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The experiences of couples who have had infertility treatment in the United Kingdom: results of a survey performed in 1997.

A questionnaire was sent to 2000 members of two of the largest national infertility support organizations as part of the National Infertility Awareness Campaign (NIAC), 1997. A total of 980 questionnaires was completed and returned to the market research company, Ballington Hall. Some 69% of the respondents were aged between 30 and 39 years. One-third of the couples had been trying for a baby for more than 3 years, including one-tenth who had been trying to conceive for more than 10 years. Some 40% of respondents were successful in conceiving, although a significant proportion of these took more than 6 years. About 75% of those surveyed had been forced to pay for some or all of their infertility treatments and investigations, whereas 18% had their treatments funded fully by the National Health Service (NHS). Funding sources for the remaining 7% were unknown. Just over one-third of respondents felt that their GP provided sufficient information about the causes of infertility investigations and treatment, while the majority said that their specialists had been helpful. One in three said that they did not fully understand the medical nature of their own or their partner's infertility. A wide range of negative emotions was experienced by respondents. One in five said they experienced suicidal feelings; one in three said that infertility had strained their relationship; and just over one-quarter found that their relationship improved as a result of the treatment. Some 71% said that they would request counselling if it were offered free, but only 12% had been provided with free counselling on the NHS.

Adult↗

Optimal use of infertility diagnostic tests and treatments. The ESHRE Capri Workshop Group.

The general definition of infertility is a lesser capacity to conceive than the mean capacity of the general population and infertile couples can be characterized in two groups: those unable to conceive without therapy and those who are hypofertile, but conceive without therapy. The initial diagnostic tests for infertility should include a midluteal phase progesterone assay, a semen analysis and a test for tubal patency such as a hysterosalpingogram. Measuring progesterone is the best test for confirming ovulation. To predict ovulation, evaluating the luteinizing hormone (LH) surge is the best single assay while measurement of LH plus preovulatory oestrogen is the best prediction. Today primary investigation of the morphology of the uterus and tubes should be by hysterosalpingography. However, ultrasound, particularly with simple contrast media, is likely to gain in importance. Laparoscopy should be reserved as a further diagnostic procedure or in combination with endoscopic surgery. There are situations in which semen analysis is of utmost importance and of absolute predictive value, namely, in cases of azoospermia. In general semen analysis remains a substantial part of the fertility workup, but any consideration of its predictive value has to be cautious. Performing genetic tests before, during and after assisted reproductive techniques (ART) is an intrinsic part of good clinical practice. These tests allow one to reach a correct diagnosis, to give adequate genetic counselling to the couple and their families in cases such as (i) women with Turner syndrome; (ii) men with 47, XXY; (iii) men or women with structural chromosomal aberration; (iv) men with Yq11 deletion or (v) men with congenital bilateral absence of vas deferens. Patients should, of course, be made aware of the occurrence of de-novo mutations taking place in the testis and in the embryo. Treatment of some causes of infertility are of proven value. For example induction of ovulation. Others are more controversial. Among the many empirical treatments suggested for the treatment of the various form of subfertility, surgical treatment of varicocele in the male, treatment of pelvic endometriosis in the female and the efficacy of the ART strategies offered to the subfertile couple are considered. Many varicocele studies are of poor quality. A few are good, but small in size. They do not show an improvement in pregnancy rates. Therefore, at the moment, there is insufficient scientific evidence for recommending routinely surgical treatment in subfertile and/or oligozoospermic men with a varicocele. Randomized, double-blind controlled trials demonstrated the modest efficacy of endometriosis ablation in increasing the pregnancy rate in infertile women while drugs suppressing ovulation are of no benefit to infertile women with endometriosis. Although the largest body of evidence available suggests that IVF success declines in repeated ART cycles, an accurate estimate of the true success rate in the 'nth' cycle of IVF treatment is not possible. Similarly little is still known of the reasons for the overall low continuation rates with IVF treatment.

Endometriosis↗

Gender-sensitive association of CFTR gene mutations and 5T allele emerging from a large survey on infertility.

