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

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.

Resumo Objetivo Análogos de hormônio liberador de gonadotrofina (GnRH-a) têm sido usados no pré-operatório de miomectomia histeroscópica para reduzir o tamanho e vascularização dos miomas, mas a evidência que suporta essa prática é fraca. Nosso objetivo foi analisar o uso de GnRH-a na redução do mioma submucoso como um facilitador de histeroscopia cirúrgica em ensaios clínicos publicados. Fonte de dados Estudos de bases de dados eletrônicas (Pubmed, Scielo, EMBASE, Scopus, PROSPERO), publicados entre 1980 e dezembro de 2018. As palavras-chave usadas foram fibroid, GnRH analogue, submucous, histeroscopy, histeroscopic resection e seus correspondentes em português. Seleção dos estudos Os critérios de inclusão foram ensaios clínicos controlados que avaliaram o tratamento com GnRH-a antes da ressecção histeroscópica de miomas submucosos. Quatro ensaios clínicos foram incluídos na meta-análise Coleta de dados Dois autores revisores extraíram os dados, sem modificarem os dados originais, usando a forma acordada. Nós resolvemos as discrepâncias através de discussão ou, se necessário, consultando um terceiro autor. Síntese dos dados A meta-análise incluiu um total de 213 mulheres e não demonstrou diferença estatisticamente significativa no uso de GnRH-a comparado com o grupo controle para ressecção completa de mioma submucoso (risco relativo [RR]: 0.94. índice de confiança [IC] 95%;: 0.80-1.11); tempo cirúrgico (diferença de média [MD]: - 3.81; IC95%;: -3.81-2.13); absorção de fluidos (MD: - 65.90; IC95%;: - 9.75-2.13); ou complicações (RR 0.92; IC95%;: 0.18-4.82). Conclusão A presente revisão sistemática não suporta o uso pré-operatório rotineiro de GnRH-a antes de miomectomia histeroscópica. No entanto, não é possível determinar sua inferioridade quando comparado aos outros métodos devido à heterogeneidade dos estudos existentes e ao pequeno tamanho da amostra.

The missing gonadotropin-releasing hormone agonist trigger leading to missing oocytes

Authors present a case of Genuine EFS in a young woman where no oocytes were retrieved in the first stimulation cycle after single ovulation trigger. However, a repeat stimulation performed with double ovulation trigger yielded enough oocytes.

Evaluation of central precocious puberty treatment with GnRH analogue at the Triangulo Mineiro Federal University (UFTM)

Objective To report our experience of treating central precocious puberty (CPP) with a GnRH analogue with respect to the final heights (FH) attained in patients who completed treatment. Subjects and methods Among 105 records of children diagnosed with precocious puberty, 62 cases (54 girls and 8 boys), who were treated with leuprolide acetate/3.75 mg/monthly, were selected, and divided into 4 groups: group 1 (G1), 25 girls who attained FH; group 2 (G2), 18 girls who completed treatment but did not reach FH; group 3 (G3), 11 girls still under treatment; and group 4 (G4), 8 boys, 5 of which attained FH. Treatment was concluded at a bone age of 12 years, and follow-up continued until FH was achieved. Results In both G1 and G2 groups, height standard deviation score (SDS), weight-SDS and percentile of body mass index (PBMI) did not show intra/intergroup differences at the beginning and at interruption of treatment, but when added, G1+G2, height-SDS and weight-SDS differed significantly (p = 0.002 and 0.0001, respectively). In G1, 19 of 25 cases attained TH, and average height gain was 16.7 cm (7.7- 27.1); there was significant difference between FH and prediction of FH at the start (PFH at start) (p = 0.0001), as well as between PFH at interruption vs TH and vs FH (p = 0.007) with FH higher than TH (p = 0.004). Significant correlation was identified between FH and height gain after treatment. Conclusion As shown by some studies, GnRH analogue treatment was effective in children with CPP reaching FH near the genetic target.

Uso de agonista de GnRH para inducir ovulación en ciclos de hiperestimulación ovárica controlada: experiencia de Clínica Monteblanco, Santiago, Chile / Use of GnRH agonist to induce ovulation cycles controlled ovarian hyperstimulation: experience of Monteblanco Clinic, Santiago, Chile

