For all the colorful stories behind the development of several fertility drugs, troubling unknowns surround a few of the major ones. Take Lupron, a medication commonly prescribed during fertility treatment to prevent premature ovulation during the ovarian stimulation process.[*7] Except it’s not FDA-approved for that use; its use during egg freezing and IVF is considered off-label. Lupron is approved to treat prostate cancer; it’s also approved for and used to reduce the size of uterine fibroids, treat endometriosis symptoms, and block early puberty. For all the good it does, the drug has a dark side, too. Most drugs do, but Lupron, the use of which among women has been linked with bone density loss, severe joint and muscle pain, and memory loss, is particularly harrowing. The FDA has received thousands of adverse event reports for Lupron products in the past decade[*8] and people have petitioned Congress for further investigation into the drug’s side effects; there’s even a website called Lupron Victims Hub.

Why are Lupron and other off-label drugs permitted to be used in ways they were not intended to be used? Because while the FDA has the authority to punish drug companies for marketing a drug for a use that it has not approved, regulating the practice of medicine is outside its jurisdiction; the agency doesn’t oversee where and how off-label drugs are being used. Fertility doctors, like doctors in other fields of medicine, can only prescribe FDA-approved medications—but the purpose for prescribing isn’t tracked. So, unless a case clearly violates ethical guidelines and safety regulations, physicians can prescribe drugs like Lupron for off-label uses without fear of consequences. I remembered something Remy’s doctor said to her: “A lot of these drugs are not FDA-approved for what we do. The pharmaceutical companies don’t spend the money getting things approved for fertility. So a lot of times there’s a black box warning on the meds…but don’t worry about it.”

What I took away from my deep dive into hormone injections was this: Fertility medications are both powerful and somewhat frightening, and OHSS is clear evidence that bodies can respond badly when pumped too full of hormones. When undergoing fertility treatment, everyone’s baseline hormone cocktail is different. Every body is different, and a person’s reaction to the drugs falls across a wide spectrum. Reproductive endocrinologists have to find the sweet spot for their egg freezing patients as they try to successfully stimulate the ovaries to produce eggs. Not too many, but not too few. Dial up, dial down, get the most eggs possible without endangering a woman’s life or ovaries. Holy shit, this is complicated, I texted a friend one day while I was absorbed in my research. Avoiding overstimulating the ovaries and causing conditions such as OHSS was clearly a complex skill that involved an artful interpretation of the science. Egg freezing’s price tag, it now occurred to me, seemed a bit more justified. And the stakes? Much higher than I’d realized.

“There Are No Known Risks” and Other Half-Truths

I turned to the second category of egg freezing’s medical risks: longer-term unknowns. While the short-term effects of injecting lots of hormones to stimulate the release of multiple eggs at once are known, I discovered that there’s almost no information on potential long-term harm, because research is so sparse. Hormone therapy typically raises a patient’s estrogen levels, and estrogen can abet the growth of, specifically, ovarian and breast cancers. Studies examining the relationship between fertility drugs and the risk of hormone-sensitive cancers show mixed results. For the most part, they conclude that the medications used during fertility treatment don’t appear to increase a woman’s risk of cancer. That’s the good news. But as I dug into the limited data, I learned that the validity of these findings may be affected by confounding variables such as small subject numbers, as well as specific characteristics of the populations being studied: women who have been diagnosed with infertility versus women—typically younger—who have not. I also happened upon dark stories, many deep in Reddit threads, and read studies that do indicate that the high doses of hormones used during fertility treatments may increase a woman’s risk of cancer. What I found as I tumbled down rabbit holes on the internet was some of the most worrisome stuff I had encountered since first learning about egg freezing.

Around this time I listened to an episode on Reveal, an investigative reporting podcast, on egg donors. It was a short but shocking story about a young woman, Jessica Wing, who by age twenty-five had donated her eggs three times and who died from colon cancer when she was thirty-one. Jessica was an undergraduate at Stanford when she saw an ad recruiting students to donate their eggs. She called her mother, a doctor, to ask her about it. Her mother had only one question: Is it safe? Jessica said she was told it was, and decided to do it, using the money to help pay for her college education. The eggs she donated resulted in a pregnancy. According to Jessica’s mother, this made the fertility clinic deem Jessica a “proven” donor, and the clinic offered Jessica twice as much money to donate again. Through Jessica’s egg donations, five healthy children were born to three formerly childless families. Four years after her third donation, Jessica learned she had metastatic colon cancer. Doctors also found tumors in her ovaries. There was no history of any early cancer or colon cancer in her family, and twenty-nine is a young age for such a diagnosis, especially in a health-conscious woman like Jessica. To this day, her mother wonders if the extensive hormone treatments her daughter had undergone as an egg donor might have stimulated the growth of the cancer.

