Medical treatment of male infertility

Although male factors contribute to approximately half of all cases of infertility, no specific cause can be found to explain the majority of abnormalities found in semen parameters. Specific and effective medical treatment is restricted to rare endocrine disorders. As a consequence, various empirical medical treatments are often used to treat idiopathic male infertility, with limited success. This review focuses on the rationale and current evidence on the efficacy of medical treatment of male infertility. Unless new studies provide high quality evidence in favour of medical treatment, assisted reproductive technologies will remain the mainstay of treatment of male infertility.     

Management of weight loss in obesity-associated male infertility: a spotlight on bariatric surgery

In recent years, there has been a paralleled increase between male obesity and infertility rates. Obesity is associated with impaired hypothalamic-pituitary-gonadal axis, aberrant semen parameters, and subfertility or infertility. Weight loss is strongly recommended for the management of obesity-associated infertility. Lifestyle modifications that include caloric restriction and increased physical activity have a short-lived impact. Bariatric surgery is a better and more durable weight loss alternative. Comprehensive information about the benefits of weight loss on obesity-associated male infertility following bariatric surgery is still emerging. In this review, we discuss the hormonal, physical and environmental mechanism contributing to obesity-associated infertility. We then assess weight loss approaches, which include lifestyle modification, medical and surgical approaches, that can improve fertility in obese men. This review focuses also on bariatric surgery for the management of obese men seeking fertility treatment. Anecdotal evidence suggesting that bariatric surgery can impair fertility is also discussed.     

Patterns of suffering and social interactions in infertile men: 12 months after unsuccessful treatment

Research shows that men diagnosed with male factor infertility experience more suffering than men with infertility due to other causes, and that it is socially unfavourable to be diagnosed with male factor infertility resulting in secrecy surrounding diagnosis, sometimes to the point that women take the blame for the couples' infertility. We investigated mental and physical health, support, and psychological and social stress in men (N = 256) prior to and after 12 months of unsuccessful treatment according to their diagnosis: unexplained, female factor, male factor, or mixed. Results suggest that men do not differ by diagnosis on any of the variables tested. When treatment was not successful, all men showed increased suffering in the form of decreased mental health, increased physical stress reactions, decreased social support, and increased negative social stress over time. These findings indicate that involuntary childlessness is difficult for all men, and is not dependent on with whom the cause lies. There was also a high level of agreement between couples and medical records on the cause of the couples' fertility arguing against the idea that women take the blame for male factor infertility.     

Management of male infertility

Male factor infertility is the commonest single reason for infertility in couples trying to have children. This article summarizes the aetiology, classification, and management of male factor infertility. The cause for male infertility can be broadly classified into pre-testicular, testicular and post testicular causes depending on the underlying pathology. A detailed history and examination are crucial alongside investigations to delineate the cause. The management for male infertility varies depending on the cause of male infertility. Treatment includes lifestyle modifications, medical management, surgical management, and surgical sperm retrieval followed by assisted reproduction.     

A preclinical evaluation of pronuclear formation by microinjection of human spermatozoa into human oocytes

In vitro fertilization (IVF) is recognized as an accepted treatment for male infertility. However, the fertilization rate is significantly lower than the fertilization rate of other IVF patient groups. Some male factor infertility patients still have a basic semen quality too poor for treatment by IVF. Microinjection of a spermatozoon directly into ooplasm has been recommended to assist fertilization in this subfertile population. This study found that oocytes from 5 of 11 patients microinjected with human spermatozoa demonstrated successful pronuclear formation and correlated with the incidence of pregnancy in these patients transferred with same-source oocytes inseminated by standard protocols. This initial evidence promotes the supposition of clinical feasibility of assisted fertilization by sperm microinjection.     

