Journal of Medicinal Plants Research Vol. 5(25), pp. 5936-5945, 9 November, 2011 Available online at http://www.academicjournals.

org/JMPR ISSN 1996-0875 2011 Academic Journals DOI: 10.5897/JMPR11.244

Review

Introduction to male infertility

Faisal Zakai1, Shahab Uddin1, M. Akram1*, E. Mohiuddin2, Abdul Hannan3 and Khan Usmanghani3
2

Department of Basic Medical Sciences, Faculty of Eastern Medicine, Hamdard University, Pakistan. Department of Surgery and Allied Sciences, Faculty of Eastern Medicine, Hamdard University, Pakistan. 3 Department of Basic Clinical Sciences, Faculty of Eastern Medicine, Hamdard University, Pakistan.
Accepted 20 September, 2011

Infertility is one of the most tragic of all marital problems. The infertility may be due to an inadequate number of spermatozoa in the semen, the failure of the spermatozoa to move with sufficient vigor towards their goal or that they are deficient in other respects. In this review article, introduction, evaluation of the male patient, routine laboratory testing, normal values for semen parameters, ejaculation difficulties, diagnostic considerations, possible causes of falling sperm counts, normal spermatogenesis, male fertility tests, therapeutic considerations, botanical medicines, male infertility statistics has been discussed herewith. Key words: Infertility, sperm count, artificial insemination (AI), assisted reproductive technology (ART), semen collection devices (SCD), precoital sexual stimulation (PSS), erectile dysfunction (ED). INTRODUCTION Infertility represents the inability to reproduce. The inability to reproduce can be from husband (male) and /or wife (female). However, male infertility presents a particularly vexing clinical problem, while semen is the initial target for diagnostic and therapeutic interventions and analysis. As a result, epidemiologic assessment regarding male reproductive dysfunction presents formidable task for the diagnosis and treatment of infertility. Infertility is defined as the inability to achieve pregnancy after one year of unprotected intercourse. An estimated, 15% of couples meet this criterion and are considered infertile (Zavos et al., 2003). Historically, the work-up for the infertile couple focused primarily on conditions of the female. Conditions of the male are estimated to account for nearly 30% of infertility cases and conditions of both the female and the male account for another 20% (Zavos et al., 1998). Conditions of the male that affect fertility are still under-diagnosed and under-treated. In general, causes of infertility in men can be explained by deficiencies in ejaculated volume, sperm concentration or too few sperm (oligospermia), complete absence of sperm in the ejaculate (azoospermia), sperm motility (asthenospermia), or sperm morphology (teratospermia). Nearly 70% of conditions causing infertility in men can be diagnosed by history, physical examination, testicular volume estimation, and hormonal and semen analysis. A rational approach is necessary to perform the appropriate work-up and to choose the best treatment options for the couple (Lawrence et al., 2000; Goodpasture et al., 1987). Technological advancements in assisted reproduction technologies make conceiving a child possible with as little as one viable sperm and one egg. While the work-up traditionally has been delayed until a couple has been unable to conceive for 12 months, beginning the work-up at the first visit is now recommended because of a recent trend towards delaying family planning. This article summarizes current knowledge of causes of infertility in men and describes its work-up, and treatment modes. Evaluation of the male patient 1. The evaluation of the male patient is three-fold: a. Detailed history taking; b. Physical examination; and c. Routine laboratory testing, including semen analysis. The evaluation of the male patient begins with a thorough

*Corresponding author. E-mail: makram_0451@hotmail.com. Tel: 92-021-6440083. Fax: 92-021-6440079.

