Skip to main content
Top
Published in: Reproductive Biology and Endocrinology 1/2021

Open Access 01-12-2021 | Infertility | Research

Cumulative live birth rates between GnRH-agonist long and GnRH-antagonist protocol in one ART cycle when all embryos transferred: real-word data of 18,853 women from China

Authors: Jingwei Yang, Xiaodong Zhang, Xiaoyan Ding, Yuting Wang, Guoning Huang, Hong Ye

Published in: Reproductive Biology and Endocrinology | Issue 1/2021

Login to get access

Abstract

Background

A consensus has been reached on the preferred primary outcome of all infertility treatment trials, which is the cumulative live birth rate (CLBR). Some recent randomized controlled trials (RCTs) and retrospective studies have compared the effectiveness of GnRH-antagonist and GnRH-agonist protocols but showed inconsistent results. Studies commonly used conservative estimates and optimal estimates to described the CLBR of one incomplete assisted reproductive technology (ART) cycle and there are not many previous studies with data of the complete cycle to compare CLBRs in GnRH-antagonist versus GnRH-agonist protocols.

Methods

A total of 18,853 patients have completed their first IVF cycle including fresh and subsequent frozen-thawed cycles during 2016–2019, 16,827 patients were treated with GnRH-a long and 2026 patients with GnRH-ant protocol. Multivariable logistic analysis was used to evaluate the difference of GnRH-a and GnRH-ant protocol in relation to CLBR. Utilized Propensity Score Matching(PSM) for sampling by up to 1:1 nearest neighbor matching to adjust the numerical difference and balance the confounders between groups.

Results

Before PSM, significant differences were observed in baseline characteristics and the CLBR was 50.91% in the GnRH-a and 33.42% in the GnRH-ant (OR = 2.07; 95%CI: 1.88–2.28; P < 0.001). Stratified analysis showed the CLBR of GnRH-ant was lower than GnRH-a in suboptimal responders(46.89 vs 27.42%, OR = 2.34, 95%CI = 1.99–2.74; P < 0.001) and no differences of CLBR were observed in other patients between protocols. After adjusting for potential confounders, multivariable logistic analysis found the CLBR of GnRH-ant group was lower than that of GnRH-a group (OR = 2.11, 95%CI:1.69–2.63, P < 0.001). After PSM balenced the confounders between groups, the CLBR of GnRH-a group was higher than that of GnRH-ant group in suboptimal responders((38.61 vs 28.22%, OR = 1.60, 95%CI = 1.28–1.99; P < 0.001) and the normal fertilization rate and number of available embryo in GnRH-a were higher than these of GnRH-ant groups in suboptimal responders (77.39 vs 75.22%; 2.86 ± 1.26 vs 2.61 ± 1.22; P < 0.05). No significant difference was observed in other patients between different protocols.

