Is there really a decrease in sperm parameters among healthy young men? A survey of sperm donations during 15 years

Purpose: Our purpose was to measure changes in semen quality and quantity in young healthy sperm donors in Jerusalem over time. Methods: A retrospective analysis of semen parameters over 15 years using linear regression analysis, in a single sperm bank in a tertiary university center. Study population consisted of 188 young, healthy medical students, aged 20 to 30 years, who donated sperm samples for Artificial insemination between 1980 and 1995. Results: There were no statistically significant changes in semen concentration and motility during the study period. The mean semen volume increased by 0.1 ml (5.1%) per year (P < 0.0001), with a concomitant mean rise of 5.8 × 10⁶ (7.7%) per year in total motile sperm count. The percentage normal morphology decreased by a mean of 1.04% per year during the entire period (P < 0.0001). Conclusions: During the past 15 years, there has been an increase in total motile sperm count, secondary to an increase in semen volume, and a decline in normal morphology that are independent of the age and the duration of abstinence in fertile men.     

External quality control program for semen analysis: Spanish experience

PURPOSE: Results from an external quality control programme for semen analysis carried out in Spain are analysed. METHODS: Quality control materials were distributed and the following seminal parameters were determined: concentration, total motility, progressive motility, rapid progressive motility, morphology and sperm vitality. The between-laboratories coefficients of variation were assessed on different types of quality control material. RESULTS: The majority of participating laboratories utilised manual versus computer-assisted semen analysis methods. Some between-laboratories coefficients of variation ranges were: 20.8-33.8% for concentration (semen pool suspension); 13.9-19.2% for total motility (videotapes); 54.2-70.2% for sperm morphology (strict criteria using stained smears); and 9.8-41.1% for sperm vitality (stained smears). There was an inverse relation between mean percentage of sperm and coefficients of variation between laboratories for sperm motility, morphology and vitality. CONCLUSIONS: These data highlight the urgent need for improvement in the overall quality of andrology testing.     

Fecundability trends among sperm donors as a measure of donor performance

OBJECTIVE: To examine fecundability trends among sperm donors. DESIGN: Retrospective analysis. SETTING: University-based sperm bank and donor insemination program. PATIENT(S): Sperm donors and recipients. INTERVENTION(S): A group of recipients underwent IUI with cryopreserved donor sperm. Fecundability was calculated for 20 sperm donors over 800 insemination cycles. MAIN OUTCOME MEASURE(S): Average fecundability per donor was compared for the first 40 cycles of a donor's use and for those donors within a group of more fertile recipients. Sperm parameters, recipient ages, and number of unique recipients for each donor were analyzed. RESULT(S): Average donor fecundability is constant; however, individual donors demonstrated differences among their fecundabilities (overall mean, 0.09; range, 0.01-0.26). These differences persisted for donors among a group of more fertile recipients (overall mean, 0.12; range, 0.02-0.35). A donor's fecundability at 15 cycles is predictive of his future performance. CONCLUSION(S): Differences in fecundability exist among sperm donors which cannot be discerned through routine semen parameters. Sperm donor fecundability should be analyzed periodically, and directors of sperm banks should consider discontinuing use of a donor whose outcome is substandard.     

Correlations between two markers of sperm DNA integrity, DNA denaturation and DNA fragmentation, in fertile and infertile men

OBJECTIVE: To evaluate two different assays of human sperm DNA integrity, DNA denaturation (DD) and DNA fragmentation (DF), and to correlate these with standard semen parameters. DESIGN: Prospective, observational study. SETTING: University infertility clinic.Patient(s): Forty consecutive semen samples from 33 nonazoospermic men presenting for infertility evaluation and 7 fertile men presenting for vasectomy. Intervention(s): Assessment of sperm concentration, motility, morphology, DD and DF. MAIN OUTCOME MEASURE(S): Sperm DD and DF in fertile and infertile men. RESULT(S): The mean (+/-SE) rates of DD and DF were significantly higher in infertile subjects compared to fertile controls, respectively: 25.4 +/- 3.0 vs. 10.2 +/- 2.3 (P=.028) and 27.6 +/- 2.5 vs. 13.3 +/- 2.5% (P=.016). DF and DD correlated strongly (r = 0.71, P<.0001). Also, DD and DF correlated negatively with standard semen parameters (concentration, motility, and morphology), the strongest correlation being with sperm motility. CONCLUSION(S): The strong correlation between sperm DD and DF, and the higher levels of sperm DNA damage in infertile compared with fertile men, indicate that male infertility is associated with poor sperm DNA integrity. Although infertile men may father children with assisted conception, fertilization with DNA-damaged spermatozoa may increase the risk of genetic disease in the offspring.     

