Table 3.

The effects of advanced paternal aging on reproductive outcomes including live birth rate, pregnancy loss rate, miscarriage rate, implantation rate, fertilization, embryo development, and embryo morphology

Fertilization type	Study population	Observed effects of paternal age	Paternal age limits	Reference
Natural	3287 couples	Delay in pregnancy onset ↑ Conceptional difficulties ↑	≥40	de La Rochebrochard and Thonneau [100]
IVF/GIFT	221 couples	Pregnancy rate ↓ Live birth rate ↓	Mean: 38.4	Klonoff-Cohen and Natarajan [101]
IVF, ICSI, CI	1023 donor oocytes (donor age; ≤35)	Live birth rate ↓ Pregnancy loss rate ↑ Blastocyst formation rate ↓ No significant difference in implantation and pregnancy rate or early embryo development	>50	Frattarelli et al. [99]
CI, ICSI	672 ovum donor cycles (donor age; <35)	Fertilization rate ↓ Day 3 embryos with >7 cells ↓ Blastocyst formation rate ↓ Implantation rate ↓ Pregnancy loss rate ↑	<40, 40–49, >50 (subgroup >60)	Luna et al. [104]
ICSI	1024 couples	For couples in which the men are oligozoospermic implantation rate ↓ (decreased by 5 % for each year of paternal age) No such difference was observed for normozoospermic men In both groups, paternal age did not influence miscarriage outcomes.	Mean: 36.85 for oligozoospermic and 37.18 for normozoospermic	Ferreira et al. [106]
IVF	237 oocyte donation cycles (donor age, 21–31)	Live birth rate ↓ (decreased by 26 % for each 5 years of paternal age)	25–66	Robertshaw et al. [102]
ICSI	4887 oocyte donation cycles (donor age, 18–35)	No differences were found in biochemical, clinical and ongoing pregnancy, miscarriage, and live birth in different male age groups	22–81	Begueria et al. [105]

IVF in vitro fertilization, IVF-ET in vitro fertilization and embryo transfer, GIFT gamete intrafallopian transfer, CI conventional insemination, ICSI intracytoplasmic sperm injection