Alexander E. Omu

Treatment of asthenozoospermia with zinc sulphate: andrological, immunological and obstetric outcome

OBJECTIVES The role of zinc therapy on infertility caused by defective sperm quality is examined. STUDY DESIGN In this study, 100 men with asthenozoospermia were randomised into two groups--250 mg twice daily zinc therapy for 3 months and no therapy. The patients were followed up for another 6 months. Sperm parameters, circulating antisperm antibodies, sex hormones and T helper cytokines were evaluated before and after treatment for the two groups. RESULTS There was significant improvement in the sperm quality; sperm count (P<.02), progressive motility (P<.05), fertilising capacity (P<.01) and a reduction in the incidence of antisperm antibodies (P<.01). Zinc/cadmium was higher in the zinc therapy group (P<.02). T helper cytokine, interleukin-4 level was significantly higher after zinc therapy (P<.02) while TNFalpha showed a significant decrease (P<.05). CONCLUSIONS Zinc therapy has a role in improving sperm parameters in men with asthenozoospermia, probably through its membrane stabilising effect as an antioxidant and its effect on cellular and humoral immunity by reducing the levels of antisperm antibodies and TNFalpha and increasing that of IL-4.

Indications of the mechanisms involved in improved sperm parameters by zinc therapy.

Objective: To determine possible indications of the mechanisms involved in improved sperm parameters by zinc therapy in asthenozoospermic men. Subjects and Methods: Forty-five men with asthenozoospermia (≧40% immotile sperm) were randomized into four therapy groups: zinc only: n = 11; zinc + vitamin E: n = 12 and zinc + vitamins E + C: n = 14 for 3 months, and non-therapy control group: n = 8. Semen analysis was done according to WHO guidelines. Malone dialdehyde, tumour necrosis factor-α (TNF-α), total antioxidant capacity, superoxide dismutase (SOD) and glutathione peroxidase were determined in the semen and serum. Antisperm antibodies IgG, IgM and IgA were evaluated by immunobeads. Sperm chromatin integrity was determined by acid denaturation by acridine orange and sperm apoptosis by light and electron microscopy. The effect of zinc on in vitro induced sperm oxidative stress by NADH was evaluated. Results: Asthenozoospermia was significantly associated with oxidative stress with higher seminal malone dialdehyde (8.8 vs. 1.8 mmol/l, p < 0.001) and TNF-α (60 vs. 12 pg/l, p < 0.001), and low total antioxidant capacity (1.8 vs. 8.4, p < 0.01), SOD (0.8 vs. 3.1, p < 0.01) and glutathione peroxidase (1.6 vs. 4.2, p < 0.05), compared to normozoospermia. Zinc therapy alone, in combination with vitamin E or with vitamin E + C were associated with comparably improved sperm parameters with less oxidative stress, sperm apoptosis and sperm DNA fragmentation index (DFI). On the whole, there was no difference in the outcome measures between zinc only and zinc with vitamin E and combination of vitamins E + C. In the in vitro experiment zinc supplementation resulted in significantly lower DFI (14–29%, p < 0.05) compared to zinc deficiency. Conclusion: Zinc therapy reduces asthenozoospermia through several mechanisms such as prevention of oxidative stress, apoptosis and sperm DNA fragmentation.

Seminal immune response in infertile men with leukocytospermia: effect on antioxidant activity

OBJECTIVE To investigate the incidence of leukocytospermia and relation to T helper cytokines, tumor necrosis factor alpha (TNFalpha) and interleukin-4 (IL-4), antisperm antibodies and antioxidant activity. DESIGN Semen samples from 176 infertile men and 24 fertile controls were investigated. METHODOLOGY The protocol included tubal patency test, hysterosalpingography and laparoscopy and dye test and ovulation through mid-luteal phase progesterone for the wives. The husbands had semen analysis, cytomorphology evaluation and semen culture. Seminal TNFalpha and IL-4, antisperm antibodies, total antioxidant activity, superoxide dismutase and zinc were determined. RESULTS Leukocytospermia occurred in 44.3% of the infertile men compared to 12.5% of the fertile men (P<0.01). Thirty-six (20.5%) men had pathogenic bacterial organisms which constituted 46.2% of those with leukocytospermia. Sperm parameters were worse with leukocytospermia in terms of sperm count (P<0.01), total motility progressive motility (P<0.01), morphology, asthenozoospermia, sperm membrane integrity and antisperm antibodies. TNFalpha and IL-4 had an inverse relationship; the expression of TNFalpha was higher with leukocytospermia and bacteriospermia (P<0.001), while IL-4 was higher in fertile controls (P<0.005). Incidence of antisperm antibodies was higher with leukocytospermia. Total antioxidant activity, superoxide dismutase and zinc were lower with leukocytospermia. CONCLUSION Leukocytospermia impairs sperm function through reduced antioxidant activity and enhanced T helper 1 modulation.

