Use of GnRH Analogues in the Reduction of Submucous Fibroid for Surgical Hysteroscopy: A Systematic Review and Meta-Analysis

Corrêa, Thayane Delazari; Caetano, Isabela Maciel; Saraiva, Pedro Henrique Tannure; Noviello, Maurício Bechara

doi:10.1055/s-0040-1712446

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Revista Brasileira de Ginecologia e Obstetrícia

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Sumário

Review Article • Rev Bras Ginecol Obstet. 42 (10) • Oct 2020 • https://doi.org/10.1055/s-0040-1712446 copy

Use of GnRH Analogues in the Reduction of Submucous Fibroid for Surgical Hysteroscopy: A Systematic Review and Meta-Analysis

Uso de análogo de GnRH na redução de mioma submucoso na histeroscopia cirúrgica: Revisão sistemática e meta-análise

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objective

Gonadotropin-releasing hormone analogues (GnRH-a) have been used preoperatively before hysteroscopic myomectomy to decrease the size and vascularization of the myomas, but evidence to support this practice is weak. Our objective was to analyze the use of GnRH-a in the reduction of submucous fibroid as a facilitator for surgical hysteroscopy from published clinical trials.

Data sources

Studies from electronic databases (Pubmed, Scielo, EMBASE, Scopus, PROSPERO), published between 1980 and December 2018. The keywords used were fibroid, GnRH analogue, submucous, histeroscopy, histeroscopic resection and their correspondents in Portuguese.

Study selection

The inclusion criteria were controlled trials that evaluated the GnRH-a treatment before hysteroscopic resection of submucous myomas. Four clinical trials were included in the meta-analysis.

Data collection

Two review authors extracted the data without modification of the original data, using the agreed form. We resolved discrepancies through discussion or, if required, we consulted a third person.

Data synthesis

The present meta-analysis included a total of 213 women and showed no statistically significant differences in the use of GnRH-a compared with the control group for complete resection of submucous myoma (relative risk [RR]: 0.94; 95%; confidence interval [CI]: 0.80-1.11); operative time (mean difference [MD]: - 3.81; 95%;CI : - 3.81-2.13); fluid absorption (MD: - 65.90; 95%;CI: - 9.75-2.13); or complications (RR 0.92; 95%;CI: 0.18-4.82).

Conclusion

The present review did not support the routine preoperative use of GnRH-a prior to hysteroscopic myomectomy. However, it is not possible to determine its inferiority when compared with the other methods due to the heterogeneity of existing studies and the small sample size.

Keywords
GnRH analogue; fibroid; hysteroscopy; myoma resection; submucous fibroid

	Muzii et al. (2010)⁸8 Muzii L, Boni T, Bellati F, Marana R, Ruggiero A, Zullo MA, et al. GnRH analogue treatment before hysteroscopic resection of submucous myomas: a prospective, randomized, multicenter study. Fertil Steril. 2010;94(04):1496–1499. Doi: 10.1016/j.fertnstert.2009.05.070 https://doi.org/10.1016/j.fertnstert.200...	Mavrelos et al. (2010)⁷7 Mavrelos D, Ben-Nagi J, Davies A, Lee C, Salim R, Jurkovic D. The value of pre-operative treatment with GnRHanalogues inwomen with submucous fibroids: a double-blind, placebo-controlled randomized trial. Hum Reprod. 2010;25(09):2264–2269. Doi: 10.1093/humrep/deq188 https://doi.org/10.1093/humrep/deq188...	Bizzarri et al. (2015)¹²12 Bizzarri N, Ghirardi V, Remorgida V, Venturini PL, Ferrero S. Three-month treatment with triptorelin, letrozole and ulipristal acetate before hysteroscopic resection of uterine myomas: prospective comparative pilot study. Eur J Obstet Gynecol Reprod Biol. 2015;192:22–26. Doi: 10.1016/j.ejogrb.2015.06.018 https://doi.org/10.1016/j.ejogrb.2015.06...	Favilli et al. (2017)¹⁴14 Favilli A, Mazzon I, Grasso M, Horvath S, Bini V, Di Renzo GC, Gerli S, et al. Intraoperative effect of preoperative gonadotropin-releasing hormone analogue administration in women undergoing cold loop hysteroscopic myomectomy: a randomized controlled trial. J Minim Invasive Gynecol. 2018;25(04):706–714. Doi: 10.1016/j.jmig.2017.11.011 https://doi.org/10.1016/j.jmig.2017.11.0...
Study location	Rome	London	Genova	Rome
Number of centers	3	1	1	1
Sample size	39	47	46	99
Lost to follow-up	0	7	3	15
Intervention	Preoperative GnRH analogues for 8 weeks Control: no preoperative GnRH	Preoperative GnRH analogues for 12 weeks Control: placebo (5ml of 1%; lignocaine)	Preoperative GnRH analogues for 12 weeks Control: no preoperative GnRH	Preoperative GnRH analogues for 12 weeks Control: no preoperative GnRH
Medication and route of administration	Triptorelin 3.75 mg intramuscular injection	Goserelin 3.6 mg Subcutaneous injection	Triptorelin 3.75 mg intramuscular injection	Triptorelin 375 mg intramuscular injection
Outcomes	Duration of the procedure in minutes, fluid absorption, difficulty of the operation, surgeon satisfaction with the procedure, intra- and postoperative complications, postoperative pain, patient satisfaction	Completeness of fibroid resection. Duration of the TCRM, fluid deficit recorded at TCRM, resolution of symptoms postoperatively, number of subsequent fibroid related operations.	Assess the incidence of incomplete resection in the study groups. Surgical and hysteroscopy time, volume of absorbed fluid, complications, operative difficulty, postoperative patient pain and satisfaction, changes in myoma volume caused by hormonal therapies.	Assess if cold loop hysteroscopic myomectomy in a single surgical procedure was facilitated by preoperative GnRH analogue administration. Distension liquid absorption, duration of the procedure
Inclusion criteria	Submucous myomas diagnosed by transvaginal ultrasonography, with a diameter between 10 and 35 mm, and a grade G0 or G1 according to the European Society for Gynecological Endoscopy classification	History of heavy and/or irregular menstrual periods and diagnosis of a Type I or Type II submucous fibroid on ultrasound	Premenopausal women with FIGO type 0, 1 or 2 myomas with diameter between 20 and 35 mm.	Women with a diagnosis of a single submucous myoma without any other intracavitary pathology and a grade G0, G1 or G2 according to the European Society for Gynecological Endoscopy classification
Exclusion criteria	Present or past history of cancer, preoperative clinical suspicion of associated multiple or large polyps (sonographic estimate being > 20 mm in largest diameter), planned associated nonhysteroscopic surgical procedures, or > 2 myomas requiring hysteroscopic resection.	Not reported	Associated polyps or other pathologies requiring hysteroscopic treatment (such as uterine septa), previous incomplete myoma resection, associated nonhysteroscopic surgical procedures, > 2 myomas requiring hysteroscopic resection.	Patients with multiple myomas, endometrial polyps, scheduled combined surgical procedures (hysteroscopy with laparoscopy), a present or past history of cancer, ongoing pregnancy, and a postmenopausal status.

