Semen quality of young men from the general population in Baltic countries.

STUDY QUESTION: What are the parameters of semen quality in Baltic men? SUMMARY ANSWER: Combined parameters of sperm concentration, motility and morphology revealed that 11-15% of men had low semen quality, 37-50% intermediate and 38-52% high semen quality. WHAT IS KNOWN ALREADY: Previous studies have revealed regional differences in semen parameters, and semen quality of Baltic men has been suggested to be better than that of other European men. STUDY DESIGN, SIZE, DURATION: This was a cross-sectional study of 1165 men aged 16-29 years from Estonia (N = 573), Latvia (N = 278) and Lithuania (N = 314) conducted in 2003-2004. PARTICIPANTS/MATERIALS SETTING METHODS: Men from the general population, median age 19.8 years, provided one semen sample each, had blood samples taken, had testis size determined, and provided information on lifestyle. Based on combined data of sperm concentration, sperm motility and morphology the cohort was classified into three categories: low, intermediate or high semen quality. Comparisons between groups (including subgroups of Estonian men of Russian versus Estonian ethnicity) were tested, adjusting for ejaculation abstinence and age. MAIN RESULTS AND THE ROLE OF CHANCE: The median sperm concentration of the Estonian, Latvian and Lithuanian populations of Baltic men was 63 mill/ml. Low semen quality was detected in 11-15% of the men, intermediate in 37-50% and high in 38-52%. No crucial differences between national subgroups were detected, except that a higher percentage (9.6%) of the subgroup of Russian Estonians reported having had cryptorchidism compared to the other men (2.5-3.6%, P < 0.001). Smoking had an adverse impact on both sperm concentration and total sperm counts (P < 0.001). LIMITATIONS REASONS FOR CAUTION: The semen quality data were collected >10 years ago. Thus, a recent change in semen quality cannot be excluded. Owing to the study design, it is assumed, but unproven, that the men were representative of the general populations. Some men were very young (16 years), however, this was also the case for other European studies of similar populations. Assessment of sperm motility is associated with inter-observer variation, and no quality control was undertaken for sperm motility assessment to account for that. Thus, estimates of sperm motility should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS: Analysis of the semen variables separately did not identify that a considerable percentage of Baltic men had low semen quality. The combined analysis, however, showed that more than one out of nine men had semen quality at a level indicating reduced fertility chances. We suggest that future studies of semen quality should be carried out reporting both results of single semen parameters and estimates that combine the most frequently assessed variables. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the EU fifth framework project Number QLK4-1999-01422 'Envir.Repro.Health' extension to Baltic countries Number QLRT-2001-02911; Estonian Science Foundation, grant numbers 2991 and PUT181. There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Varicocele Is Associated with Impaired Semen Quality and Reproductive Hormone Levels: A Study of 7035 Healthy Young Men from Six European Countries.

BACKGROUND: Present knowledge on the impact of varicoceles on testicular function is largely based on studies of subfertile and infertile men, making it difficult to extrapolate the impact of varicocele on the general population. OBJECTIVE: To describe associations between varicocele and testicular function assessed by semen analysis and reproductive hormones in men from the general population. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional multicentre study of 7035 young men, median age 19 yr, from the general population in six European countries (Denmark, Finland, Germany, Estonia, Latvia, and Lithuania) were investigated from 1996 to 2010. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We analysed results from physical examination, conventional semen variables, and serum reproductive hormones using multivariable regression analyses. RESULTS AND LIMITATIONS: A total of 1102 (15.7%) had grade 1-3 varicocele. Increasing varicocele grade was associated with poorer semen quality, even in grade 1 varicocele. In grade 3 varicocele, sperm concentration was less than half of that in men with no varicocele. Presence of varicocele was also associated with higher serum levels of follicle-stimulating hormone, lower inhibin B, and higher levels of luteinising hormone; testosterone and free testosterone were not significantly different between men with and without varicocele. This study cannot draw a conclusion on the progressiveness of varicocele or the effect of treatment. CONCLUSIONS: We demonstrated an adverse effect of increasing grade of varicocele on testicular function in men not selected due to fertility status. PATIENT SUMMARY: The presence and increasing grade of varicocele is adversely associated with semen quality and reproductive hormone levels in young men from the general population.

