History, Evolution and Current State of Ovarian Tissue Auto-Transplantation with Cryopreserved Tissue: a Successful Translational Research Journey from 1999 to 2020

Abstract

The loss of fertility and early menopause are common after gonadotoxic therapies and radical pelvic surgery. The strategy of ovarian tissue cryopreservation and auto-transplantation was introduced to prevent this significant quality of health issue. Ovarian transplantation with cryopreserved tissue has gone through remarkable evolution in the last 20 years. In this review, we detail the history and evolution of ovarian transplantation with cryopreserved tissue from its origins to the present. Ovarian cryopreservation and transplantation approach was first tested with animal models. The approach was then validated in human ovarian xenografting models before being applied to patients in pioneering clinical studies. The first orthotopic and heterotopic approaches to ovarian transplantation was developed by Oktay et al. who reported the first successful restoration of ovarian function with these approaches beginning in 2000 with first embryo development in 2004. Controversy remains on when the first live birth occurred after orthotopic ovarian transplantation with cryopreserved tissue as the patient was ovulating with elevated progesterone levels in the case reported in 2004; first live birth is likely to be the one reported by Meirow et al. in 2005. Nevertheless, the technique has evolved to reach a level where most recent live birth rates are exceeding 35% and the procedure is no longer considered experimental by many.

Keywords: Cryopreservation; Drug-related side effects and adverse reactions; Fertility preservation; Primary ovarian insufficiency; Tissue transplantation.

Fig. 1

Intrauterine ovarian transplantation as depicted by Morris in 1895. (A) Suture at the site of graft insertion; (B) ovarian graft; (C) drainage wick. In this technique, the surgeon anticipated direct ovulation into the uterus, bypassing fallopian tubes

Fig. 2

A brief timeline for the evolution of ovarian auto-transplantation with cryopreserved tissue

Fig. 3

Other techniques of ovarian tissue auto-transplantation. (A) The technique reported by Donnez et al. in 2004 where peritoneal window is created 8 days before the actual deposition of cortical pieces in the same peritoneal pocket without suturing. (B) A technique reported by Meirow et al. in 2005 by inserting thawed ovarian pieces inside the tunnels created under the cortex (left panel) of the remaining menopausal ovary