Meike Mutsaerts

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.).

Complications and outcome of assisted reproduction technologies in overweight and obese women

BACKGROUND Based on a presumed negative impact of overweight and obesity on reproductive capacity and pregnancy outcome, some national guidelines and clinicians have argued that there should be an upper limit for a womans BMI to access assisted reproductive technologies (ART). However, evidence on the risk of complications or expected success rate of ART in obese women is scarce. We therefore performed a systematic review on the subject. METHODS We searched the literature for studies reporting on complications or success rates in overweight and obese women undergoing ART. Articles were scored on methodological quality. We calculated pooled odds ratios (ORs) to express the association between overweight and obesity on the one hand, and complications and success rates of ART on the other hand. We only pooled results if data were available per woman instead of per cycle or embryo transfer. RESULTS We detected 14 studies that reported on the association between overweight and complications during or after ART, of which 6 reported on ovarian hyperstimulation syndrome (OHSS), 7 on multiple pregnancies and 6 on ectopic pregnancies. None of the individual studies found a positive association between overweight and ART complications. The pooled ORs for overweight versus normal weight for OHSS, multiple pregnancy and ectopic pregnancy were 1.0 [95% confidence interval (CI) 0.77-1.3], 0.97 (95% CI 0.91-1.04) and 0.96 (95% CI 0.54-1.7), respectively. In 27 studies that reported on BMI and the success of ART, the pooled ORs for overweight versus normal weight on live birth, ongoing and clinical pregnancy following ART were OR 0.90 (95% CI 0.82-1.0), 1.01 (95% CI 0.75-1.4) and OR 0.94 (95% CI 0.69-1.3), respectively. CONCLUSIONS Data on complications following ART are scarce and therefore a registration system should be implemented in order to gain more insight into this subject. In the available literature, there is no evidence of overweight or obesity increasing the risk of complications following ART. Furthermore, they only marginally reduce the success rates. Based on the currently available data, overweight and obesity in itself should not be a reason to withhold ART.

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

BackgroundIn 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/DesignMulticenter 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 patients weight.Outcome measures and analysisThe 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.DiscussionThe 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 registrationDutch Trial Register NTR1530

The influence of maternal and paternal factors on time to pregnancy—a Dutch population-based birth-cohort study: the GECKO Drenthe study

BACKGROUND Both maternal and paternal factors have been suggested to influence a couples fecundity. To investigate this, we examined the role of several maternal and paternal lifestyle and socio-demographic factors as determinants of time to pregnancy (TTP) in a Dutch birth-cohort. METHODS Groningen Expert Center for Kids with Obesity (GECKO) Drenthe is a population-based birth-cohort study of children born between April 2006 and April 2007 in Drenthe, a province of The Netherlands. Both partners received extensive questionnaires during pregnancy. Univariable and multivariable Cox regression analyses were used to determine the impact of the investigated factors on TTP. RESULTS A total of 4778 children were born, and the parents of 2997 children (63%) gave their consent to participate. After excluding unintended pregnancies and pregnancies as a result of fertility treatment, the data of 1924 couples were available for analysis. Hazards ratios and 95% confidence intervals of factors influencing TTP in multivariable Cox regression analysis were: maternal age 1.23 (0.98-1.54) for age <25 years, 1.17 (1.03-1.32) for age 25-30 years and 0.72 (0.61-0.85) for age >35 years (reference category: 30-35 years); paternal age: 1.31 (0.94-1.82) for age <25 years, 1.11 (0.97-1.28) for age 25-30 years and 0.91 (0.80-1.04 for age >35 years (reference category: 30-35 years); nulliparity: 0.76 (0.68-0.85) versus multiparity; menstrual cycle length: 1.12 (0.95-1.30) for 3 weeks, 0.72 (0.62-0.83) for 4-6 weeks, 0.68 (0.40-1.16) for >6 weeks and 0.66 (0.54-0.81) for irregular cycle (reference category: 4 weeks); prior contraceptive use: 0.78 (0.67-0.91) for no contraception, 1.68 (1.45-1.95) for condom use, 1.08 (0.89-1.33) for condom use combined with oral contraception, 1.40 (1.16-1.70) for intrauterine device and 0.50 (0.25-1.01) for contraceptive injection (reference category: oral contraception); and maternal educational level 0.75 (0.62-0.92) for low education level and 0.81 (0.73-0.90) for medium educational level (reference category: high educational level). CONCLUSIONS This population-based birth-cohort study performed in fertile couples who had conceived revealed neither maternal nor paternal modifiable lifestyle factors were significantly associated with TTP after adjustment for confounding by socio-demographic factors. In contrast, several non-modifiable maternal socio-demographic factors are significant predictors of a couples fecundity.

