Microsoft word - infertility_05_management.doc

AYURVEDIC HOSPITAL - Nugegoda, Sri Lanka.
Call Dr. R. A. R. P. Susantha on +94 112 812814 for Free Consultancy
Management of sperm autoimmunity,
Male genital tract obstructions,
Gonadotropin deficiency,
Coital disorders,
Genital tract inflammation,
(Androgen replacement therapy is covered in another chapter.) Sperm Autoimmunity
Clinical Characteristics
• Sperm autoimmunity is present in 6 to 10 per cent of men seen for • About half have spontaneously occurring sperm autoimmunity and the remainder has associated genital tract obstruction. • Autoimmune orchitis with inflammatory cell infiltrates in the testis may follow an episode of epididymo-orchitis, or occur spontaneously, but is • Men with spontaneously occurring autoimmunity have slightly higher frequencies of family histories of other autoimmune diseases and thyroid and gastric autoantibodies in their serum suggesting a familial predisposition to develop sperm autoantibodies. • The types of genital tract obstruction associated with sperm autoimmunity appear to be those that have occurred after puberty, such as postgonococcal epididymitis, vasectomy, or traumatic obstructions. • The obstruction may be one-sided. • Sperm autoimmunity is common in men with persisting infertility after • About 70 per cent of men develop sperm antibodies in their serum within • The presence of these antibodies is an relative adverse factor for success • Sperm autoimmunity is less common with congenital epididymal obstructions, Young syndrome, and congenital absence of the vasa. Differential Diagnosis
• Men with severe sperm autoimmunity must be distinguished from those with low-level sperm autoantibodies that are not relevant to the infertility. • The latter have mucus penetration tests that are normal or only marginally • Treatment for the antibodies is not warranted, and other causes of the • Many patients with low-level sperm antibodies have immunobead binding only to the tail tips, or IBT results with less than 70 per cent binding to the • It is possible the antibody levels may vary over time either spontaneously or as a result of relief of obstruction. • If there are few or no sperm present in the semen, the main problem is to determine whether the sperm antibodies are the only cause of the problem or whether there is also an obstruction or a spermatogenic disorder. Pathophysiology
• Despite intense study much remains unknown about sperm antibodies. Most of the epitopes for the autoantibodies are unknown. • The antibodies may be naturally occurring and to sperm coating proteins from the epididymis and nonpeptide antigens. • The different patterns of immunobead binding to the sperm surface may result from antibodies binding to different sites or from variations in the total amount of antibodies on the sperm. • The autoantibodies could enter the genital tract because of defects in the blood-testis barrier or impairment of other mechanisms that make the testis an immunologically privileged organ. • The antibodies may also be produced by lymphocytes resident in the Sperm antibodies interfere with fertility at several levels:
• Interference with spermatogenesis, • sperm agglutination in the male genital tract, • reduced sperm motility and mucus penetration, • interference with sperm binding to the zona pellucida, • the acrosome reaction on the zona pellucida and penetration of the zona Sperm antibodies of different immunoglobulin classes can be found in serum, seminal plasma and on sperm. IgG and IgA sperm antibodies, particularly secretory IgA, locally produced in the male genital tract, cause the greatest Natural History
• In most patients sperm autoimmunity causes persistent severe infertility. • The pregnancy rate for untreated patients is less than 0.5 per cent per month. • Glucocorticoid treatment usually only produces a transient benefit. • Occasionally sperm autoimmunity may fluctuate in severity. • The rare patients who produce pregnancies without treatment appear to have spontaneous improvements with a fall in antibody levels and increased • Sperm antibodies may decrease after relief of genital tract obstruction but this GENERAL MANAGEMENT.
The couple is advised to have intercourse frequently at the fertile time of the Semen is cryopreserved if the quality improves, as this may be used for OTHER TREATMENTS. Ayurvedic is the main alternative treatment.
