Thi-Qar University - College of medicine. Department of obstetrics and gynecology DONE BY SAMI BASSAM HASSAN RAMADAN ANAS TAWFIQ

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Distributional Study of Infertile Male Causes According to semen fluid analysis In a sample attend infertility center in AL- Hussein teaching hospital in Al-Nasiriyah Thi-Qar University - College of medicine Department of obstetrics and gynecology DONE BY SAMI BASSAM HASSAN RAMADAN ANAS TAWFIQ 6th stage students in Thi-Qar College of medicine SUPERVISOR Dr.Enass Saleh Head of the gynecology and obstetrics department in Thi-Qar College of medicine Date of publication: 11/4/2017 I

This study was submitted as a partial requirement for completion of the MBchB program in Thi-Qar college of medicine 2017 و ق ل ف س ي ر ى اع م ل وا للا ع م ل ك م و ر س ول ه و ال م ؤ م ن ون [ ] سورة التوبة: 501 II

Acknowledgment First and above all, thanks for God that helps us to fulfill this paper to proceed successfully. This paper wouldn't be accomplished without the help and efforts of several people, so we have to offer our sincere thanks for each one of them We would like to express our sincere gratitude to our supervisor Dr. Enass Saleh who mainly supported us continuously with patience. She faithfully supervised and directed our paper that enhanced our motivation and loving search in our study. Her continuous friendly guidance fruited in this paper We extend our thanks to the Infertility Department in AL-Hussein teaching hospital, and all the health workers and medical assistants who always receive and help us friendly. We thank also all individuals and patients who helped us in presenting this paper successfully. At last, we would like to thank our families who stand with us.helping patiently to get this work accomplished in such a way III

Introduction Definition :Infertility is a disease of the reproductive system, defined as the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse. It affects approximately 10 15% of couples, even up to 30% in some regions of the world. In general: about 20% of cases there is no clear cause, and another 20% male related causes, while the reminders are females related. Although male infertility contributes to more than half of all cases of global childlessness, infertility remains a woman s social burden, as the scientific literature and other media have neglected the male component of reproduction other than its sexual nature for a long. In recent years, male infertility has been attracting increasing interest because of evidence in decline in semen quality among young healthy men worldwide, broader public awareness, psychological health, and the continuous development of assisted reproduction techniques (ART) which solicit attempts to identify a precise diagnosis, in particular for idiopathic infertile couples and those currently undergoing ART cycles. Male infertility has been a rapidly developing area of medical science. Great interest has been raised by novel insight on numerous of male infertility, including pathogenesis, personalized therapeutic protocols, molecular changes and social effects. An increasing number of journals have appeared dealing with male infertility medicine, and the total number of published articles has grown each year. Causes of male infertility Sperm production problems Blockage of sperm transport Sexual problems (erection and ejaculation problems) Hormonal problems Sperm antibodies Chromosomal or genetic causes Undescended testes (failure of the testes to descend at birth) Infections Torsion (twisting of the testis in scrotum) Varicocele (varicose veins of the testes) Medicines and chemicals Radiation damage Unknown cause Infections Prostate-related problems Absence of vas deferens Vasectomy Retrograde and premature ejaculation Failure of ejaculation Erectile dysfunction Infrequent intercourse Spinal cord injury Prostate surgery Damage to nerves Some medicines Pituitary tumors Congenital lack of LH/FSH (pituitary problem from birth) Anabolic (androgenic) steroid abuse Vasectomy Injury or infection in the epididymis Unknown cause Symptoms Most infertile men will not have any symptoms. A man with hormonal problems may notice a change in his voice or pattern of hair growth, the development of breasts, or difficulty with sexual function. IV

