{"doi":"10.1093/humrep/deaf097.687","title":"P-381 Fertility preservation in women: Enhanced neovascularization, follicle viability and tissue quality in cryopreserved human ovarian cortex by remaining medulla tissue","abstract":"<jats:title>Abstract</jats:title>\n               <jats:sec>\n                  <jats:title>Study question</jats:title>\n                  <jats:p>Does remaining of medulla tissue during cryopreservation positively impact neovascularization, follicle viability and tissue quality in human ovarian tissue?</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Summary answer</jats:title>\n                  <jats:p>Remaining medulla tissue in cryopreserved human ovarian cortex improves vascularization, follicle survival and tissue quality after thawing and retransplantation, being crucial for effective fertility preservation.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>What is known already</jats:title>\n                  <jats:p>Fertility preservation methods have increasingly focused on ovarian cortex cryopreservation. Recent studies suggested that remaining medulla tissue with the ovarian cortex may enhance graft outcomes after cryopreservation. Studies using model systems have shown increased neovascularization and higher follicle viability in ovarian cortex grafts containing medulla tissue. Additionally, cryopreserved human ovarian tissue with medulla has demonstrated reduced apoptosis and enhanced neovascularization. However, despite these promising findings, further research focusing specifically on human tissue is essential to confirm these results.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Study design, size, duration</jats:title>\n                  <jats:p>To test whether leaving medulla attached to the cortex of ovarian tissue fragments could lead to an improved outcome of fertility protection, human ovarian tissue samples of four carcinoma patients with pure cortex, cortex with medulla and medulla tissue alone were prepared, cryopreserved and analyzed after thawing, transplantation and culturing for four days in the chicken chorioallantoic membrane model (CAM). The three different tissue preparations were compared regarding follicle vitality, neovascularization and overall tissue quality.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Participants/materials, setting, methods</jats:title>\n                  <jats:p>Ovarian biopsies were collected from four women (mean age 24,6) with different tumor entities and anti-muellerian hormone levels above 2 mg/ml for fertility preservation. Ovarian tissue was prepared as medulla-free and medulla-containing cortex and medulla-only fragments. Slow frozen cryopreserved fragments were thawed, grafted and cultured for four days onto a CAM and compared regarding neovascularization (blood vessel count), follicle viability (Calcein-AM staining) and tissue quality (histology, immunohistochemistry markers for apoptosis, proliferation, blood vessel origin).</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Main results and the role of chance</jats:title>\n                  <jats:p>Excellent tissue integrity and quality was observed in all tissue samples after cryopreservation, thawing and transplantation onto the CAM. This was demonstrated by extremely rare occurrence of apoptosis, as shown by immunohistochemical staining for caspase 3, a key marker of programmed cell death.</jats:p>\n                  <jats:p>Cortical grafts containing medulla showed significantly better results in terms of neovascularization and proliferative activity compared to medulla-free cortex fragments. This was supported by increased Ki67 staining, a well-established marker of cellular proliferation.</jats:p>\n                  <jats:p>Furthermore, medulla-containing tissue fragments showed a notably higher number of viable follicles compared to medulla-free cortex fragments. This highlights the essential contribution of medullary tissue in improving the overall success of ovarian tissue cryopreservation and transplantation.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Limitations, reasons for caution</jats:title>\n                  <jats:p>This study was limited by its small sample size (n = 4) and short cultivation period on the CAM model. To validate these findings, larger patient cohorts and extended cultivation periods, potentially by using ovarian tissue transplantation in SCID mouse models, could improve and deliver more comprehensive assessment to validate these results.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Wider implications of the findings</jats:title>\n                  <jats:p>This study highlights the potential of medulla-containing ovarian cortex to improve fertility preservation. Improved neovascularization may reduce follicle loss after transplantation, thereby optimizing clinical outcomes for women undergoing fertility preservation. These findings may inspire refinements in cryopreservation protocols, advancing fertility protection and offering better options for patients with fertility-threatening conditions.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration number</jats:title>\n                  <jats:p>No</jats:p>\n               </jats:sec>","journal":"Human Reproduction","year":2025,"id":41601,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":200185,"name":"S Eberhart","orcid":null,"position":1,"is_corresponding":false},{"id":200186,"name":"J Lehner","orcid":null,"position":2,"is_corresponding":false},{"id":200187,"name":"K Hancke","orcid":null,"position":3,"is_corresponding":false},{"id":200188,"name":"K Bundschu","orcid":null,"position":4,"is_corresponding":false},{"id":200184,"name":"L Rafensteiner","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"18998881","pmcid":null,"openalex_id":"https://openalex.org/W4411757484","authors":[],"funders":[],"total_grants":0,"fwci":0.0,"citation_percentile":0.1972429,"influential_citations":0,"citation_trend":[],"oa_status":"bronze","license":"https://academic.oup.com/pages/standard-publication-reuse-rights","oa_locations":[{"url":"https://academic.oup.com/humrep/article-pdf/40/Supplement_1/deaf097.687/63540016/deaf097.687.pdf","host_type":"journal"},{"url":"https://academic.oup.com/humrep/article-pdf/40/Supplement_1/deaf097.687/63540016/deaf097.687.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1093/humrep/deaf097.687","host_type":"journal"}],"fields_of_study":["Reproductive Biology and Fertility","Medicine"],"mesh_terms":[],"keywords":["Ovarian Cortex","Fertility preservation","Cryopreservation","Ovarian tissue","Medulla","Andrology","Ovarian tissue cryopreservation","Biology","Cortex (anatomy)","Anatomy","Gynecology","Medicine","Ovary","Fertility","Embryo","Endocrinology","Cell biology","Neuroscience","Population"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-13T02:57:53.388433Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}