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history, including duration of the problem, sexual habits, prior pregnancies and previous treatment, as well as the general health of the patient. A childhood or developmental history along with the patients medical and surgical history should be discussed, including items such as a history of diabetes, prostate surgery, or hernia repairs. Exposure to possible toxic agents such as radiation, heavy metals, and organic solvents should also be included (Goodpasture, 1987). Numerous publications (Zavos et al., 2005, 1992) have shown that smoking negatively affects male fertility in terms of sperm characteristics, sexual frequency and sexual satisfaction. If both the male and female smoke, there is also an additive effect. It has been shown via electron microscopy that smoking causes damage to the ultrastructure of the axoneme of human spermatozoa. Patients that smoke should be advised to stop smoking prior to any further infertility treatment. More recently, it has been shown, for the first time, that there is an aging effect on not only sexual behavioral characteristics but also on the seminal and sperm characteristics. The sperm parameter most commonly affected by age is the percentage normal sperm morphology. Although, there was a consistent decrease in the percentage normal sperm morphology as assessed by World Health Organization (WHO) guidelines with increasing age, this decrease was more pronounced when employing strict morphology criteria (Kuhnert et al., 2004). In summary, a number of factors that can cause or contribute to male infertility are: 1. Sexually transmitted diseases (STDs); 2. Fevers and infections; 3. Surgery of the reproductive tract; 4. Damage to the vas deferens (vasectomy); 5. Scrotal varicose veins (varicocele); 6. Use of depression or high blood pressure medications; 7. Exposure of the testes to high temperatures; 8. Use of tobacco, marijuana, or alcohol; 9. Medical conditions (diabetes); 10. Genetic or hormonal problems; and 11. Testicular injury. During physical examination, particular attention should be paid to the discerning features of hypogonadism. This would typically be viewed as poorly developed secondary sexual characteristics, eunuchoidal skeletal proportions, and the lack of normal male hair distribution. Testicular examination is essential and normal adult testes are 4.5 cm long and 2.5 cm wide on average, with a volume of approximately 20 cc. Small and firm testes may signify damaged seminiferous tubules before puberty, whereas small and soft testes may suggest possible post-pubertal damage. Epididymal irregularities suggest a previous infection and possible obstruction. Examination may reveal a small prostate with androgen deficiency or slight tenderness

(bogginess) in men with prostatic infection. Any penile abnormalities like hypospadias, abnormal curvature, or phimosis, should be looked for. The scrotal contents should be carefully palpated with the patient in both the supine and standing positions. Varicoceles can often result in smaller left testes, and a discrepancy in size between the two testes should arouse suspicion. Both vas deferens should be palpated, as 2% of infertile men have congenital absence of the vas and seminal vesicles (Zavos, 2005, 1992). Routine laboratory testing Semen analysis The initial test performed is a semen analysis, which allows the clinician to examine the sperm count, motility and morphology. The semen analysis results could provide vital information revealing the cause of the infertility. The parameters normally assessed during the evaluation are: 1. Sperm count: Normal range of 20 million /ml to 300 million sperm per milliliter with low sperm count (oligozoospermia) of fewer than 20 million per milliliter. 2. Sperm motility: Low sperm motility or movement (asthenozoospermia) may reduce the chances of conception, especially when paired with low sperm count normal sperm motility of 50%. 3. Sperm morphology: abnormally shaped sperm are often unable to swim effectively or penetrate the various oocyte investments during fertilization. A normal sperm has an oval head, slender midsection and a tail that beats in a wave-like motion. Seminal specimens should be collected after three to four days of sexual abstinence via either masturbation or at intercourse. Seminal physical characteristics are also very important as they may indicate certain deficiencies. Additional laboratory tests Depending on the results of the semen analysis, more tests can be performed to diagnose specific causes of infertility. If the semen analysis shows clumping or signs of infection, a semen culture, prostate fluid culture and urinalysis may be ordered. Antisperm antibody testing may also be considered to evaluate potential immune system disorders. Fructose testing may reveal structural problems or blockage of the seminal vesicles. New studies suggest that sperm with certain levels of DNA fragmentation (sperm chromatin structural assay) serve as a strong predictor of reduced male fertility. When considering that the central component of laboratory testing is the semen analysis, it must be

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Table 1. Normal values for semen parameters.

Parameter Volume (ml) Sperm concentration (million/ml) Motility (%) Forward progression (25%) Normal morphology by WHO criteria (%) Normal morphology by strict criteria (%) Total sperm count (million) Total motile sperm (million) Total functional sperm (million)
Source: World Health Organization (WHO, 2006).

