Poor Semen Parameters Research Articles

High Prevalence of Reduced Fecundity in Men with Congenital Adrenal Hyperplasia

Testicular adrenal rest tumors (TARTs) are regarded to contribute to the high prevalence of subfertility in males with congenital adrenal hyperplasia (CAH). Our objectives were to evaluate reduced fecundity and its possible causes in well-controlled adult males with CAH, and to investigate diagnostic tools for improved treatment monitoring with respect to fertility outcomes. In a cross-sectional study at the Department of Endocrinology at the University Hospital München, Germany, 22 adult male CAH patients (15 salt wasting and seven simple virilizing, age 19-48 yr) were clinically assessed according to their hormonal control. We performed testicular ultrasound (22 of 22), magnetic resonance imaging (18 of 22), and a semen analysis (19 of 22) in the participants. All patients had a pathological semen analysis. TART prevalence was 10 of 22 (eight salt wasting, two simple virilizing). Poor therapy control was present in five patients, and all five had TARTs. Of the other 17 well-controlled patients with normal or suppressed adrenal androgens and 17-hydroxyprogesterone levels, five presented with TARTs. There was a significant correlation between sperm concentration and functional testicular volume (r = 0.70; P = 0.002), TART volume (r = -0.70; P = 0.036), as well as inhibin B levels (r = 0.75; P < 0.0001), respectively. In several men, hormonal control parameters suggested hypogonadism, with glucocorticoid overtreatment as a relevant factor for poor semen quality. Poor semen parameters are common in male CAH patients. TARTs, most likely reflecting undertreatment, as well as inhibin B are important indicators of fecundity. On the other hand, long-term glucocorticoid overtreatment also seems to contribute to low semen quality.

A genetic survey of 1935 Turkish men with severe male factor infertility

Male factor infertility is the sole reason in approximately 25% of couples who suffer from infertility. Genetic factors such as numerical and structural chromosomal abnormalities and microdeletions of the Y chromosome might be the cause of poor semen parameters. The results of karyotype analyses and Y-chromosome microdeletions of 1935 patients with severe male factor infertility, which is the largest series from Turkey, were assessed retrospectively. The frequency of cytogenetic abnormalities among 1214 patients with non-obstructive azoospermia (NOA) and 721 patients with severe oligoasthenoteratozoospermia (OAT) were 16.40 and 5.83% respectively. The overall incidence of Y-chromosome microdeletion was 7.70%. The incidence of Y chromosome microdeletion in patients with NOA and OAT was 9.51 and 1.86% respectively. The abnormality rate increased with the severity of infertility. Some patients (n = 22) were carriers of both chromosomal abnormalities and Y-chromosome microdeletions. Results suggest the need for genetic screening and proper genetic counselling before initiation of assisted reproduction treatment.

DNA damage and chromosomal aberrations in various types of male factor infertility

To understand and delineate the nature and level of DNA damage in association to semen parameters in infertile men. A prospective experimental study. Alexandroupolis University General Hospital. Eleven fertile and 27 infertile men with various types of infertility. DNA damage was induced by addition of mitomycin C and caffeine to lymphocyte cultures. Sister chromatid exchange (SCE) levels were assessed in cultures providing a quantitative index of genotoxicity and chromosomal analysis was performed using G-banding and C-banding techniques. Karyotyping analysis indicated chromosomal fragility, trisomic lines, and marker chromosomes in some infertile men. Double minute chromosomes were noticed in 11 infertile men and were positively correlated with elevated SCE levels. Necrospermia and varicocele, irrespectively of the degree of severity, were positively correlated with elevated SCE levels. Infertile men are prone to have DNA damage; the nature and level of DNA damage varies and is associated with semen parameters. The presence of double minute chromosomes alone is associated with increased double-stranded breaks and abnormal sperm concentration. This study could provide the basis to establish whether and through which process double minute chromosomes could be related to poor semen parameters and regulation of DNA repair.

