Paternal metabolic dysfunction and pregnancy loss following assisted reproduction: a cross-sectional study.

AbstractThere is substantial heterogeneity in the relationship between paternal obesity and pregnancy outcomes following assisted reproduction, possibly related to the presence of obesity-related metabolic complications (e.g. insulin resistance, dyslipidaemia). A retrospective study of heterosexual couples aged over 18 years who underwent metabolic function testing (fasting total cholesterol, triglycerides, high-density lipoproteins, low-density lipoproteins, insulin, or glucose) within 1 year of embryo transfer was performed. Couples utilising donor sperm or oocytes or assisted reproduction in the context of malignancy were excluded. Binomial logistic regression was utilised to examine the relationship between pregnancy outcomes (conception/pregnancy loss) and both paternal 'metabolic dysfunction' (any metabolic test exceeding the laboratory reference range) and individual metabolic parameters. A total of 363 couples met the inclusion criteria, of whom 229 underwent fresh embryo transfers (63.1%) and 134 underwent frozen embryo transfers (36.9%). The overall pregnancy rate was 40.8%. Metabolic dysfunction was present in 58.4% of men and 39.4% of women. Neither paternal BMI nor metabolic dysfunction was associated with the likelihood of conception. Metabolic dysfunction was associated with pregnancy loss (odds ratio (OR) = 2.57, 95% confidence interval (CI) = 1.10, 6.04). Specifically, serum triglyceride concentration was associated with pregnancy loss both numerically (OR = 1.84, 95% CI = 1.09, 3.13) and categorically (>1.7 mmol/L: OR = 2.88, 95% CI = 1.17, 7.10), as was a Homeostatic Model Assessment of insulin resistance score > 2 (OR = 2.70, 95% CI = 1.10, 6.61). These data support an association between paternal peri-conception metabolic state and pregnancy loss. Further prospective studies are necessary to validate this association and determine whether paternal therapeutic interventions can reduce pregnancy loss.Lay summaryWe studied whether a man's metabolic health around the time of undergoing assisted reproduction was linked to pregnancy outcomes (conception and pregnancy loss). Men's weight and metabolic blood tests, including cholesterol, triglycerides, insulin and glucose, were assessed in 363 couples, of whom 41% became pregnant. More than half of all men had at least one abnormal metabolic result. We found that male body mass index and overall metabolic problems were not associated with the likelihood of conceiving; however, among couples who conceived, abnormalities in male metabolic blood tests were linked to more than twice the risk of pregnancy loss. High triglyceride levels and insulin resistance were most closely associated with pregnancy loss. Overall, the study suggests that the father's metabolic health may affect the risk of losing a pregnancy; however, further research is needed to confirm this.