Molecular insights into the causes of male infertility

Infertility is a reproductive health problem that affects many couples in the human population. About 13–18% of couple suffers from it and approximately one-half of all cases can be traced to either partner. Regardless of whether it is primary or secondary infertility, affected couples suffer from enormous emotional and psychological trauma and it can constitute a major life crisis in the social context. Many cases of idiopathic infertility have a genetic or molecular basis. The knowledge of the molecular genetics of male infertility is developing rapidly, new “spermatogenic genes” are being discovered and molecular diagnostic approaches (DNA chips) established. This will immensely help diagnostic and therapeutic approaches to alleviate human infertility. The present review provides an overview of the causes of human infertility, particularly the molecular basis of male infertility and its implications for clinical practice.     

男性不育症和Galntl5基因突变位点的相关性

目的:探讨男性不育症患者Galntl55基因的一个突变位点与男性不育症的关系及意义。方法:运用聚合酶链反应(PCR)结合琼脂糖凝胶电泳和基因序列分析等方法,对119例原发性男性不育症患者以及135名已生育的正常男性进行Galntl5基因筛查。结果:与精子形成相关的关键基因GALNTL5中1个突变位点G323A和男性不育症存在一定相关性。因此Galntl5基因蛋白质编码序列区G323A可能是特发性少精症无精症的诱发因素之一。临床上对原发性不孕不育患者进行GALNTL5基因突变筛查是十分必要。     

Obstructions des canaux éjaculateurs: diagnostic et traitements

The management of male factor infertility has been frustrated by the large group of men with idiopathic infertility in whom treatment options have been limited to either empiric medical thrapy,orassisted reproductive technologies or donor insemination. Therefore, the identification of reversible causes of infertility in these patients is extremely attractive to couples and physicians. Recent reports suggest that partial ejaculatory duct obstruction may be responsible for infertility in some men previously labelled as having idiopathic infertility. Complete ejaculatory duct obstruction is suspected in azoospermic or severely oligospermic patients with low ejaculate volume (less than 1 ml), absence of sperm from the post-ejaculatory urine, normal endocrine studies and normal testis size. Demonstration of dilatation of the seminal vesicles and/or ejaculatory ducts by transrectal ultrasonography is diagnostic of ejaculatory duct obstruction in patients with the afore-mentioned clinical features. However, in the absence of definitive transrectal ultrasonography findings, vasography remains the gold standard for the diagnosis of ejaculatory duct obstruction. Ejaculatory duct obstruction is diagnosed in approximately 5% of azoospermic infertile men and is treated by transurethral incision of the ducts. After the surgical procedure semen parameters can improve and pregnancies have been initiated. Although, the patient must be informed that surgical therapy can also fail and can be associated with significant complications.     

The role of oocyte in the genetic determinations of fertility and infertility

Oocyte specific genes play important role in the foliculogenesis, ovulation, fertilization and early embryogenesis. It is suggested that 17-20% of infertility in both sex has idiopathic aspect. This kind of infertility is mainly associated with genetic background. The study on the role of oocyte specific genes can help in our understanding of the causes of idiopathic infertility.     

Should Seminal Oxidative Stress Measurement be Offered Routinely to Men Presenting for Infertility Evaluation?

ObjectiveTo determine if seminal oxidative stress measurement should be offered routinely to men presenting for infertility evaluation.MethodsWe performed an extensive review of the English-language literature by searching MEDLINE for studies published between 1980 and 2007.ResultsResearch conducted during the last decade has provided growing support for the concept that excessive production of reactive oxygen species (ROS) is related to abnormal semen parameters and sperm damage. Routine semen analysis remains the backbone of clinical evaluation in male infertility, but determining the levels and sources of excessive ROS generation in semen is currently not included in the routine evaluation of subfertile men. However, the diagnostic and prognostic capabilities of seminal oxidative stress measurement exceed the capabilities of conventional sperm quality tests. An oxidative stress test may accurately discriminate between fertile and infertile men and identify those with a clinical diagnosis of male factor infertility who are likely to initiate a pregnancy if they are followed over a period of time. In addition, such a test can help select subgroups of patients with infertility in which oxidative stress is an important factor and those who may benefit from antioxidant supplementation. Although consensus is still required about the type and dosage of antioxidants to be used, rationale and evidence exist supporting their use in infertile men with elevated oxidative stress.ConclusionConsensus is growing about the clinical utility of seminal oxidative stress testing in infertility clinics, but standardization of protocols to measure ROS is crucial before introducing these tests into routine clinical practice. (Endocr Pract. 2008;14:484-491)     

