Because sperm DNA may be associated with embryo development, the poorer quality of sperm DNA in APA may result in poorer embryo development outcomes. In addition, adverse effects of increasing male age on blastocyst formation may be related to impairment in male genome activation that occurs after cleavage-stage [
22]. This is supported by studies that found no association between paternal age and cleavage-stage development [
126], including in ICSI cycles with donor eggs [
21]. In comparison with studies indicating poorer rates of blastocyst formation, lower quality embryos were available for cryopreservation at day 6 with greater paternal age (> 40 years) [
74]. Several studies have looked at both embryo development stages in APA couples using donor oocytes. Frattarelli et al. evaluated 1023 men using donor oocytes and found that in men > 50 years, the rates of blastocyst formation were decreased. However, the rates of early embryo development, embryo arrest, cell number, and embryo cleavage were the same across age groups [
42]. Similarly, Garcia-Ferreyra et al. evaluated 286 embryos obtained from 32 IVF/ICSI cycles using donor oocytes and found that, although the rate of good quality embryos on day 3 was not associated with paternal age, the rate of blastocyst development was decreased in cycles with men > 50 years [
45]. APA was shown to have correlation with blastocyst formation rate, but not with the rate of top quality blastocysts [
6]. In contrast to these findings, one recent study did find decreased rates of both embryo cleavage and blastocyst formation with APA (≥40 years) in comparison with younger men (97% vs. 94 and 33% vs. 24%, respectively) [
63]; although this study did not use donor oocyte cycles, and so could not control for maternal age, all couples were being treated for male factor infertility and all women were < 40 years old.