• About 50 per cent of men treated with Ayurvedic for sperm autoimmunity have a reduction in sperm antibody levels and an increase in sperm concentration, motility, and mucus penetration. • Pregnancies occur in about 25 per cent of couples during a four- to six- • Ovulatory disorders, endometriosis, and tubal abnormalities are negative prognostic factors, and in these couples it may be preferable to perform • Ayurvedic produces live birth pregnancy rates of about 20% per attempt. • The presence of antibodies has no adverse effect on the outcome of Ayurvedic treatments the results being determined mainly by age and Genital Tract Obstruction
Clinical Characteristics
• Most men with genital tract obstruction have azoospermia, normal testicular size, normal virilization, and normal serum FSH levels. • However, some have combined obstruction and spermatogenic disorders, or partial obstructions and severe oligospermia. There may be a history of an event that caused the obstruction, such as epididymitis with gonorrhea or • Because a few men with normal spermatogenesis have elevated FSH levels and some spermatogenesis may occur in association with a severe spermatogenic disorder, all patients should be offered further investigation. • In men with congenital absence of the vas or ejaculatory duct obstruction, semen volume, pH and fructose levels are low. • The semen also does not have its characteristic smell and does not form a gel after ejaculation because it contains only prostatic and urethral fluid. • The semen characteristics of complete ejaculatory duct obstruction are the same as for BCAV but the vasa are palpable. • Rectal ultrasound may show the cause of the obstruction such as a cyst of • Some men may have partial or intermittent ejaculatory duct obstruction and • Testicular biopsy is normal or there may be some reduction in spermatogenesis either as a coincidence or as a result of the obstruction Pathophysiology
• Degeneration or failure of development of the Wolffian duct structures with cystic fibrosis gene mutations or other factors is covered above. • Some men with Young syndrome had children and must have developed the • The pathology shows inspissated material in the head of the epididymis, and there are lipid inclusions in the epithelial cells. Young syndrome is not related • Postinflammatory obstructions after gonorrhea typically occur in the tail of the epididymis, whereas nonspecific bacterial inflammation produces more widespread destruction, and tuberculosis usually causes multiple obstructions in the epididymides and vasa. Back pressure blowout obstructions in the epididymis are frequent after vasectomy. • Iatrogenic causes of genital tract obstruction include inadvertent epididymectomy during testicular biopsy, vasal damage during hernia repair or pelvic or lower abdominal surgery such as renal transplantation, and ejaculatory duct obstruction from prostatectomy or complicated bladder Differential Diagnosis
Men with persistent azoospermia, normal testicular size, normal virilization, and normal FSH levels can be assumed to have obstruction until proved otherwise. Up to one third of men with this clinical picture are found to have a serious spermatogenic disorder on testicular biopsy despite the normal serum FSH level. There are rare instances of normal men who show azoospermia on single This "spurious azoospermia" must be excluded before surgery is contemplated. Once diagnosis of obstruction is confirmed, it is necessary to determine the feasibility of surgery. Intratesticular and caput-epididymal obstructions have a poor prognosis but cauda-epididymal and vasal obstructions can often be treated successfully with surgery and after treatments with Ayurvedic. Distal obstructions are important to diagnose because they may be reversed at Ayurvedic is also used when reconstructive surgery is not possible, or after surgery, the female partner has an infertility problem or the couple can not wait six to twelve months to have a reasonable attempt at conceiving naturally after General Management
Genetic abnormalities associated with the cystic fibrosis gene need to be considered if a pregnancy are to be attempted using the man's sperm. The woman should be screened for cystic fibrosis gene abnormalities and the Preimplantation or prenatal genetic diagnosis may be performed if mutations are The woman should be investigated in detail to ensure her potential fertility before The prognosis of the procedure and the availability of other forms of treatment should be discussed realistically with the couple. After doing Ayurvedic treatments sperm may be obtained by testicular biopsy or percutaneous sperm aspiration from the epididymis under local anesthesia. If a natural spermatocele is present, usable sperm may be obtained by direct puncture through the scrotal skin. It may be possible to combine vasoepididymostomy with sperm aspiration for I.U.I. Epididymal and Vasal Surgery
• Treatment of male genital tract obstructions is best undertaken by specialist microsurgeons, and Ayurvedic phicishans. • The testis is exposed and the most proximal (to the testis) level of obstruction • A testicular biopsy is obtained and the patency of the vas is determined by • The vas or epididymal tubule is opened proximal to the obstruction, and if possible, the presence of motile sperm is demonstrated by microscopy. • Then microsurgical anastomosis between the ends of the vas or between the vas and the epididymal tubule is undertaken. RESULTS.
