Skip to main content
Top
Published in: Reproductive Biology and Endocrinology 1/2020

Open Access 01-12-2020 | Infertility | Research

The effectiveness of different down-regulating protocols on in vitro fertilization-embryo transfer in endometriosis: a meta-analysis

Authors: Xue Cao, Hong-yang Chang, Jun-yan Xu, Yi Zheng, Yun-gai Xiang, Bing Xiao, Xu-jing Geng, Li-li Ni, Xi-ying Chu, Shi-bo Tao, Yan He, Gen-hong Mao

Published in: Reproductive Biology and Endocrinology | Issue 1/2020

Login to get access

Abstract

Background

To investigate the effectiveness of the GnRH-a ultra-long protocol, GnRH-a long protocol, and GnRH-a short protocol used in in vitro fertilization-embryo transfer (IVF-ET) in infertile women with endometriosis.

Methods

We searched PubMed, Embase, Web of Science, Cochrane Library, Elsevier Science Direct, OA Library, Google Scholar, China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, China Science and Technology Journal database, and the China Biology Medicine disc for randomized controlled trials (RCTs) and observational studies (non-RCTs) to evaluate the efficacy of the GnRH-a ultra-long protocol, GnRH-a long protocol, and GnRH-a short protocol in IVF-ET in infertile patients with endometriosis.

Results

A total of 21 studies in compliance with the standard literature were included, and RCT and non-RCT studies were analyzed separately. This meta-analysis showed that the GnRH-a ultra-long protocol could improve the clinical pregnancy rate of infertile patients in RCT studies, especially in patients with stages III–IV endometriosis (RR = 2.04, 95% CI: 1.37~3.04, P < 0.05). However, subgroup analysis found the different down-regulation protocols provided no significant difference in improving clinical outcomes in patients with endometriosis in the non-RCT studies.

