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Physiopathological determinants of human infertility.

Successful management of infertility involves the use of appropriate diagnostic tests and treatments, and knowledge of prognostic factors such as age of the female partner and duration of infertility. The assessment of infertility may reveal disorders that cause morbidity in the normally fertile population, which might or might not contribute to the infertility. Endocrine dysfunction is a significant cause of infertility due to amenorrhoea and dysfunctional uterine bleeding, and hirsutism is a familiar problem in the normal population. Some genetic abnormalities cause infertility in males and females and create implications for the progeny of infertile couples. Sexually transmitted diseases cause illness and healthcare expenditure among young adults, and can also result in tubal infertility. Congenital disorders of the uterus and fibromyomas are not rare and they are frequently asymptomatic, but in some cases uterine anomalies may contribute to infertility and pregnancy loss. Autoimmunity underlies some common diseases, especially among females, and it can also be associated with pregnancy loss. When such widely distributed factors are identified during the diagnostic assessment of subfertile couples, it is important to distinguish between a coincidental association and a specific relationship to the infertility.

Aging↗

Psychogenic infertility--myths and facts.

PURPOSE: The hypothesis of this review is that the role of psychological factors as the sole cause of infertility is generally overrated. METHODS: A review is given of studies concerning the influence of psychological factors on the development of infertility. RESULT: A prevalence of psychogenic infertility of 10-15 per cent must be discussed critically. A value of approximately 5 per cent is more realistic. Equating unexplained infertility with psychogenic infertility is not justified. A definition of psychogenic infertility according to the German guidelines Psychosomatics in Reproductive Medicine is presented. Spontaneous pregnancies following adoption or the decision to remain childless are the absolute exception. The association of stress and infertility in humans is still unclear. For many women the effect of infertility and notably of medical therapy is a considerable emotional stress. This may make psychosocial counseling necessary in certain cases. CONCLUSIONS: An exclusive psychological/psychodynamical point of view on the complexity of infertility is as inadequate as a strictly somatic point of view. Infertility should always be treated as a psychosomatic entirety.

Counseling↗

Psychological aspects of infertility.

It has often been claimed that psychological problems accompany infertility among some couples attending infertility clinics. Some authors have suggested that psychological factors may be a primary cause of infertility, others have suggested that the state of infertility itself can provoke psychological symptoms. The importance of psychological counselling for involuntarily childless couples has also been noted. This paper, which reviews studies that have attempted to investigate psychological aspects of infertility, is organized around three issues: psychological factors as a cause of infertility, the impact of infertility on psychological functioning, coping with infertility and the counselling needs of the infertile couple. While there seems little doubt that infertility has psychological consequences for some couples, many questions will remain unanswered unless carefully designed and conducted longitudinal studies are undertaken.

Adaptation, Psychological↗

Clinical review 100: Evaluation and treatment of the infertile couple.

