It is one thing to acknowledge that environmental influences affect egg quality, and that conventional ovarian stimulation protocols designed to help women have healthy babies may, ironically, in some cases, be harming the tiny eggs they are designed to help. It is another step to accept that removing these influences, even after years of exposure, may foster an environment that enables the maturation of healthy eggs. But it is a greater leap still to establish that there may be a medical protocol that an infertile woman can administer at home that can “cure” her eggs, enabling her to conceive. This is the leap that Dr. Bernstein and her team are making.
It is well-known that as women age, their supply of eggs diminishes. When they have fewer eggs, their inhibin level goes down. Inhibin is a protein that suppresses FSH, so when a woman’s inhibin level drops, her FSH level goes up. Although most clinicians firmly believe that FSH levels have no bearing on whether embryos have a normal complement of chromosomes, Dr. Bernstein begs to differ, noting that this conclusion is not justified by the data. Referring to studies that demonstrate that high levels of FSH strongly correlate to high numbers of embryos with trisomy, she argues that this clear correlation supports the hypothesis that high FSH is a cause of aneuploidy, particularly among older women.
Dr. Bernstein founded Pregmama to develop protocols to reduce FSH levels among women and thereby help cure their infertility. Together with her colleagues, Dr. Bernstein performed studies on midlife mice with elevated FSH, high rates of egg aneuploidy, and diminished fertility.42 When they lowered the FSH levels in the mice through treatment, the quality of their eggs increased, chromosome abnormalities decreased, and fertility significantly improved. Conversely, increasing FSH levels in the mice led to dramatically increased rates of chromosome abnormalities and reduced fertility.
Her goals are admittedly ambitious: “To bring babies into the world. To prevent egg aneuploidy and embryo death in AMA [advanced maternal age] women.43 [To reduce] the incidence of infertility, miscarriage and/or trisomic stillborns and live-borns.”44 Dr. Bernstein’s research is deeply rooted in the (scientifically supported) belief that hormone levels have an impact on egg quality. While recent research has looked at the impact of external hormones, such as the IVF injections, on egg and embryo quality, it is a woman’s internal environment, her natural hormone levels, that intrigues her. Acknowledging that the “notion that hormone levels in women may cause oocyte aneuploidy has been largely discarded by obstetricians and gynecologists,” Dr. Bernstein has a different perspective. Citing data that supports her hypothesis that it is hormonal aging that plays an important role in causing errors in meiosis, and therefore in egg and embryo quality, she believes it is possible to reduce the incidence of chromosome abnormalities in older women or those with fertility challenges by restoring the hormone balance to that of a young, fertile woman.
Dr. Bernstein’s first therapy, now in clinical trials, is called Veriploid, and she and her team are already at work on a second method called Eggtivin. “Veriploid is designed to roll back the clock to enable healthy egg maturation, meaning an egg with the correct number of chromosomes,” said Dr. Bernstein. Although still in the trial stage, Pregmama’s Veriploid therapy has already achieved its first pregnancy and live birth. A healthy baby boy was born in January 2016 to a forty-five-year-old woman who had experienced five years of infertility before agreeing to join the trial.
The treatment comprises drugs that have been used safely for many years in other medical contexts. The key difference here is the dosage, and the length of time a woman takes them. The idea of the treatment is to bring the FSH closer to its ideal levels, in order to create a cellular environment that fosters the growth and maturation of healthy, chromosomally normal eggs that may be capable of becoming fertilized naturally. Imagine that. Having a kit at home to self-administer hormones, which are carefully monitored and adjusted, and even getting pregnant the old-fashioned way.
Too good to be true? Dr. Bernstein doesn’t think so.
Tomorrow belongs only to the people who prepare for it today.
Malcolm X
14
Minding the Gaps
Reflections on the Future of Fertility
Seeing my beautiful, healthy children playing joyfully with their new (naturally conceived) baby cousin, I wonder if my daughter, in particular, will confront the challenges I faced in trying to have her own children. Did she inherit my hormone imbalances? My challenging immune system? My arcuate uterus? If so, what will treatment look like two to three decades from now? Will she be able to afford it? Will she have the critical information she will need to make informed decisions? Will the entire landscape have changed in ways I can’t even imagine?
My children, like the children of so many amazing people whom I have met in the process of writing this book, would not be here today without the incredible advances made by scientists and doctors over the past half century. Paula and Derrick’s twins; Pietro and Peter’s daughter; Robert and Jeffrey’s twins; my own Alexandra and William. They would all be just figments of our imaginations rather than the living, breathing human beings we so cherish.
Since the birth of Louise Brown, pioneering physicians have refined IVF techniques and protocols; embryologists have invented new culture mediums and greatly enhanced our understanding of embryo development and the ability of embryos to survive in the lab; geneticists have developed ever-more-accurate techniques to assess the chromosomal makeup of eggs and embryos; and the further evolution and acceptance of IVF have enabled parents in need of assistance to enlist the aid of egg donors, sperm donors, and surrogates in their quest to have a child. Indeed, for would-be parents who know how to ask the right questions and access the necessary information, there are now a myriad of treatment options available—if they can pay for those treatments, or are fortunate to live in one of the rare states with adequate insurance coverage available (or better yet, in a country with national insurance).
