Hum. Reprod. Advance Access originally published online on May 12, 2005
Human Reproduction 2005 20(9):2421-2425; doi:10.1093/humrep/dei074
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Comparison of GnRH agonists and antagonists in assisted reproduction cycles of patients at high risk of ovarian hyperstimulation syndrome
1 Infertility Unit, Department of Obstetrics-Gynaecology, University of Milan, Milan, 2 Reproductive Unit of Brunico, Bolzano and 3 Centro Scienze della Natalità, Istituto Scientifico S. Raffaele, Milan, Italy
4 To whom correspondence should be addressed. Email: g.ragni{at}icp.mi.it
BACKGROUND: During IVF or ICSI cycles, ovarian hyperstimulation syndrome (OHSS) is a major problem. The aim of this prospective, multicentre, comparative study (using historical controls) was to assess the efficacy of a GnRH antagonist protocol in preventing OHSS in selected patients who had experienced OHSS or had been at risk of OHSS in their previous IVF/ICSI attempt. METHODS AND RESULTS: Patients underwent a new cycle where the same gonadotrophin protocol was used [same dose of recombinant FSH (rFSH)] but a different protocol was used for pituitary desensitization: cetrorelix 0.25 mg multiple-dose antagonist instead of GnRH agonist long protocol. Cetrorelix 0.25 mg was administered daily, starting when the leading follicle reached a diameter of 14 mm. In other words, rFSH was administered in the new cycle according to the dosage and the step-up or step-down modalities used during the previous cycle, independently of ultrasound findings and serum estradiol (E2) levels. Eighty-seven patients entered the study. Out of the 87 cycles involving GnRH agonists, 49 (56.3%) were cancelled and out of the 87 involving GnRH antagonists 28 (32.2%) were cancelled [McNemar's test; 95% confidence interval (CI) –35.8% to –11.2%; P < 0.001]. After GnRH agonist cycles, we recorded 24 cases of OHSS (18 moderate and six severe; 27.6%), whereas after the GnRH antagonist cycles there were 10 cases of OHSS (nine moderate and one severe; 11.5%) (95% CI–26.4% to –5.7%; P=0.006). There was a statistically significant reduction in the total number of follicles with a diameter >10 mm (Wilcoxon's test; Z=6.1; P < 0.001) and of E2 levels on the day of HCG administration (2538 versus 4322.4 pg/ml; P < 0.001) in the GnRH antagonist cycles versus GnRH agonist cycles. Twenty-nine patients had an embryo transfer in the first cycle (76.3% of oocyte retrievals) and 57 in the cycle using GnRH antagonist (96.6%). This 20.3% difference was also significant (Z-test; 95% CI 6.8–36.0%; P=0.003). After the antagonist cycles, 18 pregnancies (20.7 per initiated cycle; 31.6% per embryo transfer) were obtained. CONCLUSIONS: Although this study presents some limitations owing to the use of historical controls, our data show a favourable effect of GnRH antagonists in reducing the incidence of OHSS and the number of assisted fertilization cycles cancelled because of the risk of OHSS in high responder patients. As a consequence, GnRH antagonist plus gonadotrophin administration could also increase the percentage of oocyte retrievals and embryo transfers in this high risk group of patients.
Key words: GnRH antagonist/ICSI/IVF/ovarian hyperstimulation syndrome/recombinant FSH
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