A Systematic Review of Ovarian Tissue Transplantation Outcomes by Ovarian Tissue Processing Size for Cryopreservation

Abstract

Ovarian tissue cryopreservation (OTC) is the only pre-treatment option currently available to preserve fertility for prepubescent girls and patients who cannot undergo ovarian stimulation. Currently, there is no standardized method of processing ovarian tissue for cryopreservation, despite evidence that fragmentation of ovaries may trigger primordial follicle activation. Because fragmentation may influence ovarian transplant function, the purpose of this systematic review was (1) to identify the processing sizes and dimensions of ovarian tissue within sites around the world, and (2) to examine the reported outcomes of ovarian tissue transplantation including, reported duration of hormone restoration, pregnancy, and live birth. A total of 2,252 abstracts were screened against the inclusion criteria. In this systematic review, 103 studies were included for analysis of tissue processing size and 21 studies were included for analysis of ovarian transplantation outcomes. Only studies where ovarian tissue was cryopreserved (via slow freezing or vitrification) and transplanted orthotopically were included in the review. The size of cryopreserved ovarian tissue was categorized based on dimensions into strips, squares, and fragments. Of the 103 studies, 58 fertility preservation sites were identified that processed ovarian tissue into strips (62%), squares (25.8%), or fragments (31%). Ovarian tissue transplantation was performed in 92 participants that had ovarian tissue cryopreserved into strips (n = 51), squares (n = 37), and fragments (n = 4). All participants had ovarian tissue cryopreserved by slow freezing. The pregnancy rate was 81.3%, 45.5%, 66.7% in the strips, squares, fragment groups, respectively. The live birth rate was 56.3%, 18.2%, 66.7% in the strips, squares, fragment groups, respectively. The mean time from ovarian tissue transplantation to ovarian hormone restoration was 3.88 months, 3.56 months, and 3 months in the strips, squares, and fragments groups, respectively. There was no significant difference between the time of ovarian function’ restoration and the size of ovarian tissue. Transplantation of ovarian tissue, regardless of its processing dimensions, restores ovarian hormone activity in the participants that were reported in the literature. More detailed information about the tissue processing size and outcomes post-transplant are required to identify a preferred or more successful processing method.Systematic Review Registration[https://www.crd.york.ac.uk], identifier [CRD42020189120].

Reproductive and Obstetric Outcomes after Fertility-Sparing Treatments for Cervical Cancer: Current Approach and Future Directions

“…The method has been initially considered to hold an increased risk of unsuccessful subsequent ovarian tissue transplantation, as well as was believed to activate follicular development, thus compromising fertility success [ 47 ]. However, a recent systematic review showed promising results of ovarian tissue transplantation with regard to reproductive outcomes demonstrated by the restoration of ovarian function in up to 98% of the patients [ 48 ]. Pregnancy was achieved in over 80% of cancer-surviving patients undergoing ovarian tissue transplantation whereas the live birth rate reached 56% depending on the size of cryo-preserved ovarian tissue and the technique used for cryopreservation [ 48 ].…”

“…However, a recent systematic review showed promising results of ovarian tissue transplantation with regard to reproductive outcomes demonstrated by the restoration of ovarian function in up to 98% of the patients [ 48 ]. Pregnancy was achieved in over 80% of cancer-surviving patients undergoing ovarian tissue transplantation whereas the live birth rate reached 56% depending on the size of cryo-preserved ovarian tissue and the technique used for cryopreservation [ 48 ]. Another study showed a live birth rate following ovarian tissue cryopreservation and subsequent transplantation in 21% of cancer survivors with the application of IVF treatment and in 33% of cancer survivors with spontaneously achieved pregnancy [ 49 ].…”

Freezing techniques as fertility preservation strategies: a narrative review

“…A recent systematic review on ovarian tissue processing size for cryopreservation evaluated 92 participants who underwent ovarian tissue transplantation. 36 The review reported a pregnancy rate of 81.3%, 45.5%, 66.7% and a live birth rate of 56.3%, 18.2%, 66.7% in the strip, square and fragments, respectively. This data has shown that ovarian tissue transplantation is no longer considered an experimental technique.…”

A comprehensive review and update on human fertility cryopreservation methods and tools

“…The goal of OTC is to maintain the morpho-functional characteristics of the ovary providing in this way a huge supply of primordial follicles, which can be successfully used in the future, preserving their fertility. Systematic reviews in regard to the clinical outcome of ovarian transplantation range between a minimum of 42% and a maximum of 81%, denoting the clinical importance of using this fertility cryopreservation method ( 127 , 128 ). Noteworthy, 130 healthy babies were born worldwide with the applied OTC ( 129 ) two women only worldwide have undergone transplantation with the OTC program which resulted in three live births after transplantation ( 130 , 131 ).…”