Conceivability_What I Learned Exploring the Frontiers of Fertility

by Elizabeth L. Katkin

  In the first step toward pregnancy, the tiny embryos implant in the uterine wall; if the lining of the uterine wall is too thin, the embryos don’t tend to stick around. As I began preparing my body for the frozen embryos, I took Progynova exactly as prescribed, but my body didn’t respond; my uterine lining remained too thin to attempt to implant the embryos. We abandoned the cycle. I was crushed. How could we possibly have a new problem now? We waited (again). We tried (again). The lining was too thin (again). We abandoned (again). I was at wit’s end. At this point, worried about my physical as well as my emotional health, Richard, who had long been a fan of adoption, was ready to move on. But I wasn’t there yet.

  And then, just when it couldn’t possibly get any worse, it did. In the middle of what had been a delicious, celebratory dim sum lunch with clients, my phone rang. It was Mr. P. I excused myself, hoping he might have good news—a new treatment? A new idea? No, he was calling to apologize. “I’m sorry,” he said, in his posh voice. “There’s been a mix-up. The lab didn’t get my message that the cycle was canceled, and well, it seems they have gone and thawed all your embryos by mistake. But the good news is your next cycle of IVF is on me.”

  Destroyed. My five high-quality embryos, our potential little babies: gone. I don’t know which was stronger, my fury or my despair. I had to return to a plate full of dumplings and somehow put on a smile for my clients. Richard and I easily could have sued, as we were urged to time and again by people who understood the magnitude of the loss. But we didn’t want to. We just wanted our baby. We agreed to do the free IVF cycle with Mr. P as soon as medically permissible.

  There’s something you must remember . . . you’re braver than you believe, and stronger than you seem, and smarter than you think.

  Christopher Robin to Winnie-the-Pooh

  7

  Understanding Modern ART

  Key Aspects of Assisted Reproductive Technology

  Every woman struggling to have a baby has that “aha” moment when she takes charge of her fertility. For some, it is after one failure. For others, it follows years of fruitless trying. For me, it happened four miscarriages and three years into my journey.

  I was lying alone in a hospital bed in Central London, cradling my swollen abdomen, which hours earlier had forty eggs removed in my second attempt at IVF. I was nervous. More nervous than I wanted to admit to my husband, or even to myself, I suppose. Staring at the ceiling, I wondered how I had gone so quickly from the heights of optimism about what Mr. P had called an “amazing” IVF cycle to the intense anxiety and discomfort I was experiencing because of my ovarian hyperstimulation (OHSS). After the blow of the thawed embryos, we had been so hopeful that this next (free) IVF cycle would work. Far less intimidating the second time around, we repeated essentially the same protocol as before, but with higher dosages of fertility drugs.1 My estrogen levels had soared, and Mr. P instructed me to “coast” for a few days, refraining from ingesting or injecting any hormones, while my estrogen level came down to an acceptable range. We then continued as planned. We had forty follicles, which produced twenty-six eggs, nineteen of which fertilized. Two were transferred to my womb, and ten were frozen.

  I had read about OHSS, and signed the requisite waiver acknowledging the risks. It sounded dreadful—with complications ranging from an excessively swollen uterus to possible death—but it also seemed like something that happened to someone else. Not to me. In fact, the whole thing felt like it was surreal. How was this happening? This was not the trajectory of the life I envisioned when I had joyously married Richard nearly five years earlier.

  After returning home from my thoroughly exhausting and depressing hospital stay, I finally decided to take the situation into my own hands. My first act was to start to do my own serious research into IVF. And I was shocked by what I learned. Mr. P’s techniques were out of date. He was transferring embryos on their second day of development rather than on day three or day five, when the embryos were much more mature and had demonstrably higher rates of success. And he was judging embryos on appearance alone, an antiquated practice now that state-of-the-art testing had become available. When I asked him pointed questions about his protocol versus newer advancements, he couldn’t respond. It was time to wake up and take charge of my fertility.

