Treatment strategies for women of advanced maternal age undergoing ART
- Author:
Howles Colin M.
- Publication Type:Journal Article
- MeSH:
REPRODUCTIVE TECHNIQUES, ASSISTED
- From:
Philippine Journal of Reproductive Endocrinology and Infertility
2005;2(2):86-
- CountryPhilippines
- Language:English
-
Abstract:
In the follicular phase of the spontaneous menstrual cycle, only one follicle, out of a cohort of 10-20, usually completes maturation and ovulates to release a mature oocyte. The aim of ovarian stimulation in ART protocols is to overcome the selection of a dominant follicle and to allow the growth of a cohort of follicles, thus increasing the number of oocytes and hence embryos available, thereby increasing the chance of replacing, up to 3 viable embryos. However, a major challenge in ART programs is the treatment of patients in their mid 30's and over, as the chance of pregnancy and also live birth begins to dramatically decline. Preimplantation Genetic Screening studies over the last decade have identified that a major contributor to the reduction in embryo viability in older patients is the dramatic increase in the rate of eneuploidy. It has also been demonstrated that in women of advanced maternal age, the amount of mitochondrial DNA in the oocyte cytoplasm is significantly reduced. Additionally, some recent studies suggest that the ovarian stimulation regimen may also play an important role on improving embryo viability as tailoring ovarian stimulation with supplemental LH in the mid to late follicular phase may be beneficial to this older patient group.
What could be the mechanisms by which LH supplementation may have an effect? In a recent study of Foong, et al. on low to poor respondrs to r-hFSH only stimulation, intra-follicular estradiol was significantly lower progesterone was significantly higher in poor to low responders to FSH. Previously, it has been demonstrated that in vitro, estradiol plays an important role in human oocyte cytoplasmic maturation manifesting itself im improved fertilization and cleavage rates. On the contrary, androstenedione can irreversibly block the effect of E2. Additionally in the ovine, E2 is assoiciated with upregulation of oocyte DNA repair enzymes. Studies carried out playing an aromatase inhibitor in the late stages of follicular development in the rhesus monkey, just prior to the period pf ovulation, showed reduced capacity on the oocyte to mature and a reduced rate of in vitro fertilization. Overall, it seems that LH may have a beneficial effect through a mechanism, which improves oocyte cytoplasmic maturation, either through E2 or some other intraovarian factor.
