June 16, 2010 -- Fertility experts Dr. Zev Rosenwaks and Dr. Marc Goldstein of NewYork-Presbyterian Hospital/Weill Cornell Medical Center offer advice to men and women confronting infertility in their new book "A Baby at Last! The Couple's Complete Guide to Getting Pregnant--from cutting-edge treatments to common sense wisdom."
Rosenwaks is the director of the Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine at NewYork-Presbyterian Hospital/Weill Cornell Medical. Goldstein is the director ofthe Center for Male Reproductive Medicine and Microsurgery at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.
Read an excerpt of the book below, and then head to the "GMA" Library to find more good reads.
You Are Not Alone: When to Seek Help
Claire, a thirty-seven-year-old designer, had tried unsuccessfully to have a baby for a year and a half before she went to see her gynecologist. Her doctor found she had an incompetent cervix, which he corrected surgically. Six months later, her husband, Jeff, a thirty-eight-year-old salesman, went to a urologist, who found Jeff had a very low sperm count and a cyst on one testicle. Claire did some research on the Internet into hospitals and doctors. An oncologist friend suggested they go to Weill Cornell, where a radiologist told them that Jeff's cyst was benign, but Dr. Goldstein found that Jeff had varicoceles (varicose veins in the scrotum) affecting both testicles. Microsurgery repaired the varicoceles, but Jeff's sperm count remained very low, so they decided to try an in vitro fertilization (IVF) procedure with Dr. Rosenwaks.
For the first IVF attempt, three of Claire's eggs were fertilized with Jeff's sperm and transferred into her uterus, but none progressed to a pregnancy. A few months later, Jeff had better-quality sperm surgically removed from his testicles, and those sperm were used to fertilize ten of Claire's eggs. Dr. Rosenwaks transferred four healthy embryos.
"I had prepared myself for the possibility that it wouldn't work," says Claire.
"Jeff and I talked a lot during the two-week wait about what we would do if we got bad news. We also met with a counselor at Weill Cornell, who made the process easier to deal with." When they received word that Claire was pregnant, "I couldn't believe it," says Jeff. "I'll never forget that call." Their daughter, Connie, is now eighteen months old.
Fertility is, on the face of things, a very simple process. It's a matter of getting the sperm and egg together. But the variables are plentiful, and as many couples find, it's easy for something to go wrong. You need a good quality egg and properly functioning sperm. You need enough sperm to be deposited where it's supposed to be. The sperm has to be strong enough to swim up the female reproductive tract through the fallopian tube to reach the egg to fertilize it. The fallopian tube has to be normal to be able to pick up the fertilized egg and deliver it to the uterus so it can develop fully. The woman's brain also needs to function properly, so that the pituitary gland produces adequate amounts of hormones necessary to foster follicle and egg development in the ovary. In turn the ovary, under the influence of the pituitary gland, must produce the critical hormones—estrogen and progesterone—necessary to promote uterine lining development and support for the implantation of the fertilized egg.
This whole series of events need to happen at the right time. There is an eight-to-twelve-hour window within each cycle in which the egg can become fertilized. Usually this happens between days 13 and 15 of a typical twenty-eight-day menstrual cycle. Healthy sperm can survive for several days inside the female reproductive tract, so timing sex around the middle of the cycle increases your chances of conception. Even in the best of circumstances, the chances that a woman will get pregnant are about one in four each month.
You Are Not Alone
There are many reasons a couple may find it hard to get pregnant, and these reasons can stem from a problem with either or both partners. In about 40 percent of infertile couples, the man has a problem. In another 40 percent, the woman has a problem. And in 20 percent both partners have a problem. That's why a couples-based solution is imperative.
Often both partners may have just-below-normal fertility, or subfertility, which may lead them to struggle with having a baby together. Treat- ments to improve each of their fertility levels will maximize their chances of conceiving.
