Early onset gestational diabetes (GD) as the cause for recurrent spontaneous miscarriages (RSA): RSA, pregestational metformin treatment and pregnancy outcome

Study question: Gestational diabetes is associated with RSA. A non diagnosed GD is a risk factor for RSA. Further it is known that infertility is associates with a high prevalence of early onset GD.

Objective of the study was to obtain a prevalence of impaired glucose tolerance, insulin resistance and early onset GD in association with RSA and analyze pregnancy outcome in this Population.

Materials, methods: Recruitment period 07/2011 to 12/2013. Fifty-seven women with confirmed RSA and subsequent pregnancy are included in the analysis. In all subjects a basic 75 g oral glucose tolerance test (OGTT) and insulin sensitivity testing was performed prepregnancy. All RSA-patients with and without disturbed glucose metabolism or IR received metformin treatment (standard dose 3 × 500 mg). As soon as pregnancy was confirmed a second 75 g OGTT was performed. If impaired glucose tolerance or GD was diagnosed treatment was initiated according to the current guidelines.

Results: 98.2% of the study population showed a prepregnancy disturbed glucose metabolism and/or a insulin resistance (IR). In 45.8% a GD was diagnosed in the following pregnancy. Of women diagnosed with GD 77.8% received metformin treatment prepregnancy. After initiation of metformin treatment 40 women became pregnant, 85,7% with a positive pregnancy outcome.

Summary: The high incidence of prepregnancy disturbed glucose metabolism (GM), IR and GD indicates that glucose metabolism has more influence in miscarriage than assumed. If impaired GM/IR is not diagnosed and not treated before conception or in early pregnancy, it is likely to have a negative impact on the vasculogenesis during implantation period.