Conclusion

This study suggests that the GnRH-a ultra-long protocol can improve the clinical pregnancy rate of the patients with stages III–IV endometriosis in RCT studies. Although it is generally believed that the results of RCT are more reliable, the conclusions of the non-RCT studies cannot be easily neglect, which let us draw conclusions more cautious.
Appendix
Available only for authorised users
Literature
1.
go back to reference Macer ML, Taylor HS. Endometriosis and infertility: a review of the pathogenesis and treatment of endometriosis-associated infertility. Obstet Gynecol Clin N Am. 2012;39:535–49.CrossRef Macer ML, Taylor HS. Endometriosis and infertility: a review of the pathogenesis and treatment of endometriosis-associated infertility. Obstet Gynecol Clin N Am. 2012;39:535–49.CrossRef
2.
go back to reference Young VJ, Brown JK, Saunders PT, Horne AW. The role of the peritoneum in the pathogenesis of endometriosis. Hum Reprod Update. 2013;19:558–69.CrossRef Young VJ, Brown JK, Saunders PT, Horne AW. The role of the peritoneum in the pathogenesis of endometriosis. Hum Reprod Update. 2013;19:558–69.CrossRef
3.
go back to reference Gazvani R, Templeton A. Peritoneal environment, cytokines and angiogenesis in the pathophysiology of endometriosis. Reproduction. 2002;123:217–26.CrossRef Gazvani R, Templeton A. Peritoneal environment, cytokines and angiogenesis in the pathophysiology of endometriosis. Reproduction. 2002;123:217–26.CrossRef
4.
go back to reference Matsuzaki S, Schubert B. Oxidative stress status in normal ovarian cortex surrounding ovarian endometriosis. Fertil Steril. 2010;93:2431–2.CrossRef Matsuzaki S, Schubert B. Oxidative stress status in normal ovarian cortex surrounding ovarian endometriosis. Fertil Steril. 2010;93:2431–2.CrossRef
5.
go back to reference Gupta S, Agarwal A, Agarwal R, Loret-de-Mola JR. Impact of ovarian endometrioma on assisted reproduction outcomes. Reprod Biomed Online. 2006;13:349–60.CrossRef Gupta S, Agarwal A, Agarwal R, Loret-de-Mola JR. Impact of ovarian endometrioma on assisted reproduction outcomes. Reprod Biomed Online. 2006;13:349–60.CrossRef
6.
go back to reference Borges E, Setti AS, Braga DP, Figueira R, Iaconelli A. Decline in semen quality among infertile men in Brazil during the past 10 years. Int Braz J Urol. 2015;41:757–63.CrossRef Borges E, Setti AS, Braga DP, Figueira R, Iaconelli A. Decline in semen quality among infertile men in Brazil during the past 10 years. Int Braz J Urol. 2015;41:757–63.CrossRef
7.
go back to reference Beloosesky R, Kol S, Lightman A, Itskovitz-Eldor J. Ovarian stimulation in in vitro fertilization with or without the “long” gonadotropin-releasing hormone agonist protocol: effect on cycle duration and outcome. Fertil Steril. 2000;74:166–8.CrossRef Beloosesky R, Kol S, Lightman A, Itskovitz-Eldor J. Ovarian stimulation in in vitro fertilization with or without the “long” gonadotropin-releasing hormone agonist protocol: effect on cycle duration and outcome. Fertil Steril. 2000;74:166–8.CrossRef
8.
go back to reference Ferrero S, Gillott DJ, Remorgida V, Anserini P, Ragni N, Grudzinskas JG. GnRH analogue remarkably down-regulates inflammatory proteins in peritoneal fluid proteome of women with endometriosis. J Reprod Med. 2009;54:223–31.PubMed Ferrero S, Gillott DJ, Remorgida V, Anserini P, Ragni N, Grudzinskas JG. GnRH analogue remarkably down-regulates inflammatory proteins in peritoneal fluid proteome of women with endometriosis. J Reprod Med. 2009;54:223–31.PubMed
9.
go back to reference Sallam HN, Garcia-Velasco JA, Dias S, Arici A. Long-term pituitary down-regulation before in vitro fertilization (IVF) for women with endometriosis. Cochrane Database Syst Rev. 2006;1:CD004635. Sallam HN, Garcia-Velasco JA, Dias S, Arici A. Long-term pituitary down-regulation before in vitro fertilization (IVF) for women with endometriosis. Cochrane Database Syst Rev. 2006;1:CD004635.
10.
go back to reference Zhang JP, Wu XQ, Bi XY, Chen BB, Zhang SP, Liu HP. Effect of long protocol on the outcome of in vitro fertilization-embryo transfer in patients with endometriosis compared with prolonged protocol. J Reprod Contracept. 2014;25:81–8. Zhang JP, Wu XQ, Bi XY, Chen BB, Zhang SP, Liu HP. Effect of long protocol on the outcome of in vitro fertilization-embryo transfer in patients with endometriosis compared with prolonged protocol. J Reprod Contracept. 2014;25:81–8.
11.
