Paternal age over 50 years decreases assisted reproductive technology (ART) success: A single UK center retrospective analysis

Introduction To study whether paternal age exerts an effect, independent of maternal age, on the outcomes of fresh in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI) cycles. Semen quality deteriorates with increasing paternal age; however, there is conflicting evidence for any impact paternal age may have on the outcome of IVF/ICSI. Several retrospective and prospective cohort studies have shown that paternal age increases the miscarriage rate and reduces the live birth rate. Some studies have shown no effect of paternal age on live birth rate or miscarriage rate. Studies involving donor oocytes have tended to show no independent effect of paternal age on assisted reproductive technology (ART) outcomes. The age at which paternal age may exert a significant deleterious effect on outcome is not known and there is no limit to paternal age in IVF/ICSI treatment. Material and methods A single-center retrospective cohort study was carried out at the Centre for Reproductive and Genetic Health, London, UK. Included in the analysis were all couples with primary or secondary infertility undergoing IVF/ICSI cycles in which the male partner produced a fresh semen sample and the cycle proceeded to fresh embryo transfer. All cycles of IVF/ICSI that used donor oocytes-donor sperm, frozen sperm, cycles leading to embryo storage and cycles including preimplantation genetic testing (PGT-A/PGT-M)-were excluded from analysis. The primary outcome was live birth rate and secondary outcomes were clinical pregnancy rate and miscarriage rate. Multivariate logistic regression analysis with live birth as a dependent variable and maternal and paternal age class as independent variables was performed. Results During the study period there were 4833 cycles, involving 4271 men, eligible for analysis; 1974/4833 (40.8%, 95% confiene intervals [CI] 39.5-42.2%) cycles resulted in a live birth. A significantly lower proportion of men over 51 years met World Health Organization semen analysis criteria (56/133, [42.1%, 95% CI 34.1-50.6]) compared with men under 51 years of age (2530/4138 [61.1%, 95% CI 60.0-62.6]) (p = 0.001). Both maternal and paternal age were retained in the multivariate model and for all maternal age subgroups the probability of live birth decreased with paternal age over 50 years (odds ratio [OR] 0.674, 95% CI 0.482-0.943) (p = 0.021). Paternal age over 50 years was not an independent predictor of miscarriage (OR 0.678, 95% CI 0.369-1.250) (p = 0.214). Conclusions Paternal age over 50 significantly affects the chance of achieving a live birth following ART. Paternal age does not independently affect the risk of miscarriage following ART. There should be a public health message for men not to delay fatherhood.

Automated summary

Studies have shown that paternal age has an impact on the outcomes of IVF/ICSI cycles, with older paternal age being associated with increased miscarriage rate and decreased live birth rate. However, paternal age over 50 is not independently associated with miscarriage risk following ART. It is important to communicate a public health message encouraging men not to delay fatherhood.