Article 63H7G I took an international trip with my frozen eggs to learn about the fertility industry

I took an international trip with my frozen eggs to learn about the fertility industry

by
Anna Louie Sussman
from MIT Technology Review on (#63H7G)

Like me, my eggs were flying economy class. We-my dog Stewie and I-were in seat 8D, while 12 of my cryopreserved oocytes, four straws of three eggs each, had a window seat further back. They were ensconced in a cryogenic storage flask, known as a dewar, which was packed into a rolling metal suitcase the size of a small carry-on. This was wedged upright on the floor of the seat next to Paolo, the courier overseeing their passage from a fertility clinic in Bologna, Italy, to the clinic in Madrid, Spain, where I would be undergoing in vitro fertilization (IVF) in several weeks' time.

That morning, I'd watched a team of embryologists and their colleagues at the Bologna clinic pass various papers back and forth to Paolo, who would flash these documents at the airport to ensure that the oocytes didn't get x-rayed on their way through security. The dewar was lined with a sponge that absorbs liquid nitrogen and slowly releases it, typically for a week to 10 days (depending on how large the suitcase is), keeping whatever is inside at -196 C or cooler.

Made possible by advances in cryogenics and cold-chain technology, the shipping of gametes and embryos around the world is a growing part of a booming global fertility sector. As people have children later in life, the need for fertility treatment increases each year. The ability to move eggs, sperm, and embryos across borders allows tens of thousands of patients to access this medical care if it's unavailable in their own country because of legal restrictions or prohibitive pricing. Couriers enable would-be parents to assemble all the necessary components for a baby in the same place, whether those components come from their own bodies or are provided by a donor.

Couriers enable would-be parents to assemble all the necessary components for a baby in the same place.

There are many reasons why people might need to ship eggs, sperm, and embryos from one place to another: cost, regulatory arbitrage, access to a specific selection of donor gametes, or just life changes, such as a cross-country or overseas move.

Consider that a cycle of egg freezing costs between $10,000 and $15,000 in the US, and one-third to one-half that in Bologna or Madrid. Commercial gestational surrogacy, in which a woman carries a genetically unrelated child to term on behalf of paying clients known as intended parents," is legal in some US states but not others; it can cost $100,000 to $200,000, compared with $50,000 to $60,000 in Ukraine (until recently a global surrogacy hub) or nearby Georgia. Donor eggs are abundant in places where compensation is permitted and scarce where it is not.

An estimated 2.5 million assisted reproduction cycles are performed globally each year. Mark Sawicki, the CEO of Cryoport Systems, a company headquartered in Tennessee that provides cold chain logistics for biopharmaceutical, IVF, and animal health organizations around the world, believes that around 100,000 of these cycles involve transport of frozen reproductive material.

In my case, I had frozen eggs in Bologna in 2016, and again in Madrid two years later, because it would have taken me several more years to save up for a cycle in New York. After paying for storage costs for six and four years, respectively, at 40 I was ready to try to get pregnant. Transporting the Bolognese batch served to literally put all my eggs in one basket.

Special delivery

Once upon a time, human reproduction was a proximate endeavor. Those involved had to occupy the same place, at the same time, for a sperm cell to fertilize an egg cell. It was the successful cryopreservation of human sperm cells around the mid-20th century that eventually enabled the banking of sperm and its shipment from one place to another. Advances in dewar technology (named after James Dewar, who invented a double-walled, vacuum-insulated glass flask in 1892) and cryogenics in the 1950s made it possible to transport materials at low temperatures.

Another key innovation, egg freezing, was in part a response to the regulatory and cultural environment in Italy, where Catholic attitudes-the Catholic Church views embryos as full persons-informed the country's early IVF laws. In Italy, IVF practitioners for many years were restricted in how many excess embryos created during an IVF cycle they could freeze (a similar law remains on the books in Germany, limiting patients to just three embryos-or three chances at a pregnancy-per IVF cycle, driving many to seek care elsewhere.) Unfertilized eggs would not pose the same problem. Meanwhile, scientists around the world were also searching for a way to freeze eggs for other reasons, such as to preserve fertility ahead of cancer treatment

MIT-FINAL-1a.png?w=2000NICK LITTLE

Eggs, however, proved harder to freeze and thaw successfully, owing to their structure: a large, single cell made up mostly of water, which can create ice crystals that damage the egg. Advances in freezing techniques-first a method called slow freezing and later a process called vitrification, which rapidly cools the eggs before ice crystals can form-led to a trickle of live births by the late 1980s. Although the success rate with frozen eggs varies by clinic and by the age of the patient at the time of freezing, some clinic-specific studies show success rates of IVF using frozen eggs comparable to those with fresh eggs.

