At the same time, across the pond, James Mowbray, a researcher at St. Mary’s Hospital in London, organized the first placebo-controlled, double-blind trial of LIT. The small trial, which assessed forty-seven women, divided them randomly into two groups, one of which received lymphocytes (white blood cells) from their husbands, the other of which received their own. Promisingly, 78 percent of women in the treatment group had a live birth, compared to 37 percent in the placebo group.31
All looked fantastically bright for the future of LIT. Dr. Beer and his reproductive immunology treatments rose in fame as more “Beer babies” were born. People magazine ran a cover story about him called “Injection of Hope,” while national TV networks devoted airtime to his new methods.32 Clinics around the nation and the world began to offer LIT, and an article in Newsweek called the progress in preventing miscarriage “little short of spectacular.”33
But somewhat ironically, at almost the same time, a study emerged from Norway on a treatment protocol that had even more favorable results than LIT, with 86 percent of women in the treatment group carrying to term, compared to only 33 percent in the control group, among a population that had previously experienced three consecutive miscarriages.34 The variable in the Norwegian study: tender loving care. It turned out that weekly visits to check the mothers’ and babies’ vitals provided assurance that the pregnancies were progressing smoothly. This “optimal psychological support” presumably reduced stress and anxiety, and proved as successful as the invasive LIT intervention. Seven years later, a team at a recurrent miscarriage clinic in Auckland, New Zealand, conducted a similar study, providing “formal supportive care” to their treatment group and routine care to a control group through the patients’ first trimesters. Startlingly, among a population of women who averaged four previous miscarriages, the Auckland team found the exact same result: 86 percent of the treatment group carried to term, versus 33 percent of the control group.35
The Norwegian “tender loving care” study, together with growing concerns about the risks inherent in blood transfusions—such as transferring an undetected infection or triggering an immune rejection reaction—and a lack of clear-cut evidence that LIT worked, prompted the organization of a large-scale, four-year study, known as the Recurrent Miscarriage Study, or REMIS, intended to shed definitive light on the effectiveness of the therapy. The results were much anticipated, but the trial was never completed. Quite unusually, the US government terminated the study when the reviewers noted that, contrary to what the researchers and public expected, the control group had significantly better results than the treatment group.36 On January 30, 2002, the FDA sent a letter to clinics administering LIT instructing them to refrain from any administration of LIT unless given in connection with approved clinical investigations, citing concern that the treatment may produce a higher rate of miscarriage and that it presented risks to the recipient.37
Despite the scientific evidence to the contrary, doctors and patients alike, led by Dr. Beer, were undeterred in their belief that immunology might hold the key to preventing miscarriage, and efforts to crack the code continued in earnest. Following the same theory of taming a woman’s immune system by essentially diluting it with cells from another, doctors turned toward a protocol that was already approved by the FDA, albeit for a different purpose. Instead of their husbands’ white cells, this entailed infusing women with antibodies pooled from several people through IVIG.
Notwithstanding the absence of proof that it works, IVIG remains today the frontline treatment for miscarriages believed to be caused by natural killer cells. Opponents of the practice point out numerous flaws on the pathway to supporting IVIG for preventing pregnancy loss. First, challengers note that while there is no disagreement surrounding the existence of uterine natural killer cells, the function of these uterine NK cells is completely unknown, and a link between the cells and miscarriage has not been conclusively demonstrated. On top of that, because natural killer cells found in the uterus are different from NK cells found in blood, critics argue that measuring the amount of NK cells in blood will not shed light on what is happening in the uterus. Some of the world’s leading miscarriage experts note that measuring the number of uterine NK cells through the blood tests currently in use “is akin to estimating the number and activity of black cabs in Trafalgar Square by analysing red minicabs circulating on the M25.”38I And finally, and perhaps most persuasively, experts emphasize that there is no evidence to show that immunological suppression treatments such as IVIG and steroids, which present known risks to both mother and baby, are successful. In fact, a Cochrane review of twenty randomized controlled trials in eleven countries found that none of the immunotherapy treatments provided a significant benefit in improving live birth rates or lowering the risk of future miscarriage among women who have recurrent miscarriages.39 Neither the American Society of Reproductive Medicine nor the British Royal College of Obstetricians and Gynaecologists supports its use.
Yet proponents of immunotherapy are not dissuaded. Citing their personal success stories and often their own clinics’ statistics regarding successful pregnancies following treatment, many doctors advocating IVIG maintain that they are ahead of the curve in understanding a mechanism that plays a clear and significant role in miscarriage. “In my opinion, it is very regrettable and unfortunate that so many patients are denied the ability to go from ‘infertility to family’ simply because (for whatever reason) so many reproductive specialists refuse to address the role of immunologic factors in the genesis of intractable reproductive dysfunction,” Dr. Geoffrey Sher, a renowned fertility expert, says on his website. “Hopefully this will change . . . and the sooner the better.”40 Some clinics go much further, claiming that “Intravenous immunoglobulin (IVIG) has been established as one of the most effective treatments for multiple miscarriage . . . . A large percentage of women who have experienced recurrent miscarriage have found that IVIG is an effective solution to the immunologic causes of miscarriage.”41
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In 2005, I found myself seduced by the promise of IVIG. After all my discoveries and failures, I believed that I had found the missing piece. What else did I have to hold on to? Dr. Beer argued that women with recurrent miscarriages caused by immunological factors effectively “become serial killers of their own babies.”42 If there was even a slight chance that what he said was true, how could I not try to fight that?
