This topic regularly comes up between old friends at lunch, over Starbucks with new friends, and certainly with our mothers: the dreaded biological clock. We are sure it is ticking, but the truth is few of us truly understand how fast, or how loud that little bugger is going.
The first thing to understand is that all women are in the same boat because our eggs age much faster than other cells in our body. (The guys get off easy as sperm cells can be viable well into their 70’s and 80’s.) As we get older both the quality and quantity of eggs diminish. What is not often understood, is that this loss of quality and quantity starts well before any test would reveal anything and before an average woman would see any physical changes.
When ovaries are first formed there are 5-7 million eggs. Sounds like that is more than enough, right? But by 37 years old that number has dropped to 25,000 and by menopause at around 50-years-old, there are less than 1,000 eggs remaining. Eggs age and die at different rates in each female and is unrelated to pregnancies, birth control, or when your period started.
Declining egg quality is mostly about chromosomes. As eggs age there is an increased number of eggs with abnormal number of chromosomes which result in “aneuploid” embryos which also have the wrong number. Usually these embryos will not implant to become a pregnancy or, if they do, result in miscarriage. This is common. In fact, by age 45, close to 100 percent of embryos are aneuploid. Quantity and quality issues often translate into infertility. It doesn’t happen over night but the ticking of the biological clock is very real.
The probability of achieving a pregnancy in one menstrual cycle begins to decline significantly in the early 30s (about age 32 years), with a more rapid decline a few years later (about age 37). Infertility increases significantly after age 35. In various studies, 87-99% of women are infertile by age 45. In addition, pregnancies are more likely to end in miscarriage as women age, which is a reflection of decreased quality of eggs and resulting embryos.
HOW FAST AM I LOSING EGGS?
The rate of “ticking” of each woman’s clock may be determined by a number of factors, both genetic and environmental.
Genetic factors may be the most important determinant of how many eggs a woman starts with and how fast they are lost. A family history of menopause puts a woman at risk of early menopause and likely a more rapid loss of eggs. Certain races or ethnicities are associated with earlier or later menopause—Hispanic women have earlier menopause than Caucasian women, and Japanese American women have later menopause.
There are some clearly recognized environmental factors and there may be more that we don’t recognize. We know that certain types of chemotherapy for cancer will accelerate the loss of eggs. Cigarette smoking, usually more than 10 cigarettes/day, has been associated with both infertility and with early menopause. Smoking causes premature depletion of the pool of egg cells. In addition to being associated with infertility, cigarette smoking is associated with a lower chance to conceive via IVF. Surgeries that involve the ovaries can affect their blood supply and result in a greater loss of eggs. This is one of the reasons why women who have had surgeries for endometriosis can be infertile. And other environmental pollutants may be responsible for making the biological clock tick faster: dry cleaning solvents, pesticides, certain heavy metals, even BPA in plastic water bottles.
There are ways to test your egg supply and how it might compare to that of other women your age, but none of these tests are perfect.
The most commonly used hormone measurements are FSH and AMH. An “antral follicle count” done by pelvic ultrasound can also test your egg supply.
Day 3 FSH: Follicle-stimulating hormone (FSH) is a hormone produced by the pituitary gland that gradually increases as a woman’s reproductive system ages. Thus, FSH levels on day 3 of the menstrual cycle can been used as a marker of a woman’s egg supply or “ovarian reserve.” An estradiol level should be low when the FSH is measured in order to validate the test, because early follicle development and a high estradiol will suppress FSH levels into an apparently normal range.
AMH: Antimullerian hormone is a hormone produced by the cells that surround immature eggs. Its measurement in blood has been shown to decline with age and to help predict the number of eggs that can be retrieved with stimulation, like is done in an IVF cycle. It is a relatively new test and has not yet been shown to predict spontaneous pregnancy or future fertility.
Antral follicle count: Immature eggs that are being recruited for a given menstrual cycle have a small sac of fluid around them that can be seen on ultrasound. These antral follicles can be counted, and low numbers suggest a diminished egg supply.
WHAT IS NORMAL?
Ovarian reserve is usually considered normal when at least 8-10 eggs can be matured and retrieved in a single in vitro fertilization cycle. When tests of ovarian reserve are normal, this goal can generally be achieved. When ovarian reserve is diminished, an IVF cycle may yield fewer eggs than is considered ideal. We are not certain that low ovarian reserve always translates into infertility. There may be many women with tests showing “diminished ovarian reserve” that have had no trouble getting pregnant and are never seen in a fertility clinic.
Still, tests that indicate diminished ovarian reserve suggest that significant reproductive aging has occurred already.
Typically, a day 3 FSH of more than 10 mIU/ml, AMH of <1.0, or an antral follicle count less than 6, suggest a low egg supply or “diminished ovarian reserve.” Because hormone assays are not all the same, these numbers may vary between laboratories or fertility centers.
In addition, some tests of ovarian reserve could be good and others poor. It is possible that egg quantity is lost, but quality may not be lost as quickly, as in a younger women with low AMH, but a high percent of normal good quality eggs.
SLOWING THE CLOCK
That clock is ticking but you can take some steps to slow, or quiet, the ticking. For example, avoiding toxins that could possibly accelerate the death of eggs: cigarette smoking, bisphenol-A in plastics and perhaps all plastics. But if testing suggests that your reproductive age is advancing quickly you should consider taking action. Consult a specialist in fertility to help you interpret the tests in the context of your age, history and family plans. You can also consider freezing your eggs if you are not yet positioned to start a family.
There is never a perfect time to start a family, but carefully consider your plans so that you can optimize your chances to realize your life goals. This clock thing isn’t fair, but it is very real. The key is education so women of all ages can be informed about their fertility so that family planning has as few surprises as possible.