Conceivability_What I Learned Exploring the Frontiers of Fertility

by Elizabeth L. Katkin

  Making life even more complicated for “reprotravelers”—a term I much prefer to fertility tourist, as I certainly never thought of myself as a tourist in my laser-focused medical excursions—is the fact that even in the overwhelmingly joyous event that they hit the jackpot and have their much anticipated, much desired baby, if the family worked with a donor or surrogate, the challenges to becoming a parent don’t necessarily stop at birth. Much as there is no standard protocol in the provision of ART, chaos reigns with regard to the legal status of cross-border babies.

  Enid is a single mother with dual Israeli and American citizenship.37 While living in New York, she conceived her first child with the use of a sperm donor arranged by her New York fertility clinic. When she went back to the same clinic in hopes of giving her son a baby sibling, she unexpectedly ran into egg-quality concerns she did not experience the first time. She turned to a donor egg, using sperm from the same man who sired her son, so that her son and his little brother or sister would be genetically related. Happily, the IVF worked. While pregnant, Enid and her son moved back to Israel, where her daughter was soon born.

  When a baby is born to a US citizen overseas, the child’s parent or parents must contact the nearest US embassy to apply for a consular report of birth abroad of a citizen of the United States of America (CRBA) to document that the child is a US citizen. The CRBA is critically important. It is proof of citizenship, and is necessary to obtain a US passport. In a bizarre catch-22, because a baby born to a US citizen is deemed to acquire US citizenship at birth, and because no US citizen can enter the United States with any passport other than a US passport, the newborn cannot enter the United States without a US passport, even if he or she has a valid foreign passport—even if the United States has declined to grant the family a CRBA. Without the CRBA, therefore, an American parent cannot legally bring his or her baby “home.”

  When Enid went to the US embassy in Israel to register her daughter, she naturally told them that she was a single mother, a fact made somewhat obvious by the absence of information in the “father” section of the form. When asked about the paternity of her child, Enid willingly divulged that she had used donor sperm. The officer then asked her, quite directly, if she had used a donor egg, to which she gave her shocked assent. Enid was summarily informed that she could not transfer her citizenship to her daughter, as citizenship is transferred only through DNA (although this is clearly not the case with adoptive parents). She needed proof that one of the donors was a US citizen. Both the egg and sperm donations were made in New York, most likely by US citizens, but her donors were anonymous, and there was no way to prove citizenship. Despite giving birth to her daughter, breastfeeding her, and having full legal responsibility for her well-being, Enid was told that she could not pass on her citizenship to her.

  Fortunately for Enid, and others in her situation, the long-established State Department interpretation of the Immigration and Nationality Act requiring citizens to have a genetic connection to their child was relaxed slightly in 2014, allowing gestational mothers (those who carried their babies) to pass on US citizenship to their children, provided that the gestational mother is considered the child’s legal mother under the laws of the birth country. While this is a boon to single mothers like Enid, or to women who may have a same-sex or non-US-citizen spouse or partner, it still leaves many families out in the cold. What about a couple made up of a father who is a US citizen and a mother who is not, who needs to rely on a sperm donor? Or a couple in which the mother is a US citizen and the father is not, which needs to use a traditional surrogate or egg donor and surrogate? Or a binational lesbian couple where the woman who carries is not the US citizen? In each of these cases, since the US citizen, while a legal (and actual) parent, did not supply the genes, his or her child is out of luck.

  As a lawyer who practiced overseas for nearly a decade, I am no stranger to the vagaries of international law. I had also extensively researched the pros and cons of pursuing fertility treatment in several jurisdictions. Yet when Richard and I decided on the unusual path of transferring embryos to me created of both my own egg and a donor’s egg at the same time, we did not think for one second about any implications for the citizenship of our child. In our case, had it worked, we theoretically shouldn’t have had a problem as we were married and Richard was the genetic father, but it certainly had the potential to make our lives more difficult. When we contemplated using a donor egg with Catherine, our surrogate, had I not had good eggs, we similarly never thought about the citizenship question, and we could have been walking into a minefield.

  As it was, as two married US-citizen parents, it was still quite a time-consuming and hair-pulling ordeal extracting our CRBA for our son, William, from the US embassy in London. Although recognized as his mother under English law, and possessing a birth certificate with my name listed as “mother” and Richard’s as “father,” the embassy official in London had a list of maddening demands. He asked for the hospital records of William’s birth, which, of course, listed Catherine as the admitted patient, and asked for our marriage certificate. Again, despite my name on the birth certificate, medical records of my IVF treatment, and a letter from Dr. Oxana providing assurance that the embryos were mine, he classified our son as a child born out of wedlock to a US citizen father and a British mother, a situation that would require Richard to prove paternity, further slowing down the process and adding expense. But the issue to me was much bigger than obtaining citizenship; it was being recognized as my son’s legal mother, something that came quite naturally to the Brits.

