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.
REPRODUCTIVE TECHNIQUES, ASSISTED

Unlike the GnRH agonists, which have been routinely used in ovarian stimulation protocols for almost 20 years, the GnRH-antagonist acts via a dose-dependent competetive blockade of the pituitary GnRH receptors. This results in an immediate suppression of gonadotrophin secretion (in particular LH) from the anterior pituitary. Despite the new advantages of this new class of substances, the controversial discussion about the influence of the antagonist of the implantation and embryo quality has been ongoing for the last few years. New data from recent meta analysis have demonstrated that the clinical pregnancy rate per cycle is equivalent between antagonist protocols, however there is a sugnificant reduction in the amount of FSH used and the incidence of OHSS. Recently, flexible protocols where the GnRH antagonist is applied according to leading follicle size rather than a fixed of stimulation have been developed in order to prevent a premature LH surge. A recent meta-analysis of four randomised trials comparing fixed vs flexible starting day for the GnRH antagonist concluded there was no statistically significant difference in pregnancy rates, but a significant reduction in the amount of FSH utilized in favour of the flexible protocol. A series of studies have however raised concern about late administration of the GnRH antagonist, as used in a flexible protocol. In the three studies, the implantation and pregnancy rates were higher when the antagonist was initiated on a fixed day (stimulation day 6) compared to administration in a flexible protocol according to follicle size (-15mm). Whilst Kolibianakis, et al. reported no difference in overall pregnancy rate in flexible over fixed day antagonist administration, the implantation rate was lower in the flexible protocol, when there were no follicles of -15mm on the stimulation day 6. In this group, higher concentrations of LH and oestradiol were observed to antagonist administration. In a second study, Kolibianakis, et al reported that profound suppression of LH after GnRH antagonist suppression was associated with a significantly higher ongoing pregnancy rate. They argued that exposure of the genital tract/oocyte to LH may adversely affect the implantation rate, mainly by altering endometrial receptivity. One issue here that ma have complicated the interpretation of the results is the very late administration of the GnRH antagonist (-15mm). It is generally recommended that the antagonist should administered when the leading follicle is 14mm at he very latest. Co-treatment with oral contraceptive pill (OCP) programming can also be utilized with GnRH antagonists in order to facilitate scheduling the start of FSH therapy, rather than waiting for the patient to have spontaneous menses. There are now a number of studies reporting the use of OCP pill programming with either daily 0.25mg or single dose 3mg Cetrotide in routine ART and also poor responder patients. Future studies in this area are needed to elucidate the optimal preparation protocol in GnRH antagonist cycles. However, the data that are emerging seem to support that previous cycle preparation can make a clinical contribution to the outcome of the antagonist treatment cycle.
GONADOTROPIN-RELEASING HORMONE ; OVULATION INDUCTION