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Geoffrey
Sher, M.D.
 Educated
in South Africa, Dr. Sher was a Senior Specialist of Obstetrics
and Gynecology at the prestigious Groote Schuur Hospital (the
teaching institution for the University of Cape Town), where the
world's first human heart transplant was performed. In 1975, he
was recruited by the University of North Carolina in Chapel Hill
to assume a faculty position in the Department of Obstetrics and
Gynecology. In 1979, Dr. Sher entered private practice in Nevada
where he is currently a Clinical Professor of Obstetrics and Gynecology
at the University of Nevada School of Medicine. In 1982, Dr. Patrick
Steptoe, the father of In vitro Fertilization (IVF), afforded
Dr. Sher an opportunity to study under him at Bourn Hall in England.
Dr Sher returned to the United States and in January 1983 opened
the nation's first private, non-university based IVF center (the
fourth IVF program in the USA), in Reno, Nevada. He is Board Certified
in Obstetrics and Gynecology in South Africa, England and in the
United States and also has Sub-specialty Board Certification in
Maternal-Fetal Medicine.
Between
1987 and 1998, Dr. Sher opened the California based Pacific
Fertility Medical Centers (PFMC) with three locations. During
his tenure with PFMC, Dr. Sher was largely responsible
for the Group's emergence as one of the leading IVF programs in
the nation. In ten (10) years he propelled PFMC into the forefront
of clinical performance and research, introducing several major
medical break-throughs that impacted positively on the treatment
of infertility. In 1990 Dr. Sher was the first to point to the
fact that ultrasound evaluation of the uterine lining prior to
IVF, allows for prediction as to the likelihood of a subsequent
pregnancy. In 2000 he demonstrated that the administration of
Sildenafil (Viagra) to women with poor endometrial linings, improves
uterine blood flow and enhances hormonal thickening. In the field
of reproductive immunology, DR Sher was the first to link immunologic
problems causally, to female-related resistant infertility and
repeated IVF failure, introducing immunotherapies that have virtually
doubled the IVF birthrates in such cases.
In
1995, Dr. Sher and his team introduced a novel consumer-friendly
concept in fee structuring for IVF. This so called Outcome-Based
Pricing (OBP)-arrangement granted eligible patients a 70-100%
refund of medical fees, if they did not have a successful outcome
after IVF treatment. In the absence of IVF insurance coverage,
this risk- sharing financial arrangement was welcomed by IVF patients
across the board, but was strongly criticized by almost all IVF
physicians who felt that widespread introduction of such an arrangement
would place them at financial risk. After waging a relentless
and often single-handed crusade, Dr. Sher was successful in getting
this plan accepted by SART, the IVF medical governing body, as
well as by the IVF medical community. Currently, more than 50
of an estimated 350 IVF programs in the nation offer it as an
option, in one form or another, to their patients.
DR Sher is
a strong proponent of accountability on the part of IVF programs
for the success rates they report to consumers, favoring the establishment
of an accreditation process for all centers that provide IVF and
related services. He believes that in order to render IVF treatment
affordable to all Americans, regardless of their socioeconomic
status government should mandate insurance coverage for couples
undergoing IVF through providers who meet well defined, validated
outcome-based performance standards.
Dr. Sher was
a founding Board Member of SART. He has more than 200 accredited
scientific publications and abstracts to his credit and has co-authored
two consumer-oriented medical books; "Your Pregnancy,"
published by Simon and Schuster in the 1980's and "In
vitro Fertilization, the A.R.T. of Making Babies", published
by Facts on File. The latter is currently one of the most widely
read consumer books on the subject of IVF, in the USA. "In
vitro . . . " was written to assist infertile couples
in evaluating their options with regard to the various advanced
fertility procedures.
In 1998, Dr.
