Abstract

The purpose of this study was to compare the effects of pituitary suppression (agonist or antagonist), on embryo morphology as it correlates to aneuploidy status. Prospective randomized study, interim analysis. Patients aged 35-40 years with day 3 FSH <12 ml/L undergoing ART were recruited for the study. Patients were randomized to COH and IVF using GnRH antagonist (Cetrorelix acetate, Serono, Inc.), group 1 or GnRH agonist (leuprolide acetate, Tap Pharmaceuticals), group 2 for pituitary suppression. Both groups were pretreated with oral contraceptive. All patients received 250 IU r-hFSH (follitropin alpha, Serono, Inc.) and 75 IU hMG (menotropins, Serono, Inc.) daily for fives days, after which dose adjustments according to ovarian response were allowed. Group 1 began r-hFSH + hMG daily starting day 2-3 after the last OC. Cetrorelix acetate 0.25 mg was given daily once the lead follicle reached 14 mm. Group 2 began leuprolide acetate 0.5 mg daily, decreasing dose to 0.25 mg daily following pituitary desensitization. r-hFSH + hMG began day 2-3 of menses. 250 mcg r-hCG (Ovidrel®, Serono Inc.) was used to induce final oocyte maturation. Progesterone gel 8% (Serono, Inc.) was administered twice daily for luteal phase support. Day 3 embryos suitable for preimplantation genetic screening (PGS) were categorized into high or low quality based on cell number and degree of fragmentation. PGS was performed for chromosomes 13, 18, 21, X and Y. Wilcoxon test was used to analyze between treatment groups the mean number of oocytes, fertilized oocytes, embryos and aneuploidy rates. Spearman’s p correlation was utilized to assess relationship between embryo quality and aneuploidy outcome. Twenty-six patients under went treatment with antagonist (n=13) or agonist (n=13) protocols. Both treatment groups were comparable in terms of mean age, day 3 FSH, days of gonadotropin stimulation, total r-hFSH and total hMG usage, serum estradiol day of hCG and number of follicles ≥ 14mm. In the antagonist arm, oocytes retrieved, fertilized, and cleaved were 10.4 ± 5.7, 5.9 ± 3.9 (56.5%) and 6.5 ± 3.2, respectively. In the agonist arm a mean of 10.2 ± 4.3 oocytes were retrieved, 6.4 ± 3.1 (62.7%) fertilized, resulting in 6.6 ± 3.2 embryos (p>0.05). For both treatment groups, 138 embryos were assessed for morphology, 79 (56.8%) embryos were of high quality and 59 (42.8%) poor quality. Aneuploidy rate was similar, 40.7% and 42.9% for antagonist and agonist treatment groups, respectively (p>0.05). Independent of the type of pituitary suppression, high quality embryos significantly correlated with embryos normal for aneuploidy screening (p<0.0004) while poor quality embryos significantly correlated with embryos positive for aneuploidy (p<0.02). An interim analysis comparing antagonist and agonist treatment groups have not revealed significant differences between ovarian response, laboratory outcomes and aneuploidy rates. Independent of treatment regimens, high quality embryos positively correlated with normal aneuploidy outcome while poor quality embryos correlated with embryos positive for aneuploidy using a five-probe panel for chromosomes 13, 18, 21, X and Y. Our findings confirm that further evaluation of a larger powered study currently in progress should continue.

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