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PubMed2004

Infertility in the third millennium: implications for the individual, family and society: condensed meeting report from the Bertarelli Foundation's second global conference.

Primary infertility is a key issue in the developed world, while the developing world has high rates of secondary infertility. The impact of HIV/AIDS on fertility is insufficiently explored. One of the most important barriers to access to infertility treatment is cost; at the same time the role of social and cultural factors in restricting access should not be underestimated. IVF has become the standard therapy for female infertility, and ICSI for infertility of the male partner. However, the use of these therapies should not be initiated without a thorough investigation and, whenever possible, individual diagnosis of the underlying causes of infertility. Multiple gestation remains one of the most challenging and controversial issues in the treatment of infertility. Current IVF practices are often blamed for this; in this respect, attention should also be focused on the role of ovarian stimulation in ovulation induction. National guidelines and national registries for assisted reproductive technology (ART) are becoming more widespread and are expected to play an important role in promoting best practice in ART in the future.

Adult↗
PubMed1997

HIV infection and sexual behaviour among women with infertility in Tanzania: a hospital-based study.

BACKGROUND: Infertility is common in Africa, but virtually no data exist on HIV prevalence among infertile women. Mainly anthropological studies in Africa have shown that infertile women have higher risks of marital instability and possibly also have more sexual partners than fertile women. METHOD: This study was conducted in a hospital in northwest Tanzania during 1994 and 1995. Women presenting themselves with infertility problems to the outpatient clinic were interviewed, examined and blood was drawn. Women who came to deliver in the hospital, excluding primiparae, were taken as a control group. The analysis was limited to women > or = 24 years. In total 154 infertile and 259 fertile women were included in the study. RESULTS: HIV prevalence was markedly higher among infertile women than among fertile women: 18.2% and 6.6% respectively (adjusted odds ratio [OR] for age, residence and occupation 2.7; 95%-confidence interval [CI]: 1.4-5.3). Data on past sexual behaviour showed that infertile women had more marital breakdowns, more lifetime sexual partners and a higher level of exposure to sexually transmitted diseases (STD). CONCLUSION: Women with fertility problems appear to have higher HIV prevalence, which justifies more attention for such women in the context of AIDS programmes. In addition, caution is needed when using sentinel surveillance data from antenatal clinics to monitor HIV prevalence.

Adult↗
PubMed1999

Human sperm proteome: immunodominant sperm surface antigens identified with sera from infertile men and women.

The objective of this study was to identify those immunodominant sperm antigens recognized by antisperm antibodies (ASA) in the serum samples of infertile men and women. High-resolution two-dimensional gel electrophoresis was employed to separate human sperm proteins using isoelectric focusing or nonequilibrium pH gradient electrophoresis, followed by PAGE. Serum samples from 15 infertile male subjects and 6 infertile female subjects that contained ASA as assayed by the immunobead binding test (IBT) were analyzed by Western blotting followed by enhanced chemiluminescence (ECL). Serum samples from 10 fertile subjects (5 males and 5 females) that were ASA negative by IBT were used as controls. The ECL blots were analyzed by computer scanning to compare the immunoreactivity between serum samples from fertile and infertile subjects and to identify the antigens unique to the sera of the infertile subjects; 98 sperm auto- and iso-antigenic protein spots were recognized by sera from infertile males and females but not from fertile subjects. Based on vectorial labeling with 125I at the sperm surface, a subset of 6 auto- and iso-antigens was identified as possibly relevant to antibody-mediated infertility.

Antigens, Surface↗
PubMed2000

Cost-effective treatment for the couple with infertility.

Although the evaluation of cost-effective approaches to infertility treatment remains in its infancy, several important principles have emerged from the initial studies in this field. Currently, in treating couples with infertility without tubal disease or severe male-factor infertility, the most cost-effective approach is to start with IUI or superovulation-IUI treatments before resorting to IVF procedures. The woman's age and number of sperm present for insemination are significant factors influencing cost-effectiveness. The influence of certain diagnoses on the cost-effectiveness of infertility treatments requires further study. Even when accounting for the costs associated with multiple gestations and premature deliveries, the cost of IVF decreases within the range of other cost-effective medical procedures and decreases to less than the willingness to pay for these procedures. Indeed, for patients with severe tubal disease, IVF has been found to be more cost-effective than surgical repair. The cost-effectiveness of IVF will likely improve as success rates show continued improvements over the course of time. In addition, usefulness of embryo selection and practices to reduce the likelihood of high-order multiple pregnancies, without reductions in pregnancy rates, will significantly impact cost-effectiveness. The exclusion of infertility treatments from insurance plans is unfortunate and accentuates the importance of physicians understanding the economics of infertility treatment with costs that are often passed directly to the patient. The erroneous economic policies and judgments that have led to inequities in access to infertility health care should not be tolerated.

Cost-Benefit Analysis↗
PubMed1992

Etiological implication of autoantibodies to zona pellucida in human female infertility.

PROBLEM: Autoantibodies to zona pellucida (ZP) have been implicated as a cause of infertility in woman by three lines of clinical and laboratory evidence. METHOD: First, positive anti-zona activities, as assessed by the passive hemagglutination reaction (PHAR) using bovine red blood cells sensitized with porcine zona antigen, were detected in 45 of 1,872 serum samples collected from infertile women, but in only three (two nonpregnant and one pregnant) of 592 serum samples from control subjects. Their incidence in 320 women with unexplained infertility (5.6%) was much higher than that in 1,552 women with infertility of known cause (1.7%, P < 0.01), which was comparable to the incidence observed in 193 age-matched fertile nonpregnant and pregnant women (1.5%, P < 0.05). None of the serum samples from 292 age-matched adult men and 100 children of between 5 and 10 years old gave a positive PHAR. Second, follow-up study for a minimum of 2 years with treatment revealed that no pregnancy occurred in 11 infertile women with a consistently positive PHAR, and only three pregnancies in 19 infertile women with a fluctuating positive PHAR. Third, three of seven serum samples from women who gave a consistently positive PHAR produced strong immunofluorescence reactions on human ZP even after adsorption with porcine and human AB blood cells. Pre-exposure of human ZP to the sera showing positive immunofluorescence, including that of one patient undergoing an in vitro fertilization program, greatly diminished the number of spermatozoa of normal quality that bound to and penetrated across human ZP. CONCLUSIONS: The observed high incidence of anti-zona activities and long-term resistancy to treatment in women with unexplained infertility may be closely correlated with inhibition of sperm-egg interaction by anti-zona autoantibodies produced in these women.

Antibody Formation↗
PubMed2000

Anti-sperm antibodies from infertile patients and their cognate sperm antigens: a review. Identity between SAGA-1, the H6-3C4 antigen, and CD52.

PROBLEM: The correlation of anti-sperm antibodies (ASA) with some instances of unexplained infertility implicates a role for these antibodies in blocking fertilization. Improved diagnosis and treatment of immunologic infertility, as well as a more complete understanding of the mechanism behind this phenomenon, are dependent on the identification and characterization of relevant sperm antigens. METHOD OF STUDY: In this article, we review literature on methods employed to identify sperm antigens using anti-sperm polyclonal and monoclonal antibodies from infertile patients and vasectomized men. Particular focus is given to approaches using human and mouse monoclonal antibodies to define the SAGA-1 human sperm antigen. RESULTS: ASA present in sera and genital tract secretions from infertile patients and vasectomized men have been employed in a variety of methods to identify sperm antigens. In an alternate approach, a monoclonal antibody (mAb), H6-3C4, was immortalized from the lymphocytes of an infertile woman who exhibited sperm-immobilizing titers. Subsequently, the sperm-agglutinating, murine S19 mAb was shown to react with the H6-3C4 cognate antigen. The H6-3C4 S19 cognate antigen, designated Sperm Agglutination Antigen-1 (SAGA-1), was characterized as a polymorphic, highly acidic, GPI-anchored glycoprotein on the surface of human spermatozoa. Purification with the S19 mAb followed by microsequencing demonstrated that the SAGA-1 core peptide is identical to CD52, a glycoprotein on the surface of human lymphocytes. Immunoblot analysis demonstrated that these two glycoproteins differed in carbohydrate composition. Thus, sperm SAGA-1 and lymphocyte CD52 represent glycoforms, glycoproteins with the same core peptide but with different carbohydrate structures. CONCLUSIONS: Autoimmunity to the SAGA-1 and/or CD52 glycoforms may lead to infertility. Structural and immunologic differences between these glycoproteins may be important factors in the etiology of immunologic infertility and other autoimmune disorders.

Animals↗
PubMed1998

Infertility profile at King Edward VIII Hospital, Durban, South Africa.

A prospective observational study over a 6-month period on women presenting with infertility was conducted at King Edward VIII Hospital (KEH), South Africa. The aim of the study was to establish the patient profile and investigations performed on women presenting with infertility. One hundred women were recruited. The mean age of the women was 31 years and 60% had secondary infertility. The mean duration of infertility was 7.2 years; 61% had histories suggestive of pelvic inflammatory disease and approximately half (49%), had had previous infertility investigations; 16% of the women were HIV (human immunodeficiency virus) antibody positive and 16% had positive syphilis serology. Tubal factors were identifiable in 77%, ovulatory factors in 21% and uterine factors in 21%. Male factor infertility was present in 21%. The study confirms that in developing countries, tubal factors are the commonest cause of infertility.

Adult↗
PubMed2024

Whole exome sequencing analysis of 167 men with primary infertility.

BACKGROUND: Spermatogenic failure is one of the leading causes of male infertility and its genetic etiology has not yet been fully understood. METHODS: The study screened a cohort of patients (n&#x2009;=&#x2009;167) with primary male infertility in contrast to 210 normally fertile men using whole exome sequencing (WES). The expression analysis of the candidate genes based on public single cell sequencing data was performed using the R language Seurat package. RESULTS: No pathogenic copy number variations (CNVs) related to male infertility were identified using the the GATK-gCNV tool. Accordingly, variants of 17 known causative (five X-linked and twelve autosomal) genes, including ACTRT1, ADAD2, AR, BCORL1, CFAP47, CFAP54, DNAH17, DNAH6, DNAH7, DNAH8, DNAH9, FSIP2, MSH4, SLC9C1, TDRD9, TTC21A, and WNK3, were identified in 23 patients. Variants of 12 candidate (seven X-linked and five autosomal) genes were identified, among which CHTF18, DDB1, DNAH12, FANCB, GALNT3, OPHN1, SCML2, UPF3A, and ZMYM3 had altered fertility and semen characteristics in previously described knockout mouse models, whereas MAGEC1,RBMXL3, and ZNF185 were recurrently detected in patients with male factor infertility. The human testis single cell-sequencing database reveals that CHTF18, DDB1 and MAGEC1 are preferentially expressed in spermatogonial stem cells. DNAH12 and GALNT3 are found primarily in spermatocytes and early spermatids. UPF3A is present at a high level throughout spermatogenesis except in elongating spermatids. The testicular expression profiles of these candidate genes underlie their potential roles in spermatogenesis and the pathogenesis of male infertility. CONCLUSION: WES is an effective tool in the genetic diagnosis of primary male infertility. Our findings provide useful information on precise treatment, genetic counseling, and birth defect prevention for male factor infertility.

Humans↗
PubMed1991

Cognitive appraisal and adjustment to infertility.

We examine adults' cognitive appraisals of their infertility and how these appraisals relate to each other and to psychological adjustment. In two samples, 76 women and 54 men rated their appraisals of threat, challenge, and control connected with infertility and completed measures of global and infertility-specific distress. Couples appraised their infertility as both harmful and beneficial, and as relatively uncontrollable. Partners did not differ in their appraisals or global distress, although wives reported more infertility-specific distress than their husbands. Women who were more threatened by their infertility were more distressed, as were those who felt less challenged and those who perceived less control over infertility outcomes. Males' appraisals were unrelated to distress, although men whose wives were more challenged by their impaired fertility were less distressed than their counterparts.

Adaptation, Psychological↗
PubMed2002

The evaluation of infertility.

Infertility is a significant medical problem that affects many couples. Evaluation is the starting point for treatment of infertility as it may suggest specific causes and appropriate treatment modalities. Although the history and physical examination provide important information, specific diagnostic tests are required to evaluate infertility. Because the causes of infertility can be multifactorial, a systematic approach typically is used and involves testing for male factor, ovulatory factor, uterotubal factor, and peritoneal factor. Many of these diagnostic tests are laboratory based, including semen analysis, serum progesterone level, serum basal follicle-stimulating hormone level, and clomiphene citrate challenge, and can be done by the primary care physician. Moreover, by understanding the infertility evaluation, the primary care physician can serve as an important resource for advice about infertility. This article briefly reviews the diagnostic approach to infertility, with particular emphasis on important laboratory tests used for evaluation.

Adult↗
PubMed1993

Sexually transmitted diseases and medico-social factors associated with male infertility in Nigeria.

