The Effect of Clomiphene Citrate on Different Sperm Parameters and Serum Hormone Levels in Preselected Infertile Men: A Controlled Double-Blind Cross-Over Study

In order to try to clarify the often supposed stimulating effect of clomiphene citrate on spermatogenesis a controlled double-blind cross-over trial was used. 30 pre-selected normogonadotropic infertile men were given 50 mg clomiphene citrate daily or placebo in a double-blind cross-over fashion for three months, each treatment period being separated by three to four months. On clomiphene treatment the median sperm count increased from 13.3 to 28.7 mill/ml ( P < 0.001). During the placebo treatment schedules the median sperm count remained unchanged ( P > 0.05). The increases of FSH, LH, testosterone, and oestradiol were highly significant ( P > 0.001) during the clomiphene treatment but during placebo treatment the median hormone levels did not change ( P > 0.05). Three pregnancies occured due to clomiphene treatment and one occured during placebo treatment.     

Clomiphene citrate versus varicocelectomy in treatment of subclinical varicocele: A prospective randomized study

BACKGROUND: The purpose of the study was to compare the effect of varicocelectomy with that of clomiphene citrate on seminal improvement and pregnancy rates in patients with subclinical varicocele. METHODS: A total of 42 infertile men with left subclinical varicocele were randomized to group I (21 patients, surgery) and group II (21 patients, medical therapy). The patients in group I were treated with varicocelectomy and those in group II with clomiphene citrate, 50 mg/day, orally. Sperm parameters (sperm density, motility and morphology) were recorded before and 6 months after beginning the treatment and pregnancy rates were estimated. In statistical analysis, paired and independent-samples t-tests, Kaplan-Meier and Log rank tests and Fisher's exact test were used. RESULTS: Mean +/- SD age of the series was 32.7 +/- 6.1 years, that of group I was 32.2 +/- 5.5 years and that of group II was 33.1 +/- 6.7 years (P = 0.680). All seminal parameters increased after both surgical and medical treatment, but only increases in sperm density and motility following varicocelectomy were statistically significant. Changes in seminal parameters between groups I and II were statistically insignificant. Pregnancy was seen in two cases in group I and in one in group II (P = 0.500). The cumulative pregnancy rates were 12.5% in group I and 6.7% in group II (P = 0.589). CONCLUSIONS: Clomiphene citrate did not increase sperm density and motility as effectively as subclinical varicocelectomy, but there was no statistically significant difference between surgical and medical therapy methods in terms of seminal improvement and pregnancy rate.     

In vitro effects of clomiphene citrate on sperm parameters and fertilisation rate in male NMRI mice

Clomiphene citrate (CC), as a medication in male infertility, improves the sperm parameters in oral consumption but various detrimental side effects have been reported including testicular tumours, gynaecomastia, skin allergic reactions and ocular symptoms. Therefore, this study was designed to evaluate the in vitro effects of CC on sperm parameters and fertilisation rate in IVF protocol. Sperm samples of NMRI adult mice were divided into six groups: group 1 received no treatment (control group), while groups of 2, 3, 4, 5 and 6 (experimental groups) were incubated with the doses of 0.001, 0.01, 0.1, 1 and 10 µg/ml of CC in culture medium respectively. Sperm parameters (viability, morphology and motility), DNA fragmentation levels and fertilisation rate in IVF were evaluated. The results demonstrated that the doses of 0.1 µg/ml (p = .000007 for viability and p = .00006 for fertilisation rate) and 1 µg/ml (p = .032 for viability and p = .005 for fertilisation rate) CC cause a significant improvements; also, the dose of 0.1 µg/ml CC found effective on sperm motility (p = .0003). In the field of IVF, the application of 0.1 and 1 µg/ml of CC in the culture medium may improve the sperm parameters in IVF protocol with no side effects.     

