Incidence and main causes of infertility in a resident population (1,850,000) of three French regions (1988-1989).

To estimate the prevalence and main causes of infertility, a multicentre survey was conducted over 1 year (July 1988-June 1989) in three regions of France. All the 1686 couples in these regions, who consulted a practitioner for primary or secondary infertility during this period, were included in the investigation. The prevalence rate of infertility was found to be 14.1%, indicating that one woman out of seven in France will consult a doctor for an infertility problem during her reproductive life. The main causes of female infertility were ovulation disorders (32%) and tubal damage (26%), and of male infertility oligo-terato-asthenozoospermia (21%), asthenozoospermia (17%), teratozoospermia (10%) and azoospermia (9%). Infertility was also found to be caused by disorders in both the male and female partners together; thus in 39% of cases both the man and woman presented with disorders. The woman alone was responsible for infertility in one-third of cases and the man alone in one-fifth. Unexplained infertility was found in 8% of the couples surveyed.     

The psychological influence of gender infertility diagnoses among men about to start IVF or ICSI treatment using their own sperm

BACKGROUND: The aim of the present study was to investigate the psychological influence of gender infertility diagnoses among men in couples about to start their first IVF or ICSI treatment. METHODS: The study was a part of a prospective study of 65 men with male infertility diagnosis and 101 men in couples with female, mixed and unexplained infertility diagnoses. Of the 200 men invited, 166 agreed to participate (83% response rate). The men answered questionnaires concerning psychological and social factors on three occasions, at the information meeting held 2-4 weeks prior to first treatment, 1 h before oocyte retrieval and 2 weeks after the pregnancy test. RESULTS: The main findings of this study gave no indication that male infertility influenced men negatively concerning their experience of infertility, view of life and relationships and psychological well-being. We found that men with a male factor infertility diagnosis reacted in a similar way as compared with men in couples where the diagnosis was female, mixed or unexplained infertility. CONCLUSIONS: In general, men are well adjusted with regard to a first IVF/ICSI treatment cycle, independent of gender infertility diagnoses.     

Male infertility risk factors in a French military population

We investigated infertility risk factors by conducting a population-based case-control study in the military population of the French town of Brest. Sixty couples who had sought medical advice for infertility of more than 12 months duration (cases) were compared with 165 couples who had had a child (controls). All the men in these couples had been employed by the military. The infertility risk factors studied were male and female medical factors, occupational and environmental exposures. We obtained age-adjusted odds ratios of 7.4 [95% confidence interval (CI): 1.4--39.5] for testis surgery, and 13.0 for varicocele (95% CI: 1.4--120.3) in men. In logistic regression, the age-adjusted odds ratio for men who had worked in a nuclear submarine was found to be 2.0 (95% CI: 1.0--3.7), and that for heat exposure was 4.5 (95% CI: 1.9--10.6). One limitation of this study is the lack of exposure measurements, especially for potential exposure to nuclear radiation (type of reactor used in nuclear-powered submarines, inability to obtain personal dosimeters worn by military personnel working in nuclear submarines). In conclusion, this study suggests that in this military population, having worked as a submariner in a nuclear-powered submarine, and having worked in very hot conditions, should be considered as risk factors for infertility.     

Clustering of male infertility in the families of couples treated with intracytoplasmic sperm injection

Intracytoplasmic sperm injection (ICSI) is an effective treatment modality for male factor infertility, but it could promote the transgenerational transmission of genetic defects causing gametogenic failure. Cytogenetic and molecular techniques permit the diagnosis of some infertility-causing genetic aberrations, but many more probably evade detection with currently available technology. The analysis of the recurrence pattern of infertility in infertile couples' families could define the importance of heritable factors in the pathogenesis of human infertility. We have subjected 621 consecutive infertile couples treated with ICSI in a single institution to a comprehensive genetic workup including documentation of the family history, karyotyping and various DNA tests. In all, 1302 fertile couples served as controls. Of the infertile couples 6.4% were shown to have a fertility problem with a definite genetic basis. Male, but not female fertility problems displayed a distinct pattern of familial aggregation. In addition, the infertile couples had fewer siblings than the fertile controls, a finding compatible with suboptimal fertility already among the infertile couples' parents. In summary, our data indicate that male factor infertility should be considered a potentially heritable condition. The recurrence risk for infertility in the offspring of couples treated with ICSI might be substantial.     

Varicocele--the most common cause of male factor infertility?