Normal values 24 >20 >50 25% >30 >30% >20 million >20 >6

insisted upon that this test is performed correctly. At collection the man is generally asked to obtain a specimen through masturbation. Special containers are also available for home collection, but prompt return of the specimen to the laboratory (within one hour) is mandatory. Table 1 lists normal standard values for adequate semen parameters as outlined by the WHO. It is important to note that these values are not the absolute values needed to achieve a pregnancy, but rather the statistical limits below which male infertility is more likely to be a problem. Due to significant variations in one or several semen parameters from one specimen to another, which are not uncommon, it is recommended that at least two semen specimens should be analyzed. Adherence to strict collection techniques and abstinence periods is therefore crucial to minimize variation and maximize accuracy. Ejaculation difficulties Semen collection Semen specimens collected for evaluation should resemble the ejaculate delivered during intercourse, as closely as possible, if the male infertility factor is to be properly identified and treated. The most accepted method of semen collection in humans for the purpose of semen analysis, artificial insemination (AI), or assisted reproductive technology (ART), is via masturbation. Since some males have difficulty in producing a seminal specimen via masturbation, recent developments have allowed semen collection to be performed via the use of semen collection devices (SCD). Those devices generally consist of non-spermicidal condoms made of polyurethane or silicone rubber. Due to their acceptability by patients, lack of negative effects on sperm viability, and assistance in the improvement of collected specimens to closely resemble the ejaculates obtained at intercourse, these devices may be used to better evaluate the male (Zavos, 2005).

Precoital sexual stimulation It has also been demonstrated that ejaculates produced under increasing intensity of precoital sexual stimulation (PSS), can bring about significant increases in ejaculate characteristics. PSS should therefore be considered during production of seminal specimens, particularly in patients with spermatogenic dysfunctions such as hypospermia, oligospermia, asthenospermia, or others. Erectile dysfunction Erectile dysfunction (ED) is the inability to attain and maintain penile erection sufficient to permit satisfactory intercourse and afflicts approximately 10% of the adult population of US men (Matsuda et al., 2004). This is increasingly evident in men who are asked to produce seminal specimens on demand for infertility evaluation and treatments. The inability to achieve penile erection is only part of the overall multifaceted process of male sexual function, which comprises various physical capabilities with important psychological and behavioral overtones. In addition, it should be recognized that sexual desire, orgasmic capacity and ejaculatory capacity might be intact in the presence of erectile dysfunction or may be deficient to some extent and contribute to the overall sexual dysfunction. Recently, sildenafil citrate (Viagra) has been considered as an effective treatment for erectile dysfunction (ED). Initial studies have shown that when Viagra is administered to men with ED, it can bring about erection and subsequent ejaculation. Various studies show a beneficial effect of Viagra with side effects that were not severe enough to discontinue treatment. It has been shown for the first time that not only does sildenafil citrate help males with erectile dysfunction, but also that the seminal characteristics of ejaculates produced at intercourse, along with semen preparation for use in subsequent intrauterine inseminations or ART, show normal values according to WHO criteria (Lawrence

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Table 2. Possible causes of falling sperm counts.

S/N 1 2 3 4 5 6 7 8 9

Causes of falling sperm counts Increased scrotal temperature Tight-fitting clothing and briefs varicoceles are more common Environmental Increased pollution heavy metals (lead, mercury, arsenic, etc.) Organic solvents Pesticides (DDT, PCBs, DBCP, etc.) Dietary Increased saturated fats reduced intake of fruits, vegetables, and whole grains Reduced intake of dietary fiber increased exposure to synthetic estrogens

