Obesity is associated with increased risk of first trimester and recurrent miscarriage.

Stigma and the wider social context should be considered when supporting people with fertility problems. Greater disclosure may be associated with higher distress in women.

SummaryBackgroundMaternal obesity is associated with increased birthweight, and obesity and premature mortality in adult offspring. The mechanism by which maternal obesity leads to these outcomes is not well understood, but maternal hyperglycaemia and insulin resistance are both implicated. We aimed to establish whether the insulin sensitising drug metformin improves maternal and fetal outcomes in obese pregnant women without diabetes.MethodsWe did this randomised, double-blind, placebo-controlled trial in antenatal clinics at 15 National Health Service hospitals in the UK. Pregnant women (aged ≥16 years) between 12 and 16 weeks' gestation who had a BMI of 30 kg/m2 or more and normal glucose tolerance were randomly assigned (1:1), via a web-based computer-generated block randomisation procedure (block size of two to four), to receive oral metformin 500 mg (increasing to a maximum of 2500 mg) or matched placebo daily from between 12 and 16 weeks' gestation until delivery of the baby. Randomisation was stratified by study site and BMI band (30–39 vs ≥40 kg/m2). Participants, caregivers, and study personnel were masked to treatment assignment. The primary outcome was Z score corresponding to the gestational age, parity, and sex-standardised birthweight percentile of liveborn babies delivered at 24 weeks or more of gestation. We did analysis by modified intention to treat. This trial is registered, ISRCTN number 51279843.FindingsBetween Feb 3, 2011, and Jan 16, 2014, inclusive, we randomly assigned 449 women to either placebo (n=223) or metformin (n=226), of whom 434 (97%) were included in the final modified intention-to-treat analysis. Mean birthweight at delivery was 3463 g (SD 660) in the placebo group and 3462 g (548) in the metformin group. The estimated effect size of metformin on the primary outcome was non-significant (adjusted mean difference −0·029, 95% CI −0·217 to 0·158; p=0·7597). The difference in the number of women reporting the combined adverse outcome of miscarriage, termination of pregnancy, stillbirth, or neonatal death in the metformin group (n=7) versus the placebo group (n=2) was not significant (odds ratio 3·60, 95% CI 0·74–17·50; p=0·11).InterpretationMetformin has no significant effect on birthweight percentile in obese pregnant women. Further follow-up of babies born to mothers in the EMPOWaR study will identify longer-term outcomes of metformin in this population; in the meantime, metformin should not be used to improve pregnancy outcomes in obese women without diabetes.FundingThe Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council and National Institute for Health Research partnership.

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The effect of extremes of body mass on ovulation is well recognized by clinicians. However, the effect of obesity and extreme underweight on the outcome of in-vitro fertilization (IVF) cycles has received relatively little attention. In a retrospective nested case-control study we examined the effect of the extremes of body mass index (BMI) on IVF-embryo transfer outcome at a university-based IVF unit. A total of 333 patients were included in the study; 76 obese patients (BMI > 27.9) with 152 controls, and 35 underweight patients (BMI < 19) with 70 controls. The patients were matched with their controls in age +/- 1 year, day 3 follicle stimulating hormone (FSH) concentration, daily dose of gonadotrophin (+/- 37.25 IU), gonadotrophin preparation and the year of treatment. The following parameters were compared between the study and control groups: duration of administration and dose of gonadotrophin, number of follicles aspirated, number of eggs, fertilization rate, number of embryos, serum oestradiol concentration on human chorionic gonadotrophin (HCG) day (peak oestradiol), clinical pregnancy rate, implantation rate, miscarriage rate, and incidence of ovarian hyperstimulation syndrome. Apart from a significantly lower peak oestradiol concentration (P = 0.009) in the obese patients, they and the underweight patients were not significantly different from their normal controls. The extremes of body mass index do not adversely affect the outcome of IVF-embryo transfer treatment. However, the obese patients had lower peak oestradiol concentrations than their normal controls despite receiving similar gonadotrophin doses.