Varicocele is often cited as the most common cause of male factor infertility. Arguments in support of this statement include reports of increased prevalence of varicocele in populations of infertile men compared with fertile or otherwise unselected men, association of varicocele with abnormal semen parameters, and improvements in semen parameters and/or pregnancy rates after varicocele repair. Logically, there would appear to be three possibilities regarding the relationship between varicocele and fertility: (i) varicocele has no association with or effect on male fertility; (ii) varicocele may be associated with, but is not the cause of, male subfertility; and (iii) varicocele is a direct cause of male subfertility. In the following, we review evidence from the literature for and against these three possibilities: at the current time, available evidence appears inadequate to confirm or deny any of these three possibilities. Since the ultimate goal of infertile couples is to conceive, it seem logical that future varicocele research should focus primarily on adequately powered, controlled clinical trials in well-characterized infertile couples, randomized to intervention or appropriate controlled observation, with pregnancy as the primary outcome.     

Clinical adaptation of the sperm ubuquitin tag immunoassay (SUTI): relationship of sperm ubiquitylation with sperm quality in gradient-purified semen samples from 93 men from a general infertility clinic population

BACKGROUND: The proteolytic chaperone peptide ubiquitin accumulates in defective human spermatozoa. Immunodetection of ubiquitin in human sperm samples correlates with semen quality and male fertility. METHODS: Semen samples from 93 men from couples seeking infertility treatment were separated on a PureSperm density gradient and screened by immunofluorescence microscopy with anti-ubiquitin antibodies. The percentage of spermatozoa with head ubiquitylation was recorded and compared with clinical semen evaluation and embryo development data after IVF or ICSI. Subjects were divided into the following four groups based on the initial clinical diagnosis of the couples; group 1, male factor; group 2, idiopathic infertility; group 3, female infertility with neither partner having children previously; and group 4, female infertility with male partners having children from previous relationships. RESULTS: The percentage of sperm with ubiquitylated heads remaining after PureSperm separation in the respective groups was 4.0% (male factor), 2.5% (idiopathic infertility), 0.7% (female infertility and presumed fertile male) and 0.9% (female infertility with established fertile male). Negative correlations between sperm ubiquitin and several parameters reflective of embryo development after assisted fertilization were found within the male factor group. CONCLUSIONS: Use of this simplified ubiquitin-based sperm quality assay is feasible in a clinical environment. Since the gradient separation does not completely deplete the defective spermatozoa, the modified light microscopic sperm ubiquitin tag immunoassay could add a new level of stringency to the selection of human spermatozoa for ICSI.     

Chromatin status in human ejaculated spermatozoa from infertile patients and relationship to seminal parameters

The aim of this study was to evaluate the chromatin status in different groups of patients. Five groups of men were selected: pre-vasectomy; male factor infertility; varicocele; immunological male infertility; and idiopathic infertility. Chromatin status was evaluated using flow cytometry after staining the DNA with the fluorochrome propidium iodide. Differences were observed in the state of sperm chromatin between the male factor and varicocele groups with respect to the others. These two groups presented poorer quality chromatin, as evidenced fundamentally by a lower degree of condensation. These deficiencies in chromatin status were usually accompanied by alterations in the other standard parameters of semen analysis. Individuals who are infertile due to male factor and those presenting varicocele have spermatozoa with less condensed chromatin which might, in part, explain their sterility.     

不孕症相关因素及病因分析

目的:探讨与不孕症相关的因素及病因状况。方法:收集4 234对门诊初诊不孕患者年龄、月经和生育史、以及与不孕相关的检查资料进行分析。结果:男、女性不孕患者平均年龄分别为32.1岁和29.6岁,女性高龄不孕患者占13.9%;原发不孕占60.3%,继发不孕39.7%,女方因素与男方因素或双方因素导致的原发或继发不孕构成比有明显差异（P<0.01）;主要病因所占比重：女性输卵管、盆腔病变46%,其次为男性无精子症或少弱精子症36.4%,女性排卵异常10.2%。其中994对(23.5%)存在双方因素不孕。结论:加强女性输卵管、盆腔疾病的预防和男性生精功能障碍的机制研究可能对防治不孕症起重要作用。     

Contribution of environmental factors to the risk of male infertility

BACKGROUND: An increasing number of reports suggest that chemical and physical agents in the environment, introduced and spread by human activity, may affect male fertility in humans. We investigated the relationships between exposure to environmental agents and seminal characteristics, and the concentrations of reproductive hormones in the serum of men seeking infertility treatment. METHODS: We studied 225 male partners from consecutively recruited couples, who had their first infertility consultation between 1995 and 1998, in the Litoral Sur region of Argentina, one of the most productive farming regions in the world. RESULTS: A multivariate logistic regression model showed that exposure to pesticides and solvents is significantly associated with sperm threshold values well below the limit for male fertility. We also found that men exposed to pesticides had higher serum oestradiol concentrations, and that men exposed to solvents had lower LH concentrations than non-exposed men. All of these effects were greater in men with primary infertility than in men with secondary infertility. CONCLUSION: We have shown that environmental factors contribute to the severity of infertility, and that this may worsen the effects of pre-existing genetic or medical risk factors.     