  * * *

  My friend Kathy, the ob-gyn, had heard enough too. One of the smartest and most caring people I know, it was maddening for her to have a close friend with a problem broadly in her field receiving care that she felt was substandard. And to make matters worse, she was an ocean away, hearing my unsophisticated medical reports secondhand and unable to direct my care. Between my first ob-gyn’s reluctance to perform a D&C, four miscarriages in a row, and now my fertility specialist causing ovarian hyperstimulation syndrome, she insisted that it was time to come visit her in Boston. Although Kathy is not specialized in fertility (she is a high-risk neonatal expert), she had friends who were, and was confident that I would receive better care at her hospital, Brigham and Women’s Hospital.

  I flew to Boston a bundle of nerves and excitement. I was hopeful that Kathy’s friend, Dr. Rachel Ashby, would have answers for me, but fearful that if she didn’t, it might be the end of my road. And I knew I wasn’t ready to quit yet. Meeting Rachel was a game changer, although not in the way I had necessarily hoped. She didn’t hold the golden key. She didn’t trash my doctors and their protocols. She didn’t tell me that if I came to Boston and did an IVF cycle at Brigham and Women’s I would get a different result.

  Rather, she studied my records, thought deeply about my situation, and shared with me her clear-eyed view of my case, the landscape of infertility treatment, and what I could and should be looking for in my next doctor if I wanted to keep trying. Essentially, she taught me how to look at fertility specialists and clinics more critically with respect to what they could offer me, as an individual, as opposed to generalized statistics. It may sound subtle, but this shift in thinking is, in my view, the primary reason that I was ultimately able to succeed.

  We reviewed my previous IVF protocols together, and while certainly not cutting-edge, Rachel found them to be reasonable, and not too different from what she would have prescribed, except for the time of transfer, where she strongly favored waiting until the embryo was three or five days old, rather than two, giving it more time to develop. She pointed out that most other good clinics would follow a similar protocol, perhaps tinkering at the margins. But more important, she also told me that new research and new treatments were evolving in other countries and in certain places in the United States, and that if I was determined to keep trying, I might want to consider those. She instinctively felt that my miscarriages and IVF failures most likely resulted from aneuploidy. Aneuploidy, Rachel explained, was simply an abnormal number of chromosomes in a cell, meaning a cell either had an extra chromosome (trisomy) or was missing one (monosomy) instead of having the normal pair. With the exception of a few specific abnormalities, such as trisomy 21, which results in Down syndrome, most embryos with aneuploid cells are not compatible with life and are miscarried.

  Although not offered at Brigham and Women’s at that time, Rachel explained that there was a relatively new technology called preimplantation genetic screening (PGS)2 in which a cell was removed from a three-day-old embryo (created through IVF) and assessed for common chromosomal abnormalities by testing five to seven pairs of chromosomes. Only embryos deemed to be normal were transferred to the womb. It was too early to conclusively evaluate the success of PGS, but doctors were publishing results that looked promising, and in light of what she suspected were my repeat aneuploid embryos, Rachel felt that in my case it might make sense to explore. She jotted down some names of people in New York and Europe for me to look up.

  We also discussed the topic of reproductive immunology treatment, which, like PGS, was not offered at Brigham and Women’s. Because it required suppressing the immune system, Rachel did not support that particular treatment—she felt
there was not enough evidence of efficacy to countermand the risks—but she told me where to go to look for more information to educate myself.

  I left her office feeling overwhelmed but also energized. There was so much more to learn. There were new things I could try. I was thirty-six, and I had to hurry, but my journey was not over.

  I needed to know more about the quality of my embryos. Although still in its infancy and not yet mainstream in either the United Kingdom or the United States, I discovered that PGS was available at a half-dozen clinics, several of which had very high success rates, and in our case, after four miscarriages, I believed it was essential.

  I also needed to learn more about my own immunological system. Was it possible that my immune system itself was causing the miscarriages, my own natural killer cells attacking our fetus as it would a foreign body?

