Kate Johnson

October 31, 2014

HONOLULU — Egg freezing is "an invaluable option" for female cancer patients who want to preserve their fertility before undergoing potentially sterilizing chemotherapy, according to researchers from New York University (NYU) Langone Medical Center in New York City.

"In our hands, the way we're doing it, it's working very well," Nicole Noyes, MD, professor and the director of reproductive surgery at NYU, told Medscape Medical News.

Although experimental designation has been lifted from oocyte cryopreservation for cancer patients, the choice to freeze eggs rather than embryos remains a matter of debate, according to experts here at the American Society for Reproductive Medicine (ASRM) 2014 Annual Meeting.

"In a steady couple, embryo freezing is still the preferred approach, as it provides better assurance that fertility will be preserved," Kutluk Oktay, MD, past-president of the ASRM Fertility Preservation Special Interest Group, told Medscape Medical News.

"In a young patient, there's about a 40% to 50% chance of a live birth with either frozen eggs or frozen embryos," countered Dr Noyes. "It's just that a lot of people don't have the same success that we do, so it's not like you can say it works everywhere."

Worldwide, only a dozen or so births from the thawed eggs of cancer patients have been reported, said Sarah Druckenmiller, a medical student at NYU, who reported the center's results at the meeting.

Of the 231 cancer patients who have frozen eggs or embryos at the clinic, there have been four live births to date, and an ongoing pregnancy, she said.

Although patients can choose from embryo, oocyte, or ovarian tissue cryopreservation, oocyte cryopreservation is the most popular, even among committed couples. "It offers many advantages, including increased reproductive autonomy and decreased ethical, personal, and religious dilemmas," she said

"Given the choice, single and partnered patients most often opt for reproductive autonomy, as evidenced by the fact that the majority of our patients cryopreserved oocytes as opposed to zygotes," Druckenmiller explained.

Freezing Eggs Over Embryos

"We're not saying that freezing eggs is better than freezing embryos," Dr Noyes emphasized. "The efficiency of eggs is less, meaning if you have the same number of eggs and embryos, you're probably going to have a higher chance of pregnancy with the embryos."

But, she added, "I would say, for a single person, it is better than embryo freezing. Given a woman who doesn't have a committed partner, egg freezing is a reasonable fertility preservation option; you don't have to make embryos with donor sperm today."

But some experts remain uncomfortable with the idea of promoting egg freezing, which is still considered experimental for women who do not have cancer.

Official guidelines from the ASRM emphasize that embryo freezing can have higher pregnancy rates, and suggest this might be a more reliable option (Fertil Steril. 2013;100:1224-1223).

However, for single women, creating embryos is often not possible, noted Roger Hart, MD, professor of reproductive medicine at the University of Western Australia and medical director of fertility specialists of Western Australia in Perth.

Unless she uses a sperm donor, "a woman needs a stable partner to generate embryos, and if he refuses to let her use those embryos in the future, she has no ability to conceive," he told Medscape Medical News.

The NYU study involved all 231 cancer patients referred to the center from 2005 to 2014. Median age was 31 years.

The most common cancer diagnosis was breast (84 invasive and 15 ductal cancer in situ), followed by gynecologic (39 ovarian, 18 cervical, 11 uterine, 2 vaginal, 1 vulvar), hematologic (27 Hodgkin's, 6 non-Hodgkin's, 9 leukemia), and other (10 central nervous system, 6 gastrointestinal, and 3 genitourinary).

As expected, mean age was highest for breast cancer patients (35 years) and lowest for patients with hematologic cancer (24 years). Among the gynecologic cancer patients (mean age, 30 years) was a heterogenous group of younger patients with cervical cancer and borderline ovarian tumors and older patients with uterine cancer and invasive ovarian tumors.

A mean of 18 oocytes were retrieved and a mean of 15 were frozen; however, type of cancer affected the yield.

