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

2020 ◽  
Vol 35 (7) ◽  
pp. 1648-1654 ◽  
Author(s):  
J Haas ◽  
R Bassil ◽  
N Samara ◽  
E Zilberberg ◽  
C Mehta ◽  
...  
Keyword(s):  
Oocyte Maturation ◽  
Gnrh Agonist ◽  
Interim Analysis ◽  
Birth Rate ◽  
Live Birth Rate ◽  
Clinical Pregnancy ◽  
Follicular Maturation ◽  
Final Oocyte Maturation ◽  
Randomized Controlled ◽  
Double Blinded

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

scholarly journals The Effect of Dual Trigger With GnRH Agonist and hCG on Cumulative Live-Birth Rate For Normal Responders in GnRH-Antagonist Cycles

2021 ◽  
Author(s):  
Fumei Gao ◽  
Yanbin Wang ◽  
Min Fu ◽  
Qiuxiang Zhang ◽  
Yumeng Ren ◽  
...  
Keyword(s):  
Live Birth ◽  
Oocyte Maturation ◽  
Gnrh Agonist ◽  
Birth Rate ◽  
Gnrh Antagonist ◽  
Live Birth Rate ◽  
Cumulative Live Birth Rate ◽  
Final Oocyte Maturation ◽  
Cumulative Live Birth ◽  
High Responders

Abstract It has been widely acknowledged that the dual triggering for final oocyte maturation with a combination of gonadotropin-releasing hormone (GnRH) agonist and human chorionic gonadotropin (hCG) improve clinical outcomes in high responders during IVF-ICSI GnRH-antagonist cycles. However, it remains elusive whether this dual trigger is also benifical to the normal responders. The aim of this study was to investigate this issue. In the present study, we retrospectively analysed the data generated from a total of 469 normal responders from 1st January to 31st December 2017 and final oocyte maturation was performed with dual trigger with GnRH agonist combined hCG (n=270) or hCG alone (n=199). All the patients were followed up for three years. Cumulative live birth rate was calculated as the first live birth achieved after all cycles having an embryo transfer (fresh cycles as well as thawing cycles) among both groups. Subjects in the dual trigger group achieved a slightly higher number of oocytes retrieved (11.24 vs. 10.24), higher number of two-pronuclear embryo (2PN) (8.37 vs.7.67) and a higher number of embryos available (4.45 vs.4.03). But the cumulative live birth rate, an all-inclusive success rate for assisted reproductive technology, was similar between the two groups (54.07% vs.59.30%). This study showed that the dual trigger was not superior to only hCG trigger for normal responders in GnRH antagonist cycles in terms of cumulative live birth rate.

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

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Kai-Lun Hu ◽  
Siwen Wang ◽  
Xiaohang Ye ◽  
Dan Zhang ◽  
Sarah Hunt
Keyword(s):  
Systematic Review ◽  
Pregnancy Rate ◽  
Live Birth ◽  
Gnrh Agonist ◽  
Birth Rate ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Live Birth Rate ◽  
Follicular Maturation ◽  
Hcg Trigger

Abstract Background Traditionally, final follicular maturation is triggered by a single bolus of human chorionic gonadotropin (hCG). This acts as a surrogate to the naturally occurring luteinizing hormone (LH) surge to induce luteinization of the granulosa cells, resumption of meiosis and final oocyte maturation. More recently, a bolus of gonadotropin-releasing hormone (GnRH) agonist in combination with hCG (dual trigger) has been suggested as an alternative regimen to achieve final follicular maturation. Methods This study was a systematic review and meta-analysis of randomized trials evaluating the effect of dual trigger versus hCG trigger for follicular maturation on pregnancy outcomes in women undergoing in vitro fertilization (IVF). The primary outcome was the live birth rate (LBR) per started cycle. Results A total of 1048 participants were included in the analysis, with 519 in the dual trigger group and 529 in the hCG trigger group. Dual trigger treatment was associated with a significantly higher LBR per started cycle compared with the hCG trigger treatment (risk ratio (RR) = 1.37 [1.07, 1.76], I2 = 0%, moderate evidence). There was a trend towards an increase in both ongoing pregnancy rate (RR = 1.34 [0.96, 1.89], I2 = 0%, low evidence) and implantation rate (RR = 1.31 [0.90, 1.91], I2 = 76%, low evidence) with dual trigger treatment compared with hCG trigger treatment. Dual trigger treatment was associated with a significant increase in clinical pregnancy rate (RR = 1.29 [1.10, 1.52], I2 = 13%, low evidence), number of oocytes collected (mean difference (MD) = 1.52 [0.59, 2.46), I2 = 53%, low evidence), number of mature oocytes collected (MD = 1.01 [0.43, 1.58], I2 = 18%, low evidence), number of fertilized oocytes (MD = 0.73 [0.16, 1.30], I2 = 7%, low evidence) and significantly more usable embryos (MD = 0.90 [0.42, 1.38], I2 = 0%, low evidence). Conclusion Dual trigger treatment with GnRH agonist and HCG is associated with an increased live birth rate compared with conventional hCG trigger. Trial registration CRD42020204452.

