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PubMed2003

Genetic disorders and infertility.

Many aspects of male fertility are influenced by genetics. Over 150 genes have been shown to be associated with infertility in mouse models, although translation of these findings to human male infertility has been slow. Nevertheless, it is likely that a significant number of these gene deletions may be associated with human infertility. There is much that we do not understand about the molecular basis of human male infertility; patients should be advised of this caveat. Genetic disorders in humans can lead to impaired spermatogenesis, defective sperm function, and defects in delivery of sperm. It is critical for the urologist who evaluates and treats infertile couples to have a working knowledge of these disorders. An understanding of the genetic basis of male infertility allows for the appropriate counseling of patients about treatment options and risks to their potential offspring.

Chromosomes, Human, Y↗
PubMed1999

Linkage between male infertility and trinucleotide repeat expansion in the androgen-receptor gene.

BACKGROUND: Androgens acting via the androgen receptor bring about stimulation and maintenance of spermatogenesis. If mutations in the androgen-receptor gene interfere with the receptor's function, this effect may partly account for impaired spermatogenesis. We aimed to find out whether expansion of a trinucleotide repeat in the androgen-receptor gene is associated with male infertility. METHODS: We analysed 67 coded semen and blood samples from a predominantly white group of male infertility patients and controls. Clinical analyses included cause of infertility, sperm count, and reproductive hormone concentrations. Analysis of trinucleotide (CAG) repeat length and point mutations in the androgen-receptor gene was done by PCR, single-stranded conformational polymorphism, and DNA sequencing. FINDINGS: Screening and characterisation of the androgen-receptor gene in 35 patients and 32 controls showed no point mutations in the gene. 30 of the infertile patients had idiopathic azoospermia or oligozoospermia, and these men had significantly longer CAG repeat tracts than controls (mean 23.2 [SE 0.7] vs 20.5 [0.3], p=0.0001). The odds of having CAG repeat lengths of 20 were six-fold higher for fertile men than for men with a spermatogenic disorder. INTERPRETATION: Our results indicate a relation between CAG repeat length in the androgen-receptor gene and the risk of defective spermatogenesis. With the use of intracytoplasmic sperm injection, this mutation could be inherited, possibly leading to an increase in male infertility in future generations. Should further elongation of the CAG repeat occur in these future generations, there is an added risk of increased severity of male infertility, and potentially an increased incidence of neurodegenerative disease.

Adult↗
PubMed2002

Two-dimensional electrophoretic analysis of sperm antigens recognized by sperm immobilizing antibodies detected in infertile women.

In this study, high resolution two-dimensional (2-D) gel electrophoresis was used to identify human sperm antigens recognized by the sera from infertile women having sperm immobilizing (SI) antibodies. Two-D gel electrophoresis was employed to separate Percoll purified human sperm proteins using isoelectric focusing (IEF), followed by polyacrylamide gel electrophoresis (PAGE). Sperm proteins were transferred to the nitrocellulose membranes and immunoblotted with seven sera from infertile women with high titers of SI antibodies and 6 sera from those without SI antibodies. The blots were compared to the 2-D composite image of human sperm proteins [Sperm Protein Encyclopedia] and sperm surface index and the sperm surface proteins recognized by infertile sera were identified. Fifty-two human sperm surface proteins reacted with sera containing SI antibodies, while 35 of these were reactive with the SI-negative control sera. The average numbers of protein spots reacted with test and control sera were 24.6 and 15.0 respectively. A subset of sperm surface proteins which were unique to the SI antibodies were identified by the following criteria; the sperm protein spots which were highly reactive with the infertile sera containing SI antibodies but not reactive with any of the SI-negative infertile sera. The coordinates of 4 prominent immunoreactive sperm proteins were considered as possibly relevant to antibody mediated female infertility.

Antigens, Surface↗
PubMed1991

Clinical approach to infertile male dogs with sperm in the ejaculate.