Many infertile couples striving to conceive feel isolated and helpless, but actually you are not alone. Infertility affects about 7 million Americans, which represents about one in six couples during their childbearing years. There are daunting odds, but here's the good news: while the number of infertile couples is on the rise, medical understanding of infertility is more advanced than ever. You have more treatment options today than before. Just a few decades ago, there were no drugs to induce ovulation, no microsurgical techniques to unclog fallopian tubes or blocked ducts in man, IVF was just a dream, and single-sperm injections were unheard-of. And our understanding of the nonsurgical methods of increasing fertility—diet, exercise, and other lifestyle adjustments that greatly increase the odds of conceiving—is now similarly advanced.
When to Seek Help
You may feel lots of anxiety and stress about making a baby, particularly if you have been trying for a while. So it is important to know when it is appropriate to seek advice regarding your infertility. Fertility declines rapidly after age thirty-five, so women in this age group should consider working with a fertility specialist sooner rather than later. Even if you became pregnant on your own when you were younger, you may still have difficulty conceiving when you become older. We begin to be concerned about infertility when a couple has not conceived after twelve months of unprotected intercourse if the woman is under age thirty-five, and six months of unprotected intercourse if she is age thirty-five or older. However, our policy is to recommend an evaluation if the female partner is older than age thirty and has not conceived within six months, especially if the couple has been having sexual intercourse two or three times per week.
If you are over age thirty, or if you or your partner has reason to believe there is a risk factor in your background (such as a history of genital infections, irregular periods, or cancer treatment), this certainly justifies an early fertility evaluation. We also suggest that a woman who has a history of two or more miscarriages and no live births seek out a fertility specialist. If you and your partner are over age thirty or there are clues from your past that either one of you might have a fertility problem, and you still don't get pregnant after optimizing your chances by timing intercourse around ovulation, then we believe you need not wait as long as six months before seeking medical help.
If you and your partner have been trying to have a baby for about a year with no success, you may have fertility problems as a couple. But this does not mean you will never have a baby. Fertility problems are common and shared among men and women, and treatments are available. In fact, most of the couples who seek our help will eventually have a baby.
Fertility through the Decades
We are able to help young couples in their twenties who are having a difficult time achieving a pregnancy, couples in their thirties who may already have one child but can't seem to have another one, and even women into their forties and rarely in their fifties who thought having a baby was beyond their reach.
Most women know that it's harder to get pregnant when they get older. But complications during pregnancy also become more common with age. Age increases the risk of miscarriage and the need for a cesarean delivery and also boosts the chances of pregnancy-related diabetes and of having twins.
At birth, a woman has all the eggs she will ever have. As she ages, so do her eggs. And as an egg ages, it is more likely to develop a chromosomal abnormality. A fertilized egg with abnormal chromosomes is the single most common cause of miscarriage; at least half of all miscarriages are due to abnormal chromosomes. A woman in her twenties has a 10 percent chance of having a miscarriage each time she becomes pregnant. In her late thirties, the odds of a miscarriage are about 20 percent to 30 percent because of declining egg quality, and a woman in her forties faces a 50 percent to 60 percent risk of miscarriage.
Although age has a significant impact on pregnancy outcome and infertility, advancing age alone should not prevent you from trying to become pregnant. More than one third of all pregnancies and births in the United States occur in women who are in their thirties or older. Good prenatal obstetrical care has made pregnancies in older women safer than they were twenty to thirty years ago. The following sections illustrate typical scenarios in couples achieving pregnancies at different decades of their reproductive life.
A Baby in Your Twenties
Nan, age twenty-seven, and her husband, Brad, also twenty-seven, had struggled with infertility for several years. "I had a diagnosis of polycystic ovaries from my gynecologist, who started me on fertility pills. But they didn't work. I needed something more," says Nan. They went to see Dr. Rosenwaks, who suggested they try intrauterine insemination (IUI). Two months later, they began an IUI attempt, with Nan taking gonadotropin injections during her menstrual cycle. Nan became pregnant in that first IUI attempt. Their baby, Amy, is now seven months old. "You think that if you just keep trying, it will happen. But if you have a problem, it's better to take care of it in a timely manner," says Nan.
