Management of the infertile couple: an evidence-based protocol

Background

Infertility is defined as inability of a couple to conceive naturally after one year of regular unprotected sexual intercourse. It remains a major clinical and social problem, affecting perhaps one couple in six. Evaluation usually starts after 12 months; however it may be indicated earlier. The most common causes of infertility are: male factor such as sperm abnormalities, female factor such as ovulation dysfunction and tubal pathology, combined male and female factors and unexplained infertility.

Objectives

The aim of this study is to provide the healthcare professionals an evidence-based management protocol for infertile couples away from medical information overload.

Methods

A comprehensive review where the literature was searched for "Management of infertility and/or infertile couples" at library website of University of Bristol (MetaLib) by using a cross-search of different medical databases besides the relevant printed medical journals and periodicals. Guidelines and recommendations were retrieved from the best evidence reviews such as that from the American College of Obstetricians and Gynaecologists (ACOG), American Society for Reproductive Medicine (ASRM), Canadian Fertility and Andrology Society (CFAS), and Royal College of Obstetricians and Gynaecologists (RCOG).

Results

A simple guide for the clinicians to manage the infertile couples.

Conclusions

The study deploys a new strategy to translate the research findings and evidence-base recommendations into a simplified focused guide to be applied on routine daily practice. It is an approach to disseminate the recommended medical care for infertile couple to the practicing clinicians.

     

Profil spermiologique de l’époux dans les couples infertiles en milieu négro-africain au Sénégal

Objective

To define the role of male infertility in black African couples in Senegal and to establish the semen profile.

Material and Methods

We analysed 17,459 sperm counts and 5,563 post-coital tests from patients consulting for primary or secondary infertility between January 1982 and December 2002. Negative and deficient sperm counts of post-coital tests were studied to demonstrate the responsibility of male infertility. For sperm counts, we studied the patient’s age, the mode of semen collection, the volume of ejaculate and semen characteristics.

Results

Primary sterility (68.4%) was twice as frequent as secondary sterility (31.6%). Male infertility (31.7%) was twice as frequent as female infertility (14.7%). Twenty eight per cent of patients presented hypospermia. Isolated oligozoospermia was observed in 10% of cases and azoospermia was detected in 23% of cases. Qualitative sperm changes were observed in 44.3% of cases. A positive semen culture was reported in 21.3% of cases. Combinations (qualitative sperm changes and abnormalities of number) were observed in 43.4% of cases. Oligo-astheno-teratozoospermia (OATS) with spermatozoa with an elongated head, cytoplasmic remnants and angulation, characteristic of varicocele was significantly more frequent in patients with varicocele (97% of men with right varicocele and 98.2% of men with bilateral varicocele). Reactive epididymosemino-prostatic dystrophy was observed in 11.9% of cases

Conclusion

Male infertility plays a real role. The semen profile of the husband of a sterile couple in Senegal is characterized by the importance of polymorphic alterations such as oligo-astheno-teratospermia and secretory azoospermia.     

Etiologie des infertilités secondaires de l’homme

Introduction

Secondary infertility is defined as the inability to achieve a new pregnancy for a couple that has been able to procreate in the past.

Material and methods

Over a 16-year period, 49 patients consulted for male secondary infertility. Clinical, laboratory or ultrasound assessment demonstrated the cause of infertility.

Results

These patients had a mean age of 33.6 years (range: 26 to 44 years). These couples had an average of 1 living child per family, corresponding to a girl in two-thirds of cases and a boy in one-third. In these patients, infertility was due to the presence of varicocele in 15 patients (31% of cases), infection in 14 patients (29%), and varicocele associated with infection in 11 cases (22%).

Conclusion

This assessment revealed two main aetiologies, but some causes remain obvious, such as surgery with resection of the prostate or testicles, or certain cytotoxic therapies.     

Impact of pericentric inversion of Chromosome 9 [inv (9) (p11q12)] on infertility

BACKGROUND:

One of the frequent occurrences in chromosome rearrangements is pericentric inversion of the Chromosome 9; inv (9) (p11q12), which is consider to be the variant of normal karyotype. Although it seems not to correlate with abnormal phenotypes, there have been many controversial reports indicating that it may lead to abnormal clinical conditions such as infertility. The incidence is found to be about 1.98% in the general population.

MATERIALS AND METHODS:

We investigated the karyotypes of 300 infertile couples (600 individuals) being referred to our infertility clinic using standard GTG banding for karyotype preparation.

RESULTS:

The chromosomal analysis revealed a total of 15 (2.5%) inversions, among these, 14 male patients were inversion 9 carriers (4.69%) while one female patient was affected (0.33%). The incidence of inversion 9 in male patients is significantly higher than that of normal population and even than that of female patients (P< 0.05).

