Deeba F^1*, Banu J², Ishrat S³, Anawary S A⁴, Begum N⁵

^1,3,5Associate Professor. ²Chairman, ⁴Assistant Professor, Department of Reproductive Endocrinology and Infertility, Bangabandhu Sheikh Mujib Medical University, Dhaka, BANGLADESH.

Email: deeba_51@yahoo.com

Figure 1: Distribution of study subject according to semen parameters (n=334)

Table-I: Distribution of the study patients by demographic variable (N=334)

Table-II: Distribution of the study patients by personal history (N=334)

Table-III: Distribution of the study patients by family history (N=334)

Table 4: Distribution of the study patients by endocrine evaluation (N=334)

Table 5: Pretreatment and post treatment difference in sperm count of isolated oligospermia (N=334)

Figure-II: Bar diagram showing improvement of sperm count (Ebastin N=84); (Placebo N=84)

Table 6: Pretreatment and post treatment difference in sperm motility of isolated asthenospermia (N=334).

Figure 3: Bar diagram showing improvement of sperm motility (Ebastin N=114); (Placebo N=114)

Table 7: Pretreatment and post treatment difference in rapid progress of isolated asthenospermia (N=334)

DISCUSSION

This longitudinal clinical trial was carried out with an aim to determine the effect of ebastin upon sperm count and to assess the effect of ebastin upon sperm motility. A total of 334 male patients with infertility presented in Gynaecology and Obstetrics department of Bangabandhu Sheikh Mujib Medical University, Dhaka, between January 2015 to December 2015 were included in this study. All the male patients with infertility with age belonged to 25–50 years, abnormal semen parameters i.e. Oligospermia, asthenozospermia and not attributable to any endocrine or urological abnormality were enrolled in this study. Age less than 25 years or more than 50 years, abnormalities in reproductive organ, known Hormonal disorder, known Medical disorder, pscho-sexual abnormalities and urological abnormality were excluded from the study. Mast cells (MCs), play a key role in the inflammation, hypersensitivity and fibrosis, are as well normally present in the testes.^4,8 Roaiah⁹ study suggest that there is a prominent increase in the number of testicular MCs in the testes of infertile men which may disrupt spermatogenesis. Also, it was reported that increased numbers of MCs have been associated with different types of infertility, including asthenospermia.^9-10 Therefore some of male factor infertility problems could possibly diminished if such pathogenesis agent would greatly reduce using drug that block MC mediator release. The present study findings were discussed and compared with previously published relevant studies. We found majority of the patients (n=168) had isolated asthenospermia and divided into group I (n=84) and group II (n=84). Isolated oligospermia was found (n=106) patients and divided into group I (n=53) and group II (n=53). Combined (oligospermia+ asthenospermia) was found in 60 patients in group I (n=30) and group II (n=30). In this present study it was observed that majority patients belonged to age 31-40 years in both groups, which was 106(63.5%) in group I and 108(64.7%) in group II. The mean age was found 35.8±5.8 years in group I and 34.9±6.1 years in group II. The difference was not statistically significant (p>0.05). Saharkhiz¹¹ found the male were aged 23-40 years of mean age 32.8 years, which is consistent with the current study. Similarly, Multigner¹² and Cayan¹³ showed the mean age of the infertile male patients were 32.0 years varied from 22 to 47 years and 34.5±7.2 years varied from 24 to 49 years respectively. Similar, age range also observed by Roaiah⁷ and Hussein¹⁴ in their respective studies. On the other hand, El-Karaksy¹⁵ showed 64.0% were in more than 40 years and 36.0% were in under 40 years, which is higher with the current study. The higher age range maybe due to geographical variations, racial, ethnic differences and different lifestyle may have significant influence to identified their infertility. Prostatitis causes substantial morbidity to men, through associated urinary symptoms, sexual dysfunction, and pelvic pain; however, 90% to 95% of cases have an unknown etiology obtained by Ellem.¹⁶ Regarding sexual dysfunction, no sexual dysfunction was found 155(92.8%) in group I and 160(95.8%) in group II. Mean staging together was found 5.8±4.1 years in group I and 5.6±3.9 years in group II. Mean coital frequency was found 2.8±0.9 years in group I and 2.6±1.1 years in group II. The difference was not statistically significant (p>0.05). In this current study it was observed that majority 135(80.8%) patients non smokers in group I and 141(84.4%) in group II. Smoker was found 32(19.2%) in group I and 26(15.6%) in group II. Mean duration of smoking was found 12.0±6.7 years in group I and 5.9±4.7 years in group II. Majority 164(98.2%) patients in group I and 166(99.4%) in group II were not taken alcohol. The difference was not statistically significant (p>0.05). Seminal mast cells showed higher frequency among smokers compared with nonsmokers, suggesting an aetiological relationship between smoking and mast cell abundance in infertile patients, and therefore an indirect relationship between smoking and infertility. This supports the studies that establish smoking as having an adverse effect on fertility, especially on progressive sperm motility, irrespective of total amount of cigarettes smoked per day.^17-18 In this study it was observed that majority 115(68.9%) patients in group I and 128(76.6%) patients in group II patients had no family history. 