Objetivo: Presentar la experiencia de la Unidad de Medicina Reproductiva de Clínica Monteblanco con el uso de análogos GnRh para la inducción final de la maduración ovocitaria. Método: Se registraron los casos de IVF/ICSI durante el año 2012 en los que se indujo la maduración final ovocitaria con análogos GnRh (Lupron®). Todos los ciclos fueron estimulados con FSHr (Puregon®) y gonadotrofina urinaria altamente purificada (Menopur®), para la prevención del alza prematura de LH, el día 5° de estimulación se agregó diariamente antagonista de GnRh. La maduración ovocitaria final se realizó con 1,25 mg de acetato de leuprolide (Lupron®), posteriormente se realizó aspiración folicular bajo guía ecográfica. Todos los embriones obtenidos fueron vitrificados y transferidos en ciclos posteriores. Resultados: Entre enero y diciembre del año 2012 se registraron 110 pacientes cuya inducción de maduración final ovocitaria se realizó con acetato de leuprolide. El promedio de ovocitos recuperados fue de 21, la proporción de ovocitos maduros fue de 72 por ciento y la frecuencia de fecundación fue de 64 por ciento. No hubo ningún caso de síndrome de hiperestimulación ovárico severo. Conclusiones: En los casos presentados de inducción de la maduración ovocitaria final con acetato de leuprolida, los resultados obtenidos son óptimos en términos de número de ovocitos en metafase II recuperados y en frecuencia de fecundación, mostrando ser una alternativa eficiente en la prevención del síndrome de hiperestimulación ovárico severo, sin alterar el pronóstico de las pacientes.

Objective: To present the experience of the Reproductive Medicine Unit of Clinica Monteblanco inducing oocyte final maturation by GnRh analogue administration. Methods: We analysed all IVF/ICSI cases performed in 2012, in which final oocyte maturation was induced by administration of GnRH analogue (Lupron®). Controlled ovarian hyperstimulation was achieved bydaily rFSH (Puregon®) and highly purified urinary gonadotropin (Menopur®) administration. In order to prevent premature LH rise, on the 5th day of stimulation daily GnRH antagonist (Orgalutran®) was added. Final oocyte maturation was induced by the administration of 1.25 mg leuprolide acetate (Lupron®). Follicular aspiration was subsequently performed under ultrasound guidance. All embryos were vitrified and transferred in a subsequent cycle. Results: We registered 110 patients. The mean number of recovered oocytes was 21; the proportion of mature oocytes was 72 percent, and the fecundation rate reached was 64 percent. No case of severe ovarian hyperstimulation syndrome (OHSS) was recorded. Conclusions: In this cohort, the use of leuprolide acetate for induce final oocyte maturation demonstrated to be an efficient alternative to induce oocyte final maturation, while preventing OHSS.

Gestação sem intercorrências com mioma uterino volumoso tratado previamente com agonista do hormônio liberador das gonadotrofinas / Uneventful pregnancy with large uterine leiomyomata previously treated with gonadotrophin realease hormone agonist

Introdução. Os miomas uterinos, principalmente os submucosos, estão associados a infertilidade e intercorrências durante a gestação. A miomectomia é um procedimento comumente utilizado em mulheres com miomas, que desejam engravidar. O uso clínico dos análogos de hormônio liberador das gonadotrofinas antes da cirurgia tem por objetivo reduzir as dimensões do tumor e o sangramento durante o procedimento. Relato do caso. Mulher, 26 anos de idade, G1P1C0A0, com infertilidade secundária, hiperpolimenorréia, dor em hipogástrio e volume do útero aumentado por miomas, principalmente à custa de volumoso mioma submucoso e intramural que comprometia boa parte da cavidade do útero e obstruía as trompas. A paciente manifestou desejo de gestação. Optou-se então por miomectomia, mas durante o ato cirúrgico o procedimento não foi realizado em conseqüência da grande dimensão dos tumores. Apesar de possibilidade remota de gestação, foi introduzido o tratamento com análogo do hormônio liberador das gonadotrofinas para, em seguida, se tentar novamente a miomectomia. Entretanto, ocorreu gestação espontânea logo depois da conclusão do tratamento. A gestação cursou sem más intercorrências maternas ou fetais, e o parto ocorreu com 39 semanas de gestação. Conclusão. O tratamento com o análogo permitiu redução no volume do útero, retorno da fertilidade e gestação espontânea com evolução satisfatória. Portanto, em situações como essa, em que a cirurgia radical parece ser a única escolha, o tratamento com o análogo do hormônio liberador das gonadotrofinas pode ser a opção.