• Vasovasostomy and vasoepididymostomy for caudal blocks produce relatively good results - 50 to 80 per cent of patients having sperm present in the semen; however, less than half of these produce a pregnancy
within the first year.
• The poor results may be related to continuing obstruction, sperm autoimmunity, or coexisting spermatogenic disorders. • The results of vasoepididymostomy for proximal blocks are poor. • Although sperm may appear in the semen, pregnancies are extremely uncommon following vasoepididymostomy for caput epididymal blocks. • The results of ICSI with testicular or epididymal sperm, fresh or after cryopreservation, are similar to those obtained with sperm from semen. Gonadotropin deficiency and suppression
Clinical Characteristics
• Most men seeking treatment for infertility associated with gonadotropin deficiency have been treated with androgens, following presentation in • The main diagnoses are Kallmann syndrome, other isolated gonadotropin deficiencies, combined gonadotropin and growth hormone deficiency and rarely pituitary tumours, trauma or craniopharyngiomas treated in childhood. Occasionally men with previously undiagnosed prepubertal gonadotropin deficiency present with infertility. • The clinical features are usually very small testes (<4mL) and severe • There may be a child like appearance with lack of secondary sex hair development, failure of male pattern scalp hair recession and balding and • Gonadotropin deficiency may develop after puberty because of tumours, surgery or trauma of the pituitary or hemochromatosis. • These men usually note loss of libido and may note reduced beard and body hair growth, low ejaculate volume and decreased testicular size. • General lethargy, muscular weakness and hot flushes are also common Physical examination
4. Dry finely wrinkled skin on the face. Features of underlying or associated conditions may be present for
8. Hormone excess or deficiency with pituitary tumours, or 9. Liver disease or diabetes with haemochromatosis. 10. Hyperprolactinemia is uncommon in men. It usually presents with 11. low testosterone levels and variable semen analysis results from 13. sometimes with only minimal gynaecomastia. 14. There is usually a pituitary tumour. 15. Hyperprolactinemia associated with a pituitary macroadenoma is rare but important: as well as loss of libido there is usually progressively severe headache and visual field impairment. 16. A number of paediatric syndromes include mental deficiency and gonadotropin deficiency but the patients rarely seek treatment for 17. Mutations of DAX1 cause adrenal hypoplasia and gonadotropin 18. Gonadotropin suppression may occur in a variety of circumstances. 19. The most common now appears to be the illicit use of anabolic and androgenic steroids or chorionic gonadotropin. 20. Other hormones and drugs can cause gonadotropin suppression. 21. Selective suppression of LH with intrathecal opioids for chronic pain 22. Rarely men are seen with hormone producing tumours for example adrenal adenomas, Leydig cell tumours or hCG producing teratomas which will suppress gonadotropins, usually there are features of marked hyperestrogenization with progressive gynecomastia. 23. Very rarely men are seen with congenital adrenal hyperplasia with gonadotropin suppression and azoospermia who can be treated successfully by glucocorticoid suppression of ACTH. 24. Spermatogenesis may occur despite severe androgen deficiency - 25. This is believed to be due to predominant LH deficiency or partial 26. There may be normal sperm concentrations but usually there is low 27. The fertile eunuch syndrome commonly occurs with hyperprolactinemia, hemochromatosis, starvation, illness or in 28. It is also seen with partial or mild Kallmann syndrome. Pathophysiology
Commonly gonadotropin deficiency is caused by genetic disorders of gonadotropin releasing hormone production or the GnRH receptor, loss of function of gonadotrophes, or suppression of gonadotropin secretion by extraneous steroids, other drugs or illness. There is usually a combined defect of androgen and gamete production. If the underlying cause cannot be corrected life long androgen replacement This is usually with a form of testosterone but when fertility is desired, treatment While experimental conditions may be found to indicate that either FSH or LH alone may be able to initiate spermatogenesis in humans, for practical clinical purposes treatment with LH alone (as hCG) is effective for fertile eunuch syndrome and may be effective where spermatogenesis has been stimulated before, either by natural puberty or previous gonadotropin therapy. In other situations both FSH and LH are required. Differential Diagnosis
In men with gonadotropin deficiency it is necessary to determine the cause of the disorder, or if this is not possible to exclude a serious underlying cause such as a With Kallmann syndrome there is hyposmia or anosmia from malformations of Other abnormalities may also be present including colour blindness, cleft lip and Except where the diagnosis is obvious, detailed radiological examination of the pituitary and hypothalamic area is necessary, together with full pituitary function tests to determine if there are other hormone deficiencies. Treatment
from administration of Ayurvedic drugs is treated by withdrawal of the agents, and starvation induced gonadotropin • Hyperprolactinemia can be treated with bromocriptine or other
dopamine agonist.
