In？vitro culture of ovarian preantral follicles: a promising alternative for preserving fertility in cancer patients - Fertility and Sterility

The exponential increase in the number of ovarian tissue cryopreservation (OTC) procedures in Europe in recent years, becoming similar to the number of oocyte cryopreservations for cancer patients (1x1European Society for Human Reproduction and Embryology Working Group on Oocyte Cryopreservation in Europe, Shenfield, F., de Mouzon, J., Scaravelli, G., Kupka, M., Ferraretti, A.P., Prados, F.J. et al. Oocyte and ovarian tissue cryopreservation in European countries: statutory background, practice, storage and use. Hum Reprod Open. 2017; 2017: hox003 Google ScholarSee all References)(1), is mainly due to the successful results after transplantation of cryopreserved ovarian tissue. Indeed, this strategy has led to restoration of ovarian function of ～ 95% of the patients and more than 130 live births (1x1European Society for Human Reproduction and Embryology Working Group on Oocyte Cryopreservation in Europe, Shenfield, F., de Mouzon, J., Scaravelli, G., Kupka, M., Ferraretti, A.P., Prados, F.J. et al. Oocyte and ovarian tissue cryopreservation in European countries: statutory background, practice, storage and use. Hum Reprod Open. 2017; 2017: hox003 Google ScholarSee all References)(1). As promising as these outcomes are, it is also important to bear in mind that the ischemia-reperfusion period in the first days after avascular transplantation leads to ovarian tissue damage and significant follicular loss, and negatively affects follicular activation. In addition, this procedure cannot be recommended for patients with cancer types at high risk of metastasizing to the ovaries. Currently, there are two alternatives under development to restore fertility in patients that cannot benefit from ovarian tissue transplantation or ultimately to replace transplantation: multistep in vitro culture of ovarian follicles (2x2McLaughlin, M., Albertini, D.F., Wallace, W.H.B., Anderson, R.A., and Telfer, E.E. Metaphase II oocytes from human unilaminar follicles grown in a multi-step culture system. Mol Hum Reprod. 2018; 24: 135–142 Google ScholarSee all References)(2); and the transplantable bioengineered ovary (3x3Amorim, C.A. and Shikanov, A. The artificial ovary: current status and future perspectives. Future Oncol. 2016; 12: 2323–2332 Google ScholarSee all References)(3). Regarding the first approach, in recent years we have witnessed great progress in strategies to promote survival and development of follicles in vitro. However, obtaining fertilizable human oocytes from preantral follicles developed in vitro remains a challenge. Indeed, the lack of knowledge on