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].

Keywords: fertility preservation; oncofertility; ovarian tissue cryopreservation; ovarian tissue size; ovarian tissue transplantation.

Figure 1

PRISMA Flow diagram for ovarian tissue cryopreservation and transplantation.

Figure 2

Participant diagnosis at time of OTC in (A) overall patient population (B) strips (C) squares and (D) fragments group. Diagnoses in the other category included the following in (1) overall: acute lymphocytic leukemia, adnexal mass with left adnexectomy, aplastic anemia, autoimmune vasculitis, choriocarcinoma, colorectal cancer, endometrial cancer, granulomatosis with polyangiitis, leukemia, neuroendocrine tumor, ovarian cancer, Schwachman-diamond syndrome, sickle cell anemia, synovial sarcoma of the lung and pelvic sarcoma, systemic lupus erythematosus, T-cell lymphoma (2), strips: acute lymphocytic leukemia, aplastic anemia, β-thalassemia, colorectal cancer, endometrial cancer, rectal cancer, Schwachman-diamond syndrome, sickle cell anemia, systemic lupus erythematosus, and (3) squares: autoimmune vasculitis, β-thalassemia, choriocarcinoma, Ewing’s sarcoma, granulomatosis with polyangiitis, leukemia, myelodysplastic syndrome, neuroendocrine tumor, non-Hodgkin’s lymphoma, ovarian cancer, rectal cancer, synovial sarcoma of the lung and pelvic sarcoma, T-cell lymphoma (, , , , , , , , , , , , , –93, 95, 111, 115, 118, 124).

Figure 3

Age of participant at OTC (A) and OTT (B) in different size cryopreserved and transplanted ovarian tissue. P-values greater than 0.05 were considered not significantly different (ns) (, , , , , , , , , , , , , –93, 95, 111, 115, 118, 124).

Figure 4

Total average area of tissue transplanted (A) and per 1^st OTT (B) in different size cryopreserved and transplanted ovarian tissue. P-values greater than 0.05 were considered not significantly different (ns) P-values greater than 0.05 were considered not significantly different (ns).P-values less than 0.05 (*) and 0.005(**) were considered significantly different. (, , , , , , , , , , , , , –93, 95, 111, 115, 118, 124).

Figure 5

Months to restoration of ovarian activity in different size transplanted ovarian tissues. The average time to ovarian restoration per first OTT was 3.88, 3.56, and 3 months in the strip, square, and fragment groups, respectively. P-values greater than 0.05 were considered not significantly different (ns) (, , , , , , , , , , , , , –93, 95, 111, 115, 118, 124).