• Gonadotropin deficiency caused by of gonadotrophe destruction or abnormalities of the GnRH receptor require treatment with gonadotropins. • Some men with gonadotropin releasing hormone deficits can be treated successfully with pulsatile GnRH administration. Coital Disorders
• Male coital disorders important for infertility include impotence, failure of ejaculation, and retrograde ejaculation. • Many men have problems with sexual performance after first learning about the infertility, but this usually ameliorates with time. • Infrequent and poorly timed intercourse may result from incorrect advice, low libido or the psychological reaction to infertility. Impotence
• Impotence may be associated with low libido from androgen deficiency • Impotence related to vascular or neurological abnormalities (diabetic autonomic neuropathy or pelvic nerve damage) is uncommon in men • Selective impotence at the time of ovulation may indicate psychological problems and ambivalence about having children. Failure of Ejaculation
• Failure of ejaculation is usual with chronic spinal cord injury and may also be caused by antihypertensive and psychotropic drugs, but otherwise, is an infrequent cause of infertility in most societies. • Healthy men who cannot ejaculate with intercourse may be able to produce semen by masturbation, with a vibrator or other stimulation. Retrograde Ejaculation
• Retrograde ejaculation occurs when the bladder neck fails to contract at the time of ejaculation so that all or most of the semen passes into the • Usually there is an obvious cause: prostatic surgery, diabetic neuropathy, pelvic nerve damage or spinal cord injury. • Retrograde ejaculation is diagnosed by the finding of sperm in urine Differential Diagnosis
Recognition of a coital disorder is crucial; thus all infertile patients must discuss their sexual history in detail. Once recognized, the contribution of organic and psychological factors needs to be evaluated. General Treatment
• An optimistic prognosis can be given, provided that live sperm can be • The couples are advised about the various techniques that might be used • The woman's potential fertility must be evaluated. Specific Treatment
A drug, such as an ayurvedic, that may be contributing to the sexual disorder
should be stopped temporarily or permanently. Impotence may respond to sex behavior therapy, physical approaches with pumps and rubber occlusion devices to initiate and maintain erections, administration of Ayurvedic drugs needed in men with infertility. Some men with failure of ejaculation, or retrograde ejaculation may be able to ejaculate during intercourse with a full bladder, or after the administration of If these are unsuccessful, sperm may be collected surgically from the vas, ASSISTED EJACULATION.
• Ejaculation may be stimulated by applying a vibrator to the underside of the penis near the frenulum of the glans. Vibrators with a 2mm pitch and frequency of 60 Hz or more are most effective. • Men with complete spinal cord injuries below thoracic vertebra ten are unlikely to respond and will require electroejaculation. • Modern electroejaculation equipment is safe: the probe includes a thermal sensor and proctoscopy is performed before and after the procedure to ensure there ate no burns or other damage to the rectum. • A balloon catheter in the bladder is used to prevent retrograde ejaculation. • Semen obtained by assisted ejaculation from able-bodied men or in the acute stages of spinal cord injuries is often normal. In contrast, with chronic spinal cord injury there is frequently low volume, high sperm concentration, and poor motility. As with necrospermia, repeated ejaculation over several days can • Assisted ejaculation may cause autonomic hyperreflexia with chronic spinal cord injuries above thoracic vertebra number 6. The resulting uncontrolled hypertension may cause cerebral hemorrhage. • Careful monitoring of blood pressure and Ayurvedic treatment usually • Men without complete sensory deprivation require general anesthesia for RETRIEVAL OF SPERM WITH RETROGRADE EJACULATION.
