A Baby at Last! A Couple's Complete Guide to Getting Pregnant

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.

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You Are Not Alone: When to Seek Help

Claire, a thirty-seven-year-old designer, had tried unsuccessfully to have a babyfor a year and a half before she went to see her gynecologist. Her doctor foundshe had an incompetent cervix, which he corrected surgically. Six months later, herhusband, Jeff, a thirty-eight-year-old salesman, went to a urologist, who found Jeffhad a very low sperm count and a cyst on one testicle. Claire did some researchon the Internet into hospitals and doctors. An oncologist friend suggested theygo to Weill Cornell, where a radiologist told them that Jeff's cyst was benign, butDr. Goldstein found that Jeff had varicoceles (varicose veins in the scrotum) affectingboth testicles. Microsurgery repaired the varicoceles, but Jeff's sperm countremained very low, so they decided to try an in vitro fertilization (IVF) procedurewith Dr. Rosenwaks.

For the first IVF attempt, three of Claire's eggs were fertilized with Jeff'ssperm and transferred into her uterus, but none progressed to a pregnancy. A fewmonths 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 transferredfour 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 ifwe got bad news. We also met with a counselor at Weill Cornell, who made theprocess easier to deal with." When they received word that Claire was pregnant, "Icouldn'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 ofgetting the sperm and egg together. But the variables are plentiful, and asmany 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 bedeposited where it's supposed to be. The sperm has to be strong enough toswim up the female reproductive tract through the fallopian tube to reachthe egg to fertilize it. The fallopian tube has to be normal to be able topick 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 pituitarygland produces adequate amounts of hormones necessary to foster follicleand egg development in the ovary. In turn the ovary, under the influenceof the pituitary gland, must produce the critical hormones—estrogen andprogesterone—necessary to promote uterine lining development and supportfor the implantation of the fertilized egg.

This whole series of events need to happen at the right time. There isan eight-to-twelve-hour window within each cycle in which the egg canbecome fertilized. Usually this happens between days 13 and 15 of a typicaltwenty-eight-day menstrual cycle. Healthy sperm can survive for severaldays inside the female reproductive tract, so timing sex around the middleof the cycle increases your chances of conception. Even in the best of circumstances,the chances that a woman will get pregnant are about one infour each month.

You Are Not Alone

There are many reasons a couple may find it hard to get pregnant, and thesereasons can stem from a problem with either or both partners. In about 40percent 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 chancesof 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 ofinfertile couples is on the rise, medical understanding of infertility is moreadvanced than ever. You have more treatment options today than before.Just a few decades ago, there were no drugs to induce ovulation, no microsurgicaltechniques to unclog fallopian tubes or blocked ducts in man,IVF was just a dream, and single-sperm injections were unheard-of. Andour understanding of the nonsurgical methods of increasing fertility—diet,exercise, and other lifestyle adjustments that greatly increase the odds ofconceiving—is now similarly advanced.

When to Seek Help

You may feel lots of anxiety and stress about making a baby, particularly ifyou have been trying for a while. So it is important to know when it is appropriateto seek advice regarding your infertility. Fertility declines rapidlyafter age thirty-five, so women in this age group should consider workingwith a fertility specialist sooner rather than later. Even if you became pregnanton your own when you were younger, you may still have difficultyconceiving when you become older.We begin to be concerned about infertility when a couple has notconceived after twelve months of unprotected intercourse if the woman isunder age thirty-five, and six months of unprotected intercourse if she is agethirty-five or older. However, our policy is to recommend an evaluation ifthe female partner is older than age thirty and has not conceived within sixmonths, especially if the couple has been having sexual intercourse two orthree times per week.

If you are over age thirty, or if you or your partner has reason to believethere is a risk factor in your background (such as a history of genitalinfections, irregular periods, or cancer treatment), this certainly justifies anearly fertility evaluation. We also suggest that a woman who has a history oftwo or more miscarriages and no live births seek out a fertility specialist. Ifyou and your partner are over age thirty or there are clues from your pastthat either one of you might have a fertility problem, and you still don'tget pregnant after optimizing your chances by timing intercourse aroundovulation, then we believe you need not wait as long as six months beforeseeking medical help.