Human infertility in relation to mutations affecting the cystic fibrosis transmembrane regulator (CFTR) gene has been investigated by different authors. The role of additional variants, such as the possible forms of the thymidine allele (5T, 7T and 9T) of the acceptor splice site of intron 8, has in some instances been considered. However, a large-scale analysis of the CFTR gene and number of thymidine residues, alone and in combination, in the two sexes had not yet been addressed. This was the aim of this study. Two groups were compared, a control group of 20,532 subjects being screened for perspective reproduction, and the patient group represented by 1854 idiopathically infertile cases. Analyses involved PCR-based CFTR mutations assessment, reverse dot-blot IVS8-T polymorphism analyses, denaturing gradient gel electrophoresis (DGGE) and DNA sequencing. The expected 5T increase in infertile men was predominantly owing to the 5/9 genotypic class. The intrinsic rate of 5T fluctuated only slightly among groups, but some gender-related differences arose when comparing their association. Infertile men showed a significantly enriched 5T + CFTR mutation co-presence, distributed in the 5/9 and 5/7 classes. In contrast, females, from both the control and the infertile groups, showed a trend towards a pronounced reduction of such association. The statistical significance of the difference between expected and observed double occurrence of 5T + CFTR traits in women suggests, in line with other reports in the literature, a possible survival-hampering effect. Moreover, regardless of the 5T status, CFTR mutations appear not to be involved in female infertility. These results underline the importance of (i) assessing large sample populations and (ii) considering separately the two genders, whose genotypically opposite correlations with these phenomena may otherwise tend to mask each other.

Alleles↗

Chlamydial serology among patients with tubal factor infertility and ectopic pregnancy in Alexandria, Egypt.

BACKGROUND AND OBJECTIVES: Little is known about the role of Chlamydia trachomatis in the etiology of tubal factor infertility and ectopic pregnancy in Egypt. GOAL OF THIS STUDY: To assess the association between past chlamydial infection, tubal factor infertility, and ectopic pregnancy in an Egyptian population. STUDY DESIGN: This report consists of two concurrent case-control studies. First, 51 patients with tubal factor infertility were compared with 48 healthy subjects who did not have tubal factor infertility and 53 pregnant subject subjects. Second, 66 patients with ectopic pregnancy were compared with 51 pregnant control subjects. RESULTS: Geometric mean titers for Chlamydia trachomatis were higher among patients with tubal factor infertility and ectopic pregnancy, and they were more likely to have high antichlamydial titers (> or = 1:128 immunoglobulin G). Serum titer was significantly correlated with histologic evidence of salpingitis among the patients with an ectopic pregnancy. CONCLUSION: Our findings, similar to those from Western societies, suggest that among Egyptian women, prior chlamydial infection is associated with an increased risk of tubal factor infertility and possibly ectopic pregnancy.

Adult↗

Increased infertility with age in men and women.

OBJECTIVE: To estimate the effects of aging on the percentage of outwardly healthy couples who are sterile (completely unable to conceive without assisted reproduction) or infertile (unable to conceive within a year of unprotected intercourse). METHODS: A prospective fecundability study was conducted in a sample of 782 couples recruited from 7 European centers for natural family planning. Women aged 18-40 years were eligible. Daily intercourse records were used to adjust for timing and frequency of intercourse when estimating the per-menstrual-cycle probability of conception. The number of menstrual cycles required to conceive a clinical pregnancy and the probability of sterility and infertility were derived from the estimated fecundability distributions for men and women of different ages. RESULTS: Sterility was estimated at about 1%; this percent did not change with age. The percentage infertility was estimated at 8% for women aged 19-26 years, 13-14% for women aged 27-34 years and 18% for women aged 35-39 years. Starting in the late 30s, male age was an important factor, with the percentage failing to conceive within 12 cycles increasing from an estimated 18-28% between ages 35 and 40 years. The estimated percentage of infertile couples that would be able to conceive after an additional 12 cycles of trying varied from 43-63% depending on age. CONCLUSION: Increased infertility in older couples is attributable primarily to declines in fertility rates rather than to absolute sterility. Many infertile couples will conceive if they try for an additional year.

Adolescent↗

Pattern of semen analysis of male partners of infertile couples at the University College Hospital, Ibadan.

OBJECTIVES: To evaluate the seminal patterns of the male partners of the infertile couples, towards identifying the possible contribution of the male factors to overall infertility problem in our environment. METHODOLOGY: The study is a descriptive analysis of the seminal patterns of the partners of the infertile couples, who presented at the Fertility Research Unit (a WHO collaborating centre) of the Department of Obstetrics and Gynaecology, University College Hospital, Ibadan, Nigeria, between 1st January 1990 and 31st December, 1999. RESULTS: Result of the seminal analysis of 824 male partners of infertile couples were retrieved for the study, of which 598 (73%) were referred for secondary infertility. Overall, 225 (27.3%) of these subjects had abnormal semen analyses, with Asthenozoospermia being the most common (27.8%) of the disorders observed. Fifty-four (6.7%) subjects of the study population had Azoospermia. The most common multiple factors abnormality in the study population was Astheno/Oligozoospermia (25.5%), while three factors defect--Oligo/Astheno/Teratozoospermia was noticed in 106 (13.1%) of the subjects. CONCLUSION: Abnormal semen quality remains a significant contribution to overall infertility in our environment and Asthenozoospermia is the most common seminal quality abnormality.

