title: First pregnancies, live birth, and in vitro fertilization outcomes after transplantation of frozen-banked ovarian tissue with a human extracellular matrix scaffold using robot-assisted minimally invasive surgery.
abstract: BACKGROUND
  Ovarian tissue cryopreservation is an experimental fertility preservation method and the transplantation techniques are still evolving.
  
  
  OBJECTIVE
  We attempted to improve the technique with the utility of a human decellularized extracellular tissue matrix (ECTM) scaffold, robot-assisted minimally invasive surgery, and perioperative pharmacological support.
  
  
  METHODS
  We prospectively studied 2 subjects with hemophagocytic lymphohistiocytosis (patient A) and non-Hodgkin lymphoma (patient B) who underwent ovarian tissue cryopreservation at the age of 23 years, before receiving preconditioning chemotherapy for hematopoietic stem cell transplantation. Both experienced ovarian failure postchemotherapy and we transplanted ovarian cortical tissues to the contralateral menopausal ovary 7 and 12 years later, using a human ECTM scaffold and robotic assistance. The ECTM scaffold tissue compatibility was shown in preclinical studies. Patients also received estrogen supplementation and baby aspirin preoperatively to aid in the revascularization process.
  
  
  RESULTS
  Ovarian follicle development was observed approximately 10 (patient A) and 8 (patient B) weeks after ovarian tissue transplantation. Following 8 and 7 cycles of in vitro fertilization, 9 and 10 day-3 embryos were cryopreserved (patients A and B, respectively). While the baseline follicle-stimulating hormone (range 3.6-15.4 mIU/mL) levels near normalized by 7 months and remained steady postovarian transplantation in patient A, patient B showed improved but elevated follicle-stimulating hormone levels throughout (range 21-31 mIU/mL). Highest follicle yield was achieved 14 (8 follicles; patient A) and 11 (6 follicles; patient B) months postintervention. Patient A experienced a chemical pregnancy after the third frozen embryo transfer attempt. She then conceived following her first fresh in vitro fertilization embryo transfer and the pregnancy is currently ongoing. Patient B conceived after the first frozen embryo transfer attempt and delivered a healthy girl at term.
  
  
  CONCLUSIONS
  We report the first pregnancies after the minimally invasive transplantation of previously cryopreserved ovarian tissue with an ECTM scaffold. This approach seems to be associated with steady ovarian function after a follow-up of up to 2 years.
authors.affiliation: Innovation Institute for Fertility and In Vitro Fertilization, New York, NY; Laboratory of Molecular Reproduction and Fertility Preservation, Obstetrics and Gynecology, New York Medical College, Valhalla, NY. Electronic address: koktay@fertilitypreservation.org.
authors.forename: Kutluk
authors.initials: K
authors.lastname: Oktay
authors.affiliation: Innovation Institute for Fertility and In Vitro Fertilization, New York, NY; Laboratory of Molecular Reproduction and Fertility Preservation, Obstetrics and Gynecology, New York Medical College, Valhalla, NY; Faculdade de Medicina de Ribeirao Preto-Universidade de Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Bedoschi
authors.affiliation: Innovation Institute for Fertility and In Vitro Fertilization, New York, NY; Laboratory of Molecular Reproduction and Fertility Preservation, Obstetrics and Gynecology, New York Medical College, Valhalla, NY; Classiclinica, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Pacheco
authors.affiliation: Innovation Institute for Fertility and In Vitro Fertilization, New York, NY; Laboratory of Molecular Reproduction and Fertility Preservation, Obstetrics and Gynecology, New York Medical College, Valhalla, NY; Department of Obstetrics and Gynecology, Izmir Tepecik Training and Research Hospital, Izmir, Turkey.
authors.forename: Volkan
authors.initials: V
authors.lastname: Turan
authors.affiliation: Innovation Institute for Fertility and In Vitro Fertilization, New York, NY; Laboratory of Molecular Reproduction and Fertility Preservation, Obstetrics and Gynecology, New York Medical College, Valhalla, NY.
authors.forename: Volkan
authors.initials: V
authors.lastname: Emirdar
mesh_terms: D000293:Adolescent; D000328:Adult; D043925:Angiogenesis Inducing Agents / Q000627:therapeutic use; D000818:Animals; D001241:Aspirin / Q000627:therapeutic use; D015925:Cryopreservation; D004624:Embryo Transfer; D004967:Estrogens / Q000627:therapeutic use; D005109:Extracellular Matrix; D005260:Female; D059247:Fertility Preservation / Q000379:methods*; D005307:Fertilization in Vitro; D005640:Follicle Stimulating Hormone / Q000097:blood; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D050498:Live Birth; D051359:Lymphohistiocytosis, Hemophagocytic / Q000628:therapy; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy; D051379:Mice; D019060:Minimally Invasive Surgical Procedures; D006080:Ovarian Follicle; D010053:Ovary; D010298:Parity; D011247:Pregnancy; D016649:Primary Ovarian Insufficiency / Q000139:chemically induced; D011446:Prospective Studies; D065287:Robotic Surgical Procedures; D054457:Tissue Scaffolds; D019172:Transplantation Conditioning / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D043925:Angiogenesis Inducing Agents; D004967:Estrogens; D005640:Follicle Stimulating Hormone; D001241:Aspirin
keywords: AlloDerm; fertility preservation; in vitro fertilization; ovarian cryopreservation and transplantation; robotic surgery; translational research