Age and Infertility

I'm a 39-year-old woman with 4 children. My husband and I are thinking about having another baby and -- because I had my tubes tied -- we're considering in vitro fertilization (IVF). Since our insurance won't cover the procedure, we can probably only afford one round of treatment. What are the odds that one IVF will prove successful for a woman of my age?

When it comes to the likelihood of successful tubal reversal and in vitro fertilization, the odds are against women your age and older. Fertility drops after age 35 (especially after 38), and delivery rates per IVF cycle started are only about 15% as the 40th birthday nears. This rate is similar to the live birth rate following tubal reversal for a woman of your age.

Check out IVF success rates per age at EmBIO

Before undergoing any treatment for infertility, you should consider a couple of tests to measure your fertility potential. One is called a clomiphene challenge test; the other is a day 3 FSH blood level test. If these test results come back abnormal, the likelihood of successful fertility treatment with your own eggs is even less than noted above. At our center, more than just age determines "success" with IVF, and each couple should undergo a thorough assessment to offer a complete understanding of prognosis and likely outcome.

Can you explain why it is harder for a woman to get pregnant as she gets older? Is an older egg simply harder to fertilize, but would develop normally if fertilized? Or are the eggs not harder to fertilize, but more likely to develop abnormally and so fail to implant? In other words, is the mechanism that explains higher birth defects with age the same as that which explains lower fertility?

This is an interesting question and addresses an area where much research is being carried out. The adverse effect of age does not appear to be mediated by a decrease in "fertilizability," but rather seems related to abnormal chromosomes in the egg.

Let's go back to review how the egg forms. All human cells other than sperm and egg normally have 46 chromosomes. The egg and sperm each contribute 23 chromosomes to the developing fetus. This means that as the egg and sperm are formed, the number of chromosomes needs to be reduced to 23. This process of chromosome reduction is called meiosis.

In men, the process is ongoing, and new sperm are continually being produced. In the woman, the situation is a bit different. Before her birth, while she is still an embryo, the number of her eggs increases up to about 4-7 million. After about 20 weeks of gestation, her fetal body stops producing new eggs. These eggs must also undergo the process of meiosis to reduce from 46 to 23 chromosomes. But at 20 weeks, the eggs are surrounded by an envelope of cumulus cells; this arrests the meiotic process and keeps the eggs healthy until they're needed for ovulation. An egg resumes its growth about three months before ovulation. In fact, meiosis is not actually completed until after ovulation and fertilization have occurred.

We know that older women ovulate eggs that are more likely to contain chromosomal abnormalities, such as extra or missing chromosomes. What we don't know is when this anomaly occurs. Does it occur while the eggs are dormant, in a state of suspended animation awaiting their chance to grow and ovulate? Or does it occur after hormonal signals involved in ovulation stimulate the egg to resume meiosis?

Researchers have hypothesized that perhaps the cumulus cells surrounding the egg lose their ability over time to maintain healthy eggs. Some believe that chemical abnormalities within the cell are responsible for errors in chromosomal reduction (meiosis), and that transfer of cellular material from a younger woman may resuscitate the egg. While initial studies have shown that this cytoplasmic transfer can be carried out and the egg can be fertilized and develop normally, the question of whether this corrects age-related defects has not been answered. Hopefully, we will have answers in the next two or three years.

I will be 35 in June. I am overweight but active, and I have regular cycles. My husband is 36, and we have two healthy sons, ages four and seven. We would love to have another child soon. What are the odds of our having a child with birth defects because of my age? Does it make any difference that I did not start my periods until I was 16.5 years old? Do two previous healthy uneventful pregnancies lower the chances of birth defects or chromosomal problems? I have searched the web endlessly and have not found answers to these specific questions.

One chief concern of pregnancy after age 35 is the increased risk of chromosomal abnormalities. Age-related chromosomal abnormalities such as Downs Syndrome occur in only about 1 in 200 pregnancies (about one-half of a percent) for women aged 35, so this is not a great concern for you at this time. However, for women age 40 at the time of pregnancy, the risk rises to about 1-2 percent.

Age-related chromosomal problems typically originate at the time of meiosis, when the egg cell eliminates half of its 46 chromosomes to accommodate the male's genetic contribution. The chromosomes are separated by tiny filaments called spindles, which appear to become brittle and break or become detached from the chromosomes as women age. This breakage or detachment can result in an abnormal number of chromosomes in the egg, a condition called aneuploidy. This occurs in about 33 percent of eggs at age 35 and 50 percent of eggs at age 40. Luckily, few of these irregular eggs will fertilize or develop into detectable pregnancies. As such, the risk of a genetically abnormal pregnancy is much lower than the risk of an abnormal egg.

As you age, your risk also rises for nonchromosomal birth defects and pregnancy complications such as gestational diabetes, pre-eclampsia, and intrauterine growth retardation. At age 35, however, your age plays little role in any of these complications. The age at which you began menstruating (menarche) does not seem to influence this risk, nor does your prior history of a normal pregnancy.

I'm sure you are well aware that there is a significant decrease in fertility as a woman ages, and that now we have testing available to evaluate your fertility potential.