Experience with 54 cryopreserved ovarian tissue grafts in a single centre: the devil in reporting details!

Abstract

Study question: Following transplantation of cryopreserved ovarian tissue, what are IVF outcomes per cycle and are there factors related to this technique which impact on success. Summary answer: Mature oocytes which resulted in pregnancies were largely harvested from non-ovarian grafts. Longer duration of ovarian activity correlated with increased tissue volume and follicle density. What is known already: Transplantation of cryopreserved ovarian tissue has a unique role for fertility preservation and over 140 live births have now been published. Nevertheless, uncertainties remain regarding its efficacy, with success of this technique reported inconsistently and mostly reported per patient, rather than per cycle started or embryo transferred as is used in conventional IVF. This hampers identification and optimisation of factors which may predict success, such as grafting sites and tissue volumes. Study design, size, duration: We analysed a case series of reproductive outcomes throughout the IVF treatment process following ovarian tissue transplantations at our centre (2006-2019), with tissue frozen in the years 1996-2018. This included 54 grafting procedures in 40 patients, following a diagnosis of premature ovarian insufficiency. Results of modified low-dose stimulation and oocyte retrieval, including both oocyte cryopreservation and IVF cycles were reviewed. Participants/materials, setting, methods: Ovarian tissue was harvested from 40 patients at risk from gonadotoxic treatment at median age of 26 years (range 18-39). Almost 30% of patients had their tissue frozen elsewhere. Nine of 31 patients (29%) had prior cytotoxic treatment. Following a diagnosis of premature ovarian insufficiency, ovarian tissue was grafted to pelvic sites including the ovary and adjacent pelvic side walls, as well as the anterior abdominal wall, on average five years following extraction. Main results and the role of chance: Fifty-four grafting procedures were performed in 40 women. For patients whose tissue was cryopreserved in our centre, ovarian activity resumed in 90% of grafts, and in 64% when cryopreserved elsewhere. This was after a mean period of 5.3 months. Follicle density and tissue volume grafted appear to be the strongest predictors of ovarian activity duration over 12 months, however this does not reach statistical significance. Stimulated cycles in 25 patients with low-dose modified recombinant FSH protocol from 2012, yielded an oocyte from 68% of follicles (32% rate of empty follicles) and 75% of these were retrieved from non-ovarian grafts. Mature oocytes were retrieved from mean follicular size 13.5mm (range 6-20 mm). The overall 2PN fertilisation rate was 64%. A total of 25 fresh and frozen embryos were transferred in 15 women, yielding a clinical pregnancy rate 28% (7/25) and live birth rate of 20% (5/25). There was additionally a single, ongoing spontaneous pregnancy. All pregnancies occurred in patients aged under 32 years at cryopreservation and only one of the successful patients had prior chemotherapy exposure. Limitations, reasons for caution: Trends alone can be observed from this data as the numbers are small. Wider implications of the findings: This case series adds to international understanding of this technique's results. It encourages detailed and consistent reporting, as ongoing research is needed to improve efficacy. These results support offering ovarian cryopreservation to young women who are undergoing fertility threatening treatment, with optimism for future pregnancy.