  The information I sought was not all to be found locally. I pondered the immunity question with the sympathetic wife of a client of mine, who was keeping a watchful eye on my fertility travails. She had urged me to see her doctor in Geneva for a second opinion when I was diagnosed with antiphospholipid syndrome, which I did, and now she absolutely insisted that I go to Frankfurt to see a doctor widely known for his expertise in this particular area. Not accustomed to taking no for an answer, my fertility fairy godmother arranged it all. I flew to Frankfurt, was met by a driver and translator, and whisked off to the medical campus of the University of Frankfurt, where in a one-hour meeting, one of the world’s leading scientists researching natural killer cells gave me my next medical directions: during my subsequent IVF cycle, for which he strongly urged PGS, I would suppress my immune system with intravenous immunoglobulin, or IVIG, to prevent it from potentially harming an embryo.

  Taking it all in, I felt grateful then, and many times since, that my often-too-demanding job had led to this unexpected side benefit, opening doors to doctors and practices that I would not otherwise know about, let alone have the capability to access. For the first time in my medically assisted quest to have a baby, I felt empowered rather than timidly led along.

  Returning to London, I optimistically prepared for my next IVF cycle at the highly regarded Lister Fertility Clinic in London (chosen after much research and consultation) with a great new team and a new protocol, which was to include:

  • A different level and combination of hormones to stimulate my eggs to grow3

  • Viagra to thicken my uterine lining in an effort to increase the odds of implantation4

  • Intracytoplasmic sperm injection (ICSI)—in which a sperm is injected directly into an egg in an effort to encourage fertilization—to half of my eggs to test whether, despite no indication of male factor infertility, this would improve our fertilization rate (it had no effect)

  • IVIG to convince my immune system that our tiny embryo was not a hostile foreigner

  • Genetic testing through PGS to select chromosomally normal embryos.

  One of the reasons I had chosen the Lister for treatment was its ability to do PGS. Our plan was to test all our embryos on day three, and to transfer two normal blastocysts—ideally evolved from the embryos by the time the testing is complete—to my uterus two days later.

  To my great surprise, when I went for a baseline blood test often administered before an IVF cycle commences, I discovered that I was pregnant again, naturally. This time I knew well enough not to get my hopes up, and I was smart not to do so. Despite heparin shots and IVIG transfusions to combat my blood clots and suppress my overactive immune system, my fifth pregnancy led to my fifth miscarriage, confirmed at St. Mary’s Hospital on a date I will never forget, as it was the same day as the devastating 7/7 London bombing. As I sat in the hospital waiting room for agonizing hours, listening as news about the attack trickled in, I was joined by a steady stream of injured victims. They stumbled through the doors, some bloody, some limping, some clenched in pain, some visibly in shock. By the end of the day, more than fifty people had died and hundreds were injured. Surrounded by survivors, I was forced to confront tragedies greater than my own.

  The fifth miscarriage didn’t devastate me the way the others had. I was beyond emotions now. My resolve only strengthened: I would succeed. It was the only way to be able to handle the previous losses. We would try IVF again armed with all our newfound knowledge about fertility treatments: fertilization with ICSI; genetic testing of our embryos, which we would grow to day five blastocysts; Viagra; blood thinners; immune suppression; progesterone support; acupuncture; nutritional and hormone supplements. We would leave no stone unturned. We would eliminate all chance of miscarriage again.

  And maybe we would have. It is hard to know. Because despite our collective efforts—and my doctors at this clinic were truly heroic trying everything they could throughout two more cycles—I did not get pregnant again through conventional IVF.

  * * *

  Like me, Jessica took charge of her fertility following a terrible scare. After multiple IVF cycles, multiple pregnancies, and multiple miscarriages as a well-informed but relatively passive patient, Jessica’s clinic required her to undergo yet another hysterosalpingogram (HSG), despite her objections to repeating this diagnostic test to assess the anatomical structure of the uterus. After the invasive procedure, performed on her as an outpatient, Jessica experienced extreme and continuous bleeding. She called her clinic several times that afternoon, increasingly panicked each time, but did not elicit much concern from the nurses, who merely asked how many pads she was bleeding through per hour. Finally, her husband, Ethan, a physician, called the clinic and told the nurses that Jessica was bleeding through one hundred pads in a thirty-minute time frame. He rushed her to the hospital emergency room, where doctors, discovering her uterus had been nicked in the procedure, had to cauterize and then stitch her to control the bleeding. The emergency room team saved her life. In the depths of her despair, Jessica decided two things: she wanted an apology (which never came), and she was going to take charge of her fertility.

