Success Factors
 

Age and Female Fertility

As we age, many aspects of our body and health change. This includes many subtle but important changes in the reproductive process for women. The impact of age on fertility is becoming an increasingly significant issue as more women choose to delay childbearing until later in life.
The most important factor for all women and their partners to understand is that a woman’s reproductive potential declines with age (fig. 1). When this decline begins, often around age 30, most women do not even realize that it is happening. Even though a woman may continue to have regular menstrual cycles until she reaches menopause, the ability to have children may be lost 7 to 12 years prior to menopause. Nearly one third of couples that include a woman age 35 or older will have problems with fertility. And less than 30% of women over age 40 are able to become pregnant naturally. In addition to increased difficulty with fertility, a woman’s chance of having a miscarriage also increases with age (fig. 2).

fig.1 – For most women, the ability to conceive and carry a baby to term begins to decline at age 30, and declines most rapidly after age 40.

fig. 2 – Women are more likely to have a miscarriage as their age increases.

The main factor associated with infertility in women is egg quality. As women age, their egg quality declines (fig. 3).

fig. 3 – The percentage of eggs with abnormal chromosomes increases as a woman ages.

Understanding Egg Quality
(How do we know the state of your ovaries and eggs?)

The process of declining fertility is universal and increases with age. However, the timing of this phenomenon is variable and may begin to occur in young women. Therefore, even young women need evaluation for decreased ovarian reserve.

Ovarian reserve is the term used to describe the ability of a woman’s ovaries to produce eggs that will ultimately produce a baby. As already discussed, age is an important determinant of ovarian reserve, but ovarian reserve can be severely affected even in younger women. This decline in ovarian reserve can occur due to surgery, smoking, cancer treatments, or simply a woman’s genetic make-up. To assess a woman’s ability to achieve a pregnancy, doctors will conduct an evaluation of her ovarian reserve using tests that measure important components of the reproductive system.

The evaluation process typically begins with a test to measure the naturally-occurring hormones FSH (follicle stimulating hormone), LH (luteinizing hormone) and estradiol. These hormones are measured on cycle day 2, 3, or 4. (Day 1 is defined as the first full day of menstrual flow.) The FSH level is the most important of these three tests. The measurements of LH and estradiol mainly provide a more precise understanding of FSH levels. FSH levels increase as a woman ages. Women with abnormal FSH levels often have difficulty conceiving and if a conception occurs there is an increased chance of a miscarriage (fig. 4).

fig. 4 – IVF delivery rates in women 35-years and under based on FSH levels. Regardless of age, the chance of achieving a pregnancy and delivering a baby decreases as the FSH levels increase.

A more sensitive test used to evaluate ovarian reserve is the Clomiphene Citrate Challenge Test (CCCT). In this test, women are treated with the ovulation induction agent clomiphene citrate (Clomid, Serophene) for five days. Prior to and following treatment, the woman’s FSH and estradiol levels are measured. If FSH levels are abnormal, the chances of conception and a successful pregnancy are poor.

Another specialized test to measure ovarian reserve is the basal follicle count (fig. 5). Early in the menstrual cycle, doctors use ultrasound to count a woman’s small follicles. A low number of follicles indicates a poor response to therapy and a lower chance of conception and pregnancy. Very high numbers of small follicles may indicate a tendency for the woman to over-respond to hormonal stimulation.

fig. 5 – Ultrasound photo of an ovary with few basal antral follicles (left) and an ultrasound photo of an ovary with many basal antral follicles (right). In general, women with fewer antral follicles produce fewer eggs, have fewer embryos, and have lower chances of pregnancy success. (Arrows point to follicles.)

While each of these tests is important, there is no clear measure that applies to all women at every age. These tests should be considered as a part of a larger assessment that incorporates the patient’s age, response to previous treatment, and other factors. A doctor will review many factors in assessing a woman’s health and chances of achieving a pregnancy.

Treatment

There are now many different treatments available for infertility. However, a woman’s options for treatment become more limited as she ages and ovarian function declines. Some problems can be corrected surgically, but these options can delay a woman’s ability to try to achieve a pregnancy for many months or longer. Conservative hormonal therapies (such as clomiphene citrate or gonadotropins combined with intrauterine insemination) can be effective for younger women (usually under age 40), but these options are typically less effective in older women.

