Metformin
It is well-known that increased insulin resistance and associated high blood glucose levels have a great impact on menstrual cycle frequency and reproductive outcomes. Furthermore high blood glucose levels can lead to adverse pregnancy outcomes such as miscarriage, congenital malformations, stillbirth and neonatal death however, pregnancy can adversely affect maternal health leading to worsening control of diabetes and associated consequences of cardiovascular disease, retinal and renal pathology (27). As more women are delaying conception, seeking fertility treatment and/or becoming pregnant at an older age, the prevalence of type II diabetes in pregnancy is suspected to rise. Metformin is an anti-hyperglycaemic biguanide drug used commonly in the treatment of type II diabetes mellitus (28). Inhibition of hepatic gluconeogenesis and reduction of glucagon action results in reduced serum insulin and glucose concentrations, which in turn improves ovulation, pregnancy and live birth rates (29). Women with diabetes are often advised to use metformin pre-conceptually in addition to or alternative to insulin as the benefits of improved glucose control are likely to outweigh the potential risks (30).
Diabetes Mellitus is a very common condition in the UK, and its prevalence is increasing. 1st line treatment according to the NICE guidelines for Type 2 Diabetes Mellitus is Metformin. In general, metformin is thought to be safe however there is insufficient data on its use in the first trimester and risk of miscarriage (30). Few studies have determined the effect of metformin on reproductive outcomes when used to treat diabetes. One small study of 35 women found that patients who are on metformin for diabetes had better embryo quality than patient’s undergoing insulin therapy however this did not affect the implantation, clinical pregnancy or miscarriage rate (31). Metformin is also used as an ovulation induction agent in polycystic ovary syndrome (PCOS), and a Cochrane review of 42 studies (evidence range very low to moderate) concluded that metformin alone over placebo may be beneficial for live birth rates however the evidence quality was low (29). Another Cochrane review including 9 studies of moderate quality evidence, found that metformin use compared to placebo, before and after ART treatment in patients with PCOS, increased clinical pregnancy rates and reduced the risk of complications such as ovarian hyperstimulation syndrome, however there was no convincing evidence of an effect on live birth rates (32). More information on the reproductive outcomes before and during ART with use of metformin on both male and female partners is required to help guide clinical decision-making.