Sher separated from PFMC to found the Sher Institute
for Reproductive Medicine (SIRM), a state-of-the-art facility
that offers advanced fertility treatment and research. SIRM
programs are located in programs in: Las Vegas, Los Angeles, Sacramento,
St. Louis, Central IL, Chicago and soon to be in New York City
(Spring 2004).
DR Sher has
been influential in the births of more than 6,000 of an estimated
100,000 IVF babies born in the United States, to date.
Antisperm
Antibodies in the Man
Return
to StorkNet's interview with Dr. Sher.
Visit
Dr. Sher's home page.
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MALE
FACTOR INFERTILITY: A RATIONAL BASIS FOR TREATMENT
Geoffrey
Sher, M.D.
The treatment
of male factor infertility is one of the true success stories
in the field of reproductive medicine. Disorders of sperm quality
range from a low count or motility to a complete absence of sperm
production. Deformities of the sperm cell shape (morphology) are
also important to its ability to fertilize the egg. Mild abnormalities
of semen parameters can be effectively treated using techniques
that "wash" out the seminal plasma and improve the concentration
of normally shaped motile sperm, which are then transferred to
the uterus via an intrauterine insemination. However, for more
severe conditions this treatment is inadequate. With a total motile
cell concentration of less than 10 million cells per ml or a normal
morphology of less than 4% by strict Kruger criteria, the chance
of fertilization failure is very high, even with IVF. Effective
Treatments for Male Infertility are:
- Hormonal
Therapy (Clomiphene, gonadotropins, corticosteroids, thyroid
hormone)
- Non-Hormonal
Drug therapy (bromocryptine, antibiotics)
- Surgery
(varicocelectomy, vasectomy reversal, surgical treatment of
undescended testes etc.)
- IVF-Related
procedures ( intracytoplasmic sperm injection (ICSI), Testicular
sperm extraction (TESE)
As a general
principle, if the male factor cannot be reversed in the man's
body, by simple medical or surgical treatment, then IVF with ICSI
represents the only rational approach and as stated below, the
results are excellent. Intrauterine insemination is not an effective
way of treating mild to moderate male infertility.
The Use
of Hormonal Therapy
In a relatively
small number of cases of male infertility, the failure to produce
an adequate quality of sperm relates to reduce secretion by the
pituitary gland of those hormones necessary to stimulate sperm
production. The pituitary gland in the man produces two important
hormones with regard to testicular function. The first is called
follicle-stimulating hormone (FSH), and the second is luteinizing
hormone (LH). Luteinizing hormone's predominant function is to
act on a particular variety of cells in the testicles that produces
the male hormone testosterone. These cells are referred to as
Leydig cells. A sustained reduction in FSH production, therefore,
is capable of resulting in male infertility. Usually, if there
is a reduction in either one of the components, LH or FSH, the
other one will also be low. In other words, if a man produces
a normal amount of LH and has a normal blood male hormone (testosterone,
androstenedione, dehydroepiandrosterone) level, it is very unlikely
that he will have a reduced FSH production, and, accordingly,
if his sperm function is reduced, it is unlikely to be the result
of reduced FSH production by the pituitary gland.
The woman's
cycle usually lasts about 28 days, and under normal circumstances,
she releases one egg per menstrual cycle. In the man there exists
an a cyclical production of spermatozoa. In fact the entire spermatogenic
cycle, from initiation to the production of the most mature forms
of spermatozoa, takes approximately 100 days. Accordingly, any
treatment administered to the man in order to improve sperm production
can only be properly assessed after waiting for a period of approximately
100 days. In the man, as with the woman, the pituitary gland releases
FSH and LH in response to need. In other words, is there is an
abundance of male hormone being produced? Then, the pituitary
gland, through messages received from higher centers in the brain,
reduces its production of LH. This push-pull mechanism is referred
to as a feedback response, helps the body regulate exactly how
much stimulation is needed to keep normal testicular function
going both with regard to the production of male hormones and
with regard to the production of spermatozoa.