First introduced more than 25 years ago, in vitro fertilization (IVF) continues to be the most effective therapy for women who hope to conceive using their own eggs. However, the live birth rate with IVF drops off considerably in women after age 40. Unfortunately, there is no treatment currently available that can restore or improve a woman’s egg quality (ovarian reserve). For that reason, women should be treated with the most effective options as early in their reproductive years as possible to have the very best chance of success (fig. 6).

fig. 6 – Even with the use of advanced forms of infertility treatment, a woman’s chance of achieving a pregnancy using her own eggs continues to decline with age.

Women with abnormal ovarian reserve testing have lower fertility rates regardless of age. In October 2001 the medical journal Fertility and Sterility reported on a study of almost 10,000 women where about 10% had abnormal ovarian reserve on the basis of basal FSH measurement. Among the women with abnormal ovarian reserve measures, only 28 (2.7%) achieved a pregnancy. Of those, 20 resulted in miscarriage. Only 0.7% of women in the study with abnormal ovarian reserve recorded a successful live birth (fig. 7).

fig. 7 – In a recent study, only 0.7% of women with abnormal ovarian reserve reported a successful pregnancy and live birth. Compared to women with normal ovarian reserve (blue), those women with abnormal ovarian reserve (yellow) who became pregnant were much more likely to have a miscarriage.

While pregnancy rates are low for women with abnormal ovarian reserve who try to become pregnant using their own oocytes, these women can consider other options such as oocyte donation. With oocyte donation, a woman with normal ovarian reserve donates her eggs to be used to help a couple achieve a pregnancy. This treatment option can make it possible for women to experience pregnancy and childbirth regardless of her ovarian function. As seen in fig. 8, oocyte donation results have relatively high success rates for women treated during her reproductive years, regardless of age. This again demonstrates the important role that egg quality plays in helping women to achieve a successful pregnancy at any age.

fig. 8 – Women treated with oocyte donation at any age during their reproductive years show consistent and relatively high pregnancy rates.

Aging and Male Fertility

Age also has an impact on male infertility, though the result is not as severe as it is in women. As men age, the number of sperm, the motility of sperm and the percent of normal sperm all decrease slightly. Pregnancy and birth rates decline and miscarriage rates increase when the male partner is older than age 50 (fig. 9). Despite the fact that some men can become fathers up to age 80 or older, couples should consider the effects of aging on both partners when making parenting plans and decisions.

fig 9 – Pregnancy and live birth rates decline and miscarriage rates increase when the male partner is older than age 50.

Conclusion

While there have been many important advances in our ability to treat infertility, the reality is that a woman’s chances of achieving a pregnancy that results in a live birth will decline with age. In addition, there is a great deal of variability in the time that individual women experience this inevitable decline in fertility. For this reason, the evaluation of ovarian reserve is important for all women who have difficulty conceiving. Some treatments can help women to improve their chances of success, but no treatment can stop or reverse the aging process. While oocyte donation is often an effective option, a woman will have her best chances of success when fertility problems are discovered and treated as early as possible.

Any couple that has tried to conceive a baby for a year without success should consult a physician. If a woman is over age 34, she and her partner should consult a fertility expert after trying to conceive for six months. You might begin by discussing your concerns with your gynecologist.

References:
fig. 1: Abstracted from National Bureau of Health Statistics, 2000
fig. 2: Gindoff and Jewelweicz, Fertil Steril 46:989, 1986
fig. 3: Munne S, Cohen J. Hum Reprod Update 4:842, 1998
fig. 4: Scott, RT, et al. Fertil Steril in submission, 2006
fig. 5: Basal antral follicle ultrasounds. RMA photos
fig. 6: RMA pregnancy data. Data on file.
fig. 7: Levi A, et al. Fertil Steril 75:666, 2001
fig. 8: RMA pregnancy data. Data on file
fig. 9: Frattarelli, JL, et al. Fertil Steril in submission, 2007
Navot et al. Lancet 1989; 2:645
Scott et al. Hum Reprod 1995; 10:1706
Chang et al. Fertil Steril 1998; 69:505
Scott et al. Fertil Steril 1989; 51:651
Scott et al. Obstet Gynecol 1993; 82:539