宫腔镜联合腹腔镜在女性不孕症诊治中的应用

摘要目的：探讨宫腔镜联合腹腔镜在女性不孕诊断及治疗中的临床应用价值。方法：回顾性分析60 例我院收治的采用宫腔镜联 合腹腔镜进行诊断和治疗的女性不孕症患者为研究对象,对其临床资料进行分析。结果：宫腔镜联合腹腔镜检查发现,60 例不孕 症患者中,56.7 %的患者患有慢性盆腔炎,16.7 %的患者为子宫内膜异位症,11.7 %的患者为多囊卵巢综合征;单纯腹腔镜检查的 阳性检出率为60.0 %,单纯宫腔镜检查的阳性检出率为28.3 %,宫腔镜联合腹腔镜检查的阳性检出率高达91.7 %,宫腔镜联合腹 腔镜镜检阳性发现率明显高于前二者(P < 0.05)。治疗前,双侧不通、一侧通畅和双侧输卵管通畅的患者分别为38.3 %、48.3 %和 13.3 %,经宫腔镜联合腹腔镜治疗后分别为11.7 %、50.0 %和38.3 %,差异均有统计学意义(P<0.05)。34 例原发性不孕患者,术后 13例妊娠,妊娠率38.2 %;26 例继发性不孕患者,术后15 例妊娠,妊娠率57.7 %;总妊娠率为46.7 %,其中宫外孕2例。结论：宫 腔镜联合腹腔镜检查可帮助明确女性不孕症患者明确原因及发病部位,并可针对病因进行治疗,提高女性不孕症的病因诊断准 确率及治愈率。     

宫腔镜联合腹腔镜在女性不孕症诊治中的应用

目的：探讨宫腔镜联合腹腔镜在女性不孕诊断及治疗中的临床应用价值。方法：回顾性分析60例我院收治的采用宫腔镜联合腹腔镜进行诊断和治疗的女性不孕症患者为研究对象,对其临床资料进行分析。结果：宫腔镜联合腹腔镜检查发现,60例不孕症患者中,56．7％的患者患有慢性盆腔炎,16．7％的患者为子宫内膜异位症,11．7％的患者为多囊卵巢综合征;单纯腹腔镜检查的阳性检出率为60．0％,单纯宫腔镜检查的阳性检出率为28．3％,宫腔镜联合腹腔镜检查的阳性检出率高达91．7％,宫腔镜联合腹腔镜镜栓阳性发现率明显高于前二者（P〈0．05）。治疗前,双侧不通、一侧通畅和双侧输卵管通畅的患者分别为38．3％、48．3％和13．3％,经宫腔镜联合腹腔镜治疗后分别为11．7％、50．o％和38．3％,差异均有统计学意义（P〈0．05）。34例原发性不孕患者,术后13例妊娠,妊娠率38．2％;26例继发性不孕患者,术后15例妊娠,妊娠率57．7％;总妊娠率为46．7％,其中宫外孕2例。结论：宫腔镜联合腹腔镜检查可帮助明确女性不孕症患者明确原因及发病部位,并可针对病因进行治疗,提高女性不孕症的病因诊断准确率及治愈率。     

Retentissement sexuel, conjugal et social d’une population d’hommes stériles consultants en Andrologie: le point de vue du psychiatre de liaison

Material and methods

The study population consisted of 39 subjects divided into two groups: 21 azoospermic males and 18 oligoazoospermic males. These men were selected in andrology departments over a period of six months. The andrology and liaison psychiatry departments of Lille university hospital established a general infertility questionnaire. This semi-structured questionnaire comprising 40 questions was based on clinical experience and describes the clinical and symptomatic context of infertility. An individual 50-item questionnaire was then used to analyse the psychosocial, marital and sexual effects of male infertility and the representation of the psychiatrist in the andrology department.

Results

One third of patients discovered the diagnosis of infertility when the biologist gave them the results of the semen analysis. Our patients initially envisaged marital, psychological and social problems, but very few sexual problems. They imagined that infertility was more disturbing for women than for men, from a psychological and sexual point of view. 82% of our subjects imagined that their partner had no sexual problems. 48.7% of them thought that their partner had no psychological difficulties related to their infertility. The oligoasthenospermia group considered that the partner had significantly more “psychological difficulties” compared to the azoospermia group. 41% of our patients felt guilty towards their partner because of their infertility diagnosis. 10.3% of patients presented sexual disorders before the diagnosis of male infertility and 25.6% presented sexual disorders after this diagnosis. Contrary to data in the literature, a major change of sexuality was not observed in the majority of the couples after the diagnosis. When sexuality changed, it generally consisted of a reduction of the frequency of sexual relations. Among the patients who reported sexual difficulties, only 40% related them to infertility. 50% did not report any relationship between the psychological difficulties related to infertility and the sexual difficulties. Contrary to the data in the literature, neither the loss of spontaneity during sexual relations, nor the complementary investigations necessary for artificial insemination had any influence on sexuality. 89.8% of our patients are ready to change their sexual practices in order to be more fertile without causing any sexual or psychological problems. However, only 34.3% of patients reported a concern about reproductive efficacy during sexual relations. A more marked sexuality/reproduction dissociation was observed in oligoazoospermic males than in azoospermic males. 28.2% of patients reported that talking about their sexual and/or psychological problems with a psychiatrist was helpful.