In order to
assess the potential of a male to respond to fertility drugs aimed
at stimulating the testicles to produce more spermatozoa and/or
male hormone, it is therefore necessary to first measure both
FSH and LH which are produced by the pituitary gland, as well
as prolactin and the male hormones testosterone, androstenedione,
dehydroepiandrosterone. Measurement of these hormones gives an
indication as to the likelihood of the man responding to treatment
aimed at: 1) inducing increased production of FSH or FSH/LH (
e.g.; clomiphene citrate) or, 2) the direct administration of
gonadotropins which comprise of FSH, LH or HCG [e.g. Pergonal,
Repronex, Bravelle, Follistim, Gonal F and/ or Profasi (HCG)]
- Clomiphene
Citrate: (The first approach) Clomiphene citrate is
a hormone which, through its central action in the brain, stimulates
the pituitary gland to produce natural FSH in large amounts.
The FSH, in turn, as mentioned above, stimulates spermatogenesis.
The treatment is very simple, and involves the administration
of 1/2 (25 mg.) of Clomiphene citrate every alternate day for
a period of 100 days, to perform a baseline semen analysis,
FSH, LH, and male hormone measurements immediately prior to
initiating therapy, and then to serially repeat all of these
tests throughout the treatment with Clomiphene. The final assessment
of response can only be made approximately 100 days after initiating
therapy. This administration of Clomiphene is essentially harmless
to the man. He may experience some minor side effects such as
spots in front of the eyes, dryness of the mouth, headaches,
slight changes in mood, and, rarely, hot flashes. These side
effects are all reversible upon discontinuation of therapy.
- Gonadotropin
Therapy: In cases where Clomiphene therapy fails to
be successful, or in certain situations where it is not possible
for Clomiphene to stimulate the pituitary gland into action,
it is possible to administer FSH alone or in combination with
LH in the hope of stimulating the testicles directly. This therapy,
in certain cases of male infertility, might be combined with
the administration of the hormone human chorionic gonadotropin
(HCG), which is also a natural hormone, which has a function
similar to that of LH. The basis upon which HCG would be administered
would be in order to further stimulate the production of male
hormones in cases where failed masculinization is associated
with reduced sperm production. Administration of these drugs
is usually carried out 3 times per week, again for a period
of about 100 days, and the same hormonal and sperm assessments
as stipulated for Clomiphene therapy would apply. The treatment
is, again, relatively harmless, and the minor side effects which
might occur are all reversible upon discontinuation of therapy.
- Other
hormonal therapies: There is very little evidence that
the administration of vitamin preparations or specific male
hormone administration would be of benefit in the treatment
of male infertility. In come cases, there may be systemic conditions
affecting other areas of the body which indirectly might impact
upon the pituitary gland's ability to produce the hormones necessary
to stimulate testicular function. Rare examples include administration
of Thyroid Hormone in cases of involvement of the thyroid gland,
severe diabetes mellitus, and collagen diseases amongst others.
Sometimes the pituitary gland produces too much prolactin, which
in turn inhibits the ability of FSH and LH to act on the testicles.
In such cases, it may be necessary to administer a drug called
Parlodel (Bromocriptine) to suppress prolactin production, and
thereby remove the restraining effect that prolactin might have
on the action of FSH upon the testicles. There are, of course,
many other such examples of where treatment of unrelated conditions
might improve overall male fertility, Testosterone is only mentioned
because it is prescribed so often to try and improve sperm function.
Such treatment is in fact contraindicated because prolonged
use (more than 2-3 months) of testoserone will almost always
have the reversed effect, compromising sperm count, motility
and even morphology.
If the man
is fortunate enough to respond to one of the above treatment modalities
for enhancement of sperm production, then it is possible for a
number of masturbation specimens of sperm to be collected and
frozen in liquid nitrogen in order to be kept for a number of
years so that there will always be relatively good quality sperm
on hand, even if the fertility treatment is discontinued, and
you revert back to a relatively poor production of sperm subsequently.
