Abstract
The aim of this study is to compare the efficacy of recombinant LH supplementation to recombinant follicle-stimulation hormone during controlled ovarian stimulation in GnRH-agonist protocol for IVF/ICSI cycles Meta-analysis. Search strategies included on-line surveys of databases (MEDLINE, EMBASE, Science Citation Index, Cochrane Controlled Trials Register and OVID) from 1990 to 2006. There was no language restriction and grey literature was included. The following Medical Subject Headings and text words were used: ovarian stimulation, recombinant FSH (r-FSH), recombinant LH (r-LH), GnRH-agonist (GnRH-a), and randomized controlled trial. The primary outcomes were the number of days of stimulation, the total dose of r-FSH administered, serum estradiol levels on the day of HCG administration, the number of oocytes retrieved and the number of mature oocytes (MII). The secondary outcomes were clinical pregnancy rate (CPR) per oocyte retrieval, implantation rate and miscarriage rate. The Breslow-Day statistic, Cochran Q and I2 (inconsistency) were used to determine homogeneity and the combinability of the trials. The fixed effects model was used for odds ratio (OR) and effect size (weighted mean difference-WMD). The StatsDirect® statistical software (Cheshire, UK) was used for data analysis. Four trials fulfilled the inclusion criteria (Tarlatzis et al 2006, Humaidan et al 2004, Marrs et al 2004, Lisi et al 2002). In 3 trials, the pituitary down-regulation with GnRH-a started in the mid-luteal phase of the preceding cycle and one started in the beginning of the menstrual cycle. All trials compared ovarian stimulation with r-FSH alone (control group) versus ovarian stimulation with r-FSH + r-LH (study group). In all trials, r-LH was initiated in the late follicular phase. When the meta-analysis was carried out we observed advantages for the LH supplementation protocol with respect to a fewer days of stimulation (p<0.0001; WMD:-0.198, 95% CI: -0.24, -0.16), a fewer total dose of r-FSH administered (p<0.0001; WMD:-192, 95% CI:-220, -164) and a higher serum estradiol levels on the day of HCG administration (p<0.0001; WMD: 49.4, 95% CI: 38.4, 60.4). However, these differences were not observed in number of oocyte retrieval (p:0.37; WMD:0.03, 95% CI: -0.03, 0.09), number of mature oocytes (p=0.95; WMD:0.016, 95% CI: -0.46, 0.50), the CPR per oocyte retrieval (p:0.52; OR 1.1, 95% CI: 0.85, 1.42), the implantation rate (p:0.06; OR:1.35 95% CI: 0.99, 1.83) and miscarriage rate (p:0.23; OR 0.52, 95% CI: 0.21, 1.3). In the IVF/ICSI cycles with GnRH-a protocol the use r-LH supplementation to r-FSH takes a reduction in the stimulate period, fewer dose of r-FSH and a higher level of estradiol in the day of HCG. However, cycles with or without r-LH supplementation give similar number of oocytes (retrieved and mature) and achieve similar pregnancy, implantation and miscarriages rates.
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