A paradoxical decline in semen parameters in men treated with clomiphene citrate: A systematic review

Clomiphene, a selective oestrogen receptor modulator, has been utilised in managing male sub-fertility since 1967. Numerous controlled and uncontrolled studies have been published regarding the efficacy of clomiphene citrate in male sub-fertility cohorts. Although the primary intention of treating men with clomiphene citrate is to improve sperm parameters and testosterone levels, some studies have reported paradoxical decline in semen parameters. The information available on decline in sperm parameters following treatment with clomiphene is sparse. We conducted a systemic review using PubMed, Embase, Cochrane Library and Scopus databases for original studies reporting adverse effects of clomiphene citrate therapy on sperm parameters. This systematic review includes 384 men from 11 different studies that reported adverse effects of clomiphene citrate therapy. Of the men included in these studies, 19%, 21%, 17% and 24% of clomiphene-treated men demonstrated a decrease in sperm count, concentration, motility and total motile sperm count respectively. In up to 17% of patients, deterioration of semen parameters did not recover following discontinuation of therapy. In the future, more studies should report on this aspect so the magnitude of this effect can be more clearly understood.     

Kallikrein Therapy of Infertile Men with Varicocele and Impaired Sperm Motility: Therapie mit Kallikrein bei infertilen Männern mit Varicocele und reduzierter Spermatozoenmotilität

A randomized group of 65 men with oligoasthenozoospermia and left side varicocele was subjected to a controlled study with kallikrein. Kallikrein (600 units orally per day) was given to 38 men for a period of 3 months. The other group of 27 men remained untreated but were followed up during the same period of time. After kallikrein treatment significant improvements in sperm quality could be observed: percentage of motile spermatozoa from 24.47 +/- 9.01 to 35.26 +/- 11.80, percentage of morphologically normal spermatozoa from 58.42 +/- 5.86 to 71.05 +/- 8.12. There was no improvement in sperm parameters in the untreated group of men. The results suggest that kallikrein therapy is useful for those men who refuse an operative or radiologic treatment of their varicocele and also as a primary or associated therapy of patients who underwent ligature or occlusion of spermatic veins.     

Hormonal and Seminal Parameters in Infertile Men

500 infertile patients (250 with and 250 without left side varicocele) and 33 fertile men were evaluated as far as seminal parameters and the hormonal status were concerned. Sperm motility was constantly lower in infertile patients also when infertile group was compared to fertile one with the same sperm density. Serum testosterone levels were lower in infertile groups when compared to fertile men, and this confirms the existence of an androgenic deficit as a common finding in infertility associated or not to varicocele. FSH and LH increased (p less than 0.001) when sperm density dropped to less than 5 X 10(6) spermatozoa/ml. A negative correlation was found between both gonadotropins and sperm count (p less than 0.001), also after exclusion of azoo- and oligozoospermic (less than 5 X 10(6) spermatozoa/ml) patients (p less than 0.01). Gonadotropins were moreover tightly correlated between each other (p less than 0.001). Our data suggest that both gonadotropins are tightly tuned with sperm output and thus with the spermatogenic potential.     

精索静脉曲张不育患者的精液质量和精子形态学观察

目的:观察不育伴精索静脉曲张(VC)患者的精液质量和精子形态学变化。方法:98例不育伴VC患者精液按WHO标准常规分析并对精子形态学进行评价。130例正常供精者精液检测结果作为对照。结果:VC患者正常形态精子和前向运动精子明显低于对照组(P<0.001),精子畸形的类型以梨形、锥形和不定型头部畸形为主。结论:VC可导致精子畸形率升高,后者可能是男性生育力受损的重要标志之一,经染色后的精子形态学分析是判定VC患者精子受损的一个敏感指标。     

两种精子分析系统的比较研究

目的:评估自动化精子质量分析仪SQA-V与计算机辅助精液分析(CASA)系统之间各主要参数的差异性及其在不育和生育男性精液质量分析中的应用。方法:用SQA-V和CASA系统分别检测12例正常生育者和73例不育患者新鲜精液标本,分别分析精子密度、精子活动率、活动精子浓度、精子活动力指数、精子头侧向位移、鞭打频率、精子曲线运动速度、精子前向运动速度、平均路径速度、直线性及前向性运动速度等参数,针对两者进行相关性分析。结果:不育组和生育组男性各项指标间存在显著差异,两种分析系统检测的精子密度之间(r=0.58,P<0.01)、活动精子浓度之间(r=0.75,P<0.01)、平均精子速度(SQA-V)和精子路径速度(CASA)之间(r=0.59,P<0.01)具有较好的一致性,SQA-V的活动精子指数(SMI)和CASA的前向性、曲线运动速度、精子运动的直线性、前向运动速度、平均路径速度、鞭打频率等参数具有显著相关性(P<0.05)。结论:SQA-V和CASA系统比较,在各主要参数上具有较好的一致性,能够反映临床不同组群患者精液的差异性。     