The significance of sperm nuclear DNA strand breaks on reproductive outcome

A growing body of evidence indicates that ejaculated spermatozoa from men being treated with intracytoplasmic sperm injection contain nuclear abnormalities. Many of these nuclear anomalies manifest themselves as breaks in the sperm nuclear DNA. This review examines the mechanisms involved in generating DNA strand breaks during spermatogenesis in the human, the main techniques used to assess the sperm nucleus and the evidence, in relation to assisted reproduction, showing that sperm nuclear DNA strand breaks may impact on reproductive outcome. Techniques such as the TUNEL assay and the sperm chromatin structure assay both show increased levels of DNA abnormalities in spermatozoa from men who have poor semen parameters. The reproductive parameters affected by an increased presence of DNA abnormalities in ejaculated spermatozoa include fertilization, blastocyst development, and pregnancy rates. There is accumulating evidence linking sperm nuclear DNA anomalies to poor reproductive outcome in relation to assisted reproduction technologies. The tests currently available only provide an inkling of the impact of sperm nuclear DNA abnormalities on reproductive outcomes. Although the impact an abnormal paternal genome may have on reproductive outcome is unquestionably less than that of its female counterpart, it cannot be ignored.

Role of back-up frozen semen in couples undergoing in vitro fertilization (IVF)

Role of back-up frozen semen in couples undergoing in vitro fertilization (IVF)

Increased levels of sperm ubiquitin correlate with semen quality in men from an andrology laboratory clinic population.

Ubiquitin, a house-keeping protein that marks other proteins for proteasomal degradation, tags defective sperm during epididymal passage. To establish ubiquitin as a biomarker of human infertility, the present study examines the relationships between sperm ubiquitin content and clinical semen parameters among men from an infertility clinic population with varied aetiologies. Anti-ubiquitin immunoreactivity was measured by flow cytometric sperm-ubiquitin tag immunoassay (SUTI) in sperm samples of 28 infertility patients and 15 fertile donors. Semen analyses were performed by computer-assisted semen analysis and World Health Organization morphology. Median values of ubiquitin-induced fluorescence had a strong negative correlation with sperm count (r = -0.63, P = 0.0003) and a positive correlation with % abnormal morphology (r = 0.55, P = 0.01). Infertility patients (n = 28) had significantly higher levels of sperm ubiquitin. Out of 28 patients, six reported possible occupational exposures to solvents, three were current smokers and six were ex-smokers. Within the patient group, men with known male factor infertility, those with self-reported occupational exposure to solvents and current smokers had the highest sperm ubiquitin levels. When men with jobs involving potential occupational exposure to solvents were combined with current smokers, the highest correlations were found between sperm ubiquitin and motility (r = -0.74), count (r = -0.82) and % sperm abnormalities (r = 0.73). Increased sperm ubiquitin was inversely associated with sperm count, motility and % normal morphology, supporting the use of ubiquitin as a biomarker of human semen quality. SUTI assay confirmed poor semen quality in all men with poor clinical semen parameters, but also was high in some patients with seemingly good clinical semen parameters. Occupational exposure to solvents and smoking may have contributed to high levels of sperm ubiquitin in some of these patients.

Occupational risks for male fertility: an analysis of patients attending a tertiary referral centre.

The impact of environment and occupation on male fertility is still under debate. We investigated whether certain occupations may be over- or under-represented among men attending our infertility clinic in relation to the entire population of the area. Diagnoses and semen parameters of 2054 infertile men from the district of Münster were analysed retrospectively. The patients were categorized into 29 occupational groups. The relative size of each group was compared with that of the entire population in the district of Münster. Farmers were over-represented compared with the general population. Farmers and painters/varnishers showed a significantly higher proportion of reduced sperm counts [odds ratios (OR): 2.13 and 2.17, 95% confidence intervals: 1.18-3.88 and 1.02-4.65] and severely reduced sperm concentrations compared with the entire group of infertile men; in addition, significantly more farmers presented with a history of maldescended testes than other occupational groups (OR: 2.76 and 2.84; CI: 1.12-6.75 and 1.27-6.34). Metal workers/welders formed significantly higher proportions of patients with reduced sperm motility (OR: 5.99; CI: 1.38-26.00). The relatively poor semen parameters of the painters/varnishers could be caused by exposure to toxins. This may also apply to the farmers (fertilizers, herbicides); however, the elevated rate of maldescended testes suggests an effect of exposure during prenatal development or a genetic cause. The findings for metal workers/welders may be because of heat or toxins at the workplace. The study demonstrates that certain occupations are preferentially associated with male infertility.