Evaluation of intrauterine insemination with washed spermatozoa from the husband in the treatment of infertility.

In this study, we examined the efficacy of intrauterine insemination with washed spermatozoa from the husband (AIH/IUI) in the treatment of infertility. A total of 127 treatment cycles were completed (1.95 cycles per patient). The indications for AIH/IUI were male subfertility (group I: 53 couples), cervical factor (group II: four couples), male and cervical factor (group III: six couples) and unexplained infertility (group IV: two couples). Sperm washing caused a reduction of the sperm concentration from 52 x 10(6)/ml to 44 x 10(6)/ml (P less than 0.08) and motility from 49% to 45% (P less than 0.03). Twelve pregnancies were achieved (18.5% per couple and 9.5% per cycle): eight pregnancies in group I (15.1%), one in group II (25%) and three in group III (50%). Of the 12 pregnancies, eight occurred in the first insemination cycle, three in the second and one in the third (1.4 cycles/pregnancy). Sperm motility was significantly higher in the pregnant than in the non-pregnant group (65.5% versus 46.4%, respectively; P less than 0.004), whereas no significant difference was observed in the sperm concentration between these two groups (39 x 10(6)/ml and 54 x 10(6)/ml, respectively). In conclusion, AIH/IUI is a technically easy and non-invasive procedure which offers a satisfactory pregnancy rate in selected couples with male subfertility and/or cervical factor infertility.     

The effect of an infertility diagnosis on the distress, marital and sexual satisfaction between husbands and wives in Taiwan

BACKGROUND: Few studies have explored the effect of a gender-specific infertility diagnosis on the responses of couples in Taiwan. The purpose of this research was to compare the differences in distress, marital and sexual satisfaction in husbands and wives based on an infertility diagnosis. METHODS: Three structured questionnaires were used. RESULTS: Female members of couples in which both partners were infertile expressed less marital and sexual satisfaction than their husbands. No differences in marital and sexual satisfaction were found between wives and husbands with unexplained infertility. Only wives with a diagnosed female infertility expressed higher distress to infertility than their husbands. Although no differences in psychosocial responses were found among husbands, regardless of the diagnosis, wives with a diagnosed female infertility experienced higher distress in self-esteem and less satisfaction in acceptance by in-laws than wives experiencing a diagnosed male infertility. CONCLUSIONS: These findings suggest that the diagnosis of infertility is an important factor in assessing the differences in infertility distress and marital and sexual satisfaction between husbands and wives. Health professionals can explain the gender differences when counselling infertile couples and encourage them to share each other's feelings, which may help couples to cope with the communication problems they may experience.     

The reactive oxygen species-total antioxidant capacity score is a new measure of oxidative stress to predict male infertility.

The imbalance between reactive oxygen species (ROS) production and total antioxidant capacity (TAC) in seminal fluid indicates oxidative stress and is correlated with male infertility. A composite ROS-TAC score may be more strongly correlated with infertility than ROS or TAC alone. We measured ROS, TAC, and ROS-TAC scores in semen from 127 patients and 24 healthy controls. Of the patients, 56 had varicocele, eight had varicocele with prostatitis, 35 had vasectomy reversals, and 28 had idiopathic infertility. ROS levels were higher among infertile men, especially those with varicocele with prostatitis (mean +/- SE, 3.25 +/- 0.89) and vasectomy reversals (2.65 +/- 1.01). All infertile groups had significantly lower ROS-TAC scores than control. ROS-TAC score identified 80% of patients and was significantly better than ROS at identifying varicocele and idiopathic infertility. The 13 patients whose partners later achieved pregnancies had a mean ROS-TAC score of 47.7 +/- 13.2, similar to controls but significantly higher than the 39 patients who remained infertile (35.8 +/- 15.0; P < 0.01). ROS-TAC score is a novel measure of oxidative stress and is superior to ROS or TAC alone in discriminating between fertile and infertile men. Infertile men with male factor or idiopathic diagnoses had significantly lower ROS-TAC scores than controls, and men with male factor diagnoses that eventually were able to initiate a successful pregnancy had significantly higher ROS-TAC scores than those who failed.     

