Comparison between Soft and Conventional Flexible Antagonist Protocols Regarding ICSI Outcome and Pregnancy Rate in Women with Poor Ovarian Response

Abstract

Background: Poor ovarian responders (POR) are defined as the group of infertile women who are characterized by decreased the response of the ovarian follicles to gonadotropins (Gn) and/or diminished ovarian reserve making them not respond well to standard protocols leading to recruit less number of oocytes. Until now no ideal ovarian stimulation protocol has be proved for such group of women. The conventional or classical ovarian stimulation   protocols using highest doses of Gn have been used for many years proposing to harvest more oocytes but recently the concept of using soft protocol using low doses of Gn with/without oral compounds such as letrozole. Soft ovarian stimulation protocol was suggested and accepted as a good option for this group of women. Gonadotropin-releasing hormone (GnRH) - antagonist protocols is the best choice for poor responders especially with low-dose Gn protocols. Objective: To evaluate the effect of soft versus conventional flexible GnRH-antagonist stimulation protocol in POR concerning IVF/ICSI outcome and pregnancy rate. Patients, Materials and Methods: This was a prospective randomized controlled trial study. It included 80 infertile poor responder’s women according to Bologna criteria divided to two equal groups and undergoing IVF/ICSI antagonist protocols. One group underwent soft protocol by using letrozole 2.5mg twice daily for 5 days starting from cycle day 2-3 overlapped low-dose Gn (225 IU) from cycle day 4-5. Other group received high dose Gn only (450 IU) from cycle day 2-3. Both groups continued stimulation throughout the ovarian stimulation cycle until the day of trigger using the flexible GnRH-antagonist protocol in which all women were received 0.25 mg/day Cetrorelix when at least two or more follicles reached a size of 12-14 mm. Basal physical examination and basal hormonal assessment was performed including FSH, LH, and S. prolactin, TSH, E2, P4 and AMH associated with AFC by transvaginal ultrasound. At day of trigger, serum levels of some hormones (LH, Progesterone and Estradiol) with no. of growing follicles and endometrial thickness measurement was performed. Both groups were undergone oocyte pickup, ICSI, and embryo transfer (ET) if embryos were available or case closed if no ET and cycle outcomes with pregnancy rate were compared. The data analyzed using Statistical Package for Social Sciences (SPSS) version 25 using Pearson Chi-square test (α2-test). Independent t-test and Analysis of Variance (ANOVA) (two tailed) was used to compare the continuous variables accordingly. Result(s): The demographic characteristics between the two study groups and the comparison of baseline LH and Progesterone showed no significant difference. At day of trigger, there was a statistically significant difference in the mean levels of LH and progesterone between the studied groups. The mean levels of LH and progesterone in soft protocol group were significantly higher than in conventional protocol (P= 0.001). There is no statistically significant difference (P> 0.05) in the mean of endometrial thickness. Concerning the ICSI outcome parameters including no. of retrieved oocyte, no of MII, no. of fertilized oocyte, total no. of embryos, and no. of embryo transferred to uterus, there was no significant difference (P > 0.05). Pregnancy rate and case closed rate also showed no significant difference Conclusion: The current study showed evidence in favor of soft protocol for poor responders since it is resulted in no difference in ICSI outcome and pregnancy rates associated with much less cost effectiveness.