Infertility by itself does not threaten physical health but has a strong impact on the psychological and social well-being of couples. In the last two decades, progress in caring for the infertile couple, in particular progress in the field of assisted reproduction and micromanipulation, has provided significant hope for many couples for whom hope could not have been offered in the past. This is especially true for bilateral tubal disease and for male factor infertility, as nearly all couples with male factor infertility can now undergo either one (or more) IVF or ICSI attempt(s). For couples with other causes of infertility, however, the differences in pregnancy rates often do not reach statistical significance. We must also remember that the total cost incurred for successful delivery for couples with a better chance of successful IVF (i.e. those with tubal disease) increases from approximately $55,000 in American dollars for the first cycle to $73,000 by the sixth cycle. Because of these high costs, many insurers in the United States and many public health systems in Europe do not cover or only partially cover these procedures. Consequently, the availability of IVF and related therapies frequently depends on the couple's ability to pay. Therefore, after having established the correct diagnosis, appropriate treatment should be counseled to the infertile couple keeping in mind the following points: 1) in subfertile couples expectant management should be reasonably counselled if the age of the woman is less than 30 yr and the duration of infertility is less than 36 months, even if oligozoospermia is present; 2) superovulation and timed intercourse seems also to be a reasonable approach in couples with anovulatory, mild/moderate endometriosis, and unexplained infertility; 3) in unexplained infertility, ovarian stimulation (with clomiphene or gonadotropin) and IUI seem to offer some advantage over ovarian stimulation and timed intercourse; 4) IVF can be a firstline approach in tubal sterility and when IUI or IPI cannot be performed because the number of motile sperm is insufficient, but is usually also the final treatment attempt when other methods have failed. The outcome of IVF is negatively influenced mainly by the woman's age; however, the number of deliveries is also generally lower in couples with male factor; 5) ICSI is a further option, which should be limited to couples: a) with very poor semen parameters; b) previous failed fertilization; c) presence of obstructive or nonobstructive azoospermia in which ICSI is combined with sperm extraction from the epididymis or the testis; 6) international register studies demonstrate that the risk of malformation after conventional IVF is not increased; 7) some reports suggest that incidence of congenital major and minor malformations is not increased in children born after ICSI. However, the rate of sex chromosome anomalies in ICSI fetuses has been reported to be approximately 1% in 585 prenatal diagnoses, a frequency increased by a factor of 4 if compared with naturally conceived live-born babies. ICSI bypasses the physiological selection of spermatozoa that occurs at the level of the testis and epididymis, and in the female reproductive tract as well as at the sperm-oocyte interface. As genetic abnormalities are present in a significant percentage of infertile males with impaired spermatogenesis, karyotyping and analysis of the Y chromosome for microdeletions should be carried out in all potential ICSI fathers. Screening for cystic fibrosis gene mutations should also be performed in azoospermia caused by congenital absence of the vas deferens and seminal vesicles. Appropriate genetic counseling should be made available to all ICSI couples whenever a gene or chromosomal anomaly has been identified. With most ARTs the average delivery rate per cycle is approximately 15% and the cumulative delivery rate after several cycles is about 50%. (ABSTRACT TRUNCATED)

Endocrinology↗

Thyroid disorders in infertile women.

Thyroid hormones have profound effects on reproduction and pregnancy. There is a known association of hyper- and hypothyroidism with menstrual disturbances and decreased fecundity. Women with reproductive failure also have an increased prevalence of organ specific autoimmunity compared to fertile women. The present study aims to answer the following questions: 1) is there an increased prevalence of thyroid antibodies in infertile women? 2) are thyroid antibodies associated with a particular cause of infertility? and 3) do these antibodies influence outcome of the in vitro fertilization procedure? The answers to the two first questions were evaluated with a case-control study looking at the occurrence of thyroid autoimmunity and thyroid function tests among women of infertile couples (n=438), presenting for the first time at the department of reproductive medicine. For comparison, a control population of parous women (n=100), matched for age, was included. In 45% of the infertile couples a female cause of infertility was identified: endometriosis (11%), tubal disease (30%) and ovarian dysfunction (59%). Male infertility was diagnosed in 38% and idiopathic infertility in 17% of the couples. Mean serum TSH levels were significantly higher in patients with infertility compared with control patients: 1.6 +/- 2.6 versus 1.2 +/- 0.7 mIU/L. The proportion of positive TPO-Abs was higher in all women of infertile couples, compared with controls (14% versus 8%), but the difference was not significant. Considering only the female causes of infertility a significant higher proportion of women had positive TPO-Abs compared with controls (18% versus 8%), and in particular a high prevalence of thyroid autoimmunity was found in women suffering from endometriosis (29%). Both hypo- and hyperthyroidism were more frequent when TPO-Abs were positive, compared to women without thyroid autoimmunity. The results of the present study indicate that endometriosis, increases the relative risk for associated thyroid autoimmunity to 2.3, and therefore screening for thyroid auto-antibodies could be systematically proposed in these women.

Adult↗

Macrophage-derived cytokines in the follicular fluids of women with infertility due to immunological causes. Elevated levels of interleukin 6 and low levels of granulocyte-macrophage colony-stimulating factor.