Incidence of infertifity of immune origin in a group of marriages with unexplained infertility

This study was designed to estimate the incidence of infertilityof immune origin in a group of 102 married couples with unexplainedinfertility, out of a total of 1346 couples being treated forinfertility. The tests included microagglutination of spermatozoa,microzone sera immunoelectrophoresis and sera immunodiffusionmethods. In this group the sera of 23 (22.55%) women and 21(20.58%) men contained antibodies, and these seemed to be theonly cause of infertility. In relation to the total number of1346 couples, infertility of immune origin was found in 1.70%of female and 1.56% of male partners. Conjugal immune-origininfertility was present in 0.56% of marriages. Out of 1346 treatedinfertile marriages, an immunologic factor was evidently theonly cause of infertility in 2.57%.     

Attitudes about genetic risk of couples undergoing in-vitro fertilization

Many couples undergoing in-vitro fertilization (IVF) are at a higher risk of having a child with a genetic abnormality. In a sample of 55 consecutive couples starting IVF, only 33% had no genetic risk factor. The most common genetic risks were advanced maternal age and possible abnormalities associated with severe male infertility. Despite education on these risks, 71% of couples had no interest in receiving formal genetic counselling. Only 14% of couples at risk would consider using a gamete donor to avoid transmitting a genetic disorder to a child. The triple test to screen for fetal abnormalities was acceptable to 82% of couples, but only 47% planned to have amniocentesis or chorionic villi sampling. Couples were significantly more likely to opt for prenatal testing if they would consider terminating a pregnancy should the fetus have a severe genetic abnormality (P < 0.01). Roman Catholic couples tended to have more conservative attitudes about pregnancy termination. Socio-economic status and whether the infertility factor was male or female were not predictors of a couple's attitudes.      

Tubal infertility and silent chlamydial salpingitis

Antibodies to Chlamydia trachomatis (serum IgG antibodies witha titre of at least 32) were detected in 141 (86.0%) of 164infertile women with tubal infertility (TF group) and in 20(28.6%) in 70 infertile women with normal tubes (NTF group).The difference was highly significant (P < 0.001), as wasthe difference in geometric mean titre of antibody-positivecases, 181 and 87, respectively. Pregnant, agematched womenwere used as controls. Significantly fewer of these women (P< 0.001) had antibodies, when compared with the TF group,60 (36.6%) of 164, but not when the comparison was made withthe NTF group, 31 (44.3%) of 70. There was a history of salpingitisin 64 (39.0%) of the 164 infertile women with damaged tubes.Neither the frequency nor the geometric mean titre of chlamydialantibodies differed between tubal factor infertility patientswith and without a history of salpingitis. Previous chlamydialinfection, reflected by serological markers, is strongly associatedwith tubal damage leading to tubal infertility. A large proportionof these cases run a silent course, since a majority of theantibody-positive patients with tubal infertility have neverhad salpingitis     

In-vivo transperitoneal fertilization

We present the technique of in-vivo transperitoneal fertilization (IVTPF) as a first approach to infertility treatment in couples with male subfertility or unexplained factors. The technique is statistically less successful but also less invasive than either gamete intra-Fallopian transfer (GIFT) or in-vitro fertilization - embryo transfer (IVFET) and offers considerable advantages over intrauterine insemination (IUI). The IVTPF technique involves transperitoneal transfer of processed spermatozoa within the pouch of Douglas after induction of ovulation. We report our 4-year experience with IVTPF which includes 136 treatment cycles in 89 couples. Eight pregnancies were achieved in 89 patients (9%) and 136 treatment cycles (7%). Fifty-one patients (57%) received IVTPF for only one treatment cycle; seven of the eight IVTPF pregnancies occurred in this group. An ectopic pregnancy resulted in one of the eight IVTPF pregnancies (13%). The functional quality of the sperm in those couples who achieved pregnancy was statistically superior to those couples who did not conceive. However, pregnancy was also obtained in case of severe oligozoospermia. Based on our experience, we feel IVTPF to be a very reasonable first approach in patients with no pelvic pathology and with infertility secondary to male factors or unexplained causes.     