Conclusions

It is crucial to optimize the utilization of protocols in different ovarian response patients and reconsider the field of application of GnRH-ant protocols in China.
Appendix
Available only for authorised users
Literature
1.
go back to reference Niederberger C, et al. Forty years of IVF. Fertil Steril. 2018;110:185–324.CrossRef Niederberger C, et al. Forty years of IVF. Fertil Steril. 2018;110:185–324.CrossRef
3.
go back to reference Lambalk CB, et al. GnRH antagonist versus long agonist protocols in IVF: a systematic review and meta-analysis accounting for patient type. Hum Reprod Update. 2017;23:560–79.CrossRef Lambalk CB, et al. GnRH antagonist versus long agonist protocols in IVF: a systematic review and meta-analysis accounting for patient type. Hum Reprod Update. 2017;23:560–79.CrossRef
4.
go back to reference Zhang J, et al. Effect of endometrium thickness on clinical outcomes in luteal phase short-acting GnRH-a long protocol and GnRH-ant protocol. Front Endocrinol. 2021;12:578783.CrossRef Zhang J, et al. Effect of endometrium thickness on clinical outcomes in luteal phase short-acting GnRH-a long protocol and GnRH-ant protocol. Front Endocrinol. 2021;12:578783.CrossRef
6.
go back to reference Wang R, et al. Comparisons of GnRH antagonist protocol versus GnRH agonist long protocol in patients with normal ovarian reserve: A systematic review and meta-analysis. PLoS One. 2017;12:e0175985.CrossRef Wang R, et al. Comparisons of GnRH antagonist protocol versus GnRH agonist long protocol in patients with normal ovarian reserve: A systematic review and meta-analysis. PLoS One. 2017;12:e0175985.CrossRef
8.
go back to reference Huang MC, et al. GnRH agonist long protocol versus GnRH antagonist protocol for various aged patients with diminished ovarian reserve: a retrospective study. PLoS One. 2018;13:e0207081.CrossRef Huang MC, et al. GnRH agonist long protocol versus GnRH antagonist protocol for various aged patients with diminished ovarian reserve: a retrospective study. PLoS One. 2018;13:e0207081.CrossRef
9.
go back to reference Ruggiero M, et al. Comparison between GnRH agonist and antagonist protocols for severe endometriosis in assisted reproductive cycles. Journal of Endometriosis. 2012;4:42–7.CrossRef Ruggiero M, et al. Comparison between GnRH agonist and antagonist protocols for severe endometriosis in assisted reproductive cycles. Journal of Endometriosis. 2012;4:42–7.CrossRef
10.
go back to reference Toftager M, et al. Cumulative live birth rates after one ART cycle including all subsequent frozen-thaw cycles in 1050 women: secondary outcome of an RCT comparing GnRH-antagonist and GnRH-agonist protocols. Hum Reprod. 2017;32:556–67.PubMed Toftager M, et al. Cumulative live birth rates after one ART cycle including all subsequent frozen-thaw cycles in 1050 women: secondary outcome of an RCT comparing GnRH-antagonist and GnRH-agonist protocols. Hum Reprod. 2017;32:556–67.PubMed
12.
go back to reference Maheshwari A, et al. Cumulative live birth rate: time for a consensus? Hum Reprod. 2015;30:2703–7.PubMed Maheshwari A, et al. Cumulative live birth rate: time for a consensus? Hum Reprod. 2015;30:2703–7.PubMed
13.
go back to reference Bica I, et al. From real-world patient data to individualized treatment effects using machine learning: current and future methods to address underlying challenges. Clin Pharmacol Ther. 2020;109:87–100.CrossRef Bica I, et al. From real-world patient data to individualized treatment effects using machine learning: current and future methods to address underlying challenges. Clin Pharmacol Ther. 2020;109:87–100.CrossRef
14.
go back to reference Lainas T, et al. In a flexible antagonist protocol, earlier, criteria-based initiation of GnRH antagonist is associated with increased pregnancy rates in IVF. Hum Reprod. 2005;20:2426–33.CrossRef Lainas T, et al. In a flexible antagonist protocol, earlier, criteria-based initiation of GnRH antagonist is associated with increased pregnancy rates in IVF. Hum Reprod. 2005;20:2426–33.CrossRef
16.
go back to reference Chian RC, et al. High survival rate of bovine oocytes matured in vitro following vitrification. J Reprod Dev. 2004;50:685–96.CrossRef Chian RC, et al. High survival rate of bovine oocytes matured in vitro following vitrification. J Reprod Dev. 2004;50:685–96.CrossRef
17.
go back to reference Society for Assisted Reproductive Technology, American Society for Reproductive Medicine. Assisted reproductive technology in the United States: 2000 results generated from the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology Registry. Fertil Steril. 2004;81:1207–20.CrossRef Society for Assisted Reproductive Technology, American Society for Reproductive Medicine. Assisted reproductive technology in the United States: 2000 results generated from the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology Registry. Fertil Steril. 2004;81:1207–20.CrossRef
18.
go back to reference Copperman AB, et al. Optimal usage of the GnRH antagonists: a review of the literature. Reprod Biol Endocrinol. 2013;11:20.CrossRef Copperman AB, et al. Optimal usage of the GnRH antagonists: a review of the literature. Reprod Biol Endocrinol. 2013;11:20.CrossRef
19.
go back to reference Al-Inany HG, et al. Gonadotrophin-releasing hormone antagonists for assisted conception: a Cochrane review. Reprod Biomed Online. 2007;14:640–9.CrossRef Al-Inany HG, et al. Gonadotrophin-releasing hormone antagonists for assisted conception: a Cochrane review. Reprod Biomed Online. 2007;14:640–9.CrossRef
20.
go back to reference Al-Inany HG, et al. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology. Cochrane Database Syst Rev. 2016;4:CD001750.PubMed Al-Inany HG, et al. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology. Cochrane Database Syst Rev. 2016;4:CD001750.PubMed
21.
