GnRH agonist and hCG (dual trigger) versus hCG trigger for final follicular maturation: a double-blinded, randomized controlled study

Abstract

STUDY QUESTION Does co-administration of GnRH agonist and Human chorionic gonadotropin (hCG; dual trigger) in IVF cycles improve the number of mature oocytes and pregnancy outcome compared to hCG alone? SUMMARY ANSWER Using the dual trigger for final follicular maturation increases the number of oocytes, mature oocytes and number of blastocysts (total and top-quality) compared to triggering with hCG alone. WHAT IS KNOWN ALREADY hCG is used at the end of controlled ovarian hyperstimulation as a surrogate LH surge to induce final oocyte maturation. Recently, based on retrospective studies, the co-administration of GnRH agonist and hCG for final oocyte maturation (dual trigger) has been suggested to improve IVF outcome and pregnancy rates STUDY DESIGN, SIZE, DURATION A single center, randomized controlled, double-blinded clinical trial between May 2016 and June 2018 analyzed by intention to treat (ITT). PARTICIPANTS/MATERIALS, SETTINGS, METHODS One hundred and fifty-five normal responder patients were randomized either to receive hCG or dual trigger for final oocyte maturation. Data on patients age, BMI, AMH, number of oocytes retrieved, number of metaphase 2 (MII) oocytes, zygotes and blastocysts, clinical pregnancy rate and live birth rate were assessed and compared between the dual trigger group and the hCG group. We performed a planned interim analysis after the recruitment of 50% of the patients. Based on the totality of outcomes at the interim analysis we decided to discontinue further recruitment. MAIN RESULTS AND THE ROLE OF CHANCE One hundred and fifty-five patients were included in the study. The age (36 years versus 35.3 years P = NS), BMI (24 kg/m2 versus 23.7 kg/m2) and the AMH (20.1 pmol/l versus 22.4 pmol/l) were comparable between the two groups. Based on ITT analysis, the number of eggs retrieved (11.1 versus 13.4, P = 0.002), the MII oocytes (8.6 versus 10.3, P = 0.009), total number of blastocysts (2.9 versus 3.9, P = 0.01) and top-quality blastocysts transferred (44.7% versus 64.9%; P = 0.003) were significantly higher in the dual trigger group compared to the hCG group. The clinical pregnancy rate (24.3% versus 46.1%, OR 2.65 (1.43–1.93), P = 0.009) and the live birth rate per transfer (22% versus 36.2%, OR= 1.98 (1.05–3.75), P = 0.03) were significantly higher in the dual trigger group compared to the hCG group. LIMITATIONS, REASONS FOR CAUTION None. WIDER IMPLICATIONS OF THE FINDINGS The enhanced response observed with the dual trigger might lead to better IVF outcomes were it used more widely. STUDY FUNDING/COMPETING INTEREST(S) The study was funded by TRIO Fertility. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER ClinicalTrials.gov identifier: NCT02703584 DATE OF TRIAL REGISTRATION March 2016 DATE OF FIRST PATIENT'S ENROLLMENT May 2016

GnRH agonist and hCG (dual trigger) versus hCG trigger for follicular maturation: a systematic review and meta-analysis of randomized trials

“…1 . A total of 8 randomized trials were included for analysis and no multiple publications were identified [ 13 , 14 , 19 – 24 ]. The characteristics of the included studies are presented in Table 1 .…”

“…Sample sizes varied from 23 women to 211 women. Participants were randomized on the day of trigger in two of the included studies [ 14 , 24 ] and the day that the leading follicles reached 17 mm in diameter in one study [ 20 ]. The remaining studies did not specify the time of randomization.…”

“…The remaining studies did not specify the time of randomization. Most trials enrolled women with an age range from 18 to 42 years and body mass index (BMI) 18.0–30.0 kg/m 2 [ 13 , 14 , 20 , 23 , 24 ]. Three trials excluded women with polycystic ovarian syndrome [ 20 , 22 , 23 ].…”

“…Most of these studies are retrospective cohort studies and limited by potential confounding factors. The results of recent two randomized controlled trials (RCTs) comparing live birth rate (LBR) after dual trigger and single hCG trigger are conflicting [ 13 , 14 ]. A previous meta-analysis including four randomised trials, showed that dual trigger significantly improved clinical pregnancy rate compared with hCG trigger [ 15 ].…”

Optimising Follicular Development, Pituitary Suppression, Triggering and Luteal Phase Support During Assisted Reproductive Technology: A Delphi Consensus

“…In an attempt to improve clinical outcomes, several studies have examined the potential benefits of a dual trigger with hCG and a GnRH agonist (158)(159)(160)(161)(162)(163). A systematic review and metaanalysis of four studies in 527 women undergoing ART treatment demonstrated significantly improved clinical pregnancy rates with a dual trigger (GnRH agonist + hCG) compared with hCG alone (OR 0.48 [95% CI 0.31, 0.77], p = 0.002), although there was no significant difference in ongoing pregnancy rates between the groups (158).…”