Patterns of suffering and social interactions in infertile men: 12 months after unsuccessful treatment

Research shows that men diagnosed with male factor infertility experience more suffering than men with infertility due to other causes, and that it is socially unfavourable to be diagnosed with male factor infertility resulting in secrecy surrounding diagnosis, sometimes to the point that women take the blame for the couples' infertility. We investigated mental and physical health, support, and psychological and social stress in men (N = 256) prior to and after 12 months of unsuccessful treatment according to their diagnosis: unexplained, female factor, male factor, or mixed. Results suggest that men do not differ by diagnosis on any of the variables tested. When treatment was not successful, all men showed increased suffering in the form of decreased mental health, increased physical stress reactions, decreased social support, and increased negative social stress over time. These findings indicate that involuntary childlessness is difficult for all men, and is not dependent on with whom the cause lies. There was also a high level of agreement between couples and medical records on the cause of the couples' fertility arguing against the idea that women take the blame for male factor infertility.     

Role of antioxidants in treatment of male infertility: an overview of the literature

Seminal oxidative stress in the male reproductive tract is known to result in peroxidative damage of the sperm plasma membrane and loss of its DNA integrity. Normally, a balance exists between concentrations of reactive oxygen species and antioxidant scavenging systems. One of the rational strategies to counteract the oxidative stress is to increase the scavenging capacity of seminal plasma. Numerous studies have evaluated the efficacy of antioxidants in male infertility. In this review, the results of different studies conducted have been analysed, and the evidence available to date is provided. It was found that although many clinical trials have demonstrated the beneficial effects of antioxidants in selected cases of male infertility, some studies failed to demonstrate the same benefit. The majority of the studies suffer from a lack of placebo-controlled, double-blind design, making it difficult to reach a definite conclusion. In addition, investigators have used different antioxidants in different combinations and dosages for varying durations. Pregnancy, the most relevant outcome parameter of fertility, was reported in only a few studies. Most studies failed to examine the effect of antioxidants on a specific group of infertile patients with high oxidative stress. Multicentre, double-blind studies with statistically accepted sample size are still needed to provide conclusive evidence on the benefit of antioxidants as a treatment modality for patients with male infertility.     

The role of intrauterine insemination in male infertility

Male infertility is a common condition and intrauterine insemination (IUI) is used to treat the mild to moderate forms. Male subfertility determination is usually based on routine semen analysis but recent publications have questioned its diagnostic and prognostic accuracy as well as the effectiveness of IUI itself, as a treatment modality. We carried out a structured review of the literature to assess the current evidence regarding the diagnosis of male infertility, the effectiveness and cost effectiveness of IUI in male infertility and factors that affect the outcome of IUI. There is still uncertainty regarding the criteria for diagnosing male infertility and predicting treatment outcome based on standard semen parameters. The presence of seminal defects compromises the outcome of IUI in comparison with unexplained infertility. The total motile sperm count (TMSC) appears to have a consistent, direct relationship with treatment outcome, but there is no definite predictive threshold for success. However, it is reasonable to offer IUI as first-line treatment if TMSC is greater than 10 million when balancing the risk and cost of alternate treatments, such as in vitro fertilization (IVF). Sperm DNA studies and sperm preparation techniques warrant further studies in order to establish their clinical relevance. There are limited data on the clinical and cost-effectiveness of IUI in male infertility and large high-quality randomized controlled trials are warranted. However the difficulties in organizing such a study, at the present time, are a matter for discussion.     

The role of intrauterine insemination in male infertility

Male infertility is a common condition and intrauterine insemination (IUI) is used to treat the mild to moderate forms. Male subfertility determination is usually based on routine semen analysis but recent publications have questioned its diagnostic and prognostic accuracy as well as the effectiveness of IUI itself, as a treatment modality. We carried out a structured review of the literature to assess the current evidence regarding the diagnosis of male infertility, the effectiveness and cost effectiveness of IUI in male infertility and factors that affect the outcome of IUI. There is still uncertainty regarding the criteria for diagnosing male infertility and predicting treatment outcome based on standard semen parameters. The presence of seminal defects compromises the outcome of IUI in comparison with unexplained infertility. The total motile sperm count (TMSC) appears to have a consistent, direct relationship with treatment outcome, but there is no definite predictive threshold for success. However, it is reasonable to offer IUI as first-line treatment if TMSC is greater than 10 million when balancing the risk and cost of alternate treatments, such as in vitro fertilization (IVF). Sperm DNA studies and sperm preparation techniques warrant further studies in order to establish their clinical relevance. There are limited data on the clinical and cost-effectiveness of IUI in male infertility and large high-quality randomized controlled trials are warranted. However the difficulties in organizing such a study, at the present time, are a matter for discussion.     

