Aging & Infertility

What you've heard about age and fertility is true--as a woman ages, her ability to conceive declines. This gradual decline in fertility starts very subtly in the late 20s to age 35 but then becomes more pronounced as age approaches 40 and older.

In one French study, researchers found that the pregnancy rate over one year for women younger than 31 was 74%. For women between the ages of 31 and 35 the rate declined to 62% and to 54% for women beyond 35 years of age. In another study, 87% of women age 45 and older were no longer able to bear children. But the ticking of the biological clock is not as inexorable as it once seemed. Medicine and technology are developing ways for women to improve their chances of conceiving. This article will try to explain not only why fertility declines with advancing age, but also how assisted reproductive technology can improve a woman's chances of becoming pregnant.

The reasons for the decreased fertility rate with age is multi-fold. Many women, married or unmarried, are waiting longer before attempting pregnancy. As sexually active women grow older, the likelihood that they might be exposed to sexually transmitted infections increases. These infections (such as chlamydia or gonorrhea) can permanently scar the pelvic organs which can hinder a woman's ability to become pregnant. The chance that a woman might experience fertility related complications from endometriosis or adenomyosis (disorders which involve uterine lining cells--endometrial cells--implanting in abnormal locations in the pelvis) increases with age as well.

One of the most important explanations for age-related infertility in women is the declining number of genetically normal available eggs. The peak number of eggs (also known as oocytes) is achieved long before women even consider becoming pregnant: when a female fetus is 4-5 months old, still in the mother's uterus, it possesses up to 6-7 million eggs. By birth, this number drops to 1-2 million and declines even further when, at the start of puberty in normal girls, there are 300,000-500,000 eggs. Several hundred oocytes are lost during the 3-4 decades a woman has regular menstrual cycles through the monthly development and ovulation of an oocyte. Many other oocytes are lost through triggered, natural cell death. When a woman reaches her mid- to late 30s, when she has about 25,000 eggs left in her ovaries, the loss rate of oocytes accelerates. In addition, as a woman ages the ability of her oocytes to divide and distribute the genetic contents normally declines. The likelihood that an oocyte with an abnormal number of chromosomes will be fertilized increases with age.

Older women (particularly over the age of 35) have a gradually increasing risk of pregnancies which are genetically abnormal. Most of these genetically abnormal pregnancies are miscarried in the first or second trimester of pregnancy. Unfortunately, older women (again older than 35 and especially past the age of 40) have a higher risk of miscarrying even genetically normal pregnancies. Several studies have found that for women over 40, the overall risk of miscarrying a pregnancy is about 75%.

Assisted reproductive technology--using "fertility drugs" in conjunction with artificial insemination or in vitro fertilization--may enhance an older woman's ability to conceive. Using injectable (or, in some cases, oral) medications, a woman can increase the number of available oocytes which mature and are then available for fertilization. With artificial or "intrauterine" insemination, a doctor can insert sperm directly into the uterus and time it according to when the oocytes are mature.

Although the overall pregnancy rate achieved with medications and insemination is around 14-17%, the success rate falls to less than 10% for women over 40. With in vitro fertilization (also known as IVF), a woman uses injectable hormones to stimulate her ovaries after which a doctor extracts the mature oocytes using a minimally invasive procedure. In the lab, the extracted oocytes are mixed with sperm or even directly injected with individual sperm.

If embryos develop from this in vitro fertilization process, they are then transferred into the woman's uterus. The pregnancy success rate for IVF can be as high as 50-70% in women in their 20s or early 30s and though the success rate declines with age, some centers achieve success rates over 20% for women in their early 40s.

Unfortunately, not all 40-year-old (or even 30-year-old) women respond to fertility treatments in the same way. By measuring two hormone levels-- estrogen and follicular stimulating hormone (FSH)--on the third day of a woman's menstrual cycle, a doctor can assess the likelihood that a woman may respond to stimulation. Elevated estrogen and/or FSH levels (and the values vary from lab to lab) may indicate a decline in normal, available oocytes. A woman with abnormal day 3 hormone levels possesses a much lower likelihood of responding well to fertility treatments as well as a lower chance of becoming pregnant when compared to a woman of the same age with normal estrogen and FSH levels.

For a woman with persistently elevated FSH levels and/or who has not responded well in past IVF cycles, donor egg is the last option. With donor eggs, a young donor (usually less than 35) is stimulated, her eggs are retrieved, fertilized with the sperm of the infertile woman's partner, and the resultant embryos are placed in the older patient's uterus. Even women in their late 40s or 50s can attain a pregnancy success rate of greater than 40-50% with donated eggs.

The one caveat is that all these scientific explanations of aging and fertility are not absolute. There are anecdotal accounts of women in their 40s having failed multiple IVF cycles who then become pregnant without assistance. Turning 40 does not mean a woman can no longer bear children, only that she might need medical assistance (and possibly someone else's eggs) along the way.