Female↗

Effectiveness of in vitro fertilization with intracytoplasmic sperm injection for severe male infertility.

BACKGROUND: In its 1993 report the Canadian Royal Commission on New Reproductive Technologies challenged the effectiveness of in vitro fertilization for severe male infertility. To address the Commission's concern, the authors compared the relative effectiveness of in vitro fertilization combined with intracytoplasmic sperm injection for severe male infertility and conventional in vitro fertilization for complete tubal occlusion in women. METHODS: This historical cohort study was done at the PROCREA Fertility Centre, a private tertiary human reproduction centre in Montreal. Three groups of infertile couples were compared: 122 couples with severe male infertility treated by in vitro fertilization with intracytoplasmic injection of fresh sperm from ejaculate (group 1); 27 couples with obstructive azoospermia treated by in vitro fertilization with intracytoplasmic injection of epididymal sperm (collected by microepididymal or percutaneous epididymal sperm aspiration) (group 2); and 98 couples with tubal factor infertility (bilateral tubal occlusion) treated with conventional in vitro fertilization (with sperm from ejaculate) (group 3). The main outcomes measured were rates of fertilization, pregnancy, clinical pregnancy and implantation. RESULTS: Pregnancy rates per started cycle were 35%, 40% and 34% for groups 1, 2 and 3 respectively. When prognostic factors were controlled for, none of the outcome measures differed significantly between the 3 groups. INTERPRETATION: In vitro fertilization with intracytoplasmic injection of sperm from the ejaculate or the epididymis is as effective for treating severe male infertility as conventional in vitro fertilization is for treating complete occlusion of the fallopian tubes in women.

Adult↗

[The epidemiology of infertility in families].

This study of epidemiology of infertility in families has employed the guidelines of the WHO Program on Human Reproduction. The study involved 1976 infertile couples. It elucidated major diagnosis-related groups in the female and male population and data sets of the couples. The basis of infertility remained uncertain in only 2.1% of the families. Infertility was underlied only by a female reproductive disease in 44.4% of the families, with about half of these cases being endocrine disorders. Diseases of husbands, primarily varicocele and primary testicular lesions, accounted for infertility in 19.3% of the families. Determinants of infertility in both spouses were identified in 34.2% of the families, mostly genital inflammatory diseases.

Chronic Disease↗

Clinical factors affecting pregnancy rates among infertile couples.

In a follow-up study of 1297 couples registered at a Nova Scotia infertility clinic with a complaint of infertility of at least 12 months' duration, the cumulative pregnancy rate at 36 months, with 95% confidence limits, was found to be 49 +/- 4%. The predictors of pregnancy by univariate analysis were a favourable primary clinical diagnosis (p less than 0.001), a duration of infertility of less than 3 years (p less than 0.001), a single diagnosis for the infertility (p less than 0.001), a previous pregnancy in the partnership (p = 0.001) and a length of marriage of less than 4 years (p = 0.002). Proportional hazards analysis confirmed these variables as predictors of pregnancy. The highest cumulative pregnancy rates after 12 and 36 months of follow-up were observed in cases of ovulation deficiency, and the lowest were seen in cases of tubal defects. However, before the process of diagnosing infertility begins, useful prognostic information can be determined from the length of marriage, the duration of infertility and the partnership's history of previous pregnancy.

Adult↗

Occupation and the clinical characteristics of infertile couples.

BACKGROUND: The influence of social class on the composition of infertile groups and on their use of health care services could reflect how the latter meet the non-urgent needs for health care in populations. METHODS: Clinical, demographic, and occupational variables were collected prospectively from 2,198 couples newly registered in 11 infertility clinics. Time to diagnostic laparoscopy and time to treatment were evaluated with the use of proportional hazards analysis. RESULTS: 1) In the upper quartile of family income, the duration of infertility was six months less than for couples with the lowest incomes; 2) Tubal infertility was independently associated with lower family income; 3) Occupation and income were unrelated to the likelihood of either a complete diagnostic assessment or treatment for the infertility. CONCLUSIONS: Social class seems an important factor in the distribution of infertility diagnoses, although occupation and income were not associated with important clinical management decisions.

