About this Research Topic
Egg infertility is a predisposition to miscarriages, infertility, and trisomic pregnancies caused by increased frequency of chromosome segregation errors in the eggs of women of advanced maternal age (AMA). Egg infertility is now a significant public health issue, with 1 in 5 US women now attempting her first pregnancy after age 35. Increased rates of egg infertility temporally coincide with rising levels of FSH that occur with age. By age 42, up to 87% of embryos are aneuploid, and 40-50% of women experience egg infertility.
An Introductory Editorial will present an overview of causative factors and potential therapeutic strategies to prevent egg aneuploidy and infertility.
Papers in series will be comprised of data drawn from studies performed both in animals and in humans. Part I will discuss endocrine and other molecular changes implicated in the pathogenesis of AMA oocyte aneuploidy and infertility. Section 1 will discuss defects that emerge with age in controlling the fidelity of meiotic oocyte chromosome segregation apparatus, and other molecular machinery. Topics include cohesins, cross-overmaturation, spindle checkpoint controls, aurora kinases, centromeres, microtubular oragnzation, telomeres, and DNA repair. Section 2 will discuss the impact of the molecular environment of the oocyte as a determinant of elevated aneuploidy with age. Topics to be discussed include reactive oxygen species and mitochondrial damage; elevated FSH and aberrations in levels of other sex hormones; impacts of nutritional and hormonal changes on oocyte epigenetics; changes in metabolomics, mRNA and miRNA expression in the follicle and their possible impacts on egg quality; and endocrine disruptors, and smoking.
Part II will discuss emerging strategies for increasing rates of euploid AMA pregnancies and healthy liveborns in AMA women suffering from egg infertility. Section 1 will present recent advances in therapeutic preimplantation genetic selection (PGS) of euploid embryos for transfer into AMA patients after controlled ovarian hyperstimulation and IVF-ET. These include methodologies for hormonal stimulation, biopsying embryos at optimal stages of development, and quantitating chromosome copy number. Emerging non-invasive technologies currently under development to select high quality oocytes for IVF-ET will also be discussed. Section 2 will discuss potential therapeutics for preventing AMA oocyte and fetal aneuploidy, and for increaseing pregnancy and livebirth rates. Topics include antioxidant therapies, dehydroepiandrosterone, stem cell therapies, telomere elongatation, low dose gonadotorpins in IVF-ET, and prevention of oocyte aneuploidy and infertility using hormone normalization therapies (HNTs) that lower FSH and blockade activin receptor signaling.
Keywords: oocyte, aneuploidy, infertility, female, age
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