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

Abstract

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.

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

“…The only other meta-analysis on this subject, published in 2020 by Morris and co-workers, concluded that male age does not affect live birth, clinical pregnancy or miscarriage rates when using donor oocytes (Morris et al, 2020). However, their meta-analysis only separated paternal age at 40 and 50 years, and not across the age groups of 30, 35 and 45 as was done here.…”

Paternal ageing impacts blastulation and the outcomes of pregnancy at different levels of maternal age: A clustering analysis of 21,960 oocytes and 3837 ICSI cycles

“…Those that have suggest that APA may negatively impact gamete oxidative DNA damage (Nguyen‐Powanda & Robaire, 2020) and genetics (Brandt et al, 2019; Sharma et al, 2015), conception rates (du Fossé et al, 2020; Ford et al, 2000), maternal comorbidities such as gestational diabetes (Khandwala et al, 2018; Strøm‐Roum et al, 2013) and hypertensive disorders of pregnancy (Alio et al, 2012), perinatal outcomes such as low birth weight, low‐Apgar scores and premature birth (Alio et al, 2012; Khandwala et al, 2018), and the long‐term health of offspring, such as an increased risk of neuropsychiatric disorders (schizophrenia, autism and obsessive compulsive disorder) (Brandt et al, 2019; de Kluiver et al, 2017; Hultman et al, 2011; Sharma et al, 2015; Wu et al, 2012) and cancers (leukaemia, non‐Hodgkin's lymphoma and paediatric central nervous system tumours) (Hemminki et al, 1999; Murray et al, 2002). On the other hand, several studies failed to demonstrate an effect of paternal age on reproductive outcomes (reviewed in Morris et al, 2020). This could be explained by the fact that maternal and paternal ages are highly correlated with relatively little variability in the age difference; thus, many affected couples would have to be studied to distinguish any independent paternal age effect.…”

Age-related fertility decline: is there a role for elective ovarian tissue cryopreservation?

“…This is important considering the mean paternal age has also increased globally, from 27.4 to 30.9 years observed in America ( Khandwala et al , 2017 ; Bergh et al , 2019 ), and from 29.2 in 1980 to 32.1 over the last four decades in England and Wales (Birth Statistics, 2007). In a recent systematic review, both the livebirth and pregnancy rate were increased when the male age was ≤40 years old in autologous oocyte cycles, and the miscarriage rate more likely when the male was >40 years old ( Morris et al , 2020 ). Paternal age should therefore also be considered in the management of ARFD.…”