Today, couriers often move between countries or cities with highly developed IVF sectors, some of which specialize in a given treatment or necessary components (such as Spain, which has a relatively stable and abundant supply of donor eggs compared with the rest of Europe). Until Russia's invasion, Ukraine was a frequent destination for people looking to make use of the country's relatively affordable surrogacy services and its high availability of donor eggs.

The scholars Anika Konig and Heather Jacobson describe these dynamic and shifting transport routes as reprowebs" that react to regulatory and other changes, such as covid-19. This elasticity in the global reproductive industry recalls the way clothing brands shift their manufacturing operations around the world, chasing favorable labor and investment climates while sourcing the cheapest raw materials from sprawling global supply chains.

Cryos, the world's largest sperm bank, dispatches sperm and eggs to over 100 countries.

Jurisdictional and cost arbitrage are not the only reasons courier businesses are thriving. As the Australian sociologist Catherine Waldby points out, these services make it easier for prospective parents to select from specific donor pools on the basis of desired physical or racial characteristics.

You can see people importing genetic qualities from other parts of the world that in their minds are the kind of genetic qualities that they want for their family," Waldby says. For example, in her research, women who wanted white donor eggs from the US but couldn't afford the $10,000 to $15,000 price tag might instead choose a donor of European descent from South Africa with similar skin, hair, and eye coloring, for about $2,700 USD. Very often it's about seeking certain phenotypic, basically racial, qualities," she says-and finding them at a lower price.

When I first met Helle Sejersen Myrthue at a major fertility conference in Barcelona in 2018, she was staffing Cryos International's booth, at the center of which were Viking hats with horns. Cryos, the world's largest sperm bank, is headquartered in Aarhus, Denmark with sites in the US and Cyprus. The company dispatches sperm and eggs to over 100 countries. Visitors to the booth were encouraged to try the horns on for selfies; they were a nod to the company's reputation for providing blond-haired, blue-eyed Viking sperm."

Myrthue, now Cryos's CEO, noted that as societies in Asia and South America have become somewhat more accepting of single and lesbian motherhood, demand for donor sperm has grown there. To meet this demand, Cryos must source from donors with phenotypes (observable characteristics such as physical appearance) that are less common in Denmark. And customers are quite specific about what they want, she added: A Chinese doesn't want a Japanese [donor] or a Japanese doesn't want a Filipino or someone from South Korea."

Even though clients can shop from any of their locations (subject to national regulations-some countries do not permit the import of donor eggs, for example, or have specific requirements about the anonymity of sperm donors), Myrthue acknowledged, they may have to compromise if they cannot find the donor of their dream."

Precious cargo

John Loewen met his Japanese wife when they were university students in Canada, and moved to Tokyo with her. Both had family histories of cancer; Loewen froze his sperm at a Tokyo fertility clinic while still in his early 20s as a precaution. By the time they were ready to become parents, around 2009, his wife had been diagnosed with cancer. They decided to pursue surrogacy in Thailand using a Thai egg donor. Loewen tried to find a service to ship his frozen sperm; when he couldn't find one, he decided to do it himself.

He researched the transport of animal sperm online, and completed a successful practice run with mouse sperm, moving the sample from a mouse research center near Mount Fuji to a lab in Tokyo. His next attempt was to take his own frozen sperm from the clinic in Tokyo to its counterpart in Bangkok. He bought several kinds of dewars-cheap ones, expensive ones-to see whether they'd stay cold for more than a few hours. He filled them with liquid nitrogen, and saw he could keep samples frozen at the necessary temperature.

His maiden voyage to Thailand was a success, and their first child was followed by twins, also born with the help of a Thai surrogate. Upon his return to Tokyo, he put up a website, told a few clinics about his services, and that's how it started," he says.