The cytokines are (glyco)proteins secreted by lymphoid and non-lymphoid cells which modulate several biological responses including the ovarian function. Interleukin (IL)-1 and tumour necrosis factor (TNF)-alpha suppress 17beta-estradiol (E2) and progesterone release from granulosa and luteal cells in vitro. TNF-alpha affects negatively folliculogenesis and ovarian maturation. Additional in vivo evidence for a role of this macrophage-derived cytokine came from our recent observation that women with infertility due to immunological causes have elevated intrafollicular fluid levels of TNF-alpha and decreased levels of E2 compared to women with a tubal factor of infertility. Because the macrophages are a primary component of the intrafollicular compartment, the present study was undertaken to evaluate whether other macrophage-derived cytokines are also released in the human follicular fluid. To accomplish this, we measured the levels of IL-1beta, IL-6, IL-10 and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the follicular fluids of two groups of infertile women undergoing to an in vitro fertilization program. The first group of women had a significant titre of anti-spermatozoon antibodies in the serum and/or the mucus as the only cause of infertility, whilst the second group of women was infertile because of non patent fallopian tubes. Intrafollicular cytokines levels were measured by solid-phase ELISA and steroid concentrations by radioimmunoassay. Whilst IL-1beta, IL-6, IL-10, and GLM-CSF were all measurable in the follicular fluid of both groups of women, the levels of IL-6 were found to be significantly more elevated and those of GM-CSF lower in patients with infertility due to immunological causes as compared to those with tubal infertility. The former had also decreased intrafollicular E2 levels and increased progesterone concentrations. No difference was seen in the follicular fluid levels of testosterone and androstenedione. In conclusion, several macrophage-derived cytokines are present in the follicular fluids of infertile women. Patients with infertility due to immunological causes had higher levels of IL-6 and lower concentrations of GM-CSF as compared to patient with a tubal factor of infertility. We speculate that this abnormal cytokine profile may contribute to the altered intrafollicular steroid milieu.

Adult↗

Perception of diagnosis and openness of patients about infertility.

The perception of the diagnosis of infertility and the openness of patients about infertility was investigated among 108 infertile couples. Husbands and wives answered a structured questionnaire. The perception of diagnosis was in 38% of the cases different from the medical diagnosis. Patients perceived the diagnosis of male infertility more frequently, and the diagnosis of female infertility less frequently, than these diagnoses were made. Also there are significant differences in the perception of diagnosis between husbands and wives. Among the respondents there is a tendency to ascribe the diagnosis of infertility to themselves. It is important that physicians make sure that the patients have understood the received information. Family and friends are in almost all cases informed about the infertility problem, colleagues and acquaintances in about 60% of the cases, neighbors in about 40% of the cases. The reaction to openness is positive. Husbands are less open about male infertility than about female infertility. A selective choice of confidants and a subtle way of conveying the information generally lead to a positive reaction to the disclosure of infertility.

Attitude to Health↗

Ovarian cancer risk associated with varying causes of infertility.

OBJECTIVE: To evaluate the risk of ovarian cancer as related to underlying causes of infertility. DESIGN: Retrospective observational cohort study. SETTING: Five large reproductive endocrinology practices. PATIENT(S): A total of 12,193 women evaluated for infertility between 1965 and 1988. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Ovarian cancer ascertained through 1999. RESULT(S): With 45 identified ovarian cancers, this cohort of infertility patients demonstrated a significantly higher rate of ovarian cancer than the general female population (standardized incidence ratio [SIR] = 1.98; 95% confidence interval [CI], 1.4-2.6). The risk was higher for patients with primary infertility (SIR = 2.73) than for those with secondary infertility (SIR = 1.44), and it was particularly high for patients who never subsequently conceived (SIR = 3.33). Women with endometriosis had the highest risk (SIR = 2.48; 95% CI, 1.3-4.2), with a further elevated risk among those with primary infertility (4.19, 2.0-7.7). Comparisons among the infertile women, which allowed calculation of rate ratios (RRs) after adjustment for multiple factors, also showed links with endometriosis. Compared with women with secondary infertility without endometriosis, patients with primary infertility and endometriosis had a RR of 2.72 (95% CI, 1.1-6.7). CONCLUSION(S): Determination of ovarian cancer risk should take into account the type of infertility (primary vs. secondary) and underlying causes. Further study of endometriosis may provide insights into ovarian carcinogenesis.