  When Marcy, much to her surprise, was diagnosed with low ovarian reserve at age thirty-two, she and her husband, Dan, were told that they would face an uphill battle conceiving a child. As Marcy and Dan, both lawyers, processed the shocking news that she had far fewer eggs left than a typical woman of her age, potentially of lower quality as well, they determined to approach infertility treatments with a critical eye, rapidly educating themselves about the available procedures and statistics. Yet despite all the information they collected, as they attempted to navigate the largely unfamiliar world of infertility, they generally deferred to the advice of the experts. When Marcy was rushed to the hospital in the seventh month of her pregnancy, they tragically learned that the experts are not always right. Unwilling to heed their pleas to wait for Marcy’s fertility doctor to arrive, the emergency room doctors proceeded with a plan to operate on Marcy despite her objections. Her baby’s heartbeat stopped during surgery. After losing her beloved baby at twenty-six weeks, Marcy suddenly understood: “I am the only person who will advocate for myself. I have to step up and take responsibility.”

  * * *

  Taking control of one’s fertility starts, to some degree, with ensuring that you are at the right clinic. But a great many women (myself included) choose their clinic—at least their first clinic—based on convenience or a referral from their ob-gyn. “Think of the care a couple might put into choosing a car or washing machine, yet for something as monumental as where they are going to have their IVF treatment they don’t ask the clinic any questions. They just go where a friend went,” noted the director of a fertility clinic.5

  Success rates for different age groups and conditions vary dramatically, not only around the world, but also within a city, state, or country, and it is imperative to find the best clinic available for you. The only way to do so is to be armed with the right questions.

  I realize that it may seem that I moved around and switched clinics an awful lot—two fertility clinics in London, one
in New York, and eventually one in Moscow, with consultations in Boston, Geneva, and Frankfurt. While the far-flung array of cities I frequented may be unique, clinic shopping is certainly not. In fact, most fertility patients will leave their first doctor.6 Paula began her fertility treatments consulting with one of the nation’s leading experts at a top clinic in Colorado. After her first miscarriage and four failed IUI attempts, she switched to another doctor at the same clinic. Following an unsuccessful try with IVF, she sought out a clinic with a doctor who specialized in working with older women. She got pregnant there, but suffered another miscarriage. When she eventually decided to use a donor egg, she went back to the first clinic. Later, upon learning of her immunology issues, she went to a renowned center in Chicago that offered specialized treatments.

  Sarah, from Massachusetts, similarly sought out a famous clinic in Manhattan after repeated failures in Boston; unimpressed, she continued treatment with her Boston clinic. Rose, a teacher who had to terminate her first pregnancy due to the diagnosis of her baby’s fatal brain malformation, left her first clinic after multiple tries, frustrated and feeling that the doctors there were simply following a standard protocol that didn’t make sense for her. “They had just two protocols,” she told me angrily, “that’s it. They don’t individualize.” She interviewed two new fertility clinics with outstanding success rates, and chose the one with the doctor with whom she felt more comfortable, and who offered a more personalized treatment plan.

  Anna, the social worker, started out in her hometown of Denver at a clinic with success rates among the highest in the country; she left it when she felt the doctors were unwilling, or perhaps not able, to tailor treatment to accommodate her lupus, an autoimmune problem. She sought out a clinic in Chicago that specialized in reproductive immunology, hoping to combine the recommended immune therapies with IVF at her Denver clinic. “She basically laughed in my face,” Anna recounted when telling me about her original fertility doctor. “I felt like she was saying, ‘You don’t know anything; we know everything.’ It was almost like they were insulted.” Anna turned to a different clinic in Denver with a doctor who was more than happy to work with her immunologist. “They were in so much communication, it was amazing,” she happily recalled. Anna had her daughter on their first try.