Abstract
There is currently a lack of knowledge about the feasibility of performing procedures for fertility preservation after chemotherapy treatment has been initiated. In this experimental controlled study using adolescent mice, we aimed to investigate if the chance of rescuing and growing in vitro secondary follicles (SeF) would be affected three days after a single injection of cyclophosphamide (CPA). The main outcomes included were: (1) The number of SeF with good morphologic quality obtained per ovary 3 days after CPA injection, (2) SeF development in culture, (3) small follicle density (SFD) on histology, and (4) apoptosis markers, including terminal deoxynucleotidyl transferase dUTP nick end-labelling (TUNEL), mRNA expression, and distribution of p 53 upregulated modulator of apoptosis (Puma) and phosphatase and tensin homolog (Pten). We found a 60% reduction of SeF obtained per ovary in all CPA-treated groups vs. controls. However, in vitro survival rates at culture day 12 and antrum formation were similar among all groups. On histology, SFD was only significantly reduced in the high CPA dose group. Apoptotic cells were mainly found in large growing follicles of CPA groups. Our study indicates the feasibility of SeF isolation and in vitro follicle culture 3 days following CPA treatment and a still preserved SFD, particularly following a low-dose CPA treatment.
Highlights
Survival following cancer diagnosis has significantly increased [1]
There is, a need to understand the molecular mechanisms by which chemotherapeutic agents damage the ovary and to examine the effect that such treatments might have on the clinical implementation of fertility preservation techniques [7]
In this study, using adolescent mice, we aimed to investigate the effect of a recent CPA treatment in the feasibility of isolation and culturing of secondary follicles (SeF) with good morphologic quality and their development in vitro
Summary
Survival following cancer diagnosis has significantly increased [1]. This has led to a focus on the impact that cancer treatments have on the quality of life of cancer survivors. Follicular in vitro growth is a promising method that has been proposed as a method for fertility restoration in the future, and entails the growth of early stage follicles to antral stage, whereupon ovulation can be induced using a human chorionic gonadotropin (hCG) trigger [9,10,11]. This would allow the growth of small immature follicles to a mature stage, thereby producing mature oocytes, an approach more suitable for cases with precluded re-transplantation due to an inherent risk of malignant cell invasion within the ovarian tissue. It is important to acknowledge that this technique has not yet been applied clinically, and to acknowledge its distinction from in vitro maturation (IVM), whereby immature germinal vesicle stage oocytes are obtained from antral follicles and attempts are made to mature them to metaphase II stage oocytes [12]
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