Cohort Studies↗

Infertility: testing a helpseeking model.

This paper uses data from a study of 196 infertile women from the Midwestern US to examine a general theory of helpseeking behavior applied to infertility. All of these women report meeting the medical definition of infertility--12 months or more of regular intercourse without conception--at some point in their lives. Only 35 percent of this sample of infertile women identified themselves as having had fertility problems and only 40 percent had sought medical treatment. Drawing on prior theories of helpseeking, we examine the effects of symptom salience, life course cues, attitudes, predisposing factors, and enabling conditions on helpseeking. We posit a model in which a cognitive dimension (perceived infertility) mediates between these predictors and medical helpseeking. Symptom salience (experienced infertility while actively trying to get pregnant), low parity, and poor subjective health are significantly related to perceived infertility, which is, in turn, significantly associated with helpseeking for infertility. Supporting the conclusion that the cognitive dimension of identifying oneself as infertile is critical to helpseeking, the relationship of symptom salience to helpseeking is partially mediated by perceived problems. Internal health locus of control is associated with lower odds of helpseeking but not to perceived infertility.

Adult↗

Impact of infertility on quality of life, marital adjustment, and sexual function.

OBJECTIVES: To evaluate the hypothesis that infertility may result in a decrease in quality of life and an increase in marital discord and sexual dysfunction. The burden of infertility is physical, psychological, emotional, and financial. METHODS: Couples seeking treatment for infertility were asked to complete standardized validated questionnaires assessing quality of life (Quality of Well-Being Scale-Self Administered, version 1.04), marital adjustment (Locke-Wallace Marital Adjustment Test), and sexual function (Brief Index of Sexual Functioning for Women and International Index of Erectile Function for men). Couples seeking elective sterilization served as the control subjects. RESULTS: Eighteen infertile couples and 12 couples seeking elective sterilization participated in the study. The mean age, years together, and household income were comparable. Infertile couples had made a mean of 14.5 office visits for infertility, and 83% of couples reported feeling societal pressures to conceive. The Marital Adjustment Test scores for the women of the infertile couples were significantly lower than the scores of the controls (P = 0.01); however no difference was noted in the men. A trend toward lower quality-of-life scores was noted in women (P = 0.09) but not in the men of infertile couples. No statistically significant impact on sexual functioning in women was noted; however, the men in the infertile couples had lower total International Index of Erectile Function scores (P = 0.05) and intercourse satisfaction scores (P = 0.03). CONCLUSIONS: Women in infertile couples reported poor marital adjustment and quality of life compared with controls. Men may experience less intercourse satisfaction, perhaps because of the psychological pressure to try to conceive or because of the forced timing of intercourse around the woman's ovulatory cycle.

Adult↗

Determinants of pregnancy rate and obstetric outcome after laparoscopic myomectomy for infertility.

OBJECTIVE: To determine the effect of myomectomy on infertility and to assess the factors influencing reproductive outcome. DESIGN: Retrospective study. SETTING: Tertiary care center. PATIENT(S): One hundred and three infertile women with uterine leiomyoma who had had infertility >2 years and a follow-up time >12 months were enrolled. Follow-up was complete for 88 patients, including 28 (31.8%) with primary infertility and 44 (50%) with unexplained infertility. The mean (+/-SD) age of the patients was 36.1 +/- 2.1 years. INTERVENTION(S): Laparoscopic myomectomy. MAIN OUTCOME MEASURE(S): Pregnancy rate according to patient and fibroid characteristics. RESULT(S): Forty-two patients became pregnant (40.7%). The mean (+/-SD) delay in conception was 7.5 +/- 2.6 months. Nearly 80% of the women conceived spontaneously. Of 44 pregnancies in 42 women, 36 live newborns were delivered. No dehiscence of uterine scar occurred. The pregnancy rate was significantly higher in women <35 years of age or <3 years of infertility. Women with unexplained infertility had higher pregnancy rate than did women with multifactorial infertility (P<.001). No difference was noted in pregnancy rates according to fibroid characteristics. CONCLUSION(S): Fertility and pregnancy after laparoscopic myomectomy depend primarily on patient age, duration of infertility before myomectomy, and existence of associated infertility factors.