人精浆抗精子抗体与顶体酶活性关系的探讨

目的 :研究精浆抗精子抗体 (AsAb)对精子顶体酶活力的影响。　方法 :用间接血凝法测定 34 32例不育男性和 6 5例生育男性精浆的AsAb ,并对其中的 2 882例不育男性精子用比色法进行了顶体酶活性的测定。　结果 :34 32例不育者精浆AsAb阳性率为 10 .2 0 %,2 882例进行了顶体酶活性测定的不育者精浆AsAb阳性率为 9.37%,对照组精子顶体酶活性明显高于各不育组 (P <0 .0 0 1)。不育组AsAb阳性组与AsAb阴性组比较顶体酶活性没有明显差异 (P >0 .0 5 ) ,顶体酶活性正常与异常组AsAb阳性率比较差异无显著性 (P >0 .0 5 )。　结论 :精浆AsAb对精子顶体酶活性没有影响。     

不育男性精浆总抗氧化能力与精子运动功能的关系

目的:研究不育男性精浆总抗氧化能力(TAC)与精子运动能力和方式之间的关系,探讨精浆TAC水平在男性生育中的临床意义。方法:113例精子密度正常的不育男性,28例正常生育男性作为对照组。精液于37℃液化后采用计算机辅助精液分析(CASA)系统进行精液常规分析,采用比色法进行精浆TAC分析。结果:正常生育组精浆TAC为(19.82±6.33)U,不育男性精子密度正常组精浆TAC为(14.37±8.45)U,不育男性精子密度正常组与正常生育组比较存在显著性差异(P<0.01)。精浆TAC与a级精子百分率(r=0.208,P<0.05)和(a+b)级精子百分率(r=0.231,P<0.05)呈显著正相关,精浆TAC与精子运动参数中的前向性(r=0.200,P<0.05)、直线性(r=0.208,P<0.05)、曲线速度(r=0.189,P<0.05)、直线速度(r=0.210,P<0.05)、平均移动速度(r=0.215,P<0.05)及鞭打频率(r=-0.248,P<0.01)之间有显著的相关性,其中前向性、直线性、直线速度、曲线速度、平均移动速度与TAC呈正相关(P<0.05),而鞭打频率与TAC呈负相关(P<0.01)。精浆TAC与摆动性、侧摆幅度、平均移动角度之间无显著相关。结论:精浆中TAC水平与精子运动能力和运动方式密切相关,适宜的精浆TAC为精子运动提供了良好的外部环境,精浆中过低的TAC水平与精子运动能力下降和运动方式改变有关,可能是引起男性不育的病因之一。精浆中TAC分析可为探讨男性不育的发病机制以及临床用药提供依据。     

Sperm Recovery Prediction in Azoospermic Patients Using Doppler Ultrasonography

Purpose: To evaluate power Doppler ultrasonography to predict sperm recovery in azoospermic patients. Methods: Color Doppler and power Doppler ultrasonography of testis were performed in 38 patients before testicular sperm extraction. Analysis of blood flow included the pulsatility and resistance index of intratesticular vessels and testicular artery, and power Doppler of testis. The results of power Doppler of testis were classified into three categories: 0, no vessels found; 1, one to three vessels; 2, more than three vessels found. Results: Power Doppler of both testis showed a significant difference between obstructive azoospermia and non-obstructive azoospermia (Fisher’s exact test – P = 0.02), and between the groups with and without sperm recovery (Fisher’s exact test – P = 0.001). Doppler indices of intratesticular vessels and testicular artery were similar between the groups. Conclusions: Testicular Power Doppler assessment showed that patients with obstructive azoospermia have better blood flow than patients with non-obstructive azoospermia, and power Doppler is able to predict sperm recovery in azoospermic patients.     

