Live births following fertility preservation using in-vitro maturation of ovarian tissue oocytes

Abstract

STUDY QUESTION Can oocytes extracted from excised ovarian tissue and matured in vitro be a useful adjunct for urgent fertility preservation (FP)? SUMMARY ANSWER Ovarian tissue oocyte in-vitro maturation (OTO-IVM) in combination with ovarian tissue cryopreservation (OTC) is a valuable adjunct technique for FP. WHAT IS KNOWN ALREADY Despite the impressive progress in the field, options for FP for cancer patients are still limited and, depending on the technique, clinical outcome data are still scarce. STUDY DESIGN, SIZE, DURATION This was a retrospective cohort study conducted at a university hospital-affiliated fertility clinic between January 2012 and May 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS The study included 77 patients who underwent unilateral oophorectomy for OTC. Cumulus-oocyte complexes (COCs) obtained during ovarian tissue processing were matured in vitro for 28–42 h. Oocytes reaching metaphase II stage were vitrified or inseminated for embryo vitrification. MAIN RESULTS AND THE ROLE OF CHANCE Overall, 1220 COCs were collected. The mean oocyte maturation rate was 39% ± 23% (SD). There were 64 patients who had vitrification of oocytes (6.7 ± 6.3 oocytes per patient). There were 13 patients who had ICSI of mature oocytes after IVM, with 2.0 ± 2.0 embryos vitrified per patient. Twelve patients have returned to the clinic with a desire for pregnancy. For seven of these, OTO-IVM material was thawed. Two patients had OTO-IVM oocytes warmed, with survival rates of 86% and 60%. After ICSI, six oocytes were fertilised in total, generating three good quality embryos for transfer, leading to a healthy live birth for one patient. In five patients, for whom a mean of 2.0 ± 0.8 (SD) embryos had been vitrified, seven embryos were warmed in total: one embryo did not survive the warming process; two tested genetically unsuitable for transfer; and four were transferred in separate cycles to three different patients, resulting in two healthy babies. In this small series, the live birth rate per patient after OTO-IVM, ICSI and embryo transfer was 43%. LIMITATIONS, REASONS FOR CAUTION The retrospective study design and the limited sample size should be considered when interpreting results. WIDER IMPLICATIONS OF THE FINDINGS The results of the study illustrate the added value of OTO-IVM in combination with OTC. We report the first live birth following the use of this appended technique combined with oocyte vitrification. STUDY FUNDING/COMPETING INTEREST(S) No external funding was used for this study. M.D.V. reports honoraria for lectures in the last 2 years from MSD and Ferring, outside the submitted work, as well as grant support from MSD. The other authors have nothing to declare. TRIAL REGISTRATION NUMBER N/A

Oncofertility case report: live birth 10 years after oocyte in vitro maturation and zygote cryopreservation

“…The procedure from immature oocyte collection to mature oocyte cryopreservation takes less than 48 h [9]. This technique has been proven as a viable option for preservation of the reproductive potential for oncological patients either through mature oocyte or embryo cryopreservation, particularly in urgent or when COS is not an option [10][11][12][13].…”

Perspectives on the development and future of oocyte IVM in clinical practice

“…In order to expand the sources of cryopreserved material in cancer patients, IVM can be combined with oophorectomy or ovarian biopsies from the contralateral ovary for cryopreservation of ovarian cortex [88,89]. Cumulus-oocytes complexes recovered during processing of extracorporeal ovarian tissue adds to the pool of available material [90][91][92]. Patients with high risk of malignant invasion of the ovary, such as borderline ovarian carcinoma [93], leukemia, neuroblastoma, and Burkitt lymphoma, may be most suitable for IVM of oocytes from excised ovarian tissue (OTO-IVM), given that ovarian tissue transplantation poses inherent risks for tumor reintroduction.…”

“…However, OTO-IVM remains experimental because the long-term safety studies have yet to be conducted. Moreover, lower maturation rates were observed after OTO-IVM [91], not unexpectedly, due to the fact that COCs derived from non-selected antral follicles from patients of different ages are unlikely to have completed key stages of folliculogenesis and would not be well supported by standard IVM protocols. The biphasic IVM platform described above has already shown promising results for OTO-IVM [45].…”

A View from the past into our collective future: the oncofertility consortium vision statement

“…Our colleagues in Europe specifically, many of whom are not formally part of the OC, have made groundbreaking discoveries and many of the most notable advances in oncofertility and fertility preservation. This includes live births following fertility preservation using in vitro maturation of ovarian tissue oocytes and live births reported using cryopreserved and transplanted ovarian tissue [71][72][73][74][75]. The progress made by these centers has been outstanding and we continue to applaud their work.…”