Cancer Treatment and the Ovary
Certain chemotherapeutic drugs ("alkylators") and radiation therapy are toxic to the ovaries, leading to both loss of sex steroid hormone production and infertility. Higher doses and older age at treatment are both associated with greater damage. Even patients with spontaneous menstrual cycles have evidence of decreased ovarian potential. Adolescents who are treated for cancer with these agents should be counseled about future fertility risks.
Available from: Nikos Gavalas
- "The general notion on apoptotic inhibitors is that they constitute molecules that are equipping the doctor's arsenal in combating causes for ovarian failure and more specifically assist in reducing the damage in ovarian reserves caused by standard chemotherapeutic agents and radiotherapy  . Although great progress has been achieved there, is still a necessity for further research to take place in order for targeted action of apoptotic inhibitors to occur. "
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ABSTRACT: Cancer prevalence is high, and of importance to cancer sufferers is the long term survival and normal activities resumption. Moreover,
pregnancy is drawing interest for preserving ovarian reserves in post-chemotherapy affected women, especially of younger ages.
The gonadotoxic effect of cancer treatment, involves mechanisms that are not fully understood, mainly due to the variety of molecular
pathways triggered once therapeutic agents applied. Reported rates of premature ovarian failure after the treatment effect and the application
of various treatment protocols, differ extensively due to the protocol itself but also due to the age of treated patients. Several
options for preserving ovarian reserves are currently employed in the clinique, such as ovarian transposition, embryos cryopreservation
and the use of gonadotropin-releasing hormone (GnRH) and its agonists/antagonists, but most of them are still under investigation.
This paper reviews these methods and the molecular mechanisms that are possibly involved in the action of agents such as GnRH.
Available from: Thomas Haaf
- "Disease, senescence and radio-and chemotherapy for cancer treatment can result in the complete loss of female reproductive capacity and premature ovarian failure, especially when alkylating drugs and pelvic radiation are involved (Larsen et al., 2003; Wallace and Thomson, 2003; Agarwal and Chang, 2007; Cohen, 2008; Oktem and Oktay, 2009). In order to preserve fertility, there is a demand to improve cryopreservation and follicle culture, and assess safety of cryopreservation for oocyte health and genomic integrity (Gook and Edgar, 2007; Amorim et al., 2009; Smitz et al., 2010). "
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ABSTRACT: Cryopreservation of follicles for culture and oocyte growth and maturation in vitro provides an option to increase the number of fertilizable oocytes and restore fertility in cases where transplantation of ovarian tissue poses a risk for malignant cell contamination. Vitrification for cryopreservation is fast and avoids ice crystal formation. However, the influences of exposure to high concentrations of cryoprotectants on follicle development, oocyte growth and maturation, and particularly, on the DNA integrity and methylation imprinting has not been studied systematically.
Follicle survival and development, DNA damage, oocyte growth patterns, maturation, spindle formation and chromosomal constitution were studied after Cryo-Top vitrification of mouse pre-antral follicles cultured to the antral stage and induced to ovulate in vitro. Methylation of differentially methylated regions (DMRs) of two maternally (Snrpn and Igf2r) and one paternally (H19) imprinted genes was studied by bisulfite pyrosequencing.
Vitrification results in partial or total loss of oocyte-granulosa cell apposition and actin-rich transzonal projections, a transient increase in DNA breaks and a delay in follicle development. However, the oocyte growth pattern, maturation, spindle and chromosomal constitution are not significantly different between the vitrified and the control groups. Vitrification is not associated with elevated levels of imprinting mutations (aberrant methylation of the entire DMR), although the distribution of sporadic CpG methylation errors in the Snrpn DMR appears to differ slightly between control and vitrified oocytes.
DNA breaks appear to be rapidly repaired and vitrification of oocytes inside pre-antral follicles by the Cryo-Top method does not appear to increase risks of abnormal imprinting or disturbances in spindle formation and chromosome segregation.
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