Possibilities and limitations of techniques of assisted reproduction for the treatment of male infertility

Since relatively few spermatozoa are needed for oocyte fertilization during gamete intra-Fallopian transfer (GIFT) or in-vitro fertilization (IVF), these methods have been applied in couples with infertility due to male causes. Forty-six couples with male factor infertility were enrolled in this study and results were compared with those attained in 48 couples treated with the same techniques for other than male causes. Overall, GIFT resulted in 26% ongoing pregnancies. GIFT seems to be particularly successful when the sperm concentration is 20 x 10(6)/ml or more, but sperm motility and/or morphology are poor. Nine pregnancies occurred out of 26 GIFT cycles in 18 cases selected on this basis. The ongoing pregnancy rate after IVF was 16% per patient. The latter treatment should be attempted in male immune infertility and in cases with a low sperm concentration, with or without abnormal sperm motility and/or morphology. In these circumstances, five pregnancies were attained out of 28 cycles in 14 cases. For similar sperm concentrations, the conception rate per cycle attained with techniques of assisted reproduction was more than twice that attained with conventional treatment of male infertility.     

Intra-uterine insemination versus cyclic, low-dose prednisolone in couples with male antisperm antibodies

A total of 46 couples with male immunological infertility enteredthe trial at the infertility clinic of the Family Federationof Finland. The men all showed a positive mixed antiglobulinreaction to immunoglobulin G in their semen; 31 men were alsotested for sperm-bound IgA immunoglobulins by flow cytometry.Serum antisperm antibodies were checked in a tray agglutinationtest. The women showed normal reproductive endocrinology andat least one patent Fallopian tube. The couples were randomizedto undergo either up to three intra-uterine inseminations (IUI),or timed intercourse with cyclic, low-dose (20 mg) prednisolonetherapy of the men. Cross-over was carried out if no pregnancyoccurred in the first stage. Timing of ovulation was based onurinary luteinizing hormone assay and transvaginal ultrasonographicmeasurements. In all, 40 couples either completed the studyor the female partner conceived. IUI was significantly better(P = 0.04) with nine pregnancies than timed intercourse withprednisolone (one pregnancy). There were no significant associationsbetween antibody levels, sperm count or motility versus theincidence of pregnancy. In male immunological infertility, well-timedIUI is an effective treatment method: results are obtained rapidlyand steroidal side-effects can be avoided.     

Genetics: Intracytoplasmic sperm injection in infertile patients with structural chromosome abnormalities

In the present study we investigated the results of cyto-geneticanalysis in male and female patients included in an intracytoplasmicsperm injection (ICSI) programme for severe male infertilityas well as in conceptuses resulting from these ICSI treatments.In the 261 couples treated, 11 male (4.2%) and three female(1.2%) abnormal karyotypes were found, all consisting of structuralchromosome anomalies. Chromosomal translocation exhibited thehighest frequency (eight males and two females), and there werealso three cases of chromosomal inversion (two males and onefemale) and one male with one additional marker chromosome.There was no difference in fertilization rates among coupleswith abnormal (n = 14) and normal (n = 147) cytogenetic results,and the rates of clinical pregnancy per ICSI attempt were 25.0%(5/20) and 20.6% (78/378) respectively. In pregnancies obtainedin couples with normal karyotypes, all of the 108 fetuses werefree of chromosomal abnormalities. Among the eight fetuses fromcouples with chromosome structural anomalies, three out of fiveand two out of three inherited the cytogenetic defects foundin their father or mother respectively. In this series of 83ICSI pregnancies there were no chromosomal abnormalities otherthan those inherited from the parents. These findings suggestthat normal pregnancy rates can be obtained by ICSI in casesof chromosomal translocation in couples with severe male infertility.However, until further evaluations of available data can beperformed, cytogenetic analysis must be conducted prior to ICSIin men with low sperm counts, and genetic counselling must includeprenatal diagnosis for all growing conceptuses.     

The effects on in-vitro fertilization of autoantibodies to spermatozoa in subfertile men

Thirty-six infertile couples underwent treatment by in-vitrofertilization. In 16 couples (group 1) the male partner waspositive for antisperm antibodies measured by direct mixed antiglobulinreaction, direct immunobead test, and serum and/or seminal plasmatray agglutination test. In 20 couples (group 2) the men hadno such antibodies. Men with poor sperm motility were excluded.The female partners had no antisperm antibodies, and in thecontrols (group 2) infertility was due to a known female factor.The fertilization rate in couples without antisperm antibodies(group 2) was 72.7% compared to 50.5% when the men had antibodies.However, the pregnancy rate per embryo transfer was not significantlydifferent in the two groups (46.1% in group 1, 33.3% in group2). This indicates that antisperm antibodies in the male interferewith sperm —egg fusion and subsequent fertilization butonce fertilization has occurred, the pregnancy rate remainsthe same.