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6 Extra Years of Fertility Freezing ovarian tissue is classified as experimental. Maybe it shouldn’t be.

Ovarian tissue holds way more eggs than what women commonly use for IVF. (Illustration by Kelsey Wroten)

When Jessica was diagnosed at 18 with a blood disorder that can turn into cancer, her doctors told her it could be cured with a bone marrow transplant. Unfortunately, she’d need chemotherapy to help make room in her marrow for new stem cells to propagate. And her doctors said that the harsh round of chemo would make it unlikely for her ever to have children.

“I started crying,” says Jessica, whose real name is being withheld in this story to maintain her privacy. “That to me was more serious than the possibility of the bone marrow transplant not working.”

But then her oncologist told her about a procedure that could raise her chances of getting pregnant someday. She could freeze some of her ovarian tissue before the cancer treatment and get it transplanted back into her body later, when she was healthy and ready to have a child. He advised her to freeze some of her eggs, too, just in case the new procedure didn’t work.

Jessica took her oncologist’s advice and froze tissue from her right ovary and 20 eggs. Now 31, she’s a mother of three children, but not because of the eggs she froze. It turned out that none of them survived when they were thawed. Instead what worked for her was going to St. Louis to see Sherman Silber, a pioneer of ovarian tissue transplantation. He performed a delicate surgery to implant onto Jessica’s ovary some of the tissue she’d frozen all those years earlier. She could expect it to function, he said, for up to six years.

Freezing ovarian tissue, thawing it, and transplanting it is classified as an experimental procedure in the U.S. It’s only available at a few centers, including Silber’s clinic. It’s performed mainly — though not entirely — on girls and women with cancer as a way to preserve their fertility from the harsh effects of chemotherapy and radiation. But doctors who perform the procedure say its experimental label should be lifted, opening it up as an option for more women looking to extend their reproductive years.

For one thing, it might have a better success rate for older women than egg or embryo freezing. Since women began having ovarian tissue frozen in 1999, about 38 percent of those who have had it re-implanted have gone on to have children, according to a 2017 study. It has produced more than 100 babies, two-thirds of whom were conceived naturally. The other one-third arrived through in-vitro fertilization (IVF).

Freezing ovarian tissue isn’t exactly easy, but it has advantages that could make it an attractive option for young, healthy women.

On average, women were 29 when they had their tissue removed and frozen and 33 when they had it implanted. But study author Kutluk Oktay, professor of obstetrics and gynecology at the Yale School of Medicine, says the implants should have the same success rate for women at any point in their child-bearing years. And with other fertility techniques, age matters greatly. Women who underwent IVF without ovarian tissue frozen earlier had a 35 percent success rate in 2016 if they were between 35 and 37 years old. For women 38 to 40, it was 22 percent, and it was even lower for older women.

Freezing ovarian tissue isn’t exactly easy; it requires two separate surgeries. But unlike the process of using frozen eggs or embryos, it doesn’t require women to take hormones, and in many cases it doesn’t require IVF. Ovarian tissue also contains far more eggs than the 10 to 15 that generally are retrieved for IVF. These advantages could make it an attractive option for young, healthy women planning to have children in their mid-30s and beyond.

“I couldn’t believe it”

Why does freezing ovarian tissue work? Within the tissue are fluid-filled sacs called follicles, which hold eggs. Even a small piece of ovarian tissue can contain thousands of immature eggs. Doctors can surgically remove slivers of tissue, then freeze it with a cryoprotective agent using an automated machine. To transplant the tissue back into the body, they use a minimally invasive type of surgery called laparoscopy to graft the tissue onto a woman’s existing ovary.

The transplanted tissue then has to heal and connect to nearby blood vessels. After that, it takes anywhere from three to six months for the ovary to start functioning normally.

In more than 95 percent of women who have had ovarian tissue re-implanted after cancer treatment, their ovaries began functioning again, restoring menstruation and ovulation, and putting an end to menopausal symptoms caused by cancer treatments. The effects of the transplanted tissue can last for four to eight years, Silber says. After that, more frozen tissue can be implanted.

As for why the tissue doesn’t last longer, Oktay notes that up to two-thirds of eggs can be lost while the implanted tissue is grafting back onto the body. “We are, however, making strides in that area,” he adds, with better techniques for thawing the tissue and implanting it. If that can extend the life span of the tissue, “then the technique may be more applicable in healthy women for elective reasons.”

When Silber told Jessica she might be able to get pregnant naturally after her tissue transplant, she thought it sounded like a fairy tale. Today’s other methods for delaying reproduction often require several attempts and multiple doctors’ visits. “The problem with egg and embryo freezing is that the woman has to often go through two, three, or four cycles to be relatively assured that she’s going to have a successful pregnancy,” Silber says.

Before a woman can freeze her eggs or embryos, she has to get hormone injections for about two weeks to stimulate the ovaries so they release more eggs than normal. A doctor then extracts eggs from her ovaries in a simple procedure using a long needle. If she’s going one more step and freezing embryos, her eggs are fertilized with sperm from a partner or donor in a lab.

Doctors started to explore freezing ovarian tissue — and in some cases, whole ovaries — because cancer patients often can’t put off treatment to get the hormone injections. Egg retrieval also isn’t a good option for girls who haven’t yet gone through puberty, because their ovaries aren’t mature enough. But ovarian tissue can be taken from children and even babies, says Oktay.

Though Jessica got a period six months after her ovarian tissue transplant, it took another several months to get pregnant for the first time. “When I had that positive pregnancy test, my whole body was shaking,” she says. “I couldn’t believe it.”

Kids on ice

Ovarian tissue transplantation certainly has limitations. Some women who get the transplants also do need to use IVF. And though a woman’s age at the time of the implant might not matter, her age when she first has the ovarian tissue removed is a major factor.

Even for cancer patients it’s not necessarily ideal: there’s a risk that the ovarian tissue taken from them could contain tumor cells. The American Society of Clinical Oncology recommends ovarian tissue cryopreservation in children with cancer but says, “further investigation is needed to determine if the method is safe in patients with leukemia.”

Overall, because freezing ovarian tissue is still classified as an experimental procedure by the American Society for Reproductive Medicine, insurance and employers don’t cover it, even while IVF and embryo freezing sometimes are covered. Patients who freeze ovarian tissue have to shell out tens of thousands of dollars.

However, some countries in Europe have dropped the experimental label, and Silber and Otkay hope that will happen in the U.S. A committee of the American Society for Reproductive Medicine that makes recommendations about reproductive technology is meeting this summer and might update its assessment of ovarian tissue transplantation early next year.

Two-thirds of eggs can be lost while the implanted tissue is grafting back onto the body, but “we are making strides in that area.”

Nonetheless, Sara Arian, a reproductive endocrinologist and infertility specialist at Baylor College of Medicine, says she’s skeptical that the technology will be widely used soon, largely because freezing eggs and embryos don’t require surgeries.

Meanwhile, Jessica is thinking of having a fourth child. If her implanted tissue stops functioning before then, she says, she’ll go back to Silber’s clinic to get another piece transplanted.

“Throughout my chemo and bone marrow transplant I was thinking, ‘my kids are in the freezer.’ That got me through all the hard tests and procedures and recovery just knowing that I felt like I had a future,” she says. “Each pregnancy and each birth has been a miracle.”

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