Melissa Michelson knew before she married that she would have difficulty becoming pregnant. Scar tissue from surgery 10 years earlier blocked the passage of eggs down her fallopian tubes. No longer, however, do such challenges end the dream of parenthood. Reproduction is more science than ever before, enabling with more sophistication and reliability, the conception of a much-desired child.

Michelson's obstetrician recommended the Stanford Fertility and Reproductive Medicine Center, just a couple of miles from her home in Palo Alto. The help she and her husband, Christopher Gardner, found at the center gave them Joshua, now 4, and Zachary, 20 months. "I love being a mommy," Michelson said. "I love my boys."

The process was not easy. She went through several cycles of hormone injections so her body would release more eggs than usual, and then, after a carefully selected few were fertilized and implanted, endured that difficult state of limbo between fertilization and pregnancy. "You're trying not to worry, but you're worried," she said. "You think, 'If I could just think positive I will get pregnant.' You get your hopes up and when they don't stick you're disappointed, but you know you have to think happy thoughts and it's important not to be stressed."

Mysteries unraveled

Understanding the elements of human fertility, a complicated set of interactions between biochemistry and physical structures, did not truly begin until the late 19th century, when a Swiss physician created the first accurate representations of a developing human embryo. Almost a century later, researchers were able to fertilize egg with sperm outside a woman's body and then to replace the fertilized eggs in her uterus. In 1978, Louise Brown was born, the first child conceived by IVF, or, in vitro, meaning "in glass," fertilization.

In 1993, a technique called ICSI, intracytoplasmic sperm injection, allowed sperm to be directly inserted into eggs, conquering the infertility of many men. In the decades since then, more and more of the reproductive process has been discovered, and, ultimately controlled, in ways that have made 3 million such pregnancies successful since Brown was born. Assisted reproductive technology (ART) is picking away, bit by bit, at the mysteries of eggs and sperm.

Stanford Hospital began to offer fertility treatment to patients in the early 1980s. Lynn Westphal, MD, Michelson's physician, and Barry Behr, PhD, helped expand the clinic's programs in 1998 to include fertility preservation for cancer patients. The center is now one of the largest on the West Coast and has added fertility preservation for healthy women and couples. The center serves about 20,000 patients each year. Often, they are people who have been elsewhere first without success or been told there would be no point in even trying, Westphal said. "We take patients with medical conditions that no one wants to deal with because we are willing to try new techniques and do things that maybe are a little bit out of the ordinary. Patients come to us and have unusual situations and we try to look at everyone as an individual. We know this is never going to be an easy process.''

An estimated 15 percent of American couples will fail to conceive a child after one year of trying. That infertility can have many explanations, most with clear physical origins. It may be that previous or ongoing medical issues have adversely altered either partner's reproductive physiology. It can be one tiny failure in the environment or process that prevents successful conception. In 10 to 20 percent of infertile couples, physicians can find no definable reason.

Refining knowledge

Michelson and Gardner already knew what was going on, which removed the extra stress of uncertainty. Michelson went through standard rounds of egg stimulation and retrieval, and, later, embryo implantation. When her eggs were removed, "you go to sleep so it's pretty easy," she said. "When you wake up, you go home." 

Implantation was not much more difficult. "You don't get sedated and you can watch what's happening on a screen," she said, and added jokingly, "then your husband is forced to let you lie around in bed all day eating bonbons."

What Stanford physicians accomplished with Michelson, and what many others accomplish at other fertility clinics, is an almost unbelievable feat considering the scale of the objects involved. An ovary is about the size of an almond. Twenty million sperm would still only fill a one-milliliter tube and an egg is just 120 microns across, barely the width of two human hairs.

Nor is every fertilized egg one that will succeed as a pregnancy. In the last few years, researchers have identified hundreds of genetically transmitted conditions. Pre-implantation analysis of an embryo's genetic make-up is now possible with great accuracy and less threat. Behr, director of the Stanford center's IVF/ART Laboratory, contributed an important piece of knowledge to that part of reproduction aimed at selecting the healthiest possible embryo—a recipe for a support medium to meet the special requirements embryos need to live outside a mother's body.

As the fertilized egg develops, its nutritional needs change—in the same way infants graduate from liquids to solids as they grow into toddlerhood. Behr and his colleagues discovered what those changes were and figured out how to match those different needs to support two additional days of fertilized egg growth.

That extra time exposes information crucial to predicting a pregnancy's success. Having those extra days of growth, Behr said, "is like being able to judge marathon runners at mile 22 instead of mile 2. At the start of the race, you know the winner is someone in the group, but it's much easier to pick the winner toward the end of the race." 

Beyond that better preview of the future, the extra days also gives assisted reproduction technicians, if a pre-implantation genetic diagnosis has been requested, the ability to remove an embryonic cell at a stage before all the cells begin to differentiate. 

Engaging all elements

Stanford has always taken a comprehensive approach to treatment, Westphal said. The center's team includes embryologists, reproductive endocrinologists, clinical nurses, therapists and highly trained technicians. And all the lab technicians can do every step in the clinic's various procedures. "We have to be able to step in when needed," said the lab's manager and senior embryologist Janice Gebhardt, who has watched IVF/ART evolve since she began in the field almost 20 years ago. Most people, she said, "take pregnancy for granted."

In the clinic's phone center, voices murmur quietly as patients are given results of various tests or of pregnancy status. It's another part of the process that requires a delicate approach; the news can be bad as well as good. "But when they finally bring their babies in," said the clinic's nurse manager, Amanda Schwartz, RN, "that's the best part of my job."

Schwartz and her colleagues are an important part of the clinic, helping patients through loss, when necessary. That stress and emotions can affect fertility is a definite possibility, said the clinic's therapist, Penny Donnelly, RN, MFT. She runs groups and workshops for men and women to give them a safe place to talk about what they are going through, and to give them ideas about what they can do that pharmaceuticals and medical expertise cannot. "I use the analogy of a three-legged stool," Donnelly said. "The third leg is what you as an individual can do to create your best well-being by managing your diet, nutrition, stress and thinking patterns."

It took Michelson and Gardner four cycles of egg harvesting and seven cycles of implantation to have Joshua. As soon as he reached his first birthday, the couple tried again, using embryos left from one of their previous rounds of IVF. Although another cycle of retrieval was needed, the second pregnancy came much more quickly. Michelson's attitude with this IVF procedure was far different. "I knew I could be pregnant," she said. "My brain knew it. My body knew it. A lot of the anxiety wasn't there any more."

Michelson, like many parents, is keeping scrapbooks for her children, including the very first photograph of them, as embryos just before implantation. "They look like little flowers," she said. "As they get older they will say, 'Mom, what's that?' It'll be a fun part of their story. First they were flowers and then they were babies!"