On his third or fourth trip, he learned a valuable lesson about liquid nitrogen: Don't take it on planes without first letting it soak into a sponge that will release it slowly over time. A coolant used for everything from cryopreservation to high-tech manufacturing to ice cream, it can also cold-burn the skin on contact, and it shouldn't be subject to the air pressure changes that can occur on flights. He was already several hours into an overnight flight to Bangkok when he heard a hissing sound and saw smoke rising from the dewar that he was keeping upright on the floor between his legs.

IMG_4763.jpeg?w=480IMG_4785.jpeg?w=480IMG_4787-export.jpeg?w=480

Paolo packs the cryogenic chamber into the case to safely transport Anna's oocytes through the airport and onto the plane.

Fortunately, everyone around him was sleeping, so he discreetly opened the lid to let a little bit of pressure out. The sample survived, but Loewen suffered light burns on his legs (and couldn't sleep for the rest of the flight).

Because his Tokyo-based company, CryoSend Ltd, is one of the few serving the region, the bulk of his shipments begin in Asia-Japan, Taiwan, Hong Kong, Cambodia, Malaysia, Singapore. The samples are typically destined for the US, Georgia, Russia, Mexico, Kyrgyzstan, and Cambodia (and, until this year, Ukraine), all countries with robust surrogacy sectors and different price points.

The coronavirus pandemic initially dampened business as fertility clinics around the world temporarily shuttered or significantly reduced patient loads. But after clinics reopened, borders remained shut, leading to increased reliance on courier companies like Loewen's.

Loewen reconfigured his operations to meet the new logistical reality. Instead of relying on a single courier to hand-carry a shipment from one country to another, he utilized a network of trusted local couriers in cities around the world, plus a premium carrier service offered by airlines: the biomaterials are booked as medical cargo, usually on a direct flight.

The cost of transporting my eggs was 1,300 euros, or about $1,400 at the time.

Couriers offer a variety of options for moving biomaterials from place to place. But Stefano Monaco of FlyVet Europa, which hand-transports eggs, sperm, and embryos, believes that hand carrying is far and away the best option. It's an artisanal business, not an industrial one," says Monaco, who founded the business in 2016 after learning from his brother, a gynecologist, that biomaterials delivered to his fertility clinic in Milan often arrived in suboptimal condition, damaged during transport.

Depending on what's being carried and how much they can pay, the patient or patients involved will choose either a hand-carry service, a commercial carrier such as DHL or FedEx, or something in between, such as the combination of commercial flights and local couriers that Loewen relied on during the pandemic. The cost of transporting my eggs with FlyVet Europa was 1,300 euros, or about $1,400 at the time. That includes the price of two one-way tickets for Paolo and the egg suitcase, and a few incidental expenses. (When I told Monaco how many eggs were traveling, he quipped, Uno squadro di calcio!"-a soccer team.)

CryoStork, the division of Cryoport devoted to the fertility sector, offers all three tiers of service-commercial carriers for something that can be easily replaced (sperm, in other words), a middle-tier service using local couriers and air freight, and a door-to-door hand-carry service-for prices ranging from a few hundred dollars to as much as $7,000 or $8,000 for an international hand-carry trip.

Ultimately, the pandemic boosted business for Loewen. Today, he and a team of eight colleagues, half employees and half working on a per-shipment basis, handle around 30 to 40 IVF-related shipments each month. Similarly, when the war in Ukraine began, Loewen and other colleagues received frantic requests from clients desperate to move their biomaterials out of the capital, Kiev, where most of the country's IVF clinics and surrogacy agencies are based, and business shifted to nearby Georgia. But by September, Loewen was planning to once again deliver biomaterials to Ukraine. People want to have babies-conflict or not," he says.

The right stuff

What does it take to be a tissue courier, and how does one get into the field? Everyone I spoke to said that to succeed, you must love traveling, have a calm personality (in case, as happened to Loewen, you're ever surrounded by a knot of armed Belarusian soldiers at the airport and accused of trafficking human organs), and be adept at problem-solving.

