Age and Ovarian Reserve: Predictors of Fertility Treatment Success

One of the biggest challenges in fertility treatment is the age-related decline in female fertility. It has been long recognized that pregnancy rates decline significantly as a function of chronological age. Decreased rates of conception as well as increased rates of miscarriage contribute to the significantly reduced probability of live births in women approaching age forty and older.

In populations where contraception is not used, the average age of the woman at the birth of the last child is only 40-41 in spite of the fact that women tend to have regular menstrual cycles nearly until menopause (average age 51). This decline in pregnancy rate is observed in natural conceptions as well as in advanced therapies such as in vitro fertilization (IVF). Although a decline in fertility is observed as early as age 30, this decline is relatively subtle until the late 30’s, after which fertility declines rapidly such that by age 45, the chance of a healthy childbirth is remote.

The underlying cause of age-related infertility is the increased tendency for the eggs of older women to result in chromosomally abnormal embryos. Abnormalities in the meiotic spindle (the apparatus that moves the chromosomes) may result in abnormal chromosome arrangements even prior to fertilization.

Thus in older reproductive-age women, a significant proportion of embryos (fertilized eggs) are chromosomally abnormal. Due to these abnormalities, these embryos are less likely to implant in the uterus. If they do implant, the pregnancy is more likely to result in miscarriage. Likewise, chromosomal abnormalities such as Down syndrome (trisomy 21) increase with advancing maternal age. These age-related abnormalities can be detected by prenatal testing such as early ultrasound with blood tests, chorionic villus sampling or amniocentesis. Results of IVF treatment with donor eggs provide the most compelling evidence that poor egg quality is the cause of age-related infertility. Pregnancy and miscarriage rates after egg donation correlate with the age of the egg donor, but not the recipient. National outcome data for IVF using the woman’s own eggs versus donated eggs show a steep age-related decline in live birth rate when a woman’s own eggs are used. This age-related decline disappears in donor egg recipients where the average age of the donor is relatively constant.

As a woman ages, there is a progressive loss of eggs and follicles (the structures that contain the eggs) through a process called “atresia”. By menopause, few or no eggs remain in the ovaries. At any given age, the number of eggs remaining (“ovarian reserve”) varies considerably among individual women.

Measures of ovarian reserve are available to assess relative “reproductive age” as opposed to chronological age. Ovarian reserve tests include blood tests such as FSH, estradiol, inhibin B and anti-mullerian hormone, as well as ultrasound assessment of the small follicles within the ovaries (antral follicle count). Women with low ovarian reserve have increased levels of FSH and/or estradiol, decreased levels of inhibin B and ntimullerian hormone, and/or decreased antral follicle count. Increased FSH helps to compensate for a poorly responsive ovary. Therefore, women may continue to have regular (often shorter) menstrual cycles in spite of significant loss of ovarian reserve.

Women with elevated FSH have lower pregnancy rates and do not respond as well to fertility medications, regardless of their age. Elevated FSH is a sign that the ovary is resistant to FSH usually due to lower numbers of eggs available. Consequently,
FSH elevation is a predictor of poor ovarian response to injectable fertility drugs (gonadotropins) with subsequent low numbers of developing follicles, eggs retrieved, and embryos available for transfer.

At Reproductive Partners, blood levels of FSH and estradiol, obtained on day 2 or 3 of the menstrual cycle, have provided the most utilized and reliable tests of ovarian reserve and treatment outcome. The antral follicle count may be a better predictor of ovarian response to gonadotropin stimulation.

Women with elevated FSH have lower success rates with IVF treatment. In fact, women with FSH elevation have traditionally been discouraged from participating in IVF treatment. There is no doubt that women with decreased ovarian reserve have a greater chance of cycle cancellation due to poor ovarian response (inadequate number of follicles for successful egg retrieval), lower numbers of eggs retrieved, and fewer embryos available for transfer. However, young women with decreased ovarian reserve have significantly greater implantation rate per embryo transferred than older women with similar ovarian reserve. In fact, some studies indicate that implantation rates are not significantly different than age-matched women with normal ovarian reserve testing. The conclusion from these studies is that chronological age may be a better predictor of oocyte quality and implantation rates than basal FSH level.

In conclusion, female fertility declines with age, and age is the most important predictor of treatment success. Ovarian reserve testing is an important indicator of response to treatment and pregnancy rates, and it is a recommended component of an infertility evaluation. However, most evidence indicates that FSH levels are more predictive of response to stimulation than of pregnancy rates, particularly in younger (< age 38) women. Caution should be exercised when applying strict FSH cutoffs, particularly for younger women who wish to pursue IVF treatment. It is appropriate to offer these women a trial of in vitro fertilization treatment, provided that they are carefully counseled about overall lower success due to cycle cancellation and fewer embryos from which to select for transfer. At Reproductive Partners we do not have arbitrary FSH cutoff levels above which we will not do IVF.

Arthur L. Wisot, M. D.
Reproductive Partners Medical Group, Inc.
A Southern California Fertility Center

Credits –
This information is provided by Arthur L. Wisot, M.D., F.A.C.O.G., one of the team of outstanding fertility doctors at the Southern California fertility center, Reproductive Partners Medical Group. For more information on IVF and the many available infertility treatments please visit www.reproductivepartners.com.