No decline in semen quality among potential sperm donors in Sydney,Australia, between 1983 and 2001

Purpose : To determine whether the quality of semen has changed over time in men screened for semen donation. Methods : All 448 men volunteering for semen donation between 1983 and 2001 at a donor insemination clinic in Sydney, Australia, were included in this longitudinal single centre observational analysis of semen parameters. There was no selection for fertility or marital status but all volunteers had to be aged between 18 and 40 years. Results : There was no change in the total sperm count during the study period (r = 0.065, P = 0.17) using a linear regression model. The ejaculate volume did not change (r = 0.002, P = 0.97), while an increase in sperm motility was seen (Spearman R = 0.194, P < 0.001). Conclusion : The semen quality of volunteers for sperm donation presenting to our donor insemination clinic in Sydney between 1983 and 2001 has not declined.     

Effects of folic acid and zinc sulfate on male factor subfertility: a double-blind, randomized, placebo-controlled trial

OBJECTIVE: To study the effects of folic acid and zinc sulfate treatment on semen variables in fertile and subfertile men. DESIGN: Double-blind, placebo-controlled interventional study. SETTING: Two outpatient fertility clinics and nine midwifery practices in The Netherlands. PARTICIPANT(S): One hundred eight fertile and 103 subfertile men. INTERVENTION(S): Both groups were randomly assigned to receive one of four treatments for 26 weeks: folic acid and placebo, zinc sulfate and placebo, zinc sulfate and folic acid, and two placebos. Folic acid was given at a daily dose of 5 mg, and zinc sulfate was given at a daily dose of 66 mg. MAIN OUTCOME MEASURE(S): Before and after treatment, standardized semen and blood samples were obtained for determinations of sperm concentration, motility, and morphology according to World Health Organization guidelines; semen morphology according to strict criteria; and blood folate and zinc concentrations. Effects of the four interventions were evaluated separately in subfertile and fertile men. RESULT(S): Subfertile men demonstrated a significant 74% increase in total normal sperm count and a minor increase of 4% abnormal spermatozoa. A similar trend was observed in fertile men. Pre-intervention concentrations of folate and zinc in blood and seminal plasma did not significantly differ between fertile and subfertile men. CONCLUSION(S): Total normal sperm count increases after combined zinc sulfate and folic acid treatment in both subfertile and fertile men. Although the beneficial effect on fertility remains to be established, this finding opens avenues of future fertility research and treatment and may affect public health.     

Intrauterine insemination outperforms intracervical insemination in a randomized, controlled study with frozen, donor semen.

OBJECTIVE: To assess the efficacy of intrauterine insemination (IUI) in a donor insemination program. DESIGN: Prospective randomized clinical trial. SETTING: Donor insemination program. PATIENTS, PARTICIPANTS: Women undergoing insemination were randomly assigned to receive either IUI or intracervical insemination for a maximum of six cycles. INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): Cycle fecundity rates between the two routes were compared. RESULTS: The monthly fecundity rate for intracervical insemination was 5.1% compared with 23% by IUI. By life table analysis, pregnancy rates for IUI were significantly higher than intracervical insemination (P = 0.02). CONCLUSIONS: Intrauterine insemination with quarantined donor sperm is superior to intracervical insemination.     