Figure 1:- Causes of male infertility Male Fertility Diagnosis Many infertile couples have more than one cause of infertility, so it's likely you will both need to see a doctor. It might take a number of tests to determine the cause of infertility. In some cases, a cause is never identified. Infertility tests can be expensive and might not be covered by insurance find out what your medical plan covers ahead of time. Diagnosing male infertility problems usually involves: General physical examination and medical history. This includes examining your genitals and asking questions about any inherited conditions, chronic health problems, illnesses, injuries or surgeries that could affect fertility. Your doctor might also ask about your sexual habits and about your sexual development during puberty. Semen analysis. A semen analysis measures the volume of the semen, the number of sperm, and the proportion that are moving, known as motility. Motility is further divided into rapid, slow and non-progressive movement. We recommend 24 days abstinence before a diagnostic semen analysis so that we can compare your results with what is known in the medical literature. However for treatment, we suggest 1-2 days abstinence to ensure the sperm have not aged. Masturbation is the best way to collect semen for a semen analysis, since it is more likely that all of the sample will be collected, especially the sperm-rich first portion. A semen analysis is not a definitive test, and the normal range is very wide. In addition, sperm number and quality can vary considerably between one sample and the next. Changes in sperm concentration of up to 50% (for instance from 20 million/ml to 30 million/ml the next time) and in motility of 15% (for instance from 30% motility to 45% the next time) are common. Hence, two or three semen analyses, usually one month apart, are often requested to get a representative picture. The World Health Organization (WHO) reference levels for normal semen values Semen volume Sperm concentration Proportion of sperm motile Proportion with rapid plus slow motility Proportion of sperm with a normal shape, using strict criteria WHO normal range 1.5 ml or more 15 million / ml or more 40% or more 32% or more 4% or more Your doctor might recommend additional tests to help identify the cause of your infertility. These can include: Scrotal ultrasound. This test uses highfrequency sound waves to produce images V

inside your body. A scrotal ultrasound can help your doctor see if there is a varicocele or other problems in the testicles and supporting structures. Hormone testing. Hormones produced by the pituitary gland, hypothalamus and testicles play a key role in sexual development and sperm production. Abnormalities in other hormonal or organ systems might also contribute to infertility. A blood test measures the level of testosterone and other hormones. Post-ejaculation urinalysis. Sperm in your urine can indicate your sperm are traveling backward into the bladder instead of out your penis during ejaculation (retrograde ejaculation). Genetic tests. When sperm concentration is extremely low, there could be a genetic cause. A blood test can reveal whether there are subtle changes in the Y chromosome signs of a genetic abnormality. Genetic testing might be ordered to diagnose various congenital or inherited syndromes. Testicular biopsy. This test involves removing samples from the testicle with a needle. If the results of the testicular biopsy show that sperm production is normal your problem is likely caused by a blockage or another problem with sperm transport. However, this test is not commonly used to diagnose the cause of infertility. Specialized sperm function tests. A number of tests can be used to check how well your sperm survive after ejaculation, how well they can penetrate an egg, and whether there's any problem attaching to the egg. Generally, these tests are rarely performed and often do not significantly change recommendations for treatment. Transrectal ultrasound. A small, lubricated wand is inserted into your rectum. It allows your doctor to check your prostate, and look for blockages of the tubes that carry semen (ejaculatory ducts and seminal vesicles). Prevention Most types of infertility cannot be prevented. Excessive alcohol intake or the use of certain drugs may contribute to infertility and should be avoided in couples hoping to conceive. There is some evidence that high temperatures can make sperm inactive. Although this effect is only temporary, hot tubs and steam baths also should be avoided. One obvious reason some men are infertile is that they have previously had a vasectomy. Although surgery to reverse this condition may be successful, men who are uncertain about whether they wish to father additional children should not have this procedure. Treatment Limited numbers of medical treatments are aimed at improving chances of conception for patients with known causes of infertility. Endocrinopathies A number of patients with hypogonadotropic hypogonadism respond to gonadotropin-releasing hormone (GnRH) therapy or gonadotropin replacement. Pulsatile GnRH therapy can be used in those with intact pituitary function. Gonadotropin replacement can be effective in hypothalamic and pituitary dysfunction. Human chorionic gonadotropin (hcg) is a luteinizing hormone (LH) analogue that may be used alone or in combination with human menopausal gonadotropin (hmg) for Leydig cell stimulation. hcg is biologically similar to LH, but has a longer half-life and is less costly VI

