What does my age have to do with infertility?
Women often ask “what is so important about my age? I don’t feel old, I take good care of myself, I exercise, I eat well and my aunt had a baby at age 45”. These sentiments are shared by many women who become increasingly frustrated by their infertility.
The idea that one can become pregnant at will or at any age is driven by popular media and magazine stories about high profile women conceiving until menopause, failing to mention that many of them conceived using
donor egg IVF procedures.
I know I am ovulating, so why am I having a problem conceiving?
Let us review what happens to your eggs as you get older:
Keep in mind that women have a finite number of eggs which are formed during fetal life and kept in storage in the ovaries. Ovulation only releases the eggs which were already produced in fetal life and remain in storage within the ovary for use throughout the reproductive years. Unlike the testes which continuously produce new sperm, the ovaries, lack a similar mechanism for making new eggs.
Here are some important points to keep in mind:
- A female fetus at 20 weeks gestation has about 6 million eggs in her ovaries and at birth the number of eggs declines to about 1 million.
- The decline in the number of eggs as you get older is caused by a pre-programmed process of cell death called atresia, and by puberty approximately 300,000 eggs remain.
- By age 37, the ovarian reserve is down to about 25,000 eggs, accounting for the accelerated decrease in fertility seen in older women.
- These numbers are astounding given that a woman ovulates only about 400 times during her reproductive years (12 ovulations per year x 40 years).
- A woman at age 50 has about 1000 eggs in her ovaries and may continue to ovulate into her fifties but few if any, will experience a successful pregnancy at that age.
- Fertility in women starts to decline at about age 27, and drops off more rapidly after age 35, reflecting
primarily a decrease in egg quality and quantity.
- This age-linked decrease in egg quality is the reason for the increased risk of miscarriages and chromosomal abnormalities (such as Down’s syndrome) experienced by older women. So, while only 10% of women under the age of 33 who conceived with
In Vitro Fertilization (IVF) experience a miscarriage, 30-40% of women over age 40 and 65% aged 43-44 experience fetal loss.
- Another factor contributing to the age-related decline in fertility is the increased risk for gynecologic disorders, such as
endometriosis,
pelvic infections or uterine
fibroids, which impair fertility. So, if you are over 40, you should seek evaluation and treatment without delay.
How does age affect IVF success rate?
Age is the most important factor affecting
IVF success rates. For women under 35, pregnancy rates are about 30% per cycle plummeting to approximately 5% by age of 43.
For women over 40 undergoing IVF at BocaFertility, most of the successful pregnancies occur between the ages of 40 and 42. A significant drop in live birth rate is noted in women over the age of 43 with no births occurring beyond age 45.
Whereas in women younger than age 35 only 1-2 good quality embryos are transferred, women over age of 40 should be encouraged to have all of their embryos transferred in the hope of achieving pregnancy, keeping in mind that twins occur in only 15% of pregnancies at age 40 and beyond, and that their chance of having triplets or more is miniscule.
At BocaFertility our own cumulative live birth rates between 2001 and 2009 demonstrates a similar pattern: |
Can Preimplantation Genetic Diagnosis (PGD) help?
While it appears to make sense to screen all the embryos for genetic abnormalities and transfer only healthy ones into the uterus, to date, the procedure has not been shown to be particularly helpful for older patients or in those with repeated IVF failures. In fact, embryos may be damaged during the biopsy procedure and may not be suitable for transfer while other embryos may be misread as being abnormal. The end result is that fewer embryos are available for transfer and the pregnancy rate for women over 40 undergoing IVF and preimplantation genetic diagnosis is significantly lower than those who do not have PGD.
What can be done to evaluate if my eggs are any good?
