Conceivability_What I Learned Exploring the Frontiers of Fertility

by Elizabeth L. Katkin

  “Fantastically good news!” Mr. P told me at my next appointment, as he read the letter out loud:

  “ ‘She appears to have a thrombotic aetiology to her miscarriages. She has an elevated level of Factor VIII: an impaired response to activated protein-C and thrombo-elastography demonstrates her to have a raised pre-pregnancy clot strength and an impaired fibrinolytic response.’

  “You have antiphospholipid syndrome,” he told me as he put the letter down. “Blood clots.”

  “Is that all?” I asked timidly. “It sounded like a bit more than that.”

  “No, just medical jargon for blood clots,” Mr. P replied.

  I asked him to break it down for me. I wanted to understand the diagnosis. The “thrombotic aetiology” to my miscarriages meant that I had blood clots. The “impaired fibronolyitc response” referred to an impairment in the system that is meant to prevent blood clots from growing and becoming problematic. The blood clots were actually symptoms of the antiphospholipid syndrome (APS), which he explained was an autoimmune disorder that occurs when a person’s immune system produces abnormal antibodies that mistakenly attack fats called phospholipids in the blood. This process makes the person’s blood stickier and more likely to clot in arteries and veins.

  “The good news?” I asked, a bit baffled.

  Now that we had an answer, we had a way forward, I was told. A simple blood thinner, in the form of heparin shots daily, would prevent any further miscarriage.

  Upon hearing the news, Mr. P urged us to go straight to IVF.

  * * *

  The world of assisted fertility is rife with analogies, with one of the most common being that of the slippery slope. The arguments tend to sound like this: If you allow gender selection, people will start asking for blond-haired blue-eyed babies.1 If you allow surrogacy, women will opt for a surrogate to avoid getting fat.2 If you allow a procedure that enables a woman with mitochondrial disease to have a healthy baby, it opens the door to radical genetic engineering.3

  Of course, these are valid ethical concerns and must be thought about very carefully in crafting regulations for our society that provide healthy, safe, and ethical guidelines. But from a real-world perspective, most slippery-slope analogies fail to convince me. My interviews with numerous women and couples reinforced my belief that few, if any, would opt for IVF if they didn’t have to, would choose not to carry their own baby to escape putting on weight, or would go through an invasive procedure that involves using DNA from a third party simply to create a designer baby.

  Giving voice to frustration no doubt felt by celebrities—and noncelebrities—who faced similar criticism of very personal decisions about having a baby, model Chrissy Teigen, when confronted with hostile comments about her choice, together with husband, John Legend, to select a baby girl when undergoing IVF after years of fertility problems, tweeted: “I also picked the embryo with a taste for bacon, a knack for magic and size 7 feet so she can always find shoes.”4

  People turn to these technologies because they need them to have a healthy baby.

  From my perspective as a patient, the journey through assisted fertility is more akin to a winding jungle path with hidden pitfalls, presenting moments when one has to decide to cross a rickety bridge, or even worse, to swing across by a rope with a hope and a prayer, or else admit defeat and turn back. Of course, there are lots of slippery slopes along that path, and sometimes, in sliding down toward the next bridge, you don’t even notice that your resolve, your goals, your tolerance, your strength may have changed while navigating your journey.

  Virtually every woman with whom I spoke had a resistance point, a hesitation to crossing that next bridge. For many it was IVF itself. For others it was immunotherapy, or genetic testing, or using an egg donor.

  Paula and Derrick hit the first major bump in their road when confronted with the recommendation of an egg donor. Initially favoring adoption, this was a difficult mental leap for Derrick, particularly given his, as well as Paula’s, Catholic upbringing and family pressures. They had a further challenge when confronted with a need for a surrogate, and had to work their way through emotional issues in addition to pragmatic ones, such as financing such a complicated and expensive endeavor. Jessica and Ethan’s resistance stemmed not from the radical fertility treatments but rather from the constant invasive testing and retesting required by her clinic, much of which they viewed as time wasting and unnecessary. Sarah and Evan, a couple in their early thirties who live in Boston, hesitated before opting for IVF, initially not comfortable with that type of intervention; they hit their next obstacle when contemplating intravenous immunoglobulin transfusions, a controversial therapy.