In 1970, American women typically had their first child at twenty-one. Today, most women are about twenty-five when they give birth. A woman in her twenties is likely to have healthier eggs than older women, which generally makes it easier to conceive. High-quality eggs also translate into a lower risk of birth defects. At twenty-five, the likelihood of having a baby with Down syndrome is about 1 in 1,250. Those with Down syndrome generally have one extra chromosome 21, for a total of forty-seven instead of the normal forty-six, and carrying a fetus with Down syndrome or another chromosomal disorder is often the reason women lose a pregnancy. This is one reason that miscarriage is less common in younger women. Younger women are also well equipped to handle the physical demands of pregnancy. But as many twenty-something women learn, fertility problems can arise at any age. The treatments in this book offer women in their twenties who are struggling to get pregnant the tools they need.
A Baby in Your Thirties
After four years of trying, Donna, a thirty-seven-year-old store owner, had been unable to conceive with her husband, David, thirty-nine, an independent filmmaker. "All my life I knew I wanted to be a mother," says Donna. Having seen four different doctors and spent tens of thousands of dollars on treatments, she feared that her time was running out.
Tests at Weill Cornell showed that Donna eggs were healthy but that David's sperm count was very low. The only way Donna could get pregnant was through an injection of David's sperm directly into her eggs in the laboratory, a process called intracytoplasmic sperm injection (ICSI), and then to have the fertilized egg implanted into her uterus. The procedure was a success, and Donna and David now have a one-year-old son, Don.
According to data from the National Center for Health Statistics, birth rates for women ages thirty-five to thirty-nine doubled between 1978 and 2000. In fact, 20 percent of women in the United States now have their first child after age thirty-five.
Having a baby in your early thirties is much like being pregnant in your twenties. Your health, energy, and fertility are still likely to be at high levels, and the quality of your eggs is still very good, making the risks of genetic defects low. However, once you reach age thirty-five, the risk of losing a pregnancy is higher. And once you turn thirty-five, your pregnancy should be monitored more closely because of the rising risk of birth defects. We offer all of our patients an amniocentesis and/or other screening tests to check for Down syndrome and other chromosomal abnormalities. There's no need to panic, because about 95 percent of women who undergo prenatal testing receive good news.
A Baby in Your Forties
Nicky, a forty-year-old social worker, had been trying to become pregnant for two years without success. Her gynecologist was baffled. There was no good medical reason for Nicky's infertility. She was in good health and her husband Leon, a forty-nine-year-old lawyer, had an excellent sperm count.
After extensive tests, the Weill Cornell team told them they were among the group of "unexplained" infertility, and suggested they opt for IVF. Their first try failed, and so they tried again. This time the procedure worked, and Nicky gave birth to a girl, Olivia.
Women in their forties are a lot healthier than they were even a generation ago, making pregnancy a viable—and achievable—option for these women. However, the risk of birth defects is a growing concern. Older eggs are more likely to have chromosomal abnormalities in their embryos. At age forty, the chances that a fetus will have Down syndrome is one in one hundred, and at age forty-five the chance is one in thirty. Due to these higher risks, it is essential that prenatal genetic tests be performed.
What's more, first-time mothers over forty are more likely to develop high blood pressure and diabetes during pregnancy than mothers in their twenties. And they are more likely to suffer placenta previa, a condition in which the placenta is implanted low in the uterus, which can impede delivery. This condition can cause complications, but these can often be prevented with a cesarean delivery.
If you're over forty and trying to conceive, you're in good company. Technological advances such as better IVF techniques now make it easier for women in their forties to have babies. With the extension of life expectancy for older women, the benefits of hormonal replacement therapy, and general improvement of the health and living conditions of older women, very late childbearing has become more socially acceptable. However, the chance of becoming pregnant with one's own eggs is very difficult after the age of forty-two or forty-three. Many women in this age group must turn to egg donation.
Some women who seek to conceive after age forty have no difficulty in achieving a pregnancy as long as they have a prompt, thorough evaluation and undergo aggressive treatments.
