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April 10, 2024

A systematic review and meta-analysis published by a Mayo Clinic research team in Journal of Assisted Reproduction and Genetics in December 2022 found that ovarian tissue vitrification may be superior to slow freezing for fertility cryopreservation. This determination was due to distinctions in stromal cell viability between the two methods, which was greater for cells undergoing vitrification. Stromal cells are crucial for follicular support.

Overall, says Yulian Zhao, M.D., Ph.D., director of the Fertility Testing/In-Vitro Laboratory at Mayo Clinic in Minnesota and study author, the researchers did not find enough differences between the technologies to greatly favor one over the other.

"Both technologies — vitrification and slow freezing — work," says Dr. Zhao. "And there's not a huge advantage to using one over the other."

The researchers discovered a higher number of intact stromal cells in vitrified ovarian tissue versus slow-frozen tissue, one primary outcome measure for the study. However, in pooled analyses, the researchers did not find any meaningful distinctions between vitrification and slow freezing for the study's other primary outcome measures:

• Proportion of intact primordial follicles.
• Proportion of DNA fragmentation in primordial follicles.
• Mean primordial follicle density.

The Mayo Clinic research team calls for further research comparing the two ovarian tissue cryopreservation methods in a multicenter study with similar conditions among sites.

Pediatric patients as young as infants can undergo ovarian tissue removal for the purpose of cryopreservation. As detailed in an article published on Mayo Clinic's Medical Professionals website and featured in Endocrinology Physician Update e-Edition in October 2019, Mayo Clinic Pediatric Fertility Preservation Program data show that more than 90% of the fertility-threatening conditions prompting ovarian tissue cryopreservation involve childhood cancers. The balance of other program participants has other indications such as aplastic anemia or transgender identity. Median participant age is 11 years, with ages ranging from less than 1 year to 17 years.

The need for ovarian tissue cryopreservation arises due to the toxicity and often systemic nature of treatment required for childhood cancers and other indications.

"Especially as many cancers are curable now, patients can use the cryopreserved ovarian tissue for a reimplantation to restart fertility at a post-treatment, later date," says Dr. Zhao.

Ovarian tissue cryopreservation technology

Slow freezing is the classic ovarian tissue cryopreservation method, which involves a controlled, measured process. Removal of water from the ovarian tissue is crucial, as ice formation in the cells can cause tissue damage. The most recent technology is vitrification, in which a laboratory technologist places the tissue into a cryopreservation solution and then directly plunges it into liquid nitrogen. In this process, says Dr. Zhao, the tissue avoids ice crystal formation and intracellular mechanical damage through rapid conversion of cells from liquid to glass states.

Mayo Clinic in Minnesota has used the slow freezing method of ovarian tissue cryopreservation for years. Since the advent of vitrification, Dr. Zhao and colleagues have observed and researched this technology. But Dr. Zhao says that at present, vitrification is not widely used. Though a few centers have begun using vitrification, most have not yet pursued it, she says.

Dr. Zhao and colleagues have been conducting a separate study directly comparing vitrification and slow freezing. In the meantime, they conducted the review study that appeared in Journal of Assisted Reproduction and Genetics.

The list of requirements for a medical center conducting ovarian tissue cryopreservation is significant and necessitates comprehensive services, says Dr. Zhao, including:

• Laboratory technologists.
• Surgeons.
• Collaboration among oncology, OB-GYN and other specialties relevant to each patient's needs.

Mayo Clinic is now expanding its fertility preservation program through collaboration between its Minnesota and Arizona campuses.

Mayo Clinic and ovarian tissue cryopreservation

Currently, Mayo Clinic is not moving to favor ovarian tissue vitrification over slow freezing, Dr. Zhao says, as there is no significant drive to do so.

The American Society for Reproductive Medicine declared ovarian tissue cryopreservation to be nonexperimental in 2019. Dr. Zhao highly recommends referring patients who are candidates for ovarian tissue cryopreservation to a reproductive endocrinology and fertility program such as the one offered at Mayo Clinic.

She notes that some patients will not have undergone ovarian tissue preservation prior to toxic treatment and could partially lose their fertility. The answer for those patients involves another service Mayo Clinic offers: in vitro fertilization. However, Dr. Zhao recommends ovarian tissue cryopreservation, if possible, as aggressive treatments may impact a patient's fertility entirely by damaging follicles and preventing oocyte production.

For more information

Behl S, et al. Vitrification versus slow freezing of human ovarian tissue: A systematic review and meta-analysis of histologic outcomes. Journal of Assisted Reproduction and Genetics, 2022;40:455.

The Mayo Clinic Pediatric Fertility Preservation Program. Mayo Clinic.

Refer a patient to Mayo Clinic.