The increase in young age malignancy, along with improvement in remote survival has generated a global interest in the endeavors for fertility preservation in young female patients treated by gonadotoxic chemotherapy.

The remote effects of malignancy treatment have gained a global ubiquitous interest among fertility specialists, gynecologists, oncologists, hematologists, rheumatologists, pediatricians, family physicians and actually all health care providers, and the endeavor for fertility preservation and minimizing iatrogenic ovarian failure and subsequent infertility, caused by gonadotoxic chemotherapy, assumes utmost priority. Although numerous papers on this issue have been published, numerous equivocal points still require elaboration. Up to date 21 studies [15 retrospective and 6 RCT] have reported on 2328 patients receiving GnRHa treatment before and along chemotherapy, demonstrating a significant diminution in premature menopause rate in survivor’s vs. 8 publications reporting on 509 patients, where this treatment did not bring about a significant decrease in POF rate. The patients who received GnRHa adjuvant treatment along gonadotoxic chemotherapy resumed regular menses and normal ovarian function in about 90% of cases as compared to 40% of those who received only chemotherapy, with a pregnancy rate ranging 20-70% in the GnRHa co-treated patients. Furthermore, thirteen recent metaanalyses of RCT's, and two recent international expert consensus meetings have critically summarized the issue, concluding that GnRHa adjuvant cotreatment along chemotherapy significantly minimizes the risk of POF and increases pregnancy rate in survivors . Several methods are currently experienced for fertility preservation in young female patients despite gonadotoxic chemotherapy: ovariopexy, cryopreservation of embryos, unfertilized oocytes, and ovarian fragments, and endocrine ovarian suppression using GnRHa cotreatment . However, none of the experienced modalities is perfect and none promises future fertility. IVF and cryopreservation of embrya, the only non-investigational, clinically unequivocal method, requires postponing chemotherapy for about two weeks, despite using the recently proven random start efficiency. More intriguingly, although cryopreservation of ovarian tissue and later auto-transplantation has successfully brought about over 50 deliveries, it is not completely safe and successful; the danger that the cryopreserved-thawed ovarian pieces might harbor neoplastic cells or stem cells, that could reintroduce malignancy in a cured patient has been suggested . Indeed, auto-transplantation of cryopreservedthawed ovarian fragments taken from leukemia patients may cause disease recurrence, due to possible ovarian contamination with malignant cells. Similarly, gonadal involvement with malignant cells in Ewing sarcoma or Hodgkin disease has been also published, despite appreciation that these disease do not metastasize to the ovaries. Even more alarming, Kyono et al. have discussed the potential indications for ovarian autotransplantation based on 5,571 post-mortem findings of young female patients, younger than 40. Intriguingly these investigators detected ovarian involvement with malignancy in 8-55% of overall autopsies and 4-13% gonadal involvement in lymphoma, reaching the conclusion that no reliable method exists to completely rule out possible residual malignancy in the cryopreserved ovarian fragments, and therefore reimplantation is not completely safe.

With Regards,
Sara Giselle
Associate Managing Editor
 Journal of Critical Care Obsestrics & Gynocology