3What is a systematic review a review strives to comprehensively identify and track down all the literature on a given topicincorporates a specific statistical strategy “Meta-analysis” for assembling the results of several studies into a single estimate”.
4“GnRH agonist long protocol” IntroductionCurrent practice:“GnRH agonist long protocol”EffectiveMidluteal
5Immediate suppression Dramatic reduction in duration GnRH antagonistsImmediate suppressionDramatic reduction in durationLower number of hMG ampoules
6If comparable clinical outcome These benefits would justify a change from the standard long protocol of GnRH agonists to the new GnRH antagonist regimens.
7Objective : Antagonist Vs GnRH-a Cycle Day 6 Day ofDay 2-3 of FSH hCGCycle down Day ofDay regulation hCG2-4 weeksFSHGnRH antagonistGnRH agonistFSH
8Search StrategyOn-line searching of the MEDLINE and EMBASE databases and the Cochrane Menstrual Disorders and Subfertility Group's Specialized Register from to 2001, and hand searching of bibliographies of relevant publications and reviews, and abstracts of scientific meetings.
9Selection criteriaOnly randomized controlled studies comparing different protocols of GnRH antagonists with GnRH agonists in assisted conception cycles were included in this review
10prevention of premature LH surge pregnancy rate per woman Primary outcomesprevention of premature LH surgepregnancy rate per woman
11number of oocyte retrieved per cycle Secondary outcomesnumber of oocyte retrieved per cyclepregnancy rate per oocyte retrievalpregnancy rate per embryo transferspontaneous miscarriage rateE2 level on day of hCGDuration of GnRH analogue treatment
12Secondary outcomes (cont.) Amount of gonadotrophins usedIncidence of ovarian hyperstimulation syndromeCost effectiveness as determined by cost per pregnancy
13Description of studies Albano 2000Olivennes 2000The European Orgalutran Study Group 2000The North American trial 2001The European-middle East Orgalutran Study Group2001
14Regimens usedA fixed protocol of GnRH antagonist (GnRH antagonist was given in a fixed day of the cycle ) was compared to the long protocol GnRH agonistSingle high-dose regimen (Olivennes 2000)Multiple low-dose regimen (other trials)
15Methodological quality In general, the quality of the five trials was high.All were multicenter RCTs.All trials had parallel design with true randomisation.None of the trials were double blinded
16None of these trials used power calculation to detect differences in pregnancy rates In all trials, collected data included only one treatment cycleThe authors of the trials were contacted for extra information.
38Cost effectivenessThis outcome could not be estimated as no available data in the text and no extra information on this issue could be obtained. Ideally, cost effectiveness should be expressed in term of cost / pregnancy. Then cost of complications should be added (OHSS , multiple pregnancy).
39Commentsfirst prospectiveThis is the first prospective meta-analysis on GnRH antagonist and the first prospective systematic review in the field of gynecology.
40Outcome SummaryNo significant difference in prevention of LH surgeLower number of oocytes retrievedLower pregnancy rate inspite of transfer of an equal number of embryosNo significant difference in prevention of severe OHSS
41The use of a fixed protocol that starts GnRH administration on a fixed day of the cycle with a fixed dose should be re-evaluated.Impact of GnRH antagonist on the endometrium and subsequent implantation potential should be examined.
42Data on women with polycystic ovary syndrome need to be obtained. There was no evaluation of menopausal symptoms that develop with agonist administration.
43Cycle programmingAlthough the antagonists allow short treatment regimens it causes planning problems within the centres. To overcome this practical problem some advocate the programming of the cycle with oral contraceptives but this has an immediate negative effect on the duration of the treatment!
44Implications for Practice GnRH antagonists' fixed protocol facilitates short and simple protocol for ovarian stimulation in assisted conception. However, in view of the available data, there is a small but statistically significant lower pregnancy rate that necessitates counseling subfertile couples before recommending change from GnRH agonist to antagonist.
45Implications for research The GnRH antagonist flexible protocol should be the area of research in the futureCost effectiveness analysis should be carried out to evaluate the difference between the two protocols regarding cost per pregnancy.