et al., 2000; Goodpasture et al., 1987). Treatment for male factor infertility Treatments for male infertility range from surgical intervention or intrauterine insemination (IUI) to various forms of ART, such as in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Depending on the source of the problem, sperm can be taken from the mans ejaculate for use in assisted fertilization procedures. With the advent of IVF and other modes of ART, the overall treatment of male infertility has changed dramatically. One treatment option for men who do have sperm in the ejaculate is intrauterine insemination (IUI). Intrauterine insemination is an infertility treatment in which sperm are placed directly into the females uterine cavity near the time of ovulation. IUIs are commonly performed when there is a low sperm count or low motility. The sperm that will be injected during the procedure are prepared using a process called sperm washing (Lawrence et al., 2000; Goodpasture et al., 1987). Since IUI is primarily used when there is very little or no male factor involved, a variety of ARTs are available for the male patient depending on the severity of the male factor. Patients who have suboptimal sperm counts (oligospermia) or motility (asthenospermia) in combination with a female factor should be advised to undergo 3 IVF. Only 100 103 (correct to 10 ) motile sperm are needed per egg and the resulting embryos can be transferred directly into the uterine cavity of the female for subsequent implantation. If only a few motile sperm are present with no forward progression, then the patient should be advised to have IVF in combination with ICSI. As opposed to conventional IVF, only one sperm is needed per egg, and is injected directly into the ooplasm. Confirmation of fertilization and transfer of embryos are similar to IVF. If the patient presents with azoospermia, a testicular biopsy is needed to determine whether there are any sperm in the testes, in order to diagnose the azoospermia as either

obstructive (does produce sperm) or non-obstructive (does not produce sperm). In cases of obstructive azoospermia, advanced sperm retrieval techniques, including testicular sperm aspiration (TESA), percutaneous sperm aspiration (PESA), testicular microdissection and testicular biopsy, combined with IVF and ICSI, now allow men with either a low sperm count or no sperm in their ejaculate to have the chance to produce a child. Diagnostic considerations Semen analysis is the most widely used test to estimate fertility potential in the male. The semen is analyzed for concentration of sperm and sperm quality. The total sperm count as well as sperm quality of the general male population has been deteriorating over the last few decades. In 1940, the average sperm count was 113 million per ml, in 1990 that value had dropped to 66 million (Zavos et al., 1990). Adding to this problem, the amount of semen fell almost 20% from 3.4 to 2.75 ml. Altogether, these changes mean that men are now supplying about 40% of the number of sperm per ejaculate compared to 1940 levels. The downward trend in sperm counts has led to speculation that environmental, dietary, or lifestyle changes in recent decades may be interfering with a man's ability to manufacture sperm (Paulson et al., 2001). In diagnosing male infertility on the basis of sperm concentration, it is important to point out that as sperm counts have declined in the general population, there has also been a parallel reduction in the accepted line which differentiates infertile from fertile men, that is, from 40 to either 20, 10 or 5 million/ml. One of the key reasons these values have dropped so drastically is that, researchers are learning that quality is more important than the quantity. A high sperm count means absolutely nothing if the percentage of healthy sperm is not also high (Tables 2 and 3). Whenever the majority of sperm are abnormally shaped, or are entirely or relatively non-motile, a man can

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Table 3. "Normal" spermatogenesis.

Criteria Volume Density Motility Normal forms

Value 1.5-5.0 ml >20 million sperm/ml >30% motile > 60%

be infertile despite having a normal sperm concentration. Conversely, a low sperm count does not always mean a man is infertile. Numerous pregnancies have occurred with men having very low sperm counts. For example, in studies at fertility clinics 52% (Ford et al., 2000) of couples whose sperm counts were below 10 million/mL achieved pregnancy and 40% of those with sperm counts as low as 5 million/ml are able to achieve pregnancy. Because of these confirmed successes in men with low sperm counts, it is recommended that conventional semen analysis be interpreted with caution regarding the likelihood of conception and that more sophisticated functional tests should be used, especially when screening couples for in vitro fertilization (Table 4). Until recently, pregnancy was the only proof of the ability of sperm to achieve fertilization. Now there are several functional tests which in use. The post-coital test measures the ability of the sperm to penetrate the cervical mucus after intercourse. In vitro variants of this test are also available. One of the most encouraging tests is based on the discovery that human sperm under appropriate conditions can penetrate hamster eggs. It was established that fertile males exhibit a range of penetration of 10 to 100% and that penetration less than 10% is indicative of infertility. The hamster egg penetration test is considered to predict fertility in 66% of the cases compared to about 30% for conventional semen analysis. Another important test in the percentage diagnosis of infertility is the detection of antisperm antibodies. These antibodies, when produced by the man, usually attack the tail of the sperm thereby impeding the sperm's ability to move and penetrate the cervical mucus. In contrast, the antisperm antibodies produced by women are typically directed against the head. The presence of antisperm antibodies in semen analysis is usually a sign of past or current infection in the male reproductive tract. Therapeutic considerations Standard medical treatment of oligospermia can be quite effective when the cause is known, for example, increased scrotal temperature, chronic infection of male sex glands, prescription medicines, and endocrine disturbances (including hypogo-nadism and hypothyroidism). However, as stated in the foregoing, in about 90% of the cases of oligospermia, the cause is