CONCLUSIONS:

This result suggests that inversion 9 may often cause infertility in men due to spermatogenic disturbances, which are arisen by the loops or acentric fragments formed in meiosis.     

The Use of In Vitro Fertilization in the Management of Male Infertility: What the Urologist Needs to Know

Infertility affects approximately 10% to 20% of reproductive-age couples, many of whom may present initially to a urologist. Some couples may be treated medically to increase spontaneous conception rates; however, many will require more aggressive management with in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI). IVF involves ovarian stimulation, oocyte retrieval, and fertilization outside of the body; ICSI involves injecting one sperm into the oocyte to promote fertilization. Here we provide a brief overview of IVF and ICSI along with a discussion of the risks involved to facilitate the counseling and care of the infertile couple.Key words: Intracytoplasmic sperm injection, Male infertilityInfertility, defined as the inability to conceive within 12 months of unprotected intercourse, affects approximately 10% to 20% of reproductive-age couples.¹ As couples defer childbearing until later ages and as the obesity epidemic grows, the incidence of infertility is likely to continue to rise.^2,3 Male factor infertility is estimated to contribute to two-thirds of all cases. Of men seeking care for infertility, 18.1% reported being diagnosed with male factor infertility and 13.7% with a sperm or semen problem.⁴The evaluation for male infertility includes a thorough history and physical examination, and the mainstay of diagnostic testing continues to be the semen analysis. If abnormalities are noted on semen analysis, further testing is warranted to evaluate for possible etiologies. Where applicable, treatment is initiated with the goal of improving semen quality and male fertility. Previously, in cases in which semen quality remained profoundly impaired, the successful treatment for male factor infertility was once limited to donor insemination.The development of in vitro fertilization (IVF) revolutionized the management of female infertility. As powerful a tool as this proved to be, however, IVF fertilization rates remained poor in the presence of compromised semen parameters. A significant breakthrough in the treatment of severe male infertility was the development of intracytoplasmic sperm injection (ICSI) in 1992.⁵ By allowing the injection of a single sperm into each oocyte, ICSI provides the possibility of genetic offspring to men who have very scant numbers of motile sperm on semen analysis or who require surgical harvesting.From its inception, assisted reproduction has involved a gynecologist and an embryologist. The urologist is a critical collaborator for the treatment of couples with male factor infertility. Sperm harvested by microsurgical epididymal sperm aspiration, testicular sperm aspiration, or biopsy can be used to fertilize harvested oocytes by ICSI. The urologist may be the first to evaluate a couple for infertility, and will certainly be involved if sperm harvesting is indicated. Therefore, this article reviews the process of assisted reproduction by IVF/ICSI for urologists who may be seeing patients with infertility issues.     

Evaluation of the leptin receptor in human spermatozoa

Background  

Leptin, a 167 amino acid peptide hormone, profoundly effects reproduction exerting its biological effects via interaction with the leptin receptor (ObR) which is widely expressed on peripheral tissues. In this study, we have attempted to assess leptin receptor expression in the spermatozoa of fertile males and those diagnosed with male factor infertility; both at the mRNA or protein levels.     

Lifestyle and fertility: the influence of stress and quality of life on male fertility

Background

Male infertility is a widespread condition among couples. In about 50% of cases, couple infertility is attributable to the male partner, mainly due to a failure in spermatogenesis. In recent times, the crucial role that modifiable lifestyle factors play in the development of infertility have generated a growing interest in this field of study, i.e. aging, psychological stress, nutrition, physical activity, caffeine, high scrotal temperature, hot water, mobile telephone use. Several studies have investigated associations between semen quality and the presence of lifestyle stressors i.e. occupational, life events (war, earthquake, etc.) or couple infertility; overall, these studies provide evidence that semen quality is impaired by psychological stress. In this review, we will discuss the impact of quality of life (modifiable lifestyle factors) and psychological stress on male fertility. In addition, the role that increased scrotal temperature along with inappropriate nutritional and physical exercise attitudes exert on male fertility will be presented.

Conclusion

The decline of male fertility, particularly associated with advancing age, incorrect lifestyles and environmental factors plays an important role on natality, and its consequences on the future on human population makes this an important public health issue in this century. Thus, modification of lifestyle through a structured program of educational, environmental, nutritional/physical exercise and psychological support, combined with the use of nutraceutical antioxidants can prevent infertility and therefore, may help couples to obtain better quality of life and improved possibility to conceive spontaneously or optimize their chances of conception.