It is, of course, not practical to permanently treat an individual
on potent medications such as Clomiphene, or gonadotropins.
In Vitro
Fertilization
Intracytoplasmic
Sperm Injection (ICSI): Although always a treatment of
choice for male infertility, it was not until the introduction
of ICSI in the mid 1990's that IVF became more successful
when applied in cases of male infertility than for female related
causes. ICSI is a procedure where fertilization is achieved through
the direct injection of a single sperm into the substance of each
mature egg. Even high concentrations of anti-sperm antibodies
attached to the sperm ( see below) or severe sperm defects such
as absence or abnormalities of the acrosome (the enzyme-rich attachment
at the top of the sperm-head, that enables the sperm to penetrate
the zona pellucida ["the envelopment of the egg"]),
are offset by ICSI.
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The performance
of ICSI in cases of "male factor infertility" has been
shown to slightly increase the risk of certain embryo chromosome
deletions (leading to a slight increase in early miscarriages)
as well as the potential for a resulting male offspring to have
male infertility in later life. However, there is no evidence
of any significant increase in the incidence of serious birth
defects in ICSI-offspring. More relevant is the fact that when
ICSI is performed for indications OTHER THAN male infertility
there is no reported increase in the risk of subsequent embryo
chromosome deletions, miscarriages or in the incidence of subsequent
male factor infertility in the offspring.
Testicular
Sperm Extraction (TESE) is a procedure
involving the introduction of a thin needle directly into the
testicle(s), under local anesthesia, without making a skin incision.
Hair-thin specimens of testicular tissue are removed (usually
under local anesthesia) in the space of 15 to 30 minutes. Sperm
are extracted from the tissue and each egg is injected with a
single sperm using the ICSI technique. It is most commonly done
in cases of spermatic duct (vas definers) occlusion or absence
but can also be performed in cases of ejaculatory dysfunction,
such as might occur following spinal cord injuries, after prostatectomy,
or in cases of intractable male impotency. TESE is simple, relatively
low-cost, safe, and virtually pain-free. Most men can literally
take off a few hours for the procedure and return to normal activity
straight away. Aside from the remarkable success rates with TESE/ICSI
is the fact that, unlike vasectomy reversal, the procedure allows
the man to retain his vasectomy for future contraception.
Diagnosing
and treating the causes of azoospermia (absence of sperm in the
ejaculate): The Work-up includes semen cultures, and blood
tests for Chlamydia antibodies, measurement of FSH/LH and Testosterone
blood levels and selective testicular biopsy to confirm the diagnosis
and plan treatment. If the FSH/LH is high (much over 12MIU/ml)
then it is likely that this is a testicular failure and probably
little could be done to improve matters. If the FSH/LH levels
are in the normal range (4-9 MIU/ml), especially if the testosterone
blood level is also normal... it obstruction of both sperm ducts
(vasa deferentia) becomes a distinct possibility. Confirmation
would require a thorough urological exam) and treatment would
be TESE/ ICSI. If the FSH/LH is on the low side (<4MIU/ml),
especially if this is accompanied by a blood testosterone level
below normal, it is suggestive of under-stimulation of sperm production
and could be amenable to improvement through stimulation with
Clomiphene or gonadotropins.
Sperm
DNA Integrity Assay (SDIA):
The Sperm DNA Integrity assay (SDIA) like the Sperm Chromatin
Structure Assay (SCSA) is a tool for measuring clinically important
properties of sperm nuclear chromatin integrity. The results correlate
well with the potential of sperm from a given male to produce
embryos that would be sufficiently competent to produce
a live birth. The SDIA utilizes the metachromatic features of
acridine orange (AO), a DNA probe, and the principles of flow
cytometry (FCM).