  * * *

  My first challenging decision point was agreeing to try IVF. My hesitation wasn’t religious or ethical, as it is for many. It was practical. While I had difficulty getting pregnant, I had done so twice, and I just couldn’t see how IVF was the answer for me. Mr. P, of course, didn’t agree with my amateur analysis and, presumably based on Mr. Rai’s antiphospholipid diagnosis, pushed us to go straight to IVF. But I wasn’t totally convinced. I couldn’t see how IVF held the answer for me.

  Instead of immediately jumping at his suggestion, as had been our previous pattern with every doctor, Richard and I decided to hold off on IVF. We were about to head to a tiny village in the South of France, for a vacation with some friends. I wanted to be away from everything involved in the fertility business—the Clomid, the charting, the invasive tests, the near-daily ultrasounds.

  Well, almost everything. I couldn’t part with one device—the fertility monitor.

  The way some people are addicted to their smartphones, I was addicted to my Baby Computer, which I viewed as a talisman. Cori, the friend who had given it to me, had conceived and given birth to healthy babies, as had the friend who had given it to her (and, as would the women to whom I would eventually pass it on).

  We had a wonderful wine-laden French vacation with our friends (and lots of unpasteurized cheese) as I peed on a stick and inserted it in the computer religiously every morning, checking to see if my fertility level was low, high, or peak. I returned tanned, relaxed, and healthy, and just a few weeks later, found out I was pregnant, without needing IVF. I started the blood-thinning shots that day. Knowing that the heparin shots were going to solve my miscarriage problems, I was pregnant, confident, and truly glowing. I had a wonderful month of September.

  My exuberance was short-lived. One month later, I started bleeding. I called the Recurrent Miscarriage Clinic and literally begged for an appointment with anybody on the staff, explaining that I feared I was about to have my third miscarriage. My desperation failed to convince the woman on the other end of the phone, who informed me that I would have to have had three complete miscarriages before I qualified for their care, as they only treated recurrent miscarriage patients.

  By the end of the week, I’d had “a complete miscarriage.” I qualified for the clinic’s care now that I no longer needed it. It was devastating. I had been so sure that we had discovered the cause of the miscarriages as well as the solution. Numb from the emotional pain, I don’t remember much else about it.

  But the third miscarriage was all the convincing I needed. Although I didn’t fully accept the logic of why my odds of keeping a baby conceived through IVF were greater than those of a baby conceived naturally, I nevertheless bowed to the pressures from Mr. P to try it. I was tired of doing this on my own, and I didn’t think I could take another miscarriage, either emotionally or physically. It was a lot of work managing my own health care and keeping it together at the office, the year before I was to be up for partner at a major international law firm. And I was increasingly depressed. Just getting out of bed was difficult. Two years of working so hard to become and stay pregnant was taking its toll.

  Deciding to go down the path of IVF felt like a burden was being lifted.5 I was surrendering my body and medical care to the pros, and if they got me pregnant, surely th
ey were responsible for keeping me pregnant? (It turns out not: for most fertility clinics, conception is the end of the line.)

  In early January 2004, with Christmas decorations still glittering along the streets of London, we embarked on our first IVF cycle.