Adolescent↗

The performance of primary and secondary unexplained infertility in an in vitro fertilization-embryo transfer program.

The term "unexplained infertility" is applied to a couple in whom after an elaborate workup no apparent reason for infertility is found. Between August 1985 and May 1987, 435 patients underwent 720 treatment cycles in an in vitro fertilization-embryo transfer (IVF-ET) unit. Eighty-three of the patients had unexplained infertility as their indication for IVF-ET. Fifty-two (group A) had primary unexplained infertility and 31 (group B) had secondary unexplained infertility. Group A underwent 87 and group B underwent 50 treatment cycles. Forty-six ET were performed in group A and 34 in group B. Clinical pregnancies were achieved in 20 patients of group A (11.5% per treatment cycle) and 13 of group B (26.0%), for a combined rate of 16.8% per cycle. Patients with tubal infertility treated in the program had a pregnancy rate of 18.8% per treatment cycle. The performance of the secondary unexplained infertility group is significantly better than that of the primary unexplained infertility group. However, the overall results with patients with unexplained infertility are similar to those patients treated for tubal infertility.

Embryo Transfer↗

The cost of infertility evaluation and therapy: findings of a self-insured university healthcare plan.

OBJECTIVE: To assess the total costs of infertility coverage, determine the proportion of healthcare costs related to infertility, compare infertility costs to those of other diseases, and calculate a per member per month cost of an infertility benefit. DESIGN: Historical prospective analysis. SETTING: A university-based, self-insured, fee-for-service healthcare plan. PATIENT(S): Healthcare policy members from January 1993 through December 1995. INTERVENTION(S): General and infertility-specific healthcare that included diagnostic tests for infertility, induction of ovulation, artificial insemination, donor gametes, in vitro fertilization, gamete intrafallopian transfer, zygote intrafallopian transfer, microsurgical epididymal sperm aspiration, embryo cryopreservation, and frozen embryo transfer. MAIN OUTCOME MEASURE(S): Healthcare costs, as calculated from the International Classification of Diseases, Volume 9 codes. RESULT(S): Total healthcare and infertility-specific costs of the university healthcare plan over a 3-year period were $86,445,642 and $680,921, respectively. Therefore, infertility accounted for 0.79% of the total university healthcare costs. The mean total and infertility-specific per member per month healthcare costs were $86.15 and $0.67, respectively. CONCLUSION(S): These data reveal that infertility costs account for only a small fraction of the total healthcare costs and can be attained at a nominal monthly fee.

Adolescent↗

Relationship between oxidative stress, semen characteristics, and clinical diagnosis in men undergoing infertility investigation.

OBJECTIVE: To determine whether particular semen characteristics in various clinical diagnoses of infertility are associated with high oxidative stress and whether any group of infertile men is more likely to have high seminal oxidative stress. Reactive oxygen species (ROS) play an important role in sperm physiological functions, but elevated levels of ROS or oxidative stress are related to male infertility. DESIGN: Measurement of sperm concentration, motility, morphology, seminal ROS, and total antioxidant capacity (TAC) in patients seeking infertility treatment and controls. SETTING: Male infertility clinic of a tertiary care center. PATIENT(S): One hundred sixty-seven infertile patients and 19 controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Semen characteristics, seminal ROS, and TAC in samples from patients with various clinical diagnoses and controls. RESULT(S): Fifteen patients (9.0%) were Endtz positive and 152 (91.0%) Endtz negative. Sperm concentration, motility, and morphology were significantly reduced in all groups compared with the controls (P =.02), except in varicocele associated with infection group. Mean (+/-SD) ROS levels in patient groups ranged from 2.2 +/- 0.13 to 3.2 +/- 0.35, significantly higher than controls (1.3 +/- 0.3; P<.005). Patient groups had a significantly lower mean (+/-SD) TAC from 1014.75 +/- 79.22 to 1173.05 +/- 58.07 than controls (1653 +/- 115.28, P<.001), except in the vasectomy reversal group (1532.02 +/- 74.24). Sperm concentration was negatively correlated with ROS both overall and within all groups (P</=.007), with the exception of idiopathic infertility. CONCLUSION(S): Irrespective of the clinical diagnosis and semen characteristics, the presence of seminal oxidative stress in infertile men suggests its role in the pathophysiology of infertility. Medical or surgical treatments for infertility in these men should include strategies to reduce oxidative stress.

