Microsoft word - infertility_05_management.doc
AYURVEDIC HOSPITAL - Nugegoda, Sri Lanka.
FOR INFERTILITY TREATMENTS
Call Dr. R. A. R. P. Susantha on +94 112 812814 for Free Consultancy
MANAGEMENT OF SPECIFIC CONDITIONS
• 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 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.
• 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.
• 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
• 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
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
Ayurvedic is the main alternative treatment. RESULTS.
• 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
• 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
• 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
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
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.
• 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
• 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
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.
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.
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.
from administration of Ayurvedic drugs is
treated by withdrawal of the agents, and starvation induced gonadotropin
• Hyperprolactinemia can be treated with bromocriptine or other
• 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.
• 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 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 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
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.
• 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.
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,
• 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
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.
• 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
• 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.
• 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
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.
Increased frequency of ejaculation to facilitate drainage of the accessory glands,
Varicoceles are found in about 25 per cent of men being examined for infertility.
(See page---------) FOLLOW-UP STUDIES AND CONTROLLED TRIALS
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.
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
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:
Weight reduction for the obese;
Alcohol intake reduction for the moderate to heavy drinker;
Avoidance of social drugs, including tobacco;
Reduction of stress in the workplace,
Marriage, and that engendered by the infertility;
Avoidance of heat from frequent sauna and spa baths.
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.
CHAPTER 5: SAMPLE PROBLEMS FOR HOMEWORK, CLASS OR EXAMS These problems are designed to be done without access to a computer, but they may require a calculator. 1. For each scenario below, choose the most likely method of analysis and write the corresponding letter in the blank. #1 two-sample t test #5 McNemar’s test #6 two-sample test for medians A. ___ Household incomes are often extremel
REVISIÓN EL CONTROL ANTIDOPAJE DE LOS JUEGOS OLÍMPICOS: DE LOS ANGELES (1984) A ATENAS (2004) EL CONTROL ANTIDOPAJE DE LOS JUEGOS OLÍMPICOS: DE LOS ANGELES (1984) A ATENAS (2004) OLYMPIC GAMES DOPING CONTROL: FROM LOS ANGELES (1894) TO ATHENS (2004) INTRODUCCIÓN to. El Príncipe Alexandre de Merode, de gran Eduardo Henrique recuerdo, fundador y presidente de esa Com