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.

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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.

WISP1 and betatrophin may play a key role on the pathogenesis of PCOS.