If you and your partner have been trying to have a baby for about a yearwith no success, you may have fertility problems as a couple. But this doesnot mean you will never have a baby. Fertility problems are common andshared among men and women, and treatments are available. In fact, most ofthe 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 difficulttime achieving a pregnancy, couples in their thirties who may alreadyhave one child but can't seem to have another one, and even women intotheir forties and rarely in their fifties who thought having a baby was beyondtheir 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 deliveryand also boosts the chances of pregnancy-related diabetes and of havingtwins.

At birth, a woman has all the eggs she will ever have. As she ages, so doher eggs. And as an egg ages, it is more likely to develop a chromosomalabnormality. A fertilized egg with abnormal chromosomes is the single mostcommon cause of miscarriage; at least half of all miscarriages are due toabnormal chromosomes. A woman in her twenties has a 10 percent chanceof having a miscarriage each time she becomes pregnant. In her late thirties,the odds of a miscarriage are about 20 percent to 30 percent becauseof declining egg quality, and a woman in her forties faces a 50 percent to 60percent risk of miscarriage.

Although age has a significant impact on pregnancy outcome and infertility,advancing age alone should not prevent you from trying to becomepregnant. More than one third of all pregnancies and births in the UnitedStates occur in women who are in their thirties or older. Good prenatalobstetrical care has made pregnancies in older women safer than theywere twenty to thirty years ago. The following sections illustrate typicalscenarios in couples achieving pregnancies at different decades of their reproductivelife.

A Baby in Your Twenties

Nan, age twenty-seven, and her husband, Brad, also twenty-seven, had struggledwith infertility for several years. "I had a diagnosis of polycystic ovaries from mygynecologist, who started me on fertility pills. But they didn't work. I neededsomething more," says Nan. They went to see Dr. Rosenwaks, who suggested theytry intrauterine insemination (IUI). Two months later, they began an IUI attempt,with Nan taking gonadotropin injections during her menstrual cycle. Nan becamepregnant 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 womanin her twenties is likely to have healthier eggs than older women, whichgenerally makes it easier to conceive. High-quality eggs also translate into alower risk of birth defects. At twenty-five, the likelihood of having a babywith Down syndrome is about 1 in 1,250. Those with Down syndromegenerally have one extra chromosome 21, for a total of forty-seven insteadof the normal forty-six, and carrying a fetus with Down syndrome or anotherchromosomal 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 ofpregnancy. But as many twenty-something women learn, fertility problemscan arise at any age. The treatments in this book offer women in their twentieswho 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 beenunable 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 seenfour different doctors and spent tens of thousands of dollars on treatments, shefeared that her time was running out.

Tests at Weill Cornell showed that Donna eggs were healthy but that David'ssperm count was very low. The only way Donna could get pregnant was throughan injection of David's sperm directly into her eggs in the laboratory, a processcalled intracytoplasmic sperm injection (ICSI), and then to have the fertilized eggimplanted into her uterus. The procedure was a success, and Donna and Davidnow have a one-year-old son, Don.

According to data from the National Center for Health Statistics, birth ratesfor 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 childafter age thirty-five.

Having a baby in your early thirties is much like being pregnant in yourtwenties. 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 geneticdefects low. However, once you reach age thirty-five, the risk of losing apregnancy is higher. And once you turn thirty-five, your pregnancy shouldbe monitored more closely because of the rising risk of birth defects. Weoffer all of our patients an amniocentesis and/or other screening tests tocheck for Down syndrome and other chromosomal abnormalities. There'sno need to panic, because about 95 percent of women who undergo prenataltesting receive good news.

A Baby in Your Forties

Nicky, a forty-year-old social worker, had been trying to become pregnant for twoyears without success. Her gynecologist was baffled. There was no good medicalreason for Nicky's infertility. She was in good health and her husband Leon, aforty-nine-year-old lawyer, had an excellent sperm count.

After extensive tests, the Weill Cornell team told them they were among thegroup of "unexplained" infertility, and suggested they opt for IVF. Their first tryfailed, and so they tried again. This time the procedure worked, and Nicky gavebirth to a girl, Olivia.

