In general, it should be remembered that the predictive value
(in terms of fertility) of the semen analysis is low. A man with
an abnormal semen analysis with a history of proven fertility
(prior pregnancy) without an intervening event associated with
infertility has a better prognosis than a similar man without
proven fertility.
When the cause for the semen abnormality can be identified, treatment
directed specifically at this cause is the most direct and effective
plan. In many cases, the cause for the semen abnormality will
not be discovered. In this situation, treatment is directed at
improving the sperm's ability to fertilize an egg. Even in extreme
cases of male factor infertility, if any live sperm can be retrieved
either by ejaculation, from the postejaculatory voided urine,
or through surgical retrieval from the scrotal sac there are fertility
options which have reasonable success. This section reviews these
options.
* (1) excessive exposure to heat
Limit such exposure and recheck the semen analysis 3-5 months
later to allow for a nonoverlapping cycle of spermatogenesis
* (2) substance abuse, toxin exposure, and medications
Discontinue these substances (only change medications in conjunction
with the prescribing physician) and recheck the semen analysis
3-5 months later to allow for a nonoverlapping cycle of spermatogenesis.
* (3) radiation
The effects can be transient, but are often permanent when greater
than 60 rads has been administered to the pelvic region.
* (4) surgery
Postoperative changes are rarely treatable with further surgery.
One possible exception is an obstruction in the outflow tract
from the testicle involving the epididymis, vas deferens or ejaculatory
duct.
* (5) testicular failure
These causes for azoospermia and severe
oligospermia are rarely correctable. If any live sperm can be
retrieved assisted fertilization (such as ICSI) at the time of
IVF has a good pregnancy success rate. Use of very poor quality
semen for COH/IUI or standard microdroplet IVF rarely results
in pregnancy.
* (6) antisperm antibodies
Usually treated with intrauterine inseminations (to avoid the
cervical mucus) or In Vitro Fertilization, regardless of antibody
type. Since this treatment does not change according to the site
on the sperm that is attached to the antibodies simply determining
whether the patient has an abnormal postcoital test appears to
be the most direct, simple and cost effective test for these antibodies.
Antisperm antibody titers may be suppressed with steroids. These
medications have potentially serious complications, appear to
have an effect on antisperm antibody titers only after several
months of administration, and the dosages of the medications for
this indication have not been clearly established. Therefore,
I have not tried to suppress the production of antibodies with
steroids.
* (7) varicocele
Repair is not always recommended. Specific findings on semen analysis
and/or exam suggest the utility of repair. The semen analysis
of subfertile men with a varicocele may show increased numbers
of abnormally shaped sperm, a decrease in sperm motility and/or
a decrease in sperm concentration.
Repair of a clinically detectable varicocele appears to be indicated
if a persistent abnormal semen analysis is detected, especially
if characterized by the so called "stress pattern" that
is associated with a varicocele (a decreased sperm count or an
increased number of tapered forms with an increased number of
amorphous or immature sperm)
Repair of subclinical varicoceles (varicoceles that can only be
detected by special tests like ultrasonography, doppler studies
or invasive venograms) have not been shown to result in improved
fertility. Therefore, the repair of these subclinical varicoceles
is highly controversial.
Repair of a varicocele detected in the presence of a normal semen
analysis, normal testicular exam and "unexplained infertility"
is also controversial, with no clear basis for the surgery. That
is, the mere presence of a varicocele in the context of a couple
suffering from infertility is not independently an indication
for surgery.
Following varicocele repair there usually is little improvement
in the shape of the sperm (morphology) yet there is improvement
in the sperm counts and motility in up to 70% of patients. The
improvement in fertility, the desired goal, is unpredictable and
different reports suggest a wide range of outcomes.
Some urologists have suggested hormonal treatment of varicoceles
with either Clomiphene citrate or hCG (which acts like LH on the
Leydig cells of the testes, improving parameters like testosterone
production) alone or following surgery. In general, the research
in this area is lacking. Limiting hormonal management to patients
with a solid basis for treatment (such as a documented serum FSH,
LH or testosterone concentration deficiency) seems prudent at
this time.
* (8) disorders of emission or ejaculation
Treatment with pharmacological agents attempt to optimize emission
and bladder neck closure. Ephedrine sulfate, pseudoephedrine hydrochloride,
phenylpropanolamine hydrochloride, and imipramine hydrochloride
have been used to stimulate contraction of the bladder neck. These
agents seem to work best with minor nonsurgical causes of bladder
neck flacidity. Following such operations as childhood YV plasty
the pharmocologic agents are rarely effective.If no specific cause
for the abnormal sperm is identified, treatment options include
intrauterine inseminations, controlled ovarian hyperstimulation,
and IVF with ICSI. I typically recommend a progression through
the available treatment options from less aggressive to more aggressive.
* (9) intrauterine insemination
(IUI)
Intrauterine insemination (IUI) of sperm has been a widely accepted
technique for improving fertility when there is a mild male factor.
The basis for placement of sperm within the uterine cavity or
within cervical mucus is the rapid dropoff of the number of sperm
as they "naturally" progress from the vaginal vault
to the cervical mucus to the uterine cavity to the fallopian tubes
(where fertilization normally occurs). Reportedly, when about
50-500 million sperm are placed within the vaginal vault during
intercourse (where they normally live for less than 1-2 hours),
only about 1 million sperm find their way to the "friendlier"
cervical mucus (where they normally can live for days), only a
few thousand sperm may eventually find their way to the top of
the uterine cavity where the tubal openings are located, and only
hundreds to thousands of sperm may enter the tube in search of
a mature egg. The mechanism for this tremendous dropoff of sperm
along the way to the tube is not fully understood. The theory
supporting intrauterine insemination is that placing more than
1 million sperm (many men with decreased sperm counts will have
greater than 1 million motile sperm per ejaculate) at the top
of the uterine cavity near the opening of the tubes improves the
ability of those sperm to enter the fallopian tubes in search
of fertilizable eggs.