unknown (idiopathic oligospermia). In regards to azoospermia, if the cause is ductal obstruction, new surgical techniques are showing some good results (Carlsen, 1992). In the treatment of idiopathic oligospermia or azoospermia, the rational approach is to focus on enhancing those factors which promote sperm formation. In addition to scrotal temperature, sperm formation is closely linked to nutritional status. Therefore, it is critical that men with low sperm counts have optimal nutritional intake. In addition to consuming a healthful diet, there are several nutritional factors that deserve special mention: vitamin C and other antioxidants, fats and oils, zinc, folate, vitamin B12, arginine, and carnitine. In addition, it appears important for men with low sperm count to avoid dietary sources of estrogens. Some herbs, especially Panax ginseng and Eleutherococcus senticosus, are known to increase sperm counts. BOTANICAL MEDICINES Ginseng Current scientific investigation suggests that both Panax ginseng (Chinese or Korean ginseng) and Eleutherococcus sentiosus (Siberian ginseng) are likely effective in the treatment of male infertility. Both botanicals have a long history of use as male "tonics. Panax ginseng has been shown to promote the growth of the testes, increase sperm formation and testosterone levels, and increase sexual activity and mating behavior in studies with animals. Siberian ginseng has also shown some benefit to the male reproductive function in animal studies as it has been shown to increase reproductive capacity and sperm counts in bulls. These results seem to support the use of either ginseng as a fertility and virility aid. In general, Panax ginseng is regarded as being more potent in effects (particularly stimulant effects) than Eleutherococcus senticosus. Although Siberian ginseng contains no ginsenosides and is not a true ginseng, it does possess many of the same effects that Panax ginseng exerts, but it is generally regarded as being milder. Pygeum Africanum: Pygeum may be effective in improving fertility in cases where diminished prostatic secretion plays a significant role. Pygeum has been shown to increase prostatic secretions and improve the composition of the seminal fluid (Purvis et al., 1992;

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Table 4. Causes of temporary low sperm count.

S/N 1 2 3 4 5 6 7 8

Causes of temporary low sperm count Increased scrotal temperature Infections, the common cold, the flu, etc. Increased stress Lack of sleep Overuse of alcohol, tobacco, or marijuana Many prescription drugs Exposure to radiation Exposure to solvents, pesticides, and other toxins

Table 5. Codes used in the diagnosis and management of male infertility.

ICD-9 456.4 606 606.0 606.1 606.8 606.9

Diagnosis codes Scrotal varices Male infertility Azoospermia Oligospermia Infertility due to extratesticular causes Male infertility, unspecified

Males that are 18 years or older are seen with one or more of the diagnosis codes.

Lucchetta et al., 1984). Specifically, pygeum administration to men with decreased prostatic secretion has led to increased levels of total seminal fluid plus increases in alkaline phosphatase and protein. Pygeum appears to be most effective in cases where the level of alkaline phosphatase activity is reduced (that is, less than 400 IU/cm3) and there is no evidence of inflammation or infection (that is, absence of white blood cells or IgA). The lack of IgA in the semen is a good indicator of clinical success. In one study, the patients with no IgA in the semen demonstrated an alkaline phosphatase increase from 265 to 485 IU/cm3. In contrast, those subjects with IgA showed only a modest increase from 213 to 281 3 IU/cm . Pygeum extract has also shown an ability to improve the capacity to achieve an erection in patients with BPH or prosta-titis as determined by nocturnal penile tumescence in a double-blind clinical trial. BPH and prostatitis are often associated with erectile dysfunction and other sexual disturbances. Presumably, by improving the underlying condition, pygeum can improve sexual function (Menchini-Fabris et al., 1988). Table 5 presents the diagnosis and treatment codes for the analyses detailed here. Diagnosis codes referring to laboratory abnormalities (such as oligospermia) are mixed with codes deriving from identifiable physical conditions (such as varicocele) that may result in laboratory abnormalities. Such overlapping diagnosis codes plague any analysis of available data. Table 6 lists the conditions identified in men presented for evaluation of infertility in studies of distribution of

diagnoses from 1978 and 1997. It appears that in the 20 years between these two reports, more diagnoses became available, and more risk factors for infertility were identified. Interestingly, the proportion of men labeled with idiopathic infertility remained similar, at approximately 25% in 1978 and 23% in 1997 (Clavert et al., 1986; Carani et al., 1991). OLIGOSPERMIA Cases of male infertility are at increase in the world. Quality of semen is declining over the years. In about 1% of cases significant medical pathology which needs early intervention is found. (Johnson et al., 1984) Early evaluation of the male includes semen analysis and this should be done before a treatment plan is to be instituted. Semen quality is found to decrease due to increasing amounts of environmental toxins; often oestrogenic in effect. Management starts with avoidance of life style issues that may be detrimental to sperm quality. Infertility causes mental stress as well as financial stresses when he adopts treatment plans like intrauterine insemination (IUI), In vitro fertilization, intracytoplasmic sperm injection (ICSI), percutaneous epididymal sperm aspiration (PESA), testicular sperm aspiration (TESA) or other assisted reproductive technologies. Many modern medicine medications used for unrelated conditions have negative effects on sperm quality. Surgical procedures on the aetiological factors of defective spermatogenesis like varicocoele itself are a factor may lead to oligospermia or

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Table 6. Distribution of male infertility diagnoses, 1978 and 1997.

Diagnosis Varicocele Idiopathic Obstruction Female factor Cryptorchidism Immunologic Volume Agglutination Viscosity Ejaculatory dysfunction Testicular failure Drug/radiation Endocrinologic Infection Sexual dysfunction High density Necrospermia Systemic disease Sertoli-cell only Ultrastructural defect Genetic Testis cancer

1978 percent (n = 420) 37.4 25.4 6.1 ... 6.1 ... 4.7 3.1 1.9 1.2 9.4 ... 0.9 ... 2.8 0.5 0.5 ... ... ... ... ...

1997 percent (n = 1,430) 42.2 22.7 14.3 7.9 3.4 2.6 ... ... ... 1.3 1.3 1.1 1.1 0.9 0.3 ... ... 0.3 0.2 0.2 0.1 0.1

azoospermia. In Homoeopathy, it is not discussed with enough importance by any of the authors. Rubric male infertility in most of the repertories contains only a few medicines. Defective sperm is the most common reason of male infertility and the main spermal anomalies are: a. Aspermia Failure of formation or emission of semen. b. Azoospermia Absence of sperms in the ejaculate. c. Oligospermia Reduced sperm count (< 20 million/ml). d. Asthenospermia Motility deficiency. e. Teratospermia More malformed sperm cells. f. Necrospermia Dead or motionless sperm cells. g. Polyspermia Sperm count more than normal. h. Globozoospermia Round headed sperms. i. Haematospermia Blood cells in semen. Oligospermia Definition Refers to sperm densities of less than 20 million sperm per ml of semen or a total count of less than 50 million sperm. Classification Depending on the count, oligospermia is divided into

mild, moderate and severe. Mild: 10 to 20 million sperm cells /ml. Moderate: 5 to10 million sperm cells/ml. Severe below: 5 million sperm cells/ml. Dilution oligospermia In conditions where the semen volume is 5 ml or more, count/ml may fall below normal. This is called dilution oligospermia. Prevalence of the condition About 10% of the couples suffer from the trouble of infertility. Among them 40% are caused by male factors, 30% by female factors and the rest 30% by combined factors both male and female. Azoospermia forms 10% of male infertility in long standing cases. Disorders of sperm transport cause infertility in 6% infertile men. In 5% of cases the cause is found to be the autoimmunity. Congenital bilateral absence of vas deferens is found in 1% of patients attending male infertility clinic. Aetiology May be broadly divided into physiological and

