Contribution of the male factor to unexplained infertility: a review

The more exhaustive the evaluation of couples with unexplained infertility, the more likely is the opportunity for detecting the aetiological factor responsible for infertility. Transport of spermatozoa through the upper genital tract and their ability to fertilize the oocyte are two obscure areas for the conventional evaluation of infertility. Although research in the former area is limited, there is indirect evidence that impaired sperm transport could be one of the causes of infertility in some couples with otherwise unexplained infertility. On the other hand, the availability of sperm function tests and the correlation of their results with in-vitro fertilization rates have allowed the detection of a previously hidden male factor in couples with unexplained infertility. It has been demonstrated that couples suffering unexplained infertility have significantly lower in-vitro fertilization rates in comparison with patients with tubal problems. These results can be explained because several case control studies in patients with unexplained infertility have reported defects in capacitation and sperm motion characteristics, binding of the spermatozoa to the zona pellucida, acrosome reaction, acrosin activity of the spermatozoa, and the ability of the spermatozoa to penetrate zona-free hamster cocytes. These observations suggest that methods for assessing the fertilizing capacity of the spermatozoa have to be incorporated in the evaluation of couples with unexplained infertility in order to amplify the scope of the workup and to better decide the appropiate treatment for these couples.     

AZF与男性不育研究进展

AZF微缺失的发生率在1%～55%之间不等。AZF基因缺失与严重的生精功能障碍密切相关,是最常见的导致严重少弱精子症和无精子症的分子遗传学因素。对AZF及其相关基因的研究,可从分子水平阐明精子发生障碍的机制,对男性不育症的诊断、治疗及预后判断具有非常重要的意义。本文综述了AZF基因结构和功能特点,及其与男性不育、隐睾、精索静脉曲张、Klinefelter综合征、精原细胞瘤、习惯性流产等之间的关系。     

不明原因不孕症诊断与治疗中国专家共识

有规律、未避孕的性生活1年以上,通过不孕症常规诊断评估仍未能发现明显不孕原因可诊断为不明原因不孕症(UI)。UI是一种生育能力低下的状态,属于排除性诊断。目前我国生殖医学界对UI的诊断标准与治疗策略仍存在争议,国内尚无关于UI诊断与治疗的专家共识和临床指南。亟需应用循证医学的方法制定关于UI诊断与治疗的共识用于指导临床实践,帮助医师充分了解UI的临床特点、诊断标准,做出全面合理的诊疗策略。     

Medical treatment of male infertility

After an appropriate clinical and laboratory assessment of a patient's fertility status, the clinician must often decide whether specific and empiric treatment is indicated. Specific treatment may take the form of replacement therapy (exogenous gonadotropins or GnRH) for pituitary or hypothalamic failure, inhibition of prolactin secretion, antimicrobial therapy, or immunosuppressive therapy for demonstrable immunologic infertility. Finally, ejaculatory dysfunction often requires sympathomimetic agents. Alternatively, in the normogonadotropic oligospermic patient, the major form of empiric therapy relies on the enhancement of physiologic hormone levels that influence spermatogenesis. Such "stimulation" therapy may be achieved by GnRH analogues, antiestrogens, exogenous gonadotropins, or androgens.     

Medical treatment of male infertility

The majority of male infertility is idiopathic. However, there are multiple known causes of male infertility, and some of these causes can be treated medically with high success rates. In cases of idiopathic or genetic causes of male infertility, medical management is typically empirical; in most instances medical therapy represents off-label use that is not specifically approved by the FDA. Understanding the hypothalamic-pituitary-gonadal (HPG) axis and the effect of estrogen excess is critical for the assessment and treatment of male infertility. The use of certain medical treatment has been associated with an increase in sperm production or motility, and primarily focuses on optimizing testosterone (T) production from the Leydig cells, increasing follicle-stimulating hormone (FSH) levels to stimulate Sertoli cells and spermatogenesis, and normalizing the T to estrogen ratio.     

A translational medicine appraisal of specialized andrology testing in unexplained male infertility

The diagnostic and prognostic validity of sperm function biomarkers is particularly relevant for males with unexplained infertility in which routine semen analysis fails to detect subcellular sperm dysfunctions. In this general review, we examine the role and significance of specialized andrology laboratory tests from past to present and provide a glance toward the future. We concluded that the assessment of sperm DNA damage and oxidative stress provide a relatively independent measure of fertility that yields diagnostic and prognostic information complementary to, but distinct and more significant than, standard sperm parameters. Since none of the available methods for such testing have been fully translated, further research is necessary to evaluate their cost-effectiveness when applied in large scale to daily medical practice. Application of translational medicine concepts would also be useful to accelerate the clinical application of recent discoveries in the fields of genomics, proteomics and metabolomics.     

Fibronectin levels in male ejaculate and evidence for its role in unexplained infertility

Vasovasostomy has become a popular and highly successful method of restoring fertility to those who have undergone a vasectomy. However, there is a high correlation between vasostomy and antisperm antibody production leading to spontaneous sperm agglutination and immobilization. There is still considerable disagreement on whether antibodies are the primary causative agent. Our study provides evidence that fibronectin, a ubiquitous glycoprotein whose major function is cell-to-cell adhesion, could be a "subfertility" factor and contribute to male "unexplained infertility." Semen from control, random, and vasovasostomy populations was studied using a sophisticated enzyme-linked immunosorbent assay (ELISA). The results show that fibronectin is significantly present in all groups. The mean concentrations (micrograms/mL) were 753.9 for control, 566.4 for random, followed by significantly higher 1267.3 for the vasovasostomy group (p less than 0.05). The spermatozoa were assayed for bound fibronectin by flow cytometry. The mean percentage of cells bound after background subtract was 29.7 for control and 48.2 for the vasovasostomy group; the difference was significant (p less than 0.05). We conclude that fibronectin is present in semen and bound to sperm cells in great concentrations for individuals having undergone surgical insult and may contribute to male infertility particularly by sperm agglutination.     

