the-chick-chorioallantoic-membrane-cam-model-as-tool-to-study-ovarian

The Chick Chorioallantoic Membrane (CAM) Model as a Tool to Study Ovarian Tissue Transplantation

Ovarian tissue cryopreservation and transplantation is an effective strategy for preserving fertility but has one major drawback, namely massive follicle ...

Université Catholique de Louvain

The aim was to elucidate the delay in and mechanisms of follicle activation after ovarian tissue transplantation, with particular emphasis on the role of the Akt signalling pathway.

Does the Akt pathway play a role in follicle activation after grafting of human ovarian tissue?

Our aim was to elucidate the mechanisms involved in follicle activation of the ovarian reserve after human ovarian tissue transplantation, with specific focus on the role of the effectors of the PI3K (mTOR and FOXO1) and Hippo (YAP) signaling pathways and whether they are somehow altered.

Role of the PI3K and Hippo pathways in follicle activation after grafting of human ovarian tissue.

Summary of the ISFP congress, New York, 14-16 November, 2019.

Abstracts from the 2019 ISFP meeting in NYC.

Ovarian tissue cryopreservation and transplantation is the only fertility preservation option that enables both restoration of fertility and resumption of ovarian endocrine function, avoiding the morbidity associated with premature menopause. It is also the only technique available to prepubertal patients and those whose treatment cannot be delayed for life-threatening reasons. Ovarian tissue cryopreservation can be carried out in two different ways, either as ovarian cortical fragments or as a whole organ with its vascular pedicle. Although use of cortical strips is the only procedure that has been approved by the American Society for Reproductive Medicine, it is fraught with drawbacks, the major one being serious follicle loss occurring after avascular transplantation due to prolonged warm ischemia. Whole ovary cryopreservation involves vascular transplantation, which could theoretically counteract the latter phenomenon and markedly improve follicle survival. In theory, this technique should maintain endocrine and reproductive functions much longer than grafting of ovarian cortical fragments. However, this procedure includes a number of critical steps related to (A) the level of surgical expertise required to accomplish retrieval of a whole ovary with its vascular pedicle, (B) the choice of cryopreservation technique for freezing of the intact organ, and (C) successful execution of functional vascular reanastomosis upon thawing. The aim of this systematic review is to shed light on these challenges and summarize solutions that have been proposed so far in animal experiments and humans in the field of whole ovary cryopreservation and transplantation.

Whole Ovary Cryopreservation and Transplantation: A Systematic Review of Challenges and Research Developments in Animal Experiments and Humans.

The aim of this study was to elucidate whether ovarian tissue is able to withstand a double freezing-thawing procedure.

Can frozen-thawed human ovary withstand refreezing-rethawing in the form of cortical strips?

To investigate whether adipose tissue-derived stem cells (ASCs) protect the primordial follicle pool, not only by decreasing direct follicle loss but also by modulating follicle activation pathways.

Adipose tissue-derived stem cells protect the primordial follicle pool from both direct follicle death and abnormal activation after ovarian tissue transplantation.

Chemotherapy, pelvic radiotherapy and ovarian surgery have known gonadotoxic effects that can lead to endocrine dysfunction, cessation of ovarian endocrine activity and early depletion of the ovarian reserve, causing a risk for future fertility problems, even in children. Important determinants of this risk are the patient's age and ovarian reserve, type of treatment and dose. When the risk of premature ovarian insufficiency is high, fertility preservation strategies must be offered to the patient. Furthermore, fertility preservation may sometimes be needed in conditions other than cancer, such as in non-malignant diseases or in patients seeking fertility preservation for personal reasons. Oocyte and/or embryo vitrification and ovarian tissue cryopreservation are the two methods currently endorsed by the American Society for Reproductive Medicine, yielding encouraging results in terms of pregnancy and live birth rates. The choice of one technique above the other depends mostly on the age and pubertal status of the patient, and personal and medical circumstances. This review focuses on the available fertility preservation techniques, their appropriateness according to patient age and their efficacy in terms of pregnancy and live birth rates.