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Pathological. Physiological 1. Frequent intercourse 2. Old age. Pathological Reduction in sperm density may be due to 1. Defective spermatogenesis. 2. Partial obstruction of the efferent ducts. Defective spermatogenesis are: 1. Congenital a. Undescended testes or maldescended testes. b. Cystic fibrosis. 2. Primary testicular diseases. 3. Thermal factor a. Varicocoele, big hydrocoele or filariasis. b. Using tight garments; working in hot atmosphere. c. High fevers. 4. Infections a. Mumps, orchitis after puberty. b. Systemic illness, bacterial or viral c. Infections of the seminal vesicle or prostate. d. T. mycoplasma or Chlamydia trachomatis infection. e. Orchitis occurring in lepromatous leprosy. 5. General factors. a. Chronic debilitating diseases. b. Malnutrition. c. Heavy smoking. d. Alcoholism. e. Narcotics. f. Granulomatous diseases especially lewprosy. 6. Endocrine factors a. Diabetes. b. Pituatory adenoma, hypopituitarism c. Thyroid dysfunction. d. Adrenal tumors, adrenal hyperplasia. e. Hyperprolactinoma. 7. Genetic a. Klinefetlers syndrome. b. Reinfelters syndrome. 8. Iatrogenic a. Radiation b. Drugs. 9. Mechanical a. Trauma to testes, accidental or surgical. 10. Occupational a. Exposure to toxic substances or hazards on the job such as lead, cadmium, manganese, mercury; ethylene oxide; vinyl chloride, radioactivity and x-rays.

11. Nutritional supplements a. Saw palmetto. 12. Neurological diseases a. Paraplegia. b. Dystrophica myotonica. 13. Hepatic failure. 14. Renal failure. 15. Auto immune disorders. a. Polyglandular autoimmune failure. 16. Systemic diseases a. Sickle cell disease. b. Amyloidosis. c. Hodgkins Disease 17. Immotile cilia syndrome. 18. Androgen resistance. 19. Retrograde ejaculation. 20. Idiopathic. Obstruction of the efferent ducts Obstruction may be at any level starting from rete testes, epididymis, in the vas deferens or in the ejaculatory duct. 1. Congenital a. Unilateral absence of vas deferens (C.AV.D). b. Unilateral absence of corpus or cauda epididymis. 2. Infection a. Tubercular. b. Gonococcal. c. Chlymydia. d. Leprosy. 3. Surgical trauma a. Herniorrhaphy. b. Hydrocoele operation. c. Varicocoele operation. 4. In utero Diethylstilbesterol exposure. 5. Youngs syndrome. 6. Torsion of the testis. 7. Idiopathic. Varicocoele are an enlargement of the veins that run along the spermatic cord in the scrotum, ie the pampiniform or cremasteric plexi. It may be present in 15% of males but all may not necessarily suffer from infertility or oligospermia. But it may be the cause in 30 to 40% of males. This develops when defective valves in the veins allow the normally one-way flow of blood to back up in the abdomen. Blood then flows from abdomen to scrotum where a hostile environment for sperm development is created. Prolonged elevated temperature has a detrimental effect on sperm production. Due to raised temperature of scrotum; it is also referred to as hot testicles. Abnormal venous blood flow increases metabolic waste products and decreases availability of oxygen and nutrients required for sperm development. Long term effects of compromised circulation interfere

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Table 7. Drugs thought to induce male infertility.