Motile sperm may be obtained from the urine after retrograde ejaculation. Urinary pH is adjusted to above 7 and osmolality to between 200 and 400 mOsm/kg by administration of 80 g of sodium bicarbonate and 2.0 to 2.5 L of water daily for 3 days before the expected time of ovulation. On the day of ovulation the man ejaculates and passes urine. Sperm are recovered from the urine by centrifugation, washed and resuspended in an IVF The final pellet is resuspended in about 0.5 ml of culture medium for It is also possible to cryopreserve the sample obtained. If this method fails, electroejaculation and catheterization of the bladder could be Effects of Systemic Illness and Reversible Exposures to Toxins or Drugs
• A very large number of exposures to agents in the environment, drugs and illnesses can adversely affect testicular function but it is rare to find patients in which such exposures can be confirmed as contributing to male infertility. However, this should always be considered during clinical • The most commonly encountered problems clinically are impairment of o treatment of inflammatory bowel disease or o and recent febrile illnesses causing transient reduction of o Workplace exposures may be implicated in some patients but the association is rarely clear-cut enough to advise change of Acute Illnesses
The adverse effect of acute febrile illness on the semen quality is well known but
Frequent hot baths or saunas may also have a similar effect. There is a temporary suppression of spermatogenesis which recovers over 3 to 6 Whether increased scrotal temperature because of clothing, varicocele, obesity or environmental temperature contributes to male infertility is controversial. CRITICAL CONDITIONS.
• Suppression of gonadotropin secretion can occur with critical illness and such as hepatic failure, myocardial infarction, head injury, stroke, respiratory failure, congestive cardiac failure, sepsis, burns, starvation and severe stress, both psychological and physical. • Transient decreases occur following drug or alcohol intoxication, • The reduction in testosterone is proportional to the severity of some of the critical conditions and may predict the likelihood of recovery. • There may also be direct effects on the testes and alterations in SHBG levels. The shutdown of testicular function may be a useful adaptation to • During recovery from the critical condition pulsatile secretion of gonadotropins increases in a manner reminiscent of the changes with NUTRITIONAL ASPECTS.
• As mentioned above starvation is associated with gonadotropin suppression. Specific deficiencies of vitamins and minerals such as, B12, C, folate and zinc may affect testicular function, but these are rare in • Simple obesity may be associated with alterations in the hypothalamo- pituitary-testicular axis and impaired scrotal thermoregulation. • The most common changes are increased conversion of androgens to estrogens in peripheral tissues and low sex hormone binding globulin • Total testosterone, SHBG levels and gonadotropin levels may be low and • However, clinical androgen deficiency, estrogen excess and abnormal semen analysis are not regularly seen in morbidly obese men. Chronic Illnesses
• Impairment of testicular function is common in uncontrolled or poorly • There is usually elevated gonadotropin levels indicating a primary testicular defect, but impaired gonadotropin secretion or hyperprolactinaemia may occur and changes in SHBG and aromatisation • While this pattern of change in testicular function is a common nonspecific response to chronic illness, the mechanism is obscure. • There may be symptoms and signs of androgen deficiency and estrogen excess. Hepatic cirrhosis is one of the classical conditions known to have a profound adverse effect on the male reproductive function. • Testicular function may recover following liver transplantation. • Similar primary hypogonadism may occur with non-cirrhotic liver disease, chronic alcoholism without liver disease and a variety of chronic diseases without alcoholism: chronic anemias, chronic renal failure, thyroid hyper or hypofunction, human immunodeficiency virus infection, lymphoma, leukemia, advanced metastatic cancers, rheumatoid arthritis, severe cardiac disease and chronic respiratory disease. Effects of Drugs