育子丸治疗精核蛋白异常男性不育30例临床分析

目的:研究育子丸临床治疗精核蛋白异常男性不育的方法及效果。方法:观察30例男性不育患者用育子丸治疗前后精核蛋白、精液参数、性激素的变化情况。结果:育子丸治疗1个疗程(3个月)后,治愈9例,显效15例,无效6例。治疗后,组蛋白/精核蛋白的比例[(0.72±0.32)]较治疗前[(1.34±0.52)]下降,差异有显著性(P<0.01);精液质量较治疗前明显改善(P<0.05);LH、T水平较治疗前显著提高(P<0.01)。治疗后中医症候改善25例。结论:育子丸治疗精核蛋白异常的男性不育具有良好疗效。     

Clomiphene citrate administration to normogonadotropic subfertile men: Blood hormone changes and activation of acid phosphatase in seminal fluid

Clomiphene citrate was administered as a 50 mg oral daily dose to 44 normogonadotrophic (serum FSH 2–10 mIU/ml) subfertile men for 3 months. The treatment resulted in significant increases in FSH and LH concentrations, whereas prolactin remained unchanged. Serum testosterone and oestradiol both increased highly significantly. The increased testosterone levels suggest that the elevated LH levels had not led to "down regulation" of Leydig cell LH/hCG receptors, neither had the greatly increased estradiol led to depletion of these receptors. This is suggested to be a result of the blocking of testicular oestradiol receptors by the estrogen antagonist, clomiphene. Sperm count increased highly significantly during the treatment. The spermatic fluid concentrations of zinc and magnesium ions were also increased, whereas fructose remained unchanged. The katalytic activity of acid phosphatase in spermatic fluid increased highly significantly, whereas the concentration of the main prostate-specific acid phosphatase, as measured by a specific radioimmunological method, remained unchanged. Therefore, the increased Zn and Mg ion concentrations may be responsible for activation of acid phosphatase (s) in semen, or the treatment led to increased secretion of other prostatic acid phosphatase(s) than the main enzyme. However, it is clear that the secretion of the main prostatic acid phosphatase into semen is under different control than that of Zn⁺⁺ and Mg⁺⁺.     

生脉注射液在体外对精子运动能力和存活时间的影响

目的:观察生脉注射液对人精子运动参数和存活时间的影响。方法:将33例正常生育男性精液均分为两份,一份与生脉注射液+Hams-F10孵育,一份与Hams-F10共孵育。于0.5、1、2、4、8、12 h取样,检测精子存活率、并应用计算机辅助精子分析系统(CASA)测定精子的直线运动速度(VSL)、曲线运动速度(VCL)、平均路径速度(VAP)和头部侧摆幅度(ALH)等精子运动参数。结果:生脉组在孵育8 h时VCL明显高于Hams-F10组(P<0.05),12 h时生脉组VCL显著增高(P<0.01)。孵育4、8、12 h,生脉组VSL和VAP明显高于Hams-F10组(P<0.05)。孵育2、4、8、12 h时生脉组ALH明显高于Hams-F10组(P<0.05)。两份精液各时间段的精子死活比率相比,除12 h时有明显差异(P<0.05)外,其他各时间段无明显差异。结论:生脉注射液能提高精子的运动能力、延长精子的体外存活时间。     

Effects of Experimental Hyperprolactinemia and Clomiphene on Pituitary Responsiveness to LHRH and TRH in Men

The effect of clomiphene citrate during sulpiride-induced hyperprolactinemia on pituitary function was tested in 8 healthy men, who ingested 100 mg of clomiphene, 150 mg of sulpiride or 100 mg of clomiphene + 150 mg of sulpiride daily for 7 days. Clomiphene treatment increased FSH and LH plasma concentrations and this increase was unaffected by sulpiride-induced hyperprolactinemia. Sulpiride intake alone did not alter serum gonadotropin concentrations. A reduced LH response to LHRH during sulpiride intake was seen, whereas the FSH response was unchanged. The prolactin response to TRH was unaffected during the combined sulpiride + clomiphene ingestion. Sulpiride treatment did not change the basal and/or clomiphene-stimulated gonadotropin secretion in healthy men. Thus, oligozoospermic men using psychotropic drugs and/or with hyperprolactinemia may be suitable candidates for clomiphene treatment.     

