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 scaffold, robot-assisted minimally invasive surgery and peri-operative pharmacological support.
Study design
We prospectively studied 2 subjects with Hemophagocytic Lymphohistiocytosis (P-A) and Non-Hodgkin Lymphoma (P-B) who underwent ovarian tissue cryopreservation at the age of 23, before receiving preconditioning chemotherapy for hematopoietic stem cell transplantation. Both experienced ovarian failure post-chemotherapy and we transplanted ovarian cortical tissues to the contralateral menopausal ovary 7 and 12 years later, using a human extra cellular tissue matrix scaffold and robotic-assistance. The extra cellular tissue matrix scaffold-tissue compatibility was shown in pre-clinical studies. Patients also received estrogen supplementation and baby aspirin preoperatively to aid in the revascularization process.
Results
Ovarian follicle development was observed approximately ten (P-A) and eight (P-B) weeks after ovarian tissue transplantation. Following eight and seven cycles of in vitro fertilization, nine and ten day-3 embryos were cryopreserved (P-A and P-B, respectively). While the baseline FSH (range: 3.6–15.4 mIU/mL) levels near-normalized by seven months and remained steady post ovarian transplantation in P-A, P-B showed improved but elevated FSH levels throughout (range: 21–31 mIU/mL). Highest follicle yield was achieved 14 (8 follicles; P-A) and 11 months (6 follicles; P-B) post intervention. P-A experienced a chemical pregnancy after the third frozen embryo transfer attempt. She then conceived following her first fresh in vitro fertiliza tion-embryo transfer and the pregnancy is currently ongoing. P-B conceived after the first frozen embryo transfer attempt and delivered a healthy boy at term.
Conclusions
We reported the first pregnancies after the minimally-invasive transplantation of previously cryopreserved ovarian tissue with an extra-cellular tissue matrix scaffold. This approach seems to be associated with steady ovarian function after a follow up of up to 2 years.
In women with cancer undergoing FP, letrozole appears to enhance response to ovarian stimulation while the presence of BRCA mutations is associated with lower oocyte and embryo yield.
These findings do not suggest increased risk of subsequent cancers in patients with BOT. However, population-based studies are needed for evaluating exact risk of developing second primary malignancies in women with BOTs.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.