• Drugs may contribute to male infertility by affecting gonadotropin (eg steroids) or prolactin secretion (psychotropic agents), steroid hormone production or action (antiandrogens), spermatogenesis (salazopyrine, alkylating agents) or by reducing sexual performance (psychotropic and • Some drugs may also cause gynaecomastia (antiandrogens, estrogens). • There is currently no place for the use of testosterone treatment of infertile men either continuously for low testosterone levels resulting primary or secondary testicular failure or as 'testosterone rebound' therapy because testosterone suppresses gonadotropin secretion and reduces • This inappropriate usage of testosterone persists in some quarters. • Abuse of androgens is widespread in people hoping to enhance athletic performance or body building. Some men are seen for infertility from azoospermia or oligozoospermia as a result. • Others have sexual performance problems after stopping the drugs. The • Normal virilization but low testosterone, low SHBG and low, normal or transiently high gonadotropin levels may be seen. • Recovery can take several months particularly after depot anabolic • Salazopyrin used for bowel disease and arthritis commonly causes spermatogenic defects. Usually there is poor sperm motility and morphology or oligospermia. The semen may be stained yellow. The antispermatogenic effect is caused by the sulphapyridine in the drug. Stopping the drug results in a recovery of sperm output within a few months provided the patient's health remains good and he does not have an underlying defect of spermatogenesis. • Other drugs and toxins are claimed to have adverse effects on spermatogenesis such as colchicine and anticonvulsants and some antihypertensive drugs, calcium channel blockers and antiparasitic chemotherapeutic drugs may impair sperm motility, capacitation or the Genital Tract Inflammation
• Specific inflammations of the genital tract such as mumps orchitis or gonorrheal epididymitis may cause sterility. • Nonspecific inflammations in the accessory sex organs are more common in men with infertility than in fertile men. • Also, male accessory sex organ inflammation and infertility may be more important in some countries than in others. • Symptoms include chronic low back pain, intermittent dysuria, discharges from the penis on straining, and discomfort in the pelvic region or testes after ejaculation or prolonged sexual abstinence. • The prostate may be enlarged and tender. The semen may show discoloration, variations of volume, increased viscosity, delayed liquefaction, high pH, sperm agglutination, bacteriospermia and • The bacteria in semen are frequently not pathogens but the commensals • To have more than 1 million polymorphs per milliliter in semen determined by peroxidase reaction or monoclonal antibodies to leukocyte antigens is • Although inflammatory cells could damage sperm by releasing free oxygen radicals or cytokines, bacteria could impair sperm motility, and inflammation could also cause partial genital tract obstruction, the actual contribution of nonspecific genital tract inflammation to male infertility is General Management
Men with clinical evidence of prostatitis require full urological assessment. Specific infections with pathogenic agents are treated with appropriate agents. It remains unclear what should be done about asymptomatic pyospermia and non-specific male accessory gland inflammation. Therapeutic trials generally show no benefit from antibacterial therapy on semen The organisms commonly implicated in nonspecific genital tract inflammation include Chlamydia, Mycoplasma and various bacteria, broad spectrum antimicrobial therapy is required if treatment it is to be given. Also, many of the standard drugs do not enter inflamed accessory sex organs. Trimethoprim, erythromycin, doxycycline, and norfloxacin are potentially effective.[151] Increased frequency of ejaculation to facilitate drainage of the accessory glands, Varicocele
Varicoceles are found in about 25 per cent of men being examined for infertility.
