Fertility and Fatherhood: Don’t Wait Too Long

Increasing paternal age reduced the chance of achieving live birth following assisted reproductive technology (ART), according to a retrospective study.

After adjusting for maternal age, the probability of a successful live birth through in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) decreased with paternal age over 50 versus age ≤35 (OR 0.674, 95% CI 0.482-0.943, P=0.021), reported Guy Morris, MBChB, of the Centre for Reproductive and Genetic Health in London, and colleagues.

“There should be a public health message for men not to delay fatherhood,” the authors suggested in Acta Obstetricia et Gynecologica Scandinavica.

In better news for older fathers-to-be, paternal age over 50 was not an independent predictor of miscarriage (OR 0.678, 95% CI 0.369-1.250, P=0.214).

Increasing age in women is associated with reduced success with ART, Morris and colleagues noted. However, there is less evidence on the impact that increasing paternal age has on ART outcomes.

The issue of paternal age has become increasingly relevant, they said, as delayed parenthood is becoming more common among both men and women, and increasing age in men is associated with a deterioration in semen quality.

The retrospective cohort analysis included data on all couples that underwent IVF or ICSI with fresh embryo transfer from December 2009 to August 2018 at Morris’s institution in London.

The study’s primary outcome was live birth rate, while secondary outcomes included clinical pregnancy rate (CPR) and miscarriage rate. Male partners were grouped by age ranges of ≤35, 36-40, 41-45, 46-50, and ≥51 years, while women were grouped by age ranges of ≤35, 36-37, 38-39, and ≥40 years. Age ≤35 was the reference group for comparisons.

During the study period, there were 4,833 ART cycles involving 4,271 men (133 older than 50 years) eligible for analysis. Of these cycles, 40.8% resulted in live births (40.4% of IVF cycles and 41.3% of ICSI cycles).

The team found that live birth rates decreased with increasing paternal age, from 48.9% for men ≤35 to 29.5% for men ≥51, as well as increasing maternal age, from 50.3% for women ≤35 to 20.8% for women ≥40.

CPR also declined with both increasing paternal age (from 49.8% for men ≤35 to 30.5% for men ≥51) and maternal age (from 51.9% for women ≤35 to 22.3% for those ≥40).

The odds of suffering a miscarriage significantly increased with maternal age of 38-39 years (OR 1.542, 95% CI 1.197-1.986) and ≥40 years (OR 1.529, 95% CI 1.169-2.001).

Morris and colleagues noted that while they were able to account for a major confounding variable — maternal age — they were not able to incorporate other paternal measures that could affect ART outcomes, such as body mass index, smoking, previous conceptions, and comorbidities. They were also unable to control for the cause of subfertility.

“Irrespective of the cause of infertility, increased male age is associated with a reduced live birth and CPR but does not affect the rate of miscarriage,” the authors concluded. “Further work on the possible mechanisms of this effect and whether there are enhanced sperm selection techniques that can mitigate it, is required.”