analysis it appears that early elevated P levels are associated with a lower OPR in GnRH antagonists. The incidence of such a condition, however, is low. CLINICAL TRIAL REGISTRATION NUMBER: NCT00866034.

The LIFESTYLE study: costs and effects of a structured lifestyle program in overweight and obese subfertile women to reduce the need for fertility treatment and improve reproductive outcome. A randomised controlled trial.

BACKGROUND: In the Netherlands, 30% of subfertile women are overweight or obese, and at present there is no agreement on fertility care for them. Data from observational and small intervention studies suggest that reduction of weight will increase the chances of conception, decrease pregnancy complications and improve perinatal outcome, but this has not been confirmed in randomised controlled trials. This study will assess the cost and effects of a six-months structured lifestyle program aiming at weight reduction followed by conventional fertility care (intervention group) as compared to conventional fertility care only (control group) in overweight and obese subfertile women. We hypothesize that the intervention will decrease the need for fertility treatment, diminish overweight-related pregnancy complications, and will improve perinatal outcome. METHODS/DESIGN: Multicenter randomised controlled trial in subfertile women (age 18-39 year) with a body mass index between 29 and 40 kg/m2. Exclusion criteria are azoospermia, use of donor semen, severe endometriosis, premature ovarian failure, endocrinopathies or pre-existent hypertensive disorders.In the intervention group the aim is a weight loss of at least 5% to10% in a six-month period, to be achieved by the combination of a diet, increase of physical activity and behavioural modification. After six months, in case no conception has been achieved, these patients will start fertility treatment according to the Dutch fertility guidelines. In the control group treatment will be started according to Dutch fertility guidelines, independently of the patient's weight. OUTCOME MEASURES AND ANALYSIS: The primary outcome measure is a healthy singleton born after at least 37 weeks of gestation after vaginal delivery. Secondary outcome parameters including pregnancy outcome and complications, percentage of women needing fertility treatment, clinical and ongoing pregnancy rates, body weight, quality of life and costs.Data will be analysed according to the intention to treat principle, and cost-effectiveness analysis will be performed to compare the costs and health effects in the intervention and control group. DISCUSSION: The trial will provide evidence for costs and effects of a lifestyle intervention aiming at weight reduction in overweight and obese subfertile women and will offer guidance to clinicians for the treatment of these patients. TRIAL REGISTRATION: Dutch Trial Register NTR1530.