溴隐亭治疗多囊卵巢综合征不育的系统评价
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摘要
目的采用循证医学的方法评价溴隐亭治疗多囊卵巢综合征(polycystic ovary syndrome,PCOS)不育的有效性及安全性。方法计算机检索Pubmed、CochraneLibrary、Embase、中国知网数据库、重庆维普数据库、中国生物医学文献数据库及万方数据库,寻找国内外随机对照试验,检索时间均为建库至2017年8月,按照纳入与排除标准筛选、纳入文献,然后评价方法学质量,最后采用RevMan5.0软件进行meta分析。结果纳入6个随机对照试验,共469例患者,其中溴隐亭治疗组231例,对照组238例。Meta分析结果显示,溴隐亭治疗组与对照组相比较,在排卵率(合并效应量=0.20,P=0.84)、妊娠率(合并效应量=1.88,P=0.06)、卵泡发育(合并效应量=0.51,P=0.61)及流产率(合并效应量=0.98,P=0.33)方面,差异均无统计学意义;而在成熟卵泡数(合并效应量=3.62,P=0.000 3)及子宫内膜厚度(合并效应量=2.77,P=0.006)方面,2组比较差异均有统计学意义,溴隐亭治疗组成熟卵泡数及子宫内膜厚度均高于对照组。结论溴隐亭虽然可增加PCOS患者成熟卵泡个数及子宫内膜厚度,但不能改善卵泡发育,也不增加排卵率、妊娠率及流产率。鉴于本研究纳入的文献样本量较小,且存在一定的方法学质量问题,导致可能有较高的偏倚风险,因此结论尚待设计严谨的多中心、大样本研究加以论证。
OBJECTIVE To assess the effectiveness and safety of bromocriptine in women with infertility, caused by polycystic ovary syndrome. METHODS Pubmed database, the Cochrane Library, the Embase database, the CNKI database,the VIP database, the CBM database and the Wanfang database were searched to identify relevant randomized controlled trials(RCTs) from the day of database builded to August 2017. RCTs which met the inclusion criteria were selected, reviewed and analysised by Revman 5.0 software. RESULTS Six RCTs involving 469 patients were included in this study, 231 patients in the bromocriptine group and 238 patients in the control group. Meta-analysis results showed that the rates of ovulation(Z=0.20,P=0.84), pregnancy(Z=1.88, P=0.06), follicular development(Z=0.51, P=0.61) and abortion(Z=0.98, P=0.33) did not differ significantly among the groups. However, the mature follicle(Z=3.62, P=0.000 3) and the endometrial thickness(Z=2.77,P=0.006) were significantly greater in the bromocriptine group than those in control group. CONCLUSION It is found that no evidence suggesting that bromocriptine improves the rates of ovulation, pregnancy, follicular development and abortion, though it showed benefit in terms of mature follicle and endometrial thickness. Limitations included imprecision(small design trials) and poor reporting of study methods. Large, well-designed RCTs are necessary to further evaluate the role of bromocriptine in polycystic ovary syndrome.
OBJECTIVE To assess the effectiveness and safety of bromocriptine in women with infertility, caused by polycystic ovary syndrome. METHODS Pubmed database, the Cochrane Library, the Embase database, the CNKI database,the VIP database, the CBM database and the Wanfang database were searched to identify relevant randomized controlled trials(RCTs) from the day of database builded to August 2017. RCTs which met the inclusion criteria were selected, reviewed and analysised by Revman 5.0 software. RESULTS Six RCTs involving 469 patients were included in this study, 231 patients in the bromocriptine group and 238 patients in the control group. Meta-analysis results showed that the rates of ovulation(Z=0.20,P=0.84), pregnancy(Z=1.88, P=0.06), follicular development(Z=0.51, P=0.61) and abortion(Z=0.98, P=0.33) did not differ significantly among the groups. However, the mature follicle(Z=3.62, P=0.000 3) and the endometrial thickness(Z=2.77,P=0.006) were significantly greater in the bromocriptine group than those in control group. CONCLUSION It is found that no evidence suggesting that bromocriptine improves the rates of ovulation, pregnancy, follicular development and abortion, though it showed benefit in terms of mature follicle and endometrial thickness. Limitations included imprecision(small design trials) and poor reporting of study methods. Large, well-designed RCTs are necessary to further evaluate the role of bromocriptine in polycystic ovary syndrome.
引文
[1]中华医学会妇产科学分会内分泌学组.多囊卵巢综合征的诊断和治疗专家共识[J].中华妇产科杂志,2008,43(7):553-555.
[2]ROTTERDAM ESHRE/ASRM-SPONSORED PCOSCONSENSUS WORKSHOP GROUP.Revised 2003consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome[J].Fertil Steril,2004,81(1):19-25.
[3]LEGRO R S,ARSLANIAN S A,EHRMANN D A,et al.Diagnosis and treatment of polycystic ovary syndrome:an Endocrine Society clinical practice guideline[J].J Clin Endocrinol Metab,2013,98(12):4565-4592.
