Clinical trial NCT05200663: Efficacy Comparison of Tamoxifen and Tamoxifen With Antioxidants on Semen Quality of Male With Idiopathic Infertility
Official title: Comparison of the Efficacy of the Tamoxifen and Tamoxifen With Antioxidants on Semen Quality of Infertile Male With Abnormal Semen Parameters.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Oligoasthenoteratozoospermia
Male Infertility
Keywords: Tamoxifen citerate
Anti oxidants
Lead sponsor: Sharif Medical Research Center
Sponsor class: OTHER
First posted: 2022-01-21
Enrollment: 110
Sex: MALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 110 patients are recruited into two groups .55 patients in group A will be given tamoxifen 10 mg twice a day and 55 patients in group B will be given tamoxifen 10 mg twice a day and vit E 400mg once a day.
Primary purpose: TREATMENT

Brief summary: Objective of the study is to compare the efficacy of tamoxifen alone \& tamoxifen with antioxidant on semen quality of infertile male with abnormal parameters (sperm count, motility, vitality, morphology) .Infertility is defines as inability to conceive after one year of unprotected and regular intercourse. Infertility is the most important issue in the married couples and is one of the major clinical problem affecting people medically and psychologically .It affects about 5.8 to 44.2 % couples in the developing countries. Male infertility contributes to about 50% of the overall infertility. Antiestrogens are considered as one of the old and most commonly prescribed treatment of idiopathic infertility.Many studies has shown that it improves idiopathic oligozoospermia, count, motility and vitality. Spermatozoa are also prone to oxidative damage.

Men who have high reactive oxygen species(ROS) may have lower fertility potential as compared to men with low ROS. High levels of ROS in semen have been correlated with reduced sperm motility and damage to sperm nuclear DNA. High levels of cytokines in the semen is correlated with sperm injury like cell membrane lipid peroxidation in the presence of raised IL-6 .Antioxidents are the most important form of protection for spermatozoa against ROS. So oral antioxidents are commonly prescribed to males with idiopathic abnormal semen parameters and infertility to reduce the oxidative stress and improves infertility.

It is a single blinded randomized control trial to be conducted in Sharif Medical and Dental college, Lahore with sampling technique of probability randomized consecutive sampling technique. 110 male patients with idiopathic male infertility and abnormal semen parameters will be recruited . Pre treatment semen analysis and LH, FSH and serum testosterone will be done. 55 patients will be given tamoxifen alone ad 55 patients will be given tamoxifen with antioxidant. Then at the interval of 3 and 6 months after treatment , semen analysis and hormonal profile will be repeated. Pre-treatment and post treatment semen parameters will be compared using paired sample t-test. P-value \< 0.05 will be taken as significant.

Detailed description: Infertility is considered as the most important issue among the married couples and it represents major clinical problems affecting people not just medically but also psychologically .

Infertility affects about 5-8% of couple in developed countries and 5.8 - 44.2% in developing nations. In Pakistan incidence of oligozoospermia is around 21 percent and 12.32 % of patients presents with azoospermia (2). Male infertility contributes to about 50% of the cases of infertility . Cause of male infertility with abnormal semen parameters remains unknown in about 25% of men Men with idiopathic infertility may receive number of empirical therapies by clinicians. Commonly prescribed medications include hormonal medications such as follicular stimulating hormone (FSH), androgens like testosterone and mesterolone, antiestrogens ( tamoxifine, clomiphene citrate) , antioxidents like vitamin E, glutathione and sperm vitalizer such as L-carnitine ,coQ10.

Antiestrogens are considered to be one of the oldest and most commonly prescribed treatment for the idiopathic male infertility. Antiestrogen given for 6-9 months reported to have pregnancy rate of 20-40% . According to WHO tamoxifen citerate is the first line treatment for idiopathic ologozoospermia . Previously tamoxifen citrate was given as the empirical treatment for oligozoospermia and later it was found that after the use of 3-6 months it improves sperm count, motility and viability . The exact mechanism by which tamoxifen increase sperm parameters is not known , however it is found that it has stimulatory action on gonadotrophin secretion and directly effects leydig cell function . Tamoxifen is also known for the treatment of breast cancer worldwide.

Oxidative stress has been widely studied previously as one of the cause of the male infertility. Like other aerobic cells , spermatozoa are also prone to the oxidative damage because they have large polyunsaturated fat content in their membrane. Men who have high reactive oxygen species(ROS) may have lower fertility potential as compared to men with low ROS. High levels of ROS in semen have been correlated with reduced sperm motility and damage to sperm nuclear DNA. High levels of cytokines in the semen is correlated with sperm injury like cell membrane lipid peroxidation in the presence of raised IL-6 . Interferone gamma and TNF alpha have shown to decrease the motility of spermatozoa. This is commonly present in genitourinary infections and inflammation in which oxidative mechanism can leads to oxidative stress . Antioxidents are the most important form of protection for spermatozoa against ROS. So oral antioxidents are commonly prescribed to males with idiopathic abnormal semen parameters and infertility to reduce the oxidative stress and improves infertility.

Though assisted reproductive techniques are being widely offered to infertile couples, however before referring the patients for these expensive treatment options , relatively economical and practical methods should be considered first.

