Prevention of chemotherapy-induced ovarian damage: possible roles for hormonal and non-hormonal attenuating agents.
BACKGROUND
Current options for female fertility preservation in the face of cytotoxic treatments include embryo, oocyte and ovarian tissue cryopreservation. However these methods are limited by the patient age, status or available timeframe before treatment and they necessitate invasive procedures. Agents which can prevent or attenuate the ovotoxic effects of treatment would provide significant advantages over the existing fertility preservation techniques, and would allow patients to retain their natural fertility without the necessity for costly, invasive and risky procedures. Recent studies have contributed to our understanding of the mechanisms involved in cytotoxicity-induced ovarian follicle loss and highlight a number of agents that may be able to prevent or reduce this loss.


METHODS
This paper reviews the relevant literature (research articles published in English up to December 2013) on the mechanisms of cytotoxic-induced ovarian damage and the implications for fertility preservation. We present a comprehensive discussion of the potential agents that have been shown to preserve the ovarian follicle reserve in the face of cytotoxic treatments, including an analysis of their respective advantages and risks, and mechanisms of action.


RESULTS
Multiple molecular pathways are involved in the cellular response to cytotoxic treatments, and specific cellular reactions depend on variables including the drug class and dose, cell type, and cell stage. A number of agents acting on different elements of these pathways have demonstrated potential for preventing or reducing ovarian follicle loss, although in most cases, the studies are still very preliminary.


CONCLUSIONS
Advances in our understanding of the mechanisms and pathways involved in both cytotoxic ovarian damage and follicle growth and development have opened up new directions for fertility preservation. In order to bring these agents from the lab to the clinic, it will be vital to accurately evaluate the efficacy of each agent and additionally to demonstrate that co-treatment with these agents will not interfere with the anti-cancer activity of the chemotherapy drugs, or produce genetically comprised embryos.
Fertility Preservation Research Laboratory, IVF Unit, Department of Obstetrics and Gynecology, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel hroness@gmail.com.
Hadassa
H
Roness
Fertility Preservation Research Laboratory, IVF Unit, Department of Obstetrics and Gynecology, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel The Safdie Institute for AIDS and Immunology Research, The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University Ramat-Gan, Ramat-Gan 52900, Israel.
Lital
L
Kalich-Philosoph
Fertility Preservation Research Laboratory, IVF Unit, Department of Obstetrics and Gynecology, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Dror
D
Meirow
D000970:Antineoplastic Agents / Q000009:adverse effects*; D015925:Cryopreservation / Q000379:methods; D005260:Female; D005298:Fertility / Q000187:drug effects / Q000502:physiology; D059247:Fertility Preservation / Q000379:methods*; D006801:Humans; D007247:Infertility, Female / Q000139:chemically induced / Q000517:prevention & control*; D009369:Neoplasms / Q000188:drug therapy; D009865:Oocytes / Q000187:drug effects; D006080:Ovarian Follicle / Q000187:drug effects*
D000970:Antineoplastic Agents
female fertility; fertility preservation; oocyte quality; ovarian reserve; ovary