SDIA data
are not well correlated with classical sperm quality parameters
and have been solidly shown to predict sub/infertility and poor
reproductive performance. The SDIA measures DNA damage. The degree
of abnormalities in the genetic material of the sperm is expressed
numerically as the DNA Fragmentation Index (DFI). DNA damage may
be present in sperm from both fertile and infertile men. Therefore,
this sperm DNA damage analysis may reveal a hidden abnormality
of sperm DNA in infertile men classified as unexplained based
on apparently normal standard sperm parameters. Infertile men
with abnormal sperm characteristics exhibit increased levels of
DNA damage in their sperm. Sperm from infertile men with normal-appearing
sperm may have DNA damage to a degree comparable to that of infertile
men with abnormal-appearing sperm. The data suggests that an abnormal
SDI assay is more likely to occur in cases of abnormal semen parameters.
Thus the assay is ideally suited to fertility clinics to assess
male sperm DNA integrity as related to fertility potential and
embryo development as well as effects of reproductive toxicants.
Since SDI/ SCS assay parameters are independent of conventional
semen parameters, results may allow physicians to identify male
patients for whom IVF and intracytoplasmic sperm injection ( ICSI)
will be far less likely to result in initiation of viable (>12
weeks) pregnancy.
Cancer treatments
are well known to adversely affect male fertility. Reduction of
sperm output arises from the cytotoxic effects of chemo-or radiotherapy
upon the spermatogenic epithelium. However, even if the epithelium
survives there is a hazard to reproduction as the transgenerational
in expression and present with effects ranging from infertility
to miscarriage and there is an association with infertility and
reproductive performance. Optimal sperm chromatin packaging seems
necessary for full expression of the male fertility potential.
SDI assays emerge as predictors of the probability to conceive
and carry the pregnancy to viability.
The improvement
seen in sperm motility after sperm separation and Percol processing
is not associated with a similar improvement in sperm DNA integrity
(SDIA assay results). These data suggest that sperm processing
techniques will not minimize sperm DNA damage and the potential
transmission of genetic mutations in assisted reproductive cycles.
It is important
to add that most current data available on the significance of
abnormal SDIA results in infertile couples seeking treatment has
emanated from non-IVF pregnancies. Within a few months a large
data base of information on the clinical role of the SDIA in patients
undergoing IVF will be available through research currently underway
at our Institute. In the interim, our preliminary data suggests
the following:
- The viable
(>12 weeks) IVF pregnancy rate (and thus presumably also
the birth rate) could be as much as 2 times lower in women under
33 years of age, whose husbands have abnormal SDI assays (with
a DFI of <30%). Results become progressively worse with advancing
maternal age such that at 35 yrs+, the viable pregnancy rate
could be as much as 3-4 times lower.
- Although
it is possible for abnormal SDIA results to sometimes spontaneously
revert back to normal, this probably occurs quite infrequently.
- Although
abnormal SDIA results are detected in men with apparently normal
semen analyses, abnormal results are more commonly seen in cases
of men who have abnormal sperm parameters (abnormal sperm count,
motility and/or morphology).
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There
is some suggestion that the use of antioxidant therapy (Pycnogenol
200mg daily, L-Carnitine 3 grams per day, acetyl carnitine
500mg per day, Vitamin C 1,000mg per day and Vitamin E 800IU
per day) taken for 6-8 weeks, can causes the SDI assay to
revert to normal in many cases. There is some suggestion that
men who have varicoceles (a collection of distended veins
in the scrotum) associated with an abnormal SDI assay may
experience a reversion of the SDI assay back to normal, 3-6
months following surgical or radiological ablation of the
varicocele.
In summary,
an abnormal SDI assay augers poorly for the outcome of fertility
treatment in general and IVF/ICSI in specific. In such cases,
the fertilization rate and pregnancy rates are reduced and the
chance of early pregnancy loss appears to be increased significantly.