The reason Jessica’s story stuck with me—besides its objectively tragic nature—was because I knew how similar egg donation is to egg freezing. Egg donation, a multimillion-dollar and poorly regulated industry, has been around a lot longer than egg freezing. The processes of donating eggs and freezing one’s own eggs are exactly the same up until the last step: An egg donor is compensated for her eggs, which are used for research or to help another person or couple have a baby, while an egg freezer’s eggs go into a cryotank and remain hers. But egg freezers undergo the same hormone treatments as egg donors do. And like egg donors, egg freezers often cycle more than once if not enough viable eggs are obtained on a first attempt.[*9]

You would think that after more than forty years, we’d know more about long-term effects for women who use ART. But in fact large gaps in our knowledge persist. Part of the problem is a dearth of follow-up data, especially in our fragmented American health system, which lacks national medical records. While organ registries exist for many kinds of organ donation in the United States, there is no egg donor registry. Because of the anonymity of egg donors, there are no other databases from which to cull numbers. The rationale is that not having a registry protects egg donors’ privacy. But not monitoring an egg donor’s health after the fact means not knowing anything about the potential long-term risks of egg donation—which, in turn, means knowing little about the long-term risks of egg freezing. Egg banks have rules about women donating more than a few times, but because the government doesn’t maintain an egg donor registry, there isn’t any centralized tracking of who has donated eggs and where and when.[*10] It’s easy for a young woman to donate eggs at different clinics and be a repeat donor as many times as she wants; once she walks out of a facility’s door, she’s lost to medical history.

Another difficulty arises when subsets of patients are treated alike even when they’re not. Most of the research conducted on egg retrievals has focused on women undergoing IVF—the first half of which, you’ll recall, involves ovarian stimulation, as do egg donation and egg freezing. And so, similar to how much of the limited data that exists on egg freezing success rates relies partially on data extrapolated from IVF (discussed in chapter 8), the health risks to women who freeze or donate their eggs have been extrapolated from research on IVF patients—but the populations are different. Most women undergo IVF because they are struggling with infertility, which can be a symptom of other health problems. Egg donors, by contrast, are chosen precisely because they have zero health problems (or at least, very few and not serious ones) and are not infertile. They’re almost always younger, unlike most women undergoing IVF, who tend to be a good deal older. Egg donors are also typically given higher amounts of hormones to stimulate the production of eggs, and many undergo the procedure several times. So, OHSS rates among egg donors differ from those of IVF patients, too. The point is, using IVF patients to draw conclusions about ovarian stimulation’s risks to egg donors and egg freezers is about as helpful as using kindergartners to draw conclusions about car seats for infants.

I read several cases about people who donated eggs and then developed cancer while relatively young. None of these egg donors had an apparent genetic risk for the disease. (Of course, cancer also develops in young people who haven’t donated their eggs.)[*11] In most of the reports, women hadn’t been given any information about the long-term risks of egg donation—in part because no such information exists. More studies on egg donors in the United States, which a national egg donor registry would help to facilitate, would give us more to rely on than anecdotal evidence of women who served as egg donors and later developed cancer, struggled with infertility, or experienced other health issues. Without such long-term follow-up data, it’s impossible to gather information to estimate the prevalence of cancer in egg donors or draw conclusions about the possibility of an increased risk compared to the general population. In a statement to Reveal, the CDC said, “Better understanding the long-term outcomes of fertility treatments for donors…is a priority within the field.” Is it, though? The CDC collects data on IVF. It or the Department of Health and Human Services could also collect data on egg donors that would help shed light on the potential link between hormone treatments and increased risk of cancer and other health issues in patients donating or freezing eggs.

The pessimistic take is that there isn’t any incentive for anyone to study the health risks to egg donors because the system as it stands now seems like a win-win-win: Fertility clinics get business, egg donors are well compensated, and infertile couples have a better chance to conceive a baby. An embryologist[*12] I spoke with who manages the lab of a well-known fertility clinic on the East Coast told me: “In the early days of IVF, everybody talked about the concerns of the drugs putting women at risk for certain cancers. Now, it’s just so swept under the rug. And before the question even comes out of people’s mouths, REIs [reproductive endocrinologists] say, ‘There’s absolutely no clinical evidence to suggest it,’ ” the embryologist continued, referring to the potential long-term health risks associated with fertility medications. “The question isn’t even allowed in the room anymore.”

