Fertility Preservation: A Review of the Reproductive Strategies

Considerable advances in treatment modalities for cancer over the last two decades have significantly improved 5-year survival rates. However, both radiation therapy and chemotherapeutics agents are known to be gonadotoxic and can cause premature ovarian failure and infertility. As a result, both young and reproductive-aged patients must consider ways to preserve their future fertility.

Currently several options are available for fertility preservation in young women with cancer. In this issue of Seminars in Reproductive Medicine, the most recent advances in the reproductive strategies to preserve fertility—albeit still considered experimental—are summarized.

The contents of this issue are structured along a continuum to provide the readers first with a historical overview of fertility preservation by Gosden followed by the article by Arav and Natan describing the technical challenges that had to be overcome (i.e., eliminating the risk of formation of ice crystals, the supercooling, and the latent heat when considering the freezing of large organs).

Two articles report the latest clinical data on oocyte cryopreservation according to two methodologies: slow freezing or vitrification. The first one, slow freezing, is written by Borini and Coticchio from Italy, known leaders of this technology. Their review offers a very elegant and detailed explanation of the cellular bases of oocyte sensitivity to cryopreservation and provides the most recent clinical data on the efficiency of slow freezing and update of live births.

The technology of oocyte vitrification, the alternative to slow freezing is detailed by Nagy et al, and a case is made for considering vitrification as the method of choice for oocyte cryopreservation. This article is also important for updating the worldwide success of vitrification. The article by Xao and Chian on in vitro maturation and cryopreservation by vitrification explains clearly the limitations of cryopreservation in in vitro matured oocytes as opposed to in vivo matured metaphase II oocytes. Nonetheless, this strategy is a valid tool for situations of extreme emergency when there is either no time to stimulate the ovaries or when ovarian stimulation is contraindicated (e.g., in some cases of breast cancer) because of the risks associated with hormonal manipulations.

Because the ovarian cortex has abundant quantities of primordial and primary follicles, cryopreservation of the ovarian cortex has been a successful strategy for fertility preservation. The cortex is removed surgically via laparoscopy or laparotomy and cut into thin strips to allow for proper penetration of cryoprotectants. Once the tissue is cryopreserved, patients can opt for reimplantation (autotransplantation). The success (generating a pregnancy) of ovarian cortical strips transplants with both fresh and frozen/thawed tissue is nicely summarized by the elegant and up-to-date articles of Donnez et al and Silber.

However, the success of all transplanted tissue depends on time to reestablish revascularization to prevent ischemia. Although follicular function appears normal after transplantation, the follicular reserve is significantly compromised by the long period of time required for full neovascularization to occur.

A new strategy has been proposed by Bromer and Patrizio to bypass the ischemic damage consisting of cryopreserving whole ovaries with their vascular pedicle intact in order to perform vascular reanastomosis at the time of the retransplant. Transplantation of frozen/thawed whole ovaries has been successfully accomplished in animal models but has not been performed in humans yet. However, Silber performed a fresh whole ovary transplant successfully with the very first birth obtained a few months ago. In his article he describes the methods and the technical challenges of carrying out ovarian artery vascular reanastomosis.

Finally, Oktem and Oktay provides an update on ovarian stimulation strategies for patients with a diagnosis of breast cancer. The protocols and the results including follow-ups are the most up to date on this common and important topic.