In a post-Roe world, Amazon’s newest series Dead Ringers is unapologetically visceral and poignantly clinical. A gender-flipped, highly divergent remake of David Cronenberg’s 1988 film follows the complicated relationship of Elliot and Beverly Mantle (both played by Rachel Weisz), twin obstetrician-gynecologists whose brilliance tests the equilibrium of their bond, the lens through which the disequilibrium between women and their bodies is explored.
Warning: Spoilers for Dead Ringers below!
Channeling the psychosexual thriller qualities of its cinematic progenitor, Dead Ringers rides its science hard at times. At the Mantle’s holistic birthing center, where babies and bioethical conundrums are very much thematic twins, uber-wealthy women want to use the Mantle’s intellect to skirt legal regulations around surrogacy and create bespoke services that promise everlasting youth and longevity.
In particular, Elliot Mantle, the more scientifically driven of the pair, boasts that menopause — a natural biological process marking the end of an individual’s reproductive years with the permanent cessation of menstruation — is as easily malleable as a magician bending a spoon.
“We can postpone it. We can delay the onset of it,” says Elliot at a dinner meeting with potential investors for the new birthing center in the second episode. “It’s a good example of something that we technically know how to do, but we’re limited by law, ethics, finances, bodies to experiment on.”
Elliot makes an even bolder claim that menopause could be prevented indefinitely through a real-life procedure called ovarian tissue freezing. Such a technique, the twin insists, would have women preserving their own ovarian tissue when they’re brimming with estrogenic youthfulness and re-implanting on the rainy days of hot flashes and unsexy infirmity.
It’s a not-so-subtle dig at the booming anti-aging culture so dependent on making us feel bad for sprouting a crow’s feet or two. But is it really possible to counter menopause — really, reproductive aging — with a simple tissue implant? The prospect of that feminine fountain of youth is much closer than you think, although it is questionable whether it’s even worth it.
WHAT IS OVARIAN TISSUE FREEZING?
Also known as ovarian tissue cryopreservation, it’s a still-experimental procedure where a portion of an individual’s ovarian tissue is surgically removed and then placed into cold storage for fertility preservation and future use, Elizabeth Rubin, an obstetrician-gynecologist and reproductive endocrinology fellow at Oregon Health and Science University, tells Inverse.
“Typically, [it’s done] in situations in which people with ovaries are about to undergo an extremely gonadotoxic therapy, such as certain types of chemotherapy, or are known to have a condition, usually genetic, in which they will go through menopause, either around or even before the time of puberty,” she explains.
While there are other routes to preserve future fertility, such as egg or embryo freezing, these aren’t options for individuals who are too young, can’t delay their cancer treatment, or recently had chemotherapy.
“The ASRM [American Society for Reproductive Medicine] still considers ovarian tissue cryopreservation or freezing experimental,” Michelle Roach, assistant professor of obstetrics and gynecology at Vanderbilt University Medical Center, tells Inverse. “It’s not something routinely done… except at a few centers… the best way to preserve fertility, it’s still egg freezing or oocyte preservation.”
The magic is in the anti-freeze solution and technologies, explains Kutluk Oktay, professor of obstetrics and gynecology at the Yale School of Medicine and medical director of Innovation Fertility Preservation and IVF.
“You cannot just take the tissue and stick it in your fridge or freezer,” Oktay tells Inverse. He says that when you freeze a cell this way, ice crystals form and damage the delicate components of the cell. Instead, “you prepare very thin slices [of ovarian tissue] that fit into test tubes fitted to specialized machines, and then you mix them with cryoprotectants.”
Once locked away like Han Solo in carbonite according to a specific freezing formula, these slices of mostly the ovarian cortex — the outer layer of the ovary containing primordial follicles (aka immature eggs) — are kept under watchful eyes for several years in specially equipped storage facilities.
When someone is ready to use their iced eggs for pregnancy, the tissue is thawed and then placed back into the body near any remaining ovarian tissue or where it was initially removed. It may also be placed, as suggested by Dead Ringers’ Elliot Mantle, in the armpit, which is nicely vascularized and rich in blood, but more on that later.