[4]KOUSTA E,WHITE D M,FRANKS S.Modern use of clomiphene citrate in induction of ovulation[J].Hum Reprod Update,1997,3(4):359-365.
[5]PRITTS E A.Treatment of the infertile patient with polycystic ovarian syndrome[J].Obstet Gynecol Surv,2002,57(9):587-597.
[6]WOLF L J.Ovulation induction[J].Clin Obstet Gynecol,2000,43(4):902-915.
[7]NAVOT D,BERGH P A,LAUFER N.Ovarian hyperstimulation syndrome in novel reproductive technologies:prevention and treatment[J].Fertil Steril,1992,58(2):249-261.
[8]KAMPHUIS E I,BHATTACHARYA S,VAN DER VEEN F,et al.Are we overusing IVF?[J].BMJ,2014,348:g252.
[9]BUVAT J,BUVAT-HERBAUT M,MARCOLIN G,et al.Adouble blind controlled study of the hormonal and clinical effects of bromocriptine in the polycystic ovary syndrome[J].J Clin Endocrinol Metab,1986,63(1):119-124.
[10]LI W Y,HAN Y F,WANG Z Y,et al.Effects of bromocriptine in assisted reproductive therapies of infertility patients with refractory polycystic ovarian syndrome[J].Henan Med Res(河南医学研究),2015,24(9):22-24.
[11]HIGGINS J P,THOMPSON S G.Quantifying heterogeneity in a meta-analysis[J].Stat Med,2002,21(11):1539-1558.
[12]PARSANEZHAD M E,ALBORZI S,NAMAVAR JAHROMIB.A prospective,double-blind,randomized,placebocontrolled clinical trial of bromocriptin in clomiphene-resistant patients with polycystic ovary syndrome and normal prolactin level[J].Arch Gynecol Obstet,2004,269(2):125-129.
[13]李冰,蒋亚玲,刘明星,等.溴隐亭治疗难治性多囊卵巢综合征不育的临床观察[J].生殖医学杂志,2007,16(6):430-431.
[14]李洪英.溴隐亭治疗多囊卵巢综合征不育的临床观察[J].中国现代药物应用,2012,6(11):71-72.
[15]TRIPATHY S,MOHAPATRA S,MUTHULAKSHMI M,et al.Induction of ovulation with clomiphene citrate versus clomiphene with bromocriptine in PCOS patients with normal prolactin:A comparative study[J].J Clin Diagn Res,2013,7(11):2541-2543.
[16]Excellence,National Collaborating Centre for Women’s and Children’s Health/National Institute for Clinical.Fertility problems:assessment and treatment[K].National Collaborating Centre for Women’s and Children’s Health,2013.
[17]LEGRO R S,BARNHART H X,SCHLAFF W D,et al.Clomiphene,metformin,or both for infertility in the polycystic ovary syndrome[J].N Engl J Med,2007,356(6):551-566.
[18]SHI S Q,JIANG F F,HONG T,et al.Efficacy of letrozole and human menopausal gonadotropin for ovulation induction in clomiphene resisance polycystic ovary syndrome patients[J].Chin J Mod Appl Pharm(中国现代应用药学),2013,30(7):782-785.
[19]ESMAEILZADEH S,AMIRI M G,BASIRAT Z,et al.Does adding dexamethasone to clomiphene citrate improve ovulation in PCOS patients?A triple-blind randomized clinical trial study[J].Int J Fertil Steril,2011,5(1):9-12.
[20]ELNASHAR A,ABDELMAGEED E,FAYED M,et al.Clomiphene citrate and dexamethazone in treatment of clomiphene citrate-resistant polycystic ovary syndrome:a prospective placebo-controlled study[J].Hum Reprod,2006,21(7):1805-1808.
[21]SEIBEL M M,OSKOWITZ S,KAMRAVA M,et al.Bromocriptine response in normoprolactinemic patients with polycystic ovary disease:a preliminary report[J].Obstet Gynecol,1984,64(2):213-219.
[22]KUBOTA T,KAMADA S,ASO T.Combined therapy with bromocriptine and clomiphene citrate for patients with normoprolactinemic amenorrhea[J].Int J Fertil,1992,37(5):277-282.
[23]BROWN J,FARQUHAR C.Clomiphene and other antioestrogens for ovulation induction in polycystic ovarian syndrome[J].Cochrane Database Syst Rev,2016(12):CD002249.Doi:10.1002/14651858.CD002249.pub5.
[24]VAIL A,GARDENER E.Common statistical errors in the design and analysis of subfertility trials[J].Hum Reprod,2003,18(5):1000-1004.
[2]ROTTERDAM ESHRE/ASRM-SPONSORED PCOSCONSENSUS WORKSHOP GROUP.Revised 2003consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome[J].Fertil Steril,2004,81(1):19-25.
