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The number of eggs present in the ovary declines with age. The process of losing eggs over time, called atresia, begins early in life. A female fetus has 6 to 7 million eggs at 20 weeks development. At birth that number reduces to 1 to 2 million eggs and at puberty only 300,000 viable eggs remain. It is no surprise, then, that fertility declines as a woman ages. In fact, a measurable decline in female fertility begins at around age thirty.
This decline in fertility corresponds with a decline in egg quality as well as egg quantity. It is also well known that older women have pregnancies with a higher risk of genetic abnormalities and a higher risk for miscarriages. In addition, one half of those miscarriages are due to chromosomal abnormalities in the fetus. Since studies have indicated that the majority of pregnancies are lost in the earliest of stages, it seems logical to conclude that many of those embryos are defective. Some of those embryos never implant, some implant resulting in miscarriage and some make it to term and a chromosomally abnormal baby is born. To detect this abnormal child, techniques such as chorionic villi sampling and amniocentesis have been developed and are widely used by women over 35.
Early studies examining the genetic information from embryos derived from in vitro fertilization (IVF) suggested that many embryos were abnormal. Some had extra chromosomes or were missing chromosomes (aneuploidy), some had multiple copies of chromosomes (polyploidy), and others had cells which did not have the same chromosomal makeup as other cells derived from the same embryo (mosaic). It has now been shown that in women over 40, greater than 50% of normal appearing embryos are genetically abnormal whereas in women less than 40, less than 10% were abnormal. A large percentage of IVF failure results from transferring embryos that look healthy under the microscope but are not viable because of genetic abnormalities.
What does this mean for the older patient contemplating pregnancy by either natural conception or IVF? Most physicians advise the older patient of the lower odds for success but patients have a difficult time accepting this. However, it is a fact that the chance of the older patient getting pregnant is limited by the genetic makeup of the egg and embryo. This age related factor is not a reversible cause of infertility and will not be changed by altering diet, sleep, medicine or stress levels, or anything else. There is no medication that will undo the genetic ageing process of the oocyte (egg). The process is natural, normal and is different for each individual. Data shows it affects a large percentage of women over 40. The lesson for the individual, however, is to accept these facts and use this information to make logical decisions regarding attempting infertility treatment. Attempts are warranted but only in selected individuals.
In women over 40 who have cycle day 3 FSH levels of 12 or lower, attempts at treating are warranted. In spite of the reduced overall success rate in this age group, many patients still achieve a pregnancy. When looking at population data, it is clear that the pregnancy rate declines with each year over 40 and very few successful outcomes in women 45 and older. However, one cannot use population data to predict which individuals will succeed in these advanced reproductive age groups. Measuring cycle day 3 FSH hormone levels is helpful in predicting who is more likely to succeed. For patients who have a cycle day 3 FSH level over 12 in more than one cycle, there is less than a 3% chance that they will ever become pregnant no matter what the treatment. If a woman falls into the favorable group treatment may result in a pregnancy, but there certainly no guarantee. If she falls into the unfavorable group, then donor egg or adoption is recommended to resolve her infertility.
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