Glibenclamide and metfoRmin versus stAndard care in gEstational diabeteS (GRACES): a feasibility open label randomised trial.

BACKGROUND: Metformin is widely used to treat gestational diabetes (GDM), but many women remain hyperglycaemic and require additional therapy. We aimed to determine recruitment rate and participant throughput in a randomised trial of glibenclamide compared with standard therapy insulin (added to maximum tolerated metformin) for treatment of GDM. METHODS: We conducted an open label feasibility study in 5 UK antenatal clinics among pregnant women 16 to 36 weeks' gestation with metformin-treated GDM. Women failing to achieve adequate glycaemic control on metformin monotherapy were randomised to additional glibenclamide or insulin. The primary outcome was recruitment rate. We explored feasibility with uptake, retention, adherence, safety, glycaemic control, participant satisfaction and clinical outcomes. RESULTS: Records of 197 women were screened and 23 women randomised to metformin and glibenclamide (n = 13) or metformin and insulin (n = 10). Mean (SD) recruitment rate was 0.39 (0.62) women/centre/month. 9/13 (69.2%, 95%CI 38.6-90.9%) women adhered to glibenclamide and all provided outcome data (100% retention). There were no episodes of severe hypoglycaemia, but metformin and insulin gave superior glycaemic control to metformin and glibenclamide, with fewer blood glucose readings <3.5 mmol/l (median [IQR] difference/woman/week of treatment 0.58 [0.03-1.87]). CONCLUSIONS: A large randomised controlled trial comparing glibenclamide or insulin in combination with metformin for women with GDM would be feasible but is unlikely to be worthwhile, given the poorer glycaemic control with glibenclamide and metformin in this pilot study. The combination of metformin and glibenclamide should be reserved for women with GDM with true needle phobia or inability to use insulin therapy. TRIAL REGISTRATION: www.clinicaltrials.gov registration number:NCT02080377 February 11th 2014.

Recurrent miscarriage.

Recurrent miscarriage, the occurrence of three consecutive first-trimester losses of pregnancy, affects 1% of women. The purported causes of recurrent miscarriage include chromosomal abnormalities, thrombophilia, metabolic disorders, anatomical causes and immune factors. At present, the only recommended investigations are testing for lupus anticoagulant and anticardiolipin antibody levels (to diagnose antiphospholipid syndrome, an acquired thrombophilia) and the karyotyping of both parents for chromosomal abnormalities. Women with antiphospholipid syndrome should be offered treatment with aspirin and low molecular weight heparin. Couples with chromosomal abnormalities should be referred to a clinical geneticist with whom the options of prenatal diagnosis, pre-implantation genetic diagnosis, donor gametes and adoption in subsequent pregnancies should be discussed. Couples with unexplained recurrent miscarriage should be offered appropriate emotional support and reassurance that they have a good prognosis for future pregnancies.