go back to reference Xiao J, et al. Effectiveness of GnRH antagonist in the treatment of patients with polycystic ovary syndrome undergoing IVF: a systematic review and meta analysis. Gynecol Endocrinol. 2013;29:187–91.CrossRef Xiao J, et al. Effectiveness of GnRH antagonist in the treatment of patients with polycystic ovary syndrome undergoing IVF: a systematic review and meta analysis. Gynecol Endocrinol. 2013;29:187–91.CrossRef
23.
go back to reference Kolibianakis EM, et al. Among patients treated for IVF with gonadotrophins and GnRH analogues, is the probability of live birth dependent on the type of analogue used? A systematic review and meta-analysis. Hum Reprod Update. 2006;12:651–71.CrossRef Kolibianakis EM, et al. Among patients treated for IVF with gonadotrophins and GnRH analogues, is the probability of live birth dependent on the type of analogue used? A systematic review and meta-analysis. Hum Reprod Update. 2006;12:651–71.CrossRef
24.
go back to reference Pasello G, et al. Real world data in the era of immune checkpoint inhibitors (ICIs): increasing evidence and future applications in lung cancer. Cancer Treat Rev. 2020;87:102031.CrossRef Pasello G, et al. Real world data in the era of immune checkpoint inhibitors (ICIs): increasing evidence and future applications in lung cancer. Cancer Treat Rev. 2020;87:102031.CrossRef
25.
go back to reference Racca A, et al. Do we need to measure progesterone in oocyte donation cycles? A retrospective analysis evaluating cumulative live birth rates and embryo quality. Hum Reprod. 2020;35:167–74.CrossRef Racca A, et al. Do we need to measure progesterone in oocyte donation cycles? A retrospective analysis evaluating cumulative live birth rates and embryo quality. Hum Reprod. 2020;35:167–74.CrossRef
26.
go back to reference Law YJ, et al. The number of oocytes associated with maximum cumulative live birth rates per aspiration depends on female age: a population study of 221 221 treatment cycles. Hum Reprod. 2019;34:1778–87.CrossRef Law YJ, et al. The number of oocytes associated with maximum cumulative live birth rates per aspiration depends on female age: a population study of 221 221 treatment cycles. Hum Reprod. 2019;34:1778–87.CrossRef
29.
go back to reference Venetis CA, et al. Is more better? A higher oocyte yield is independently associated with more day-3 euploid embryos after ICSI. Hum Reprod. 2019;34:79–83.CrossRef Venetis CA, et al. Is more better? A higher oocyte yield is independently associated with more day-3 euploid embryos after ICSI. Hum Reprod. 2019;34:79–83.CrossRef
31.
go back to reference Bahceci M, et al. Frozen-thawed cleavage-stage embryo transfer cycles after previous GnRH agonist or antagonist stimulation. Reprod Biomed Online. 2009;18:67–72.CrossRef Bahceci M, et al. Frozen-thawed cleavage-stage embryo transfer cycles after previous GnRH agonist or antagonist stimulation. Reprod Biomed Online. 2009;18:67–72.CrossRef
32.
go back to reference Rackow BW, et al. GnRH antagonists may affect endometrial receptivity. Fertil Steril. 2008;89:1234–9.CrossRef Rackow BW, et al. GnRH antagonists may affect endometrial receptivity. Fertil Steril. 2008;89:1234–9.CrossRef
33.
go back to reference Li C, et al. Oocytes and hypoxanthine orchestrate the G2-M switch mechanism in ovarian granulosa cells. Development. 2020;147:dev184838.CrossRef Li C, et al. Oocytes and hypoxanthine orchestrate the G2-M switch mechanism in ovarian granulosa cells. Development. 2020;147:dev184838.CrossRef
34.
go back to reference Huang J, et al. The regulation of the follicular synchronization and sensitivity of rats with PCOS by AMH during prolonged pituitary downregulation. Gene. 2019;721:144106.CrossRef Huang J, et al. The regulation of the follicular synchronization and sensitivity of rats with PCOS by AMH during prolonged pituitary downregulation. Gene. 2019;721:144106.CrossRef
36.
go back to reference Hernandez ER. Embryo implantation and GnRH antagonists: embryo implantation: the Rubicon for GnRH antagonists. Hum Reprod. 2000;15:1211–6.CrossRef Hernandez ER. Embryo implantation and GnRH antagonists: embryo implantation: the Rubicon for GnRH antagonists. Hum Reprod. 2000;15:1211–6.CrossRef
37.
go back to reference Ruan HC, et al. Ovarian stimulation with GnRH agonist, but not GnRH antagonist, partially restores the expression of endometrial integrin beta3 and leukaemia-inhibitory factor and improves uterine receptivity in mice. Hum Reprod. 2006;21:2521–9.CrossRef Ruan HC, et al. Ovarian stimulation with GnRH agonist, but not GnRH antagonist, partially restores the expression of endometrial integrin beta3 and leukaemia-inhibitory factor and improves uterine receptivity in mice. Hum Reprod. 2006;21:2521–9.CrossRef
38.
go back to reference Chen Q, et al. Comparative proteomics reveal negative effects of gonadotropin-releasing hormone agonist and antagonist on human endometrium. Drug Des Devel Ther. 2019;13:1855–63.CrossRef Chen Q, et al. Comparative proteomics reveal negative effects of gonadotropin-releasing hormone agonist and antagonist on human endometrium. Drug Des Devel Ther. 2019;13:1855–63.CrossRef
40.
go back to reference Ding W, et al. Impact of female obesity on cumulative live birth rates in the first complete ovarian stimulation cycle. Front Endocrinol. 2019;10:516.CrossRef Ding W, et al. Impact of female obesity on cumulative live birth rates in the first complete ovarian stimulation cycle. Front Endocrinol. 2019;10:516.CrossRef
Metadata
Title
Cumulative live birth rates between GnRH-agonist long and GnRH-antagonist protocol in one ART cycle when all embryos transferred: real-word data of 18,853 women from China
Authors
Jingwei Yang
Xiaodong Zhang
Xiaoyan Ding
Yuting Wang
Guoning Huang
Hong Ye
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2021
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/s12958-021-00814-0

Other articles of this Issue 1/2021

Reproductive Biology and Endocrinology 1/2021 Go to the issue