Influence of the abstinence period on human sperm quality

OBJECTIVE: To determine the influence of ejaculatory abstinence on within-subject semen parameters and DNA fragmentation. DESIGN: Prospective study. SETTING: Private infertility institute and university-based research laboratory. PATIENT(S): Sixteen consenting male volunteers undergoing infertility investigation. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Within-subject analysis of World Health Organization semen parameters and sperm DNA fragmentation and chromatin packaging after 1, 3, 5, and 8 days' abstinence. RESULT(S): Of 16 men recruited, data for 11 men were included for statistical analysis because 5 men did not strictly comply with abstinence criteria. Duration of abstinence had a statistically significant positive influence on sperm concentration and semen volume. Abstinence had no statistically significant influence on pH, viability, total and grade A motility, or morphology. The percentage of DNA fragmentation remained unchanged relative to abstinence. The percentage of sperm with immature chromatin was statistically significantly increased with 1 day of abstinence. CONCLUSION(S): This is the first study to report on within-subject semen parameter, DNA fragmentation, and chromatin packaging variations after specified target days of abstinence. Sperm numbers and semen volume increased with duration of abstinence. Abstinence did not influence pH, viability, morphology, total or grade A motility, or sperm DNA fragmentation. A short (24-hour) abstinence period negatively influenced chromatin quality.     

Sperm function in workers exposed to N,N-dimethylformamide in the synthetic leather industry

OBJECTIVE: To determine whether occupational exposure to N,N-dimethylformamide (DMF) for men has adverse effects on sperm function. DESIGN: Cross-sectional study. SETTING: A synthetic leather factory in Taiwan. PATIENT(S): Twelve DMF-exposed workers in a synthetic leather factory and 8 socioeconomically matched control workers from another non-DMF-exposed manufacturing plant in the vicinity were recruited. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Breathing-zone monitoring of DMF exposure covering the full work shift was implemented on each participant. Urine specimens were collected from each worker immediately after their work shift in parallel with environmental sampling. Environmental DMF and urinary N-methylformamide (NMF) levels were measured by gas chromatograph. Analysis of semen samples was performed to measure semen volume, sperm concentration, morphology, and motility in accordance with World Health Organization criteria. RESULT(S): Both conventional microscopy and computer-assisted semen analysis showed that sperm motility in DMF-exposed group was significantly reduced from that in controls. Motility parameters were related to urinary NMF in a dose-response manner but were not related to airborne DMF. CONCLUSION(S): Workers occupationally exposed to DMF could be at risk of sperm motility perturbation. The responsible toxicant for the alterations of sperm function could be the active NMF metabolite instead of DMF, but this conclusion warrants a further complete investigation.     

Reasons for rejecting potential donors from a sperm bank program

Purpose: Recruiting donors to a sperm bank program is difficult and slow because of high dropout rates and high rejection rates. The profile of successful and unsuccessful donors was determined at our sperm bank. Methods: A total of 199 men was screened from 1986 to 1994 in the anonymous sperm bank donor program; 174 (87%) men dropped out or did not meet minimum guidelines. The study included 25 accepted donors and 20 rejected men (of 52 rejected donors, only 20 donors who came for two consecutive semen analyses were selected). Sperm quality variables and demographic data were compared between the groups. Results: Accepted donors had significantly better semen quality in motility, velocity, linearity, and ALH than did rejected donors (P < 0.01). More rejected donors than accepted donors were single (P < 0.01). A higher percentage of accepted donors consumed caffeine (P < 0.001), and they were more likely to have college degrees (P < 0.03). Conclusions: These results indicate that loss of interest and poor semen quality were the major reasons for rejection of donors in our anonymous donor sperm bank program.     

Comparison of protective media and freezing techniques for cryopreservation of human semen