Categories of infertility are defined according to semen characteristics. Assessment of daily sperm output and carefully planned matings to determine the extent of infertility and to manage insemination to maximize fertility are described. The contributions of baseline laboratory data, evaluation of reproductive hormones, and testicular biopsy in determining the causes of infertility are discussed. Treatments of infertility secondary to systemic disease, infertility caused by accessory gland infections, and infertility associated with abnormal gonadotropin concentrations are reviewed.

Adrenal Gland Diseases↗
PubMedDate not supplied

[Genital infection and infertility].

BACKGROUND: Genital infection is the most important cause of infertility worldwide, affecting not only Fallopian tubes but all anatomic urogenital sites, both male and female. METHODS: We present a randomized,prospective and normalized study about sexually transmitted diseases(STD). We include 487 patients, 376 of whom were infertile and the remaining 111 were not and act as control group. RESULTS: 47.3% of infertile patients showed at least one infection: 10.7% had Chlamydia trachomatis infection, whereas only 0.3% had gonococal infection. We found none syphilis. 12.9% of the patients showed yeast belonging to genus Candida, 5% bacterial vaginosis, 3.8% Escherichia coli and 0.3% Klebsiella pneumoniae. The percentage of isolation of Ureaplasma urealyticum and Mycoplasma hominis were 23.5% and 4.8%, respectively. We detected antibodies against Hepatitis B (any serological marker) in 7.8% of the cases. Chlamydial infection and the presence of U. urealyticum were related with infertility (X 12=6,070, p<0.005 and X12=8,782, p<0.005,respectively). CONCLUSIONS: We think these results conclude that is necessary to perform routine tests to screen for C. trachomatis, N. gonorrhoeae, and for infections caused by micoplasma as well, among infertile patients. These patients must be considered of being at risk of acquiring STD, since the percentage of these diseases is higher than the percentage we found among the control group. It is important to insist on prevention and early diagnosis and treatment as a main goal to decrease the number of tubal occlusion and infertile couples.

Adult↗
PubMed2006

[Sophrology: a different tool for infertile couples].

Because of the high degree of complexity of assisted reproduction techniques (ART), the human and conscious dimensions of infertility problems are often neglected. Different strategies may help infertile couples coping with infertility and related treatments; among these, Caycedian sophrology relies on the cognitive, emotional, and somatic aspects of consciousness. In the present article, the authors report on their experience with sophrologic support for infertile patients by a midwife qualified in caycedian sophrology. Overall, since 1988, 310 couples have benefied from this kind of support, with an average of 10 sophrologic trainings per patient. Whereas some couples consider sophrology as a short time training to better cope with any particular aspect of their infertility treatment, others want to undertake more profound work on their body scheme. The authors wish to call the attention of ART professionals to this kind of medical support for infertile couples, and also to the particular role of midwives with sophrologic competence in an ART center.

Adult↗
PubMed1997

Infertility in the Gambia: traditional and modern health care.

In order to understand the problems of unwanted infertility in a country--the Gambia--where the desire for children and the fertility is very high, a population-based survey was undertaken. All infertile women in 24 randomly selected enumeration areas were assessed. The study included a review of the problems faced and coping mechanisms employed by infertility clients and types of health care available for infertile couples in the different types and levels of the formal and traditional health system. Half of the infertile couples failed to seek formal health care, and they have to reach a certain level of care in order to properly managed. Alternative care is often sought. Child fostering is also a frequent solution to childlessness. In-depth interviews revealed that traditional care like healers and spiritual leaders are frequently consulted long before formal health care. This delay could be a problem in those cases where infertility is caused by infections.

Adolescent↗
PubMed2003

Male factor infertility.

