注射用尿促卵泡素治疗严重少弱精子症的多中心临床研究
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摘要
目的观察尿促卵泡素(u FSH,产品名丽申宝)治疗严重少弱精子症患者的有效性和安全性。方法采用多中心、开放性、自身前后对照的临床研究方法,对43例严重少弱精子症患者采用丽申宝肌肉注射治疗,每3天1次注射75单位,连续治疗24周。比较治疗前及治疗后8、16、24周后患者精子浓度、前向运动精子比例等精液参数和生殖激素的变化情况,同时观察配偶妊娠情况,以评价丽申宝的治疗效果。结果精子浓度在用药8、16、24周后分别增加了334%、258%和460%,在用药24周后精子浓度上升到(7.79±8.44)×10~6/mL,[治疗前(1.39±1.58)×10~6/mL],与治疗前比较,差异具统计学意义(P<0.05);前向运动精子比例在用药8、16、24后也呈明显上升趋势(分别增加了71%、135%和143%),在用药24周后前向运动精子比例达到(18.77±17.16)%[治疗前(7.74±11.41)%],与治疗前比较,差异具统计学意义(P<0.05);精子活力和总数、血清促卵泡素(FSH)水平在治疗后也显著提高,差异均具统计学意义(P<0.05)。但患者的精液量和黄体生成素(LH)、睾酮(T)等生殖激素水平在治疗前后无明显差异。1例严重少精子症患者在用药期间发生临床妊娠。结论丽申宝可显著提高严重少弱精子症患者的精液质量,未见明显不良反应。
Objective To observe the efficacy and safety of Li Shen Bao(u FSH) in the treatment of severe oligoasthenospermia. Methods Using a multi-centered, open and self-controlled clinical trial, we treated 43 patients with severe oligoasthenospermia with Li Shen Bao 75 IU/3 d, i.m, for 24 weeks, and evaluated the the semen parameters including sperm concentration and the percentage of progressive motile sperm, reproductive hormone, adverse reaction and pregnancy condition of their spouse at 8, 16 and 24 weeks. Results Compared with baseline, the sperm concentration was increased by 334%, 258% and 460% respectively at 8, 16 and 24 weeks, elevating from the baseline of(1.39±1.58)×10~6/mL to(7.79±8.44)×10~6/mL at 24 weeks. The percentage of progressive motile sperm was significantly improved(increased by 71%, 135% and 143% respectively at 8, 16 and 24 weeks). There was also an increase in terms of sperm motility and total number, and serum FSH, while no significant changes were observed in sperm volume, LH and T. One patient with severe oligoasthenospermia has pregnancy during the treatment. Conclusion Li Shen Bao can evidently improve the seminal quality of oligoasthenospermic patients with no obvious adverse events.
Objective To observe the efficacy and safety of Li Shen Bao(u FSH) in the treatment of severe oligoasthenospermia. Methods Using a multi-centered, open and self-controlled clinical trial, we treated 43 patients with severe oligoasthenospermia with Li Shen Bao 75 IU/3 d, i.m, for 24 weeks, and evaluated the the semen parameters including sperm concentration and the percentage of progressive motile sperm, reproductive hormone, adverse reaction and pregnancy condition of their spouse at 8, 16 and 24 weeks. Results Compared with baseline, the sperm concentration was increased by 334%, 258% and 460% respectively at 8, 16 and 24 weeks, elevating from the baseline of(1.39±1.58)×10~6/mL to(7.79±8.44)×10~6/mL at 24 weeks. The percentage of progressive motile sperm was significantly improved(increased by 71%, 135% and 143% respectively at 8, 16 and 24 weeks). There was also an increase in terms of sperm motility and total number, and serum FSH, while no significant changes were observed in sperm volume, LH and T. One patient with severe oligoasthenospermia has pregnancy during the treatment. Conclusion Li Shen Bao can evidently improve the seminal quality of oligoasthenospermic patients with no obvious adverse events.