OBJECTIVE: To evaluate the influence of cryopreservation medium and freezing-thawing techniques on human sperm motility and morphology. STUDY DESIGN: 63 semen samples were obtained from 39 donors to the artificial insemination programme. Possible effects of the sperm dilution with cryomedium on the motility were examined 10 min after exposure of 24 high initial quality semen samples to TEST-yolk ?zwitterion-citrate-egg yolk extender containing TES [N-Tris (hydroxymethyl) methylaminoethane sulfonic acid] and Tris [(hydroxymethyl) aminomethane]? and human sperm preservation medium (HSPM). Post-thaw sperm motility from 24 frozen semen samples was examined comparing the cryoprotective efficacy of TEST-yolk and HSPM following different freezing techniques (vapour freezing, fast programmable freezing and slow programmable freezing). The relationship of sperm morphology to the effects of freezing was investigated on 39 semen samples following different freezing techniques. Post-thaw sperm motility from 39 frozen semen samples was compared among three groups divided according to the percentage of morphologically normal cells (<40, 40-50 and >50%) in fresh semen. RESULTS: Exposure of spermatozoa to cryomedia for 10 min at room temperature significantly reduced motility in TEST-yolk treatment group for 9% and in HSPM treatment group for 18% (P<0.01). The recovery of motile sperms (mean+/-standard deviation) was 49+/-15.7, 43+/-15.2 and 52+/-16.8% when TEST-yolk was used and 34+/-17.8, 32+/-18.2 and 50+/-13.6% when HSPM was used as a cryopreservative following vapour freezing, and fast and slow programmable freezing, respectively. Following vapour freezing and also following fast programmable freezing, the recovery of motile sperm was significantly higher (P<0.05) after addition of TEST-yolk medium than after addition of HSPM. Post-thaw motility of the sperm cryopreserved in HSPM showed significant differences (P<0.05) after three different freezing techniques. The recovery of motile sperms was 57+/-26.4, 38+/-8.6 and 38+/-17.3% in groups with >50, 40-50 and <40% morphologically normal cells, respectively. The percentage of morphologically normal spermatozoa was reduced 8% after vapour freezing and 6 and 3% after fast and slow programmable freezing, respectively. The results were statistically analysed using SAS/STAT software. CONCLUSIONS: Slow programmable freezing was superior to vapour freezing and fast programmable freezing as a method for sperm cryopreservation. However, none of these methods of freezing had discernible effects on sperm morphology. Motility of spermatozoa decreased due to the exposure of semen to cryomedium. TEST-yolk was a superior cryomedium to HSPM. Fresh semen with more than 50% of morphologically normal cells showed the best recovery of motile cells after freezing and thawing.     

A comparison of intrauterine versus intracervical insemination in fertile single women

OBJECTIVE: To compare the efficacy of intrauterine insemination (IUI) and intracervical insemination (ICI) when used by fertile single women in a donor insemination program. DESIGN: Prospective randomized crossover study. SETTING: Donor insemination program (not an infertility clinic). PATIENT(S): Single fertile women choosing to inseminate with frozen donor semen. INTERVENTION(S): Clients received procreative counseling and screening and were then randomly assigned to begin office insemination with ICI or IUI. If additional insemination cycles were required, the clients used the method opposite their previous method of insemination until pregnancy was achieved. MAIN OUTCOME MEASURE(S): Monthly fecundity rate was compared between the two methods of insemination. RESULT(S): Sixty-two women contributed a total of 189 cycles, 94 by IUI and 95 by ICI. The monthly fecundity rate for IUI was 15%, as compared with 9% for ICI, (P=0.14). When the analysis was confined to cycles in which only one insemination was performed (64 IUI and 65 ICI cycles), the monthly fecundity rates were 14% for IUI and 5% for ICI (P=0.04). CONCLUSION(S): Intrauterine insemination with frozen donor sperm is more effective than intracervical insemination for single women without known fertility problems.     

Does Seasonality Alter Intrauterine Insemination Outcomes: A 5-Year Study

PURPOSE: To determine if seasonal changes alter pregnancy rate in intrauterine insemination (IUI) patients. METHODS: One-thousand and eighty semen analyses prepared for IUI were evaluated in this retrospective cohort study of 496 patients. RESULTS: Volume, pH, sperm concentration, and pregnancy rates were not altered by season. However, the percent motility, the total motile spermatozoa in the ejaculate, the straight-line velocity (VSL) of spermatozoa, as well as the morphology of sperm were altered by season. In a subset of these patients that were defined as normal, only the VSL and the morphology of the spermatozoa were altered by seasonal changes. CONCLUSIONS: Seasonality alters sperm motility parameters as well as morphology, but these changes are not significant enough to alter pregnancy rates.     

