Comparison of pre-treatment with OCPs or estradiol valerate vs. no pre-treatment prior to GnRH antagonist used for IVF cycles: An RCT

Abstract

Background:Both oral contraceptive pills (OCPs) and estradiol valerate (E2) have been used to schedule a gonadotropin-releasing hormone antagonist in vitro fertilization (IVF) cycles. Since the suppression of follicle-stimulating hormone by OCPs can stay 5-7 days after stopping the pills, it seems that starting the gonadotropin-releasing hormone (GnRH) after 6 days of pre-treatment discontinuation may be important in IVF outcomes.Objective:The aim of the present study was to determine the number of mature oocyte and pregnancy rate of three pretreatment methods for fresh embryo transfer cycles.Materials and Methods:In this randomized controlled trial, two-hundred ten women (18-35 yr and less than 2 previous IVF attempts) undergoing IVF with the GnRH antagonist protocol were randomized to the OCP, E2, and no pretreatment arms. OCP group (n=53) received OCP (ethinyl estradiol30 μg and levonorgestrel150 μg), E2 group (n=63) received 4 mg/day oral E2 (17β‐E2) for 10 days from day 20 of the previous cycle and GnRH antagonist stimulation was started 6 days after the interruption of OCP and E2. The control group (n =70) did not receive any pretreatment.Results:No significant difference was observed in the mean number of the mature oocyte, endometrial thickness, and embryo quality. The pregnancy rate in E2 group was higher than the two other groups (42.9% vs 39.6% and 34.3% in OCP and control group, respectively), but the difference was not statistically significant (p=0.59).Conclusion: It seems OCP or E2 pretreatment could not improve the fresh IVF-embryo transfer outcomes.

What is the optimal GnRH antagonist protocol for ovarian stimulation during ART treatment? A systematic review and network meta-analysis

“…However, E2 pretreatment compared with no pretreatment was associated with significantly higher mean total dose of gonadotrophins (WMD 192.73 IU, 95% CI 140.22 to 245.23; 5 RCTs; 711 participants; I 2 = 4.6%; low certainty evidence) ( Fanchin et al , 2003 ; Cédrin-Durnerin et al , 2007 ; Blockeel et al , 2012 ; Cédrin-Durnerin et al , 2012 ; Fernandez-Prada et al , 2022 ). No significant difference in the number of oocytes retrieved was detected between E2 pretreatment compared with no pretreatment (WMD 0.39 oocytes, 95% CI −0.32 to 1.09; 6 RCTs; n = 851 participants; I 2 = 0%; low certainty evidence) ( Cédrin-Durnerin et al , 2007 ; Blockeel et al , 2012 ; Cédrin-Durnerin et al , 2012 ; Erdem et al , 2015 ; Shahrokh Tehrani Nejad et al , 2018 ; Fernandez-Prada et al , 2022 ). No difference was reported or there were insufficient data for pairwise meta-analyses of the remaining comparisons ( Table II ).…”

“…Fourteen trials reporting on pretreatment versus no pretreatment were included ( Fanchin et al , 2003 ; Huirne et al ., 2006a ; Kolibianakis et al , 2006 ; Rombauts et al , 2006 ; Cédrin-Durnerin et al , 2007 ; Andersen et al , 2011 ; Kim et al , 2011 ; Vilela et al , 2011 ; Blockeel et al , 2012 ; Cédrin-Durnerin et al , 2012 ; Hauzman et al , 2013 ; Erdem et al , 2015 ; Shahrokh Tehrani Nejad et al , 2018 ; Fernandez-Prada et al , 2022 ). OPR was lower with OCP pretreatment compared with no pretreatment (RR 0.79, 95% CI 0.65 to 0.97 I 2 = 0%; 5 RCTs, n = 1318 participants; low certainty evidence) ( Fig.…”

“…Pretreatment with OCP was associated with a non-significant difference in the duration of stimulation compared with no pretreatment (WMD 0.66 days, 95% CI −0.48 to 1.81; 8 RCTs; n = 1223 participants; I 2 = 95.9%; very low certainty evidence) ( Huirne et al ., 2006a ; Kolibianakis et al , 2006 ; Rombauts et al , 2006 ; Cédrin-Durnerin et al , 2007 ; Kim et al , 2011 ; Vilela et al , 2011 ; Shahrokh Tehrani Nejad et al , 2018 ; Fernandez-Prada et al , 2022 ) and no significant difference in the mean total dose of gonadotrophins compared with no pretreatment (WMD 289.43 IU, 95% CI −115.18 to 694.05; 7 RCTs; n = 1100 participants; I 2 = 94.6%; very low certainty evidence) ( Huirne et al ., 2006a ; Kolibianakis et al , 2006 ; Rombauts et al , 2006 ; Cédrin-Durnerin et al , 2007 ; Kim et al , 2011 ; Vilela et al , 2011 ; Fernandez-Prada et al , 2022 ). Progestin pretreatment was not associated with a significantly higher mean total dose of gonadotrophins compared with no pretreatment (WMD 138.12 IU, 95% CI −287.06 to 563.30; 2 RCTs; n = 392 participants; I 2 = 0%; low certainty evidence) ( Cédrin-Durnerin et al , 2007 , 2012 ).…”

Hormonal Pretreatment for Ovarian Stimulation: A Narrative Review

“…Microsoft® Excel 2016 was used to create the data extraction form and summarize the findings. The articles selected for the narrative review were the following: A randomized controlled trial conducted in Spain, A proof-of-concept study also carried out in Spain, An updated meta-analysis carried out in Germany, A randomized controlled trial conducted in China, A randomized control trial conducted in Iran, A meta-analysis conducted in the Republic of Korea, A retrospective study carried out in Spain, A cohort study carried out in Brazil [13][14][15][16][17][18][19][20].…”

Ovarian stimulation in assisted reproductive technology cycles for varied patient profiles: An Indian perspective

“…[ 1 34 ] Pre-treatment with oestrogen, progesterone or oral contraceptive pills (OCP) prior to COS do not offer any benefits in normo-responders. [ 35 36 ] A recent meta-analysis showed a significantly lower ongoing pregnancy rate with antagonist compared to long agonist protocol. [ 37 ] However, this outcome was noted only with the combination of oral hormonal pre-treatment and flexible antagonist protocol, while no such difference was evident between fixed antagonist and agonist protocol.…”