引文
1 Practice Committee of the American Society for Reproductive Medicine.Diagnostic evaluation of the infertile male:a committee opinion.Fertil Steril 2015;103(3):e18-e25
2 Winters BR,Walsh TJ.The epidemiology of male infertility.Urol Clin North Am 2014;41(1):195-204
3 Simoni M,Weinbauer GF,Gromoll J,et al.Role of FSHin male gonadal function.Ann Endocrinol(Paris)1999;60(2):102-106
4 Walker WH,Cheng J.FSH and testosterone signaling in Sertoli cells.Reproduction 2005;130(1):15-28
5 Valenti D,La Vignera S,Condorelli RA,et al.Folliclestimulating hormone treatment in normogonadotropic infertile men.Nat Rev Urol 2013;10(1):55-62
6 Acosta AA,Khalifa E,Oehninger S.Pure human follicle stimulating hormone has a role in the treatment of severe male infertility by assisted reproduction:Norfolk's total experience.Hum Reprod 1992;7(8):1067-1072
7 Yoshida M,Kawano N,Yoshida K.Control of sperm motility and fertility:diverse factors and common mechanisms.Cell Mol Life Sci 2008;65(21):3446-3457
8 Foresta C,Bettella A,Garolla A,et al.Treatment of male idiopathic infertility with recombinant human follicle-stimulating hormone:a prospective,controlled,randomized clinical study.Fertil Steril 2005;84(3):654-661
9 Palomba S,Falbo A,Espinola S,et al.Effects of highly purified follicle-stimulating hormone on sperm DNAdamage in men with male idiopathic subfertility:a pilot study.J Endocrinol Invest 2011;34(10):747-752
10 Ramaswamy S,Weinbauer GF.Endocrine control of spermatogenesis:Role of FSH and LH/testosterone.Spermatogenesis 2014;4(2):e996025
11 Ding LJ,Yan GJ,Ge QY,et al.FSH acts on the proliferation of type A spermatogonia via Nur77 that increases GDNF expression in the Sertoli cells.FEBSLett 2011;585(15):2437-2444
12 Ramaswamy S,Plant TM.Operation of the folliclestimulating hormone(FSH)-inhibin B feedback loop in the control of primate spermatogenesis.Mol Cell Endocrinol 2001;180(1-2):93-101
13 Mc Lachlan RI,O'Donnell L,Meachem SJ,et al.Identification of specific sites of hormonal regulation in spermatogenesis in rats,monkeys,and man.Recent Prog Horm Res 2002;57:149-179
14 Foresta C,Selice R,Ferlin A,et al.Hormonal treatment of male infertility:FSH.Reprod Biomed Online 2007;15(6):666-672
15陈晓会,孙伟.FSH治疗特发性少、弱精子症的临床疗效观察.中国性科学2012;21(7):12-13,29
16 Sairam MR,Krishnamurthy H.The role of folliclestimulating hormone in spermatogenesis:lessons from knockout animal models.Arch Med Res 2001;32(6):601-608
17崔毓桂,陈子庆,沙家豪.激素对精子发生的调控.中华男科学杂志2004;10(6):465-467
18李江源.精子发生的内分泌激素调节.生殖医学杂志2014;23(9):697-702
19杨念钦,王国民.HCG、FSH联合治疗低促性腺激素性性腺功能减退症29例报告.中国男科学杂志2009;23(12):39-41
20 Foresta C,Bettella A,Merico M,et al.Use of recombinant human follicle-stimulating hormone in the treatment of male factor infertility.Fertil Steril 2002;77(2):238-244
21 Paradisi R,Busacchi P,Seracchioli R,et al.Effects of high doses of recombinant human follicle-stimulating hormone in the treatment of male factor infertility:results of a pilot study.Fertil Steril 2006;86(3):728-731
22 Paradisi R,Natali F,Fabbri R,et al.Evidence for a stimulatory role of high doses of recombinant human follicle-stimulating hormone in the treatment of malefactor infertility.Andrologia 2014;46(9):1067-1072
23 Ashkenazi J,Bar-Hava I,Farhi J,et al.The role of purified follicle stimulating hormone therapy in the male partner before intracytoplasmic sperm injection.Fertil Steril 1999;72(4):670-673
24 Dirnfeld M,Katz G,Calderon I,et al.Pure folliclestimulating hormone as an adjuvant therapy for selected cases in male infertility during in-vitro fertilization is beneficial.Eur J Obstet Gynecol Reprod Biol 2000;93(1):105-108
25 Colacurci N,Monti MG,Fornaro F,et al.Recombinant human FSH reduces sperm DNA fragmentation in men with idiopathic oligoasthenoteratozoospermia.J Androl2012;33(4):588-593