The bottom line is this: The absence of information on egg donors has led to inadequate attention to potential health risks in egg freezers. And both groups aren’t appropriately counseled about the nature of that absence of information. Which brings us to the issue of informed consent. In the United States, the informed consent agreements that fertility clinics give to egg donors include minimal information on long-term risks. And the information they do provide is based on studies of infertile women rather than egg donors—and doesn’t include the crucial fact that this is a different group.

There are no known risks. That’s how most fertility clinics characterize the possible association between fertility drugs and health concerns, particularly cancers.[*13] The problem is with the word “known”: Can we really say there aren’t any long-term adverse effects associated with hyperstimulating ovaries unless such effects have been systematically researched? A 2020 New York Times article titled “What We Don’t Know About I.V.F.” summed up the issue well with a quote from an NYU School of Medicine professor: “We have no idea what this level of hormonal stimulation at this time in a woman’s life might be doing to her body.” All women who take fertility medications and undergo ovarian stimulation, especially more than once, should be told that such risks amount to a big fat question mark. But they’re not. Instead, patients are told there is no evidence proving harm, when in fact there remains considerable uncertainty about the true extent and severity of ovarian stimulation’s potential long-term health risks—especially to egg donors and egg freezers.

The podcast episode about Jessica wasn’t the first cautionary tale I had heard about the potential correlation between fertility drugs and cancer, but it was the most alarming—until I met Lesley. A nurse in Colorado, Lesley froze eighteen eggs when she was thirty-five and going through a divorce. She was driving to work one morning when, on the radio, she heard an interview with a Google employee who had frozen her eggs and used the company’s fertility benefit to pay for the procedure. Lesley felt like biology might be passing her by, and egg freezing sounded like a good idea. “It seemed harmless,” she told me. Lesley mentioned it to her mom, had a consultation at a fertility clinic, and afterward thought, Why not? Kind of expensive, but seems worth it. Using some of her savings, money from her parents, and some help from insurance (they covered a portion of the medications), she froze her eggs. Eighteen months later, she found out she had breast cancer.

Lesley’s biopsy showed that her cancer was highly hormone-driven. When she brought up with her radiologist and fertility doctor the possible connection between the egg freezing medications she’d taken and her cancer diagnosis, “they wouldn’t even open the door to go there. It was a hard stop. It’s really something that seems like it’s not talked about at all even though, logically, there seems like there would be a correlation.” While undergoing thirty rounds of radiation and a radical mastectomy—meaning the whole breast, lymph nodes under the arm, and the chest wall muscles under the breast are removed—Lesley met several other women battling cancer who also had been through fertility treatment. She learned more about how bodies have varying abilities when it comes to blocking estrogen receptors and metabolizing harmful toxins, which can make someone more susceptible to disease.

“I think we’re all these hormonal Frankensteins,” she said, sounding almost in awe of something she’d long known as a nurse but now understood in a much more personal way: the major influence hormones have on our bodies and our health. “Looking back, I probably had a ductal carcinoma in situ”—cancer cells present in her breast’s milk ducts, meaning non- or pre-invasive breast cancer—“that probably would’ve stayed dormant for forty years…and then I go and pour fuel on the fire by pumping myself up with all those hormones.” Lesley, now remarried, does not plan on using her frozen eggs. “I feel disillusioned. The trust has been fractured. And then I think, what would having a baby mean for my chances of a cancer relapse? I don’t want to have a baby and then not be there to raise it.” Looking back at her egg freezing experience, Lesley told me: “I have these eggs now that I paid a fortune for, but it doesn’t seem like it was worth it.” Her biggest regret is not doing more research beforehand. Ultimately, she told me, she wishes she hadn’t done it.

Learning about the longer-term unknowns of egg freezing that are rarely discussed between fertility doctors and patients made me frustrated—a bit angry, even. Concerned, too: I already worried when I felt a small cramp that it was another cyst on my ovary, that I was going to lose the ovary. Now I was afraid if I froze my eggs in the next few months I’d just be trading that fear for this other paranoid fear in which I’m just hoping I don’t develop a random cancer. I reminded myself that the journal articles and studies that did indicate a link showed correlation, not causation, between fertility medications and cancer. But the disquieting lack of long-term safety data, and the unsettling personal stories I’d absorbed, gave me serious pause—more than anything else I had encountered thus far on this journey.