  Frustrated and unable to budge the embassy ourselves, I called Ann, the English court-appointed social worker assigned to guide us through our case. We had known Ann since our daughter, Alexandra, was born, and she had helpfully and cheerfully steered us through the comparatively straightforward UK process to obtain our parental order and birth certificate. She was as outraged as I was, noting that the US stance of disregarding our British birth certificate was a treaty violation, and she contacted an English judge to ask him to intervene on our behalf. A few days later, we were back at the embassy in front of a Homeland Security officer, now willing to accept my maternity. Finally, after nearly two months stranded in London, we received from the US embassy William’s consular report of birth abroad, listing me as his mother and Richard as his father.

  Two days later, US passports in hand, our internationally conceived British-American family of four boarded the plane home to New York.

  The world is full of hopeful analogies and handsome dubious eggs called possibilities.

  George Eliot, Middlemarch

  13

  The Good, the Bad, and the Eggs

  The Fundamental Debate About Egg Integrity

  I’d like to believe that I knew at the time how lucky I was to have met Dr. Oxana when I did. But if I didn’t know it then, I certainly had figured it out by the time she found good eggs in me. And I was a downright acolyte by the time William was born. But it was when I was sitting quietly in the back of the hotel ballroom in New York City in 2016 observing the ART World Congress that I truly comprehended how fortunate Richard and I were.

  I had attended the medical conference as part of my ongoing effort to understand the impact, if any, of IVF on egg quality. Alexandra was nine years old, and William six, and although I was no longer trying to have children, I was still pursuing concrete answers to the questions raised for me that first day I met Dr. Oxana—questions that plagued me during and after my own fertility pursuit and success. I needed to keep digging as part of my effort to help others, but also, honestly, because I couldn’t let it go.

  In digesting how superior contemporary PGS techniques are to those available when we were trying to conceive, I realized yet again that we had beaten the odds. The ability to test embryos with the remarkable precision that exists in 2017 has shed much light onto the size and nature of the mosaicism problem, which had previously languished in the dark.1 It t
urns out that at the time we had our genetic testing for Alexandra, using the first-generation FISH technology, as many as half of the day three embryos tested may have been mosaic. That means that when Richard and I were told in New York in 2006 that three were normal, we were pretty darn lucky that at least one of the two that we transferred actually was normal. We had no idea at the time that we were running that risk. We basked confidently in the glow of knowing that we had a perfect little girl growing inside. It also means that when my next two batches of embryos were tested in 2008 using FISH, and none turned out to be normal (zero out of five, followed by zero out of eight), one of those little guys might have turned out all right. But how could we know?

  Yet look at what that first-generation technology did for our family: after six miscarriages (many with complex abnormalities) in a row without PGS, we had two healthy children with PGS.

  During the 2016 ART World Congress, renowned geneticist and PGS pioneer Dr. Santiago Munné noted that even among those using the most sophisticated PGS techniques, there are stark differences in aneuploidy rates (embryos with abnormal chromosomes) between different fertility clinics and even among doctors within the same clinic. One study, he pointed out, showed the rates of abnormal embryos to range from 18 percent to 60 percent,2 while the different rates of mosaic embryos ranged from 16 percent to 44 percent.3 Dr. Munné reflected that these differences likely resulted from the different stimulation protocols and culture media used by the various doctors and clinics. He looked up as he addressed an audience of the world’s leaders in the field.

  “Aneuploidy is not only produced by maternal age but also by ourselves, by the IVF procedures . . . . We have looked at hormone stimulation forever and it’s really hard to pinpoint how this could happen, but it is the likely suspect. We are producing chromosomal abnormalities and we now need to determine how we can improve results just by changing things in the lab.”4

  I sat up straighter in my chair. Was one of the foremost experts in genetic screening in the United States declaring to the scientific community that IVF as commonly practiced here was detrimental to egg quality? That the fertility labs were likely creating some of the chromosomal abnormalities the new technologies were working to weed out?

  Dr. Munné concluded his remarks. This could be good news, he said. “If we can create chromosomal abnormalities, we can fix them.”

  This was music to my ears. Dr. Munné’s words lent scientific validity to what I had firmly believed for a number of years. A belief that I felt was so important that it was one of the driving forces that compelled me to write this book.

  I looked around me to gauge the reaction of the crowd. In a roomful of scientists, researchers, and practitioners from abroad, far more heads than I expected were nodding in agreement.

  I was also very gratified to hear Dr. Munné’s words because, while I have long believed that Richard and I would not have our precious children if not for the existence of PGS, I am also well aware that the PGS would not have been worth much if, as I had been told, I indeed had no good eggs, and therefore no good embryos, left to find. Luckily for Richard and me, we had decided to give Dr. Oxana’s radical “philosophy” on non-static egg quality a chance. A philosophy that I had just heard legitimized by one of the top fertility scientists in the United States.

  All About Eggs

  Egg quality, it turns out, not only matters, it is everything. Without a healthy egg, there can be no healthy embryo. What do women with infertility, repeated IVF failures, and multiple miscarriages have in common? Abnormally high numbers of eggs with chromosomal abnormalities.

