Gestational diabetes mellitus and polycystic ovary syndrome individually cause significant morbidity. The two conditions are interlinked and together increase the incidence of preeclampsia, pregnancy-induced hypertension and neonatal hypoglycaemia. The therapeutic merits of metformin are under review
Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance which starts during pregnancy. It is associated with increased foetal and maternal morbidity as well as long-term complications in both mothers and offspring. The prevalence ranges from 2 to 20% of all pregnancies, depending on the population studied and the diagnostic tests employed. Common risk factors of GDM include nonwhite race/ethnicity, older age, obesity and prior history of abnormal obstetric experience.
Polycystic ovarian syndrome (PCOS) is characterized by chronic anovulation, insulin resistance and androgen excess. Affected women have an increased risk of glucose intolerance, leading to type 2 diabetes mellitus (T2DM). The risk of GDM is higher in women with PCOS than in women without PCOS1 and several studies have observed an increased prevalence of the signs and symptoms of PCOS in women with prior GDM. PCOS is associated with adverse pregnancy outcomes, such as preeclampsia and macrosomia.2 Lean women with PCOS have a higher incidence of GDM and pregnancy-induced hypertension than lean controls.3 In this study, women with PCOS and GDM had more than twofold increased odds of preeclampsia and pregnancy-induced hypertension than women without these conditions. Maternal PCOS and GDM were also associated with threefold increased odds of neonatal hypoglycemia.
There are some metabolic similarities between women with PCOS and women with GDM. It is still uncertain, however, to what extent coexisting GDM and PCOS affects pregnancy outcome. In a case-control study conducted with 261 women with GDM, the findings emphasized that pregnant patients with GDM and PCOS should be monitored carefully for various pregnancy and neonatal complications, including hypertension and hypoglycemia.4
Metformin is an effective insulin sensitizer for treating T2DM and for preventing T2DM in high risk populations. In GDM, use of metformin is associated with a lower risk of hypoglycemia and potentially a lower weight gain. It may be preferable to insulin for maternal health if it controls hyperglycemia sufficiently; however, metformin may slightly increase the risk of premature birth.5 To date, long-term outcome in offspring has not been evaluated. Thus, patients treated with metformin should be informed that the drug does cross the placenta and, while no adverse effects on the foetus have been demonstrated, long-term studies are lacking.
Metformin may improve ovulatory function in patients with PCOS. Meta-analyses of randomized, placebo-controlled trials involving women with PCOS have shown increased pregnancy rates but not increased live birth rates among women who received metformin.6 However, metformin is not recommended as a first-line treatment for anovulatory infertility, although there is a study which found that infertile patients with PCOS taking metformin were more likely to conceive with or without other ovulation-inducing agents, compared with patients who did not take metformin. These results showed that continuous metformin therapy throughout pregnancy in women with PCOS can improve pregnancy outcomes by decreasing spontaneous miscarriage rates and preventing GDM with its inherent comorbidity and mortality rate.7 Whether metformin could reduce the occurrence of GDM in women with PCOS is still controversial, with a recent meta-analysis, using a fixed model, showing that metformin had no significant effect on GDM in women with PCOS.8
- Lo JC, et al. Increased prevalence of gestational diabetes mellitus among women with diagnosed polycystic ovary syndrome: A population-based study. Diabetes Care 2006;29:1915–7.
- Qin JZ, et al. Obstetric complications in women with polycystic ovary syndrome: a systematic review and meta-analysis. Reprod Biol Endocrinol 2013;11:56–62.
- Wang Y, et al. Risks for gestational diabetes mellitus and pregnancy-induced hypertension are increased in polycystic ovary syndrome. Biomed Res Int. 2013;2013:182582.doi:10.1155/2013/182582. Epub 2013 Nov 25.
- Foroozanfard F, et al. Obstetric and neonatal outcome in PCOS with gestational diabetes mellitus. J Family Reprod Health 2014;8:7–12.
- American Diabetes Association. Standards of medical care of diabetes 2016: Management of diabetes in pregnancy. Diabetes Care 2016;39(Suppl. 1):S94–S98.
- Tang T, et al. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database Syst Rev 2012;5:CD003053.
- Hameed AAE, et al. The role of continuing metformin therapy during pregnancy in the reduction of gestational diabetes and improving pregnancy outcomes in women with polycystic ovary syndrome. Middle East Fert Soc J 2011;16:204–8.
- Zhuo Z, et al. Effect of metformin intervention during pregnancy on the gestational diabetes mellitus in women with polycystic ovary syndrome: A systematic review and meta-analysis. J Diabetes Res 2014;2014:381231. doi: 10.1155/2014/381231. Epub 2014 May 21.