Chronic cadmium toxicity to sperm of heavy cigarette smokers: immunomodulation by zinc.

The aim of the study was to investigate the role of zinc therapy in 125 male cigarette smokers with infertility. The mechanism involved in the zinc/cadmium relationship was evaluated through the effect of a zinc-deficient diet and supplementation on testes of male adult Sprague-Drew rats. Heavy smoking was associated with low sperm count, motility, and morphology and increased seminal cadmium levels. Zinc therapy improved sperm quality and increased seminal IL-4, but reduced TNF-alpha and IFN-gamma. A zinc-deficient diet led to high cadmium testicular accumulation comparable with those supplemented with cadmium. Cadmium had a linear correlation with TNF-alpha and IFN-gamma, but not with IL-4. Cytology of testicular aspirate and histopathology were normal in supplemented groups as in controls. These results indicate that zinc modulates the putative effect of cadmium through its enhancement of T-helper 2 cytokines expression and down-regulation of T-helper 1 cytokines.

Prevalence of Chlamydia trachomatis, Mycoplasma hominis, Mycoplasma genitalium, and Ureaplasma urealyticum Infections and Seminal Quality in Infertile and Fertile Men in Kuwait

This study was undertaken to determine the prevalence of Chlamydia trachomatis, mycoplasmas, and ureaplasmas in semen samples of infertile compared with fertile men and to evaluate the seminological variables of semen from infected and noninfected men. A total of 127 infertile and 188 fertile men seen in a maternity hospital clinic were recruited into the study over a period of 14 months. Specimens were obtained by masturbation and examined for the presence of Ureaplasma urealyticum, Mycoplasma hominis, Mycoplasma genitalium, and C trachomatis by polymerase chain reaction. Semen analysis was performed according to World Health Organization guidelines. U urealyticum, M hominis, M genitalium, and C trachomatis were demonstrated in the semen samples of 31 (24.4%) vs 49 (26.1%), 22 (17.1%) vs 61 (32.4%), 6 (4.7%) vs 6 (3.2%), and 5 (3.9%) vs 7 (3.7%), respectively, of infertile and control men. Mixed infections were detected in 14 (11%) of infertile and 29 (15.4%) of fertile men. The infertile men positive for M hominis had semen samples that showed statistically significant differences in the mean of sperm pH and leukocyte count between infected and uninfected men (P < .03 and P < .001, respectively). Similarly, there was statistically significant difference in the leukocyte counts of M genitalium and C trachomatis in infected compared with uninfected men. A similar trend was noted in infected fertile compared with uninfected men. The difference in prevalence of these urogenital pathogens among infertile compared with fertile men was not statistically significant. However, genital mycoplasmas and chlamydial infections appeared to influence semen quality negatively.

Lymphocyte subpopulations in pregnancy complicated by hypertension

The immune responsiveness of women is altered during pregnancy in order to retain protective properties against disease and at the same time allow tolerance of the fetus. Diseases such as pre-eclampsia (PE) have been suggested to arise as a result of maladaptations in these immune alterations. Here we evaluate the effect of PE on the composition of peripheral blood lymphocyte subpopulations using lymphocyte surface antigen expression. Fifty-four women of various parities with pregnancy-induced hypertension (PIH) (39 non-proteinuric and 14 proteinuric) and matched controls (30 normotensive pregnant women (NTP) and 15 healthy non-pregnant women (NP)) were investigated. Monoclonal antibodies specific for human T lymphocytes and subpopulations: CD2, CD3, CD4, CD8, CD19 and activation markers: CD25, CD45RA, CD45RO, CD54 AND HLA m DR were used and detected using a two-colour fluorescence analysis with an automated flow cytometer. The total number of T lymphocytes: CD2, CD3, CD4, CD8 and CD19 were significantly decreased in PIH particularly PE ( P <0.05). T cells expressing NK surface markers (CD3/CD16 + CD56) and CD4 cells expressing HLA m DR were higher in PE. CD8 + HLA m DR + cells and T-helper cells expressing adhesion molecules) CD4 + CD54 + ) were higher in NTP than in NP and PE ( P <0.05, 0.05). PE is associated with elevated levels of CD4 + HLA m DR + , and CD3 + NK cells but decreased total numbers of T lymphocytes, and the CD3 + CD25 + subpopulation. These findings indicate systemic alterations in maternal immunity associated with the PE state. This feature of the disease may contribute to abnormal adaptation to pregnancy resulting in PE and PIH, promoting adverse outcomes including pregnancy loss.