26 Bartoov B,Eltes F,Lunenfeld E,et al.Sperm quality of subfertile males before and after treatment with human follicle-stimulating hormone.Fertil Steril 1994;61(4):727-734
2 Winters BR,Walsh TJ.The epidemiology of male infertility.Urol Clin North Am 2014;41(1):195-204
3 Simoni M,Weinbauer GF,Gromoll J,et al.Role of FSHin male gonadal function.Ann Endocrinol(Paris)1999;60(2):102-106
4 Walker WH,Cheng J.FSH and testosterone signaling in Sertoli cells.Reproduction 2005;130(1):15-28
5 Valenti D,La Vignera S,Condorelli RA,et al.Folliclestimulating hormone treatment in normogonadotropic infertile men.Nat Rev Urol 2013;10(1):55-62
6 Acosta AA,Khalifa E,Oehninger S.Pure human follicle stimulating hormone has a role in the treatment of severe male infertility by assisted reproduction:Norfolk's total experience.Hum Reprod 1992;7(8):1067-1072
7 Yoshida M,Kawano N,Yoshida K.Control of sperm motility and fertility:diverse factors and common mechanisms.Cell Mol Life Sci 2008;65(21):3446-3457
8 Foresta C,Bettella A,Garolla A,et al.Treatment of male idiopathic infertility with recombinant human follicle-stimulating hormone:a prospective,controlled,randomized clinical study.Fertil Steril 2005;84(3):654-661
9 Palomba S,Falbo A,Espinola S,et al.Effects of highly purified follicle-stimulating hormone on sperm DNAdamage in men with male idiopathic subfertility:a pilot study.J Endocrinol Invest 2011;34(10):747-752
10 Ramaswamy S,Weinbauer GF.Endocrine control of spermatogenesis:Role of FSH and LH/testosterone.Spermatogenesis 2014;4(2):e996025
11 Ding LJ,Yan GJ,Ge QY,et al.FSH acts on the proliferation of type A spermatogonia via Nur77 that increases GDNF expression in the Sertoli cells.FEBSLett 2011;585(15):2437-2444
12 Ramaswamy S,Plant TM.Operation of the folliclestimulating hormone(FSH)-inhibin B feedback loop in the control of primate spermatogenesis.Mol Cell Endocrinol 2001;180(1-2):93-101
13 Mc Lachlan RI,O'Donnell L,Meachem SJ,et al.Identification of specific sites of hormonal regulation in spermatogenesis in rats,monkeys,and man.Recent Prog Horm Res 2002;57:149-179
14 Foresta C,Selice R,Ferlin A,et al.Hormonal treatment of male infertility:FSH.Reprod Biomed Online 2007;15(6):666-672
15陈晓会,孙伟.FSH治疗特发性少、弱精子症的临床疗效观察.中国性科学2012;21(7):12-13,29
16 Sairam MR,Krishnamurthy H.The role of folliclestimulating hormone in spermatogenesis:lessons from knockout animal models.Arch Med Res 2001;32(6):601-608
17崔毓桂,陈子庆,沙家豪.激素对精子发生的调控.中华男科学杂志2004;10(6):465-467
18李江源.精子发生的内分泌激素调节.生殖医学杂志2014;23(9):697-702
19杨念钦,王国民.HCG、FSH联合治疗低促性腺激素性性腺功能减退症29例报告.中国男科学杂志2009;23(12):39-41
20 Foresta C,Bettella A,Merico M,et al.Use of recombinant human follicle-stimulating hormone in the treatment of male factor infertility.Fertil Steril 2002;77(2):238-244
21 Paradisi R,Busacchi P,Seracchioli R,et al.Effects of high doses of recombinant human follicle-stimulating hormone in the treatment of male factor infertility:results of a pilot study.Fertil Steril 2006;86(3):728-731
22 Paradisi R,Natali F,Fabbri R,et al.Evidence for a stimulatory role of high doses of recombinant human follicle-stimulating hormone in the treatment of malefactor infertility.Andrologia 2014;46(9):1067-1072
23 Ashkenazi J,Bar-Hava I,Farhi J,et al.The role of purified follicle stimulating hormone therapy in the male partner before intracytoplasmic sperm injection.Fertil Steril 1999;72(4):670-673
24 Dirnfeld M,Katz G,Calderon I,et al.Pure folliclestimulating hormone as an adjuvant therapy for selected cases in male infertility during in-vitro fertilization is beneficial.Eur J Obstet Gynecol Reprod Biol 2000;93(1):105-108
25 Colacurci N,Monti MG,Fornaro F,et al.Recombinant human FSH reduces sperm DNA fragmentation in men with idiopathic oligoasthenoteratozoospermia.J Androl2012;33(4):588-593
26 Bartoov B,Eltes F,Lunenfeld E,et al.Sperm quality of subfertile males before and after treatment with human follicle-stimulating hormone.Fertil Steril 1994;61(4):727-734