There is a male factor involved in up to half of all infertile couples. Potential causes of male factor infertility are many and require thorough evaluation for their accurate elucidation. A complete medical history in conjunction with a focused examination can allow for an appropriate choice of laboratory and imaging studies. The semen analysis is a crucial first step, but it is by no means sufficient to determine cause or dictate therapy. A systematic approach is necessary to help guide the evaluation and exclude less likely causes. The causes discussed within this article are broad, and the prognosis for any given couple depends, in large part, on the cause of the infertility. Without a firm understanding of the genetics, anatomy, physiology, and their interactions necessary to permit full functioning of the male reproductive system, the evaluation becomes an inefficient exercise that often fails to elucidate the precise cause of infertility. Treatment success relies not just on a clinical diagnosis but on a determination of the cause of the male factor infertility. Therefore, couples with a component of male factor infertility need a systematic evaluation directed at the male partner to maximize their reproductive potential.

Cryptorchidism↗
PubMed1998

The genetic basis of male infertility.

Defective spermatogenesis can be the end result of a multitude of causes, such as systemic disease, malnutrition, endocrinologic disorder, genetic defects, anatomic obstruction of the passage of spermatozoa, infections, and environmental toxins. A genetic basis of infertility is thought to exist in a majority of infertile men currently classified as having idiopathic infertility. Despite advances in molecular technology, the pathophysiology of spermatogenic failure in a majority of infertile men remains unknown. Although a large number of genes and loci in experimental animals are associated with sterility, the human homologues of most of these genes have not been cloned yet. Infertility is a heterogeneous syndrome in men; therefore, it is likely that a multitude of genes and loci will be implicated in different infertility subsets.

Animals↗
PubMed2000

Contemporary approach to the male infertility evaluation.

Evaluation of infertile couples has revealed that male factor infertility contributes to the problem in up to 50% of cases. Evaluation of the male infertility patient may include endocrine studies, sophisticated semen testing, and select radiographic studies. Reversible and life-threatening causes of male infertility should be identified before proceeding directly to assisted reproductive technology. For cases with irreversible causes, a proper evaluation can identify patients who may be treated with the breakthrough method of intracytoplasmic sperm injection. Many men who were previously thought to be infertile may now initiate their own biologic pregnancies. This article emphasizes the essentials of the contemporary approach to evaluating the male factor in an infertile couple.

Diagnostic Imaging↗
PubMed1991

Resources for infertility treatment.

Infertility is common, a serious medical problem in both advanced and underdeveloped countries. At present, medical resources are often used very haphazardly and frequently extravagantly to combat fertility problems. Whilst it seems very unlikely that society will be able to prevent infertility effectively, there is no doubt that the resources available could be better organized for greater benefit. There is evidence of poor co-ordination of services, of inadequate financial planning by health managers, and squandering of limited resources by professionals. Better organization of in vitro fertilization (IVF), with the promotion of larger regional services, would be an effective use of finances. IVF is too often only available to the wealthy and the selection of patients for treatment is frequently arbitrary; many fertility treatments are of unproved value and are wasteful. It is argued, for example, that many patients receiving gamete intrafallopian transfer (GIFT) for so-called 'unexplained infertility' would be better treated by other, less expensive, methods which are often more effective. Many useful treatments, such as tubal surgery, are being disregarded or misused and there is need for better education of specialists who treat infertile patients. Better primary care of infertile patients should include non-medical counselling, and investigation and firm diagnosis before treatment is commenced. The heavy accent on high technology in the treatment of infertility is often misplaced, and we need to strike a careful balance if resources are to be properly allocated.

Adaptation, Psychological↗
PubMed1997

The genetics of male infertility in relation to cystic fibrosis.

