Good Eggs and Bad Eggs

    Fertile Eggs for FertilizationThe concept of a woman's "egg quality" is derived from the observation that the probability of embryo implantation is strongly related to the age of the woman who provides the egg and to her ovarian reserve. Therefore, "egg quality" is synonymous with "the probability of embryo implantation." Egg quality cannot be determined by looking at the egg, measuring its receptivity to fertilization by sperm, or observing initial embryo division. Just because an embryo looks good in the laboratory, does not mean that it will implant. Just as the proof of the pudding is in the eating, the proof of egg quality is in the embryo implantation.

    Some of the noteworthy contributing factors to embryo implantation failure are:

    1. Diminished Ovarian Reserve
    2. Advanced Maternal Age
    3. Diminished Egg Quality

    Diminished Ovarian Reserve

    There are several blood tests to check for a woman's egg quality. The oldest test is done on cycle day 3 for the hormone called FSH (follicle stimulating hormone). A woman who has elevated FSH levels on cycle day 3 is said to have diminished "ovarian reserve." What this means physiologically is that the ovary is producing less feedback signal to the pituitary gland, and the body responds by making more FSH in an effort to stimulate the ovary. It has been observed over the past ten years in thousands of cycles of fertility treatment that women with elevated FSH levels have markedly decreased egg quality and rarely conceive with their own eggs (they do, however, become pregnant readily with donor eggs). The precise physiological reason for this is unclear. However, we do know that when eggs are obtained from women with elevated FSH levels, they appear normal, they fertilize normally, and undergo initial embryonic cleavage at a normal rate. However, they rarely divide beyond the 8 cell stage and almost never implant.

    A newer test to check ovarian reserve is AMH or anti-Mullerian hormone, a hormone secreted by cells in developing egg sacs (follicles). The level of AMH in a woman's blood is generally a good indicator of her ovarian reserve.  

    An AMH or anti-Mullerian hormone test gives us some insight into the remaining quantity of eggs and number of fertile years you may have, but it cannot tell us much about the quality of those eggs. AMH does not change during your menstrual cycle, so the blood sample can be taken at any time of the month - even while you are using oral contraception.

    Ovarian Reserve Testing

    Almost one in ten women who present for for infertility evaluation will have such poor ovarian function that they are extremely unlikely to achieve pregnancy. At the current time, this problem cannot be fixed. Therefore, assessment of a woman through ovarian reserve testing is the most important fertility test that a physician does.

    Women have all the eggs they are ever going to have in their lives before they are born. By the time of birth, the ovarian reserve - the number of remaining eggs stored in the follicles - has decreased dramatically. For the rest of her life, ongoing follicular depletion will reduce the number of eggs remaining in the ovaries. In fact, far more eggs will be lost by degeneration than are lost by ovulation.

    There are a few different tests that can assess ovarian reserve:

    Ovarian reserve testing is not the same thing as testing for ovulation. A woman can ovulate normally and have very regular menstrual cycles and still have a low probability of becoming pregnant. One author even coined the term "Occult Ovarian Failure" to describe the triad of infertility, regular menstrual cycles and decreased ovarian reserve.

    Tests of ovarian reserve are only predictive of fertility when they come back ABNORMAL. A normal test does NOT mean that the ovaries work well. It just means that no test has yet demonstrated that they work poorly. These tests do not find all women with poorly functioning ovaries.

    Advanced Maternal Age

    Even if FSH levels are normal, the age of the woman providing the eggs plays a major role in determining Egg Quality. Just as with women with elevated FSH levels, eggs obtained from women in their late 40's appear normal, fertilize normally, and undergo initial embryonic cleavage in a normal manner. However, such embryos almost never implant. Because of low implantation rates in women over 45 years old, normal FSH levels are not considered "reassuring."

    Egg Quality and FertilityDiminished Egg Quality

    One way to think of diminished egg quality is a battery analogy. Consider each egg as possessing a number of batteries that provide its energy stores. The batteries are analogs of tiny organelles called mitochondria, which are the energy producers of mammalian cells. As we grow older, the energy-producing capacity of the mitochondria decreases (this is why older people run slower than young people). The egg is connected to the circulation prior to ovulation, and it is connected again after embryo implantation. But during the seven days between ovulation and implantation, the egg and the embryo that results from it, are contained within the zona pellucida and are dependent on energy coming from the mitochondria, which were in the egg at the moment of ovulation (no mitochondrial replication takes place until after implantation). The older egg usually looks normal at the time of ovulation and its initial fertilization and embryonic development remain normal. This is because its energy stores are still adequate. However, it soon runs out of batteries and stops dividing. Implantation is not achieved because the embryo stops dividing before it reaches the implantation stage. We do not yet know how to increase the energy stores to an egg prior to ovulation. When egg quality is low, the only therapy that has a proven track record and produces reliable results is egg donation.