than LH. hmg is a purified combination of follicle-stimulating hormone (FSH) and LH. When using hcg in combination with hmg or FSH, one should use hcg first, as it increases testosterone levels, which is essential for spermatogenesis and thus may better augment the overall effect of the therapy. FSH alone is not effective in inducing spermatogenesis, although recent studies suggest otherwise. Estrogen modulators can also be of use. Aromatase inhibitors (eg, anastrozole) block the conversion of testosterone to estrogen, thus increasing the serum testosterone concentration. They are especially useful in improving semen parameters in patients with decreased testosterone: estradiol ratios. Clomiphene citrate is a weak estrogenreceptor antagonist that works by blocking the negative feedback inhibition of estrogen on the anterior pituitary, thus increasing the release of FSH and LH. This will then result in increased testosterone production, ultimately augmenting spermatogenesis. Clomiphene citrate is effective in improving the semen parameters in patients with hypogonadotropic hypogonadism. Tamoxifen is another estrogen-receptor antagonist that, in combination with clomiphene, can increase sperm concentration, sperm motility, and pregnancy rates in males with idiopathic infertility. Patients with congenital adrenal hyperplasia (CAH) may respond to therapy with glucocorticoids, while those with isolated testosterone deficiency may respond to testosterone replacement. Exogenous testosterone decreases intratesticular testosterone production, thus inhibiting Sertoli cell function and spermatogenesis. Treat patients with hyperprolactinemia with dopamine antagonists, such as bromocriptine or cabergoline. Antisperm antibodies Patients with antisperm antibody levels greater than 1:32 may respond to immunosuppression using cyclic steroids for 3-6 months. However, patients need to be aware of the potential side effects of steroids, including avascular necrosis of the hip, weight gain, and iatrogenic Cushing syndrome. Retrograde ejaculation Imipramine or alpha-sympathomimetics, such as pseudoephedrine, may help close the bladder neck to assist in antegrade ejaculation. However, these medicines are of limited efficacy, especially in patients with a fixed abnormality such as a bladder neck abnormality occurring after a surgical procedure. Alternatively, sperm may be recovered from voided or catheterized post ejaculatory urine to be used in assisted reproductive techniques. The urine should be alkalinized with a solution of sodium bicarbonate for optimal recovery. More recently, the injection of collagen to the bladder neck has allowed antegrade ejaculation in a patient who had previously undergone a V-Y plasty of the bladder neck and for whom pseudoephedrine and intrauterine insemination had failed. Semen processing Patients with poor semen quality or numbers may benefit from having their semen washed and concentrated in preparation for intrauterine insemination. VII

Couples with an abnormal postcoital test result due to semen hyperviscosity may benefit from a precoital saline douche or semen processing with chymotrypsin. Lifestyle Patients should be encouraged to stop smoking cigarettes and marijuana and to limit environmental exposures to harmful substances and/or conditions. Stress-relief therapy and consultation of other appropriate psychological and social professionals may be advised. Infections should be treated with appropriate antimicrobial therapy. Dietary supplements and vitamins Safarinejad et al published a prospective, double-blind, randomized controlled trial assessing the effects of coenzyme Q 10 (ubiquinol) 200 mg po daily (n = 114 men) compared with placebo (n = 114 men) over 26 weeks. The authors found a statistically significant increase in sperm concentration, motility, and strict morphology in subjects who received ubiquinol compared to those who received placebo, and these effects gradually returned to baseline levels during the off-drug time period. While pregnancy rates were not tracked or reported, the study does appear to support the use of ubiquinol in men trying to achieve a pregnancy based on improvement in semen parameters. Aim of study The aim of this study was to evaluate the main cause of male infertility in center at AL_HUSSAIN TEACHING HOSPITAL depending on seminal fluid analysis. Materials and Methods This was a Cross sectional descriptive study of presumably infertile male attend to infertility center of in AL_HUSSAIN TEACHING HOSPITAL. In which we examined them systematically. 286 consecutive men fertility counselling provided a semen sample by masturbation following an instructed abstinence period of 3 days. One sample per patient was collected in the center, and analysed by routine criteria the semen quality measures of volume, sperm concentration, motility and morphology by WHO and Kruger strict criteria were performed for all samples following liquefaction. Statistical tests used are described in the corresponding results section. Site and Study Design A cross sectional descriptive study of presumably infertile male, recruited from the outpatient center of al Hussein-hospital. This hospital was chosen because this is the largest hospital in the city and people from all socio-economic and ethnic backgrounds visit this centers. Data sources Data for the research component were collected from center records from January to December in 2016, the whole number was 630 but the sample taken is 286 according to the abnormal seminal fluid data. VIII