—

Even though I now lived in Houston, I had decided I would fly back to New York to freeze with Dr. Noyes. I had forgotten to tell the fertility clinic I had moved, though, and it had been a long time since our last communication. The ball was in my court; if and when I was ready to freeze, the next step was working with the clinic’s nurses to schedule the process around my menstrual cycle, including going off the Pill, before starting the injections.

I dug around my desk in The Bungalow looking for my notes from my egg freezing orientation at the clinic. The two-hour session had been similar to the one Mandy had attended, with a handful of other women and couples. Diligent student that I was, I’d scratched out notes until my hand ached, circling the parts I’d need to figure out later, which was most of what I wrote down. The nurse talked quickly as she flipped through the slides. I turned to a fresh page in my notebook and began writing a list of to-dos. Contact patient coordinator one month prior to date of egg freezing cycle to confirm medication protocol and cycle schedule. Do online injection training. Get red sharps container from pharmacy and take needles to doc’s office. Think about disposition of eggs re: custody in event of death—donate for research or discard or…? I remember feeling flustered as I sat in the dim conference room that morning, scribbling names of drugs and medication protocols that might as well have been in Latin. In the months that followed, some of my confusion would abate as I learned more about egg freezing’s science. But my apprehension would only grow. I’d felt uneasy at the egg freezing orientation because much of it felt foreign. Now, reviewing these notes, the uneasiness was because it felt much more real—because of my trying to decide about whether or not to freeze my eggs, but also because of Ben.

Skip Notes

*1 Houston IVF was rebranded in 2018 and is now CCRM Houston.

*2 While the urine of any postmenopausal women would work, nuns provided Serono with an extra advantage: Because hormones from pregnant women would contaminate the batch, it was critical there be no chance any of the women were pregnant. Working with nuns improved the odds.

*3 The ovary cells of this type of rodent are commonly used in biological and medical research and are a cell line of choice for scientists because they produce proteins that are similar to those produced in humans.

*4 For a helpful resource on all fertility treatment medications, see resolve.org/​learn/​what-are-my-options/​medications/​types-of-medications/.

*5 In addition to young age and high egg count, other OHSS risk factors include having low BMI, having high AMH, and having a very high estrogen level during treatment.

*6 While it’s true that most fertility doctors act in the best interest of their patients, it’s also true that some are incentivized to give patients more intense hormone regimes in order to harvest as many eggs from them as possible, which can lead to spikes in OHSS.

*7 Yet, the Lupron label warns of birth defects in rodents and advises against using the drug when one is considering pregnancy.

*8 A list on the FDA’s website, noting Lupron’s potential serious risks, says the agency is “evaluating the need for regulatory action.”

*9 Many egg freezers I interviewed had done three or four cycles.

*10 When I went looking for hard data on the number of egg donors in the United States, the closest statistic I could find was the number of IVF cycles that used frozen donor eggs, which increased to 22,563 in 2020 from 7,733 in 2011.

*11 Also, though, while there’s no single cause of, for example, gynecologic cancers, there are many risk factors that could contribute to their development—such as the use of fertility drugs, especially if used repeatedly over the course of multiple egg retrievals.

*12 They asked to remain anonymous out of concern of pushback from their boss and colleagues in the field.

*13 Sometimes fertility doctors don’t even hedge with the word “known.” A 2023 episode on the podcast This Is Uncomfortable featured a twenty-one-year-old egg donor who, speaking about the clinic’s doctors and nurses reassuring her about the procedure, said, “I specifically remember them saying, ‘No study has shown that there are any negative side effects from egg donation.’ ” Shortly after her egg retrieval, she was hospitalized with OHSS.

11 Scar Tissue

Marrying Eggs to Sperm

By this point, I had arrived at the darker side of egg freezing. The deeper I went, the more questions I had about some of my unsettling discoveries. At the same time, I was much clearer on the process of vitrification, egg freezing success rates, and financing the procedure (I understood the avenues to paying, at least, even if I had no idea how I would afford to do it myself). I knew, too, that for all of the horror stories like Lauren’s and Lesley’s, egg freezing goes perfectly right most of the time. Now I was ready to turn to another facet of fertility preservation: the healthy debate over egg versus embryo freezing. Anyone considering freezing reproductive cells should consider the trade-offs between the two.