scholarly journals Does an FSH surge at the time of hCG trigger improve IVF/ICSI outcomes? A randomized, double-blinded, placebo-controlled study

2020 ◽  
Vol 35 (6) ◽  
pp. 1411-1420
Author(s):  
Qi Qiu ◽  
Jia Huang ◽  
Yu Li ◽  
Xiaoli Chen ◽  
Haiyan Lin ◽  
...  
Keyword(s):  
Pregnancy Rate ◽  
Birth Rate ◽  
Implantation Rate ◽  
Live Birth Rate ◽  
Fertilization Rate ◽  
Clinical Pregnancy ◽  
Clinical Pregnancy Rate ◽  
Double Blinded ◽  
Hcg Trigger

Abstract STUDY QUESTION Does an artificially induced FSH surge at the time of hCG trigger improve IVF/ICSI outcomes? SUMMARY ANSWER An additional FSH bolus administered at the time of hCG trigger has no effect on clinical pregnancy rate, embryo quality, fertilization rate, implantation rate and live birth rate in women undergoing the long GnRH agonist (GnRHa) protocol for IVF/ICSI. WHAT IS KNOWN ALREADY Normal ovulation is preceded by a surge in both LH and FSH. Few randomized clinical trials have specifically investigated the role of the FSH surge. Some studies indicated that FSH given at hCG ovulation trigger boosts fertilization rate and even prevents ovarian hyperstimulation syndrome (OHSS). STUDY DESIGN, SIZE, DURATION This was a randomized, double-blinded, placebo-controlled trial conducted at a single IVF center, from June 2012 to November 2013. A sample size calculation indicated that 347 women per group would be adequate. A total of 732 women undergoing IVF/ICSI were randomized, using electronically randomized tables, to the intervention or placebo groups. Participants and clinical doctors were blinded to the treatment allocation. PARTICIPANTS/MATERIALS, SETTING, METHODS Patients aged ≤42 years who were treated with IVF/ICSI owing to tubal factor, male factor, unexplained, endometriosis and multiple factors were enrolled in this trial. Subjects all received a standard long GnRHa protocol for IVF/ICSI and hCG 6000–10 000 IU to trigger oocyte maturation. A total of 364 and 368 patients were randomized to receive a urinary FSH (uFSH) bolus (6 ampules, 450 IU) and placebo, respectively, at the time of the hCG trigger. The primary outcome measure was clinical pregnancy rate. The secondary outcome measures were FSH level on the day of oocyte retrieval, number of oocytes retrieved, good-quality embryo rate, live birth rate and rate of OHSS. MAIN RESULTS AND THE ROLE OF CHANCE There were no significant differences in the baseline demographic characteristics between the two study groups. There were also no significant differences between groups in cycle characteristics, such as the mean number of stimulation days, total gonadotrophin dose and peak estradiol. The clinical pregnancy rate was 51.6% in the placebo group and 52.7% in the FSH co-trigger group, with an absolute rate difference of 1.1% (95% CI −6.1% to 8.3%). The number of oocytes retrieved was 10.47 ± 4.52 and 10.74 ± 5.01 (P = 0.44), the rate of good-quality embryos was 37% and 33.9% (P = 0.093) and the implantation rate was 35% and 36% (P = 0.7) in the placebo group and the FSH co-trigger group, respectively. LIMITATIONS, REASONS FOR CAUTION This was a single-center study, which may limit its effectiveness. The use of uFSH is a limitation, as this is not the same as the natural FSH. We did not collect follicular fluid for further study of molecular changes after the use of uFSH as a co-trigger. WIDER IMPLICATIONS OF THE FINDINGS Based on previous data and our results, an additional FSH bolus administered at the time of hCG trigger has no benefit on clinical pregnancy rates in women undergoing the long GnRHa protocol in IVF/ICSI: a single hCG trigger is sufficient. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the National Key Research and Development Program of China (2016YFC1000205); Sun Yat-Sen University Clinical Research 5010 Program (2016004); the Science and Technology Project of Guangdong Province (2016A020216011 and 2017A020213028); and Science Technology Research Project of Guangdong Province (S2011010004662). There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER The trial was registered in the Chinese Clinical Trial Registry (ChiCTR-TRC-12002246). TRIAL REGISTRATION DATE 20 May 2012. DATE OF FIRST PATIENT’S ENROLMENT 10 June 2012.

