Lifestyle study

Go to the Lifestyle website.

Rationale

Subfertility affects approximately one in ten couples planning conception. Among subfertile women, about 30% are overweight or even obese. Epidemiological data suggest that the reduction of overweight will increase the chances of conception, decrease pregnancy complications and improve perinatal outcome. In small intervention studies beneficial reproductive effects of improvement of lifestyle leading to a reduction in body weight have been demonstrated. The British Fertility Society advises that fertility treatment be withheld if the body mass index (BMI) is over 35.
In the Netherlands, there is at present no agreed standard of care for subfertile women with overweight or obesity. Some centres simply withhold treatment of couples in whom the woman is overweight or obese, but most fertility centres treat overweight or obese women irrespective of their BMI. In a few centres, support is offered to women to help them lose weight. 
 

Objective

In view of this lack of evidence and strong practice variation we propose a randomized clinical trial in overweight and obese subfertile women, in which we compare the costs and effects of a six months structured lifestyle program, aimed at weight loss, to “usual care”. The intervention aims to prevent unnecessary fertility treatment, complications associated with fertility treatment and obesity related pregnancy complications, thus improving pregnancy chances and perinatal outcome. 
 

Study design

Multicenter randomised clinical trial. 
 

Study population

Subfertile women (age 18-38) with a BMI between 29 and 40. Exclusion criteria are: azoospermia, severe endometriosis, chronic anovulation due to WHO III and endocrinopathies. Women with preexistent hypertension or diabetes, or pregnancy induced hypertension, preeclampsia, eclampsia or HELLP syndrome in a previous pregnancy are also excluded.
 

Intervention

The intervention consists of a structured lifestyle program of six months, which aims at realistic weight loss of at least 5% to10%, achieved by the combination of a healthy diet (caloric reduction of 600kCal/day), increase of physical activity (aiming at 10.000 steps per day) and two to three times a week sporting activity, and behavioural modification. The structured lifestyle program, in which practice variation is minimized using a structured software program, has been developed, used and evaluated previously (Zon-MW project 50-50110-98-078; the Groninger Overweight And Lifestyle study (GOAL)). Following six months of lifestyle intervention patients will start fertility treatment as indicated in the “usual care” group.
In the “usual care” arm fertility treatment will be started if this is justified by the individual prognosis (guideline NVOG)
All randomised women will fill in questionnaires concerning: diet, eating behaviour and  physical activity: SF-36, FFQ, DEBQ, Squash list, at inclusion, and at 12 weeks, 6 months, 12 months and 24 months after randomisation.  Blood samples (10 cc) will be taken at the start, 3 months and 6 months after the start of the study
 

Main study parameters/endpoints
Primary endpoint is the birth of a healthy singleton after vaginal delivery of at least 37 weeks gestation.
Secondary outcome parameters are number of fertility treatments (OI, IUI, IVF, ICSI) , clinical and ongoing pregnancy rates, perinatal outcome, complications and quality of life as well as body weight, waist circumference, behaviour influencing weight, i.e. nutritional habits and exercise pattern, blood pressure, hormonal and metabolic profile and costs.
 

DATA ANALYSIS

Analysis will be by intention to treat. Randomisation will be stratified for the presence or absence of anovulation and per treatment center. We expect an improvement in vaginal singleton delivery beyond 37 weeks from 45% to 60%. Anticipating drop out of 20% in the intervention arm ad a 5% loss to follow up in the study, we need to include two groups of 285 women (two-sided test, alpha error.05, beta-error .20). 
 

STUDY DURATION

Preparation of the study, including the training of the nurses, will take three months. Inclusion of the couples will take 24 months and the lifestyle intervention will take six months. Follow up is continued for 24 months after randomisation. Database cleaning and analysis of the study will take 6 months. Duration of the study: 57 months

Projectleaders
M.A.Q. Mutsaerts, MD, researcher, UMCG

A.Hoek, MD/PhD, gynecologist, UMCG

J.A.Land, MD/PhD, gynaecologist, UMCG

W.Bemelmans PhD, epidemiologist RIVM

Health Technology Assessment
H. Groen, MD/PhD, epidemiologist, UMCG

Methodology
B.W. Mol MD/PhD, gynaecologist-epidemiologist AMC

Subsidy
ZonMw: 50-50110-96-518

Contact

M.A.Q. Mutsaerts, MD, researcher, UMCG. Tel. 050-3613174.

E-mail: m.a.q.mutsaerts@og.umcg.nl

A. Hoek, MD/PhD,gynaecologist, UMCG. Tel: 3613153.

E-Mail:  a.hoek@og.umcg.nl