Development of Ovarian Tissue Autograft to Restore Ovarian Function: Protocol for a French Multicenter Cohort Study

Abstract

BackgroundSterility is a major late effect of radiotherapy and chemotherapy treatments. Iatrogenic sterility is often permanent and greatly impacts long-term quality of life. Ovarian tissue cryopreservation (OTC) performed before gonadotoxic treatments with subsequent autograft is a method of fertility preservation available for girls and women. Its application in prepubertal girls is of particular value as it is the only possible approach in this patient group. In addition, it does not require a delay in cancer therapy and no ovarian stimulation is needed.ObjectiveThe primary aim of this protocol is to help increase the implementation of ovarian tissue autografting in France. Knowledge is still lacking regarding the efficacy of ovarian transplantation in restoring ovarian function and regarding the safety of this procedure, especially the risk of cancer cell reseeding in certain types of cancer. A secondary aim of this study is to generate data to improve our understanding of these two essential aspects.MethodsThe DATOR (Development of Ovarian Tissue Autograft in Order to Restore Ovarian Function) study is ongoing in 17 university hospitals. The DATOR protocol includes the autograft of ovarian cortex fragments. Candidates are identified from an observational prospective cohort (called the Prospective Cohort of Patients Candidates for Ovarian Tissue Autograft [PERIDATOR]) of patients who have undergone OTC. Enrollment in the study is initiated at the patient’s request and must be validated by the center’s multidisciplinary team and by the study steering committee. The DATOR study begins with a total medical checkup. Ovarian tissue qualification and residual disease detection, if required, are performed.ResultsThe study is ongoing. Currently, 38 patients have provided informed consent and have been entered into the DATOR study. Graft has been performed for 34 of these patients. An interim analysis was conducted on the first 25 patients for whom the period of at least 1 year posttransplantation was achieved. Out of these 25 patients, 11 women succeeded in becoming pregnant (pregnancy rate=44% [11/25]; delivery rate=40% [10/25]). Among these, 6 women conceived twice, and 1 pregnancy led to a miscarriage.ConclusionsOur preliminary analysis appears to be coherent with the accumulating body of evidence indicating the potential utility of ovarian tissue autograft for patients with premature ovarian failure. All these elements justify the pursuit of our study.Trial RegistrationClinicalTrials.gov NCT02846064; https://clinicaltrials.gov/ct2/show/NCT02846064International Registered Report Identifier (IRRID)DERR1-10.2196/12944

Minimal residual disease detection by multicolor flow cytometry in cryopreserved ovarian tissue from leukemia patients

“…Indeed, ovarian cortex transplantation is the only established technique for re-use of ovarian cortex, with a high success rate [15,17,18,20,[50][51][52]. Our team has set up a study in France called DATOR (Development of Ovarian Tissue Autograft in Order to Restore Ovarian Function) (NCT02846064) with the aim of assessing the safety and e cacy of ovarian cortex transplantation [19]. However, in leukemic patients, this technique incurs a risk, with the possibility of cancer reseeding.…”

“…Embryo and oocyte cryopreservation are well-established techniques. Ovarian tissue cryopreservation (OTC) has only recently been classed as an established procedure by the American Society for Reproductive Medicine [14], according to reports in the literature of successful reuse of ovarian cortical tissue with subsequent live births [15][16][17][18][19][20]. For the European Society for Medical Oncology and European Society of Human Reproduction and Embryology, OTC is an alternative and recommended procedure when embryo/oocyte cryopreservation is not feasible [21,22], whereas the American Society for Clinical Oncology stilled considered it experimental as of 2018 [10].…”

Updating the recommendations of the Working Group for the Preservation of Fertility in Oncological and Hematological Patients and Other Patients Treating Gonadier Therapies "ONCOFERTILITY" (GROF) of the Polish Society of Oncological Gynecology regarding cryopreserves and autologous transplant

“…In 85% of cases, ovarian tissue cryotransplant function was restored within four months. The effectiveness of the method was assessed at 40%, counting at least one child per patient treated with this method [10,12]. More recent data estimate the efficacy of ovarian tissue autograft measured as restoration of menstrual function and a reduction in FSH < 20 IU/mL as 94%, while the return of procreative function, measured as at least one pregnancy, was estimated at 50%, and delivery to nearly 42% [4].…”

Untitled

“…The ovarian tissue is then preserved in small pieces (1 cm/0.5 cm each). There is an accumulating evidence of utility success of ovarian auto graft to prevent or postpone the premature ovarian failure [28]. The implanted ovarian tissue called artificial ovary could restore the endocrine function and the ability to get successful pregnancy [29].…”