The success of procedures that attempt to optimize the sperm's
natural fertilizing ability is limited by the inherent sperm quality.
When equal numbers of motile sperm are separated from sperm initially
with a normal semen analysis versus sperm initially with a poor
semen analysis, there appears to be better function of the sperm
from the normal sample.
Insemination of sperm can be into the cervix or into the uterus.
Intracervical insemination is ideal if the couple's only apparent
problem with fertility is the inability to complete intercourse.
Otherwise, this is a technique with limited proven utility. The
primary indication for intrauterine insemination without the addition
of controlled ovarian hyperstimulation is an abnormal postcoital
test. Intrauterine insemination requires that the sperm is "washed"
free of the semen since semen
*contains molecules (called prostaglandins) that cause painful
contractions of the uterus if placed into the uterine cavity,
*may contain bacteria, and
* may have oxygen reactive species of molecules that could interfere
with fertilization.
Techniques to separate sperm from semen can partially determine
the amount and quality of sperm inseminated. Many infertility
specialists have suggested that 1 million motile sperm following
the sperm separation procedure is the minimum amount of sperm
associated with a reasonable chance of pregnancy success at intrauterine
insemination. The basis of this suggestion is not clear from a
review of the literature, however, my own personal experience
is in general agreement.
In sperm with decreased motility, chemical agents similar to caffeine
have been used to enhance motility. These agents include pentoxyfylline
which when applied to sperm will often improve motility considerably.
Many sophisticated sperm labs apply these agents to sperm.
The criteria for the timing of inseminations should be clearly
established. The goal is to perform the insemination at about
the time of ovulation. Ovulation occurs about 36 hours after the
onset of the LH surge (signal from the brain to the ovaries to
ovulate) in a natural cycle. Ovulation predictor kits detect LH
in the urine after metabolism and excretion into the urine. The
LH in the urine reacts with the test kit material which then changes
color (pink or blue). The detection of high levels of LH in the
urine correlates with the occurrence (not the onset) of the LH
surge in the blood. Generally, ovulation occurs the day of or
the day following the positive LH ovulation predictor kit result,
but exact timing of ovulation with these kits is not possible.
On occasion, ovulation may occur 2 days after the kit's detection
of the LH surge.
I have normally recommended that the patient have an IUI the day
of or the day following the positive kit result. If the patient
cannot return to the office for an insemination until 2 days following
the positive result, I will allow an IUI if the patient understands
that there may be a somewhat decreased chance of success. The
mature egg is most likely fertilizable for 24 hours following
release from the ovary. If intercourse rather than IUI is planned,
then the couple should have relations each day for 3-4 days starting
the day of the positive kit result. I have not found there to
be an improved success in pregnancy outcome when 2 rather than
1 IUI is performed per natural cycle. However, there are some
reports in the literature claiming improvement of pregnancy rates
with 2 rather than 1 IUI.
If ovulation is triggered using hCG then injection of this medication
simulates the LH surge. If hCG is given when there is a mature
egg present in an ovarian follicle then ovulation should occur
about 36 hours later. With hCG triggered ovulation, some research
suggests a higher pregnancy outcome when 2 IUIs are performed
with the initial procedure at 18 hours and the second procedure
at 42 hours. These findings have not been widely accepted.
Controlled ovarian hyperstimulation (COH) uses fertility medication
to mature greater than one egg per month and may be useful in
the treatment of male factor infertility. By maturing multiple
eggs in a given month you increase the number of "targets"
for available sperm. The use of menotropins with intrauterine
insemination is a widely accepted approach of moderate level aggressiveness
for mild to moderate male factor infertility. COH/IUI is also
used for unexplained infertility and ovulatory dysfunctions resistant
to or intolerant to clomiphene citrate.
The literature regarding the use of these techniques is not abundant,
but does suggest
* for male factor infertility or couples with an abnormal postcoital
test, menotropins with IUI increase the pregnancy rate up to 4
fold over no treatment, to a success rate of 10-15% per cycle
for male factor and slightly higher for those with only an abnormal
postcoital test;
* for unexplained infertility the per cycle success rates in one
study are about 3% for IUI alone, 6% for menotropins alone, and
26% for menotropins with IUI;
* clomid, menotropins and IUI alone are relatively ineffective
in the treatment of male factor or unexplained infertility
When the sperm quality is not adequate to recommend COH/IUI, or
if this management has not resulted in pregnancy within a reasonable
trial period (3-6 cycles with good apparent multiple egg development)
then alternative treatment plans should be considered.
* (10) donor sperm:
The use of donor sperm is a major decision and absolutely must
be discussed by both members of a couple and agreed upon prior
to initiating treatment. Indeed, both members of the couple will
sign the consent for the donor insemination.
* (11) ICSI:
The use of assisted fertilization techniques have evolved over
the past decades from (a) making small nicks or incisions in the
shell of the egg (zona pellucida) called zona drilling or partial
zona dissection (PZD), to (b) inserting a small number of sperm
under the shell of the egg but not within the plasma membrane
(oolemma) of the egg called subzonal insertion (SUZI), to (c)
inserting individual sperm under the plasma membrane of the egg
directly into the contents (cytoplasm) of the egg called intracytoplasmic
sperm injection (ICSI). ICSI has far greater success than the
earlier techniques in terms of pregnancy. The only sperm requirement
of ICSI is having as many alive (generally motile) sperm as there
are eggs for injection.
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