Egg freezing entails cryopreserving eggs for future fertilization. Embryo freezing is cryopreserving eggs that have been fertilized with sperm. To create an embryo, an embryologist fertilizes one or more of a woman’s harvested eggs with the sperm of a partner or donor, then observes the embryos as they develop (remember attrition rates?) in a petri dish over several days. Then, using vitrification technology we discussed earlier, the embryologist freezes the embryos. Mature, chromosomally normal eggs help to make good embryos (the quality of the sperm, of course, matters, too), which is why the younger a woman is when she freezes eggs, the more likely she is to freeze healthy eggs. Clinicians can tell if eggs are mature when they freeze them, but they can’t know if the eggs are genetically normal—that is, viable—until they thaw and fertilize the eggs, then test the resulting embryos.

It’s not currently possible to tell whether eggs are good quality at the time of freezing. This is egg freezing’s biggest weakness. Eggs, you’ll remember, are trickier to thaw than embryos. An egg is a single cell, whereas a developing embryo contains more than one hundred cells, each of which is less vulnerable to damage. Frozen eggs are less sturdy than frozen embryos; more than 95 percent of embryos typically survive the thawing process, compared to 80 to 90 percent of eggs.[*1] So, a major advantage of freezing embryos over eggs is that embryos that develop successfully can be biopsied and tested for the presence and correct number of chromosomes—forty-six—giving the person or couple more information about each embryo’s likelihood of leading to a successful pregnancy and a healthy child. Embryos can also be screened for a specific gene, which is especially helpful if one or both of the people providing the eggs and the sperm are known to have a certain gene mutation or be a carrier of a genetic disorder. (More on genetic testing in chapter 15.) In short: A benefit of freezing embryos is that you have a better idea of what you have in the freezer.

A downside of freezing embryos is that it costs a few thousand dollars more than egg freezing; on top of that, preimplantation genetic testing is another $4,000 to $6,000 or so, depending in part on the number of embryos tested. Another con is the possibility of creating excess embryos that the couple may never need in the future, after they’ve attained their ideal family size. This can pose a practical dilemma—the ongoing cost to store them, hundreds of dollars per year—as well as an ethical and more personal one: Many couples who have leftover frozen embryos after they’re done having children struggle with whether to discard them, donate them, or pay to keep them on ice even if they never plan to use them.[*2] Still, the fact that frozen embryos are sturdier than frozen eggs and can be genetically tested have contributed to embryo freezing becoming an increasingly popular option: Between 2015 and 2020, procedures to freeze embryos rose nearly 60 percent.

—

Ben remained supportive of whatever I decided to do about egg freezing. His encouragement and steadiness when it came to my work as well as my more personal endeavors had been a dependable constant of our relationship. But it was still surprising when one evening he walked into my quasi-office in the kitchen, his frame filling the doorway and a twinkle in his eye, and said, half-jokingly, “So, are you saying you would like some of my sperm? Wanna make a zygote?” He had overheard some of the phone conversations I’d been having as part of my research, like with Mandy, when during one of our long phone calls I had pressed her about her decision to freeze embryos with her husband, an option she learned about after she’d said yes to egg freezing. I laughed—what is it with men and their feeling macho about their sperm readying for a mission?—and unfolded my body from its hunched-over, deep-in-work-mode position to go hug him. He wrapped his arms around me and I relaxed into our familiar, comforting embrace, smiling into his chest.

Though Ben had been half-joking in that moment, I thought about the proposition more seriously in the context of my egg freezing plans. Marrying my eggs to Ben’s sperm would be a big biological and legal commitment. I learned that some women do half-and-half: fertilize some of the retrieved eggs to make embryos, but leave the rest, resulting in both eggs and embryos on ice.[*3] If I froze my eggs, I could theoretically mix half of them with Ben’s sperm to make embryos—our future children—and leave the other half unfertilized, just in case. The rest of that sentence that I didn’t want to say out loud was: in case we break up. If Ben and I froze embryos and broke up, our embryos would belong to both of us. But my eggs would still be just mine.

It was time to make another list: Pros of freezing just eggs:

Retain sole control and optionality over whose sperm to fertilize with

Fewer issues surrounding ownership

Fewer up-front costs

In short: fertility preservation autonomy Pros of freezing embryos: