ISI Impact Factor (2004): 1.096

Editor-in-Chief
Prof. Yi-Fei WANG,

Male infertility: risk factors in Mongolian men

G. Bayasgalan¹, D. Naranbat¹, J. Radnaabazar¹, T. Lhagvasuren², P. J. Rowe³

Asian J Androl  2004 Dec; 6: 305-311           

Keywords: male infertility; semen quality; risk factors; azoospermia; sexually transmitted infections; testis injury

Abstract

Aim: To determine the most common risk factors of male infertility in Mongolian men attending an infertility clinic. Methods: A prospective, case-control study was conducted in which 430 men were enrolled. All the men had sought their first infertility evaluation between 1998-2002 in the State Research Center on Maternal Child Health, Ulaanbaatar, Mongolia. They were divided into two groups depending on the results of their semen analysis: 191 with abnormal semen and 239 with normal semen profile. Univariate and multivariate analyses were performed to determine any association between risk factors and semen abnormality. Results: Logistic regression analysis demonstrated that the testicular volume, a history of sexually transmitted infections (STI), epididymitis and testicular damage all have statistically significant associations with semen abnormality, when controlled for multiple risk factors. Adjusted odds ratios of 3.4 for mumps orchitis, 2.3 for other orchitis and 3.9 for testicular injury were found. Gonorrhoea, the most commonly reported STIs in this study, gave an adjusted odds ratio of 1.0 for having one or more sperm abnormality. An adjusted odds ratio for subjects with a history of other STIs was 2.7. However, as a predictor of azoospermia, STIs had very high odds ratio, being 5.6 in patients with gonorrhoea and 7.6 in patients with other STIs. Conclusion: A history of pathology involving testicular damage appeared to have the strongest impact on male infertility in Mongolia. STIs have less impact on semen quality except when complicated by orchitis, epididymitis and vasal obstruction.

1 Introduction

Infertility, defined as the inability to conceive after at least one year of unprotected intercourse, affects about 8 % - 12 % of all married couples. In about one third of these couples, a male factor is the primary problem and in another one quarter, both the male and the female partner contribute to the infertility [1]. As male infertility is not a diagnostic entity and only reflects a variety of different pathological conditions, there is no consensus on its effective management. It is noteworthy that even today, recognizable causes of male infertility are present in only 40 % of cases [2]. In the other 60 %, infertility presented as an isolated abnormality in the semen analysis without diagnosable pathology. This would explain why male infertility is generally regarded as a condition that is difficult to treat, especially in the low-cost settings of many developing countries, where advanced methods of assisted reproductive techniques, such as intracytoplasmic sperm injection, are not available.

In developing countries, patterns of infertility are quite different from those in developed countries. Generally speaking, the incidence of preventable infertility is much higher in developing countries and Mongolia is no exception [4]. A hospital-based study using the WHO protocol for the "Standardized Investigation of the Infertile Couple" has shown that 43.7 % of women and 30.7 % of men suffered from secondary infertility and that there was a preponderance of preventable causes of infertility in both women and men [5]. Since many cases of male infertility are preventable and in general it requires sophisticated, expensive treatment, the prevention of male infertility appears to be one of the priority tasks of infertility programmes in the developing countries.

In men, infertility risk factors, such as male accessory gland infection (including epididymitis and prostatitis), mumps orchitis, varicocoele and cryptorchidism are well documented [3-5]. Several studies have demonstrated the hazardous effect of environmental factors such as toxic substances, pesticides and radiation on male reproductive function [6-7]. The abuse of tobacco, alcohol and caffeine also have been linked with male infertility [8-9]. However, it should be noted that there are different intensities of risk factors for male infertility in different countries and regions and the identification of major risk factors in any particular country would have important public health significance.

Although there are known limitations in its objectivity, including the temptation to assume so-called "normal" values, semen analysis is a key element in the fertility evaluation of men and permits male reproductive potential to be evaluated in association with possible risk factors. However, semen samples are difficult to obtain in general population studies and the participation rate, which is usually less than 20 %, may invalidate conclusions when extrapolated to the general population [10]. Studies of populations, in which men are seeking infertility treatment, avoid this problem, because semen analysis is a key part of their fertility evaluation. If the different bias and confounding factors are taken into account, this population provides the opportunity to study the associations between the risk factors and the outcomes. Therefore, the objective of the present study was to determine the most common risk factors of male infertility in Mongolian men attending the infertility clinic.

2 Materials and methods

The study was carried out in the State Research Centre for Maternal Child Health, Ulaanbaatar, Mongolia, the first andrological laboratory established with the financial and technical assistance of the WHO Special Programme of Research, Development and Research Training in Human Reproduction. The Centre provides infertility services for men from Ulaanbaatar and other provinces. The study sample consisted of 430 male partners of infertile couples who had infertility for more than one year and who sought their first infertility evaluation between January 1998 and December 2002. The subjects were divided into two groups depending on the results of their semen analysis. In 191 cases one or more of the semen parameters were classified as abnormal according to WHO criteria [11]. The remaining 239 men with normal semen profiles served as the control group. Approval for this study was obtained from the Institutional Review Board.

All men enrolled in this study gave written consent after the procedures had been described to them and they had had the opportunity to ask questions. The infertility history, examination and laboratory investigations used are those described in detail in the "WHO Manual for the Standardized Investigation of the Infertile Couple" [12]. These comprised a detailed medical history and a complete physical examination. The structured questionnaire of this protocol was designed to obtain information about demographic characteristics, medical and reproductive health history, lifestyle, possible risk factors for infertility and the physical status of the patient.

Two semen analyses of not less than fourteen and not more than ninety days apart were routinely undertaken. Semen samples were obtained by masturbation in the clinic after 3 - 5 days sexual abstinence. Semen　assessment was performed as soon as the samples were liquefied, but within one hour from collection according to the routine method described by WHO [11]. Seminal volume was measured in a graduated pipette accurate to within 0.1 mL. Sperm concentration was determined by a haemo-cytometer (improved Neubauer counting chamber) after an appropriate dilution. Sperm motility was assessed by direct observation under a microscope (×400). Sperm morphology was assessed under a microscope (×1 000) using a staining technique (Eosin-Nigrosin). Reference values for normal semen were adopted from the WHO manual on semen analysis [11]. Azoospermia was defined as total absence of sperm in the semen; oligozoospermia as sperm concentration of <20×10⁶/mL or sperm count of < 40×10⁶ per ejaculate. Asthenozoospermia was defined as < 50 % spermatozoa with forward progression or < 25 % spermatozoa with rapid progression; teratozoospermia as reduced percentage (<30 %) of morphologically normal spermatozoa. Abnormal seminal plasma is referred as seminal volume less than 2.0 mL or abnormal physical characteristics of semen with normal spermatozoa.

Data were expressed as mean±SEM and the level of significance for comparison set at P<0.05. The dependent variable (semen quality) was recoded into dichotomous values, namely normal and abnormal semen. Comparisons between the two groups were made using the c²-test for categorized independent variables and the t-test and analysis of variance (ANOVA) for continuous independent variables. In order to determine the most significant factors in subjects with abnormal semen and azoospermia, multivariate logistic regression tests were carried out. Odds ratios showed the likelihood of having abnormal semen and azoospermia, under the influence of a selected factor, controlled by others. Analyses were carried out using SPSS for Windows version 10.

The general characteristics of the men with abnormal and normal semen, enrolled in this study are shown in Table 1. The mean age for patients with abnormal semen was 31.2±0.4 versus 30.9±0.3 for the control group with normal semen analysis (P>0.05). There were statistically non-significant differences between groups in age distribution and residence. Secondary infertility was more prevalent in men with normal semen in which 39.75 % had previously conceived a child versus 29.4 % in patients with abnormal semen.

Table 1. Basal condition in 430 men.^bP<0.05, ^cP<0.01, compared with men with normal semen.

The delay in seeking treatment for infertility was longer in men with abnormal semen (62.7±2.8 months) compared to the controls (54.8±2.3 months). The majority of men in both groups sought medical consultation after waiting for more than two years and only 27 men amongst the cases and 44 men in the controls sought infertility treatment within two years.

3.2 Semen analysis

Two hundred and thirty-nine (55.6 %) men had normal semen analysis and 191 (44.4 %), abnormal seminal parameters (Table 2). The most commonly detected abnormality was azoospermia, which was found in 88 cases (20.5 %). In the remaining cases, oligozoospermia was detected in 50 (11.6 %) cases and asthenozoospermia, in 32 (7.4 %) cases. Abnormal seminal plasma and teratozoospermia were found in 16 (3.7 %) and 5 (1.2 %) patients, respectively.

Table 2. Semen analysis.

1 Total absence of sperm in the semen; 2 Sperm concentration of <20×10⁶/mL or Total count <40?06/mL; 3 <50% spermatozoa with forward progression; 4 Seminal volume less than 2.0 mL or abnormal physical characteristics of semen with normal spermatozoa; 5 Reduced percentage (<30 %) of morphologically normal spermatozoa.

Comparisons of some major determinants of infertility between men with normal and abnormal semen analysis, using univariate analysis are shown in Table 3. A history of systemic disease, alcohol consumption and tobacco smoking were similar in both groups. All other variables had statistically significant associations with impaired semen quality. The main risk factors identified for infertility were testicular volume and histories of STIs, epididymitis, testicular damage and maldescent. In addition, previous histories of surgery, urinary infection and varicocoele had statistically significant associations with impaired semen quality.

Table 3. Cross tabulation between possible risk factors for male infertility and semen abnormality (P values calculated by c² test for categorical variables and t-test for continuous variables)

¹ Grade 1, a distinct dilatation of the internal spermatic veins palpable during a Valsalva manoeuvre when upright; Grade 2, a-palpable vein when upright with no Valsalva manoeuvre; Grade 3, a vein both palpable and visible through the scrotal skin when upright, with no Valsalva manoeuvre.

In addition, 53.4 % of men with a semen abnormality and 46.8 % of patients with no in seminal abnormality gave a previous history of sexually transmitted infections (STI) (P<0.01). Gonorrhoea, the most prevalent STI, appeared to have less effect on impaired semen quality compared to other infections. The percentage of men with previous gonorrhoea was similar in each group, 28.3 % in cases versus 24.7 % in controls (P=0.06). Incidences of STIs other than gonorrhoea were higher in cases (25.1 %) than that in patients with no abnormality in the semen (12.1 %) (P<0.01).

There was statistically significant association between the history of STI and epididymo-orchitis. Prevalence of epididymitis and orchitis were 17.9 % and 12.1 %, respectively in patients with a history of STIs as compared to 10.0 % and 6.3 % in those without (P<0.05).

A previous history of epididymitis was reported to have 22.0 % of men with abnormal semen versus 6.7 % in patients with normal semen (P<0.01). Pathology with a potential to induce testicular damage was detected in 41.4 % of males with impaired semen quality versus 16.7 % in men with normal semen (P<0.01). There was a high incidence of testicular injury in men in this study. Altogether 74 (17.2 %) men had testicular injury, of which 48 (11.2 %) had abnormal semen (P<0.01). The proportion of men with a previous history of orchitis was higher in the abnormal semen group (16.3 %) than that in the normal group (5.8 %) (P<0.01). Testicular maldescent was diagnosed in 12 (2.8 %) men, only two had normal semen parameter (P<0.01).

In the abnormal semen group, 26.1 % had previous surgery and 40.8 % had had past urinary infection versus 13.4 % and 26.8 %, respectivley, in the patients with normal semen (P=0.01). Varicocoele was detected in 18.4 % of men with abnormal semen versus 8.0 % in the men with normal semen (P<0.01). Testicular volume of men with abnormal semen (13.1±0.3 mL) was significantly smaller than those of men with normal semen (14.7±0.2 mL) (P<0.01).

Multivariate logistic regression analysis was performed to investigate the role of possible risk factors in abnormal semen quality. The variables that had a statistically significant correlation with sperm abnormality were: testicular volume, varicocoele, previous histories of STIs, epididymitis, testicular damage, surgery, urinary infection and testicular maldescent. As azoospermia was the most prevalent type of semen abnormality, the effects of risk factors in patients with azoospermia were also studied. Two dependent variables were recoded into dichotomous values: abnormal semen or not and azoospermia or not.

