Ovarian tissue grafting: Lessons learnt from our experience with 55 grafts

Rozen, Genia; Avagliano, Stephanie; Agresta, Franca; Gook, Debra A.; Polyakov, Alex; Stern, Catharyn

doi:10.1002/rmb2.12380

Cited by 18 publications

(10 citation statements)

References 55 publications

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“…This result is supported by a report that primordial follicles are dormant and not vulnerable to chemotherapy 7 . These results suggest that OTC in children who have not yet menstruated is not inferior to OTC in adulthood, and the duration of ovarian function after OTT correlates positively with primordial follicle density 38 …”

Section: Discussionsupporting

confidence: 80%

Primordial follicles remaining in young cancer survivors who received chemotherapy

Ogino¹,

Wakimoto²,

Nakagawa³

et al. 2023

J of Obstet and Gynaecol

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Aim Ovarian tissue cryopreservation (OTC) is performed for fertility preservation in cancer patients undergoing chemotherapy. Although anti‐Müllerian hormone is used as a marker for ovarian reserve, serum levels do not always correlate with the number of follicles. Additionally, the follicle development stage most affected by chemotherapy is unclear. We examined the association between serum anti‐Müllerian hormone levels and the number of remaining primordial follicles after chemotherapy, as well as which follicle stage is most affected by chemotherapy before ovarian cryopreservation. Methods Thirty‐three patients who underwent OTC were divided into the chemotherapy (n = 22) and non‐chemotherapy (n = 11) groups; their ovarian tissues underwent histological examination. Pathological ovarian damage induced by chemotherapy was assessed. Ovarian volumes were estimated from weights. We compared the number of follicles at each developmental stage as a percentage of primordial follicles between the groups. The relationship between serum anti‐Müllerian hormone level and primordial follicle density was analyzed. Results The chemotherapy group had a significantly lower serum anti‐Müllerian hormone level, ovarian volume, and density of developing follicles than the non‐chemotherapy group. Serum anti‐Müllerian hormone levels correlated with primordial follicle density only in the non‐chemotherapy group. The chemotherapy group had significantly lower numbers of primary and secondary follicles. Conclusions Chemotherapy induces ovarian damage and follicle loss. However, serum anti‐Müllerian hormone level does not always reflect the number of primordial follicles after chemotherapy, and chemotherapy more significantly affects primary and secondary follicles than primordial follicles. Many primordial follicles remain in the ovary after chemotherapy, supporting OTC for fertility preservation.

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Section: Discussionsupporting

confidence: 80%

Primordial follicles remaining in young cancer survivors who received chemotherapy

Ogino¹,

Wakimoto²,

Nakagawa³

et al. 2023

J of Obstet and Gynaecol

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“…The Royal Women’s Hospital in Victoria, Australia also reported processing ovarian tissue into multiple different sizes ( 1 ): strips: 5 x 1 ( 2 ), squares: 5 x 5 ( 3 ), fragments: 2 x 2, 3 x 3, 4 x 3 mm 2 ( Table 2 ). Over 40 participants at this site had ovarian tissue processed into squares at the mean age of 26 (range 17.8 – 40.7), these participants had wide range of diagnoses ( 79 ). Also at this site 17 participants that had a mean age of 27.4 (range 17.8 – 35.9) at OTC had their ovarian tissue processed and cryopreserved into 5 x 1 mm 2 strips ( 68 ).…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2022

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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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“…Fifteen studies were included for OTC (2 prospective ( Oktay and Oktem, 2010 ; Diaz-Garcia et al , 2018 ) and 13 retrospective ( Imbert et al , 2014 ; Meirow et al , 2016 ; Lambertini et al , 2018 ; Silber et al , 2018 ; Liebenthron et al , 2019 ; Poirot et al , 2019 ; Pretalli et al , 2019 ; Dueholm Hjorth et al , 2020 ; Marklund et al , 2020 ; Dolmans et al , 2021 ; Karavani et al , 2021 ; Rozen et al , 2021 ; Vatel et al , 2021 )). Seven studies reported orthotopic transplantation ( Meirow et al , 2016 ; Lambertini et al , 2018 ; Silber et al , 2018 ; Liebenthron et al , 2019 ; Pretalli et al , 2019 ; Dueholm Hjorth et al , 2020 ; Rozen et al , 2021 ), one reported heterotopic transplantation, four reported both ( Imbert et al , 2014 ; Poirot et al , 2019 ; Dolmans et al , 2021 ; Vatel et al , 2021 ) and three did not provide this information ( Diaz-Garcia et al , 2018 ; Marklund et al , 2020 ; Karavani et al , 2021 ). The time between OTT and first menstruation varied from 3.9 to 94.3 months.…”