Antioxidants↗

Infertility in rural Ghana.

OBJECTIVES: This study measured the prevalence of self-reported infertility, as well as the level of knowledge of causes of infertility. Infertility was defined as failure to achieve conception after a minimum of 12 months of exposure. METHODS: Prevalence and knowledge of infertility were assessed in a representative community-based survey using a structured questionnaire in a rural district in Ghana among a random sample of 2,179 men and women from 15 to 49 years. RESULTS: The prevalence of infertility was 11.8% among women and 15.8% among men. The knowledge of causes of infertility was limited; only 46.5% of the respondents reported any cause. Most respondents failed to identify reproductive tract infections as causes of infertility. CONCLUSIONS: Infertility in Ghana and other sub-Saharan countries deserves more recognition as a public health problem. Prevention and treatment of infertility should be incorporated in reproductive health programs, while male participation in reproductive health programs and research needs to be encouraged. Public education about the causes of infertility is recommended.

Adolescent↗

Human leukocyte antigen class II DQ alleles associated with Chlamydia trachomatis tubal infertility.

OBJECTIVE: To investigate epidemiologic tubal infertility risk factors and the relationship between HLA class II alleles and Chlamydia trachomatis tubal infertility. METHODS: Forty-seven women with tubal infertility and 46 fertile controls were studied in Nairobi, Kenya. A questionnaire was administered and serum collected for measurement of C trachomatis antibodies. HLA class II molecular typing was done with DNA extracted from peripheral blood lymphocytes. The prevalence of C trachomatis microimmunofluorescence antibody, chlamydia heat shock protein 60 antibody, and HLA class II alleles was compared among cases of tubal infertility and fertile controls. RESULTS: Women with tubal infertility more often had histories of pelvic inflammatory disease (15% versus 0%; odds ratio [OR] 16; 95% confidence interval [CI] 5.5, 47) histories of spontaneous abortion (34% versus 7%; OR 6.7; 95% CI 2.8, 16), and antibodies to C trachomatis (53% versus 26%; OR 3.2; 95% CI 1.3, 7.7) than controls. Among infertile women, DQA*0101 and DQB*0501 alleles were positively associated with C trachomatis tubal infertility (OR 4.9; 95% CI 1.3, 18.6, and OR 6.8; 95% CI 1.6, 29.2, respectively). DQA*0102 was negatively associated with C trachomatis tubal infertility (OR 0.2; 95% CI 0.005, 0.6). CONCLUSION: Chlamydia trachomatis infection is an important cause of tubal infertility in Nairobi. The association of specific HLA class II alleles with C trachomatis microimmunofluorescence seropositivity among women with tubal infertility suggests that the DQ locus might modify susceptibility to and pathogenicity of C trachomatis infection.

Adult↗

Psychological evaluation test for infertile couples.