Differential Levels of Interleukin 6 in Maternal and Cord Sera and Placenta in Women with Pre-Eclampsia

Background: Interleukin 6 (IL-6) is a T helper 2 cytokine with a variety of properties including pro-inflammatory characteristics. It has, therefore, been implicated in the pathophysiology of abnormal pregnancies. Objective: To investigate the association between IL-6 and pre-eclampsia by estimating the differential levels of IL-6 in maternal and cord serum and supernatant of homogenized placental tissue. Methods: 50 primigravidae with pre-eclampsia and 50 matched normotensive primigravidae served as controls. At delivery, maternal and cord blood were collected and the serum extracted. Placental blocks were homogenized and sonicated in RPMI solution and the supernatant collected. The total protein concentration was determined and IL-6 levels assayed with an ELISA technique. Results: Placental IL-6 (170 and 186 pg/mg protein) was threefold that in the maternal (64 and 58 pg/mg protein) and cord serum (63 and 72 pg/mg protein; p < 0.01). There was no significant difference in the mean IL-6 levels in maternal and cord serum or placenta in both pre-eclamptic women and normotensive controls nor in pre-eclamptic patients with babies with intra-uterine growth restriction or in pre-eclamptic patients with babies with an appropriate birth weight and in normotensive controls. Conclusion: There are no differences in the maternal and cord sera and placental levels of IL-6 in pre-eclamptic and normotensive women, indicating that IL-6 may not have a role in the pathophysiology of pre-eclampsia.

Pregnancy-Associated Changes in Peripheral Blood Lymphocyte Subpopulations in Normal Kuwaiti Women

It has recently been reported that healthy pregnancy is associated with systemic immunosuppression. The aim of this study was to evaluate the numbers and distribution of lymphocyte subpopulations in normal, healthy pregnant Kuwaiti women. Thirty-four healthy normotensive women in the 3rd trimester of pregnancy were studied using flow cytometry to define lymphocyte subpopulations and were compared with 16 non-pregnant women. A decrease in the absolute numbers of lymphocytes was observed affecting T cells (CD3+, CD4+, CD8+), B cells (CD19+), and natrural killer cells (CD16+/CD56+). When analyzed as a percentage of the total lymphocyte population, there was a significant decrease in B cells and an increase in CD4+ T cells. The T cell population revealed increased expression of CD25 on CD4+ and CD8+ cells, of HLA-DR on CD8+ cells, and of CD54 on CD4+ T cells. The reduced number of lymphocytes suggests that Kuwaiti females may be immunosuppressed in the 3rd trimester of pregnancy. The presence of activated CD4+ T cells could indicate the expression of a regulatory suppressor T cell population, as Treg cells are CD4+CD25+, and suppressor T cells are thought to be CD8+. Future work is required to explore the significance of these T cell populations in pregnancy.

Hormone profile of Kuwaiti women with hyperemesis gravidarum

Abstract Objective: To evaluate the incidence of hyperemesis gravidarum among pregnant women in Kuwait and the status of HCG, TSH, Total T4 and Free T4 in the serum of patients with hyperemesis gravidarum compared with a control group of women. Methodology: During a 6-month period all patients admitted to Maternity Hospital with features of hyperemesis gravidarum (excessive vomiting and ketonuria) were enlisted into the study. In fifty of these patients and their fifty normal controls, the status of serum total βhCG, TSH, total T4 and freeT4 were evaluated with AXSYM micro particle enzyme immunoassay. Results: The incidence of hyperemesis in the maternity population was 45 per 1000 deliveries. Total βhCG and Total T4 and FreeT4 were significantly higher in the hyperemesis patients than in the normal controls (p<0.0001, p=0.004 and p=0.01 respectively). TSH levels were significantly lower in hyperemesis patients than in their normal controls (p<0.0001). There was a strong positive correlation between the total βhCG and the gestational age (r=0.8). Conclusion: There is a high incidence of hyperemesis gravidarum in the Kuwaiti population. Total βhCG, Total T4 and Free T4 titers were significantly higher in patients with hyperemesis gravidarum, but none of the patients showed signs of hyperthyroidism.

Allopurinol provides long-term protection for experimentally induced testicular torsion in a rabbit model

To assess the effect of five antioxidants on exocrine function of rabbit testes retained in situ for 24 h and 3 months after experimental torsion.