Endometriosis related infertility

From the literature, the crucial knowledge were drawn among endometriosis related infertility. Endometriosis is an important factor of infertility in minimal or light stages and a major one in mild or moderate stages. Thus, a laparoscopy must be performed to confirm endometriosis when suggestive clinical or biological signs exist. In absence of them, laparoscopy can be delayed after intra-uterine inseminations (IUI). The first line treatment is laparoscopic surgery. Its efficacy is proven. It is useless to prescribe a post-operative medical treatment (GnRH analogues). Surgery leads to 25 to 40% of deliveries. It is dependant on age, infertility duration, tubo-ovarian adhesion and tubes involvement. But, surgery can be avoided and the patient is directly referred to In Vitro Fertilization (IVF) when the lesions extension is so important that surgery exposes to complications or when there is a permanent other indication for IVF (severe male infertility). When infertility persists 6 to 12 months after surgery and without patent recurrence, ovulation stimulations and IUI are performed as the second line treatment. After IUI failure, or in case of recurrence, IVF must be applied. A second surgery is not recommended. The IVF results are not impaired by the presence of endometriosis and even of endometriomas. Thus, it is useless to operate again endometriosis before IVF. In opposition, in severe stages or in cases of recurrence, a pre-IVF medical treatment (GnRH analogues) improves the results. IVF do not increased the risk of endometriosis acute growth. In case of infertility and pain, infertility is considered as the first target. But medical treatment can be prescribed between the IVF attempts.     

Influence of age, diagnosis, and cycle number on pregnancy rates with gonadotropin-induced controlled ovarian hyperstimulation and intrauterine insemination.

OBJECTIVE: To determine whether age, diagnosis, and cycle number influence cycle fecundity associated with gonadotropin-induced controlled ovarian hyperstimulation/IUI. DESIGN: Retrospective analysis. SETTING: The Center for Reproductive Medicine at the Brigham and Women's Hospital, a tertiary care academic medical center. PATIENT(S): Two hundred seventy-four women who underwent controlled ovarian hyperstimulation with gonadotropins and IUI. INTERVENTION(S): Infertility treatment with gonadotropins and IUI. MAIN OUTCOME MEASURE(S): Pregnancy rates according to patient age, infertility diagnosis, and number of treatment cycles. RESULT(S): Pregnancy rates decreased with increasing patient age. The cumulative pregnancy rates varied greatly by diagnosis from 13% for patients with male factor infertility to 84% for patients with ovulatory factor infertility. Average cycle fecundity was considerably less varied by diagnosis. All pregnancies among patients with male factor infertility and tubal factor infertility were achieved during the first two cycles. CONCLUSION(S): There is a clear age-related decline in fecundity associated with gonadotropin-induced controlled ovarian hyperstimulation/IUI. Patients <40 years of age and those with male factor infertility or tubal factor infertility have a particularly poor prognosis.     

Infertilit?t des Mannes

The reasons for male infertility can be endocrine, testicular and/or exogenous in origin. In depth diagnostic techniques aim to detect treatable causes and should include a review of the medical history, clinical and sonographical examinations, endocrinological tests and ejaculate analyses. If no medical or surgical treatment is applicable, methods of assisted reproductive fertilisation may be advisable depending on the female reproductive functions. Semen analysis gives details on sperm count, motility and morphology as well as infections, immunological factors and problems of the seminal ducts. Approximately 12% of patients are azoospermic. This severe form of male infertility mostly results from genetic disorders, and the most common numerical chromosomal disorder is Klinefelter??s syndrome. In cases of non-obstructive azoospermia testicular sperm extraction offers the chance for intracytoplasmic sperm injection in 50% of patients. In cases of obstructive azoospermia microsurgical reconstruction procedures are preferable to testicular sperm extraction.     