Reproductive physiology in young men is cumulatively affected by FSH-action modulating genetic variants: FSHR -29G/A and c.2039 A/G, FSHB -211G/T.

Follicle-Stimulating Hormone Receptor (FSHR) -29G/A polymorphism (rs1394205) was reported to modulate gene expression and reproductive parameters in women, but data in men is limited. We aimed to bring evidence to the effect of FSHR -29G/A variants in men. In Baltic young male cohort (n = 982; Estonians, Latvians, Lithuanians; aged 20.2 ± 2.0 years), the FSHR -29 A-allele was significantly associated with higher serum FSH (linear regression: effect 0.27 IU/L; P = 0.0019, resistant to Bonferroni correction for multiple testing) and showed a non-significant trend for association with higher LH (0.19 IU/L) and total testosterone (0.93 nmol/L), but reduced Inhibin B (-7.84 pg/mL) and total testes volume (effect -1.00 mL). Next, we extended the study and tested the effect of FSHR gene haplotypes determined by the allelic combination of FSHR -29G/A and a well-studied variant c.2039 A/G (Asn680Ser, exon 10). Among the FSHR -29A/2039G haplotype carriers (A-Ser; haplotype-based linear regression), this genetic effect was enhanced for FSH (effect 0.40 IU/L), Inhibin B (-16.57 pg/mL) and total testes volume (-2.34 mL). Finally, we estimated the total contribution of three known FSH-action modulating SNPs (FSHB -211G/T; FSHR -29G/A, c.2039 A/G) to phenotypic variance in reproductive parameters among young men. The major FSH-action modulating SNPs explained together 2.3%, 1.4%, 1.0 and 1.1% of the measured variance in serum FSH, Inhibin B, testosterone and total testes volume, respectively. In contrast to the young male cohort, neither FSHR -29G/A nor FSHR haplotypes appeared to systematically modulate the reproductive physiology of oligozoospermic idiopathic infertile patients (n = 641, Estonians; aged 31.5 ± 6.0 years). In summary, this is the first study showing the significant effect of FSHR -29G/A on male serum FSH level. To account for the genetic effect of known common polymorphisms modulating FSH-action, we suggest haplotype-based analysis of FSHR SNPs (FSHR -29G/A, c.2039 A/G) in combination with FSHB -211G/T testing.

Genetically determined dosage of follicle-stimulating hormone (FSH) affects male reproductive parameters.

CONTEXT: The detailed role of FSH in contributing to male testicular function and fertility has been debated. We have previously identified the association between the T-allele of the FSHB promoter polymorphism (rs10835638; G/T, -211 bp from the mRNA start) and significantly reduced male serum FSH. OBJECTIVE: In the current study, the T-allele carriers of the FSHB -211 G/T single nucleotide polymorphism represented a natural model for documenting downstream phenotypic consequences of insufficient FSH action. DESIGN AND SUBJECTS: We genotyped rs10835638 in the population-based Baltic cohort of young men (n = 1054; GG carriers, n = 796; GT carriers, n = 244; TT carriers, n = 14) recruited by Andrology Centres in Tartu, Estonia; Riga, Latvia; and Kaunas, Lithuania. Marker-trait association testing was performed using linear regression (additive, recessive models) adjusted by age, body mass index, smoking, and recruitment center. RESULTS: Serum hormones directly correlated with the T-allele dosage of rs10835638 included FSH (additive model, P = 1.11 × 10(-6); T-allele effect, -0.41 IU/liter), inhibin-B (P = 2.16 × 10(-3); T-allele effect, -14.67 pg/ml), and total testosterone (P = 9.30 × 10(-3); T-allele effect, -1.46 nmol/liter). Parameters altered only among TT homozygotes were reduced testicular volume (recessive model, P = 1.19 × 10(-4); TT genotype effect, -9.47 ml) and increased serum LH (P = 2.25 × 10(-2); TT genotype effect, 1.07 IU/liter). The carrier status of rs10835638 alternative genotypes did not affect sperm motility and morphology, calculated free testosterone, serum SHBG, and estradiol concentrations. CONCLUSION: We showed for the first time that genetically determined low FSH may have wider downstream effects on the male reproductive system, including impaired testes development, altered testicular hormone levels (inhibin-B, total testosterone, LH), and affected male reproductive potential.

