Age and Female Infertility

Almost everyone is familiar with the concept of the “biological clock”. We have known for years that a woman’s fertility declines as a function of her age. This is usually because of the declining ability of the eggs to be fertilized and/or develop into a normal embryo. This decline is evaluated by the techniques mentioned in the preceding section which discusses ovarian reserve.

A number of studies have been done looking at various cultural or religious groups who never practiced contraception. These studies evaluated the likelihood of the women in that group becoming pregnant strictly as a function of their age. What these studies showed was, not surprisingly, that there is a slight decrease in fertility after the age of 30, a more significant decrease after the age of 35, and there is a major decrease after age 40. These studies, however, made no attempt to determine what individual characteristics might be affecting this decline in fertility – it was simply raw population data.

Although most of the decline in fertility after age 35, and especially after age 40, is the result of diminishing ovarian reserve, a study from Israel published in Fertility and Sterility in September 2000 clearly shows that other factors are at work.

This study looked at women over 40 going through in vitro fertilization. It is important to remember that before they would even be selected as a candidate for IVF, they would have to have normal ovarian reserve testing. This group, therefore, at least on the surface, would appear to be appropriate candidates for IVF.

What the study showed was that given their normal ovarian reserve testing, 87% of the women’s ovarian response to stimulation was good enough to allow for ovum retrieval and subsequent fertilization. An 87% fertilization rate is very respectable by anyone’s standards.

Despite this, the overall pregnancy rate was approximately 5% (the range was 2-7%) – far far less than you would expect in younger women. Furthermore, no women over the age of 44 became pregnant.

Another study from Germany published a number of years ago looked at pregnancy rates in women going through donor insemination. By looking at this group of women, the confounding effect of the male factor was essentially eliminated. What this study showed was that whereas in younger women (under the age of 30), you would expect most of your pregnancies to occur within the first 4 or perhaps 6 insemination cycles (numbers that are consistent with our own office results). For women over 35, it would often take 10 or 12 cycles of insemination to achieve a pregnancy.

Lastly, experimental studies in mice which have been confirmed in humans clearly show that it is a function of the eggs – not the uterus. If invitro fertilization is performed using the eggs from an old animal or an older woman and those subsequent embryos are transferred to a younger animal or woman, the success rates are poor. On the other hand, young mouse eggs transferred to the uterus of an older mouse do quite well and the same is true for the human experience.

The bottom line – there is a biological clock. The battery that runs this clock begins to deteriorate with age. Many women for a large variety of reasons do not begin to pursue their fertility until after age 35. While we will make every effort to help them achieve a pregnancy (and often we are successful), they must understand that the one thing we cannot fix is the calendar.

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