go back to reference Maged AM, Rashwan H, Mahmoud M, Mazny AE, Farouk M, Belal DS, et al. Effect of prolonged GnRH agonist Downregulation on ICSI outcome in patients with Endometriomas of less than 5 cm: a randomized controlled trial. Reprod Sci. 2018;25:1509–14.CrossRef Maged AM, Rashwan H, Mahmoud M, Mazny AE, Farouk M, Belal DS, et al. Effect of prolonged GnRH agonist Downregulation on ICSI outcome in patients with Endometriomas of less than 5 cm: a randomized controlled trial. Reprod Sci. 2018;25:1509–14.CrossRef
12.
go back to reference Decleer W, Osmanagaoglu K, Verschueren K, Comhaire F, Devroey P. RCT to evaluate the influence of adjuvant medical treatment of peritoneal endometriosis on the outcome of IVF. Hum Reprod. 2016;31:2017–23.CrossRef Decleer W, Osmanagaoglu K, Verschueren K, Comhaire F, Devroey P. RCT to evaluate the influence of adjuvant medical treatment of peritoneal endometriosis on the outcome of IVF. Hum Reprod. 2016;31:2017–23.CrossRef
13.
go back to reference Rickes D, Nickel I, Kropf S, Kleinstein J. Increased pregnancy rates after ultralong postoperative therapy with gonadotropin-releasing hormone analogs in patients with endometriosis. Fertil Steril. 2002;78:757–62.CrossRef Rickes D, Nickel I, Kropf S, Kleinstein J. Increased pregnancy rates after ultralong postoperative therapy with gonadotropin-releasing hormone analogs in patients with endometriosis. Fertil Steril. 2002;78:757–62.CrossRef
14.
go back to reference Surrey ES, Silverberg KM, Surrey MW, Schoolcraft WB. Effect of prolonged gonadotropin-releasing hormone agonist therapy on the outcome of in vitro fertilization-embryo transfer in patients with endometriosis. Fertil Steril. 2002;78:699–704.CrossRef Surrey ES, Silverberg KM, Surrey MW, Schoolcraft WB. Effect of prolonged gonadotropin-releasing hormone agonist therapy on the outcome of in vitro fertilization-embryo transfer in patients with endometriosis. Fertil Steril. 2002;78:699–704.CrossRef
15.
go back to reference Jiang HL. Research on different GnRH-down-regulation protocols for in vitro fertilization and embryo transfer in infertile women with endometriosis. Mod Med Health Res. 2018;2:1–3.CrossRef Jiang HL. Research on different GnRH-down-regulation protocols for in vitro fertilization and embryo transfer in infertile women with endometriosis. Mod Med Health Res. 2018;2:1–3.CrossRef
16.
go back to reference Dai L, Chen LZ. Different GnRH-a down-regulation protocols for in vitro fertilization-embryo transfer in infertility patients with endometriosis. Chin J Clin Lab Sci (Electronic Edition). 2017;6:212–3. Dai L, Chen LZ. Different GnRH-a down-regulation protocols for in vitro fertilization-embryo transfer in infertility patients with endometriosis. Chin J Clin Lab Sci (Electronic Edition). 2017;6:212–3.
17.
go back to reference Lin WQ, Lin JJ, Ye BL, Zhao JZ, Zhou Y, Hung XF. Effect of gonadotropin-releasing hormone agonist on the outcomes of in vitro fertilization-embryo transfer in patients with severe endometriosis. Chin J Obstet Gynecol. 2004;39:51–2. Lin WQ, Lin JJ, Ye BL, Zhao JZ, Zhou Y, Hung XF. Effect of gonadotropin-releasing hormone agonist on the outcomes of in vitro fertilization-embryo transfer in patients with severe endometriosis. Chin J Obstet Gynecol. 2004;39:51–2.
18.
go back to reference Sõritsa D, Saare M, Podar TL, Peters M, Sõritsa A, Matt K, et al. Pregnancy rate in endometriosis patients according to the severity of the disease after using a combined approach of laparoscopy, GnRH agonist treatment and in vitro fertilization. Gynecol Obstet Investig. 2015;79:34–9.CrossRef Sõritsa D, Saare M, Podar TL, Peters M, Sõritsa A, Matt K, et al. Pregnancy rate in endometriosis patients according to the severity of the disease after using a combined approach of laparoscopy, GnRH agonist treatment and in vitro fertilization. Gynecol Obstet Investig. 2015;79:34–9.CrossRef
19.
go back to reference Tamura H, Takasaki A, Nakamura Y, Numa F, Sugino N. A pilot study to search possible mechanisms of ultralong gonadotropin-releasing hormone agonist therapy in IVF-ET patients with endometriosis. J Ovarian Res. 2014;7:100.CrossRef Tamura H, Takasaki A, Nakamura Y, Numa F, Sugino N. A pilot study to search possible mechanisms of ultralong gonadotropin-releasing hormone agonist therapy in IVF-ET patients with endometriosis. J Ovarian Res. 2014;7:100.CrossRef
20.
go back to reference Ma C, Qiao J, Liu P, Chen G. Ovarian suppression treatment prior to in-vitro fertilization and embryo transfer in Chinese women with stage III or IV endometriosis. Int J Gynaecol Obstet. 2008;100:167–70.CrossRef Ma C, Qiao J, Liu P, Chen G. Ovarian suppression treatment prior to in-vitro fertilization and embryo transfer in Chinese women with stage III or IV endometriosis. Int J Gynaecol Obstet. 2008;100:167–70.CrossRef
