There are few things in life that are certain: death, taxes and the decline in female fertility with advancing age. The age at which a woman undergoes menopause, 51, remains constant across all ethnicities and cultures. Women experience peak fertility at age 22 and fertility starts to decline before age 30. There is a second sharp decline in fertility around age 35 and again after 40.
The testes contain stem cells that produce sperm continuously from puberty to the end of life. The ovaries, however, do not have stem cells and contain a fixed number of eggs that form during fetal development and decline from birth until menopause. As women age, both the quantity and quality of eggs decreases.
During a menstrual cycle a single egg is recruited and ovulated from the available pool of eggs in the ovary. This egg grows within a follicle and eventually is released after the brain produces a surge of luteinizing hormone, the LH surge. Though only one egg is ovulated, an entire group of eggs is lost each month. Fertility drugs work by increasing the number of follicles that can grow and develop in a month and therefore increase the number of eggs that can be released. A younger woman generally will be able to produce many more eggs in a single stimulated cycle than an older woman. Women lose eggs every month even when on birth control pills and when pregnant. The only way to prevent the loss of eggs is to harvest those eggs, remove them from the body and store them for the future.
What is ovarian reserve screening?
Ovarian reserve is the functional capacity of the ovary. It aims to measure both the number of eggs that can be harvested in a single month as well as measure the overall egg supply within the ovary. There are four different tests that are often performed in concert with each other:
Antral follicle count: A measure of the number of resting follicles the ovary contains each month. The antral follicle count (AFC) is one of the most important tools that can be used to predict how many eggs can be retrieved in a single month with the use of fertility drugs.
Anti-Mullerian hormone: A hormone produced by the cells that surround the egg in the (granulosa cells) ovarian follicles, this is one of the most sensitive predictors of overall egg supply within the ovary. AMH does NOT test egg quality. There is no available test to measure egg quality, just quantity. AMH number peaks at age 18 and declines throughout the reproductive life span, becoming undetectable several years prior to the onset of menopause.
Follicle stimulating hormone (FSH): A hormone released from the brain in order to stimulate the ovary to ovulate. After ovulation, the remaining egg supply in the ovary send a signal back to the brain to prevent premature release of FSH. A high FSH level in the beginning of the menstrual cycle is a sign of low egg supply.
Day 3 estradiol level (aka "estrogen"): Estradiol suppresses the release of FSH. It must also be checked at the time FSH is checked to ensure that FSH is not falsely low due to suppression.
It is critical to understand that there is no test that can distinguish between a fertile and an infertile female. Infertility is a clinical diagnosis. It can only be made after one year of trying to conceive without success prior to age 35 or 6 months after age 35. Ovarian reserve screening is an indicator of egg quantity but cannot be used to predict infertility nor can it predict the time it would take to achieve pregnancy. AMH is a sensitive marker of the size of the remaining pool of eggs in the ovary and may be used to help in counseling on who should freeze eggs and when. A low AMH in someone who has never tried to conceive does not indicate infertility.
The below table is data collected from more than 17,000 ART cycles in the United States and has information on age- related normative values for AMH. This data can be used to assess AMH relative to the average levels by age. It can help to determine who may have a lower egg supply but this information needs to be used with great caution. There is no long-term data available yet to fully understand the implications of low AMH in young women without infertility.
As women have sought education and career opportunities, the mean age of women at first childbirth is increasing. With the competing interests of education, career and peak fertility, innovation and technology has intersected with medical science in attempts to freeze the biological clock. The closest one can come to freezing fertility potential is through oocyte vitrification or “egg freezing.”
In order to pursue egg freezing, a woman must take hormone injections to stimulate the ovaries to produce multiple eggs and allow these eggs to undergo maturation. The eggs are then removed from the ovaries during a minor procedure called an egg retrieval which is done under sedation. The number of eggs that can be removed depends on the woman’s age and her ovarian reserve. Younger women are able to produce more eggs than older women. The below table shows the average number of eggs retrieved by age.
The high risk of undergoing an unnecessary procedure must be carefully weighed against the potential to have age-related infertility. Egg freezing is often seen as an insurance policy. It cannot be understated, however, that this is far from a perfect policy. The success of egg freezing when one returns to use the eggs is, at best, equivalent to IVF success at the age when the eggs were originally frozen. In good-prognosis patients, IVF success rates hover around 50% per cycle (table below). The number of eggs needed to achieve a live birth has not been definitely determined, but has been estimated to be between 15-30 depending on the woman’s age. Given that the average number of eggs a woman produces in a single attempt at egg freezing ranges between 4-15, multiple rounds of ovarian stimulation are needed to increase the likelihood of success beyond 50%.
One of the most common questions asked by patients who have frozen eggs is how best to utilize the frozen eggs to optimize the likelihood of success. One study showed through mathematical modeling that the highest chance of having a live birth is by undergoing IVF with fresh eggs prior to the age of 40. If IVF attempts are unsuccessful, only then would one use her frozen eggs. This option was the costliest, but the most successful. This was contrasted with two other scenarios: never having frozen eggs (least expensive, least successful option) or having frozen eggs and using those as first line therapy (moderate cost, moderate success). In general, it is best to pursue IVF with fresh eggs prior to the age of 40 and use frozen eggs as first line after the age of 40.