Paternal age does not jeopardize the live birth rate and perinatal outcomes after in vitro fertilization: an analysis based on 56,113 frozen embryo transfer cycles

Abstract

BackgroundThe global trend of delaying childbearing has led to an increasing number of couples seeking in vitro fertilization. The adverse effects of advanced maternal age on pregnancy and perinatal outcomes are well-documented, regardless of the conception method. Advanced paternal age may also contribute to poor reproductive potential due to high levels of sperm DNA fragmentation. However, it remains challenging to provide guidance to older men regarding the impact of paternal age on pregnancy and birth outcomes in the field of assisted reproduction. ObjectiveTo investigate the association of paternal age with live birth and perinatal outcomes following in vitro fertilization-frozen embryo transfer. Study DesignA retrospective study was performed at a university-affiliated fertility center, involving women who were younger than 36 years and had undergone frozen embryo transfer from January 2011 to June 2021. Subjects were categorized into 6 groups based on paternal age: <25, 25-29, 30-34, 35-39, 40-44, and ≥45 years of age. A generalized estimating equation logistic regression model was used to account for the clustered nature of data and to adjust for confounders. Paternal age between 25-29 years served as the reference group in the logistic regression models. ResultsA total of 56,113 women who met the inclusion criteria were included for final analysis. On unadjusted analyses, the reproductive outcome parameters showed a significant decline with increasing male age. The live birth rate decreased from 47.9% for men aged 25-29 years to 40.3% for those aged ≥40 years. Similarly, the clinical pregnancy rate decreased from 54.4% in the reference group to 47.8% in the ≥40 years age group. Conversely, the miscarriage rate increased as male age increased, from 10.2% among men aged 25-29 years to 13.5% for those aged ≥45 years. However, the differences in the reproductive outcomes mentioned above were no longer significant in the multivariable models. Compared to the younger controls, advanced paternal age was not associated with a lower chance of live birth (adjusted odds ratio [OR], 0.94; 95% confidence interval [CI], 0.85-1.04, and adjusted OR, 0.93; 95% CI, 0.79-1.10, for males aged 40-44 years and ≥45 years, respectively). Additionally, the rates of clinical pregnancy (adjusted OR, 0.95; 95% CI, 0.85-1.05, and adjusted OR, 0.94; 95% CI, 0.79-1.12, for males aged 40-44 years and ≥45 years, respectively) and miscarriage (adjusted OR, 1.05; 95% CI, 0.85-1.31, and adjusted OR, 1.07; 95% CI, 0.77-1.50, for males aged 40-44 years and ≥45 years, respectively) were comparable between the reference and advanced paternal age groups. Furthermore, men in the youngest age group (<25 years) did not have worse pregnancy outcomes compared to those in the reference group. Regarding perinatal outcomes, there were no differences between the study cohorts in terms of preterm birth, low birthweight, macrosomia, small-for-gestational-age, and large-for-gestational-age, both in the unadjusted and confounder-adjusted models. ConclusionThis study did not demonstrate a significant association between paternal age and live birth and perinatal outcomes following in vitro fertilization-frozen embryo transfer when the female partners were younger than 36 years. With the global trend towards delaying childbirth, our findings provide useful information for counseling patients that increasing paternal age may not adversely affect pregnancy and perinatal outcomes in assisted reproduction.