While age alone is currently the most reliable indicator of egg number and quality, several tests are available to evaluate the woman’s ability to produce good quality eggs capable of fertilization. Most tests are typically performed on day 3 of the menstrual cycle:
- Follicle Stimulating Hormone (FSH) level – FSH is an important hormone that regulates the development of your eggs. In general, if you are under age 40, a low FSH level is reassuring, and indicates that you probably have good quality eggs. A high level of FSH level suggests that there is a reduction in both the number and quality of eggs remaining in your ovaries (Diminished Ovarian Reserve – DOR). The most reliable indicator of egg quality, however, is your age. So if you are 44 years old and you have a normal FSH level, you can not assume that the quality of your eggs is good. In fact, your chance of conceiving with IVF is only 2%. Likewise, young women with high FSH may have fewer eggs remaining but their egg quality may still be good yielding satisfactory IVF pregnancy rates. High FSH levels are typically seen in older women, and in women with history of ovarian surgery, chemotherapy, radiation and/or endometriosis. Generally speaking FSH levels below 10miu/ml are reassuring, while FSH levels in the 12-15miu/ml range indicate lower egg quality and poorer IVF success rates. Women with FSH levels over 20miu/ml rarely benefit from treatment utilizing their own eggs and they should be encouraged to consider donor egg IVF or adoption.
- Estradiol (E2) level – High estrogen level on day 3 of cycle is indicative of Diminished Ovarian Reserve (DOR) even if the FSH level is completely normal. So it is very important to measure both day 3 FSH and estrogen (E2) levels since an elevation in one or both tests may be equally predictive of decreased egg number and lower egg quality. Ideally, day 3 estrogen levels should be less than 50pg/ml. Day 3 estrogen levels greater than 100pg/ml is considered abnormal.
- Clomiphene Citrate Challenge Test (CCCT) – this test is used to detect poor ovarian reserve in women whose day 3 FSH level is still normal. The test is performed as follows:
- Day 3 of cycle – blood test to measure FSH and estradiol levels.
- Clomiphene (100 mg) is given on days 5-9 of the cycle.
- FSH level is repeated on day 10 of the cycle.
The test is considered abnormal if the FSH level on either day 3 or day 10 is greater than 12. The test is also considered abnormal if the day 3 estradiol level is greater than 100. The test has not been universally accepted because the CCT appears to have no significant advantage over a simple cycle day 3 FSH level when evaluating the ovarian reserve. - Antral Follicle Count (AFC) – This is an ultrasound examination performed between days 2-4 of the menstrual cycle to determine the number of antral follicles (immature eggs smaller than 10mm) present within the ovary. Low numbers of antral follicles (less than 4) is suggestive of DOR (Diminished Ovarian Reserve) and may correlate with poorer IVF outcome.
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- Inhibin-B level - This hormone level measured on day 3 of the cycle decreases in women with poor ovarian reserve. Several studies suggested that low day 3 serum inhibin-B may be predictive of a poorer response to ovulation induction as compared with women with a high day 3 inhibin-B. Many centers, however, do not order this test because abnormal values have not been clearly established.
- Antimullerian Hormone (AMH) level - Studies have demonstrated a gradual decrease in AMH levels as a woman gets older. This decline has been attributed to a decreasing number of eggs within the ovary. A low level of AMH suggests that the ovary may be depleted of eggs, and is predictive of low egg production (poor response) during In Vitro Fertilization (IVF).
What are my treatment options?
If you are between 40-41 years old with a normal day 3 FSH and Estrogen level and you have satisfactory antral follicle count, and there is no
male factor,
tubal factor or
endometriosis,
IVF is your best bet, but you may also consider 1 or 2 cycles of
gonadotropin injection treatment if you are not ready yet to proceed with
IVF. If your FSH level is in the high normal range, you have a tubal factor or
endometriosis, or if your partner has a low sperm count,
IVF should be considered without delay.
When should I consider donor egg IVF?
When making a decision between IVF with one’s own eggs or donor eggs, a woman must take into consideration whether or not it is worthwhile to spend about $15,000 at age 44 for a 2-3% chance of a successful pregnancy when live birth rates with donor egg IVF exceed 50%.
Donor egg
IVF, adoption or surrogacy is advised if:
- You have ovarian failure (premature menopause, surgery, radiation or chemotherapy).
- You are age 44 or older.
- Your ovaries are no longer producing good quality eggs.
- You have a high FSH level, abnormally low Anti Müllerian Hormone (AMH) level or low antral follicle count.
- You have experienced repeated unsuccessful IVF cycles.
- You are a carrier for a serious genetic disease and you want to lower the risk of transmitting the disease to your child.
What is the success rate with donor egg IVF?
Our cumulative pregnancy rate regardless of the recipient age is 75% per transfer and 65% live birth rate per transfer. |