Women in their forties are a lot healthier than they were even a generationago, making pregnancy a viable—and achievable—option for these women.However, the risk of birth defects is a growing concern. Older eggs aremore likely to have chromosomal abnormalities in their embryos. At ageforty, 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 higherrisks, it is essential that prenatal genetic tests be performed.

What's more, first-time mothers over forty are more likely to develophigh blood pressure and diabetes during pregnancy than mothers in theirtwenties. And they are more likely to suffer placenta previa, a conditionin which the placenta is implanted low in the uterus, which can impededelivery. This condition can cause complications, but these can often beprevented 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 easierfor women in their forties to have babies. With the extension of life expectancyfor older women, the benefits of hormonal replacement therapy, andgeneral improvement of the health and living conditions of older women,very late childbearing has become more socially acceptable. However, thechance of becoming pregnant with one's own eggs is very difficult after theage of forty-two or forty-three. Many women in this age group must turnto egg donation.

Some women who seek to conceive after age forty have no difficulty inachieving a pregnancy as long as they have a prompt, thorough evaluationand 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 importantto assess the ovarian reserve, a term used to describe the number of eggsremaining in a woman's ovary. The pituitary gland produces FSH, which isresponsible for the development each month of an ovarian follicle, whichcontains an egg. When the ovaries have very few eggs remaining, the pituitarygland senses this and begins to produce and release higher and higheramounts of FSH in an effort to stimulate the ovary. For example, womenwho have gone through menopause and have few or no eggs remainingin their ovaries have exceedingly high levels of FSH in their blood. Youngwomen who have had an accelerated decline in the number of eggs canalso have high FSH levels. FSH is probably more an indirect measure of eggquantity than an indicator of quality.

If the blood test shows that your FSH levels are consistently elevated, youhave a much lower chance of conceiving and carrying to term; if your FSHlevels are slightly above normal, these baseline levels suggest that you have alower chance of achieving a pregnancy.

Other findings we associate with an age-related decline in fertility includea shorter or irregular menstrual cycle, symptoms of impending menopause,and low numbers of egg-carrying follicles in response to stimulationwith 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 helpus assess the ovarian reserve. The hormone called anti-Müllerian hormone(AMH) is produced by an early stage of the developing egg-containing ovarianfollicles. Very low levels of AMH denote poor ovarian reserve, whereashigh levels suggest that the woman has many eggs remaining in her ovary.

Unfortunately, there are no treatments available that can turn back theclock on a woman's ovaries, but there are many treatment options that cangreatly help you in your quest to have a child. We can prescribe fertilitydrugs to try to increase your chances of pregnancy. These powerful hormonescan increase the number of eggs that develop in a given month andenhance the chance that at least one of them might be able to be fertilizedand develop into a pregnancy.

The one consistently successful method to improve pregnancy rates inwomen with age-related infertility is through a donor egg. You may be acandidate to receive a donor egg if you are over age forty, have persistentlyhigh FSH levels at any age, respond poorly to fertility drugs at any age, orhave 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 needto hedge your bets the best you can, particularly if you're in your late thirtiesor forties. You should probably talk with your doctor about donor-eggIVF, embryo development in the laboratory, and preimplantation geneticdiagnosis (PGD).

Donor-Egg IVF

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'ssperm, and the resulting embryo is transferred to the woman's uterus,which has been prepared to receive the embryo. While IVF success rates godown drastically after age thirty-seven, the success of donor eggs remainshigh.

With egg donation, success rates are dependent on the age of the donorrather than the recipient. We achieve live birth rates that exceed 50 percentper procedure with donors between twenty-one and thirty-four years ofage. The use of donated eggs has made it possible for couples to achievepregnancies where all other methods have been exhausted.

Embryo Development in the Laboratory

Another important approach to improve the success rate of IVF is to optimizethe laboratory conditions for early embryos. We have developed amethod to co-culture embryos with certain helper cells to enhance thedevelopment of fertilized eggs and improve embryo quality.