     

Sperm DNA fragmentation and oxidation are independent of malondialdheyde

Background  

There is clinical evidence to show that sperm DNA damage could be a marker of sperm quality and extensive data exist on the relationship between DNA damage and male fertility status. Detecting such damage in sperm could provide new elements besides semen parameters in diagnosing male infertility. We aimed to assess sperm DNA fragmentation and oxidation and to study the association between these two markers, routine semen parameters and malondialdehyde formation.     

The measurement of reactive oxygen species in human neat semen and in suspended spermatozoa: a comparison

Background  

It is generally accepted that oxidative stress is an important factor in male infertility because it may impair the physiological function of spermatozoa at the molecular level. Nevertheless, although several approaches have been reported, the imbalance between production of reactive oxygen species (ROS) and activity of the antioxidant defense system in semen is difficult to investigate and remains poorly understood.     

Factors Associated with Failed Treatment: an Analysis of 121,744 Women Embarking on Their First IVF Cycles

Background

In-vitro fertilization (IVF) is the treatment of choice for unresolved infertility. It comprises a number of key steps, each of which has to be negotiated before the next is attempted, but the factors which are associated with failure at each stage have not been reported.

Methods and Findings

We analyzed anonymised national data on women undergoing their first fresh autologous IVF and intracytoplasmic sperm injection (ICSI) cycle in the United Kingdom between 2000 and 2007 to predict factors associated with overall lack of livebirth as well as the chance of non-progress at different stages of an IVF cycle. A total of 121,744 women were included in this analysis. Multivariable models underlined the importance of increased female age and duration of infertility, lack of previous pregnancy, and a diagnosis of tubal or male factor infertility in predicting the risk of not having a live birth in an IVF treatment. At each stage, a woman’s chance of proceeding to the next stage of IVF treatment is affected by increased age and duration of infertility. The intention to use intra-cytoplasmic sperm injection (ICSI) is associated with a decreased risk of treatment failure in women starting an IVF cycle (RR 0.93, 99% CI 0.92, 0.94) but this association is reversed at a later stage once fertilisation has been confirmed (RR=1.01, 99%CI 1.00, 1.03).

Conclusions

Female age is a key predictor of failure to have a livebirth following IVF as well as the risk of poor performance at each stage of treatment. While increased duration of infertility is also associated with worse outcomes at every stage, its impact appears to be less influential. Women embarking on ICSI treatment for male factor infertility have a lower chance of treatment failure but this does not appear to be due to increased chances of implantation of ICSI embryos.     

Evaluation of factors associated with the anxiety and depression of female infertility patients

Background

Because the primary aim of infertility treatment is to achieve pregnancy, mental health care during this treatment is often neglected. However, the inability to conceive children is stressful for couples throughout the world. Thus, the purpose of this study was to investigate factors related to the anxiety and depression of female infertility patients.

Methods

Participants included 83 Japanese women who initially visited the Reproduction Center of the Tokyo Dental College Ichikawa General Hospital to undergo testing and receive infertility treatment between February and April 2008. We administered two psychological tests, the Self-rating Depression Scale (SDS) test and the Hospital Anxiety and Depression Scale (HADS) test. We then examined the association of the test results with age, pregnancy and delivery history, employment status, duration of infertility, infertility treatment history, and male infertility.

Results

As patient age increased, total HADS and depression scores also increased. No correlation was observed between duration of infertility and SDS or HADS scores. Results were similar when the presence and absence of delivery history was compared. Patients who underwent infertility treatment were more likely to have high HADS depression scores compared to patients who had not undergone treatment. Additionally, patients whose husbands were infertile had significantly lower total HADS and anxiety scores than those whose husbands were not infertile.

Conclusions

Age and male infertility are factors that influence the presence of anxiety and depression in female infertility patients.     

Leptin interferes with 3',5'-Cyclic Adenosine Monophosphate (cAMP) signaling to inhibit steroidogenesis in human granulosa cells

Background  

Obesity has been linked to an increased risk of female infertility. Leptin, an adipocytokine which is elevated during obesity, may influence gonadal function through modulating steroidogenesis in granulosa cells.     

Genome-wide profiling of gene expression in the epididymis of alpha-chlorohydrin-induced infertile rats using an oligonucleotide microarray

Background  

As one of the chlorinated antifertility compounds, alpha-chlorohydrin (ACH) can inhibit glyceraldehyde-3-phosphate dehydrogenase (G3PDH) activity in epididymal sperm and affect sperm energy metabolism, maturation and fertilization, eventually leading to male infertility. Further studies demonstrated that the inhibitory effect of ACH on G3PDH is not only confined to epididymal sperm but also to the epididymis. Moreover, little investigation on gene expression changes in the epididymis after ACH treatment has been conducted. Therefore, gene expression studies may indicate new epididymal targets related to sperm maturation and fertility through the analysis of ACH-treated infertile animals.     