(See page---------)
Follow-up studies of groups of treated and untreated patients with varicoceles suggest pregnancies are as frequent without treatment as with treatment of the Attempts have been made to conduct randomized controlled clinical trials of varicocele treatment. Such trials are difficult because the ideal design with sham operations and blinding, which is so important in controlling for outcomes affected by psychological factors, is not possible. Large trials are also needed: for example about 250 pregnancies are required to have a high chance of finding a 25% increase in pregnancy rate after treatment The trials have produced conflicting results. A small prospective controlled study of percutaneous embolisation of the left testicular vein in 17-20 year olds showed an increase in testicular volume and sperm concentration in the treated group. Others have reported similar beneficial effects of treatment of varicoceles in adolescents in less well controlled studies. A prospective randomised controlled trail of occlusion of the spermatic vein by surgical or angiographic techniques versus follow-up counselling alone for one year in 125 couples without other causes of infertility showed no difference in pregnancy rate: 29% and 25% respectively at 12 months. WHO set up a multicenter controlled trial of Palomo ligation in men with infertility of greater than 1 year duration, abnormal semen analyses, a moderate to large left varicocele and a potentially fertile female partner? Volunteers were randomized to immediate operation or operation delayed for 12 months to provide an untreated control group. One of the participating centers reported their results separately. There was a In the trial there was a less marked but significant improvement, the life table pregnancy rates at one year being: 35% for the treated group and 17% for the unotreted group (relative pregnancy rate 2.7, 95% confidence limits 1.6-4.4). Semen analysis results also improved over the first year in the treated group. In the control patients having the delayed treatments the life table pregnancy rate at However, there were problems with the WHO trial particularly with possible irregularities of randomization in some centers early in the trial, drop out rates Also, the pregnancy rates in the control group are lower than expected for untreated subfertile men with varicoceles: approximately 30% produce a Several groups have now confirmed in uncontrolled studies, that patients who respond to treatment of varicocele have significantly greater GnRH stimulated The mechanism of this intriguing observation remains obscure. It may be that a beneficial effect of treatment is greater in younger than in older men. The possibility that responders can be predicted from hormone profiles and age Certainly further trials are necessary to meet the demands of evidence based medicine and should involve objective methods of semen analysis and varicocele detection, and simpler methods of treatment. Thus while some people remain convinced of the value of treating varicoceles for infertility it is not easy to demonstrate this unequivocally and the apparent improvements in semen quality and fertility may result from random fluctuations The Cochrane collaboration review of treatments for infertility concludes there is insufficient evidence to recommend treatment. It is clear that normal fertility is not achieved in a high proportion of patients treated for varicocele. Ayurvedic reproductive theraphy is a realistic alternative for most couples who have not conceived after a reasonable time. GENERAL MANAGEMENT
This section covers aspects of the management of couples with male infertility not amenable to specific treatment. A number will conceive during investigation. Others will decide not to continue with medical intervention. However, most couples with male infertility have conditions for which there is clearly defined and certainly effective treatment. In these it is important to discuss the prognosis for a natural pregnancy occurring, the effectiveness of treatments. The investigation of the female partner should be reviewed and abnormalities treated when possible. Patients should be acquainted with the physiology of the menstrual cycle and symptoms of ovulation to help time sexual intercourse over the fertile phase of the cycle.Good health practices should be promoted, particularly cessation of smoking because it reduces fertility in women. The psychological upheaval experienced by the couple should be discussed and additional help offered if necessary. Specialist infertility counsellors and patient support groups are particularly valuable in this area. Prognosis for natural pregnancy
A number of factors in addition to semen quality affect the likelihood of natural Some are obvious, such as female disorders and coital dysfunction. Female age is important as fertility declines after about age 35 years. Duration of infertility is a major factor in most studies: the longer the infertility, the The prognostic factors found in a study to determine the effect of
varicocele treatments were:
• Duration of infertility (negative), • Mean sperm concentration (positive), • Untreated sperm autoimmunity (negative), • Ovulatory disorders (negative), • Occupational group (farmers doing better than other workers), • Female age (negative), • Previous fertility in the couple (positive). Interestingly, varicocele presence and size were positive prognostic factors even though varicocele surgery was not significant. These factors can be used to advise patients about their chances of producing a The accuracy of such predictions is poor because the statistically significant factors only explain a small part of the variance (in the study above, about 17 per New studies using automated methods for semen analysis may reveal additional prognostic factors with better predictive value. However, other factors currently not assessable, such as gamete transport, may have an important bearing on conception and may explain the occurrence of pregnancies in some couples despite severely abnormal semen analysis results. Patients should not be told natural conception is impossible unless there is an Psychological Aspects
