New insights for fertility preservation by ovarian tissue cryopreservation and transplantation in pediatric cancer patients

Abstract

Premature gonadal failure is a long-term health issue in young cancer patients. For these patients, ovarian tissue cryopreservation and transplantation is currently their only available option to preserve fertility. The first successful ovarian tissue transplantation resulting in a live birth occurred in 2004; significant progress has been made to increase the efficacy of this as-yet-considered experimental procedure, resulting in >130 live births globally. Nevertheless, investigations to further improve and standardize cryopreservation and transplantation technologies continue worldwide. Pediatric patients represent a challenging clinical population because they cannot benefit from standard established fertility preservation (FP) methods such as oocyte and embryo vitrification because of their premenarcheal status (1Duncan F.E. Pavone M.E. Gunn A.H. Badawy S. Gracia C. Ginsberg J.P. et al.Pediatric and teen ovarian tissue removed for cryopreservation contains follicles irrespective of age, disease diagnosis, treatment history, and specimen processing methods.J Adolesc Young Adult Oncol. 2015; 4: 174-183Crossref PubMed Scopus (20) Google Scholar). Thus, FP by ovarian tissue banking with the intent of future transplantation or in vitro follicle growth may be the only acceptable chance for prepubertal girls to achieve pregnancy in later life. But are these technologies appropriate in young pediatric cancer patients? In the FP field, understanding of ovarian tissue from these patients is limited (2Anderson R.A. McLaughlin M. Wallace W.H. Albertini D.F. Telfer E.E. The immature human ovary shows loss of abnormal follicles and increasing follicle developmental competence through childhood and adolescence.Hum Reprod. 2014; 29: 97-106Crossref PubMed Scopus (98) Google Scholar), inasmuch as most reported research is based on the adult ovarian cortex. Thus, results published recently by Masciangelo et al. (3Masciangelo R. Chiti M.C. Philippart C. Amorim C. Donnez J. Camboni A. et al.Follicle populations and vascularization in ovarian tissue of pediatric patients before and after long-term grafting.Fertil Steril. 2020; 114: 1328-1336Abstract Full Text Full Text PDF Scopus (5) Google Scholar) in Fertility and Sterility should be considered relevant data for enhancing quality of life and reproductive lifespan in this specific population. In that recent publication, Masciangelo et al. (3Masciangelo R. Chiti M.C. Philippart C. Amorim C. Donnez J. Camboni A. et al.Follicle populations and vascularization in ovarian tissue of pediatric patients before and after long-term grafting.Fertil Steril. 2020; 114: 1328-1336Abstract Full Text Full Text PDF Scopus (5) Google Scholar) implemented an elegant study to characterize the distinctive features of ovarian tissue transplantation in very young pediatric patients (median age 3 years) compared with adult ovarian tissues. The results show that follicle density is significantly higher in pediatric than in adult patients. These results confirm and reinforce earlier studies reporting distinctive features of prepubertal ovaries, such as age-related decreased follicular populations (2Anderson R.A. McLaughlin M. Wallace W.H. Albertini D.F. Telfer E.E. The immature human ovary shows loss of abnormal follicles and increasing follicle developmental competence through childhood and adolescence.Hum Reprod. 2014; 29: 97-106Crossref PubMed Scopus (98) Google Scholar). Moreover, pediatric ovarian tissue is characterized by numerous large immature vessels. This contributes to an accelerated revascularization process by the formation of more structured vessels with the ability to properly perfuse the tissue, whereas adult samples mainly contain mature vasculature. This is of paramount relevance because of the burnout effect resulting from ischemic damage during revascularization is a main limitation for survival of follicles in the graft. However, follicles with abnormal features were observed in pediatric ovarian tissue but not in ovarian tissues from adult patients. The high rates of morphological abnormalities and atresia reported by Masciangelo et al. (3Masciangelo R. Chiti M.C. Philippart C. Amorim C. Donnez J. Camboni A. et al.Follicle populations and vascularization in ovarian tissue of pediatric patients before and after long-term grafting.Fertil Steril. 2020; 114: 1328-1336Abstract Full Text Full Text PDF Scopus (5) Google Scholar) corroborate previous findings in prepubertal ovaries (2Anderson R.A. McLaughlin M. Wallace W.H. Albertini D.F. Telfer E.E. The immature human ovary shows loss of abnormal follicles and increasing follicle developmental competence through childhood and adolescence.Hum Reprod. 2014; 29: 97-106Crossref PubMed Scopus (98) Google Scholar) and could partially explain the reduction of follicular endowment from birth to puberty, given that both findings significantly diminish as age increases. For the first time, the authors demonstrate differential behaviour of ovarian tissue after transplantation in a cohort of very young pediatric patients. Permitting a proper FP before anticancer treatments in these types of patients will enhance their future quality of life and reproductive outcomes. In addition to ovarian cortex cryopreservation and transplantation, the next step in the field is development of an artificial ovary (4Díaz-García C. Herraiz S. The artificial ovary: any new step is a step forward.Fertil Steril. 2014; 101: 940Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar, 5Campo H. Cervelló I. Simón C. Bioengineering the uterus: An overview of recent advances and future perspectives in reproductive medicine.Ann Biomed Eng. 2017; 45: 1710-1717Crossref PubMed Scopus (22) Google Scholar). These artificial organs can use support scaffolds made of different materials or extracellular matrix derived from decellularized tissues for grafting ovarian tissue. This new approach will increase the safe options for future motherhood, not only for prepubertal girls but also for all young women with hematologic malignancies for whom ovarian transplantation is not recommended and those in whom oncologic treatment cannot be delayed. Supported by the Instituto de Salud Carlos III through a Health Research Project program ( PI17/01039 and CP19/00149 to I.C.; PI18/00322 and CP19/00141 to S.H.) (Spanish Government); FEDER , PROMETEO/2018/137 from Valencian Government (Spain); and the IVI-RMA IVI Foundation . Follicle populations and vascularization in ovarian tissue of pediatric patients before and after long-term graftingFertility and SterilityVol. 114Issue 6PreviewTo characterize ovarian tissue from pediatric patients by evaluating development and vascularization in follicle populations and comparing it with adult tissue after xenografting. Full-Text PDF