Relationship between human semen parameters and deoxyribonucleic acid damage assessed by the neutral comet assay

OBJECTIVE: To explore the association between semen parameters and sperm DNA damage. DESIGN: Cross-sectional. SETTING: Andrology clinic. PATIENT(S): Two hundred fifty-seven men undergoing infertility assessment. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Sperm concentration and motility were measured using computer-assisted sperm analysis; morphology was scored using the strict criteria. The neutral comet assay was used to measure sperm DNA damage. Comet assay parameters included comet extent, percent DNA in the comet tail, and tail distributed moment, an integrated measure of length and intensity. We also scored cells that were too long to measure (>300 microm), which we referred to as cells with high DNA damage. RESULT(S): Men older than 35 years had a statistically significant increase in the number of cells with high DNA damage as compared with younger men. In age-adjusted regression analyses, the most consistent associations were found between semen parameters and the number of cells with high DNA damage. For an interquartile range change in the number of cells with high DNA damage, sperm concentration declined 14.2 x 10(6)/mL, motility declined 4.3%, and morphology declined 0.5%. Comet extent and percent DNA in the comet tail were also associated with a decline in sperm concentration and motility, respectively. CONCLUSION(S): Although there were associations between semen and comet assay parameters, their magnitudes were weak, suggesting that the comet assay provides additional independent information on sperm function.     

Use of carnitine therapy in selected cases of male factor infertility: a double-blind crossover trial

OBJECTIVE: To determine the efficacy of L-carnitine therapy in selected cases of male factor infertility. DESIGN: Placebo-controlled, double-blind, crossover trial. SETTING: University tertiary referral center. PATIENT(S): One hundred infertile patients (ages 20-40 years) with the following baseline sperm selection criteria: concentration, 10-20 x 10(6)/mL; total motility, 10%-30%; forward motility, <15%; atypical forms, <70%; velocity, 10-30 micro/s; linearity, <4. Eighty-six patients completed the study. INTERVENTION(S): Patients underwent L-carnitine therapy 2 g/day or placebo; the study design was 2 months of washout, 2 months of therapy/placebo, 2 months of washout, and 2 months placebo/therapy. MAIN OUTCOME MEASURE(S): Variation in sperm parameters used in the patients selection criteria, in particular, sperm motility.Excluding outliers, a statistically significant improvement in semen quality, greater than after the placebo cycle, was seen after the L-carnitine therapy for sperm concentration and total and forward sperm motility. The increase in forward sperm motility was more significant in those patients with lower initial values, i.e., <5 x 10(6) or <2 x 10(6) of forward motile sperm/ejaculate or sperm/mL. CONCLUSION(S): Based on a controlled study of efficacy, L-carnitine therapy was effective in increasing semen quality, especially in groups with lower baseline levels. However, these results need to be confirmed by larger clinical trials and in vitro studies.     

微流控芯片优选人类精子研究

目的:探讨微流控芯片技术对精子的优选能力。方法:自行设计和制造微流控芯片,利用芯片对40例人精液标本进行精子分选实验,优化其分选条件,观察芯片处理前后精液各参数变化。同时对其中30例精液标本(A组:a+b级精子<20%组,n=15;B组:a+b级精子≥20%组,n=15)同时用芯片法和密度梯度离心法分选,比较2种方法分离前后精子活力、形态等参数的变化。结果:①优选后精子活力和精子正常形态率都可见显著提高(P<0.001;P<0.01)。②在精子活动力优选上A、B组芯片法均明显优于密度梯度离心法(P<0.01),尤其在A组这种优势更为明显(P<0.001)。而在精子形态优选上,2种方法无显著差异(P>0.05)。结论:微流控芯片技术在优选精子中具有较高的分选效率,且具有操作简单、分选时间短,对精子损伤小的特点,在辅助生殖技术中特别是体外受精中将有良好的应用前景。     

Fertility potential of individual sperm donors

OBJECTIVE: To study the fertility potential of individual semen donors with ejaculates of optimal as compared to suboptimal quality. METHODS: 363 semen donations were obtained from 11 donors between January 1993 and September 1997. 270 samples were cryopreserved and 1,399 straws obtained from 120 ejaculates were used in 495 insemination cycles. RESULTS: 52 pregnancies were achieved in 128 recipients (40.6%). No significant differences were found between donors of high fecundability and those of low fecundability regarding sperm parameters. The mean donor fecundability index was 10.5%. The optimal and suboptimal samples yielded similar results. Donors with suboptimal semen quality had an increased number of samples rejected after thawing. CONCLUSION: Traditional semen analysis parameters do not differentiate high from low fecundability donors. Suboptimal results of the semen analysis should not exclude potential donors from an artificial insemination donor (AID) program.     