Yet regrettably, despite many laudable advances, significant gaps persist in the United States in the provision of nearly every aspect of fertility treatment, limiting our ability to treat those in need in the most effective, efficient, and fair manner. There is a gap between the costs of treatment and the amount most people can afford to pay; a gap between the fruits of scientific research and the understanding and treatment options offered by many, if not most, practitioners to their patients; and a gap between the life-giving possibilities that are quickly evolving with the advent of new technologies and the policies and laws in place that govern not only the provision of fertility services but also the recognition of parenthood itself. In order to take advantage of the many remarkable advances in treating infertility and increase availability to all who desire and would benefit from the advances, we need to close these gaps.
The Financial Gap
The stark reality is that in America, in 2016, overcoming infertility is only for the rich, and the lucky few who live in Connecticut, Illinois, Maryland, Massachusetts, New Jersey, or one of the other few states that require insurers to cover, at least to some extent, IVF. In a country in which only one-third of the population has $1,000 or more available to them in an emergency, the high costs of IUI, IVF, and other fertility advances clearly leave many who require them in need. Those who can afford expert advice, IVF at the best clinics, expensive egg donors if need be, the fees charged by legitimate agencies, compensation for surrogates if necessary, and legal fees, are much more likely to have the baby they dream of than those who cannot.
But it doesn’t need to be this way. Those seeking fertility assistance in Canada, Australia, Sweden, Spain, France, Denmark, the Netherlands, even Saudi Arabia, don’t face this first, often prohibitive, obstacle. In these nations, and a host of others, infertility is considered a medical problem like diabetes or cancer, and treatments that aim to address it are covered by the national health system as with any other disease. Moreover, their free or highly subsidized care is often accompanied by l
ive birth rates that rival those of some of the expensive clinics in the United States. Many insurance carriers in the United States, in contrast, not required by federal law to treat it as they treat other medical conditions, tend to regard infertility as a social issue—an elective procedure—rather than a medical one. As is the case with elective plastic surgery, for example, insurance companies often deny coverage altogether, or perhaps allow patients to purchase supplemental coverage as an “add-on.” Yet few women “elect” being infertile.
Given the current political climate, in which the Affordable Care Act and Medicare seem perilously at risk, it is difficult to imagine the type of broad sweeping support of fertility treatment in the United States that is a given in other developed countries, but as with the provision of health care generally, I believe there is a moral imperative to treat aspiring parents more evenly throughout society. Do we want to live in a country where affluent, predominantly white people confronting infertility are able to afford the medical teams and treatments they need to help them have a baby, while their less financially secure neighbors cannot? A country where those fortunate to live in a state like Illinois, which covers IVF, may sit side by side in a fertility clinic waiting room with counterparts from Wisconsin, only 5 percent of whom have insurance that covers IVF? Imagine the frustration of women who live in a state like New York, which requires that insurers cover diagnostic tests such as hysterosalpingograms, endometrial biopsies, blood tests, and ultrasounds—all given in order to detect medical problems—but does not mandate that those insurers provide coverage for procedures such as IVF to remedy the fertility problems that the tests may reveal.1
Insurance is shaping treatments in ways that are neither best for the patient nor financially sound—often leading women, for example, to transfer higher numbers of embryos in hopes of avoiding another cycle, mandating treatment at certain clinics and prohibiting it at others, and forgoing testing that could help ensure against abnormalities. Even in “good states,” like Massachusetts, insurance coverage can be maddeningly inconsistent. Nina, the physician in Boston, and her husband, Ken, felt fortunate to live in Massachusetts, where their insurance covered IVF treatments. Indeed, Nina recalls laughing when they discovered that their insurance would pay for six cycles, which seemed to them like a very high number.
“We thought there was no way we would ever be in the position of trying IVF six times,” she told me. “I thought I would give up way before then. But you wake up one day, and you are there.”
Embarking on their adventure full of hope, Nina did not anticipate the cycle of pregnancy and miscarriage that was to follow. Almost paralleling my history, she experienced five miscarriages, all naturally conceived, four of which resulted from chromosomal abnormalities. Complicating her situation, Ken had a mitochondrial disorder, and the doctors had no idea whether this was playing a role. After three failed IVF cycles, neither Nina, Ken, nor their doctors felt it wise to continue IVF without genetic testing that would identify any normal embryos. The physical and emotional toll was just too high. Their insurance company, however, wouldn’t pay for the testing. It would cover three more cycles of IVF, at approximately $15,000 a pop, but would not cover $3,000 for the genetic testing that might take them off their dreadful treadmill. In order to get the testing they and their doctors believed was necessary, they paid out of pocket. Coincidentally, Nina’s sister, at virtually the same time, was also trying to conceive in Massachusetts. She learned that she and her husband were carriers of Canavan disease, a recessive degenerative disorder that causes damage to nerve cells in the brain, and that any child they might have had a one in four chance of having Canavan as well. Their Massachusetts insurance covered up to six cycles of IVF with PGD. Nina has yet to have a child, while her sister, with the help of IVF with PGD, gave birth to a healthy girl.
