The 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:
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.
Testing of ovarian reserve may do several things:
- Inform patients regarding their reproductive lifespan and menopausal timing
- Aid in counseling and treatment strategy planning of young female cancer patients receiving gonadotoxic therapy.
- Help in establishing the diagnosis of PCOS and provide insight into disease severity.
- Ovarian reserve testing may also be considered as a screening tool in selected populations of women for assisting in their reproductive life planning.
- Help identify patients who will have poor response or hyperresponse to ovarian stimulation for ART and individualize treatment protocols to achieve optimal response while minimizing safety risks.
The Ideal Ovarian Testing
The ideal ovarian reserve test should be convenient, be reproducible, display little if any intracycle and intercycle variability, and demonstrate high specificity to minimize the risk of wrongly diagnosing women as having DOR and accurately identify those at greatest risk of developing OHSS prior to fertility treatment.
There is currently no perfect ovarian reserve test. Both AFC and AMH level have good predictive value and are superior to day-3 FSH.AMH assay make this test the preferred biomarker for the evaluation of ovarian reserve in most women because of it's convenience of untimed sampling, age-specific values, availability of an automated platform, and potential standardization. It is important to consider age-specific values when interpreting results and to remember that conditions such as PCOS and hormonal suppression can affect the values obtained.
A test to check your ovarian reserve usually involves two steps:
- a vaginal ultrasound and
- blood tests to measure hormone levels, which must be conducted when a woman is menstruating.
Women who are on birth control (and therefore not really ovulating) are told to go off birth control for several months before the test.
Between the ultrasound and blood tests, a doctor can determine how many eggs you might be able to grow in one round with the help of hormones. While a 21-year-old woman might grow 30 to 40 eggs in one round, by age 40, that number drops to six or eight eggs. The older you get, the harder it becomes to produce eggs.
Bear in mind that having a low ovarian reserve now does not necessarily predict your pregnancy chances for the future; it simply predicts how many eggs you can grow now. Some women may have a low ovarian reserve, but then conceive naturally.
There are a few different tests that can assess ovarian reserve:
- AMH or anti-Mullerian hormone (blood test)
- Clomid Challenge Test (blood test)
- Antral Follicle Count (ultrasound)
- Ovarian Volume Assessment (ultrasound)
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.
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."
Diminished 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.