Absence, dysfunction or low levels of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein result in a broad range of clinical manifestations with CF with pancreatic insufficiency at the severe end of the phenotypic spectrum and, at the other end relatively mild clinical conditions, including several forms of male infertility. The condition of congenital bilateral absence of the vas deferens (CBAVD) is in 75-80% of the patients associated with defects in the CFTR gene. In the remaining patients, CBAVD is also associated with urinary tract malformations, and this form of CBAVD is not related to CF. Congenital unilateral absence of the vas deferens also seems to be associated with CF except when associated with renal abnormalities at the ipsilateral side of the absent vas. A possible role of the CFTR protein in the aetiology of infertility due to defects in sperm production and maturation has also been suggested recently. In contrast, Young's syndrome is probably not related to CF. The relation between some conditions of male infertility and CF implies appropriate clinical examination of the patients, CFTR mutation analysis and genetic counselling. Because infertility can now in many cases be treated by artificial reproductive technology couples have an increased risk of having children with CF or infertility if the female partner is also a carrier of a CFTR mutation. Couples should be well informed about these risks and risk prevention including pre-implantation diagnosis. Follow-up studies of children born to these couples are mandatory, whether male infertility is linked to CF or not.

Cystic Fibrosis↗
PubMed2002

[Male infertility and microdeletions of the Y chromosome].

It is estimated that about 10% of men suffer from male infertility. Male infertility is associated with a reduction in the quantity, reduced mobility or abnormal morphology of sperm. In about 50-60% of cases the etiology can be identified. When the cause is unknown, it is referred to as idiopathic infertility. A genetic cause is suspected in some of the latter cases since chromosome anomalies and familial forms of male infertility have been reported. Three different regions of the Y chromosome, termed AZFa, AZFb and AZFc are recurrently deleted in about 15% of cases of idiopathic azoospermia or severe oilgozoospermia. AZFc deletions form the majority of these deletions. The presence of a Y microdeletion does not seem to alter the fertilisation of the oocyte or the development of the embryo. However, if the child is a boy, he will inherit the deletion from his father and will most likely be infertile when he is an adult. In the absence of any other information concerning an association between Y chromosome microdeletions and other development anomalies of the child, in genetic counselling the principal risk for male offspring appears to be infertility.

Diagnosis, Differential↗
PubMed2003

Polycyclic aromatic hydrocarbon-DNA adducts in human sperm as a marker of DNA damage and infertility.

Severe DNA damage, which might prevent egg fertilization or the development of the embryo, could be a cause of infertility. In order to assess whether polycyclic aromatic hydrocarbon (PAH)-DNA adducts are an early marker of sperm genotoxicity and infertility, we studied 205 men consecutively recruited from 1 January to 30 May 2001 through the Infertility Clinic of the University of Milan (Italy), with morphological abnormalities in the sperm. No known causes of infertility were present in their female partners. Sperm were collected after 3-5 days of abstinence, fixed on polylysine slides, and frozen at -20 degrees C. PAH-DNA adducts were measured by immunofluorescence using a polyclonal antiserum. A questionnaire was filled out at the time of the visit, with demographic information, smoking and drinking habits, and occupational history. Data on PAH-DNA adducts were available for 182 men. The mean age of the subjects was 35.5+/-5.0 years; 38.6% of them were current smokers. PAH-DNA adducts were negatively correlated with the percentage of physiologic forms (r=-0.18; P=0.016) and with abnormalities of the neck of the sperm cell (r=-0.21; P>/=0.009), while they were positively correlated with morphological abnormalities of the head (r=0.30; P>0.0001). Occupational exposure to PAH, but not smoking, was significantly associated with higher levels of PAH-DNA adducts. A significant negative association was observed between daily alcohol consumption and PAH-DNA adducts in sperm (P=0.01). PAH-DNA adducts levels were significantly higher in infertile versus fertile men (P=0.04). These results suggest a role for DNA damage in infertility.

Adult↗
PubMed2003

Cancer risks associated with the diagnosis of infertility.

The effects of infertility and its treatment on cancer risk are of concern to many infertile couples. Infertile women appear to be at no higher risk for breast cancer although they may be more at risk for cancers of the uterus, particularly if they have ovulation disorders. Most studies show no increase in the risk of invasive ovarian cancer in infertile women, but ovarian tumours of borderline malignancy are more common. There seems to be no overall increase in cancer risk associated with fertility drug treatment, but questions remain about risk in subgroups of infertile women. Male infertility has been associated with an increased risk of testis cancer. Cancer incidence in children born after fertility treatment appears to be similar to that in the general population. Discussion of cancer risks in the context of other reproductive and community risks can be helpful to patients.

