Current approach to fertility preservation by embryo cryopreservation

Abstract

The ovaries are susceptible to damage following treatment with gonadotoxic chemotherapy, pelvic radiotherapy, and/or ovarian surgery. Gonadotoxic treatments have also been used in patients with various nonmalignant systemic diseases. Any women of reproductive age with a sufficiently high risk of developing future ovarian failure due to those medical interventions may benefit from embryo cryopreservation though the tools of assessment of such a risk are still not very precise. Furthermore, the risk assessment can be influenced by many other factors such as the delay expected after chemotherapy and the number of children desired in the future. Embryo cryopreservation is an established and most successful method of fertility preservation when there is sufficient time available to perform ovarian stimulation. This publication will review the current state, approach, and indications of embryo cryopreservation for fertility preservation.

FIGURE 1

“Pyramid” of fertility preservation. Medical interventions including chemotherapy, radiotherapy, and surgery act as insults to ovarian reserve and may result in premature ovarian failure and infertility. However, of all the patients at risk for premature ovarian failure, only a fraction will be referred to fertility preservation consultation (FPC) (5). Of those even a smaller fraction will be undergoing fertility preservation due to social, economic, or technical hurdles. Of all techniques offered, embryo cryopreservation is most commonly used, followed by oocyte cryopreservation, ovarian tissue freezing, and other methods, in that order.

FIGURE 2

A simplified scheme for fertility preservation options. In pre-pubertal girls, ovarian cryopreservation may be the only practical option. In post-pubertal females, a wider range of options is available with embryo cryopreservation being the most established method for patients with a male partner or who wish to use donor sperm. Oocyte cryopreservation, now considered an established method of fertility preservation by the American Society for Reproductive Medicine (7), is an option for older post-pubertal female children and single women. In cases where there is insufficient time for ovarian stimulation, ovarian cryopreservation as well as immature oocyte retrieval for in vitro maturation (followed by oocyte or embryo cryopreservation) may also be considered. In vitro growth (IVG) of isolated immature follicles is a theoretical option that may offer advantages in the future for females who have undergone ovarian freezing when there is a risk of ovarian involvement with cancer. The simplest approach to fertility preservation could have been a pharmacological intervention; however there is no proven hormonal treatment to preserve fertility. In the future, with the discovery of the mechanisms responsible for the chemotherapy-induced damage to the primordial follicles (8, 66), targeted pharmacological methods may be developed.