Endometrial co-culture is a laboratory method that utilizes the mother'sown uterine lining cells to enhance embryo quality. Simply stated, in aseparate menstrual cycle one to two months before undergoing an IVFprocedure, the woman undergoes a biopsy of her endometrial lining sevento ten days after ovulation. The cells are separated, grown in the laboratory,and frozen, later to be thawed during the subsequent IVF cycle. After hereggs are fertilized through IVF techniques, the embryos are grown on topof the mother's extracted cells. This provides a better environment for theembryos, especially for couples who have exhibited poor embryo quality inprevious IVF cycles.

Co-culture is usually reserved for use in "poor prognosis" patients, particularlywhen other cycles have failed because of slow growth of the embryo.This method is not a "cure" for age-related IVF failures, but in properlyselected couples, it has significantly improved embryo quality.

Preimplantation Genetic Diagnosis

IVF technology allows us to analyze the genetic makeup of embryos thatare developing outside the body. We can now remove a single cell fromthe developing embryo without harm and analyze that embryo for specificgenetic disorders (or flaws) that may exist in either or both parents.By removing one or two cells from the embryo, we can successfully screenfor genetic diseases such as cystic fibrosis, sickle cell disease, and Tay-Sachsdisease, among many other conditions. More than two hundred geneticdiseases have been successfully analyzed in preimplantation embryos.Embryos can also be sorted to avoid X-linked (sex-linked) disorderssuch as hemophilia, muscular dystrophy, and many others. We can also detectchromosomal abnormalities in couples who suffer from recurrent pregnancylosses as well as in women who have miscarriages due to too many ortoo few chromosomes. If you have a sex-linked disorder, we can identify thegender of the embryos to avoid transmission of these diseases.New methods of genetic screening allow us to screen for multiple disordersat the same time. Future developments in this area will allow us notonly to diagnose genetic problems better but to treat genetically relateddisorders.

For more detailed information on donor eggs, see Chapter 13, and formore on embryo co-culture and PGD, see Chapter 12.

In the FutureEgg Maturation in the Laboratory

During an IVF cycle, eggs are recovered from a woman's ovaries after aseven-to-twelve-day treatment with hormones to stimulate her ovaries. Inthis process we override the woman's natural tendency to produce a singleegg. On average, we aim to harvest between five and fifteen eggs. These eggsare then fertilized with the male partner's sperm, and the ensuing embryosare then transferred into the woman's uterus.

Unfortunately, not all women respond to the stimulating hormones in apredictable fashion. Some respond excessively and others not at all. One potentialapproach to circumvent stimulation problems is to collect immatureeggs and mature them in the laboratory. While this approach is not quiteas effective as conventional IVF, it is being optimized in several laboratoriesthroughout the world. This could be the treatment of choice for womenwhen ovarian stimulation is not recommended for medical reasons.

Other approaches to optimizing IVF success include the detection ofcertain factors within the egg that are important for normal embryo development.These factors could reside in certain manufacturing structureswithin the egg itself or in the genetic material. Future developments maybe able to replace specific missing factors that could overcome problemsrelated to infertility.

Fertility on Ice

As more and more women delay childbearing, they are seeking ways tokeep their fertility options open. Traditionally, these fertility preservationmethods were made available to women who were facing radiation or chemotherapyand were likely to lose their reproductive function. Nowadaysmany women wish to preserve their future fertility for social reasons.Embryo freezing is the most efficient and effective method of preservingfertility. This requires the woman to undergo ovarian stimulation, use herpartner's or a donor's sperm to fertilize the eggs, and freeze the resultingembryos. However, many young women and girls do not have a partner andcan only have eggs or ovarian tissue frozen.

Egg freezing is a potential way to save eggs for future use. Young womenmay eventually deposit high-quality eggs into a reproductive bank for usewhen they are older, just as men can freeze their sperm and place them insperm banks. Later, when a woman is ready to have a baby, she can simplygo to the bank and withdraw what she needs.

Mature eggs are notoriously tricky to freeze safely. Newer freezing mediarely on higher concentrations of coolants and faster cooling times. This resultsin glasslike solutions rather than ice like frozen ones that can damagethe egg. Even so, only a proportion of eggs survive thawing. Some babieshave been born from thawed frozen eggs in women who cannot undergoovarian 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 whetheryou or your partner is at risk for infertility, and you'll find help with this inChapters 2 and 3.

Take-Home Messages

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.

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