S/N 1 2 3 4 5 6 7

Drug type Anti-androgens spironolactone, cimetidine, flutamide Androgen suppressors ketoconazole and leuprolide Oestrogens and hormones oestrogen agonists, growth hormone, and anabolic steroids Drugs of abuse anabolic steroids, alcohol, marijuana, cocaine and nicotine. Psychoactive agents tricyclic antidepressants, amphetamine, tranquillisers and phenytoin. CVS agents propanolol, digoxin and Ca2+ channel antagonists. GIT and antibiotics, sulphasalazine and nitrofurantoin

with androgen (hormone) production. They may be small, develop slowly with no symptoms. Some are large and are visible in scrotum. Other symptoms include painless testicular lump, scrotal swelling or bulge within scrotum. Although they can develop on either side on either side of testicle; 85% develop on similar side. They are nontender twisted mass that feel similar to a bag of worms. It disappears on lying down. To be properly identified during physical examination the patient must stand and must be asked to bear down (or cough). It develops between ages 15 to 25 years old. More than 80% of men with secondary infertility have varicocoele. It progresssively declines fertility (Greenberg et al., 1978). Semen analysis Recommendation for standards in semen analysis was done by parameter recommendation/ normal value as follows: (1) Abstinence 5 (3 to 7 days). (2) Collection masturbation (coitus interruptus). (3) Volume (2 to 6 ml). (4) Viscosity full liquefaction within 60 months. (5) Sperm density (40 to 250 million/ml). (6) Sperm motility (7) Progressive (8) Quantitative (9) Good- Very good. (10) First hour - greater than or equal to 60%. 2 to 3 h greater than or equal to 50%. (11) Vitality (Less than or equal to 35% of dead cells). (12) Sperm morphology (greater than or equal to 60% normal). (13) Acid phosphatase (25,000 to 60,000 IU/ml). (14) Zinc (90 to 250 g /ml). (15) Fructose (150 to 600 mg/ml). (16) Medicines for male infertility and oligospermia (on the basis of Homoeopathic literature). Drugs have been implicated in the development of male infertility; however, many of them are commonly used drugs (Table 7).

Conventional methods for treatments for male infertility

the

diagnosis

and

The following is a summary of the key methods currently used to diagnose male infertility. 1. 30% of the cases of male infertility the causative factors are idiopathic. 2. Standardized laboratory models for the diagnosis of male infertility are unavailable. 3. Conventional therapeutic strategies are based on speculative concepts and clinical observations 4. Consider female reproductive function in relation to male infertility treatments, (timing of ovulation). 5. Develop good clinical experimental trials are necessary that include endocrino-logical evaluation of reproductive hormones. 6. Continuous record of technician performance are mandatory for internal quality control. 7. Semen analysis only useful for determining azoospermia and oligospermia (Sigman et al., 1997). MALE INFERTILITY STATISTICS Population Censuses in Pakistan have included standard questions on fertility, but relatively little use has been made of resulting data. The principal reason for this neglect has been a concern over data quality. Some of the estimates derived from previous censuses have been so clearly defective that there has been a general reluctance to invest effort in detailed analysis of the data. According to UN projections, it will become the third most populous by the year 2050. It is one of only ten countries as of the 1998 with a population in excess of 100 million in combination with a TFR in excess of five births per woman (United Nations, 1999). Pakistan stands apart from its populous neighbors in South Asia, all of which (with the exception of Nepal) experienced substantial declines in fertility prior to 1990 and therefore shows markedly lower fertility in 2001. Intercensal growth rates between 1951 and 1981 indicated a rise in the population growth rate in the 60's and 70's largely attributed to the sharp declines in mortality seen in the 50's and 60s, which were not followed by any decline

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in fertility in those decades. Intercensal growth rates actually peaked in the 1961 to 1972 period and continued at fairly high levels in 1972 to 1981 after which they began to decline. The 1981 to 1998 period records a decline to 2.6 indicating that growth rates in the last few years of the 17 years intercensal period are likely to have been lower. While the validity of the 1998 Census has generally been endorsed, a post enumeration survey was not carried out. A revised figure issued by the Census Organization places Pakistans population in 1998 at 131.6 million and in 2001 this is likely to be closer to 140 million. Demographic surveys from the 60s until the 90s also concur that growth rates peaked in the 70 and 80s and have come down quite sharply for the first time since then. The PDS 1998 shows a rate of natural increase of 2.4, which is one of the lowest figures recorded since the 60s. The following table attempts to extrapolate the aforementioned incidence rate for male infertility to the populations of various countries and regions. As discussed in the foregoing, these incidence extrapolations for male infertility are only estimates and may have very limited relevance to the actual incidence of male infertility in any region.
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