scholarly journals Effect of a “Dual Trigger” Using a GnRH Agonist and hCG on the Cumulative Live-Birth Rate for Normal Responders in GnRH-Antagonist Cycles

2021 ◽  
Vol 8 ◽  
Author(s):  
Fumei Gao ◽  
Yanbin Wang ◽  
Min Fu ◽  
Qiuxiang Zhang ◽  
Yumeng Ren ◽  
...  
Keyword(s):  
Live Birth ◽  
Oocyte Maturation ◽  
Birth Rate ◽  
Gnrh Antagonist ◽  
Live Birth Rate ◽  
Cumulative Live Birth Rate ◽  
Final Oocyte Maturation ◽  
Cumulative Live Birth ◽  
High Responders

“Dual triggering” for final oocyte maturation using a combination of a gonadotropin-releasing hormone agonist (GnRHa) and human chorionic gonadotropin (hCG) can improve clinical outcomes in high responders during in vitro fertilization–intracytoplasmic sperm injection (IVF–ICSI) GnRH-antagonist cycles. However, whether this dual trigger is also beneficial to normal responders is not known. We retrospectively analyzed the data generated from 469 normal responders from 1 January to 31 December 2017. The final oocyte maturation was undertaken with a dual trigger with a GnRHa combined with hCG (n = 270) or hCG alone (n = 199). Patients were followed up for 3 years. The cumulative live-birth rate was calculated as the first live birth achieved after all cycles having an embryo transfer (cycles using fresh embryos and frozen–thawed embryos) among both groups. Women in the dual-trigger group achieved a slightly higher number of oocytes retrieved (11.24 vs. 10.24), higher number of two-pronuclear (2PN) embryos (8.37 vs. 7.67) and a higher number of embryos available (4.45 vs. 4.03). However, the cumulative live-birth rate and the all-inclusive success rate for assisted reproductive technology was similar between the two groups (54.07 vs. 59.30%). We showed that a dual trigger was not superior to a hCG-alone trigger for normal responders in GnRH-antagonist cycles in terms of the cumulative live-birth rate.

scholarly journals Endometrial Preparation for Frozen–Thawed Embryo Transfer With or Without Pretreatment With Gonadotropin-Releasing Hormone Agonist in Regular Menstrual Cycles: Results of a Retrospective Cohort Study

2021 ◽  
Author(s):  
Fu Wei ◽  
Liling Liu ◽  
Mei Dong ◽  
Ying Tan ◽  
Xiqian Zhang ◽  
...  
Keyword(s):  
Pregnancy Rate ◽  
Live Birth ◽  
Gnrh Agonist ◽  
Birth Rate ◽  
Live Birth Rate ◽  
Clinical Pregnancy ◽  
Clinical Pregnancy Rate ◽  
Menstrual Cycles ◽  
Endometrial Preparation ◽  
Long Acting

Abstract ObjectsTo compare the treatment outcomes of FET in hormonal replacement treatment (HRT) protocol with and without long-acting gonadotropin-releasing hormone agonist (GnRHa) pretreatment in patients with regular menstrual cycles. MethodsA total of 5049 patients from three centers were recruited in this retrospective study. The study population was divided into two groups. In HRT with GnRHa group, endometrial preparation with supplement estrogen 6mg daily initiated following down-regulation of long-acting GnRH agonist. In HRT group, the same dose of estrogen administration only for two weeks. Live birth rates were the primary outcomes measured in both groups. ResultsThere were no differences in implantation rate, β-HCG positive rate, clinical pregnancy rate, and early miscarriage rate between the two groups. The ongoing pregnancy rate and the live birth rate were higher in HRT group compared to the agonist group (47.3% vs 42.7% and 44.7% vs 39.8%, respectively). However, the co-treatment with GnRH agonist in HRT protocol was not associated with clinical pregnancy rate (OR 0.94; 95% CI 0.78 to 1.12) and live birth rate (OR 0.82; 95% CI 0.71 to 1.02) after logistic regression analysis. In the first FET cycle, patients in HRT group achieved higher clinical pregnancy rate and live birth rate. In addition, there was no differences in clinical pregnancy rate and live birth rate between the two groups in standard patients.ConclusionsThe HRT protocol for FET seems to be as effective as the HRT protocol involving preliminary pituitary suppression with GnRH agonist in regular menstrual cycles.

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