Evaluation and management of women with endometriosis

Endometriosis is a condition that often leads to a variety of symptoms that range from pain complaints to infertility. Endometriosis is also found in women who are asymptomatic. The diagnosis of endometriosis can be made clinically with reliability similar to that of one made surgically. Medical treatment options are effective, as are surgical treatment options. Complications associated with surgery, however, push the balance in favor of medical therapy whenever possible. Based on the body of evidence available at present, women with endometriosis-related complaints should be treated with a first-line medical therapy. If that fails, a second-line medical therapy is warranted under most conditions. Laparoscopic surgery should be reserved for patients in whom second-line medical therapy has failed or is contraindicated by desire to conceive immediately or as soon as possible.     

Stem cell therapeutic possibilities: future therapeutic options for male-factor and female-factor infertility?

Recent advances in assisted reproduction treatment have enabled some couples with severe infertility issues to conceive, but the methods are not successful in all cases. Notwithstanding the significant financial burden of assisted reproduction treatment, the emotional scars from an inability to conceive a child enacts a greater toll on affected couples. While methods have circumvented some root causes for male and female infertility, often the underlying causes cannot be treated, thus true cures for restoring a patient’s fertility are limited. Furthermore, the procedures are only available if the affected patients are able to produce gametes. Patients rendered sterile by medical interventions, exposure to toxicants or genetic causes are unable to utilize assisted reproduction to conceive a child – and often resort to donors, where permitted. Stem cells represent a future potential avenue for allowing these sterile patients to produce offspring. Advances in stem cell biology indicate that stem cell replacement therapies or in-vitro differentiation may be on the horizon to treat and could cure male and female infertility, although significant challenges need to be met before this technology can reach clinical practice. This article discusses these advances and describes the impact that these advances may have on treating infertility.Infertility is a condition that affects an estimated 15% of couples worldwide. Recent advances in assisted reproduction treatment have enabled some couples with severe infertility issues to conceive, but the methods are not successful for all cases. Notwithstanding the significant financial burden of assisted reproduction treatment, the emotional scars from an inability to conceive a child enacts a greater toll on affected couples. Stem cells represent a future potential avenue for allowing sterile patients to produce offspring. Advances in stem cell biology indicate that stem cell replacement therapies may be on the horizon to treat and possibly cure male and female infertility, although significant challenges need to be met before this technology can reach clinical practice. Here, we discuss these recent advances and describe the impact that these advances may have on treating infertility.     

Oxidative stress and medical antioxidant treatment in male infertility

Oxidative stress (OS) has been recognized as one of the most important cause of male infertility. Despite the antioxidant activity of seminal plasma, epididymis and spermatozoa, OS damages sperm function and DNA integrity. Since antioxidants suppress the action of reactive oxygen species, these compounds have been used in the medical treatment of male infertility or have been added to the culture medium during sperm separation techniques. Nevertheless, the efficacy of such a treatment has been reported to be very limited. This may relate to: (i) patient selection bias; (ii) late diagnosis of male infertility; (iii) lack of double-blind, placebo-controlled clinical trial; and/or (iv) use of end-points that are not good markers of the presence of OS. This review considers the effects of the main antioxidant compounds used in clinical practice. Overall, the data published suggest that no single antioxidant is able to enhance fertilizing capability in infertile men, whereas a combination of them seems to provide a better approach. Taking into account the pros and the cons of antioxidant treatment of male infertility, the potential advantages that it offers cannot be ignored. Therefore, antioxidant therapy should remain in the forefront of preventive medicine, including human reproductive medicine.     