  IVF Basics

  The goal of IVF, as practiced in the United States and the United Kingdom over the last thirty-five years, is to hormonally stimulate production of as many eggs as possible, extract the eggs from a woman’s ovaries, fertilize them in a lab, and place one or more fertilized embryos back into the woman’s uterus. I call this, quite unoriginally, the “needle in the haystack” approach, as it was described this way to me by a half dozen or so doctors. They are looking for the one (or two or three) good egg(s) from a pile they have procured through ovarian stimulation. While technology developed over the last two decades can now shed light on the quality of the embryos, it used to be that embryos were judged by appearance alone—size, shape, the extent of fragmentation. In many clinics, this is still how embryos are selected: by appearance under a microscope and how many days they survive.6

  My IVF initiation began in a small white examination room in Mr. P’s Victorian mansion on Harley Street. Eunice, the compassionate nurse in charge of my care, flitted about the room speaking quickly but very clearly and precisely in her comforting British accent. I wondered why she was whirling about, until she turned to face me with a handful of syringes and a few little glass bottles that would have been adorable if they weren’t so threatening sitting on their clinical metal tray. “Right . . . . Now”—she looked me straight in the eye—“let’s teach you how to do your injections properly.”

  She explained each step to me. Some injections came in easy-to-dispense preloaded pens, while others were much more “self-serve.” As is common in conventional IVF, I was to begin, counterintuitively, with birth control pills. I can think of few things more frustrating than to be forced to take the Pill after literally years of trying to get pregnant, but, as I have been told time and again, that’s the protocol. The goal is to essentially stop the menstrual cycle to restart and control it. Five days after stopping the pills, I was to start poking myself with follicle stimulating hormone (FSH), necessary to stimulate the follicles in my ovaries to develop into the beautiful eggs we were all hoping for. Thankfully, the Puregon I was prescribed, a brand of recombinant FSH (also known as Gonal-f or Follistim, among others), came in a very easy-to-use dispenser called the Puregon Pen.7 I have long been a fan of good packaging and stylish little kits—yes, I take the fancy shampoo and lotions from nice hotels—and the Puregon Pen didn’t disappoint. The bright yellow-and-blue pen, hardly intimidating, was housed in an appropriately serious blue box, which conveniently held the cartridges and instructions too. Eunice taught me how to twist the dial to dispense 150 IUs, my daily dosage, and how to change the cartridge when the first was empty. Then came the main event. In her no-nonsense way, she showed me how to pinch the fat around my abdomen, hold the pen at exactly the right angle, and slowly inject myself. Not as bad as I had feared. Thinking I was done, I started to get up from my chair.

  “Good, that’s the first step done then,” she said. “Did you need some water?” she asked as she saw me rise.

  “Uh, no, just the ladies’,” I replied, embarrassed that I thought it was that simple.

  When I returned, we moved on to Orgalutran, a brand name for ganirelix, which is a gonadotropin-releasing hormone (GnRH) antagonist, meaning that it blocks the function of GnRH, which starts the process of ovulation. Its very important function was to prevent premature ovulation of these wonderful eggs we were cooking in my ovaries. The Orgalutran is also a subcutaneous injection, meaning that it goes under the skin and is relatively easy to inject as precision is not essential. Eunice suggested that we place this one in my thigh. She advised me that the doctor would tell me when to start that one, probably five or six days after starting the Puregon.

  Then came the big gun. “The trigger shot,” she said gravely. “It is critical that you get this right.” No pressure there. The Profasi,8 or human chorionic gonadotropin (HCG), injection controls the final maturation and ovulation of the eggs. Injected thirty-six hours before the intended egg collection, the timing of this shot is critical, Eunice intoned again. “If it’s too soon, you may ovulate prematurely and all of your eggs will be lost. Too late and the eggs may be difficult to collect and you could have fewer available.” And that wasn’t all. I had to mix this injection at home from a powder—with no mistakes of course—and the concoction was then to be injected by my husband through a very large needle into a muscle in precisely the right spot in my buttocks. But not to worry, Eunice assured me kindly. When the time came, she would mark the spot for my husband with an X by Sharpie.

  Miraculously, ours was a perfect cycle, we were told, and it wasn’t even too unpleasant, once I got used to giving myself the dreaded shots, with needles significantly less friendly than the acupuncture needles to which I’d grown accustomed. I had twenty follicles, which produced sixteen eggs, that in turn led to twelve fertilized embryos, of which seven were high quality—fabulous numbers, they said. After enduring just over two weeks of blood tests, hormone injections, ultrasounds, and the final, daunting intramuscular injection delivered by Richard into my derriere, two grade I, two-day-old embryos were transferred to my uterus. Unlike in the treatment of most other women, my shots didn’t stop then. On the day of the embryo transfer, I began my daily shots of Clexane (the blood thinner for my antiphospholipid syndrome) into my tummy. Everyone was optimistic.

