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.     

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.     

Risk factors for female and male infertility: results of a case-control study.

In order to evaluate male and female risk factors for infertility in a case-control study, we have compared all couples in a French administrative region consulting for primary or secondary infertility (of more than one year's duration) with couples in which the woman had given birth during the year of the study. For any one couple, a history of varicocele, male genital infections or testis damage multiplies the risk of primary infertility by a factor of 28, 3 and 4 respectively, and previous female infections (salpingitis) multiply the risk by 45. Similarly, a history of ectopic pregnancy, sexually transmitted diseases or salpingitis multiplies the risk of secondary infertility by a factor of 5, 4 and 7 respectively, and a history of varicocele multiplies this risk by 4.     

Molecular analysis of microdeletions of the Y chromosome in Venezuelan males with idiopathic infertility

Today infertility is a major health problem affecting about 10-20% of couples. A male factor is assumed to be responsible in about 50% of the infertile couples. The origin of reduced testicular sperm function is unknown in about 60-70% of cases. There are several causes of male infertility such as varicocele, spermatic duct obstruction, and endocrine disorders. Micro-deletions in the Yq are known to represent the pathogenic mechanisms for infertile males. Three different non-overlapping regions designated as AZFa, AZFb, and AZFc are located in interval 5-6 of Yq, and are associated with impaired spermatogenesis in humans. To determine the prevalence of Y chromosomal microdeletions in Venezuelan males with idiopathic infertility, chromosomal, seminal, histological and molecular analyses were carried out in 29 Venezuelan males with idiopathic azoospermia or oligoospermia. Y-microdeletions analyses were performed using a multiplex polymerase chain reaction (PCR)-based technique with 22 sequences-tagged-sites (STSs). One of 29 patients (3.4%) had Yq microdeletions on AZFc. The frequency of AZF microdeletions in Venezuelan patients was similar to other populations with different ethnical or geographical origin.     

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。     

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.     

Comparison of in-vitro fertilization in male and tubal infertility: a 3 year survey.

The in-vitro fertilization and embryo transfer (IVF-ET) procedure was compared in 175 couples with male infertility and 480 couples with tubal infertility. In cases of male infertility, more oocytes were recovered but fewer oocytes were fertilized. Although the cleavage rate was decreased, no difference in embryo quality was found. In male infertility, fewer transfers were performed and the average number of embryos per transfer was lower. The total pregnancy rate was also lower per cycle (12.8 versus 22.9%), but not per transfer (25.4 versus 25.7%). The further obstetrical outcome was similar in both groups. We conclude that male infertility can be treated by IVF-ET but results are still disappointing when compared to a control group with normal spermatozoa.     

Chromosome studies in patients with defective reproductive success

PROBLEM: The objective of this study was to evaluate the contribution of chromosomal anomalies to decreased fertility in humans. METHOD OF STUDY: In order to investigate the aetiology of infertility in our population and to assess the karyotype in a group of infertile couples and individuals with fertility problems, 782 persons (259 couples, 158 male and 106 female) with different clinical diagnoses of sterility and infertility were analysed cytogenetically. RESULTS: The overall frequency of major chromosomal aberration was 13.1% (103/783), which suggests that fertility or sterility problems in this population are due to chromosomal aberrations. Couples experiencing repeated spontaneous abortions, having malformed children or having sterility problems had chromosomal abnormalities in 18.0% (47/259 couples) of the population studied, and constituted chromosomal disorders occured in couples seeking IVF and ICSI with prevalence of 22.2% (8/38 couples), especially minor mosaicism of sex chromosomes in the female partners. The prevalence of chromosome abnormalities in infertile men was 17.7% (28/158), and in subfertile females, it was 26.4% (28/106). CONCLUSIONS: These results could indicate an increased tendency to miotic sex chromosome non-disjuction in humans.     

Effect of female age on the diagnostic categories of infertility

BACKGROUND: As more women choose to delay childbearing, increasing numbersof them face age-related fertility problems. We aimed to explorethe association between age and diagnosed causes of female infertility. METHODS: Anonymized data (age of male and female partner, year of firstvisit, diagnosis, duration and type of infertility) were obtainedon all couples attending Aberdeen Fertility Centre from 1993–2006.The prevalence of different causes of infertility was determinedfor women <35 and 35 years of age at the time of their firstclinic visit. Binary logistic regression and multinomial regressionwere used to determine the association between age and diagnosticcategories of infertility. RESULTS: Of a total of 7172 women, 26.9% were over the age of 35 yearsand 51.4% of the total had primary infertility. The mean femaleage was 31.2 (5.2 SD) years. There was an association betweenfemale age and the cause of female infertility (likelihood ratio,P < 0.001). More women over 35 had unexplained infertility(26.6 versus 21.0%, P < 0.001). Compared with women under30 years, the adjusted odds ratio (95% confidence intervals,CI) of the following diagnoses in women over 35 were: unexplainedinfertility = 1.8 (1.4–2.2), ovulatory dysfunction = 0.3(0.3–0.4) and tubal factor = 2.2 (1.7–2.7). CONCLUSIONS: The causes of infertility in older women are different fromthose in younger women. Women over 35 years of age are nearlytwice as likely to present with unexplained infertility.     