The results of this logistic regression demonstrated that testicular volume and a history of STIs, epididymitis and testicular damage have statistically significant associations with sperm abnormality, when controlled for multiple risk factors (Table 4). A history of pathology causing testicular damage had the strongest impact on male infertility (P<0.01). Adjusted odds ratios of 3.4 for mumps orchitis, 2.3 for other orchitis and 3.9 for testicular injury were found.

Table 4. Logistic regression analysis (odds ratios for the relationship between selected risk factors and sperm abnormality and azoospermia). ^bP<0.05, ^cP<0.01.

A history of epididymitis was strongly associated with sperm abnormality. The odds of having impaired semen quality were 2.2 in cases with unilateral epididymitis and 5.3 with bilateral epididymitis, compared to patients with no history of epididymitis. The likelihood of having impaired semen quality was 2.2 times more in men with a testicular volume less than 12 mL compared to those with normal testicular volume There was a high adjusted odds ratio for patients with cryptorchidism (OR=6.7), it did not achieve statistical significance (P>0.05). Grade 2 varicocoele, but Grades 1 or 3, was found to have a significant correlation with sperm abnormality (odds ratio 3.9).

Gonorrhoea, the most commonly reported STIs in this study, gave an adjusted odds ratio of 1.0 for having one or more sperm abnormality. An adjusted odds ratio for subjects with a history of other STIs was 2.7. However, as a predictor of azoospermia, STIs had very high odds, 5.6 in patients with gonorrhoea and 7.6 in patients with other STIs.

An another significant determinant for azoospermia was testicular injury with an odds ratio of 5.6. In addition, both unilateral and bilateral epididymitis had a significant correlation with azoospermia (odds ratio of 2.3 and 3.7, respectively).

4 Discussion

The male factor is the cause of the infertility in about 50 % of infertile couples and is regarded as a condition that is difficult to treat in a low-cost setting. The risk factors of male infertility differ from one country to another, so it is important that any developing country should determine the most influential factors in their population.

The level and patterns of infertility differ significantly between countries and regions. This variability is believed to be related to the difference in risk factors in different regions [13,14]. This study evaluated the effect of risk factors of male infertility on semen abnormality in Mongolian men attending an infertility clinic. Comparisons were made between men with normal semen and men with impaired sperm characteristics. However, as patients with no abnormality in the semen in this study also complained of one or more years of infertility, the results of this study should be interpreted with caution.

In developing countries, reproductive tract infections including STI's are regarded as the major determinants of female infertility. However, for male infertility, the effects of STI's are not so clear-cut and research results are conflicting [15]. Even with possible underestimation , this study recorded a high percentage (44.2 %) of men with a past history of STI's. As this study was carried out by questionnaire it was not possible to determine precisely the type of STI that the respondent had had in the past, especially in cases when men had STI's other than gonorrhoea. Hence, all other STI's were classified into one group and this group had a significant association with abnormal semen. As compared to a non-gonorrhoea group, men with gonorrhoea had a weaker association with impaired semen quality. Greendale et al [16] reported that infertile men were 3.4 times more likely to have a high titer of IgG anti-chlamydial antibodies. Similar results have been reported by other authors, suggesting the Chlamydia trachomatis as one of the most important infectious agents for male infertility [17, 18].

This study was consistent with reports of the other authors [3, 19] demonstrating a significant association between epididimo-orchitis and male infertility. However, it should be kept in mind that epididimo-orchitis are strongly associated with STIs [20]. Hence, it seems that STI's have less impact on semen quality except when complicated by orchitis, epididymitis and vasal obstruction . This may partly explain why STI's had a very high association with azoospermia in the present study.

In conclusion, together with reproductive tract infections, as STI's, orchitis and epididymitis, testicular injury must be regarded as a serious problem in male infertility in Mongolia. It might be related to the traditional lifestyle in rural areas, where most men ride horses and may have a higher risk of testicular injury. However, further study is needed to explore testicular injury and its consequences among the infertile men and the general population in Mongolia.