Conclusion

Many contradictions and underestimations were observed in the answers to the questions. We confirmed the existence of a psychological and sexual distress, but which was quantitatively less severe than that described in “gynaecological” populations. However, a real psychological and sexual distress does exist in our population, which is why we propose from the outset a psychosomatic and sexological treatment of infertility in order to prevent the onset of these sexual difficulties. Our questionnaire was based on clinical experience and helped our patients to identify their psychological and sexual difficulties related to infertility and its treatment. It would therefore be useful for the practitioner, andrologist or psychiatrist, to help the patient express the effects related to this “new medicalized sexuality”.     

Genetics of male infertility: the new players

Approximately 10-15% of couples experience infertility and male factors contribute to half of these cases. It was usually thought that infertility cannot be transmitted, but accumulating evidence indicates that many cases are indeed caused by genetic defects, some inherited. The use of single nucleotide polymorphisms (SNP) arrays allowing to genotype the totality of the genome recently led to identify several genes which, when mutated, generate specific infertility phenotypes. With the tremendous progresses in high throughput sequencing techniques, we can expect many more new genes involved in fertility to be identified in the next years. For the patients concerned, these findings mean the possibility of an accurate diagnosis and improved prognosis. Furthermore, these data will lead to a better understanding of the molecular mechanisms underlying spermatogenesis and thus should contribute to identify and offer new therapeutic strategies for the treatment of infertility.     

Centrosomal function assessment in human sperm using heterologous ICSI with rabbit eggs: a new male factor infertility assay

Sperm centrosomal function was assessed by immunocytochemical analysis after the injection of human sperm into mature rabbit eggs. Three hours after intracytoplasmic sperm injection (ICSI), an astral microtubule array from the base of the human sperm was observed in the rabbit eggs. This sperm aster expanded in the egg cytoplasm, concomitant with pronuclear formation, and a dense microtubule array was organized at the time of pronuclear centration. Using fertile donor sperm, the sperm aster formation rate at 3 hr after ICSI was 35.0 +/- 1.5%. Using sperm from infertile patients, the average aster formation rate was lower (25.4 +/- 14.8%, P<0.05). Among infertile cases, there was no correlation between sperm aster formation rates and conventional parameters of semen analysis. However, the sperm aster formation rate correlated with the embryonic cleavage rate following human in vitro fertilization (IVF). These data suggest that this assay reflects sperm function during embryonic development after sperm entry and that reproductive success during the first cell cycle requires a functional sperm centrosome. Furthermore, sperm centrosomal function cannot be predicted from conventional parameters of semen analysis. We propose that insufficient centrosomal function could be the cause of certain cases of idiopathic infertility. These assays may lead to the discovery of new types of infertility, which have previously been treated as "unexplained infertility," and may also lead to the treatment of infertility incurable even by ICSI. Consequently, an accurate and relevant assay to help assure couples of the success of fertilization is warranted, perhaps prior to ICSI therapy.     

Prevention de l’infertilite d’origine infectieuse chez l’adolescent

Some causes of infertility can be prevented, as is the case for infertility of infectious origin. Genital infections represent a major source of infertility. Prostato-epididymitis consecutive to an urinary infection can be prevented by identifying and treating prostatic localizations at an early stage of urinary infection. The prevention of sexually transmitted diseases (STD), which cause male and female infertility, is, at the moment, accomplished by the prevention of the sexual transmission of the HIV. Teenagers represent a target of choice for the educational campaigns promoting condom use. The role of physicians, especially when teenagers are asking for a contraception, must be complementary to the public health campaign to decrease the spread of HIV and other STDs.     

精索静脉曲张导致不孕机制及治疗分析

精索静脉曲张(VC)是男性尤其是生育期男性常见的一种泌尿生殖系统疾病。WHO已将VC作为引起男性不育的首要原因。但目前的研究仍然没有明确其发病机制,因此探讨精索静脉曲张致男性不育的机制具有重要意义。其发病机制虽不明确,但手术治疗可以明确改善VC患者的不孕状况。这个结论已在临床上得到了大多数学者的认可。     

Prevention de l’infertilite d’origine infectieuse chez l’adolescent

Some causes of infertility can be prevented, as is the case for infertility of infectious origin. Genital infections represent a major source of infertility. Prostato-epididymitis consecutive to an urinary infection can be prevented by identifying and treating prostatic localizations at an early stage of urinary infection. The prevention of sexually transmitted diseases (STD), which cause male and female infertility, is, at the moment, accomplished by the prevention of the sexual transmission of the HIV. Teenagers represent a target of choice for the educational campaigns promoting condom use. The role of physicians, especially when teenagers are asking for a contraception, must be complementary to the public health campaign to decrease the spread of HIV and other STDs.     