Occupational risks for male fertility: an analysis of patients attending a tertiary referral centre

The impact of environment and occupation on male fertility is still under debate. We investigated whether certain occupations may be over‐ or under‐represented among men attending our infertility clinic in relation to the entire population of the area. Diagnoses and semen parameters of 2054 infertile men from the district of Münster were analysed retrospectively. The patients were categorized into 29 occupational groups. The relative size of each group was compared with that of the entire population in the district of Münster. Farmers were over‐represented compared with the general population. Farmers and painters/varnishers showed a significantly higher proportion of reduced sperm counts [odds ratios (OR): 2.13 and 2.17, 95% confidence intervals: 1.18–3.88 and 1.02–4.65] and severely reduced sperm concentrations compared with the entire group of infertile men; in addition, significantly more farmers presented with a history of maldescended testes than other occupational groups (OR: 2.76 and 2.84; CI: 1.12–6.75 and 1.27–6.34). Metal workers/welders formed significantly higher proportions of patients with reduced sperm motility (OR: 5.99; CI: 1.38–26.00). The relatively poor semen parameters of the painters/varnishers could be caused by exposure to toxins. This may also apply to the farmers (fertilizers, herbicides); however, the elevated rate of maldescended testes suggests an effect of exposure during prenatal development or a genetic cause. The findings for metal workers/welders may be because of heat or toxins at the workplace. The study demonstrates that certain occupations are preferentially associated with male infertility.

High incidence of single nucleotide substitutions in the mitochondrial genome is associated with poor semen parameters in men.

Single nucleotide polymorphisms (SNPs) in 7000 bp of the mitochondrial genome, encompassing 15 coding regions from COI to ND5, were characterized by single strand polymorphism analysis and confirmed by DNA sequencing. About 2.4% of normozoospermic men and 8.4% of men with poor semen quality had at least one nucleotide substitution. Most of the substitutions occurred in the third codon and did not change the amino acid. Hydrophobicity plots of the proteins with changes in an amino acid as a result of a nucleotide substitution suggested that they did not affect the function of the protein. The two most common substitutions at nucleotide (nt) 9055 and 11719 had significantly higher frequencies in men with reduced sperm motility. Eleven percent of the men with poor semen parameters and 1.3% of normozoospermic men had a 9055 substitution, 12% of the men with poor semen parameters had a substitution at nt 11719, but none of the normozoospermic men had this substitution. All the patients with these substitutions had reduced sperm motility and/or low sperm count. These SNPs in the mitochondrial genome were in a homoplasmic state. Thus, we propose that possessing these mitochondrial mutations compromises the semen quality of these men.

Does leukocytospermia associate with poor semen parameters and sperm functions in male infertility?: The role of different seminal leukocyte concentrations

To investigate the effect of leukocytospermia on standard semen analysis and sperm function tests such as acrosome reaction, hypoosmotic swelling, antisperm antibody binding and cervical mucus penetration, a prospective clinical study was performed. Two hundred and nineteen male infertility patients undergoing investigation and treatment were included in the study. There was a significant association between acrosome reaction positivity and leukocytospermia according to WHO (World Health Organization) criteria. Increased hypoosmotic swelling test score, higher sperm concentration and enhanced acrosome reaction were closely related to leukocytospermia. When the patients were divided into subgroups according to seminal leukocyte concentrations, acrosome reaction and hypoosmotic swelling were observed to be higher in semen samples with higher leukocyte concentrations compared to those with low seminal leukocyte concentration. In addition, higher sperm concentrations were observed in semen samples with increased leukocyte levels compared to semen samples with low leukocyte levels. These results suggest that leukocytospermia may have a favorable effect on some sperm functions at seminal leukocyte concentrations between 1 and 3×10 6/ml.

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

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

Is leukocytospermia clinically relevant?

To evaluate the relationship between seminal leukocytes and abnormal semen parameters in a large population of infertility patients. Prospective clinical study. Center for Reproductive Medicine at Brigham and Women's Hospital, Boston, Massachusetts. One thousand seven hundred ten male partners in infertile couples attending the Center for Reproductive Medicine. Seminal leukocyte concentrations, sperm count, motility and morphology, and the prevalence of samples with < 10 x 10(6) motile sperm per ejaculate (a parameter defined by IVF as the most clinically significant predictor of male infertility). There was a strong relationship between increasing leukocyte concentrations in semen and abnormal semen parameters. Statistically significant differences in sperm concentrations and morphology were observed at leukocytospermia thresholds of 5 x 10(5) and 2 x 10(6) granulocytes/mL, respectively. The percentage of suboptimal semen specimens as defined by IVF criteria (< 10(7) total motile sperm per ejaculate) significantly increased with increasing seminal granulocyte concentrations. A twofold increased prevalence in such suboptimal semen specimens was observed at the leukocytospermia threshold of 2 x 10(6) granulocytes/mL. There is a relationship between increasing seminal granulocyte concentrations and poor semen parameters. At seminal granulocyte concentrations > 2 x 10(6)/mL, semen parameter abnormalities were observed that were both statistically and clinically significant.

