Does advanced paternal age affect outcomes following assisted reproductive technology? A systematic review and meta-analysis

Infertility affects more than 14% of couples, 30% being caused by male factor infertility. This meta-analysis includes 28 studies, selected according to PRISMA guidelines. Data were extracted from these studies to collate cycles separating paternal age at 30, 35, 40, 45 and 50 years (±1 year). Primary outcomes of interest were clinical pregnancy, live birth and miscarriage rates. Secondary outcomes were the number of fertilized eggs, cleavage-stage embryos and blastocysts, and embryo quality per cycle. Fixed-effects and random-effects models giving pooled odds ratios (OR) were used to assess the effect of paternal age. This meta-analysis included a total 32,484 cycles from 16 autologous oocyte studies and 12 donor oocyte studies. In autologous cycles, a statistically significant effect of paternal age <40 years was noted in clinical pregnancy (OR 1.65, 95% confidence interval [CI] 1.27–2.15), live birth (OR 2.10, 95% CI 1.25–3.51) and miscarriage (OR 0.74, 95% CI 0.57–0.94) rates. Paternal age <50 years significantly reduced miscarriage rate (OR 0.68, 95% CI 0.54–0.86), and increased blastocyst rate (OR 1.61, 95% CI 1.08–2.38) and number of cleavage-stage embryos (OR 1.67, 95% CI 1.02–2.75) in donor oocyte cycles, where maternal age is controlled. This is an important public and societal health message highlighting the need to also consider paternal age alongside maternal age when planning a family.