Oral contraceptive (OcP) pretreatment achieves better pregnancy rates in in vitro fertilization (IVF) antagonists GnRH flexible protocols: a prospective randomized study

Vilela, M.; Marconi, Marcelo; Zappacosta, M.P.; Porrati, L.; Valcárcel, A.; Marconi, Guillermo

doi:10.1016/j.fertnstert.2011.07.968

Cited by 2 publications

(2 citation statements)

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“…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.…”

Section: Resultsmentioning

confidence: 99%

“…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 ).…”

Section: Resultsmentioning

confidence: 99%

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

Venetis

Storr

Chua

et al. 2023

Human Reproduction Update

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BACKGROUND Several GnRH antagonist protocols are currently used during COS in the context of ART treatments; however, questions remain regarding whether these protocols are comparable in terms of efficacy and safety. OBJECTIVE AND RATIONALE A systematic review followed by a pairwise and network meta-analyses were performed. The systematic review and pairwise meta-analysis of direct comparative data according to the PRISMA guidelines evaluated the effectiveness of different GnRH antagonist protocols (fixed Day 5/6 versus flexible, ganirelix versus cetrorelix, with or without hormonal pretreatment) on the probability of live birth and ongoing pregnancy after COS during ART treatment. A frequentist network meta-analysis combining direct and indirect comparisons (using the long GnRH agonist protocol as the comparator) was also performed to enhance the precision of the estimates. SEARCH METHODS The systematic literature search was performed using Embase (Ovid), MEDLINE (Ovid), Cochrane Central Register of Trials (CENTRAL), SCOPUS and Web of Science (WOS), from inception until 23 November 2021. The search terms comprised three different MeSH terms that should be present in the identified studies: GnRH antagonist; assisted reproduction treatment; randomized controlled trial (RCT). Only studies published in English were included. OUTCOMES The search strategy resulted in 6738 individual publications, of which 102 were included in the systematic review (corresponding to 75 unique studies) and 73 were included in the meta-analysis. Most studies were of low quality. One study compared a flexible protocol with a fixed Day 5 protocol and the remaining RCTs with a fixed Day 6 protocol. There was a lack of data regarding live birth when comparing the flexible and fixed GnRH antagonist protocols or cetrorelix and ganirelix. No significant difference in live birth rate was observed between the different pretreatment regimens versus no pretreatment or between the different pretreatment protocols. A flexible GnRH antagonist protocol resulted in a significantly lower OPR compared with a fixed Day 5/6 protocol (relative risk (RR) 0.76, 95% CI 0.62 to 0.94, I2 = 0%; 6 RCTs; n = 907 participants; low certainty evidence). There were insufficient data for a comparison of cetrorelix and ganirelix for OPR. OCP pretreatment was associated with a lower OPR compared with no pretreatment intervention (RR 0.79, 95% CI 0.69 to 0.92; I2 = 0%; 5 RCTs, n = 1318 participants; low certainty evidence). Furthermore, in the network meta-analysis, a fixed protocol with OCP resulted in a significantly lower OPR than a fixed protocol with no pretreatment (RR 0.84, 95% CI 0.71 to 0.99; moderate quality evidence). The surface under the cumulative ranking (SUCRA) scores suggested that the fixed protocol with no pretreatment is the antagonist protocol most likely (84%) to result in the highest OPR. There was insufficient evidence of a difference between fixed/flexible or OCP pretreatment/no pretreatment interventions regarding other outcomes, such as ovarian hyperstimulation syndrome and miscarriage rates. WIDER IMPLICATIONS Available evidence, mostly of low quality and certainty, suggests that different antagonist protocols should not be considered as equivalent for clinical decision-making. More trials are required to assess the comparative effectiveness of ganirelix versus cetrorelix, the effect of different pretreatment interventions (e.g. progestins or oestradiol) or the effect of different criteria for initiation of the antagonist in the flexible protocol. Furthermore, more studies are required examining the optimal GnRH antagonist protocol in women with high or low response to ovarian stimulation.

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