"Hematologic patients had the most oocytes, despite the fact that they had a full tumor load at the time of retrieval. As expected, being the oldest and having aromatase inhibitor cotreatment, breast cancer patients had the lowest peak estradiol and tended to have the lowest number of oocytes," Druckenmiller explained. "However, they still achieved an adequate number, with an average of 10 frozen per cycle. Patients with ovarian cancer also had fewer oocytes because many of them had some or most of their ovarian tissue removed prior to retrieval of the eggs. Patients with uterine cancer tended to have more oocytes because they have endocrine abnormalities that tend to be consistent with polycystic ovarian syndrome."

In terms of relationship status, 61% of women were single at the time of fertility preservation and 39% had partners. Mean age at the time of cryopreservation was 34 years.

The vast majority of single women (98%) chose to preserve oocytes only, but 2% chose to preserve oocytes and embryos created with donor sperm.

Fewer partnered women chose oocyte cryopreservation, but this was still the majority choice (52%), which is "evidence of how important reproductive autonomy is," she said.

To date, a mean of 2.3 years after cryopreservation, 10% of patients have returned to thaw their eggs or embryos.

The pregnancy rate for thawed fertilized oocytes is 40% per transfer and for thawed embryos is 25% per transfer. Gestational carriers were used by one breast cancer and three gynecologic cancer patients.

The results should not be interpreted as being superior for frozen oocytes, Dr Noyes noted. "I don't think you can conclude that the pregnancy rate for one is better than the other based on our numbers; that's not what we were pointing out," she said. "It relates to how many eggs and embryos we thawed. I was thawing fewer embryos, so I didn't get the same pregnancy rate."

 
We need to be cautious about recommending this technique over embryo freezing in couples.
 

Overall, the center's preliminary success rates using cryopreserved oocytes appears to be similar to results with fresh oocytes in healthy women undergoing in vitro fertilization (IVF), and the quality of oocytes from cancer patients appears to be equivalent to those from patients without cancer, Druckenmiller explained. "Thirty-six percent of noncancer patients who cryopreserve oocytes at ages 41 and 42 have achieved a live birth at our clinic. Based on these data, we think it is reasonable to offer fertility preservation up to a woman's 43rd birthday," she said.

"Oocyte cryopreservation now represents an invaluable fertility preservation option for cancer patients, affording them the potential for family after cure," Druckenmiller noted. "Based on these data, we can conclude that with effective communication across disciplines and appropriate treatment strategies, prompt commencement and successful completion of fertility preservation treatment can be achieved with adequate numbers of mature oocytes cryopreserved."

The study's pregnancy rate with frozen oocytes "has not been our experience," said Dr Oktay, who is professor and director of the Innovation Institute for Fertility Preservation at New York Medical College in New York City. "I agree with the autonomy issue, but every bit of evidence indicates that fresh eggs or frozen embryos do better than the frozen eggs," he told Medscape Medical News.

"There is no question that oocyte freezing is an important tool for fertility preservation and that this is an important study," said Dr Oktay, who is cochair of the American Society for Clinical Oncologists (ASCO) committee on fertility preservation.

However, he added, "given the small number of cancer patients who returned to use their frozen oocytes in this study, we need to be cautious about recommending this technique over embryo freezing to couples. I am looking forward to a follow-up with a larger number of cancer patients."

Dr Noyes and Ms Druckenmiller have disclosed no relevant financial relationships. Dr Oktay reports being a member of the medical advisory board of OvaScience, a company that is developing techniques to improve oocyte quality and reserve through oogonial stem cell technologies. Dr Hart reports being part owner and shareholder of an IVF company; receiving travel grants and honoraria from pharmaceutical manufacturers of gonadotrophins; and being on the medical advisory board of pharmaceutical companies that manufacture gonadotrophins.

American Society for Reproductive Medicine (ASRM) 2014 Annual Meeting: Abstract O-154. Presented October 22, 2014.

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