Treatment of the infertile patient with polycystic ovarian syndrome

Polycystic ovarian syndrome is associated with infertility due to anovulation caused by this disorder. Many treatments can increase both ovulation and fertility rates in these women. This is a comprehensive review of the literature, with an emphasis on randomized controlled trials of the medical and surgical treatment options for women with polycystic ovarian syndrome and infertility. Both standard and novel treatments are addressed. In the past, clomiphene citrate was the first-line medical treatment for subfertility in these women, followed by gonadotropins with or without gonadotropin releasing-hormone agonists for those women with clomiphene-resistance. Surgical treatments such as ovarian drilling were occasionally added to these regimens. The introduction of the insulin-sensitizing agents as adjuvants to clomiphene citrate and gonadotropins has changed the treatment strategy. The evidence in support of this change will be discussed. Data on the use of glucocorticoids, opioid receptor antagonists, and antiandrogens as adjuvants to standard therapies, as well as surgical treatments such as wedge resection and ovarian drilling will also be discussed. Based upon the evidence, medical treatment remains the primary therapy for women with this syndrome, especially in light of the recent introduction of insulin-sensitizing agents to the treatment armamentarium. These drugs have allowed us to develop less aggressive therapies that are safer and easier for women to utilize, and may in the future become the primary treatment for women with this syndrome. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader will be able to explain the pathophysiology of PCOS, to list the factors that predispose women to develop PCOS, and to outline the treatment regiments for PCOS-associated infertility.     

Observation of spermatozoa by a high-magnification microscope

Semen analyses are the primary tool for evaluating male infertility, as semen parameters are useful for predicting potential fertility. In the field of assisted reproductive technology (ART), the single best motile spermatozoon should be selected, especially when performing intracytoplasmic sperm injection (ICSI). In this context, the motile sperm organelle morphology examination (MSOME) was developed as a method of assessing the detailed morphology of motile spermatozoa in real time at a magnification of up to 6,300× on a video system. The use of ICSI with MSOME-selected sperm is called intracytoplasmic morphologically selected sperm injection (IMSI). IMSI improves the outcomes of ICSI. MSOME can be also applied to evaluate male infertility. Among MSOME parameters, the presence of sperm nuclear vacuoles is the most important finding. Large sperm nuclear vacuoles (LNV) are related not only to poor ART outcomes, but also to poor semen quality and sperm DNA damage, such as DNA fragmentation and chromatin condensation failure. It has been suggested that sperm head vacuoles are produced at earlier stages of sperm maturation. It is possible that the number of LNV can be decreased by surgical or medical treatment for male infertility. Therefore, the level of LNV has the potential to be used as an alternative parameter of semen quality and a new tool for evaluating the therapeutic effects of treatment in male patients with infertility.     

Impact of infertility and infertility treatments on quality of life and levels of anxiety and depression in women undergoing in vitro fertilization

Abstract

This study aims to evaluate levels of anxiety and depression in women, correlated with infertility per se and with infertility treatments, highlighting predictors of higher levels of distress. Two validated standardized questionnaires, the Hospital Anxiety and Depression Scale (HADS) and the Fertility Quality of Life (FertiQoL), were administered to 89 women both before their first cycle of infertility treatment and again at the end of the ovarian stimulation for in vitro fertilization (IVF). Women's levels of anxiety were significantly higher before the treatment than during the treatment itself. Stratifying the women in three groups based on principal cause of infertility (male infertility, female infertility, or both male and female), we found significantly higher levels of anxiety and general distress in patients under treatment for female infertility. Higher anxiety levels in our sample before the treatment are probably an effect of not knowing what they are expected to do to solve their problem. Moreover, when the cause of infertility is exclusively female, women experience higher levels of anxiety and general distress both before and during the treatment, probably correlated to a sense of guilt. These data help the treating physician to better counsel patients and to provide a more focused psychological support.     

热休克蛋白和男性不育

热休克蛋白主要作用是参与应激反应和作为细胞管家蛋白。作为后者 ,多种热休克蛋白参与了精子发生过程和男性不育的病理发生过程 ,其所引起男性不育的机理各不相同。深入研究热休克蛋白与男性不育之间的关系 ,将有助于加深我们对男性不育发病机理的认识 ,从而提高治疗效果