  I thought the hard part was over, but unfortunately, we were only halfway to the finish line. No one warns you that the “two-week wait” is the most excruciating part of IVF. Through the weeks of shots, I was too busy and focused keeping track of my daily calendar and too stressed about getting everything right to think much about the outcome. Also, I think that taking such active steps as shooting yourself with a needle every day is oddly empowering; “taking control” of my reproductive system made me feel optimistic that it would work. Then, abruptly, all the activity comes to a stop and the only job is to wait, leaving enormous amounts of time for anxiety to build.

  I don’t know if any woman undergoing IVF actually makes it to the clinic blood test without testing at home first, but I certainly didn’t. Nor did Paula or Jessica or Sarah or any of the women I spoke with. Nina, a physician from Boston, was so anxious she sometimes tested multiple times per day. I bought so many home pregnancy tests, Richard and I joked that we should have bought stock in the company.

  Finally, the day arrived. It worked! I became pregnant for the fourth time. I so wished we had done this sooner. It wasn’t so bad. Why had I been resistant to IVF?

  Less than a month later, the day before my first ultrasound scan was scheduled, I began to spot. Panicked, I called Eunice. She assured me that spotting was normal, especially with IVF, and that I should come in for a scan. But I knew. I was pregnant no longer. My fourth miscarriage in less than three years. Devastation, frustration, anger, tears. We had done everything right. What was the problem?

  Fortunately, the clinic had frozen five good-looking embryos, which my doctor suggested we use in the next cycle. But, of course, we had to wait. The one constant in fertility treatment, the inevitable mandate we could never escape, was the wait—this time, a few months before we could attempt our frozen embryo transfer. At least the embryo transfer was supposed to be much easier on my body.

  Frozen Embryo Transfer

  Since the early 1980s, when IVF was in its relative infancy, excess embryos produced during a cycle have for the most part been frozen, through a slow freezing process, for future use. Although many healthy children have been born of slow-frozen embryos, as many as 40 percent of embryos were lost during the thawing process, and those that survived experienced substantially lower implantation rates than those of fresh embryos.

  A new method of ultrafast freezing, called vitrification, has radica
lly improved post-thaw survival rates and pregnancy rates. First introduced in Spain in 2007, and in use in an increasing number of US clinics since 2008, vitrification has boosted survival rates of frozen embryos from 60 percent to as much as 95 percent.9 Pregnancy success rates with blastocyst vitrification are so high, rivaling those of fresh blastocysts, that doctors are now increasingly turning toward “freeze all” cycles, particularly when used in conjunction with preimplantation genetic testing.

  With a frozen embryo transfer, whatever the freezing method, there is no need to stimulate egg production as with traditional IVF. Rather, the challenge when working with a frozen embryo is to trick the body into preparing to welcome the embryo as it would in a normal ovulatory cycle, without ovulation actually occurring. As with a fresh cycle, this is done with hormones. Eunice instructed me again, and thankfully this time it was a lot easier than the first, as there were barely any injections. I began once more with birth control pills, cringing each morning as I swallowed my pill before brushing my teeth. The day before I stopped the Pill, I began sniffing Synarel (also known as nafarelin) twice a day to downregulate my cycle. A GnRH agonist, Synarel stops the production of natural hormones that control the release of eggs from the ovaries, and is best ingested through nasal passages. Although it wasn’t my favorite smell, I was very grateful that it was not a shot. After about three weeks of sniffing Synarel every morning and night, I cut down to once a day, and added in a daily tablet of Progynova, a form of oral estrogen critical to the most important step of a successful transfer—thickening the uterine lining, known as the endometrium, to receive the embryo.