21.
go back to reference Nakamura K, Oosawa M, Kondou I, Inagaki S, Shibata H, Narita O, et al. Menotropin stimulation after prolonged gonadotropin releasing hormone agonist pretreatment for in vitro fertilization in patients with endometriosis. J Assist Reprod Genet. 1992;9:13–117.CrossRef Nakamura K, Oosawa M, Kondou I, Inagaki S, Shibata H, Narita O, et al. Menotropin stimulation after prolonged gonadotropin releasing hormone agonist pretreatment for in vitro fertilization in patients with endometriosis. J Assist Reprod Genet. 1992;9:13–117.CrossRef
22.
go back to reference Wang F, Ke X, Li M. Effect of different dosage forms of Gonadotrophin-re leasing hormone agonist on in-vitro fertilization-embryo transfer in patients with mild endometriosis. J Pract Obstet Gynecol. 2017;33:869–72. Wang F, Ke X, Li M. Effect of different dosage forms of Gonadotrophin-re leasing hormone agonist on in-vitro fertilization-embryo transfer in patients with mild endometriosis. J Pract Obstet Gynecol. 2017;33:869–72.
23.
go back to reference Du H, Zhang WJ, Zhu M, Shi MF, Liu M, Liu XM, et al. Gonadotropin hormone agonist super-long protocol elevates pregnancy rate of assisted reproductive technique in patients with moderate-to-severe endometriosis. Acad J Second Mil Med Univ. 2017;38:852–6. Du H, Zhang WJ, Zhu M, Shi MF, Liu M, Liu XM, et al. Gonadotropin hormone agonist super-long protocol elevates pregnancy rate of assisted reproductive technique in patients with moderate-to-severe endometriosis. Acad J Second Mil Med Univ. 2017;38:852–6.
24.
go back to reference Jiang YH, Kong W, Liu Y, Wen J. The effect of three down-regulation protocols on pregnancy outcomes in patients with endometriosis. Prog Obstet Gynecol. 2016;25:535–7. Jiang YH, Kong W, Liu Y, Wen J. The effect of three down-regulation protocols on pregnancy outcomes in patients with endometriosis. Prog Obstet Gynecol. 2016;25:535–7.
25.
go back to reference Zhang QF, Chen GY, Liu Y, Song YF. Effect of different kinds of GnRH agonist down regulation protocols on clinical outcome of IVF in women with endometriosis. J Reprod Med. 2015;24:732–6. Zhang QF, Chen GY, Liu Y, Song YF. Effect of different kinds of GnRH agonist down regulation protocols on clinical outcome of IVF in women with endometriosis. J Reprod Med. 2015;24:732–6.
26.
go back to reference Song N, Sun LJ, Sun GQ, Dong XZ, Ma XJ, Hu JJ, et al. Effect of different down-regulation protocols on the outcome of in vitro fertilization-embryo transfer in patients with endometriosis. J Chongqing Med Univ. 2014;39:545–8. Song N, Sun LJ, Sun GQ, Dong XZ, Ma XJ, Hu JJ, et al. Effect of different down-regulation protocols on the outcome of in vitro fertilization-embryo transfer in patients with endometriosis. J Chongqing Med Univ. 2014;39:545–8.
27.
go back to reference Deng HL, Ye H, Pei L, Zeng PH, Huang GN. Study on outcome of IVF-ET conducted with different GnRH-a down-regulation protocols on infertility patients with endometriosis. Chongqing Med. 2012;41:333–335+338. Deng HL, Ye H, Pei L, Zeng PH, Huang GN. Study on outcome of IVF-ET conducted with different GnRH-a down-regulation protocols on infertility patients with endometriosis. Chongqing Med. 2012;41:333–335+338.
28.
go back to reference Sun YL, Cao YX, Cheng LH. Influencing factor analysis of different ovarian stimulation programs on the outcome of assisted reproductive Technology in Patients with endometriosis. J Pract Obstet Gynecol. 2012;28:49–53. Sun YL, Cao YX, Cheng LH. Influencing factor analysis of different ovarian stimulation programs on the outcome of assisted reproductive Technology in Patients with endometriosis. J Pract Obstet Gynecol. 2012;28:49–53.
29.
go back to reference Niu HY, Chen MY, Duo YL. Effect of different down-regulation protocols on the outcome of IVF-ET in patients with endometriosis. Chin J Birth Health Heredity. 2011;19:113+36. Niu HY, Chen MY, Duo YL. Effect of different down-regulation protocols on the outcome of IVF-ET in patients with endometriosis. Chin J Birth Health Heredity. 2011;19:113+36.
30.
go back to reference Cheng D, Yang J, Xu WM, Luo J, Li J. Comparison of the outcome of different GnRH agonist Down- regulation regimens during in vitro fertilization-embryo transfer on endometriosis. Chin J Reprod Contracep. 2010;30:170–3. Cheng D, Yang J, Xu WM, Luo J, Li J. Comparison of the outcome of different GnRH agonist Down- regulation regimens during in vitro fertilization-embryo transfer on endometriosis. Chin J Reprod Contracep. 2010;30:170–3.
