HOW OLD IS TOO OLD?
The suggestion made is based upon the condition as it applies to “middle-age women”. Does going straight to IVF make sense as women age? Understanding the reason age affects fertility helps explain the suggestion of moving quickly to IVF. To conceive, three things have to work: sperm, a woman’s anatomy (uterus) and her eggs (oocytes). There have been recent suggestions that age can affect a man’s ability to have a child. While this may be true, the effect of age on a man’s ability to have a child is far less than the effect on women.
Is it just the eggs that are affected by aging? How about the uterus? This is challenged by the use of donor oocytes in women over the age of 45, demonstrating that the uterus remains highly functional as women age, some so far as carrying a child in their early 60’s. Yet, a woman’s monthly chance of conceiving begins to decline early in her life. One well done study demonstrated that at age 31, 50% of women begin o experience a decline in their monthly chance of having a child. By age 41, 50% of women will never conceive a child that is genetically theirs. By age 45, very few women retain the ability to conceive using their own eggs. While the media has sensationalized some Hollywood actresses’ pregnancy when they in their late 40s, the same articles do not mention, or do not realize, how frequently these pregnancies result from the use of donor eggs.
LOOKING AT REPRODUCTIVE AGING FROM THE INSIDE OUT
So how does age reduce a woman’s chance of having a child? Two physiologic factors explain this. The first involves Quantity. This decline in the quantity of a woman’s eggs starts as life begins. By the time a woman is born, her egg supply has been reduced from 6-7 million eggs to 2-3 million. By the time menstruation begins, that number has gone down to 300,000 to 400,000 eggs. Each month, during a woman’s early years (of menstruating), 1000 eggs will develop, from which the ovary will release only one, the remainder of which will die off. When a woman reaches menopause, usually in her early 50’s, her egg supply has been virtually depleted. Why then does a 38 year old woman, with as many as 50,000 eggs left, have a reduced chance of conceiving?
The answer lies in the second physiological factor, Quality. Simply put, as a woman ages, more of her eggs are damaged. This damage may be due to the fact the ovary may chose the best eggs first, at an earlier age, and thus only those eggs the ovary did not select remain as a woman ages. Or the environmental effects upon the eggs may causes damage just like any aging cell. For example, smoking accelerates the aging process for women. Either way, as women age, more of the remaining eggs are physically damaged. Clinically this is seen as an increase in the risk of have a child with Down syndrome as women age. It is also seen clinically in the fact that as women age, the chance of having a miscarriage increases. The majority of age-related miscarriages are due to pregnancies that have the wrong number of chromosomes.
DOES IVF ‘REDUCE’ AGING?
IVF is a process whereby women are treated with the hormone FSH, so that they develop a number of eggs. These are then removed, fertilized and then allowed to develop for 3 to 5 days. These embryos are then placed in the uterus. Other forms of treatment for women include a medication taken by mouth called clomiphene citrate (Clomid) or using FSH in combination with an Intrauterine Insemination (IUI). While these many be useful measures for other causes of Infertility, many studies have demonstrated that Clomid is not useful for woman over 40 and may actually decrease their chances of success. FSH with IUI has a very low chance of success of any given cycle, and thus when considering cost and time, is not as successful as IVF. So based upon success rate per try, IVF is better than the alternatives.
Even more compelling are recent advances in technology that allow for testing the embryo for the correct number of chromosomes before transferring it to the woman’s uterus. This has two advantages. First only embryos with the correct number of chromosomes can be transferred. When this is done, the pregnancy rates are very high. Since the effect of age is on the ability of an egg to create an embryo with the correct number of chromosomes, knowing an embryo has the correct number of chromosome removes the age- related effect upon the chance for a pregnancy.
A second benefit of utilizing IVF and embryo testing is to help identify woman who never, or almost never, produce embryos with the correct number of chromosomes. This is tragic news but it is valuable information in trying to decide what to do next. For women who almost always produce embryos with the wrong number of chromosomes, they probably have no increased chance of conception using IVF than if they just try on their own, as long as there are sperm and the anatomy is normal. Knowing this, a person can choose to spend their efforts and money on alternatives such as no treatment, donor oocytes, or adoption and avoid unnecessary treatment.
THE (BABY) BOTTOM LINE OF IVF AND AGING
The major problem now with screening embryos for chromosome number is cost, since this is a new technology and is still expensive. However, if IVF is evaluated on a cost- per- baby basis (a concept most patients and physicians find seamy). IVF using chromosome screening may turn out to be highly cost effective. Patients may find it useful to discuss this with their physicians and see if it is the correct path for their particular situation.
The bottom line is that age has a devastating effect on fertility for women. We know that women with normal fertility, whether they are young or in their late thirties or early forties, will conceive quickly. A 38 year old female who is trying to get pregnant should be able to do so within the first 6 months of trying. If that is not happening then it is appropriate to do an infertility investigation to determine if age is the cause. If so, aggressive treatment, such as doing IVF, may afford that woman a chance to have a child that is genetically hers. Waiting can remove that chance.