One simple blood test—measuring the level of follicle-stimulating hormone (FSH) in your blood on day 3 of your menstrual cycle—is important to assess the ovarian reserve, a term used to describe the number of eggs remaining in a woman's ovary. The pituitary gland produces FSH, which is responsible for the development each month of an ovarian follicle, which contains an egg. When the ovaries have very few eggs remaining, the pituitary gland senses this and begins to produce and release higher and higher amounts of FSH in an effort to stimulate the ovary. For example, women who have gone through menopause and have few or no eggs remaining in their ovaries have exceedingly high levels of FSH in their blood. Young women who have had an accelerated decline in the number of eggs can also have high FSH levels. FSH is probably more an indirect measure of egg quantity than an indicator of quality.
If the blood test shows that your FSH levels are consistently elevated, you have a much lower chance of conceiving and carrying to term; if your FSH levels are slightly above normal, these baseline levels suggest that you have a lower chance of achieving a pregnancy.
Other findings we associate with an age-related decline in fertility include a shorter or irregular menstrual cycle, symptoms of impending menopause, and low numbers of egg-carrying follicles in response to stimulation with hormones. If you have had previous surgery affecting your ovaries, such as the removal of an ovarian cyst or partial removal of ovarian tissue, that might also lead to an earlier loss of ovarian function.
In the last few years we have added another ovarian marker to help us assess the ovarian reserve. The hormone called anti-Müllerian hormone (AMH) is produced by an early stage of the developing egg-containing ovarian follicles. Very low levels of AMH denote poor ovarian reserve, whereas high levels suggest that the woman has many eggs remaining in her ovary.
Unfortunately, there are no treatments available that can turn back the clock on a woman's ovaries, but there are many treatment options that can greatly help you in your quest to have a child. We can prescribe fertility drugs to try to increase your chances of pregnancy. These powerful hormones can increase the number of eggs that develop in a given month and enhance the chance that at least one of them might be able to be fertilized and develop into a pregnancy.
The one consistently successful method to improve pregnancy rates in women with age-related infertility is through a donor egg. You may be a candidate to receive a donor egg if you are over age forty, have persistently high FSH levels at any age, respond poorly to fertility drugs at any age, or have poor-quality embryos after undergoing an IVF cycle.
Lots of Options
You never know where you will fall in the fertility lottery, so you may need to hedge your bets the best you can, particularly if you're in your late thirties or forties. You should probably talk with your doctor about donor-egg IVF, embryo development in the laboratory, and preimplantation genetic diagnosis (PGD).
For some women, the only hope is to use donor eggs. In this process, another woman's eggs are fertilized, either with her husband's or a donor's sperm, and the resulting embryo is transferred to the woman's uterus, which has been prepared to receive the embryo. While IVF success rates go down drastically after age thirty-seven, the success of donor eggs remains high.
With egg donation, success rates are dependent on the age of the donor rather than the recipient. We achieve live birth rates that exceed 50 percent per procedure with donors between twenty-one and thirty-four years of age. The use of donated eggs has made it possible for couples to achieve pregnancies where all other methods have been exhausted.
Embryo Development in the Laboratory
Another important approach to improve the success rate of IVF is to optimize the laboratory conditions for early embryos. We have developed a method to co-culture embryos with certain helper cells to enhance the development of fertilized eggs and improve embryo quality.
Endometrial co-culture is a laboratory method that utilizes the mother's own uterine lining cells to enhance embryo quality. Simply stated, in a separate menstrual cycle one to two months before undergoing an IVF procedure, the woman undergoes a biopsy of her endometrial lining seven to ten days after ovulation. The cells are separated, grown in the laboratory, and frozen, later to be thawed during the subsequent IVF cycle. After her eggs are fertilized through IVF techniques, the embryos are grown on top of the mother's extracted cells. This provides a better environment for the embryos, especially for couples who have exhibited poor embryo quality in previous IVF cycles.
Co-culture is usually reserved for use in "poor prognosis" patients, particularly when other cycles have failed because of slow growth of the embryo. This method is not a "cure" for age-related IVF failures, but in properly selected couples, it has significantly improved embryo quality.