Adult↗

The role of the anti-sperm autoantibodies in the management of patients with primary infertility.

The role of antibody mediated infertility in patients with primary/secondary unexplained infertility is the subject of current interest worldwide. A prospective study was conducted to study the role of anti sperm antibodies in Pakistani patients with infertility. Patients reporting in the outpatient clinic of a local gynaecology department with problem of infertility were subjected to a detailed scrutiny by history and clinical examination including post-coital test and hysterosalpingography. Hormonal profile consisting of serum FSH, LH, Prolactin and Progesterone was assessed. Most of the ladies also underwent a pelviscopic examination. A total of 117 patients were selected where post-coital test was abnormal, semen analysis was not satisfactory or who had unexplained infertility. Tests were performed on the serum specimen from the husbands, wives and in some cases on the seminal plasma as well, for the measurement of the anti sperm agglutinating and anti-sperm immobilizing antibodies by the microagglutination technique. Fifteen of these patients were found positive for these antibodies, 7 were positive for the agglutinating antibody, 6 for the immobilizing antibody and two for both types. These results indicate that immunomodulation may be responsible for some cases of infertility in our population.

Autoantibodies↗

[Diagnosis and treatment in infertile marriage].

The paper gives data on the frequency and pattern of infertile marriage by referrals to the clinic of infertility, Center of Obstetrics, Gynecology, and Perinatology, Russian Academy of Medical Sciences. Tubuloperitoneal disorders are the leading and challenging abnormality in aphoria. Endometriosis and endocrine types of infertility occupy the second place in their incidence. Emphasis is laid on the role of laparoscopy in the complex examination of infertile females. Analysis of the causes of male infertility suggests that abnormalities resultant from sexually transmitted diseases are prevalent. The diagnosis and treatment of marriage infertility caused by immunological and psychogenic factors call for further development.

Adult↗

A prospective study of infertility due to ovulatory disorders, ovulation induction, and incidence of breast cancer.

BACKGROUND: Anovulation has been hypothesized to decrease the risk of breast cancer. Therefore, infertility attributed to ovulatory disorders and ovulation-induction therapy may influence breast cancer risk. METHODS: We analyzed prospectively collected data from the Nurses' Health Study II, a cohort of 116,671 female registered nurses aged 25 to 42 years at baseline. Information on infertility was assessed every 2 years starting in 1989, ovulation induction was assessed every 2 years from 1993 to 1997, and incident cases of breast cancer were included through 2001. RESULTS: During 1,275,566 person-years of follow-up (1989-2001), 1357 incident cases of invasive breast cancer were diagnosed. Overall, women who reported infertility due to ovulatory disorder had a significantly lower incidence of breast cancer than women who did not report problems conceiving during a 12-month period (covariate-adjusted hazard ratio, 0.75; 95% confidence interval, 0.59-0.96). The incidence of breast cancer was lowest among women with infertility due to ovulatory disorder who received ovulation-induction therapy (covariate-adjusted hazard ratio, 0.60; 95% confidence interval, 0.42-0.85). CONCLUSIONS: Among women who participated in the Nurses' Health Study II, we observed an inverse association between infertility due to ovulatory disorder and breast cancer incidence. We observed the greatest reduction in the incidence of breast cancer for women who reported ovulatory disorder and use of ovulation-induction therapy, but these results should be interpreted with caution because these women may be the most infertile.

Adult↗

Association between female infertility and agricultural work history.

Lifetime industrial and occupational histories of women with a medically-confirmed diagnosis of infertility (n = 281) were compared to a group of postpartum women (n = 216) for risks of infertility. Controlling for age of first pregnancy or self-report of infertility, date of outcome, cigarette use, and employment in other types of industries, women were at increased risk of infertility if they had worked in industries associated with agriculture (OR = 7.0, 95% CI 2.3-20.8; cases = 11.7%, controls = 1.9%). Among the occupations in which women worked prior to outcome, only those in agriculture were at significantly elevated risk (adj. OR = 11.3, CI 2.6-48.8; cases = 10.0%, controls = 0.9%). Among those who resided on a farm, the risk of infertility was significantly increased (adj. OR = 1.8, CI 1.2-2.7; cases = 37.4%, controls = 25.8%) although yearly duration of farm residence was not (adj. OR = 0.99, CI 0.95-1.03). Farm residence did not alter the OR seen in agricultural industries or occupations. The risk of being diagnosed with an ovulatory or tubal factor increased 4-16-fold among those who had worked in agricultural industries or occupations. These data suggest that, as has been established in men, agriculturally-related exposures may be a significant risk for infertility in women.