This study received financial support from the WHO Special Programme of Research, Development and Research Training in Human Reproduction. Authors wish to thank Prof G. Waites for his comments on the paper.

References

[1] World Health Organization. Infertility: a tabulation of available data on prevalence of primary and secondary infertility. Geneva, WHO, Programme on Maternal and Child Health and Family Planning, Division of Family Health. 1991.
[2] Bhasin S, de Kretser DM, Baker HW. Pathophysiology and natural history of male infertility. J Clin Endocrinol Metab 1994; 79: 1525-9.
[3] Melecos MD, Asbach HW. Epididymitis: aspects concerning etiology and treatment. J Urol 1987; 138: 83-6.
[4] Mieusset R, Bujan L. Testicular heating and its possible contributions to male infertility: a review. Int J Androl 1995; 18: 169-84.
[5] The influence of varicocele on parameters of fertility in a large group of men presenting to infertility clinics. World Health Organization. Fertil Steril 1992; 57: 1289-93.
[6] Spira A, Multigner L. The effect of industrial and agricultural pollution on human spermatogenesis. Hum Reprod 1998; 13: 2041-2.
[7] Hoyes KP, Morris ID. Environmental radiation and male reproduction. Int J Androl 1996; 19: 199-204.
[8] Zhang JP, Meng QY, Wang Q, Zhang LJ, Mao YL, Sun ZX. Effect of smoking on semen quality of infertile men in Shandong, China. Asian J Androl 2000; 2: 143-6.
[9] Skakkebaek NE, Giwercman A, de Kretser D. Pathogenesis and management of male infertility. Lancet 1994; 343: 1473-9.
[10] Bonde JP, Ernst E, Jensen TK, Hjollund NH, Kolstad H, Henriksen RS, et al. Relation between semen quality and fertility: a population-based study of 430 first-pregnancy planners. Lancet 1998; 352: 1172-7.
[11] World Health Organization. WHO Manual for the Examination of Human Semen and Sperm-cervical Mucus Interaction 1999. Fourth edition. Cambridge University Press.
[12] World Health Organization. WHO Manual for the Standardized Investigation and Diagnosis of Infertile Couples 1993. Cambridge University Press.
[13] Cates W, Farley TM, Rowe PJ. Worldwide patterns of infertility: is Africa different? Lancet 1985; 2: 596-8.
[14] Leke RJ, Oduma JA, Bassol-Mayagoitia S, Bacha AM, Grigor KM. Regional and geographical variations in infertility: effects of environmental, cultural, and socioeconomic factors. Environ Health Perspect 1993; 101 Suppl 2: 73-80.
[15] Ness RB, Markovic N, Carlson CL, Coughlin MT. Do men became infertile after having sexually transmitted urethritis? An epidemiologic examination. Fertil Steril 1997; 68: 205-13.
[16] Greendale GA, Haas ST, Holbrook K, Walch B, Schachter J, Philips RS. The relationship of Chlamydia trachomatis infection and male infertility. Am J Public Health 1993; 83: 996-1001.
[17] Custo GM, Lauro V, Saitto C, Frongillo RF. Chlamydial infection and male infertility: an epidemiological study. Arch Androl 1989; 23: 243-8.
[18] Segnini A, Camejo MI, Proverbio F. Chlamydia trachomatis and sperm lipid peroxidation in infertile men. Asian J Androl 2003; 5:　47-9.
[19] Osegbe DN. Testicular function after unilateral epididymo-orchitis. Eur Urol 1991; 19: 204-8.
[20] Mulcahy FM, Bignell CJ, Rajakumar R, Waugh MA, Hetherington JW, Ewing R, et al. Prevalence of Chlamydial infection in acute epididymo-orchitis. Genitourin Med 1987; 63: 16-8.

home

Correspondence to: Dr. Gendaram Bayasgalan, Registrar, Department of Reproductive Health, State Research Center on MCH and HR. PO.Box 44/45, Ulaanbaatar, Mongolia.
Tel: +976-11-362 886, Fax: +976-11-325 935
Email: gendaram@yahoo.com
Received 2004-03-12 Accepted 2004-07-14