Women are born with all the eggs they are going to have, so when are my eggs too old?
These eggs appear in the developing ovary very early in gestation, so it is necessary to add almost one year to the person’s chronologic age, to get the actual age of the remaining eggs. The peak fertility for women is reached around age 25 and remains about the same until approximately age 35, when it begins to decline. At age forty, the rate of decline accelerates and by age 42 a woman has lost almost 70% of her fertility potential. In fact, studies have shown that by age 42, around 93% of the remaining eggs are abnormal (aneuploidic). This trend continues until menopause, which occurs around age 51 (range: 40-55yrs) in the U.S.
At the time of puberty, a woman has about 500,000 eggs and she loses them at a rate of approximately 1,000 per month. Between one and 50 of the 1,000 eggs will start maturing during the ensuing 5-7 days in fluid filled spaces called follicles. At this time, one (and sometimes two) follicle(s) becomes dominant and all the rest start to absorb. Only the dominant follicle(s) ovulate(s) about a week later. All the remaining eggs of the initial 1,000 degenerate and are absorbed. Actually, the analogy I sometimes use to describe involves a group of tigers in a cage. Let’s assume there are five tigers in a cage. If I throw food into the cage that’s only sufficient to feed three of the tigers, two will not eat and hence become weaker. The next day, I throw food in sufficient to feed only two tigers. The tigers start fighting with each other for the food and because those that did not eat yesterday are weak, they will not prevail in the battle today for limited resources. Therefore, they will degenerate. This process continues along until the emergence of the single dominant follicle — the “survivor”, which is then ovulated.
The development of eggs is controlled by the pituitary gland which releases amongst others, a hormone called Follicle Stimulating Hormone (FSH). FSH signals the ovary to make a group of follicles grow. Inside of each follicle is an egg. The follicle produces estrogen, which signals the brain that the system is working. At the beginning of a woman’s reproductive life span, the ovary responds readily to stimulation from the brain to produce a mature egg. However, over time the ovary uses up its best eggs. As with a barrel of apples, at some point there are only the bad ones left at the bottom. These remaining eggs do not respond as easily to the FSH signal from the brain. The brain then makes more FSH in an attempt to coax the ovary to produce an egg. We measure the FSH (in conjunction with Estradiol (E2) and Inhibin B (see below) on the second or third day of the menstrual cycle as an indication of ovarian reserve. Since E2 can falsely suppress FSH, the interpretation of FSH requires that the E2 concentration be less than 60 – 70pg/ml on same day. The Inhibin B test is rather complex and there are only a handful of laboratories in the United States that can perform it reliably.
An FSH level above 9 mIU/ml in association with an E2 concentration of <70pg/ml and an Inhibin B level of less than 35 pg/ml, on day 3 of the cycle, point to a degree of ovarian resistance that is associated with reduced response to fertility drugs. It mandates that the stimulation protocol be individualized and modified and that the dosage and type of fertility drugs used be modified appropriately. Often fertility drugs will be needed, as allowing a natural cycle to evolve is not likely to result in the development of a mature follicle, capable of initiating a pregnancy. The higher the FSH and the lower the Inhibin B levels on Day 3, the more resistant the ovaries are. In such situations, the eggs are likely to be diminished in number, as well as being abnormal (aneuploidic) at higher percentages. Also, in those patients who do go on to have IVF, there are likely to be fewer numbers of follicles available at the time of egg retrieval.
An FSH of >15mIU/ml is indicative of severe ovarian resistance. An elevated FSH level does not necessarily mean that the woman is about to enter menopause (although it can), but rather suggests that she has entered the climacteric, which is the 4-8 year period that precedes the onset of menopause when the woman’s reproductive potential starts declining precipitously. Most women with increased FSH levels continue to have regular periods and may even ovulate, although less frequently and often in a dysfunctional manner on their own, until Menopause. Women with markedly elevated FSH levels (greater than 15mIU/ml), usually do not respond adequately to stimulation with fertility medications and are best treated using donor eggs. This is even more highly indicated when raised FSH levels are detected in a woman over 40 whose egg quality is likely to be reduced.
I frequently get asked by patients if the FSH level fluctuates month to month and whether this means anything with respect to prognosis. What is vital to understand is that a patient is really “only as good as her worst/highest FSH level”. So, in reality, even though the FSH level may fall with interventions such as herbs, this does not always predict what can be anticipated from her treatment. This is why it is important to intervene with IVF sooner than later.
It is important to realize that while FSH/Inhibin B levels are relatively reliable indicators of ovarian vitality and sensitivity to fertility hormones; it is largely the woman’s age that determines her inherent egg quality. Simply stated: While a woman in her 30’s with a raised FSH is likely to have ovarian resistance to fertility drugs, the quality of those eggs she does produce should by and large be good (ie; reflective of her chronologic age). On the other hand, while a woman in her 40’s with normal FSH/Inhibin B levels is likely to produce multiple eggs, their quality is likely to be adversely influenced by her age.
Fertile women in their early 40’s have an expected birth rate of about 2-3% per month and 15-25% per year. This is about 4-5 times lower than for comparable fertile women in their mid-thirties. It is a fact that neither the administration of fertility drugs [with or without intrauterine insemination- (IUI)], nor reproductive pelvic surgery will significantly improve this statistic. Only IVF, through facilitating the delivery of multiple embryos to the uterus, can enhance the birthrate in such women. IVF is accordingly the treatment of choice for infertile women in their early forties, who simply do not have the time to waste on relatively non-efficacious alternatives.
If all else fails, there is always Ovum Donation, which promises outstanding success rates regardless of the woman’s age or FSH level. Ovum Donation pregnancy rates (regardless of the woman’s age) are about 55% (following the transfer of all embryos/blastocysts derived from a single egg retrieval procedure). It is important however, that patients do not feel like they have been “cheated” by not being allowed to at least try a cycle with their own eggs, using aggressive stimulation, with or without estrogen priming. It remains incumbent upon the physician to give honest assessments of the situation and not provide false hope to the patients.