[3]LEGRO R S,ARSLANIAN S A,EHRMANN D A,et al.Diagnosis and treatment of polycystic ovary syndrome:an Endocrine Society clinical practice guideline[J].J Clin Endocrinol Metab,2013,98(12):4565-4592.
[4]KOUSTA E,WHITE D M,FRANKS S.Modern use of clomiphene citrate in induction of ovulation[J].Hum Reprod Update,1997,3(4):359-365.
[5]PRITTS E A.Treatment of the infertile patient with polycystic ovarian syndrome[J].Obstet Gynecol Surv,2002,57(9):587-597.
[6]WOLF L J.Ovulation induction[J].Clin Obstet Gynecol,2000,43(4):902-915.
[7]NAVOT D,BERGH P A,LAUFER N.Ovarian hyperstimulation syndrome in novel reproductive technologies:prevention and treatment[J].Fertil Steril,1992,58(2):249-261.
[8]KAMPHUIS E I,BHATTACHARYA S,VAN DER VEEN F,et al.Are we overusing IVF?[J].BMJ,2014,348:g252.
[9]BUVAT J,BUVAT-HERBAUT M,MARCOLIN G,et al.Adouble blind controlled study of the hormonal and clinical effects of bromocriptine in the polycystic ovary syndrome[J].J Clin Endocrinol Metab,1986,63(1):119-124.
[10]LI W Y,HAN Y F,WANG Z Y,et al.Effects of bromocriptine in assisted reproductive therapies of infertility patients with refractory polycystic ovarian syndrome[J].Henan Med Res(河南医学研究),2015,24(9):22-24.
[11]HIGGINS J P,THOMPSON S G.Quantifying heterogeneity in a meta-analysis[J].Stat Med,2002,21(11):1539-1558.
[12]PARSANEZHAD M E,ALBORZI S,NAMAVAR JAHROMIB.A prospective,double-blind,randomized,placebocontrolled clinical trial of bromocriptin in clomiphene-resistant patients with polycystic ovary syndrome and normal prolactin level[J].Arch Gynecol Obstet,2004,269(2):125-129.
[13]李冰,蒋亚玲,刘明星,等.溴隐亭治疗难治性多囊卵巢综合征不育的临床观察[J].生殖医学杂志,2007,16(6):430-431.
[14]李洪英.溴隐亭治疗多囊卵巢综合征不育的临床观察[J].中国现代药物应用,2012,6(11):71-72.
[15]TRIPATHY S,MOHAPATRA S,MUTHULAKSHMI M,et al.Induction of ovulation with clomiphene citrate versus clomiphene with bromocriptine in PCOS patients with normal prolactin:A comparative study[J].J Clin Diagn Res,2013,7(11):2541-2543.
[16]Excellence,National Collaborating Centre for Women’s and Children’s Health/National Institute for Clinical.Fertility problems:assessment and treatment[K].National Collaborating Centre for Women’s and Children’s Health,2013.
[17]LEGRO R S,BARNHART H X,SCHLAFF W D,et al.Clomiphene,metformin,or both for infertility in the polycystic ovary syndrome[J].N Engl J Med,2007,356(6):551-566.
[18]SHI S Q,JIANG F F,HONG T,et al.Efficacy of letrozole and human menopausal gonadotropin for ovulation induction in clomiphene resisance polycystic ovary syndrome patients[J].Chin J Mod Appl Pharm(中国现代应用药学),2013,30(7):782-785.
[19]ESMAEILZADEH S,AMIRI M G,BASIRAT Z,et al.Does adding dexamethasone to clomiphene citrate improve ovulation in PCOS patients?A triple-blind randomized clinical trial study[J].Int J Fertil Steril,2011,5(1):9-12.
[20]ELNASHAR A,ABDELMAGEED E,FAYED M,et al.Clomiphene citrate and dexamethazone in treatment of clomiphene citrate-resistant polycystic ovary syndrome:a prospective placebo-controlled study[J].Hum Reprod,2006,21(7):1805-1808.
[21]SEIBEL M M,OSKOWITZ S,KAMRAVA M,et al.Bromocriptine response in normoprolactinemic patients with polycystic ovary disease:a preliminary report[J].Obstet Gynecol,1984,64(2):213-219.
[22]KUBOTA T,KAMADA S,ASO T.Combined therapy with bromocriptine and clomiphene citrate for patients with normoprolactinemic amenorrhea[J].Int J Fertil,1992,37(5):277-282.
[23]BROWN J,FARQUHAR C.Clomiphene and other antioestrogens for ovulation induction in polycystic ovarian syndrome[J].Cochrane Database Syst Rev,2016(12):CD002249.Doi:10.1002/14651858.CD002249.pub5.
[24]VAIL A,GARDENER E.Common statistical errors in the design and analysis of subfertility trials[J].Hum Reprod,2003,18(5):1000-1004.