How Age Impacts Fertility in Men and Women and How It Differs
Age is perhaps the most important factor in determining a woman’s potential to become pregnant. Due to a variety of societal factors, including delayed marriage and an increasing number of women pursuing higher education and demanding careers, the average age in the United States for first pregnancy increased from 22 in 1980 to nearly 27 in 2018. Advanced age in women is associated with a significant increase in subfertility and infertility, and a concomitant demand for reproductive assistance.
At 20 weeks gestation, a female fetus possesses approximately 7 million eggs (oocytes) in her ovaries; by birth, that number has decreased markedly to 0.5 million to 2 million eggs. These eggs are contained within follicles composed of hormone-producing cells. Depletion of follicles continues throughout childhood and adolescence, and eggs are lost continuously through pre-ovulation cell death as well as ovulation itself. Unlike men, who produce new sperm throughout their lives, women do not produce any new eggs during their lifetimes. A woman will typically release between 300-500 eggs during her reproductive years. The number of eggs available for reproduction is largely genetically determined; therefore the fertility potential of women as they age and the onset of menopause, when the supply of viable eggs and follicles is nearly depleted, varies significantly among women. Ovarian aging corresponds to a substantial decline in monthly pregnancy rates from the early thirties to mid-forties. The chance of a woman conceiving in her lifetime is 80-90% when she is 25 and declines to approximately 50% at ages 35-37 and less than 30% by ages 40-42. Increased rates of pregnancy loss occur as women age, and by age 40 more than half of pregnancies end in miscarriage. Genetic abnormalities within the eggs are the primary cause for the diminished pregnancy rate and heightened miscarriage rate with age. A loss of hormone producing cells within the follicles as well as faulty separation of chromosomes and accumulated DNA damage within the nucleus and mitochondria of eggs result in reproductive failure.
The adverse effects of age on reproductive potential are not limited to women. As men age they experience a significant reduction in the number of both Sertoli cells and Leydig cells within the testicles. Sertoli cells are essential to the function of sperm producing cells, and Leydig cells are responsible for Testosterone production. Hence, sperm production and Testosterone production are diminished in aging men. Age is also associated with a reduction in testicular blood flow. While data are conflicting, several studies have demonstrated a reduction in sperm counts and motility (percentage of moving sperm), as well as an increase in the percentage of abnormally-shaped sperm, with age > 40. In addition, multiple studies have shown that advanced male age is associated with an increased rate of chromosome and other forms of DNA damage in sperm. All of these changes translate to a significantly greater time to conception and increased miscarriage rates even when controlling for the age of the woman. Of particular interest is an increase in genetic mutations within sperm cells as men age. These mutations, as well as epigenetic factors (i.e. non-genetic factors that can alter gene expression) may contribute to the substantially increased rate of schizophrenia, bipolar disease and autism among the offspring of older fathers compared to younger fathers.
It is essential that all couples planning to reproduce strongly consider the irreversible effects of advanced age on reproductive success. Couples in which a woman is 35 years of age or older should consult with a reproductive endocrinologist if not pregnant within six months of trying. For women who are considering egg freezing, the data suggest the younger a woman is at the time of retrieval, the more likely she is to have a successful outcome. While pregnancies have resulted from eggs frozen by women in their forties, the best outcomes are achieved when eggs are retrieved in their early to mid-thirties. Men should be aware of their compromised fertility potential as well as the increased incidence of genetic abnormalities and certain disease states as they age.