Ovarian tissue cryopreservation in young females with cancer and its impact on ovarian follicle density

Abstract

Background: Cancer therapy in young females results in irreversible damage to their ovaries potentially leading to premature ovarian failure (POF) and infertility. Ovarian follicle density (FD) serves as a key predictor of reproductive potential for a woman. FD is significantly reduced after cryopreservation in adult women with cancer. FD in young females with cancer has not been investigated. The specific aim of this study was to assess the efficacy of ovarian tissue cyropreservation (OTC) in young females with cancer by evaluating its impact on FD.

Methods: An IRB approved prospective human and animal trial enrolled girls (ages 6-18 years) with cancer at high risk for POF from July 1, 2012 through June 30, 2018. All participants underwent pre-operative ultrasounds evaluating their ovaries. Following a normal ultrasound, each patient underwent a left ovarian tissue harvest prior to cancer therapy. The ovarian tissue was sectioned for use in pathologic analysis, fertility preservation and xenotransplantation before and after cryopreservation. Comparative statistical analyses of the means of FD before and after cryopreservation were implemented using mixed regression modeling that accounted for the correlation among samples from the same patient and differences in age.

Results: Six girls were enrolled (mean, 12 years; median, 13 years, range, 6-17 years). Pathologic analysis was carried out in all viable grafts and ovarian follicle densities were determined. Mean ovarian follicle density (+/- SEM) before cryopreservation was 50.5 +/- 4.26 follicles/mm² and after cryopreservation was 44.1 +/- 4.25 follicles/mm², p < 0.001. Following cryopreservation, on average the ovarian tissue retained 89.0.% of the FD of paired fresh samples (95% CI 82.8%, 95.2%).

Conclusions: FD in young females with cancer is significantly reduced following OTC. However, the degree of reduction may be less than that reported in adult women. This is the first study in adolescent girls to provide histologic evidence of preservation of ovarian follicle density and potential efficacy of the ovarian tissue cryopreservation strategy. By providing this evidence base, the potential benefit to young females with cancer and their family may be prognostically and clinically significant.

Keywords: Fertility preservation; Ovarian cryopreservation; Ovarian follicle density; Young female cancer.