Sarah and Evan are grateful for the reproductive immunology treatments. After three miscarriages, all following natural conceptions, they decided to see a fertility specialist, who informed them that Sarah had a blood-clotting disorder. Her doctor prescribed the blood thinner Lovenox to be started immediately, before conception. Sarah became pregnant a fourth time and continued the Lovenox, but it failed to prevent her fourth miscarriage. This devastating loss prompted them to leave their comfortable Boston clinic and excellent Massachusetts insurance plan and head to a famous reproductive immunology clinic in New York City, where they had their “first glimpse of fertility as a business.” While their Massachusetts insurance had covered $150,000 of Sarah’s treatment costs in Boston, their consultation in NY, together with two phone calls and lab tests, cost $6,000 (paid out of pocket), despite the fact that their doctor ate lunch through their meeting and called Sarah the wrong name. But it may have been worth it. Sarah was advised to do an IVF cycle while taking Lovenox (daily) to thin her blood, steroids (daily) while also undergoing IVIG (every three weeks) to tame her immune system, and preimplantation genetic testing (PGS) to select a healthy embryo. In the end, they had one healthy, chromosomally normal embryo transferred into Sarah’s immune-suppressed womb, and welcomed their baby eight months later.
Sarah and Evan will never know if it was the immunotherapy that gave them their baby. Perhaps it was the genetic testing, which helped in selecting a normal embryo. Or maybe it was luck.
One of the greatest obstacles to evaluating miscarriage therapies is the fact that many, if not the maj
ority, of women who conceive will carry to term with no intervention, even if they have miscarried in the past. In fact, studies indicate that 95 percent of women who miscarry will conceive again in the two years following the miscarriage, and that approximately 85 percent of women who have experienced one miscarriage and as many as 70 percent of women with recurrent pregnancy loss will succeed in subsequent pregnancies.43 Ironically, in much the same way that most miscarriages still go unexplained, pregnancy success following recurrent miscarriage can also go unexplained. This conundrum highlights the need for large-scale, randomized double-blind studies to test the effectiveness of treatments. But only a few such studies have been conducted, and patients are rarely made aware of their findings. Rather, doctors tend to measure the efficacy of a treatment against their own patient pool, or against an individual patient’s own history, which may or may not have validity for others.
There are untold variables to every pregnancy, and patients also tend to use their own success as a yardstick against which to measure practices. If a woman carries to term after taking aspirin and heparin every day, or has a baby following surgery to fix a septate uterus, or after enduring IVIG infusions, she will ascribe her success to the relevant treatment. But if a doctor tells a pregnant woman to drink orange juice every day throughout her pregnancy and she carries to term, does that mean that the orange juice prevented miscarriage?
Compounding these “rational” problems is the ever-present reality that dealing with repeated losses of desperately longed-for babies does not place most people in a rational or analytical mind-set. With each miscarriage, I felt more and more distressed, but also more determined, and increasingly open to trying drastic measures. I would try anything and everything. With any sliver of hope of success, I was willing to throw a Hail Mary. Doing nothing never felt like an option to me.
Yet ironically, the hard-learned lessons from treatments such as DES and LIT teach us that opting to do nothing—which can be much harder than trying something, anything—is often the wiser choice.
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I. Or for Americans, akin to estimating the number of people in Times Square by the number of cars on the Long Island Expressway.
It takes three to make a child.
e. e. cummings
9
Down the Rabbit Hole of Third-Party Parenting
Gestational Surrogacy
When my mother first suggested I consider using a surrogate, I absolutely was not ready to hear it, despite four miscarriages and many known pregnancy obstacles. This was before anyone ever really talked about surrogacy—before Nicole Kidman and Sarah Jessica Parker, before Baby Mama hit the big screen. She mentioned it gingerly on the phone, telling me how excited their good friends were that their son and his male partner had just had a baby with a surrogate mother; she e-mailed me articles from the New York Times, her equivalent of the Bible. I ignored her, in that very special way that daughters do with mothers. But my mother had succeeded; the seed had been planted.