Dropout is a problem in lifestyle intervention programs for overweight and obese infertile women: a systematic review

STUDY QUESTION What are the dropout rates in lifestyle intervention programs (LIPs) for overweight and obese infertile women and can intervention- or patient-related baseline factors associated with dropout be identified in these women? SUMMARY ANSWER The median dropout rate was 24% in overweight and obese infertile women who participated in a LIP; clinical useful intervention or patient-related factors associated with dropout could not be identified. WHAT IS KNOWN ALREADY Overweight and obese infertile women might improve their chance of conception when they improve their lifestyle and lose weight. Dropout from LIPs reduces the chance of losing considerable weight and is therefore considered to be an important limiting factor of the success of LIPs. STUDY DESIGN, SIZE, DURATION This systematic review included 15 studies published between January 1980 and December 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS The included studies investigated the effect of LIPs for overweight and obese infertile women with infertility. From these studies, dropout rates and intervention- and patient-related baseline factors associated with dropout, as well as weight loss and pregnancy rates, were recorded. MAIN RESULTS AND THE ROLE OF CHANCE There were 15 studies identified, of which 10 reported dropout rates. The median dropout rate was 24% (range: 0-31%). Four studies reported baseline characteristics of women who dropped out, but modifiable predictors of dropout could not be identified. Weight loss and pregnancy rates were lower in women who dropped out than in women who completed the LIPs. LIMITATIONS, REASONS FOR CAUTION There were limited numbers of studies investigating patient-related factors associated with dropout. The heterogeneity in the studies precluded us from drawing firm conclusions on the relation between the type of intervention and dropout. WIDER IMPLICATIONS OF THE FINDINGS Dropout from LIPs is a major drawback because it predisposes to less weight loss and lower pregnancy rates. Identification of predictors of dropout is needed to identify overweight and obese infertile women who are prone for dropout. These women might benefit from extra support and monitoring, to potentially increasing adherence rates, weight loss and pregnancy chances. STUDY FUNDING/COMPETING INTEREST(S) M.A.Q.M. was supported by a research grant from the Dutch Organization for Health Research and Development (ZonMw). The department of obstetrics and gynaecology received research grants from Merck Sharpe and Dohme BV, feering pharmaceuticals, Merck Serono, the Netherlands.

Effects of paternal and maternal lifestyle factors on pregnancy complications and perinatal outcome. A population-based birth-cohort study: the GECKO Drenthe cohort