  While most US fertility doctors have traditionally advocated the position that chromosomal errors in eggs accumulate gradually over thirty to forty years and are beyond our control, multiple research studies show that many chromosomal abnormalities actually occur in the couple of months before an egg is ovulated,5 indicating that improving the quality of eggs is, to some extent, within our control.

  As conventional wisdom maintains, girls are born with a set number of eggs. However, the eggs, which begin developing in the tiny ovaries in utero, are not mature, or fully developed at birth; rather, each immature egg exists in a state of suspended animation, waiting its turn to develop into a fully mature egg, capable of surviving ovulation and perhaps fertilization. (The vast majority of eggs, incidentally, will die off in the process.) The eggs grow and develop through a process called meiosis, a complex mechanism of cell division and recombination by which immature eggs create their own distinct genetic patterning—their DNA—as they develop into mature eggs. An egg starts out as a single cell, which divides into two, then divides again into four, each time ejecting copies of chromosomes. Ideally, each of the four daughter cells has a single strand of twenty-three chromosomes, half the chromosomes of the original parent. Sperm similarly go through meiosis, through a slightly different process, and end up with a corresponding string of twenty-three chromosomes. When fertilization occurs between one sperm and one of the four daughter cells, the chromosomes pair, resulting in forty-six chromosomes in the embryo. When something goes wrong in the process, abnormalities—such as a missing chromosome or an extra chromosome—result. These chromosomally abnormal eggs—aneuploid eggs—when fertilized, form aneuploid embryos, the vast majority of which miscarry.

  Although meiosis begins and is largely completed while a female fetus is still in the womb, each egg does not go through its final stage of meiosis until many years later, approximately six to sixteen weeks before it is ovulated. There is, therefore, a long time period, lasting throughout a woman’s entire reproductive life span, in which things can go awry. Contrary to the long-held view that chromosomal abnormalities occur gradually over decades as a woman ages, numerous European studies clearly indicate that many chromosomal abnormalities in eggs arise during the final stages of meiosis, occurring in the weeks and months before ovulation.6 What’s more, embryos obtained through IVF more frequently have multiple complex abnormalities that occur during this latter stage of meiosis than those of naturally occurring pregnancies, in which abnormalities usually involve only a single error from a far earlier stage of development.7

  If we know that the environment during meiosis, not merely the passage of time itself, can foster the development of abnormal eggs, we can change the environment.8 There is a brief window of opportunity during the growth phase before ovulation in which women can increase their odds of developing healthy eggs, through, for example, increasing certain nutrients and supplements known to support normal egg growth and development, and eliminating exposure to known toxins, such as BPA and phthalates.

  Understanding this window of opportunity is important for those trying to conceive on their own; and it is critical to anyone undergoing or considering assisted reproductive technologies. For it is precisely during this time of meiosis that women undertaking IVF undergo ovarian stimulation protocols, which—as we now know—at high levels, may have a negative effect on egg quality.

  In 2002, distinguished reproductive technology expert Lord Winston, in response to a study that indicated a high number of chromosomally abnormal embryos following IVF, noted that it was “not clear whether the incidence of chromosomal abnormalities is increased after administration of gonadotropin, perhaps as a result of over-riding natural checkpoints.”9 Lord Winston speculated that “the majority of these chromosomal abnormalities may arise after resumption of meiosis, just before ovulation” and remarked that it was worrying that elevated incidence of chromosomal abnormalities following IVF “has attracted so little attention from those practising and regulating IVF.”10

  In spite of his prominence, Lord Winston’s theory remained largely unexplored for years. Yet over the last decade, research teams in the Netherlands,11 Spain,12 Italy,13 India,14 Japan,15 and Russia16 have found that conventional ovarian stimulation protocols may have a negative effect on egg quality, causing women to produce fewer normal eggs and embryos than those with a mild stimulation prot
ocol (or no stimulation at all). In study after study, these scientists concluded that lower doses of stimulation drugs could significantly improve embryo quality and fertilization rates.

  This is an exciting time for confronting infertility, for if egg quality is not predetermined and does not follow a one-way street into decline, then women can theoretically—and in reality it turns out—improve their egg quality and increase their chances of conceiving a healthy baby. As the conventional Anglo-American thinking about eggs is being turned on its head, there are both natural and interventional methods available to right the sinking ship.

  Optimizing Your Environment for Healthy Eggs

  “Widespread exposure to toxic environmental chemicals threatens healthy human reproduction,” the International Federation of Gynecology and Obstetrics warned in a landmark statement in 2015.17 The announcement was made largely in response to the rampant growth of endocrine disruptors, chemicals found in many everyday products that imitate sex hormones and often confuse the body’s own systems. Endocrine disruptors are everywhere, lurking in items ranging from plastics, food cans, and cash register receipts to personal care products like soaps, shampoos, and cosmetics. The Endocrine Society, an international association of doctors and scientists specializing in the hormonal system, concurs, noting the mounting evidence linking endocrine disruptors to infertility, as well as a host of cancers (breast, uterine, ovarian, testicular, and prostate, to name a few). We are unwittingly exposed day after day.