After the fifth miscarriage, Richard decided to step in as well. We had long talked about the possibility of adoption, and with five miscarriages and five years under our belt, and IVF clearly failing us, he tenderly told me it was time to explore this path. I wanted to be comfortable with it, but the truth was I was just not ready to give up on biological children. I had been pregnant five times! I knew I could have a baby. Looking back, I think that after the heartbreak of grieving over five miscarriages, I had the strange but fixed notion that a successful natural-born child would somehow wipe out the pain of the five I had lost. In a way, I felt I was fighting for the life of the same baby each time. I know this is irrational, but it is how I felt.
In this respect too we were not alone, although we did not know it then. Married nine years, after four IVF cycles and four miscarriages, Paula’s husband, Derrick, was ready to give up on the fertility industry. Facing too much heartbreak, too many expenses, and too little assurance of a baby to take home, like Richard, he was ready, and eager, to pursue adoption. But Paula wasn’t there yet. The fiery and determined Brazilian-Italian told me: “You’d have had to kill me then for me to give up on having my own child.” Although theoretically open to considering adoption in the future, like me, she was too focused on trying to get her body to conceive to give any other path a chance.
Living in an international city like London, I frequently heard reports of triumphant successes in countries that were not too far away, and I felt that, having come this far, we owed it to ourselves to explore clinics overseas. Although not ready to admit it, I also had my mother’s voice in the back of my head . . . .
Richard, a consummate option maximizer, convinced me that we should pursue all the options simultaneously. We began the process to get approved to adopt in the United Kingdom, starting with required adoption classes and a home study with a social worker, a process that takes on average nine months to complete in the United Kingdom as opposed to one to three months in the United States. We also started exploring avenues to finding a baby to adopt, a search that can take years. We quickly settled on Russia as our preferred country, in part because we are both of Eastern European descent, and largely because we had connections from our professional lives to people who were well positioned to help us expedite the process there. We had each been working on projects in Moscow on and off for a number of years, and by 2005, we were spending nearly half of our time there.
Ironically, although we complained bitterly about Britain’s required group adoption classes at the start—primarily about waking up early on invariably gray Saturday mornings and taking the Tube to South London to spend the better part of our precious free day in the comparably gray concrete classroom building—we came to appreciate the importance of urging onto prospective adopters the responsibilities and unique challenges many adoptive parents face.
At the same time, in contravention of the adoption rules (which required that potential adoptive parents stop all other efforts to have a child), I researched fertility clinics in Spain, Cyprus, and the United States and started to tiptoe into the complicated world of surrogacy, a realm in which regulation and practice vary from country to country and clinic to clinic, and strangers are involved in your most intimate affairs. In addition to the already time-consuming task of evaluating the performance of the clinics, I compared the medical regimes, legal ramifications, costs, and practical aspects of how to find a surrogate in the United States and the United Kingdom, the two countries that were home to me.
Since Richard and I were living in London, we ultimately decided to pursue surrogacy in the United Kingdom so that we could fully participate in the pregnancy, see the little heartbeat on the ultrasound scan, follow the milestones. But the United Kingdom had its own complications. Our doctor at the Lister refused to perform gestational surrogacy, saying that it would not be approved by the hospital’s ethics committee. Of course, that same clinic paid healthy young women to “donate” their own eggs and allowed would-be parents to buy eggs—transactions that last a lifetime—with no ethical concerns; but they had a problem allowing a woman to voluntarily carry an embryo made up of my egg and my husband’s sperm and then give our baby back to us? A favor, albeit a huge one, that lasts nine months? We were told that in contrast to the almost universal (apart from the very religious) acceptance of egg and sperm donation, controversy persisted regarding the question of whether a woman should be allowed to “rent” her womb, a practice critics have accused of being akin to selling babies. This response was particularly frustrating in light of the fact that surrogates in the United Kingdom, by law, are not permitted to be paid.
Once again, it was time to find a new clinic and a new doctor.
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Dr. Joel Batzofin, a South African–born, New York–based fertility specialist, opened our trans-Atlantic phone conversation with “Your buns are fine, but your oven is broken.” He later asked, “Do you want to carry your baby or be a mother to your baby?” Aside from h
is stellar credentials—after university in South Africa, he was educated at Harvard Medical School and Baylor College of Medicine, followed by a stint on the faculty at Stanford University—and twenty-odd years of experience leading top fertility clinics, his warmth and compassion won me over. By the end of our conversation, I had a new doctor and a new plan. It was nearing Thanksgiving 2005. I intended to go to New York to see him just after the New Year.
The visit didn’t happen as planned. By December, I was pregnant again—having naturally conceived.
How much had changed since that Thanksgiving in New York with my parents in 2000. Now, five years later, the United States was involved in two wars, and I was waging an ongoing battle to have a baby. In 2000, I’d spent New Year’s Eve hoping the year would find me pregnant, and now I spent my New Year’s Eve worried that I was losing time by being pregnant. I wanted to be joyous, but with my track record, anxiety ruled the day; if I miscarried again, it would only prolong the wait before I could try with this promising new doctor in New York supervising my care.
Conceivability_What I Learned Exploring the Frontiers of Fertility Page 13