Hyperplasie surrénalienne par bloc en 21 hydroxylase: une cause rare d’hypofertilité masculine et de tumeur du testicule

The authors report the case of a 29-year-old man with bilateral testicular adrenal-like tumors in a context of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Inadequate suppression of ACTH secretion is a dominant etiological factor in the development of testicular masses in CAH. Destruction of the testicular tubules by the adrenal rests and longstanding suppression of the pituitary-gonadal axis can lead to infertility. The presence of testicular adrenal rests must be investigated in any man with CAH due to 21-hydroxylase deficiency and infertility. Similarly, it is important to investigate possible 21-hydroxylase deficiency in patients with bilateral testicular tumors.     

IVF and women's interests: an analysis of feminist concerns

Feminist objections to the new reproductive technologies are examined. The author argues that although these technologies entail significant risks and costs to women, help only a small minority, and do not address the underlying social causes of infertility, women's interests do not demand the rejection of research on and use of reproductive technologies. Their potential threat to female reproductive autonomy can be counteracted by protecting individual civil rights. Warren urges that women, as well as members of various racial, ethnic, and socioeconomic groups, be represented in decisions on reproductive technologies, participate in their development and funding, and supervise their provision.     

Epididymis as a target for contraception

Advantage of using a vaccine based on sperm antigens is that it can be used both in males and females as individuals who have antisperm antibodies are usually infertile but otherwise healthy. Several sperm specific antigens identified as prospective candidates for immunocontraception are of testicular origin. For the purpose of immunocontraception it may be desirable not to disrupt spermatogenesis and testicular function. Concept of post testicular maturation of spermatozoa has been very well established. During post testicular voyage spermatozoa undergo a series of complex and sequential events which transforms the immature immotile spermatozoa into mature sperm. Acquisition of functional maturity is necessary for progressive motility, zona pellucida recognition culminating in sperm egg binding. Importance of epididymal maturation is highlighted by the fact that high percentage of male infertility in human originates from the malfunction of the epididymis. The epididymis has also shown to be involved in sperm storage and provides an adequate environment for final maturation of the sperm. It provides a conducive microenvironment by virtue of which the spermatozoa are protected during the storage. In view of this it is imperative that more attention needs to be focused on epididymal antigens. The information obtained will enable us to identify epididymal antigens relevant to fertility and also help in infertility diagnosis.     

L’infertilité masculine: Nos connaissances ne doivent pas faire oublier notre ignorance

About 15% of couples worldwide are affected by reduced fertility. In 20% of cases of couple infertility, the problem can be predominantly attributed to the male. In 20% of cases, a genetic cause of male infertility can usually be identified. The main genetic causes are: autosomal and sex chromosomal abnormalities, microdeletions within regions of the Y-chromosome containing candidate gene families for spermatogenesis and mutations in theCFTR gene. However, despite enormous progress in the understanding of human reproductive physiology, the underlying cause of male infertility often cannot be elucidated. Candidate gene strategies, linkage analysis in large familial forms of male infertility, targeted mutagenesis in the mouse and studies of chromatin reorganization during spermatid maturation should provide rapid progress in our understanding of the genetic factors that contribute to male infertility, which may open up new approaches to the treatment of this condition.     

Experiencing infertility--social work dilemmas in child adoption procedures

The research deals with experiencing infertility and its consequences in the adoption of a child and focuses on infertile couples that have wished to adopt a child and joined a program preparing them to be foster parents. The results show that most of the infertile couples experience infertility very much as being different from couples with children as well as having to cope with the feelings of deep emotional loss resulting from the inability to reproduce biologically. There is therefore the question whether these facts should be taken into account by the profession (i.e. social workers) when dealing with child adoption as, according to most of the respondents of our survey, the process of coming to terms with infertility and its consequences is an important factor in establishing healthy family relationships and the child's identity within the adoptive family. We concluded from the results of the research that the infertile couples preparation program for adopting a child carried out by the Society of Adoptive Families "Deteljica", is a comprehensive autopoietic social workers' answer to the needs of participants for a successful adoption of a child, as it makes it possible to supply these future adoptive parents with the requisite information and experience and provides support to the entire family upon accepting a child in its midst, while its fundamental attribute is offering help to couples in overcoming the traumas resulting from their infertility.