Adolescent↗

Heterologous ovum penetration test and seminal parameters in fertile and infertile men.

Sperm penetration rates in the heterologous ovum penetration test were correlated with results of routine semen analysis in 30 fertile and 50 infertile men. There was no difference in penetration rates when comparing infertile men with normal and abnormal seminal parameters, nor was any difference seen between fertile (15-83%) and infertile men (8-83%). Of the 22 infertile men with normal seminal characteristics, seven had partners with no discernible reproductive dysfunction. The penetration rates of these men (38-81%) did not differ from those of fertile men. Stepwise regression analysis of seminal characteristics, with penetration as the dependent variable, indicated that sperm count and morphology are the most important seminal parameters for fertility assessment. Discrimination analysis revealed that sperm numbers and morphologic variables provide significant information for discriminating between fertile men and infertile men with normal or abnormal seminal characteristics. Sperm penetration and motility were not indicated as important factors. The present data suggest that, in unselected male patients seeking reproductive evaluation, the sperm penetration assay did not yield any additional information on the cause of infertility.

Adult↗

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

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

Animals↗

Decreased protein tyrosine phosphorylation and membrane fluidity in spermatozoa from infertile men with varicocele.

Varicocele is a prevalent pathology among infertile men. The mechanisms linking this condition to infertility, however, are poorly understood. Our previous work showed a relationship between sperm functional quality and the ability of spermatozoa to respond to capacitating conditions with increased membrane fluidity and protein tyrosine phosphorylation. Given the reported association between varicocele, oxidative stress, and sperm dysfunction, we hypothesized that spermatozoa from infertile patients with varicocele might have a combined defect at the level of membrane fluidity and protein tyrosine phosphorylation. Semen samples from infertile patients with and without grade II/III left varicocele were evaluated for motion parameters (computer-assisted semen analysis [CASA]), hyperactivation (CASA), incidence and intensity of protein tyrosine phosphorylation (phosphotyrosine immunofluorescence and western blotting), and membrane fluidity (Laurdan fluorometry), before and after a capacitating incubation (6 hr at 37 degrees C in Ham's F10/BSA, 5% CO(2)). Spermatozoa from varicocele samples presented a decreased response to the capacitating challenge, showing significantly lower motility, hyperactivation, incidence and intensity of tyrosine phosphorylation, and membrane fluidity. The findings reported in this article indicate that the sperm dysfunction associated to infertile varicocele coexists with decreased sperm plasma membrane fluidity and tyrosine phosphorylation. These deficiencies represent potential new pathophysiological mechanisms underlying varicocele-related infertility.

Adult↗

Chlamydia specific IgG and IgA antibodies in women with obstructive infertility as determined by immunoblotting and immunoperoxidase assays.

The prevalence rate of IgG and IgA antibodies to Chlamydia was analyzed in 50 women with laparoscopy-verified tubal infertility and in 50 age-matched control women by single serovar (L2) inclusion immunoperoxidase assay (IPA) and by immunoblotting technique (IB). Women with tubal infertility had significantly (p less than 0.001) elevated IPA Chlamydia IgG antibody titer greater than or equal to 128 and greater than or equal to 256 than controls (64% vs 16%. Odds ratios = 9.3 and 50% vs 10%, Odds ratio = 9 respectively). The prevalence rate of IPA IgA antibody titer (greater than or equal to 16) to Chlamydia was also significantly higher (p less than 0.001) in women with tubal infertility than controls (48% vs 8%, Odds ratio = 10.6). Antibodies to at least 19 chlamydial structural polypeptides ranging in molecular weight from 30 kD to 204 kD, were detected by the IB technique in the IPA seropositive sera. Antibodies to 57-60 kD were detectable in almost all the IPA IgG and IgA seropositive sera. The prevalence rate of IgG antibody to 57 kD-60 kD was significantly higher in women with obstructive infertility than healthy woman (84% vs. 56% p less than 0.01; Odds ratio = 3.8). More significantly, higher differences to 57-60 kD polypeptide were found in the case of IgA between the infertile women and controls (52% vs. 10%, p less than 0.001; Odds ratio = 9.7). The significance of IPA and IB technique for screening of infertile women is discussed.

Adult↗