The surgical treatment of male infertility

Experience with the examination and treatment of 162 patients with excretory (79) and secretory (83) forms of male infertility is analysed. With regard for the data of spermography, biopsy of a testicle, the results of surgical treatment of the patients with the use of microvascular technique were evaluated. Microsurgical correction of different forms of male infertility has the best prospects.     

Varicocele and male factor infertility treatment: a new meta-analysis and review of the role of varicocele repair

Context

Varicocele is a common condition, found in many men who present for infertility evaluation.

Objective

To assess the effect of varicocelectomy on male infertility.

Evidence acquisition

A literature search was performed using Embase and Medline. Literature reviewed included meta-analyses and randomized and nonrandomized prospective (controlled and noncontrolled) studies. In addition, a new meta-analysis was performed.

Evidence synthesis

Four randomized controlled trials reporting on pregnancy outcome after repair of clinical varicoceles in oligozoospermic men were identified. Using the random effect model, the combined odds ratio was 2.23 (95% confidence interval [CI], 0.86-5.78; p = 0.091), indicating that varicocelectomy is moderately superior to observation, but the effect is not statistically significant. We identified 22, 17, and 5 prospective studies reporting on sperm concentration, total motility, and progressive motility, respectively, before and after repair of clinical varicocele. The random effect model combined improvement in sperm concentration was 12.32 million sperm per milliliter (95% CI, 9.45-15.19; p < 0.0001). The random effect model combined improvement in sperm total and progressive motility were 10.86% (95% CI, 7.07-14.65; p < 0.0001) and 9.69% (95% CI, 4.86-14.52; p = 0.003), respectively. These results indicate that varicocelectomy is associated with a significant increase in sperm concentration as well as total and progressive motility. Prospective studies also show that varicocelectomy reduces seminal oxidative stress and sperm DNA damage as well as improving sperm ultramorphology. Studies indicate that a microsurgical approach to a varicocele repair results in less recurrence and fewer complications than other techniques.

Conclusions

Although there is no conclusive evidence that a varicocele repair improves spontaneous pregnancy rates, varicocelectomy improves sperm parameters (count and total and progressive motility), reduces sperm DNA damage and seminal oxidative stress, and improves sperm ultramorphology. The various methods of repair are all viable options, but microsurgical repair seems to be associated with better outcomes.     

Evaluation of the immunological cause of male infertility

Summary. The presence of antisperm antibodies was considered as one of the main causes of maleinfertility. This study was conducted on 776 semen samples of the male partners of infertile couples in order to evaluate the immunological factor. The detection of antisperm antibodies was performed by means of the direct Mixed Antiglobulin Reaction (MAR) test. A positive test was found in 35 samples. Hence, the prevalence of immunological infertility in this study is 4.5% among the male partners of infertile couples. Further explorations were performed on men with positive results, in order to detect the presence of antibodies in the sera by means of the indirect MAR tests, and sperm immobilization tests for quantitating the cytotoxic activity of the antibodies. The indirect MAR tests showed that 97% of the antibodies were present in sera, whereas 51% of the samples were cytotoxic. Routine semen analysis indicated that around 60% of the semen samples with antisperm antibodies were good. Semen culture showed that positive results were detected in 40% of samples. Clinical evaluations revealed that the presence of antisperm antibodies may have been the cause of long-standing infertility, on average 5 years, and were not all primary. Evaluations of all clinical and laboratory findings indicated that unilateral testis obstruction and male accessory gland infection were the main pathologies found.     

Sperm chromosome aneuploidy as related to male factor infertility and some ultrastructure defects

Some men have elevated levels of sperm chromosome aneuploidy. In this study, we have evaluated and summarized sperm aneuploidy rates in male infertility patients and control groups. The mean aneuploidy rate for five chromosomes (X, Y, 13, 18, 21) was 1.2 +/- 0.1 for fertile controls, 1.4 +/- 0.1 for a general population control group, and 5.8 +/- 1.14 for the patients. When the patients were classified by the type of male factor infertility, the total aneuploidy rate was 2.6 +/- 0.3 in men with moderately diminished semen quality (n = 7), 4.0 +/- 0.3 patients with severe teratoasthenooligozoospermia, and 15.9 +/- 3.8 for men with rare ultrastructure defects such as round head only syndrome or severe tail agenesis. Some infertility patients have a severely elevated level of sperm chromosome aneuploidy, which may contribute to infertility or diminish the likelihood of a successful outcome from IVF/ICSI. The severity of sperm chromosome aneuploidy appears to be proportional to the severity of abnormal semen quality: in particular, abnormal morphology. The high rates of aneuploidy in patients with severe ultrastructure defects suggest that caution should be employed in counseling those patients prior to IVF/ICSI.     

代谢组学在男性不育诊疗中的应用研究

代谢组学是研究生物体内源性小分子代谢物的新兴学科。代谢组学通过对体液、细胞及组织的研究,在男性不育疗效评价中发挥着重要作用。这种高信息量、无创、快速的研究技术进入临床应用将成为未来的发展趋势。本文介绍了代谢组学及其分析技术和数据处理过程,并介绍了代谢组学对男性不育有害物质暴露、生物标志物和药物治疗等的研究,对其在男性不育病因探究和诊疗中的最新研究进展进行了综述,最后提出代谢组学在男性生殖领域的研究前景。