Fertility Preservation: How to Preserve Ovarian Function in Children, Adolescents and Adults.

We report successful clinical outcomes after transplantation of refrozen-rethawed cortical strips from a cryopreserved whole ovary in a patient diagnosed with stage IIIb rectal adenocarcinoma. Whole ovary cryopreservation was proposed as a fertility preservation strategy in 2006 prior to radiotherapy, chemotherapy and oncological surgery. To allow for minimal residual disease screening before ovarian reimplantation, the whole ovary was thawed and dissected into cortical strips. While awaiting the results, the majority of the cortical strips were refrozen. These refrozen-rethawed cortical strips were laparoscopically grafted to 2 sites: the previously irradiated pelvic cavity and the non-irradiated extrapelvic cavity. Ovarian function resumption was assessed by recovery of menses, hormone levels, ultrasound and oocyte pick-up following controlled ovarian stimulation (COS). Restoration of ovarian function occurred 6 months after reimplantation, with recovery of menses and estradiol secretion. A total of 12 cycles were followed by the IVF department. A second reimplantation was performed 1.5 years later, since the grafts were found to have stopped functioning for >3 consecutive months. Overall, 3 fertilizable oocytes were retrieved transabdominally from the extrapelvic graft following COS, yielding 2 embryos and culminating in one fresh embryo transfer, but no pregnancy. Concerning the reimplantation site, no ovarian activity was detected in the graft placed in the previously irradiated pelvic cavity. Indeed, only fibrotic-looking tissue was observed in the pelvic site at second laparoscopy 1.5 years later, while ovarian activity was noted in the extrapelvic graft, showing a large antral follicle. All in all, transplantation of refrozen-rethawed cortical strips from a cryopreserved whole ovary can lead to ovarian function resumption and embryo development if grafted to a non-irradiated field.

Transplantation of Refrozen Ovarian Cortical Strips Retrieved from a Cryopreserved Whole Ovary: Proof of Feasibility.

To study the effect of freezing, in vitro culture (IVC) and grafting to chorioallantoic membrane (CAM) on follicle outcomes in human ovarian tissue.

Article	Year
Does the Akt pathway play a role in follicle activation after grafting of human ovarian tissue? Reproductive biomedicine online\| PubMed ID: 31204257	2019
Role of the PI3K and Hippo pathways in follicle activation after grafting of human ovarian tissue. Journal of assisted reproduction and genetics\| PubMed ID: 31732846	2020
Summary of the ISFP congress, New York, 14-16 November, 2019. Journal of assisted reproduction and genetics\| PubMed ID: 32222948	2020
Abstracts from the 2019 ISFP meeting in NYC. Journal of assisted reproduction and genetics\| PubMed ID: 32236903	2020
Whole Ovary Cryopreservation and Transplantation: A Systematic Review of Challenges and Research Developments in Animal Experiments and Humans. Journal of clinical medicine\| PubMed ID: 33023111	2020
Can frozen-thawed human ovary withstand refreezing-rethawing in the form of cortical strips? Journal of assisted reproduction and genetics\| PubMed ID: 33025402	2020
Adipose tissue-derived stem cells protect the primordial follicle pool from both direct follicle death and abnormal activation after ovarian tissue transplantation. Journal of assisted reproduction and genetics\| PubMed ID: 33184773	2021
Fertility Preservation: How to Preserve Ovarian Function in Children, Adolescents and Adults. Journal of clinical medicine\| PubMed ID: 34830528	2021
Transplantation of Refrozen Ovarian Cortical Strips Retrieved from a Cryopreserved Whole Ovary: Proof of Feasibility. Journal of clinical medicine\| PubMed ID: 36078872	2022
Follicle outcomes in human ovarian tissue: effect of freezing, culture, and grafting. Fertility and sterility\| PubMed ID: 36481098	2023

Camille Hossay

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