Ovarian transplantation with robotic surgery and a neovascularizing human extracellular matrix scaffold: a case series in comparison to meta-analytic data

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].

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“…For instance, Oktay et al. have implemented the use of extracellular matrix scaffolds, which show promise in extending graft longevity ( 136 ).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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“…If the start of oncological treatment cannot be postponed by two weeks, OTC procedure should be offered as a valid and effective technique [11,46]. This technique al-lows the collection and cryopreservation of small fragments of ovarian cortical tissue, each one containing hundreds of follicles [47].…”

Section: Assisted Reproductive Technologiesmentioning

confidence: 99%

“…A combined procedure with oocyte or embryo cryopreservation may increase fertility preservation potential [48]. OTC is no longer considered an experimental technique since December 2019 by the American Society of Reproductive Medicine [11] and recently Oktay et al [46] reported 152 live births and ongoing pregnancies. Research on OTC is still going on because this FR technique still has limitations such as the longevity of the transplanted graft (median 33.7 months) [46] and the risk of reintroducing malignant cells [10].…”

Section: Assisted Reproductive Technologiesmentioning

confidence: 99%

“…In fact, first line therapy usually has a low risk for gonadotoxicity instead conditioning chemotherapy has a high risk for permanent amenorrhea (see "Oncological treatments with a negative impact on female fertility" paragraph for details). Up to date, few leukaemia survivors received ACOTT and had live births [46]. OTC is recommended also in these women because in the next future new fertility preservation technologies could be applied on cryopreserved tissue without encountering a high risk of disease relapse (see "future possibilities" paragraph for details).…”

Section: Prepubertal Patientsmentioning

confidence: 99%

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Fertility Preservation in Girls and Women: State of Art and Future Possibilities

Marin¹,

Ambrosini²,

Esposito³

et al. 2022

Clin. Exp. Obstet. Gynecol.

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Background: Many women worldwide are diagnosed with cancer in prepubertal, postpubertal and childbearing age. Oncological treatments can compromise future fertility through different mechanisms mainly depending on the type of treatment and the age of the patient. International societies recommend that cancer patients should receive information regarding the effects of oncological treatments on their reproductive health and cancer survivors should not be discouraged from becoming pregnant. About a quarter of these patients still do not receive an adequate counselling and young cancer survivors may face several barriers to conceiving a pregnancy due to the concerns from gynaecologists and oncologists. Methods: This review aims to investigate the infertility risk for female cancer patients who undergo oncological treatments and to provide an overview of actual and future fertility preservation possibilities for female cancer patients. Results: Different fertility preservation techniques have been developed in order to ensure the possibility for cancer survivors to complete their family planning after cancer. Oocyte/embryo freezing and ovarian tissue cryopreservation are the established choices, but the research is still going on to increase the success rate of these techniques and to develop other techniques to overcome actual limitations. Patients with a systemic oncological disease such as leukaemia could particularly benefit from the new experimental techniques which involve the creation of an artificial ovary or the in vitro growth of follicles or even the obtaining of mature oocytes from stem cells. All these techniques would allow the achievement of pregnancy without the risk of reintroducing malignant cells within autologous cryopreserved ovarian tissue transplantation. Regarding the concerns over pregnancy in cancer survivors, research is rapidly advancing and reassuring data are increasing. Conclusions: The rate of utilisation of gametes, embryos or ovarian tissue previously stored for fertility preservation is still low and the motivations can be various. Further data are needed in order to reassure both women and oncologists about the safety of pregnancy in cancer survivors and in order to increase the rate of women experiencing pregnancy after cancer.

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“…For prepubertal girls, ovarian tissue cryopreservation is the only fertility preservation option for systemic cancer treatments ( 9 ). Thawed ovarian cortical tissue auto-transplantation later in life successfully restored fertility and prolonged ovarian endocrine function in cancer survivors ( 10 , 11 ). However, there are currently no pharmacological and nonsurgical methods to preserve follicle reserve and long-term ovarian endocrine function after chemotherapy-induced damage ( 9 , 12 ).…”

Section: Introductionmentioning

confidence: 99%

CHEK2 signaling is the key regulator of oocyte survival after chemotherapy

Emori,

Boucher,

Bolcun-Filas

2023

Sci. Adv.

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Cancer treatments can damage the ovarian follicle reserve, leading to primary ovarian insufficiency and infertility among survivors. Checkpoint kinase 2 (CHEK2) deficiency prevents elimination of oocytes in primordial follicles in female mice exposed to radiation and preserves their ovarian function and fertility. Here, we demonstrate that CHEK2 also coordinates the elimination of oocytes after exposure to standard-of-care chemotherapy drugs. CHEK2 activates two downstream targets—TAp63 and p53—which direct oocyte elimination. CHEK2 knockout or pharmacological inhibition preserved ovarian follicle reserve after radiation and chemotherapy. However, the lack of specificity for CHEK2 among available inhibitors limits their potential for clinical development. These findings demonstrate that CHEK2 is a master regulator of the ovarian cellular response to damage caused by radiation and chemotherapy and warrant the development of selective inhibitors specific to CHEK2 as a potential avenue for ovario-protective treatments.

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Ovarian transplantation with robotic surgery and a neovascularizing human extracellular matrix scaffold: a case series in comparison to meta-analytic data

Cited by 36 publications

References 74 publications

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

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

Fertility Preservation in Girls and Women: State of Art and Future Possibilities

CHEK2 signaling is the key regulator of oocyte survival after chemotherapy

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