STUDY QUESTION Do paternal and maternal lifestyle factors influence the risk of hypertensive pregnancy complications, gestational diabetes mellitus (GDM), spontaneous preterm birth and small-for-gestational-age (SGA)? SUMMARY ANSWER Paternal lifestyle factors do not exert an independent effect on the investigated outcomes while maternal prepregnancy BMI and maternal smoking during pregnancy influence the risk of hypertensive pregnancy complications, GDM and SGA. WHAT IS KNOWN ALREADY Maternal lifestyle factors are associated with perinatal complications, but the impact of paternal lifestyle factors is unclear. STUDY DESIGN, SIZE, DURATION Data from the GECKO (Groningen Expert Center for Kids with Obesity) Drenthe cohort, a prospective population-based birth-cohort of children born between April 2006 and April 2007 in a northern province of The Netherlands, were analysed. The parents of 2958 children (62% of those approached) gave their consent to participate in the study and the data of 2264 (77%) couples were available for analysis. PARTICIPANTS/MATERIALS, SETTINGS, METHOD All pregnant women in the Dutch province of Drenthe with an expected date of delivery between April 2006 and April 2007 were invited to participate and included during the third trimester of their pregnancy or within 6 months after delivery. All consenting couples received extensive questionnaires including lifestyle, biological and socio-demographic-related questions covering the period of 6 months prior to conception. Outcome data were obtained from midwives and hospital registries. Univariable and multivariable logistic regression analyses were used to determine the impact of the lifestyle factors on the primary outcome measures. MAIN RESULTS AND THE ROLE OF CHANCE Of all 2264 women, 241 women (10.6%) developed a hypertensive pregnancy complication, 50 women (2.2%) developed GDM, 79 (3.5%) children were spontaneously delivered preterm and 155 children (6.8%) were SGA. All paternal and maternal lifestyle factors were positively correlated. Multivariable analysis showed that paternal lifestyle factors did not have an independent influence on the investigated outcomes. Of the maternal factors, prepregnancy BMI was independently associated with an increased risk of a hypertensive disorder during pregnancy (odds ratio (OR): 1.12, 95% CI 1.09-1.16), a higher risk of GDM (OR BMI >23 kg/m(2), per BMI unit: 1.13, 95% CI 1.08-1.18) and with a decreased risk of SGA (OR per BMI point 0.94, 95% CI 0.90-0.99). Maternal smoking during pregnancy was significantly associated with SGA (OR 3.00, 95% CI 1.80-4.99) in multivariable analysis. LIMITATIONS, REASONS FOR CAUTION The retrospective nature of the questionnaire may have induced recall bias. Selection bias might have occurred, as ethnic minorities were less willing to co-operate in the GECKO Drenthe study. The possibility of misclassification bias regarding the primary outcome measures cannot be ruled out. Inclusion bias might have occurred as not all questionnaires of the parents of the children participating in the GECKO Drenthe cohort were completed. WIDER IMPLICATIONS OF THE FINDINGS Paternal lifestyle factors do not have an independent effect on the investigated adverse pregnancy outcomes. However, as paternal and maternal lifestyles are positively correlated, both partners should be involved in preconception counselling regarding the investigated outcome measures.

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).

Association between periconceptional weight loss and maternal and neonatal outcomes in obese infertile women

Background Obesity in women of reproductive age has deleterious effects on reproductive and offspring health. In this study, we aimed to evaluate the association between the magnitude of periconceptional body-mass index (BMI) change and maternal and neonatal outcomes in obese infertile women who participated in the LIFEstyle study. The LIFEstyle study was a randomized controlled trial, evaluating if a six-month lifestyle intervention program prior to infertility treatment in obese infertile women improved birth rates, compared to prompt infertility treatment. Methods and findings This is an exploratory post hoc analysis of the LIFEstyle study. We recorded periconceptional BMI change in women with an ongoing pregnancy, pooling data of all women, regardless of randomization arm. Periconceptional BMI change was calculated using weight at randomization and the periconceptional weight (measured in kilograms 12 weeks before or after conception and expressed as BMI change in units BMI (kg/m2)). Subsequently, women were categorized into quartiles according to the magnitude of their periconceptional change in BMI. The odds of maternal and neonatal outcomes were calculated using logistic regression analysis, comparing women in each of the first three weight change quartiles separately, and combined, to women in the fourth quartile. The fourth quartile was chosen as reference group, since these women had the least weight loss. We adjusted for periconceptional BMI, nulliparity and smoking status. In addition, we performed a subgroup analysis for singleton pregnancies. In the LIFEstyle study, 321 obese infertile women achieved an ongoing pregnancy which was conceived within 24 months after randomization. Periconceptional BMI change was available in 244 of these women (76%). Median BMI at randomization was 35.9 kg/m2. Women in the first quartile (Q1) had a periconceptional BMI change of <-2.1 kg/m2, women in the second quartile (Q2) -2.1 to -0.9 kg/m2, women in the third quartile (Q3) -0.9 to 0.1 kg/m2 and women in the fourth quartile (Q4) gained ≥0.1 kg/m2. There were no significant differences between women in the quartiles regarding rates of excessive gestational weight gain (in term pregnancies), gestational diabetes, preterm birth, induction of labor, spontaneous vaginal birth and Caesarean section. Compared to women in Q4, the adjusted odds ratios, aOR, and 95% confidence interval for a hypertensive complication were; 0.55 (0.22–1.42) for women in Q1, 0.30 (0.12–0.78) for women in Q2, 0.39 (0.16–0.96) for women in Q3 and 0.39 (0.19–0.82) for women in Q1 to Q3 combined. In the subgroup analysis, investigating singleton pregnancies only, the statistically significant decreased rate of a hypertensive complication remained in women in Q2 (aOR 0.27, 95% CI 0.10–0.72) and Q3 (aOR 0.39, 95%CI 0.16–0.98) and when comparing women in Q1 to Q3 together to women in Q4 (aOR 0.38, 95%CI 0.18–0.80). Furthermore, there was a significantly decreased aOR (95%CI) of preterm birth in women in Q2 (0.24, 0.06–0.98) and when combining women in Q1 to Q3 (0.37, 0.14–0.97) compared to women in Q4. Conclusions These results suggest that a periconceptional decrease in BMI in obese infertile women could lead to a decrease of the rates of hypertensive pregnancy complications and preterm birth. The results are limited by the exploratory nature of the analyses and further evidence is necessary to provide more definitive conclusions.

