부산대학교 도서관

STUDY QUESTION: What is the optimum ovarian stimulation protocol for a first treatment cycle of IVF/ICSI and preimplantation genetic diagnosis (PGD) in terms of i. number of good quality embryos for biopsy at cleavage stage, ii. clinical pregnancy rates per first treatment cycle and iii. incidence of ovarian hyperstimulation syndrome (OHSS). SUMMARY ANSWER: There is no difference in number of embryos for biopsy according to the type of ovarian stimulation protocol used. The clinical pregnancy rate (CPR) per started first-rank cycle is higher in the agonist group. The incidence of OHSS is low in both the agonist and the antagonist group. WHAT IS KNOWN ALREADY: The most recent meta-analyses do not show a significant difference in pregnancy rates between agonist and antagonist stimulation protocols, although there is a consensus on a lower risk of ovarian hyperstimulation syndrome (OHSS) and a lower number of oocytes when using GnRH antagonist. There is a shift of focus in PGD in view of the necessity of an optimal number of embryos for genetic analysis. Data on optimal stimulation protocols for PGD are lacking. STUDY DESIGN, SIZE, DURATION: Prospective randomized (blocks of 6; concealed) trial with intention-to-treat analysis. A sample size of 120 subjects was required to allow 80% power with a significance level of 5% in order to detect a difference of 2 embryos for biopsy. The duration of the study was 18 months. PARTICIPANTS/MATERIALS, SETTING, METHODS: Tertiary referral centre for PGD. Inclusion criteria: i. age <39 years ii. BMI <30 iii. first treatment iv. regular menstrual cycles. Exclusion criteria: i. genetic conditions associated with potentially poor ovarian response ii. PCOS iii. endocrine abnormalities iv. endometriosis AFS III/IV. Ovarian stimulation was performed with hMG at a starting dose of 225IU/d. The pituitary suppression was randomized to GnRH agonist in a long protocol (A) versus GnRH antagonist in a fixed protocol (B). MAIN RESULTS AND THE ROLE OF CHANCE: 132 patients were recruited; of these 129 were randomized; 5 patients dropped out of the study leaving 124 cases for analysis. There was no significant difference in background variables.There was no difference in number of oocytes (13.2 (SD 7.3) v 12.6 (SD 7.1)) and number of embryos for biopsy (6.7 (SD 4.8) v 6.4 (SD 4.2)(NS) in A versus B respectively. The transfer rate was lower in group B (62%) than in group A (84%)(p = 0.006).The clinical pregnancy rate (CPR) per cycle was higher in group A (49.2%) than in group B (26.2%)(p = 0.008). The CPR per embryo transfer was not different (42.1% v 58.4% in B versus A respectively).The incidence of OHSS was 1.6% in each group; both cases were mild. LIMITATIONS, REASON FOR CAUTION: Though the clinical pregnancy rate per first rank PGD cycle showed a significant difference, the results need to be interpreted with caution as the study was not powered for this analysis. The data apply exclusively to PGD for monogenic or chromosomal disorders and not for preimplantation genetic screening (PGS). WIDER IMPLICATIONS OF THE FINDINGS: This is the first prospective randomised trial by intention-to-treat analysis comparing the two most common ovarian stimulation protocols and their effect on number of embryos for biopsy and clinical pregnancy rate in PGD. The number of embryos for biopsy is not affected by the type of ovarian stimulation protocol used, however the transfer rate is different indicating qualitative differences in embryogenesis. PGD patients, mostly (68%) fertile, may have a lower risk of OHSS. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by an unconditional grant by Ferring Pharmaceuticals Belgium. The authors have no competing interests. TRIAL REGISTRATION NUMBER: av