Effect of paternal age on outcomes in assisted reproductive technology cycles: systematic review and meta-analysis

Objective

To investigate whether paternal age exerts an independent effect on the clinical outcomes of assisted reproductive technology (ART) cycles.

Evidence Review

Observational studies were identified through a systematic search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and National Health Service evidence. Data for women aged ≤39 years were extracted and analyzed. We included all studies, both autologous and donor oocyte, into separate analyses of the effect of paternal age on ART outcome. We excluded studies in azoospermic men, women aged ≥40 years, ART including preimplantation genetic testing, and involving donor sperm. The included studies scored well on the Newcastle-Ottawa Quality Assessment Scale for observational studies. The primary outcome was live birth rate and secondary outcome measures were clinical pregnancy rate and miscarriage rate. When pooling data, the random-effects model was used to counter the effect of heterogeneity in the studies.

Result(s)

Live birth rate was reported in three autologous oocyte studies (2,926 cycles) and five donor oocyte studies (7,648 cycles). Live birth rate was found to be increased significantly when male age was <40 years in autologous oocyte studies but no difference in live birth rate was found in donor oocyte studies. Clinical pregnancy rates were found to be statistically higher when the paternal age was under 40 years in autologous oocyte studies, however, there was no difference in clinical pregnancy in the same age category when donor oocyte studies were analyzed. Miscarriage rate was reported in two autologous oocyte studies (970 cycles) and four donor oocyte studies (3,741 cycles). Miscarriage was found to be more likely with male age >40 years in autologous studies. In donor oocyte studies, the miscarriage rate was not increased when male age was >50 years. All of the autologous oocyte studies reported a statistically significant association between male age and female age.

Conclusion(s)

The findings of this review and meta-analysis, based on the donor oocyte model, suggest that advanced paternal age does not exert an independent effect on the outcome of ART cycles. Miscarriage rates do not appear to be increased even for men >50 years of age after treatment with donor oocytes. The meta-analysis of autologous oocyte studies suggests that increasing male age may have a deleterious effect on the outcome of ART, however, this may be confounded by the strong association with increasing maternal age.