34(20.4%) patients had DM in group I and 26(15.6%) in group II. 13(7.8%) and 9(5.4%) had infertility in group I and group II respectively. The difference was not statistically significant (p>0.05). In this present study it was observed that mean serum TSH was found 2.3±1.9 miu/ml in group I and 2.4±2.0 miu/ml in group II. Mean prolactine was 8.0±4.0 ng/dl in group I and 7.8±4.1 ng/dl in group II. Mean serum free testostosterone was found 12.3±8.5 ng/dl and 12.1±8.4 ng/dl in group I and group II respectively. The difference was not statistically significant (p>0.05). Cayan¹³ showed the serum testosterone values was 5.5±2.6 ng/mL varied from 1.7 to 12.6 ng/mL, which is lesser with the present study. Ketotifen's (Mast cell blocker) androgenic effects on male infertility, associated with oligospermia and asthenospermia, have been reported by Olivia and Multigner¹⁹ Studies have also shown that it may counteract the ability of MCs to trigger an inflammatory response. It is worth mentioning that the number of MCs sometimes increases more than normal in the testicular tissue of infertile men.²⁰ In another study Schill⁵ also suggested that ketotifen (Mast cell blocker) can be more helpful to improve the patients’ sperm count and sperm motility with idiopathic oligo/asthenospermia. In this current study it was observed that in group I, mean sperm count was 10.32±2.71 million/ml in pretreatment and 18.87±9.56 million/ml in post treatment. The difference was statistically significant (p<0.05). In group II, mean sperm count was 10.19±1.75 million/ml in pretreatment and 10.18±1.95 million/ml in post treatment. The difference was not statistically significant (p>0.05). In this present study it was observed that in group I, mean sperm total mortality was 24.86±12.02% in pretreatment and 34.29±9.35% in post treatment. The difference was statistically significant (p<0.05). In group II, mean sperm total mortality was 21.96±6.17% in pretreatment and 22.44±4.81% in post treatment. The difference was not statistically significant (p>0.05). Saharkhiz¹¹ showed the mean sperm motility increased significantly from 16.7% to 21.4% after ketotifen (Mast cell blocker) treatment (p<0.001). This sperm motility improvement was more pronounced in the primary infertility cases (p<0.05). In 52.0% of infertile men's semen, the percentage of sperm motility was increased from 5% to 35% and this sperm motility improvement was also observed in 33% of necrospermia (0% motility) cases. In group I, mean rapid progress was found 11.81±7.76 % in pretreatment group and 19.99±11.31 % in post treatment. The difference was statistically significant (p<0.05). In group II, mean rapid progress was found 11.25±1.67% in pretreatment group and 11.4±1.59% in post treatment. The difference was not statistically significant (p>0.05). In this study 63.9% oligospermic male showed improvement in sperm count in ebastin group and 18.1% in placebo group. Which was statistically significant (p<0.05). Improved sperm motility was 75.4% of asthenozospermic male in ebastin group and 19.3% in placebo group. Which was statistically significant (p<0.05). Saharkhiz¹¹ found 52% of infertile men's semen, the percentage of sperm motility was increased from 5% to 35% and this sperm motility improvement was also observed in 33% of necrospermia (0% motility) cases. Multigner (2006) observed 23.6% patients presented a sperm concentration of <20 ×10⁶ /mL and a sperm motility of <50% in 65.4%, which is comparable with the current study. Matsuki²¹ investigated the effect of ebastine, a mast cell blocker, on semen quality in idiopathic oligozoospermic men reporting 66.7% of the patients had improved semen quality. Olivia and Multigner¹⁹ carried out a study to assess the efficacy of daily administration of ketotifen (Mast cell blocker), on the semen quality of men with leukocytospermia and unexplained infertility. They noticed that ketotifen diminished the white blood cell count in semen and so the sperm motility has been dramatically improved. Moreover, the number of morphologically normal spermatozoa was more pronounced at 8 weeks of treatment and these changes remained until at least 4 weeks after stopped of ketotifen (Mast cell blocker) treatment. Ketotifen (Mast cell blocker) was used several years ago for treating patients with idiopathic oligozoospermia and asthenozoospermia (independent of the presence of leukocytospermia). This led to a very moderate but statistically significant improvement in sperm count and sperm motility.⁵ Matsuki²¹ showed that the mast cell blocker ebastine significantly improved semen quality in idiopathic oligozoospermia. Hibi⁷ reported that tranilast improved semen parameters in severe oligoasthenozoospermia, but not for long-term administration. Matsuki²¹ observed the effect of mast cell blocker (ebastine) on semen quality was evaluated in 15 idiopathic oligozoospermic males and 66.7% showed definite improvement in the semen quality. It would appear that mast cell blocker (ebastine) significantly improves semen quality in men with idiopathic oligozoospermia. Nagai²² had shown that the number of mast cells in testicular tissue was increased and the ratio of mast cell subtypes (chymase and tryptase) was changed in idiopathic azoospermia and oligozoospermia. Yamamoto²³ prescribed randomly mast cell blocker (tranilast) or placebo for 3 months infertile males with severe idiopathic oligozoospermia, showing significant improvement in semen parameters.

