The Impact of Age on Female Fertility
I. Getting pregnant after 35 II. Getting pregnant after 35 Fertility Assessment Helps Women Plan Ahead
One of the most important considerations in the success of fertility treatments is the age of the female partner. After reaching peak reproductive capacity (fecundity) in their early to mid-20's, women undergo a steady decline in the ability to conceive and deliver a child with advancing age. Although most women will have regular, cycles until two to four years prior to menopause (average age 51), loss of fertility occurs much earlier, with the average age at the birth of the last child being only 41 in fertile populations who do not practice contraception.
There are two main features of reproductive aging in women - decline in the number of eggs and decline in egg quality. At birth, female infants are endowed with a finite supply of eggs for their lifetime, on the order of several hundred thousand. Only a few hundred eggs will ovulate during a woman's reproductive lifespan, whereas the vast majority of eggs die off continuously by a process called atresia. The factors which determine the rate of atresia are unknown; however, this steady drop off in egg number is independent of lifestyle, hormonal influences, and pregnancy. When the number drops critically low, ovulation ceases and menopause occurs.
With regard to fertility, the more critical effect of aging is a decline in egg quality. As women enter their late 30s and early 40s, the majority of the ovulated eggs (present since birth) are unable to properly manage their chromosomes (genetic material). As a result, when these eggs fertilize, they are likely to result in embryos that contain chromosomal abnormalities (aneuploidy). An example of such a chromosome abnormality that can occur in a live born infant is trisomy 21, or Down's Syndrome. The vast majority of chromosomally abnormal embryos do not even implant in the uterus; if they do implant, they are more likely to miscarry. Fortunately, this natural "filter" is highly efficient, with only a small minority of abnormal embryos resulting in an ongoing pregnancy. The rate of clinically significant cytogenetic abnormalities in live births rises from about 1/500 for women under 30, to 1/270 at age 30, 1/80 at age 35, 1/60 at age 40, and 1/20 at age 45. Fortunately, all of these age-related chromosomal abnormalities can be detected with prenatal testing such as amniocentesis.
The most compelling evidence for the role of oocyte quality in age-related infertility lies in the results of egg donation. Pregnancy and delivery rates after egg donation are almost solely correlated with the age of the egg donor rather than the recipient. According to annual reports published by the Society for Assisted Reproductive Technology and Centers for Disease Control and Prevention, no significant age-related decrease in success rates is observed after oocyte donation, with average delivery rates over 50% per embryo transfer. Therefore, replacement of the defective oocyte with that of a younger woman appears to largely, if not completely, reverse the age-related decline in female fertility.
Women seeking pregnancy after the age of 35 should seek early basic fertility assessment if they are unable to conceive after six months of attempted conception. It is appropriate to initiate both evaluation and treatment earlier in this age group due to the rapid decline in success of treatment over time. Any abnormalities present should be addressed, and appropriate therapy initiated to optimize the chance of pregnancy. Tests to determine ovarian reserve (i.e., an estimation of the number of oocytes available) are especially helpful to assess the chance of pregnancy and/or response to fertility medications.
Treatment of age-related infertility is limited, with no specific treatment available for oocyte abnormalities or decreased ovarian reserve. In general, fertility therapy for normal older women is directed toward increasing the number of available oocytes through fertility medications and/or assisted reproductive technologies such as in vitro fertilization (IVF). However, due to the low implantation rates (in spite of increased egg production and normal fertilization), these treatments are associated with disappointing success rates beyond the age of 41. On the other hand, excellent success rates can be achieved through oocyte donation in women up to and beyond the age of 50 years.
In summary, female fertility is significantly reduced in older reproductive age women due to poor egg quality that results in chromosomally abnormal embryos. There is significant variability in ovarian reserve in women after 35, with corresponding differences in ovarian response and success rates with fertility medications and IVF. Ovarian reserve testing is useful to determine relative "reproductive age" and prognosis. Beyond age 41, the only highly successful treatment for age-related infertility is oocyte donation. Women over 35 should seek early infertility evaluation and treatment.
