First Baby From Immature Egg Born to Patient With Cancer

Liam Davenport

February 19, 2020

UPDATED with comments  February 20, 2020 //  In a world first, a breast cancer survivor has successfully given birth after having immature eggs harvested, matured in the laboratory, and then frozen.

The procedure was carried out by a team of French doctors.

The now 34-year old woman was diagnosed at age 29 with grade III hormone receptor positive, HER2-negative invasive ductal carcinoma of the left breast, and was also found to have a positive lymph node.

She was scheduled for adjuvant chemotherapy, placing her at risk of becoming infertile, and she could not undergo ovarian stimulation because of the potential risk for the hormones on the cancer spreading.

So the team extracted immature oocytes, put them through in vitro maturation (IVM), and then through vitrification (rapid freezing in liquid nitrogen), so they could be cryopreserved.

Five years later, the eggs were unfrozen, inseminated, and implanted.

"We were delighted that the patient became pregnant without any difficulty and successfully delivered a healthy baby at term," commented lead author Michaël Grynberg, MD, PhD, head of reproductive medicine and fertility preservation at Antoine Béclère University Hospital, Clamart, France.

The case was described in a letter and published online today in Annals of Oncology.

"This success represents a breakthrough in the field of fertility preservation," Grynberg commented in a press release.

His team had been using the technique for some time. "We have accumulated lots of eggs that have been vitrified following IVM for cancer patients and we expected to be the first team to achieve a live birth this way," he said.

"We continue offering IVM to our patients in combination with ovarian tissue cryopreservation when ovarian stimulation cannot be considered," he added.

While acknowledging that eggs matured in this way are of "lower quality" than those obtained after ovarian stimulation, Grynberg added that their success "shows that this technique should be considered a viable option for female fertility preservation, ideally combined with ovarian tissue cryopreservation as well."

He also acknowledged that "egg or embryo vitrification after ovarian stimulation is still the most established and efficient option" for fertility preservation for young patients with cancer. "However, for some patients, ovarian stimulation isn't feasible due to the need for urgent cancer treatment or some other contraindication," he pointed out.

Experts welcomed the announcement.

"Getting eggs to mature successfully after removal from the ovary has been a challenge, so this is a very welcome positive step," commented Richard Anderson, MD, PhD, head of section of Obstetrics and Gynaecology, MRC Centre for Reproductive Health, University of Edinburgh, Scotland.

Although the technique is not "widely available," Anderson said the report "shows it can work, when time is very short."

"Freezing eggs at this stage also means that they remain the woman's own property, without the complication that using a partner's sperm to fertilize them brings, in that embryos are then the couple's joint property," he said.

This technique is "particularly important for cancer patients," he said. "but it's also a step toward easier and less invasive IVF for other women and couples needing assisted reproduction."

However, another expert emphasized that this is a "single case study."

Alastair Sutcliffe, MD, PhD, University College London and Great Ormond Street Institute of Child Health, London, UK, added that "caution must be considered in any new advance."

Nevertheless, Sutcliffe commented that "this new technique could in future be an additional tool for women who have the tragedy of cancer before reproduction to have their own genetic child."

Details of the Case Report

After surgery for her breast cancer, the patient was scheduled to have adjuvant chemotherapy three weeks later.

"I saw the 29-year-old patient following her diagnosis of cancer and provided fertility counseling," Grynberg said.

Due to the positive lymph node, she could not undergo ovarian stimulation, so "I offered her the option of egg freezing after IVM and also freezing ovarian tissue," Grynberg continued. "She rejected the second option, which was considered too invasive."

A transvaginal ultrasound showed that there were 17 small, fluid-filled sacs containing immature eggs in her ovaries. However, using hormones to stimulate her ovaries to ripen the eggs would have taken too long and also carried the risk of stimulating cancer growth and recurrence.

Therefore, an emergency procedure was scheduled 6 days later without ovarian stimulation, and the team retrieved seven immature oocytes before her chemotherapy started.

These seven immature oocytes were then matured in IVM medium, and six underwent successful vitrification. This involves rapidly freezing the eggs in liquid nitrogen, reducing the chances of ice crystals forming and damaging the cells. The six eggs were then cryopreserved.

Five years later, the woman tried to conceive for a year but was unsuccessful. She was advised by oncologists that she should avoid ovarian stimulation, so the decision was taken to reuse her cryopreserved oocytes.

Following estradiol simulation of the endometrium, six oocytes were successfully thawed and inseminated using intracytoplasmic sperm injection.

From five zygotes obtained, one Cleavage-stage embryo was transferred to the uterus and the patient became pregnant, delivering a healthy baby boy at term.

An American expert welcomed the news, and also placed it into context, noting that the technique has already been used in non-cancer patient populations.

"We certainly celebrate the technology of in vitro maturation of oocytes as an alternative to standard, non-experimental means of fertility preservation, because it represents a potential option for selected cancer patients who might not have sufficient time to undergo non-experimental means of fertility preservation (ovarian stimulation and egg freezing or embryo freezing)," commented Jovana Lekovich, MD, director of the Oncofertility Program for Reproductive Medicine Associates in New York City.

"That being said, for the average patient, experimental advances in precision medicine should be taken with caution, given that we don’t have enough data at this time," she added.

"Since the first live birth from IVM oocytes in 1994 (for a non-cancer indication) over 5000 IVM babies have since been born. What makes this case report so special is the fact that the patient underwent IVM of oocytes in the setting of cancer (whereas all the other cases in the past have been pursued for other indications, including ovarian hyperstimulation syndrome and PCOS), and that the eggs have been frozen upon IVM," she pointed out. Lekovich is also assistant professor of Obstetrics, Gynecology and Reproductive Science at the Icahn School of Medicine at Mount Sinai in New York City.

"We sincerely look forward to further evaluating the efficacy of this technology in cancer patients," Lekovitch said. "As you can imagine, this is a fragile patient population that we always strive to treat using proven, as opposed to experimental, methods whenever possible, but this sentinel case report opens the door for new strategies."

No funding has been declared. The authors have disclosed no relevant financial relationships. Anderson and Sutcliffe have disclosed no relevant financial relationships.

Ann Oncology. Published February 19, 2020. Full text

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