Effect of estrogens on boar sperm capacitation <Emphasis Type="Italic">in vitro</Emphasis>

Background  

Mammalian sperm must undergo a series of controlled molecular processes in the female reproductive tract called capacitation before they are capable of penetrating and fertilizing the egg. Capacitation, as a complex biological process, is influenced by many molecular factors, among which steroidal hormone estrogens play their role. Estrogens, present in a high concentration in the female reproductive tract are generally considered as primarily female hormones. However, there is increasing evidence of their important impact on male reproductive parameters. The purpose of this study is to investigate the effect of three natural estrogens such as estrone (E1), 17beta-estradiol (E2) and estriol (E3) as well as the synthetical one, 17alpha-ethynylestradiol (EE2) on boar sperm capacitation in vitro.     

Immune function and parasite resistance in male and polymorphic female Coenagrion puella

Background  

Colour polymorphisms are widespread and one of the prime examples is the colour polymorphism in female coenagrionid damselflies: one female morph resembles the male colour (andromorph) while one, or more, female morphs are described as typically female (gynomorph). However, the selective pressures leading to the evolution and maintenance of this polymorphism are not clear. Here, based on the hypothesis that coloration and especially black patterning can be related to resistance against pathogens, we investigated the differences in immune function and parasite resistance between the different female morphs and males.     

Coolidge effect in pond snails: male motivation in a simultaneous hermaphrodite

Background  

The simultaneously hermaphroditic pond snail, Lymnaea stagnalis, can mate in the male and female role, but within one copulation only one sexual role is performed at a time. Previous work has shown that male motivation is determined by the availability of seminal fluid in the prostate gland, which is detected via a nervous connection by the brain area controlling male behaviour. Based on this knowledge, patterns of sexual role alternations within mating pairs can be explained.     

Autonomic neuropathy in Fabry disease: a prospective study using the Autonomic Symptom Profile and cardiovascular autonomic function tests

Background  

Fabry patients have symptoms and signs compatible with autonomic dysfunction. These symptoms and signs are considered to be due to impairment of the peripheral nervous system, but findings indicative of autonomic neuropathy in other diseases, such as orthostatic intolerance and male sexual dysfunction, are infrequently reported in Fabry disease. The aim of our study was to investigate autonomic symptoms and cardiovascular autonomic function in a large cohort of male and female Fabry patients.     

MTHFR 677C>T Polymorphism Increases the Male Infertility Risk: A Meta-Analysis Involving 26 Studies

Background and Objectives

Methylenetetrahydrofolate reductase (MTHFR) polymorphism may be a risk factor for male infertility. However, the epidemiologic studies showed inconsistent results regarding MTHFR polymorphism and the risk of male infertility. Therefore, we performed a meta-analysis of published case-control studies to re-examine the controversy.

Methods

Electronic searches of PubMed, EMBASE, Google Scholar and China National Knowledge Infrastructure (CNKI) were conducted to select eligible literatures for this meta-analysis (updated to June 19, 2014). According to our inclusion criteria and the Newcastle-Ottawa Scale (NOS), only high quality studies that observed the association between MTHFR polymorphism and male infertility risk were included. Crude odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of association between the MTHFR polymorphism and male infertility risk.

Results

Twenty-six studies involving 5,575 cases and 5,447 controls were recruited. Overall, MTHFR 677C>T polymorphism showed significant associations with male infertility risk in both fixed effects (CT+TT vs. CC: OR = 1.34, 95% CI: 1.23–1.46) and random effects models (CT+TT vs. CC: OR = 1.39, 95% CI: 1.19–1.62). Further, when stratified by ethnicity, sperm concentration and control sources, the similar results were observed in Asians, Caucasians, Azoo or OAT subgroup and both in population-based and hospital-based controls. Nevertheless, no significant association was only observed in oligo subgroup.

Conclusions

Our results indicated that the MTHFR polymorphism is associated with an increased risk of male infertility. Further well-designed analytical studies are necessary to confirm our conclusions and evaluate gene-environment interactions with male infertility risk.     

Dehydroepiandrosterone (DHEA) reduces embryo aneuploidy: direct evidence from preimplantation genetic screening (PGS)

Background  

Follicle stimulating hormone (FSH) and anti-Müllerian hormone (AMH) represent the two most frequently utilized laboratory tests in determining ovarian reserve (OR). This study determined the clinical significance of their concordance and discordance in female infertility patients.