This study has been designed to determine the improvement of semen quality of infertile male with abnormal parameters after treatment with tamoxifen \& tamoxifen with antioxidants thus the chances of conception and pregnancy rates are expected to be improved.

OBJECTIVE:

To compare the efficacy of tamoxifen alone \& tamoxifen with antioxidant on semen quality of infertile male with abnormal parameters (sperm count, motility, vitality, morphology) .

OPERATIONAL DEFINITIONS:

Infertility: Inability to conceive after one year of unprotected and regular intercourse.

Abnormal Semen parameters:

Oligospermia: A sperm count of less than 15 million/ml .

Azoospermia: Absence of spermatozoa in the semen. Asthenozoospermia: reduced sperm motility. Teratozoospermia: presence of spermatozoa with abnormal morphology Asthenoteratozoospermia: Abnormal sperm motility and morphology

MATERIALS AND METHODS:

Study Design: Single Blind Randomized Controlled Trial Setting: Department of Obstetrics and Gynecology, Sharif Medical City, Lahore for 1 years.

Sampling Technique: Probability Randomized Consecutive Sampling Technique.

SAMPLE SELECTION:

Sample Size: A sample size of 110 (55in each group) with 95% confidence interval at 5% level of significance.

DATA COLLECTION PROCEDURE:

After approval of proposed synopsis from the ethical review board, infertile males with abnormal semen parameters will be included in the study after written informed consent. Randomization will be done by lottery method to divide the patients into group A \& group B.

In group A: Tab. Tamoxifen 10 mg ,per oral twice daily will be given for six months.

In group B: Tab. Tamoxifen 10mg twice a day and Cap Evion 400mg once a day will be given for six months.

Semen analysis will be performed, according to the WHO criteria 20101, on all the patients for measurement of semen parameters ( volume, sperm concentration, total sperm number, motility \& morphology) All samples will be collected in a private room at the laboratory in Sharif medical city, wide-mouth container kept at body temperature, after abstaining from any sexual activity for no less than 3 and no more than 7 days. Masturbation will be used as the method of sample production, without the use of any lubricants, after washing and drying both the hands and the penis. The sample is then incubated at 37 ºC till liquefaction is complete.

Semen volume will be measured in a graduated cylinder, whereas, sperm count and morphology will be assessed by microscopy. Sperms appearing within a square on the grid pattern will be counted to determine the sperm count.

Hormonal profile such as Serum FSH, serum LH and Serum Testosterone of all patients will also be analyzed before starting the treatment. Semen samples and hormonal profile will be analyzed pre-treatment and at interval of three months and six months after treatment. All the research data will be taken on a pre-designed Performa.

DATA ANALYSIS:

Data analysis will be done using SPSS v 23. Quantitative variables such as age, sperm count, motility, and vitality concentration will be analyzed and mean and standard deviation will be calculated. Independent sample test will be used to compare quantitative variables between the groups. While pre-treatment and post treatment semen parameters will be compared using paired sample t-test. P-value \< 0.05 will be taken as significant. Bias will be reduced by using the same laboratory for all tests. Data, will be stratified for age, BMI, smoking ,alcohol drinking, baseline sperm parameters (sperm count, concentration , motility, vitality) and hormone assays (follicular stimulating hormone (FSH), luteinizing hormone(LH) and testosterone).

Eligibility criteria: Inclusion Criteria:

- All infertile male with idiopathic infertility and abnormal semen analysis.

Exclusion Criteria:

* 1. Leukocytospermia i.e. significant WBCs seen in the semen, 2. Severe oligospermia (sperm count \<5 million per ml),

Primary outcomes:
measure: Semen Volume
timeFrame: at 3 months posttreatment
measure: Semen Volume
timeFrame: at 6 months posttreatment
measure: Total sperm Count
timeFrame: 3 months posttreatment
measure: Total sperm Count
timeFrame: 6 months posttreatment
measure: Sperm concentration
timeFrame: 3 months posttreatment
measure: Sperm concentration
timeFrame: 6 months posttreatment
measure: Progressive motility
timeFrame: 3 months posttreatment.
measure: Progressive motility
timeFrame: 6 months posttreatment
measure: Sperm Morphology:
timeFrame: 3 months posttreatment
measure: Sperm Morphology:
timeFrame: 6 months posttreatment
measure: Vitality
timeFrame: 3 months posttreatment
measure: Vitality
timeFrame: 6 months posttreatment
measure: Leutinizing hormone
timeFrame: 3 months posttreatment
measure: Leutinizing hormone
timeFrame: 6 months posttreatment
measure: Follicular stimulating hormone
timeFrame: 3 months posttreatment.
measure: Follicular stimulating hormone
timeFrame: 6 months posttreatment.
measure: Serum Testosterone
timeFrame: 3 months posttreatment.
measure: Serum Testosterone
timeFrame: 6 months posttreatment.
Secondary outcomes:
Other outcomes:
Locations:
city: Lahore
country: Pakistan
facility: Sharif Medical And Dental College
state: Punjab
Study officials:
affiliation: Sharif Medical And Dental College
name: Anees Fatima, MBBS,FCPS
role: PRINCIPAL_INVESTIGATOR
References:
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