Loewen looks for people with experience in the travel sector, who can navigate new cities and won't be rattled by a flight cancellation or a grumpy customs official. Mark Sawicki of Cryoport has several former pilots now working as couriers; their security clearances enable them to move through airports more easily than civilians.

Nicole Dorman, 43, has always loved children; she jokes that her current job as a courier is babysitting." She has three kids, aged 14 to 22, and has been a teacher's aide and a school crossing guard, following four years in the US Army. When she's home for a week or two at a time with her kids in between gigs, she also makes deliveries for DoorDash in Clarksville, Tennessee.

DB7AA4-crop.jpeg?w=2500Nordisk Cryobank devised the Sperm Bullitt" to transport samples to fertility clinics. The bicycle is fitted with a giant sperm cell containing a cooler compartment so that metal containers with sperm donations can be kept cold.WENN RIGHTS LTD / ALAMY STOCK PHOTO

Dorman had begun by transporting stem cells for a Frankfurt-based courier service. When she was looking for work in November of 2020, she emailed a half-dozen IVF courier companies and heard back from Loewen within 15 minutes. She has been working for him ever since, and also does US shipments for the Ukrainian company ARK Cryo, as well as EmbryoPort, a UK-based firm.

Dorman is on the road roughly 70% of each month; when we spoke in mid-May, she was preparing for a weeklong trip beginning with a pickup in Indianapolis, a drop-off in Bratislava, a train ride from there to Prague for another pickup, and then a flight to Greece. Like all couriers who've been working for any length of time, she has frequent flier status. In the 18 months since she started, she has transported more than 90 shipments. Now I can pretty much do it in my sleep," she says.

Until the pandemic, Paolo had been an insurance salesman, living and working in Varese, a small city outside Milan. When business slowed, he took up an offer from his cousin Marco to join FlyVet Europa, which is how he ended up with my shipment.

After our arrival in Madrid, Paolo showed me a graph of the dewar's internal temperature, which had ranged between -196 and -200 C. All went according to plan, but I do wonder if the transport affected the oocytes. When it came time to thaw them, only seven of the 12 from the Bolognese batch-theoretically a younger, healthier bunch, retrieved when I was 34-survived, compared with seven out of the seven that were retrieved in Madrid when I was 36.

Peter Hura, founder of the Kiev-based courier service ARK Cryo, says courier companies are often blamed if something goes wrong, when in fact the fault may lie with the embryologist who prepares the shipment. In my case, the survival rate was so much lower than average for the Bolognese batch-58%, compared with a more typical 80 to 90%-that the Spanish embryologist who thawed all of my eggs in Madrid thought the Bologna clinic might have used an outdated vitrification protocol.

When I asked the clinic, someone from the embryology lab confirmed that the protocol was the same as the one used in Spain, and suggested that the low survival rate came down to human biology. Cryopreservation techniques are standardized, but not the oocytes' biology," a lab worker said. Transport inference effects on the cryopreserved materials have never been demonstrated, and if the temperature logs are ok, there is nothing more that we can say about the event."

Although Hura, Monaco, and Loewen said they'd never had a mishap, there is not much anyone can do if something goes wrong in transport, since insurance for this industry only covers financial losses incurred in the creation of the embryos, typically based on bills for IVF services-small consolation for patients whose own gametes or embryos have been damaged or destroyed. Cryoport, as a large global company, offers an insurance policy which covers the cost of the transport plus a payout of $40,000 toward new IVF cycles to replace the lost biomaterials. While the company aims for a 0% loss rate, sometimes things happen that are beyond the control of a courier, such as when a tank was sitting on the tarmac at Montreal airport and a forklift accidentally drove right through it.

Still, of my eggs that survived the thaw process, 13 out of 14 were successfully fertilized, and seven embryos made it to the five-day-old blastocyst stage. One was transferred into my uterus, and the rest were vitrified, taking a return trip back to the dewar. I no longer have a potential squadro di calcio," but it's comforting to know that six more chances at a pregnancy are waiting for me in Spain-and that, if necessary, they can board a flight, chaperoned by a courier, and come on home to New York.

Correction: An earlier version of this story misstated the title of Mark Sawicki. He is the CEO of Cryoport Systems, not its parent company Cryoport.

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