Cigarette smoking and waiting time to pregnancy: results of a pilot study.

Waiting time to pregnancy is an important characteristic of human reproductive health, which has not been investigated in Lithuania until now. Data on waiting time to pregnancy have been collected from medical records of 111 women admitted to the Department of Obstetrics, Klaipeda Hospital. Seven women in whom pregnancy was the result of infertility treatment were excluded from the analysis, and the rest 104 cases were analyzed. We evaluated waiting time to pregnancy in respect to the age of couples, contraceptive use, cigarette smoking of both partners, and some other features of obstetric history. The mean waiting time to pregnancy in the cohort was 5.21+/-7.03 months. If both partners smoked, the mean waiting time to pregnancy was significantly longer than in nonsmoking couples (7.68+/-9.41 vs. 4.30+/-5.73, P<0.05). Risk to have waiting time to pregnancy longer than 6 months was significantly higher if both partners smoked as compared to nonsmoking couples (OR 3.32, 95% CI 1.07-10.30, P=0.03), while paternal smoking and smoking of any partner did not increase this risk significantly. The other possible factors - age, living place (rural or city), previous contraceptive use, regularity of menstrual cycle, and frequency of intercourse - did not influence waiting time to pregnancy significantly. Results obtained from this pilot study enable us to plan and implement a larger-scale study of waiting time to pregnancy in Lithuanian population.

Association of in utero exposure to maternal smoking with reduced semen quality and testis size in adulthood: a cross-sectional study of 1,770 young men from the general population in five European countries.

Between 1996 and 1999, the authors invited all young men from five European countries who were undergoing compulsory medical examination for possible military service to participate in a study on male reproductive health. The participation rate was 19% in two cities in Denmark (n = 889), 17% in Oslo, Norway (n = 221), 13% in Turku, Finland (n = 313), 14% in Kaunas, Lithuania (n = 157), and 19% in Tartu, Estonia (n = 190). Each man provided a semen sample, was examined by a physician, and, in collaboration with his mother, completed a questionnaire about general and reproductive health, current smoking habits, and exposure to smoking in utero. After adjustment for confounding factors, men exposed to smoking in utero had a reduction in sperm concentration of 20.1% (95% confidence interval (CI): 6.8, 33.5) and a reduction in total sperm count of 24.5% (95% CI: 9.5, 39.5) in comparison with unexposed men. Percentages of motile and morphologically normal sperm cells were 1.85 (95% CI: 0.46, 3.23) and 0.64 (95% CI: -0.02, 1.30) percentage points lower, respectively, among men exposed in utero, and exposed men had a 1.15-ml (95% CI: 0.66, 1.64) smaller testis size. The associations were present when data from the study centers were analyzed separately (though not in Lithuania, where only 1% of mothers smoked during pregnancy), although the strength of the association varied. Maternal smoking may have long-term implications for the reproductive health of the offspring. This is another good reason to advise pregnant women to avoid smoking.

Regional differences in semen qualities in the Baltic region.

Recent prospective studies of male reproductive health have shown differences between several European countries. Our objective was to evaluate the current situation in the two Baltic States Estonia and Lithuania. In 1997-99 we investigated semen parameters, levels of reproductive hormones and general health factors of 196 men from the general population in Lithuania; from Estonia, 79 men from the general population and 118 soldiers were investigated. Adjusted for interlaboratory differences and abstinence period, sperm concentration of Lithuanian and Estonian men from the general populations were shown to be 55 and 67 million/mL, respectively. The Estonian soldiers had the highest sperm concentration, 82 million/mL. The frequencies of morphologically normal spermatozoa were 6.2, 7.7 and 9.6%, respectively. In contrast to the semen qualities, highest Inhibin B levels were detected in the Lithuanians (233 pg/mL) followed by Estonian men from the general population (220 pg/mL) and Estonian soldiers (185 pg/mL). The soldiers had also the lowest level of testosterone and oestradiol. The sperm counts of the Estonian and Lithuanian men investigated here are higher than recently shown for Norwegian, Danish, Estonian and Finnish men. Comparisons should be cautiously drawn as the groups are not completely comparable. Still, even within the Baltic region, geographically close and sharing common recent social history, differences in semen quality and levels of reproductive hormones are apparent.