Good diabetic control prior to conception lowers the risk of fetal abnormality and complications of pregnancy, whereas diabetes in men is associated with poorer quality sperm and increased DNA damage. However, there is less certainty about the impact of glucose intolerance or hyperinsulinism on human fertility although both women and men with fertility problems have an increased risk of developing diabetes later in life. Women with polycystic ovarian disease have a particularly high risk, often demonstrating hyperinsulinism and higher rate of euploid miscarriage and gestational and type 2 diabetes. In animal models, exposure of embryos to high glucose environments resulted in delayed blastulation and reduced embryo viability, whereas endometrial effects included lower rates of viable implantation and reduced weight of the fetoplacental unit. The underlying mechanism for these fertility impacts was increased glycosylation of intracellular proteins and enzymes, leading to oxidative stress and DNA damage. Inflammatory cytokines and immune changes were also seen.
Disorders of glucose metabolism are thus likely to impact negatively on fertility and miscarriage yet there is little clinical evidence to support this premise. Apart from recommendations to test for diabetes in the pre-published PCOS guidelines, there is poor consensus regarding screening for hyperinsulinism, glucose intolerance or diabetes in couples with infertility.
We surveyed fertility specialists and found a significant variety of clinical practice in screening and treating couples for disorders of glucose metabolism. Barriers to effective screening include a lack of consensus on the appropriate test to do and when in treatment to undertake testing. Male testing was particularly controversial. Further research is needed to determine the role of aberrant insulin and glucose metabolism in infertility and miscarriageand how best to approach screening, testing and treatment to improve fertility outcomes.