Given this uneven and complicated landscape, what is a woman or couple confronting infertility or recurrent miscarriage to do? Or a gay couple or single woman who desires to have a child? As things stand now, in the absence of deep resources, the best people can do is to try to game the system:
Get as many tests covered by insurance as possible. Even in states without mandated fertility coverage, basic diagnostic procedures, such as blood tests and ultrasounds, which can shed a great deal of light on fertility problems, will often be covered.
Shop around for fertility drugs. When living in London, I ordered my IVF medicines (after a cycle that was completely funded by the National Health Service) from a group called the International Pharmacy Organisation, which delivered them directly to me at prices far lower than those offered by my New York clinic. Some Americans save money by ordering their medications online either domestically or looking to countries such as Canada, Israel, or the United Kingdom.2
Look for a job with a company that covers infertility treatment. Seriously, for some, this is the answer. Go work for Spotify, Bank of America, Discovery Communications, Time Warner, Chanel, Intel, Apple, Facebook, Perkins Coie, Zappos, and a host of other companies that provide excellent fertility care. Job switching for fertility benefits has become common enough to spark web forums, such as “Jobs With Infertility Coverage”;3 coverage in mainstream media like Fortune;4 and a shout-out in FertilityIQ,5 a company whose raison d’être is to help patients navigate the infertility treatment maze. Although just over a quarter of employers in America provide infertility coverage, the number is growing, led in large part by technology companies that are pouring more money into fertility benefits than any other industry in an effort to attract and retain talent and create a work environment where working parents and aspiring parents can thrive. Recognizing that “the impact [fertility] benefit[s] can have on an employee’s life is immeasurable,” Southwest Airlines now offers partial coverage to its team members, more than one hundred of whom use the benefit annually.6
Talk to doctors about protocols that maximize the return on dollars spent. Patients may wish to consider financial considerations in shaping their treatment plan. Mini IVF, for example, which requires the purchase of far fewer drugs as well as lower cycle costs, may be an appropriate course to pursue for many women. Given the low success rates of IUI, raise the question of skipping the usual three cycles of IUI before moving on to IVF, potentially saving time and money in the process. In the same vein, although PGS may seem to add to the costs of IVF, it could potentially eliminate the need for follow-on cycles.
Consider traveling to lower-cost places. Jenny went to Spain; Sandra went to Mexico; I went to Russia. Articles abound of couples traveling to Israel, India, Thailand, and, more recently, Argentina and Barbados. Fertility tourism, or reprotravel, may offer a viable solution for those with the time, ability, and appetite for travel. Treatment in some of these countries is offered at costs less than the cost of the drugs in the United States, while maintaining high success rates. A cycle of IVF costs on average $6,000 in Spain, $7,800 in Mexico, $3,300 in India, and $3,000 in Russia, as opposed to $12,000 to $25,000 in the United States.7
There is much work to be done to make quality infertility care affordable to a far greater percentage of the population, but in the meantime, there are steps individuals can take to improve their access to the best care available. It is imperative that fertility patients get informed about their own challenges and the paths available to them. Be aware that a purchaser of infertility care is a consumer, not just a patient, and must approach the acquisition of fertility treatment to some degree as one would any other significant purchase. One IVF cycle in the United States costs as much as a car. Doesn’t it deserve as much research effort?
The Information Gap
Paula spent hours, days, late nights, bent over her computer researching her own fertility problems, intent on understanding them and having a say in her care. Likewise, Jessica, with the help of her physician husband, invested so much time educating herself on all aspects of her fertility care that it became her “secret second job.” Marcy, Susan, and I, all lawyers,
attacked our problems as we would a complex legal problem, tracking down every available piece of information and analyzing it from all angles.
Reflecting on my numerous conversations with these amazingly persistent women, I realize that there is a common thread beyond, for some of us, a JD. We all sought to educate ourselves about our challenges, outside the sphere of what our doctors told us. Of course, we all sought and received medical advice from our doctors, and much of it was helpful, but, despite being in different cities with different doctors and different problems, we each came to the same conclusion: that the information we had been given was insufficient; that the protocols were not necessarily tailored to our individual situations; that we were rarely presented with options. Instinctively, we all knew that we weren’t being given the full story—that there must be something more.
The instinct, especially in the age of instant information, to google medical problems is certainly not limited to sussing out infertility. When I painfully damaged my knee, tearing my ACL and meniscus, my orthopedist told me that I needed to have surgery and suggested a cadaver graft. I promptly went to the Internet, not because I didn’t believe what he was saying but because I wanted to learn about the surgery and understand what it entailed. I read the views of others who had been through it, digesting the pros and cons of using a cadaver versus my own patellar tendon. Nothing I read contradicted what my orthopedic specialist told me, and I did not question his judgment; I simply wanted to supplement his advice and prepare myself for the long recovery.
Conceivability_What I Learned Exploring the Frontiers of Fertility Page 24