The use of semen parameters to identify the subfertile male in the general population

AIMS: To present a structured review of the literature published on semen parameters and in vivo fertility potential and to establish fertility/subfertility thresholds for sperm morphology using Tygerberg strict criteria, sperm concentration, and sperm motility. METHOD: The published literature comparing fertile and subfertile populations between 1983 and 2002 was reviewed. RESULTS: A total of 265 articles were identified by the sourcing methodology, but only four articles provided data that could be tabulated and analyzed. Using receiver-operating characteristics curves, morphology proved to be the best predictor of subfertility in 2 of the 4 articles, with concentration and motility also showing good predictive power. The thresholds calculated ranged between 4 and 10% for morphology, between 13.5 x 10(6)/ml and 34 x 10(6)/ml for concentration, and between 32 and 52% for motility. A second set of much lower thresholds was calculated in three of the articles using either a 15 or 50% prevalence of subfertility in the population or the tenth percentile of the fertile population. The adjusted thresholds were between 3 and 5% for morphology, between 9 x 10(6)/ml and 20 x 10(6)/ml for concentration, and between 20 and 30% for motility. CONCLUSIONS: Because these lower thresholds have a much higher positive predictive value, we suggest that thresholds of <5% normal sperm morphology, a concentration <15 x 10(6)/ml, and a motility <30% should be used to identify the subfertile male. The lower threshold for morphology also fits in vitro fertilization and intrauterine insemination data calculated previously. Using the parameters in combination increases the clinical value of semen analysis.     

The semen of fertile men. II. Semen characteristics of 100 fertile men.

From a population of men applying for voluntary sterilization, 100 consecutive cases were selected according to the following criteria: (1) each man had fathered at least two children; (2) at the time of the request for a vasectomy the man's wife was pregnant; and (3) a complete prevasectomy semen analysis, including sperm morphology, was available. The usual parameters of human semen evaluation are reported: the mean volume of the ejaculates was 3.3 ml +/- 0.84 SD (range, 0.5 to 11 ml); the mean sperm density was 81 million/ml +/- 57 SD (range, 4 to 318); while the geometric mean, which according to the sample distribution is more representative, was 68. The mean percentage of motile sperm was 63% +/- 16 SD (range, 10 to 95%); the grade of forward progression was 3 +/- 0.55 SD (range, 2 to 4); and for sperm morphology the mean number of sperm with oval heads was 75% +/- 6 SD (range, 21 to 90%). Statistical comparison of these findings with those of our previous study of the semen of 1300 fertile men revealed complete agreement; minor statistical differences, on single parameters, with three similar studies are indicated. A positive relationship between the different variables, sperm density and sperm motility (in percentage of motile sperm and degree of forward motion), as well as between the two variables of sperm motility and sperm morphology to the other variables was confirmed.     

Novel associations between specific sperm morphological defects and leukocytospermia

OBJECTIVE: To examine the relationship between leukocyte concentrations in semen and sperm morphology in a group of infertile men and healthy fertile donors. DESIGN: A prospective clinical study. SETTING: Male infertility clinic at a tertiary care teaching hospital and a reproductive medicine unit at a Women's Hospital in the United Kingdom. PATIENT(S): Fifty-six infertile men and 13 healthy fertile sperm donors (control). INTERVENTION(S): Standard semen analysis, seminal leukocyte concentration, and the assessment of sperm morphology and sperm deformity index (SDI), applying Tygerberg's strict criteria. MAIN OUTCOME MEASURE(S): Granulocyte concentrations in semen, percentages of different sperm morphological abnormalities, and SDI scores. RESULT(S): Leukocyte concentrations were statistically significantly and negatively correlated with the proportion of sperm with damaged acrosomes, cytoplasmic droplet, tail defects, and SDI scores with normal and borderline morphology. The percentage sperm motility was significantly and negatively correlated with leukocytic concentration in semen. However, the leukocytic concentration was not significantly correlated with sperm concentration. CONCLUSION(S): This is the first study to report a significant positive correlation between leukocytospermia and sperm tail defects, acrosomal damage, and high SDI scores. These observations suggest that leukocytospermia is associated with compromised sperm structural integrity.