Introduction. Uterine leiomyomata, mainly the submucous, are associated to infertility and events during pregnancy. Myomectomy is a common procedure in women who want to get pregnant. Clinical use of the gonadotrophin release hormone analogues previously to surgery has an objective of reducing tumor size as well as the intraoperative bleeding.Case report. Woman, 26 years old, one previous normal pregnancy, with secondary infertility, hyperpolimenorrhea, hypogastric pain and enlarged uterus with myomas, mainly a big submucous and intramural myoma affecting most of the uterus cavity and obstructing the fallopian tubes. The patient declared her wish to get pregnant again. The option was, then, to myomectomy, but such procedure was not possible due to the intraoperative findings of many highly enlarged tumors. Even with small chances of pregnancy, treatment with a gonadotrophin release hormone analogue was initiated, so that myomectomy could be tried again latter. Nevertheless, spontaneous pregnancy occurred right after the end of the hormonal treatment. The pregnancy presented no abnormal maternal or child events, and delivery came up at the 39th week. Conclusion. The treatment with gonadotrophin release hormone analogue allowed reduction of tumor size, fertility recovery and spontaneous pregnancy with satisfactory evolution. In cases when radical surgery may appear as the only choice, the treatment with gonadotrophin release hormone analogues may be an option.

Evaluation of the effect of a 3rd GnRH injection administered six days after the 2nd GnRH injection of Ovsynch on the reproductive performance of Japanese black cows

This study was designed to evaluate the reproductive performance of Japanese black cows following the 3rd injection of gonadotropin releasing hormone (GnRH) analogue administered concurrently with Ovsynch-based treatment on day 6 (day 1 = the day of ovulation). In Experiment 1, 12 cows were allocated into three groups: a control group that was subjected to Ovsynch treatment and then injected with a placebo on day 6; group 1 (Ovsynch + GnRH), which was subjected to Ovsynch treatment and was injected with GnRH analogue on day 6, and group 2 (Ovsynch + controlled internal drug-release (CIDR) + GnRH), which received Ovsynch-CIDR treatment and was injected with GnRH analogue on day 6. Blood collection and ultrasonographic observation of the ovaries were conducted daily. Both treatments induced the formation of an accessory corpus luteum and significantly increased the cross-sectional area of the luteal tissue when compared to the control. However, plasma progesterone (P(4)) was significantly higher in the treatment groups than in the control group on days 11, 12, 17 and 18 in the group 1 and from day 10 to 21 in the group 2. In Experiment 2, 41 cows were assigned to the same three groups described above and then artificially inseminated on day 1. The pregnancy rates on day 45 did not differ among groups. In conclusion, administration of GnRH analogue on day 6 following Ovsynch-based treatment did not improve the reproductive performance of Japanese black cows, even though the P(4) concentration was higher in groups that received the GnRH.

Benign Metastasizing Pulmonary Leiomyoma with Hemoptysis / 결핵및호흡기질환

A benign metastasizing pulmonary leiomyoma(BMPL) is a rare disease that is usually detected years after a hysterectomy or myomectomy. Despite the benign pathological appearance, these tumors can metastasize and become clinically malignant. Recently, we experienced case of BMPL with hemoptysis. A 43-year-old woman, who had undergone a hysterectomy due to uterine leiomyoma 8 years ago, visited our department complaining of intermittent hemoptysis. A chest CT showed bilateral multiple nodular lesions. Video-associated thoracoscopy was performed. The resected small nodular lesion revealed the proliferation of spindle cells without mitosis or nuclear atypism. The lesions tested positive to the smooth muscle marker (actin) by immunohistochemical staining. Therefore, the multiple nodules were considered as benign metastasizing pulmonary leiomyoma from a uterine leiomyoma. GnRH analogue therapy was initiated. A chest CT showed that the size and number of pulmonary lesions did not change after 3 months, and the patient was symptom free.

Benign Metastasizing Pulmonary Leiomyoma with Hemoptysis / 결핵및호흡기질환

A benign metastasizing pulmonary leiomyoma(BMPL) is a rare disease that is usually detected years after a hysterectomy or myomectomy. Despite the benign pathological appearance, these tumors can metastasize and become clinically malignant. Recently, we experienced case of BMPL with hemoptysis. A 43-year-old woman, who had undergone a hysterectomy due to uterine leiomyoma 8 years ago, visited our department complaining of intermittent hemoptysis. A chest CT showed bilateral multiple nodular lesions. Video-associated thoracoscopy was performed. The resected small nodular lesion revealed the proliferation of spindle cells without mitosis or nuclear atypism. The lesions tested positive to the smooth muscle marker (actin) by immunohistochemical staining. Therefore, the multiple nodules were considered as benign metastasizing pulmonary leiomyoma from a uterine leiomyoma. GnRH analogue therapy was initiated. A chest CT showed that the size and number of pulmonary lesions did not change after 3 months, and the patient was symptom free.

