Comparison of GnRH agonists and antagonists in assisted reproduction cycles of patients at high risk of ovarian hyperstimulation syndrome.
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.


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 (E(2)) 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 E(2) 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.
Ragni
G
G
Infertility Unit, Department of Obstetrics-Gynaecology, University of Milan, Italy. g.ragni@icp.mi.it
Vegetti
W
W
Riccaboni
A
A
Engl
B
B
Brigante
C
C
Crosignani
P G
PG
D000328:Adult; D005260:Female; D005307:Fertilization in Vitro / Q000009:adverse effects*; D005640:Follicle Stimulating Hormone / Q000627:therapeutic use; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists* / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D006727:Hormone Antagonists / Q000627:therapeutic use; D006801:Humans; D015994:Incidence; D007247:Infertility, Female / Q000188:drug therapy*; D016471:Ovarian Hyperstimulation Syndrome / Q000453:epidemiology / Q000517:prevention & control*; D011247:Pregnancy; D011256:Pregnancy Outcome; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use; D012307:Risk Factors; D020554:Sperm Injections, Intracytoplasmic / Q000009:adverse effects
D006727:Hormone Antagonists; D011994:Recombinant Proteins; D007987:Gonadotropin-Releasing Hormone; D005640:Follicle Stimulating Hormone; C062876:cetrorelix