	Muzii et al. (2010)⁸8 Muzii L, Boni T, Bellati F, Marana R, Ruggiero A, Zullo MA, et al. GnRH analogue treatment before hysteroscopic resection of submucous myomas: a prospective, randomized, multicenter study. Fertil Steril. 2010;94(04):1496–1499. Doi: 10.1016/j.fertnstert.2009.05.070 https://doi.org/10.1016/j.fertnstert.200...	Mavrelo et al. (2010)⁷7 Mavrelos D, Ben-Nagi J, Davies A, Lee C, Salim R, Jurkovic D. The value of pre-operative treatment with GnRHanalogues inwomen with submucous fibroids: a double-blind, placebo-controlled randomized trial. Hum Reprod. 2010;25(09):2264–2269. Doi: 10.1093/humrep/deq188 https://doi.org/10.1093/humrep/deq188...	Bizzarri et al. (2015)¹²12 Bizzarri N, Ghirardi V, Remorgida V, Venturini PL, Ferrero S. Three-month treatment with triptorelin, letrozole and ulipristal acetate before hysteroscopic resection of uterine myomas: prospective comparative pilot study. Eur J Obstet Gynecol Reprod Biol. 2015;192:22–26. Doi: 10.1016/j.ejogrb.2015.06.018 https://doi.org/10.1016/j.ejogrb.2015.06...	Favilli et al. (2017)¹⁴14 Favilli A, Mazzon I, Grasso M, Horvath S, Bini V, Di Renzo GC, Gerli S, et al. Intraoperative effect of preoperative gonadotropin-releasing hormone analogue administration in women undergoing cold loop hysteroscopic myomectomy: a randomized controlled trial. J Minim Invasive Gynecol. 2018;25(04):706–714. Doi: 10.1016/j.jmig.2017.11.011 https://doi.org/10.1016/j.jmig.2017.11.0...	Total	I²	RR or MD (95%; CI)
Sample size	39 (20 vs 19)	47 (24 vs 23)	43 (20 vs 23)	84 (42 vs 42)	213	-	-
Complete resection of the fibroid	20/20 (100%;) vs 19/19 (100%;)	14/24 (58.3%;) vs 16/23 (69.5%;)	20/20 (100%;) vs 22/23 (95.6%;)	31/42 (73.8%;) vs 39/42 (92.9%;)	85/106 (80.2%;) vs 96/107 (89.7%;)	74%;	0.90 (0.81 to 1.00)
Operating time	M 15.9 (SD 3.1) vs M 21.3 (SD 4)	M 30.1 (SD 11.7) vs M 33.8 (SD 22.7)	M 26.4 (SD 6.4) vs M 36.7 (SD 8.4)	M 26.62 (SD 15.308) vs M 20.71 (SD 15.052)	-	82%;	−3.81 [−9.75 to 2.13]
Complications^* * Complications (excessive intraoperative bleeding, uterine perforation, bowel injury).	2/20 (10%;) vs 1/19 (5.2%;)	1/21 (4.8%;) vs 2/19 (10.5%;)^ 1 woman in the placebo group had abdominal myomectomy and 3 women were not operated. In the GnRH analogue group, 1 woman had abdominal myomectomy, 1 had allergic reaction and 1 was not operated.	0/20 (0%;) vs 0/23 (0%;)	0/42 (0%;) vs 0/42 (0%;)	3/103 (2.9%;) vs 3/103 (2.9%;)	0%;	0.92 [0.18 to 4.82]
Fluid absorption	M 378 (SD 137) vs M 566 (SD 199)	M 662.5 (SD 668.3) vs M 568.75 (SD 785.8)	M 340 (SD 112) vs M 457 (SD 139)	M 135.85 (SD 217.2) vs M 62.44 (SD 130.66)	-	85%;	−65.90 [−207.79 to 75.99]

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[1] Address for correspondence Isabela Maciel Caetano, Rua Juramento, 1464, Belo Horizonte, MG, 30285-408, Brazil (e-mail: isabelamcaetano@gmail.com).