Limitations of the study

The study population was selected from one selected tertiary hospital in Dhaka city, so that the results of the study may not reflect the exact picture of the community. The present study was conducted at a very short period of time. Small sample size was also a limitation of the present study. Therefore, in future further study may be under taken with large sample size. Although the present study had a number of restrictions; first, it was not double blind. Sample size and power to detect clinically essential outcomes were small. The trial was not designed with sufficient power to address important basic outcomes. Nevertheless, it was shown that it seems the failure rate of infertility treatments can be decreased if MC blockers such as Ebastin and Placebo can be given to the oligospermic and asthenozospermic men before intrauterine insemination (IUI) or ART cycles of treatment. Indeed, it seems that further research is necessary to identify the precise capacity of Ebastin to improve quality of semen parameters and whether this MC blocker has effects on the cumulative outcome of reproduction.

CONCLUSION AND RECOMMENDATIONS

From this paper we found that sperm count, Sperm motility and rapid progress had significantly improved after three months’ treatment period with Ebastin. Therefore, this study suggested that mast cell blocker ebastin can be helpful to improve the patients’ sperm count and sperm motility with oligospermia and asthenospermia. Further community based or multicentre, double blind placebo controlled studies can be undertaken by including large number of patients and Ebastin can be given to the oligospermic and asthenozospermic men before intrauterine insemination (IUI) or ART cycles of treatment.

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