Demonstration of Chlamydia trachomatis IgG antibodies in the male partner of the infertile couple is correlated with a reduced likelihood of achieving pregnancy

BACKGROUND: The objective of this study was to determine the prevalence of Chlamydia trachomatis among both men and women seeking help at an infertility clinic, and to prospectively follow the effect of previous infection on pregnancy rates and pregnancy outcome after a long follow-up period (mean 37 months). METHODS: A total of 244 infertile couples was tested for C. trachomatis IgG antibodies, and IgG(+) couples were also tested for C. trachomatis DNA by PCR in a first-void urine sample. Study parameters were serology, PCR results, clinical diagnoses, treatments, pregnancy rates and pregnancy outcome. As controls, age-matched and spontaneously pregnant women were also tested with serology. RESULTS: The prevalence of IgG antibodies was 24.2, 20.1 and 15.6% among infertile women, infertile men and control women respectively. The prevalence of C. trachomatis DNA was 6.8 and 7.1% among tested women and men respectively. The presence of C. trachomatis IgG antibodies in women was related to tubal factor infertility (TFI) (P = 0.002). Decreased pregnancy rates were seen in couples where the man was IgG(+) (P = 0.005) with no relationship to TFI. Among women who achieved pregnancy, there was no difference in pregnancy outcome between IgG(+) or negative couples. CONCLUSIONS: C. trachomatis IgG antibodies in the man of the infertile couple was related to decreased pregnancy rates and to the presence of IgG antibodies in the woman. There was a high prevalence of asymptomatic persistent infections among infertile couples.     

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%.     

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.     

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.     

Patients' attitudes towards donation of surplus cryopreserved embryos for treatment or research

BACKGROUND: The aim of the study was 2-fold: first, to investigate couples' reasons for not using cryopreserved embryos within the maximum storage period; second, to study their attitudes towards potential embryo donation for specific purposes. METHODS: A questionnaire was sent to 284 IVF/ICSI couples who experienced destruction of their cryopreserved embryos (n=1180) because the cryopreservation period exceeded the Danish legislative limit of 24 months. RESULTS: Seventy-four per cent of the couples responded. The main reasons for not utilizing surplus embryos was 'successful delivery' (85%), 'consider family completed' (61%) and 'too short legislative limit for cryopreservation' (59%). Sixty per cent of the couples agreed to the concept of donation of cryopreserved embryos for infertility research, 57% responded affirmatively to donation for stem cell research and 49% for stem cell treatment, but only 29% agreed to the concept of donation to infertile couples. Multiple logistic regression analysis showed that delivery of a child after IVF treatment (OR 3.8, 95% CI 1.4-10.2) and female age <35 years (OR 2.2, 95% CI 1.3-6.0) were predictive of agreement to the idea of donation for stem cell research and stem cell treatment respectively; however, male age, duration of infertility, mode of conception (IVF or ICSI) and having IVF children were not significant predictors. The following predictive variables were entered into the analysis: female and male age, duration of infertility, IVF versus ICSI, donor semen and +/- IVF children. CONCLUSIONS: This study shows that 23% of all couples having cryopreserved embryos do not utilize them for further treatment within the legislative storage period of 2 years. A major reason is successful delivery. More than half of these patients agreed to the concept of donation of surplus outdated embryos for research, whereas less than one-third agreed to donation to other infertile couples. Based on these figures, an alternative utilization of surplus embryos for stem cell research would require a 100-fold larger pool of available embryos to provide a realistic basis for this purpose.     

特发性男性不育症的遗传学分析

不孕症指夫妇同居生活两年、未避孕而未怀孕者。大约15%育龄夫妇患不孕症,其中男性因素占一半。造成男性不育的因素很多,比如内分泌、感染、生殖器畸形、免疫、遗传等原因,然而多半男性不育症患者找不到明确原因,我们称之为特发性男性不育症。生精障碍是男性不育的主要原因,多数男性不育症患者最初通过精液常规检查被确诊。精液常规检查可发现多种异常,比如无精子症、少精子症、弱精子症、畸精子症、死精症以及脓精症等,大约30%前来遗传咨询的男性不育患者患有特发性无精子或少精子症。已确定与特发性无精子症或少精子症有关的遗传异常包括染色体异常、精子mtDNA突变、单基因遗传病、多基因遗传病以及遗传因素引起的内分泌异常等,本文就特发性男性不育症的以上遗传学因素作一综述。     

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.     