Corrigendum: Effectiveness of lifestyle intervention in subgroups of obese infertile women : A subgroup analysis of a RCT

Study question: Do age, ovulatory status, severity of obesity and body fat distribution affect the effectiveness of lifestyle intervention in obese infertile women? Summary answer: We did not identify a subgroup in which lifestyle intervention increased the healthy live birth rate however it did increase the natural conception rate in anovulatory obese infertile women. What is known already: Obese women are at increased risk of infertility and are less likely to conceive after infertility treatment. We previously demonstrated that a 6-month lifestyle intervention preceding infertility treatment did not increase the rate of healthy live births (vaginal live birth of a healthy singleton at term) within 24 months of follow-up as compared to prompt infertility treatment in obese infertile women. Natural conceptions occurred more frequently in women who received a 6-month lifestyle intervention preceding infertility treatment. Study design, size, duration: This is a secondary analysis of a multicenter RCT (randomized controlled trial), the LIFEstyle study. Between 2009 and 2012, 577 obese infertile women were randomly assigned to a 6-month lifestyle intervention followed by infertility treatment (intervention group) or to prompt infertility treatment (control group). Subgroups were predefined in the study protocol, based on frequently used cut-off values in the literature: age (≥ 36 or < 36 years), ovulatory status (anovulatory or ovulatory), BMI (≥ 35 or < 35 kg/ m) and waist-hip (WH) ratio (≥ 0.8 or < 0.8). Participants/materials, setting, methods: Data of 564 (98%) randomized women who completed follow-up were analyzed. We studied the effect of the intervention program in various subgroups on healthy live birth rate within 24 months, as well as the rate of overall live births (live births independent of gestational age, mode of delivery and health) and natural conceptions conceived within 24 months. Live birth rates included pregnancies resulting from both treatment dependent and natural conceptions. Logistic regression models with randomization group, subgroup and the interaction between randomization group and subgroup were used. Significant interaction was defined as a P-value <0.1. Main results and the role of chance: Neither maternal age, ovulatory status nor BMI had an impact on the healthy live birth rate within 24 months, nor did they influence the overall live birth rate within 24 months after randomization. WH ratio showed a significant interaction with the effect of lifestyle intervention on healthy live birth rate (P = 0.05), resulting in a lower