Study variables Numerous studies have shown that the measurement of traditional semen variables is of clinical value for predicting the likelihood of success of in-vitro fertilization (IVF). Perhaps the most significant single variable is morphology, whether estimated using strict criteria or by more traditional methods. When correctly performed, techniques of conventional semen analysis may give reproducible results for certain sperm characteristics. Internal quality control is mandatory and strict standards for technical accuracy must be applied. In doing so, acceptably low levels of inter and intra-observer variability can be obtained and the results may have clinical relevance. Result In 2016, about 630 male consult infertility center in AL_HUSSAIN TEACHING HOSPITAL, from which 286 person were taken in study depending on abnormal seminal fluid data. By criteria of cause, asthenozoospermia is the common one in male. Below table show Cause Percentage No. of cases Asthenozoospermia 47% 195 Oligospermia 11% 46 Azospermia 7% 29 Low volume 10% 43 Immotile sperm 15% 63 Teratospermia 2% 9 Infected semen 8% 32 distribution of male infertility by causes. Figure 2 percentage of causes in male at studied year Causes of Infertile Male According to Semenal Fluid Analysis %15 %2 %8 %10 %7 %11 %47 Low volume Azospermia Oligospermia Asthenozoospermia Immotile Sperm TeratoSpermia Infected Semen 9

Discussion Discussion So far as we know, these data are the first evidence that study that discuss the seminal fluid analysis in Thi-Qar Alnassryia. Our findings support previous reports that the quality of human semen seems to be falling. In particular, we have observed a decline in sperm progressive motility and the total number of sperm and of motile sperm in the ejaculate. Auger et al observed that the decline in sperm concentration was some 2.6% per annum with later year of birth, Unlike Auger et al, we could not show the independent effect of older age on semen quality, reflecting the larger number of subjects, greater age range, and longer data collection period in their study. As the within subject coefficient of variation for the conventional criteria of semen quality is high, it has been suggested that it may be more valid to use multiple semen samples from each donor. In this study we included only the first sample provided by each volunteer to minimize the effects of selection bias resulting from the later exclusion of donors with subnormal semen quality. Although we did not record the duration of abstinence separately, all donors were asked to abstain for three to four days before giving their first sample. The duration of abstinence affects several measures of semen quality, most notably ejaculate volume, and younger donors would be expected to have shorter periods of abstinence, confounding the assessment of semen quality. However, no association was seen between either age (at ejaculation) or year of birth and ejaculate volume. Limitations Due to the variety of possible sperm and semen abnormalities, a comprehensive approach using several tests is generally employed to assess the integrity of semen specimens. There is no single test that can absolutely confirm an individual s fertility or infertility. It should be emphasized that semen is an exception among biological fluids as its parameters display very wide intra-and inter-individual variations More than one specimen is required to establish that a man consistently produces abnormal semen. The diagnosis of a semen sample as «abnormal» or «normal» using the WHO guidelines is artificial and has little diagnostic Nevertheless the several less comprehensive studies have examined the predictive value of traditional semen characteristics for in vivo fertility and concluded that these parameters are predictive of pregnancy outcome There is no records for HT,DM,smoking and the data is large in number. 01

Recommendations Avoid excessive heat (avoid heated waterbeds, saunas, whirlpool hot baths, very tight fitting underwear or pants (such as bicycle racing pants), etc. Wear loose underwear such as boxer shorts. Limit coffee to 1 or 2 cups per day. Do not smoke. Do not use marijuana, cocaine, or other recreational drugs. Marijuana stays in the testes for over 2 weeks; so even using it once every two weeks could have a negative effect. Exercise regularly but moderately. Maintain a healthy weight: Men that are overweight have been shown to have lower sperm counts and reduced sperm quality. Limit alcohol intake to a maximum of 1-2 drinks per day and avoid binge drinking Maintain good nutritional habits, especially a diet rich in fresh fruits and leafy vegetables Do not hesitate to ask for medical help if have problems maintaining an erection or ejaculation. Try to reduce stress. Consider massage, yoga, meditation, acupuncture and/or moderate exercise. Conclusion This study provided a distribution of infertile male cause in infertility center of AL_HUSSAIN TEACHING HOSPITAL studies during the period 2016. The result show most predominant cause of male infertility is asthenozoospermia in about 47% of infertile male followed by 15% of sample due to immotile sperms as second cause, then 11% of sample for Oligospermia, and the morphology of sperm about 2% of infertile male sample as rare cause on infertility in males 00

Reference 1- Ten teacher in obstetrics and gynecology. 2- Bailey & Love's Short Practice of Surgery 3- https://en.wikipedia.org/wiki/male_infertility 4- http://emedicine.medscape.com/article/436829-treatment 01