PURPOSE: The infertility can lead to various emotional changes (anxiety, depression, somatization, aggressiveness, etc.). The objective of the present study was to develop a psychological evaluation test (PET) in an attempt to identify couples requiring psychological support when they face the problem of infertility. MATERIAL AND METHODS: A total of 251 infertile couples were submitted to the PET of the Center for Human Reproduction, "Sinhá Junqueira" Maternity Foundation. The causes of infertility were male-related in 45% of cases, female-related in 48%, and both male- and female-related in 7%. Infertility was primary in 74% of cases and secondary in 26%. The mean age of the women was 34 +/- 4.2 years and the mean age of the men was 36.8 +/- 6.5 years. The PET of the infertile couples was evaluated using a questionnaire with 15 questions selected in order to detect emotional reactions. The responses were assigned four grades with respect to frequency (1 = never or rarely; 2 = sometimes; 3 = many times, and 4 = always). The sum of the responses corresponded to a PET score ranging from 15 to 60 points. A PET score of >30 points was defined as cut-off point for necessity of specialized psychological evaluation. Data were analyzed statistically by the Student's t test and the Mann-Whitney and Fisher tests, with the level of significance set at 5%. The reliability of the questionnaires was determined on the basis of the alpha coefficient of Cronbach. RESULTS: The mean PET score for women (27 +/- 8) was significantly higher (p < 0.01, Mann-Whitney test) than the PET score for men (22 +/- 7). The alpha coefficient of Cronbach was 0.88, and was identical for the female and male questionnaires. CONCLUSIONS: The data demonstrate that one of the characteristics of Brazilian infertile couples is that women are habitually more affected by the situation of infertility than men. The PET is a simple and efficient tool for the identification of women and/or men requiring psychological support due to infertility. The team of the Center for Human Reproduction (employees, biologists, nurses, doctors etc.) has started to use the information provided by the PET in the daily routine, and all patients are informed and counseled about the factors generating emotional changes in infertility. Advice is provided (practicing sports, traveling, activating personal projects etc.) in order to help combat distress. A specialized psychological evaluation was indicated in selected cases (PET score >30 points).

Adult↗

Cytogenetic and molecular analysis of the Y chromosome: absence of a significant relationship between CAG repeat length in exon 1 of the androgen receptor gene and infertility in Indian men.

The genetic basis of male infertility remains unclear in the majority of cases. Recent studies have indicated an association between microdeletions of the azoospermia factor a (AZFa)-AZFc regions of Yq and severe oligospermia or azoospermia. Increased (CAG)n repeat lengths in the androgen receptor (AR) gene have also been reported in infertile men. Therefore, in order to assess the prevalence of these genetic defects to male infertility, 183 men with non-obstructive azoospermia (n = 70), obstructive azoospermia (n = 33), severe oligospermia (n = 80) and 59 fertile men were examined cytogenetically and at molecular level for Yq deletions, microdeletions, and AR-CAG repeat lengths along with hormonal profiles [luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone (T)]. We used high resolution cytogenetics to detect chromosome deletions and multiplex polymerase chain reaction (PCR) involving 27 sequence-tagged site (STS) markers on Yq to determine the rate and extent of Yq microdeletions. PCR amplification with primers flanking exon 1 of AR gene was used to determine the AR-(CAG)n repeat lengths. Hormonal profiles (LH, FSH and T levels) were also analysed in infertile and fertile men. Testicular biopsies showed Sertoli cell only (SCO) morphology, maturation arrests (MA) and hypospermatogenesis. No chromosome aberrations were found in infertile men but there was a significant increase (p < 0.001) in the association of acrocentric chromosomes including the Y chromosome. Yq microdeletions were found in 16 non-obstructive azoospermic men (16 of 70; 22%) and seven severe oligospermic individuals (seven of 80; 8.7%) and most of them had deletions in the sY240 locus. No Yq microdeletions were detected in patients with obstructive azoospermia. No statistically significant difference in the mean length of CAG repeats in AR gene was observed between infertile and fertile men (22.2 +/- 1.5 and 21.5 +/- 1.4 respectively). No significant increase or decrease in levels of LH, FSH and T was observed in infertile and fertile men. In some infertile men, significantly elevated levels of FSH alone or in combination with LH were found to be indicative of failure of spermatogenesis and/or suggestive of testicular failure. Y-chromosome microdeletions contribute to infertility in some patients but no relationship could be established with the (CAG)n repeat lengths in exon 1 of the AR gene in infertile Indian men.

Adenine↗