31.
go back to reference Wang L, Huang P, Liu WX, Zhao CY, Yan FY. Effect of endometriosis with different Down-regulation protocol on pregnancy outcome of IVF-ET. Chin J Reprod Contracep. 2009;29:613–6. Wang L, Huang P, Liu WX, Zhao CY, Yan FY. Effect of endometriosis with different Down-regulation protocol on pregnancy outcome of IVF-ET. Chin J Reprod Contracep. 2009;29:613–6.
32.
go back to reference Becchetti A, Arcangeli A. Integrins and ion channels in cell migration: implications for neuronal development, wound healing and metastatic spread. Adv Exp Med Biol. 2010;674:107–23.CrossRef Becchetti A, Arcangeli A. Integrins and ion channels in cell migration: implications for neuronal development, wound healing and metastatic spread. Adv Exp Med Biol. 2010;674:107–23.CrossRef
33.
go back to reference Oehninger S, Brzyski RG, Muasher SJ, Acosta AA, Jones GS. In-vitro fertilization and embryo transfer in patients with endometriosis: impact of a gonadotrophin releasing hormone agonist. Hum Reprod. 1989;4:541–4.CrossRef Oehninger S, Brzyski RG, Muasher SJ, Acosta AA, Jones GS. In-vitro fertilization and embryo transfer in patients with endometriosis: impact of a gonadotrophin releasing hormone agonist. Hum Reprod. 1989;4:541–4.CrossRef
34.
go back to reference Bilotas M, Barañao RI, Buquet R, Sueldo C, Tesone M, Meresman G. Effect of GnRH analogues on apoptosis and expression of Bcl-2, Bax, Fas and FasL proteins in endometrial epithelial cell cultures from patients with endometriosis and controls. Hum Reprod. 2007;22:644–53.CrossRef Bilotas M, Barañao RI, Buquet R, Sueldo C, Tesone M, Meresman G. Effect of GnRH analogues on apoptosis and expression of Bcl-2, Bax, Fas and FasL proteins in endometrial epithelial cell cultures from patients with endometriosis and controls. Hum Reprod. 2007;22:644–53.CrossRef
35.
go back to reference Lessey BA. Medical management of endometriosis and infertility. Fertil Steril. 2000;73:1089–96.CrossRef Lessey BA. Medical management of endometriosis and infertility. Fertil Steril. 2000;73:1089–96.CrossRef
36.
go back to reference Liu XY, Yang YJ, Tang CL. Effect of starting time of ovarian stimulation on outcomes of in vitro fertilization in women with endometriosis. Chin J Reprod Contracep. 2017;37:633–7. Liu XY, Yang YJ, Tang CL. Effect of starting time of ovarian stimulation on outcomes of in vitro fertilization in women with endometriosis. Chin J Reprod Contracep. 2017;37:633–7.
37.
go back to reference Georgiou EX, Melo P, Baker PE, Sallam HN, Arici A, Garcia-Velasco JA, et al. Long-term GnRH agonist therapy before in vitro fertilisation (IVF) for improving fertility outcomes in women with endometriosis. Cochrane Database Syst Rev. 2019;11:CD013240. Georgiou EX, Melo P, Baker PE, Sallam HN, Arici A, Garcia-Velasco JA, et al. Long-term GnRH agonist therapy before in vitro fertilisation (IVF) for improving fertility outcomes in women with endometriosis. Cochrane Database Syst Rev. 2019;11:CD013240.
38.
go back to reference Li XX, Zhang A, Quan S. Effect of GnRH-a ultra-long protocol on clinical outcomes of IVF/ICSI-ET in patients with different stages of endometriosis: a meta-analysis. J Int Reprod Health Fam Plan. 2019;38:35–42. Li XX, Zhang A, Quan S. Effect of GnRH-a ultra-long protocol on clinical outcomes of IVF/ICSI-ET in patients with different stages of endometriosis: a meta-analysis. J Int Reprod Health Fam Plan. 2019;38:35–42.
39.
go back to reference Lin XN, Wei ML, Tong XM, Xu WH, Zhou F, Huang QX, et al. Outcome of in vitro fertilization in endometriosis-associated infertility: a 5-year database cohort study. Chin Med J. 2012;125:2688–93.PubMed Lin XN, Wei ML, Tong XM, Xu WH, Zhou F, Huang QX, et al. Outcome of in vitro fertilization in endometriosis-associated infertility: a 5-year database cohort study. Chin Med J. 2012;125:2688–93.PubMed
Metadata
Title
The effectiveness of different down-regulating protocols on in vitro fertilization-embryo transfer in endometriosis: a meta-analysis
Authors
Xue Cao
Hong-yang Chang
Jun-yan Xu
Yi Zheng
Yun-gai Xiang
Bing Xiao
Xu-jing Geng
Li-li Ni
Xi-ying Chu
Shi-bo Tao
Yan He
Gen-hong Mao
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2020
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/s12958-020-00571-6

Other articles of this Issue 1/2020

Reproductive Biology and Endocrinology 1/2020 Go to the issue