Breast Neoplasms↗
PubMed2004

Effects of repeated treatment failure on the quality of life of couples with infertility.

OBJECTIVE: To determine the impact of repeated treatment failure of clomiphene and intrauterine insemination on the quality of life of couples with infertility. METHODS: A prospective comparative study involving 3 groups of 50 couples each. The first group consisted of infertile couples with repeated treatment failure (group FT), the second group consisted of infertile couples who had never attempted any medical treatment (group NT), and the third was a control group of couples with at least 1 child and no history of infertility. Participants completed a comprehensive questionnaire to assess 16 areas of quality of life. RESULTS: The quality of life score of the control group was higher than the scores reported by groups NT and FT (P <.001). There was no significant difference in the quality of life score reported by group NT and group FT or between male and female partners. Among the women, a high quality of life was reported by 22% in group FT, 14% in group NT, and 54% in the control group. Among the men, a high quality of life was reported by 14% in group FT, 12% in group NT, and 60% in the control group. In contrast to their male partners, the women with repeated treatment failure placed higher importance on children and home than their counterparts who had not started the treatment (P <.05). CONCLUSION: Although couples with repeated treatment failure of clomiphene and intrauterine insemination do not demonstrate a lower overall quality of life than other infertile couples beginning baseline assessment, the quality of life of infertile couples is lower than that of fertile couples.

Adult↗
PubMed1998

Infertility and risk of fatal ovarian cancer in a prospective cohort of US women.

OBJECTIVES: It is difficult to separate the possible role of fertility drugs from underlying infertility as risk factors for ovarian cancer. The present study examined the relationship between self-reported infertility and death from ovarian cancer among married women unlikely to have been exposured to fertility drugs. METHODS: Women were selected for study from the 676,526 female participants in Cancer Prevention Study II (CPS-II). After twelve years of follow-up, 797 deaths from ovarian cancer were observed among women with no prior history of cancer or hysterectomy and 40 years of age or older in 1967 when ovulatory stimulants were approved in the United States. Cox proportional hazards modeling was used to compute rate ratios (RRs) and to adjust for other potential risk factors. RESULTS: Overall, self-reported infertility was not significantly associated with ovarian cancer mortality (adjusted rate ratio (RR) = 1.1, 95 percent confidence interval (CI) = 0.9-1.3). Ovarian cancer death rates among nulligravid women with self-reported infertility, however, were 40 percent higher than for nulligravid women who never tried to become pregnant (RR = 1.4, 95 percent CI = 0.9-2.4). Multigravid women who reported infertility problems were not at increased risk. CONCLUSIONS: These results suggest that infertility itself, without concomitant exposure to fertility drugs, may increase risk of fatal ovarian cancer among nulligravid women.

Adult↗
PubMed2001

Delayed motherhood increases the probability of sons to be infertile.

PURPOSE: To ascertain whether advanced maternal age at birth is associated with offspring infertility. METHODS: A written questionnaire was completed by infertile couples attending our clinic in the presence of a researcher. RESULTS: Maternal age at birth (odds ratio 1.236, 95% CI 1.100-1.388) and birth order of all respondents and their respective siblings (odds ratio 0.551, 95% CI 0.351-0.865) were significant predictors of male infertility. The probability of a man being infertile increased as mother's age at birth increased (regression coefficient +/- standard error 0.212 +/- 0.059; P < 0.001), but decreased as birth order increased (regression coefficient +/- standard error -0.596 +/- 0.230; P = 0.010). CONCLUSIONS: Delayed motherhood may enhance the probability of sons to be infertile. The probability of a man being infertile would be greater if he comes from a small family than if he comes from a large family.

Female↗