Development and implementation of intracytoplasmic sperm injection (ICSI).

The purpose of this paper is to elucidate the experimental steps that led to the development of intracytoplasmic sperm injection (ICSI) and its application in the human. ICSI has become the most successful micromanipulation procedure for treating male infertility. A total of 355 in vitro fertilization (IVF) cycles utilizing ICSI are described; 180 couples were previously treated in 509 IVF cycles but achieved no fertilization and 175 couples could not be treated by IVF because of extremely poor semen parameters. Of the 3063 metaphase II (M II) oocytes retrieved, 2970 were injected with a survival rate of 93.6%, yielding 1917 bipronuclear zygotes (64.5%). In 148 patients, a foetal heart was evidenced by ultrasound; 11 of these patients miscarried between 7 and 13 weeks of gestation. The ongoing pregnancy rate was 38.6% (137/355) per retrieval and 40.5% (137/338) per embryo replacement. At the time of writing, there were 22 deliveries and one therapeutic abortion for a trisomy 21 chromosomal abnormality. In addition, 66 singleton, 37 twin, 10 triplet and 1 quadruplet pregnancies were ongoing. The concentration of motile spermatozoa in the ejaculate only slightly influenced the fertilization rate (P < 0.001) and the pregnancy outcome (P < 0.01). A preliminary injection procedure utilizing intracytoplasmic injection of isolated sperm heads was performed in 35 M II human oocytes with resultant fertilization and cleavage rates of 74% and 73% respectively. Skills in ICSI were acquired by injecting hamster and unfertilized human oocytes with human sperm. ICSI can be used to successfully treat couples who have failed IVF or who have too few spermatozoa for conventional in vitro insemination.(ABSTRACT TRUNCATED AT 250 WORDS)

Is routine pre-treatment cryopreservation of semen worthwhile in the management of patients with testicular cancer?

Post-treatment fertility was evaluated in 147 patients with testicular cancer, All had pre-treatment sperm cell analysis following orchiectomy during the years 1979 to 1987. For only 17 patients was the question of future fertility of no importance. Pre-treatment semen cryopreservation was requested by 91 patients, but poor semen parameters made this procedure impossible in 38. Of 99 evaluable patients, 44 had a post-treatment sperm count greater than or equal to 10 x 10(6)/ml and 22 of these fathered a child after treatment. Post-treatment fertility was observed to the same degree in patients who had pre-treatment semen cryopreservation as in those in whom this procedure could not be performed. Four of 53 patients used their deep-frozen semen but only 1 pregnancy resulted. The intensity of treatment, especially the extent of retroperitoneal surgery, had a significant effect on post-treatment fertility in the individual patient. Pre-treatment cryopreservation of semen may be psychologically useful in patients with newly diagnosed testicular cancer, but its clinical significance is doubtful.

Cumulative pregnancy rates for in vitro fertilization

Data on 575 couples undergoing 1057 consecutive cycles of in vitro fertilization (IVF) were used to calculate cumulative pregnancy rates for repeated IVF cycles. Excluding preclinical abortions and couples in whom the male partner had poor semen parameters, calculated cumulative pregnancy rates for cycles 1 to 6 were 13.6%, 24.8%, 37.2%, 47.8%, 52.2%, and 59.6%, respectively. A parametric model used to fit these data yielded a strong correlation between observed and predicted pregnancy rates (r = 0.99, P less than 0.001). Predicted cumulative pregnancy rates after 9 and 12 cycles were 75% and 84%, respectively. Excluding preclinical abortions, the pregnancy rate per cycle was approximately constant, at approximately 15% over repeated cycles. As the cost of IVF declines and as treatment cycles become more easily tolerated, persistence in IVF can lead to successful pregnancy for a large proportion of couples.