The Efficacy of GnRH Analogue on Pain Treatment after Laparoscopic Cystectomy of Endometrioma / 대한산부인과학회잡지

OBJECTIVE: To estimate the efficacy of GnRH analogue on pain treatment after laparoscopic cystectomy of endometrioma. METHODS: During a 12-month period from March 2000 to February 2001 in Chonnam National University Hospital, Sixty five patients with ovarian cysts were diagnosed as endometrioma by clinical examination, ultrasonogram and serum CA 125 level. The laparoscopic cystectomy was performed and 65 consecutive women were biopsy-proved endometrioma. They were treated with GnRH analogue intramuscular injection every 4 weeks over a period of 6 months after operation. 10-point linear visual analogue scales for pelvic pain were completed pre- and post- treatment at 6 months and 12 months. RESULTS: A total of 96 endometriotic cysts (21 cysts were bilateral) were found in the 65 patients. 65 patients had a pain associated with endometriosis. 40 patients of them complained of a dysmenorrhea, 14 patients for dyspareunia, and 24 patients for non-menstrual pain. At preoperative, the mean pain score was 5.85 +/- 2.28 (mean +/- SD) for dysmenorrhea; for dyspareunia, 5.29 +/- 1.49; for non-menstrual pain, 5.33 +/- 2.10. At 6 months and 12 months, the mean pain score was 3.20 +/- 1.68 and 2.42 +/- 1.9 for dysmenorrhea; for dyspareunia, 3.71 +/- 1.73 and 3.57 +/- 1.79; for non-menstrual pain, 3.63 +/- 2.26 and 3.29 +/- 1.97. The mean pain score for pelvic pain decreased after combined treatment. CONCLUSION: The laparoscopic cystectomy of ovarian endometrioma is an effective treatment for pelvic pain and the combination therapy with GnRH analogue is more useful to relieving pelvic pain after operation.

Inhibitory Effect of Keishi-bukuryo-gan on CGRP-induced Elevation of Skin Temperature in GnRH Analogue-treated Male Rats / 日本東洋医学雑誌

The gonadotropin-releasing hormone (GnRH) analogue (Leuplin/^®1.0mg/kg, s. c.) induced not only a decrease in the serum concentration of testosterone but also potentiation of calcitonin gene-related peptide (CGRP: 10μg/kg, i. v.)-induced elevation of skin temperature in male rats. Keishi-bukuryo-gan (1, 000mg/kg, p. o.) and 17β-estradiol (0.010mg/kg, s. c.) significantly inhibited the elevation of skin temperature as well as teststerone (1.0mg/kg, s. c.) replacement. However, Keishi-bukuryo-gan and 17β-estradiol did not affect the low concentration of serum testosterone, although the hormone replacement of testosterone restored the plasma level. These results suggest that Keishi-bukuryo-gan, which does not have testosterone activity to serum, may be useful for the treatment of hot flushes due to testosterone deficiency after GnRH therapy in men with prostatic carcinoma, as well as 17β-estradiol.

A Case of Catamenial Hemoptysis Treated successfully with Gonadotropin-releasing Hormone (GnRH) Analogue / 결핵

Catamenial hemoptysis is syndrome characterized by bleeding from the bronchial trees and lungs that occurs synchronously with the female menstrual cycle. Etiologic mechanism of pulmonary endometriosis is still controversial, and the diagnosis is usually made on the basis of the clinical history and exclusion of other causes of recurrent hemoptysis. Serial computed tomograms of the chest during and in the interval between menstruations have been proved to be a useful confirmatory test. We experienced a 33-year-old female patient who had been previously diagnosed as pelvic endometriosis pathologically, experienced cyclic hemoptysis during menstruations. The diagnosis of pulmonary endometriosis was made based on her history and changes in the character of the lesions as documented on radiologic studies of the chest. She was treated successfully with GnRH analogue and there is no evidence of recurrence.

EFFECTION OF GnRH ANALOGUE ON INTRACELLULAR CALCIUM MOBILIZATION IN CULTURED RAT STOMACH SMOOTH MUSCLE CELLS / 解剖学报

Objedctive To study the mechanism of GnRH agalogus(Alarelin)on[ Ca2 + ]; mobilization in stomach smooth muscle cells (SSMc)of rats. Methods Cells were cutured and loaded with Fluo-3-AM. [Ca2 + ]; was measured by nuomeent intensity(FL) in each cell with confocal micoopy. Results (1 ) In Hanks solution. l0-7, l0-6, l0 - 5mol L- 1 Alarelin can elevate[ Ca2 + ], its peak - resting values reached 6. 00 ?0. 50 .9. 23 ?0. 62. l8. 97 ?2. 42 respectively, which indicate that the level of [Ca2+ ]; act in an deede- pendent and time - dependent. (2) thntredly. when Alarelin was 10 4mol?Ｌ－１, its peak - resting value only reached 6. 32 ?0 .67, conpared with Alarelin l0 5m.l L－1 which was sigificantly lower(P 0. 05 ). (5 )When pertreatment with Lacidipine in Hanks solution, the effect of Alarelin l0 5mol L-1.as partly inhibited(P