Medico-social factors such as type of infertility, sexually transmitted diseases (STD), drug abuse, erectile dysfunction, divorce, and polygamy were evaluated among 64 infertile men (i.e. 32 oligo-asthenozoospermic and 32 azoospermic) and 23 men of proven fertility in Jos University Teaching Hospital, Jos, Nigeria. Of the 64 infertile men, 27 (42%) and 37 (58%) had primary and secondary infertility respectively. A history of STD, indicated by purulent urethral discharge, was recorded among 40 (63%) with 22 (55%) of this number having had repeated exposures to STD. While 17 (43%) of the infected infertile men were treated by qualified medical doctors, 23 (57%) either had self-medication or received treatment from quacks. Five (8%) of the 64 infertile men used hard drugs, 11 (17%) had erectile dysfunction, 15 (23%) were re-married due to broken marriage relationship or divorce, and 7 (11%) were polygamous. All the fertile men were monogamous with no history of either erectile dysfunction or usage of hard drugs. One (4%) of the fertile men had a history of a broken marriage relationships. Six (26%) had a history of STD with 5 (26%) of them having received treatment from qualified medical doctors. Although the study population is small, the results obtained in this study reveal higher incidences of STD, marital instability, and multiple marriage partnerships (polygamy) among infertile men than the fertile in Jos.

Africa↗
PubMed2003

The frequency of antisperm antibodies in infertile couples--a Polish pilot study.

BACKGROUND: One of every four Polish married couples is infertile. Numerous factors may contribute to the lack of conception in these couples, one of which may be the presence of antisperm antibodies in semen, cervical mucus and serum in infertile individuals. Thus immunological examinations of these individuals should be standard diagnostic practice. In the present paper we studied the frequency of antisperm antibodies among infertile Polish couples. MATERIAL/METHODS: Serum samples from infertile women (n=194) and men (n=186) were tested by means of the indirect immunobead-binding test. Also, cervical mucus samples obtained from 155 women were investigated using the same test. Semen samples from 202 men were tested with the direct immunobead-binding test. RESULTS: 4.1% of the serum samples from infertile women were positive for antisperm antibodies, as well as 7% of the serum samples from infertile men, and 3.2% of the cervical mucus samples. 10.4% of the samples had spermatozoa-coated antibodies. In the respective control samples, the immunobead-binding test did not reveal any positive cases when given the applied 'cut-off' values. CONCLUSIONS: This preliminary report attempts to determine for the first time the frequency of antisperm antibodies in a Polish population of infertile married couples.

Adult↗
PubMedDate not supplied

[Importance of genetic factors in the pathogenesis of gonadal and postgonadal human infertility].

The infertility is a important health problem, affecting about 10-15% of couples. The important role of genetic factors in pathogenesis of infertility is now increasingly recognized and our knowledge in this field are improved each day. For these reasons we review the most important genetic causes of infertility. In this paper we analyse the genetic implications in gonadal and postgonadal infertility. Gonadal infertility affects both sexes and are characterised by hypergonadotrophic hypogonadism. Gonadal infertility is produced by chromosomal or monogenic mutations. Chromosomal causes are represented by gonosomal aneuploidy and structural chromosomal abnormalities. The monogenic disorders are consequences of a recessive mutations of hormone, hormonal receptor or enzymes genes. Postgonadal infertility is present in men and is the result of some obstructive disorders.

Female↗
PubMed1982

The incidence, characteristics, and prognosis of patients whose infertility is unexplained.

Review of the case records of 500 consecutive couples attending one Scottish infertility clinic revealed a group of patients whose infertility remained unexplained after completion of a standard protocol of investigations. The incidence of this condition in the clinic population was 24%. Various patient characteristics were examined, and no differences from patients with a detectable, organic cause for their infertility were found. Life-table analysis was used to provide a prognostic guide for such couples. About 34% of those with primary infertility and 21% of those with secondary infertility will remain infertile after 9 years of attempting to conceive.

Actuarial Analysis↗
PubMed2006

Potential association between infertility and spinal neural tube defects in offspring.

