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 R40 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. (Fertil Steril Rev Ò 2020;1:16-34. Ó2020 by American Society for Reproductive Medicine.

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 | 1859 MORRIS et al. | MATERIAL AND ME THODSThis was a retrospective cohort study conducted at the Centre for Reproductive and Genetic Health, London, UK.Data for in vitro fertilization (IVF) cycles carried out in our unit are held on a clinical database (IDEAS, version 6 Mellowood Medical software). We created a database query to retrieve data on all couples that underwent an IVF or intracytoplasmic sperm injection (ICSI) cycle with fresh embryo transfer from 1 December 2009 to 1 August 2018. We excluded cycles that used donor gametes (oocytes/sperm) and those that used frozen or surgically retrieved sperm. Our study did not include donor oocyte cycles to allow analysis of the effect 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...