Age and Infertility, Ovarian Reserve
Increasing female age is perhaps the greatest enemy of fertility. “Reproductive life” begins with the first menstruation and culminates in the menopause where few, if any, viable eggs remain. Many women delay childbearing until they are older and have established their careers. The age at which females are marring has also increased. Unfortunately, the societal clock and biological clock are not always in “sync”. These delays in childbearing are partially responsible for the increased incidence of infertility related to age.
Infertility in “younger women” is defined by the American Society for Reproductive Medicine as the inability to achieve pregnancy after one year of regular, unprotected intercourse. In women aged 35 or older, the time is often shortened to six months. Women in their mid-late thirties should not delay seeing a reproductive endocrinologist/ fertility specialist as fertility can decline very rapidly.
A woman is born with more than enough eggs for her reproductive lifetime. In a normally ovulating female each month one, or more, of these eggs are recruited and develop under the influence of FSH. Usually they more sensitive eggs (to FSH)) are recruited first. Several hundred more start to undergo maturation and then become atretic and “die off” each month. As females age, egg quality declines.
Women differ in the number of eggs that become atretic each month, thus some women use up their egg supply faster than others. As a female ages, the less sensitive eggs remain and require more FSH stimulation in order to undergo final maturation.
The pituitary gland at the base of the brain tries to compensate for this decreased egg sensitivity by increasing the FSH levels. High FSH levels suggest decreased ovarian egg sensitivity and indirectly suggest decreased egg quality.
While female age is directly related to infertility; unfortunately, some women experience menopause at an early age, a condition known as premature ovarian failure. When the ovaries are releasing eggs that have diminished capability to fertilize and develop normally, the condition is termed “diminished ovarian reserve.” The ovaries, and therefore the eggs within them, can also be damaged by cancer, cancer chemotherapy, radiation, severe pelvic infections, or rarely women are born without one or both ovaries.
One measure of ovarian reserve is the level of FSH measured on day 3 of the menstrual cycle. An elevated level (>10) may be an indication of diminished ovarian reserve. The Clomiphene Citrate Challenge Test (CCCT) is administered to women at risk for elevated FSH levels to help “predict” their chances of success with IVF. An abnormal CCCT test (FSH >12) means there is a poor prognosis for IVF success. FSH levels >20 predict almost a 0% chance for conception using the woman’s own eggs.
Different laboratories use various methods for measuring FSH so it is important to use a laboratory that your infertility specialist is familiar with. Reproductive Care Center uses a TOSOH hormone assay machine and has correlated the information with results from Immunolite machines (used in some other large labs in Utah).
Around 2004 another fertility test was shown to be useful for evaluating ovarian reserve. Anti-mullerian hormone (AMH) or müllerian inhibiting substance (MIS) is a blood test that can be obtained at any time during the menstrual cycle. It can also be tested while a woman is taking oral contraceptives. As female age increases and ovarian reserve decreases so does the AMH/MIS result, while FSH usually rises. It is a useful adjunctive test when the FSH results are confusing or inconsistent.
This is a test that is usually done in a regional laboratory that specializes in infertility testing. Results between 0.7 and 5.0 are usually considered to be in the normal range. Levels less than 0.7 suggest decreasing ovarian reserve. Ideally we like to see the AMH levels above 1.2 for better ovarian stimulation results. Levels above 5.0 can be indicative of polycystic ovarian syndrome.
We believe that the best single test for ovarian reserve from a single blood test is the Ovarian Assessment Report (OAR). This test is done by performing a pelvic ultrasound on day 3 (2-4) of the menstrual cycle to make sure that there are no large cysts and to determine ovarian volume and antral follicle counts.
Blood is drawn and sent to ReproSource in Boston, MA for comprehensive testing that includes Age, Follicle stimulating hormone (FSH), Estradiol (E2), Luteinizing hormone (LH), Antimüllerian hormone (AMH) and Inhibin B.
As a female ages, and egg quality (and quantity) goes down, the FSH level increases and AMH and Inhibin B goes down. Each individual score is reported and an egg retrieval score is calculated using a linear regression model developed in conjunction with the Boston IVF Fertility program. The egg retrieval score gives a good estimate of the number of eggs that might be retrieved using an optimal conventional IVF stimulation protocol.
The egg score usually ranges between 1 and 20. Patients scores are also placed in a category – Excellent (16-20), Good (11-15), Fair (6-10) and Reduced (<6). This test is very helpful in predicting and categorizing a woman’s “egg quality”. The result is very helpful in designing custom egg stimulation protocols for IVF and for helping to predict pregnancy rates from various therapies. The cost for this test for self pay (prepaid) patients is less than $150 (June 2012). We recommend this test routinely as part of the initial infertility evaluation or at the time of IVF, if not done previously.
Prior to IVF, women with ovarian disease (severely decreased ovarian reserve) had no treatment options. With today’s technologies, pregnancy can often be achieved in older females using an egg donor.
Egg donors are young with healthy eggs and are carefully screened using many physiologic and psychological tests. If a donor’s eggs are used in an IVF cycle with the husband’s sperm, the success rates usually coincide with the donor’s age, and are typically high (>50% delivered pregnancy rate if 2 good embryos are transferred). In fact, successful pregnancies using donor eggs have been achieved in women in their fifties. The offspring will have the genetic makeup of the father and the egg donor.
There are new technologies currently available at RCC that allow young women to reliably freeze their eggs for use in future IVF cycles when they are older. If a woman underwent FSH ovulation induction, she could produce many eggs that could be cryopreserved for future thawing, fertilization and subsequent embryo transfer when she is older.
Over 3000 pregnancies have been delivered using frozen/thawed eggs. If a patient needs to undergo chemotherapy or radiation therapy egg freezing should be considered. Egg freezing can also be performed for social indications (desire to preserve fertility and not currently married or married and not currently desiring pregnancy).