Preimplantation Genetic Diagnosis
IVF technology allows us to analyze the genetic makeup of embryos that are developing outside the body. We can now remove a single cell from the developing embryo without harm and analyze that embryo for specific genetic disorders (or flaws) that may exist in either or both parents. By removing one or two cells from the embryo, we can successfully screen for genetic diseases such as cystic fibrosis, sickle cell disease, and Tay-Sachs disease, among many other conditions. More than two hundred genetic diseases have been successfully analyzed in preimplantation embryos. Embryos can also be sorted to avoid X-linked (sex-linked) disorders such as hemophilia, muscular dystrophy, and many others. We can also detect chromosomal abnormalities in couples who suffer from recurrent pregnancy losses as well as in women who have miscarriages due to too many or too few chromosomes. If you have a sex-linked disorder, we can identify the gender of the embryos to avoid transmission of these diseases. New methods of genetic screening allow us to screen for multiple disorders at the same time. Future developments in this area will allow us not only to diagnose genetic problems better but to treat genetically related disorders.
For more detailed information on donor eggs, see Chapter 13, and for more on embryo co-culture and PGD, see Chapter 12.
In the Future Egg Maturation in the Laboratory
During an IVF cycle, eggs are recovered from a woman's ovaries after a seven-to-twelve-day treatment with hormones to stimulate her ovaries. In this process we override the woman's natural tendency to produce a single egg. On average, we aim to harvest between five and fifteen eggs. These eggs are then fertilized with the male partner's sperm, and the ensuing embryos are then transferred into the woman's uterus.
Unfortunately, not all women respond to the stimulating hormones in a predictable fashion. Some respond excessively and others not at all. One potential approach to circumvent stimulation problems is to collect immature eggs and mature them in the laboratory. While this approach is not quite as effective as conventional IVF, it is being optimized in several laboratories throughout the world. This could be the treatment of choice for women when ovarian stimulation is not recommended for medical reasons.
Other approaches to optimizing IVF success include the detection of certain factors within the egg that are important for normal embryo development. These factors could reside in certain manufacturing structures within the egg itself or in the genetic material. Future developments may be able to replace specific missing factors that could overcome problems related to infertility.
Fertility on Ice
As more and more women delay childbearing, they are seeking ways to keep their fertility options open. Traditionally, these fertility preservation methods were made available to women who were facing radiation or chemotherapy and were likely to lose their reproductive function. Nowadays many women wish to preserve their future fertility for social reasons. Embryo freezing is the most efficient and effective method of preserving fertility. This requires the woman to undergo ovarian stimulation, use her partner's or a donor's sperm to fertilize the eggs, and freeze the resulting embryos. However, many young women and girls do not have a partner and can only have eggs or ovarian tissue frozen.
Egg freezing is a potential way to save eggs for future use. Young women may eventually deposit high-quality eggs into a reproductive bank for use when they are older, just as men can freeze their sperm and place them in sperm banks. Later, when a woman is ready to have a baby, she can simply go to the bank and withdraw what she needs.
Mature eggs are notoriously tricky to freeze safely. Newer freezing media rely on higher concentrations of coolants and faster cooling times. This results in glasslike solutions rather than ice like frozen ones that can damage the egg. Even so, only a proportion of eggs survive thawing. Some babies have been born from thawed frozen eggs in women who cannot undergo ovarian stimulation, but this is still considered a largely experimental treatment. Technological advances such as these, along with ever-improving IVF techniques, make it possible for more women than ever before to have babies.
You'll learn more about these fertility treatments as you read A Baby at Last! The first step to get you started on the right path is to figure out whether you or your partner is at risk for infertility, and you'll find help with this in Chapters 2 and 3.
If you are a woman over age thirty and have not conceived within six months of having sexual intercourse two to three times per week, you should have a fertility workup.
Advancing age impacts a woman's fertility and pregnancy outcome but should not prevent you from trying to have a baby.
Two of the most important tests to assess the number of eggs remaining in a woman's ovary are measurements of FSH and AMH in the blood on day 3 of the menstrual cycle.
If you are a woman in your late thirties or forties, talk with your doctor about donor egg IVF, embryo development in the laboratory, and preimplantation genetic diagnosis.