BACKGROUND: We examined the possible association between infertility and spinal neural tube defects (NTDs). METHODS: This is a nested case-control study within the Kaiser Permanente Medical Care Program (KPMCP) in Northern California. Among a birth cohort of 110,624 singleton infants > or = 36 weeks gestation, 1994-1997, we electronically identified cases of spinal NTDs and confirmed the diagnosis by chart review. Controls (n = 1,608) were randomly selected from the birth population. History of infertility was defined as: (1) physician diagnosis of infertility; (2) prescription for an infertility medication noted in the KPMCP pharmacy; and/or (3) evaluation at 1 of 15 infertility clinics in Northern California. RESULTS: Eighteen infants diagnosed with spinal NTDs (prevalence 1.6/10,000) included 13 with spina bifida cystica and 5 with spina bifida occulta. Case mothers were more likely to have a history of infertility (4/18 vs. 96/1,608, OR 4.3, 95% CI 1.01-14.0), and to have been prescribed clomiphene citrate within the window spanning 60 days before to 15 days after conception (3/18 vs. 32/1,608, OR 11.7, 95% CI 2.0-44.8). CONCLUSION: This exploratory study suggests that infertility may be associated with an increased risk of spinal NTDs among liveborn, term infants.

California↗
PubMedDate not supplied

Morphology of spermatozoa in infertile men with and without varicocele.

This study was carried out to evaluate the morphology of spermatozoa in infertile men with and without varicocele. A series of 285 ejaculates were fully evaluated for seminal volume, sperm count, motility, and morphology, and classified into fertile (165 subjects), infertile without varicocele (93 subjects) and infertile with varicocele (27 subjects). Sperm morphology was classified by multiple entry criteria and recorded as normal, abnormal with head, midpiece, or tail single anomaly or abnormal with simultaneous multiple abnormalities. Semen volume was almost identical in the three groups. Among the infertile men, sperm count was lower in those having a varicocele, but conversely those with varicocele had a higher percentage of motile spermatozoa, higher percentage of spermatozoa with forward movement and higher sperm velocity. There were higher proportions of spermatozoa with abnormal morphology, total number of anomalies, and multiple anomalies in infertile men, both with and without varicocele, than in fertile men. The percentage of abnormal spermatozoa was higher in infertile men with varicocele than in those without varicocele. The pattern of sperm morphology differed between the infertile and the fertile group, and with the presence or absence of varicocele. In the presence of varicocele, only the incidence of elongated (tapered) forms was significantly increased.

Humans↗
PubMed2003

Comparison of uterine and spiral artery blood flow in women with unexplained and tubal infertility.

OBJECTIVE: To evaluate the possible difference in uterine and spiral artery impedance to blood flow among women with unexplained and tubal infertility during spontaneous and gonadotropin-stimulated cycles. METHODS: We prospectively compared uterine and spiral artery pulsatility index and peak systolic velocity in a longitudinal study in women with either unexplained infertility (n = 20) or tubal infertility (n = 18). Measurements of uterine and spiral artery impedance were taken on days 11-12, 16-17 and 21-23 of the spontaneous cycle and on days 1, 5 and 10 during gonadotropin stimulation. In addition, measurements were taken on the days of oocyte pick-up and embryo transfer. RESULTS: A clinical pregnancy was achieved in 8/20 (40%) women with unexplained and 6/18 (33.3%) women with tubal infertility with in-vitro fertilization treatment. There were no differences in the uterine artery pulsatility index or peak systolic velocity during the spontaneous or the in-vitro fertilization cycle between the two groups. The impedance to blood flow in the uterine or spiral artery did not differ between women conceiving with in-vitro fertilization-embryo transfer and those who did not. However, the spiral artery pulsatility index on the 5th day of gonadotropin stimulation was significantly lower among women with unexplained infertility (0.96 +/- 0.25) compared to women with tubal infertility (1.24 +/- 0.30; P < 0.05), but on the other days of gonadotropin stimulation the spiral artery pulsatility index and peak systolic velocity were similar. CONCLUSIONS: Impaired uterine or spiral artery blood flow is not an important factor in unexplained infertility.

Adult↗
PubMed1992

Infertility in industrialized countries: prevalence and prevention.

We discuss the prevalence and aetiology of infertility and the relevance of this information for national infertility services and prevention programmes. The prevalence of infertility in industrialized countries has been said to be as high as 10-20%. This estimate, and the argument that little can be done to prevent infertility, have been used as justification for increased government investment in, or expansion of, services for medically assisted conception. However, population prevalence surveys indicate that far fewer couples of reproductive age are actually infertile. For example, a recent survey in the United States reported that 8.5% of married couples with a wife age 15-44 were infertile. 4% of the sample were childless and reported having a condition which impaired fecundity, while less than 2% were childless, had impaired fecundity and were over 35 years of age. Other studies show that nearly a third of couples have difficulty conceiving at some point during their reproductive lives but few actually remain childless. A significant proportion of infertility could be prevented through more aggressive application of standard public health measures.

Adolescent↗