International estimates of infertility prevalence and treatment-seeking: potential need and demand for infertility medical care

INTRODUCTION The purpose of the present study was to review existing population surveys on the prevalence of infertility and proportion of couples seeking medical help for fertility problems. METHODS Population surveys, reporting the prevalence of infertility and proportion of couples seeking help in more and less developed countries, were reviewed. RESULTS Estimates on the prevalence of infertility came from 25 population surveys sampling 172 413 women. The 12-month prevalence rate ranged from 3.5% to 16.7% in more developed nations and from 6.9% to 9.3% in less-developed nations, with an estimated overall median prevalence of 9%. In 17 studies sampling 6410 women, the proportion of couples seeking medial care was, on average, 56.1% (range 42-76.3%) in more developed countries and 51.2% (range 27-74.1%) in less developed countries. The proportion of people actually receiving care was substantially less, 22.4%. Based on these estimates and on the current world population, 72.4 million women are currently infertile; of these, 40.5 million are currently seeking infertility medical care. CONCLUSIONS The current evidence indicates a 9% prevalence of infertility (of 12 months) with 56% of couples seeking medical care. These estimates are lower than those typically cited and are remarkably similar between more and less developed countries.     

Frequency of CFTR gene mutations in males participating in an ICSI programme.

A higher prevalence of cystic fibrosis transmembrane regulator (CFTR) gene mutations has been suggested both in men affected by congenital aplasia of the vas deferens, and in individuals presenting with reduced sperm quality. In this case, an increased risk for offspring being affected by cystic fibrosis (CF) can be expected in couples who are planning to undergo intracytoplasmic sperm injection (ICSI), since most of the male partners suffer from infertility. In order to determine the risk for these couples more precisely, we offered them a test for the most frequent CF mutations prevalent in the German population. The frequency of mutations within the CFTR gene in the female group was in the same range as expected for the general population (six out of 150). In 10 out of 207 males tested, infertility could be explained by exogenous factors not related to CFTR. Among the remaining 197 males with idiopathic infertility, we detected 13 heterozygotes for a mutation within the CFTR gene. This slightly, but significantly (P = 0.014), elevated rate could indicate that infertile males have, compared with the general population, an increased risk of being a carrier of a CFTR gene mutation.     

Fertilization failure in IVF: why and what next?

Among 297 couples who underwent 587 oocyte collection procedures,95 (16%) total fertilization failures (FF) were observed. Thisfrequency is similar in couples with either normal or only mildlydeficient spermatozoa (16.2 and 13.7% respectively) but is almostdoubled in cases of moderately and severely defective sperm(26.5%). However, this latter group accounts for only 19% ofFF events. The fertilization rate per oocyte (FR) follows aninverse trend. FR was correlated with the final (i.e. afterswim-up) sperm count and with initial and final motility ofthe sperm sample. If the final count and motility were <2x 10⁶/ml and 40% respectively, the FF frequency in the groupwith partner's spermatozoa was significantly higher and FR significantlylower. FR was inversely correlated with the number of oocytesrecovered but FF was found significantly more frequently onlywhen fewer than three eggs were retrieved. No correlation wasfound between FF and either female causes of infertility, ageor dosage of stimulation treatment. However, in the group withdonor spermatozoa the FR was significantly lower amongst tubal,endocrinopathic and endometriotic patients (67.6, 67.2 and 56.6respectively versus 79.7% in harvests from idiopathic cases).FR was decreased and FF increased when ovulation induction resultedfrom a spontaneous LH peak supplemented with human chorionicgonadotropin (HCG), as compared to induction by HCG alone. Inthe group using normal or mildly defective spermatozoa, if FFoccurs at the first attempt, the frequency of recurrence inFurther trials is high (29%) and the probability of pregnancyafter completed trials is low (12.5%). In the group with donorspermatozoa this recurrence rate is lower (14.3%) and the pregnancyrate remains unmodified (31.2%) as compared to cases withoutany FF amongst other trials.     

Infertility: Infertility evaluation in fertile women: a model for assessing the efficacy of infertility testing

A standard infertility evaluation consists of a semen analysis,hysterosalpingogram, post-coital test, endometrial biopsy andlaparoscopy. Although these tests are well grounded in clinicalexperience, information on their ability to discriminate betweenfertile and infertile couples is limited. In this study, weperformed standard infertility tests plus two others-sperm antibodiesand cervical culture for Mycoplasma hominis and Ureaplasma urealyticum–onfertile and infertile couples. Women in the fertile group wereselected from those who had delivered a child within the previous2 years and who were scheduled for a laparoscopic tubal ligation.Women in the infertile group were selected from those presentingfor an infertility evaluation (mean duration of infertility4.2 years), and they were matched by age (±3 years) andrace with fertile subjects. Subjects were recruited from bothprivate and clinic patients. A total of 64 couples (32 matchedpairs) completed the evaluation. At least one ’abnormal‘infertility test was found in 69% of fertile and 84% of infertilecouples. With the exception of tubal damage and endometriosis,which as expected were more common in infertile couples, nosignificant differences between groups for remaining infertilityfactors could be demonstrated. Despite the small size of thecurrent study, these results confirm the feasibility and importanceof comparisons of the prevalence of infertility factors in fertileand infertile couples.