Effect of Varicocele on Sperm Respiration and Metabolism

Semen samples from 41 infertile male patients (30 with varicocele and 11 controls) were examined, lactic and pyruvic acids were measured and the oxygen consumption was determined. Decreased sperm count, diminished motility, decreased lactic acid concentration and oxygen consumption were noticed among the varicocele patients as compared to controls. Pyruvic acid concentration was slightly increased in the varicocele group. It was concluded that a decrease in lactic dehydrogenase activity may be one of the abnormalities in the semen of varicocele patients.
Einfluß der Varikocele auf die Atmung und den Stoffwechsel der Spermatozoen

Zusammenfassung

In einer experimentellen Arbeit wurden die Spermaproben von 41 unfruchtbaren Männern (30 × Varikocele, 11 Kontrollen) hinsichtlich des Sauerstoffverbrauches der Spermatozoen sowie des Gehaltes an Milchsäure und Pyruvat im Sperma untersucht. Bei den Vari-kocele-Patienten fanden sich herabgesetzte Spermatozoendichte, verminderte Motilität sowie herabgesetzte Milchsäurekonzentration und verminderter Sauerstoffverbrauch. Pyruvat war in der Varkocele-Gruppe geringgradig erhöht. Es wird festgestellt, daß möglicherweise eine herabgesetzte Milchsäure-dehydrogenase-Aktivität eine der Abnormitäten im Sperma von Männern mit Varikocele ist.     

Long-Term, Pulsatile, Low Dose, Subcutaneous Luteinizing Hormone-Releasing Hormone Administration in Men with Idiopathic Oligozoospermia Failure of Therapeutic and Hormonal Response

In four normal men with a history of long standing infertility, severely disturbed sperm qualities (determined in at least three spermiograms), normal serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels (measured over a time period of 90 minutes), and lack of evidence of further andrological or other obvious endocrine disorders the effectiveness of luteinizing hormone-releasing hormone (LH-RH) treatment was investigated. LH-RH was administered subcutaneously with a portable, comterized infusion pump (Zyclomat) for 3 months, with administration intervals of 90 minutes and bolus dosages of 5 micrograms (three patients) and 20 micrograms (one patient). Semen qualities during and after LH-RH treatment, as compared to pretreatment values, showed no improvement in volume of ejaculate, number of sperms per milliliter and motility. During or at the end of the treatment period no evident differences were observed in serum LH, FSH and testosterone levels (measured over a 90 minutes period) compared with hormonal values before LH-RH therapy, nor at the low-dose (5 micrograms) neither at the high-dose (20 micrograms) administration schedule. It is concluded that pulsatile subcutaneous LH-RH treatment in normogonadotropic, oligozoospermic men does not seem to improve the therapeutical arsenal.     

精索静脉曲张对精子染色质结构及运动能力的影响

目的:探讨精索静脉曲张对精子染色质结构及运动能力的影响。方法:对精索静脉曲张组(无慢性疾病及生殖系统病史者,n=74)和对照组(n=89)进行精子染色质结构分析(SCSA)和精液常规分析(精液量、粘稠度、pH值、精子顶体完整率、精子存活率、畸形率、精子密度、活动率及各运动参数)。结果:精索静脉曲张组精子密度、a+b级精子百分率和精子存活率[分别为(41.4±38.7)×106/ml,(31.7±16.9)%,(62.8±22.2)%]显著低于对照组[分别为(80.9±63.1)×106/ml,(46.8±20.5)%,(77.2±17.5)%],P均<0.05;精子运动参数VCL、VSL、VAP精索静脉曲张组分别为(37.4±12.5)、(23.4±7.8)、(26.5±8.2)μm/s,对照组分别为(42.4±10.7)、(27.3±7.3)、(30.7±7.8)μm/s,精索静脉曲张组与对照组相比显著降低(P均<0.05),而MAD显著增加(P<0.01),SCSACOMPαt值精索静脉曲张组(为23.2±16.2)明显高于对照组(为14.1±11.8)(P<0.05)。结论:精索静脉曲张引起精子DNA损伤和精子运动能力的改变,可能是导致男性不育的主要原因之一。     

口服锌硒宝对少弱精子症患者精子质量的影响

目的 :探讨微量元素锌和硒对少弱精子症患者精子质量的影响。　方法 :34例少弱精子症患者口服锌硒宝 ,5片 /次 ,3次 /d ,连服 90d。每个月末行计算机辅助精液分析 (CASA)。　结果 :服用 6 0d和 90d后 ,患者的精子质量明显改善 ,显效 5例 (14 .7% ) ,有效 2 5例 (73.5 % ) ,无效 4例 (11.8% )。　结论 :补充锌和硒可明显改善少弱精子症患者的精子质量。