HOW SUCCESSFUL IS OVARIAN TISSUE FREEZING?
According to Memorial Sloan Kettering Cancer Center, around 200 babies worldwide have so far been born from preserved ovarian tissue, with half of those pregnancies occurring naturally and the other half with help from assisted reproductive technology techniques like in vitro fertilization (or IVF).
In his clinic, Oktay — who performed the first reported ovarian tissue autotransplantation (going back into the tissue donor versus someone else) in 1999 — says he’s seen it work for patients in whom ovarian tissue was harvested when they were teenagers, a decade and one ovarian tissue transplant later were able to have two or three children, either naturally or through IVF.
But as with anything in science, there’s always a catch. One impediment to the success of ovarian tissue cryopreservation is that when the tissue is reimplanted, the number of eggs you start with isn’t the number of eggs you end with. This is crucial because every individual with ovaries, for the most part, is born with a set number of eggs that slowly dwindle with age.
“The one hurdle we have, which we’re overcoming with time, is that freezing and thawing doesn’t kill that many eggs,” says Oktay. “But when you transplant, there’s an ischemic stage… by the time the blood vessels are formed, according to animal models, you could lose 60 percent of all the eggs [in the transplanted tissue].”
Oktay and his colleagues at Yale are investigating pharmacological ways to stave off primordial follicle death — “We predict we can reduce those losses to about 20 percent,” he says. But even before that, there’s the risk this fertility preservation could, ironically, trigger menopause, which brings us to the much-anticipated answer.
ARE WE CLOSE TO STOPPING REPRODUCTIVE AGING?
When we jump to episode three, Elliot performs ovarian tissue freezing on a young 24-year-old woman named Stacy to a live audience watching behind a glass window amid the dark lighting and eerie red surgical gowns.
“When Stacy is on the precipice of the menopause, her frozen ovarian tissue will be thawed out and grafted back into her body… thus restoring her declining sex hormones and delaying the menopause for potentially 20 years,” says Elliot in the show.
Oktay says in his own clinic, he’s definitely seen ovarian tissue transplantation (OTT) stall menopause in some individuals, but never as long as 20 years. In one small 2020 study where about four healthy menopausal women around 47 years old had their banked ovarian tissue successfully grafted back, the tissue was functional for at least six months.
There’s also a possibility that ovarian tissue freezing can trigger early menopause, rendering efforts to safeguard future reproductive health kind of futile and impractical.
“For example, if you were under 18 and we took a whole ovary, you may experience early menopause earlier by seven years, based on some studies looking at people who had their ovaries removed for medical reasons,” says Oktay. “But as you get older, that number is less and less.”
For example, shooting for ovarian tissue freezing between ages 30 and 40 may harken menopause a year or two earlier than expected. However, you have to balance that with the fact nothing trumps younger eggs when it comes to quality and survivability and, in turn, what will be more effective at keeping menopause at bay for longer when you’re older.
“We’re working with mathematicians, and we’ve put together molecular and clinical information and mathematical formulas in a model, which would be available to patients to enter their age, the desire [time] of delay, and that will tell them whether [going with ovarian tissue freezing] makes sense for them or how much tissue to take out,” says Oktay.
(In the show, the character Elliot mentions the possibility of grafting tissue from one individual to another unrelated individual. Oktay and Rubin of OHSU say, just like you need matching between donors, you would run into the same challenge with OTT.)
Rubin and Roach of VUMC feel that ovarian tissue freezing as a means to delay menopause is a bit much. Thanks to modern medicine, individuals experiencing this completely natural life transition have many therapies available to help cope with symptoms like hot flashes, low sex drive, or other mood symptoms. These therapies include exogenous hormone replacement with estrogen or progesterone, what’s known as hormone replacement therapy, as well as antidepressants and even cognitive behavioral therapy.
Whether the future holds a cure for reproductive aging, the researchers say that’s hard to determine. Aging is inevitable, and so too could be our attitude of whole-hearted self-acceptance if we so choose.