Section: Ovarian Tissue Cryopreservationmentioning

confidence: 99%

Live birth rate after female fertility preservation for cancer or haematopoietic stem cell transplantation: a systematic review and meta-analysis of the three main techniques; embryo, oocyte and ovarian tissue cryopreservation

et al. 2022

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STUDY QUESTION What are the chances of achieving a live birth after embryo, oocyte and ovarian tissue cryopreservation (OTC) in female cancer survivors? SUMMARY ANSWER The live birth rates (LBRs) following embryo and oocyte cryopreservation are 41% and 32%, respectively, while for IVF and spontaneous LBR after tissue cryopreservation and transplantation, these rates are 21% and 33%, respectively. WHAT IS KNOWN ALREADY Currently, fertility preservation (FP) has become a major public health issue as diagnostic and therapeutic progress has made it possible to achieve an 80% survival rate in children, adolescents and young adults with cancer. In the latest ESHRE guidelines, only oocyte and embryo cryopreservation are considered as established options for FP. OTC is still considered to be an innovative method, while it is an acceptable FP technique in the American Society for Reproductive Medicine guidelines. However, given the lack of studies on long-term outcomes after FP, it is still unclear which technique offers the best chance to achieve a live birth. STUDY DESIGN, SIZE, DURATION We performed a systematic review and meta-analysis of published controlled studies. Searches were conducted from January 2004 to May 2021 in Medline, Embase and the Cochrane Library using the following search terms: cancer, stem cell transplantation, FP, embryo cryopreservation, oocyte vitrification, OTC and reproductive outcome. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 126 full-text articles were preselected from 1436 references based on the title and abstract and assessed via the Newcastle–Ottawa Quality Assessment Scale. The studies were selected, and their data were extracted by two independent reviewers according to the Cochrane methods. A fixed-effect meta-analysis was performed for outcomes with high heterogeneity. MAIN RESULTS AND THE ROLE OF CHANCE Data from 34 studies were used for this meta-analysis. Regarding cryopreserved embryos, the LBR after IVF was 41% (95% CI: 34–48, I2: 0%, fixed effect). Concerning vitrified oocytes, the LBR was 32% (95% CI: 26–39, I2: 0%, fixed effect). Finally, the LBR after IVF and the spontaneous LBR after ovarian tissue transplantation were 21% (95% CI: 15–26, I2: 0%, fixed-effect) and 33% (95% CI: 25–42, I2: 46.1%, random-effect), respectively. For all outcomes, in the sensitivity analyses, the maximum variation in the estimated percentage was 1%. LIMITATIONS, REASONS FOR CAUTION The heterogeneity of the literature prevents us from comparing these three techniques. This meta-analysis provides limited data which may help clinicians when counselling patients. WIDER IMPLICATIONS OF THE FINDINGS This study highlights the need for long-term follow-up registries to assess return rates, as well as spontaneous pregnancy rates and birth rates after FP. STUDY FUNDING/COMPETING INTEREST(S) This work was sponsored by an unrestricted grant from GEDEON RICHTER France. The authors have no competing interests to declare. REGISTRATION NUMBER CRD42021264042.

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Ovarian tissue grafting: Lessons learnt from our experience with 55 grafts

Cited by 18 publications

References 55 publications

Primordial follicles remaining in young cancer survivors who received chemotherapy

Primordial follicles remaining in young cancer survivors who received chemotherapy

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

Live birth rate after female fertility preservation for cancer or haematopoietic stem cell transplantation: a systematic review and meta-analysis of the three main techniques; embryo, oocyte and ovarian tissue cryopreservation

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