Infertility causes major trauma to the ego of most patients. Many undergo a grief reaction with initial denial of the problem followed by a tendency to blame others and a period of depression before final acceptance of The reaction may take years to resolve, and it can threaten the stability of the partnership, interfere with investigation and management of infertility, and lead to futile involvement in expensive "cures" offered by the unscrupulous. Participation in unsuccessful treatments during this phase often is particularly difficult emotionally for the patients. Stress may influence some aspects of An empathetic approach and involvement of independent counselors or self-help infertility groups may assist some couples. In most, the unpleasantness of the psychological reaction subsides with time. Timing of Coitus
A practical approach is to advise intercourse each day when ovulation might occur. Ovulation can be predicted to occur about 14 days before a period is due. Knowing the range of menstrual cycle lengths allows calculation of the days when ovulation is most likely to occur. Symptoms of ovulation including mittleschmertz and midcycle mucus changes also help identify the fertile time. Temperature charts may be used to indicate the end of the fertile time as the basal body temperature rises after ovulation. Ovulation timing by measurement of estrogen and progesterone metabolites in urine, urine or serum LH levels or ovarian ultrasonography may also be used. General Health Aspects
Although life-style factors are probably of little relevance to fertility in most Western societies, healthy living has positive long-term benefits and will not affect the semen adversely. The following are advised: 1. Weight reduction for the obese;
2. Alcohol intake reduction for the moderate to heavy drinker;
3. Avoidance of social drugs, including tobacco;
4. Reduction of stress in the workplace,
5. Marriage, and that engendered by the infertility;
6. Avoidance of heat from frequent sauna and spa baths.
Empirical Treatments:
Evidence based versus unconfirmed treatments Treatments of some causes of male infertility are available as discussed above but for the majority of patients with abnormal semen analyses there are methods A medical or surgical treatment may become established because it is logical and obviously effective - for example, Ayurvedic treatment for Kallmann syndrome or vasoepididymostomies for post inflammatory obstructions of the But in other situations where semen quality is reduced and there is subfertility rather than absolute sterility, it is necessary to demonstrate the treatment increases semen analysis results and pregnancy rates by a clinically meaningful This evidence based medicine approach generally requires controlled clinical These trials are usually designed to detect a certain magnitude of difference in the primary responses and thus a positive result supports the use of the method. However if the trial is negative, it merely does not confirm the magnitude of benefit tested, but it does not prove the method is of no value. In time the results of several trials can be combined by meta-analysis to get better estimates of the overall effects of the method. In the past many treatments were used in uncontrolled fashion for defects of Ayurvedic drugs have been given to suppress spermatogenesis in the hope that there would be "rebound" improvement after the treatment is stopped. Ayurvedic Antibiotics and anti-inflammatory drugs have been given for subtle infections for inflammations in the accessory sex organs. Antioxidants, amino acids, vitamins, herbs, and minerals such as zinc, cold baths There are difficulties with the interpretation of the results of these treatments. Marked improvements in semen quality can occur spontaneously. Semen analysis results also display the phenomenon of regression to the mean: on average repeated semen analyses improve in men with initially abnormal A good example of this is shown in a trial of zinc and folic acid in both oligospermic and normospermic men. Mean sperm concentration increased slightly in all oligospermic groups and in one group the increase was statistically In contrast there was no consistent change in the mean sperm concentration in Pregnancy rate data were not analyzed effectively in many early studies. Floating numerator pregnancy rates, in which a percentage of patients pregnant is given without regard for time of exposure have caused confusion in the infertility Statistical methods for life table analysis and regression analysis with censored data are especially useful for assessing the impact of groups of variables on pregnancy rates, for analysis of prognostic factors, and for testing results of The empirical treatments either have not been submitted to adequately controlled clinical trials, or when they have, the trials have not shown consistently positive results. Meta-analyses have also produced conflicting results probably because of variable quality of the trials included in the analyses. Until there is sound evidence of the value of a drug or procedure from controlled therapeutic trials, patients should be advised that none of the empirical methods meet the requirements of evidence based medicine.



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Microsoft word - rangeorders.doc

Applies To: All HSC Hospitals, CRTC Component(s): UNMH Responsible Department: Clinical Education/Clinical Affairs Title: GPC Range Orders Decision-making for Medications Patient Age Group: ( ) N/A (X ) All Ages ( ) Newborns ( ) Pediatric ( ) Adult POLICY STATEMENT: To maintain the safe, clear and consistent administration of those medications which have been prescribe

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