Cost-effectiveness analysis of lifestyle intervention in obese infertile women

STUDY QUESTION What is the cost-effectiveness of lifestyle intervention preceding infertility treatment in obese infertile women? SUMMARY ANSWER Lifestyle intervention preceding infertility treatment as compared to prompt infertility treatment in obese infertile women is not a cost-effective strategy in terms of healthy live birth rate within 24 months after randomization, but is more likely to be cost-effective using a longer follow-up period and live birth rate as endpoint. WHAT IS KNOWN ALREADY In infertile couples, obesity decreases conception chances. We previously showed that lifestyle intervention prior to infertility treatment in obese infertile women did not increase the healthy singleton vaginal live birth rate at term, but increased natural conceptions, especially in anovulatory women. Cost-effectiveness analyses could provide relevant additional information to guide decisions regarding offering a lifestyle intervention to obese infertile women. STUDY DESIGN, SIZE, DURATION The cost-effectiveness of lifestyle intervention preceding infertility treatment compared to prompt infertility treatment was evaluated based on data of a previous RCT, the LIFEstyle study. The primary outcome for effectiveness was the vaginal birth of a healthy singleton at term within 24 months after randomization (the healthy live birth rate). The economic evaluation was performed from a hospital perspective and included direct medical costs of the lifestyle intervention, infertility treatments, medication and pregnancy in the intervention and control group. In addition, we performed exploratory cost-effectiveness analyses of scenarios with additional effectiveness outcomes (overall live birth within 24 months and overall live birth conceived within 24 months) and of subgroups, i.e. of ovulatory and anovulatory women, women <36 years and ≥36 years of age and of completers of the lifestyle intervention. Bootstrap analyses were performed to assess the uncertainty surrounding cost-effectiveness. PARTICIPANTS/MATERIALS, SETTINGS, METHODS Infertile women with a BMI of ≥29 kg/m2 (no upper limit) were allocated to a 6-month lifestyle intervention programme preceding infertility treatment (intervention group, n = 290) or to prompt infertility treatment (control group, n = 287). After excluding women who withdrew informed consent or who were lost to follow-up we included 280 women in the intervention group and 284 women in the control group in the analysis. MAIN RESULTS AND THE ROLE OF CHANCE Total mean costs per woman in the intervention group within 24 months after randomization were €4324 (SD €4276) versus €5603 (SD €4632) in the control group (cost difference of -€1278, P < 0.05). Healthy live birth rates were 27 and 35% in the intervention group and the control group, respectively (effect difference of -8.1%, P < 0.05), resulting in an incremental cost-effectiveness ratio of €15 845 per additional percentage increase of the healthy live birth rate. Mean costs per healthy live birth event were €15 932 in the intervention group and €15 912 in the control group. Exploratory scenario analyses showed that after changing the effectiveness outcome to all live births conceived within 24 months, irrespective of delivery within or after 24 months, cost-effectiveness of the lifestyle intervention improved. Using this effectiveness outcome, the probability that lifestyle intervention preceding infertility treatment was cost-effective in anovulatory women was 40%, in completers of the lifestyle intervention 39%, and in women ≥36 years 29%. LIMITATIONS, REASONS FOR CAUTION In contrast to the study protocol, we were not able to perform the analysis from a societal perspective. Besides the primary outcome of the LIFEstyle study, we performed exploratory analyses using outcomes observed at longer follow-up times and we evaluated subgroups of women; the trial was not powered on these additional outcomes or subgroup analyses. WIDER IMPLICATIONS OF THE FINDINGS Cost-effectiveness of a lifestyle intervention is more likely for longer follow-up times, and with live births conceived within 24 months as the effectiveness outcome. This effect was most profound in anovulatory women, in completers of the lifestyle intervention and in women ≥36 years old. This result indicates that the follow-up period of lifestyle interventions in obese infertile women is important. The scenario analyses performed in this study suggest that offering and reimbursing lifestyle intervention programmes in certain patient categories may be cost-effective and it provides directions for future research in this field. STUDY FUNDING/COMPETING INTEREST(S) The study was supported by a grant from ZonMw, the Dutch Organization for Health Research and Development (50-50110-96-518). The department of obstetrics and gynaecology of the UMCG received an unrestricted educational grant from Ferring pharmaceuticals BV, The Netherlands. B.W.J.M. is a consultant for ObsEva, Geneva. TRIAL REGISTRATION NUMBER The LIFEstyle RCT was registered at the Dutch trial registry (NTR 1530). http://www.trialregister.nl/trialreg/admin/rctview.asp?TC = 1530.