An abnormal SDIA result does not totally preclude a successful
pregnancy. The prognosis worsens progressively as the age of the
egg provider advances beyond 33 years. Although abnormal SDIA
results rarely revert to normal spontaneously this can and does
happen on occasion. Selective surgical ligation of a varicocele
and medical anti-oxidant treatment may be effective in restoring
the SDIA to normal.
If in spite
of treatment (which presently should be regarded as
being in the "investigational realm") an abnormal SDIA
result fails to revert to normal, the use of donor sperm should
be seriously considered, especially where the egg provider is
over 35 and facing a "rapidly ticking" biological clock.
Antisperm
Antibodies in the Man
Immunity to
sperm, whether in the male or female, is not an absolute cause
of infertility. Sperm antibodies reduce fertility, but do not
invariably prevent conception. Rather, the effects are graduated;
i.e., the larger the immunologic response, the less likely it
is that a pregnancy will occur.
Like any other
kind of antibody manufactured by the body, sperm antibodies are
formed in response to antigens. These antigens are proteins, which
appear on the outer sperm membranes as the young sperm cells,
develop within the male testes. Antigens can only stimulate antibody
production when they come in contact with components of the blood.
Under normal conditions, blood and sperm do not mix. Direct contact
between the two is prevented by a cellular structure in the testes
called the blood/testis barrier. This barrier is formed by Sertoli
cells, which abut very closely against each other, forming tight
junctions that separate the developing sperm cells from the blood
and prevent immunologic stimulation. However, the blood/testis
barrier can be broken by physical or chemical injury or by infection.
When this barrier is breached, sperm antigens escape from their
immunologically protected environment and come in direct contact
with blood elements that launch an immunologic attack.
In the female's
body, deposited sperm are regarded as foreign invader cells and
as such would normally be targeted for attack and destruction
by circulating antibodies. Yet sperm, which are immunologic aliens
to the woman, do not usually cause an antibody response. Although
usually exposed to billions of sperm during her lifetime, few
women develop sperm antibodies. Why this is so is not well understood.
It is known that the cellular construction of the vagina provides
a physical barricade somewhat similar to the blood: testis barrier
in the male. Here, too, physical damage or infection will increase
the likelihood of sperm and blood mixing and subsequent antibody
production.
Once sperm
and blood come in contact, whether in the male or female, specific
antibodies are produced against them by specialized blood cells
called T- and B-lymphocytes. The three main types of sperm antibodies
produced are Immunoglobulin G (IgG), Immunoglobulin A (IgA) and
Immunoglobulin M (IgM). These antibodies bind to the proteins
(antigens) on the sperm head, midpiece or tail. The antibodies
formed may be of the circulatory type (in the blood serum) or
secretory type (in the tissue). This is important because high
levels of antibodies in the blood do not always mean that antibodies
will find their way to the semen where they can affect the sperm.
For example, the concentration of IgG is much lower in secretions
of the reproductive tract that it is in the blood. Conversely,
the local level of IgA is higher in the reproductive secretions
than in the blood. This is an important point, which we will return
to later.
Once sperm
antibodies have formed, they can affect sperm in several different
ways. Some antibodies will cause sperm to stick together (agglutinating
antibodies). Agglutinated sperm clump together in huge masses
and are unable to migrate through the cervix and uterus. Other
antibodies mark the sperm for attack by Natural killer (NK) cells
of the body's immune system (opsonizing antibodies). Some antibodies
cause reactions between the sperm membrane and the cervical mucus
preventing the sperm from swimming through the cervix (immobilizing
antibodies). Antibodies can also block the sperm's ability to
bind to the zona pellucida of the egg, a prerequisite for fertilization.
Finally, there is evidence that the fertilized egg shares some
of the same antigens that are found on the sperm. It is possible
that sperm antibodies present in the mother can react with the
early embryo, resulting in its destruction by phagocytic cells.
There are
a number of diagnostic tests available to detect the presence
of sperm antibodies. These are flow cytometry and the ELISA (enzyme-linked
immunoabsorbent assay), the Franklin-Dukes sperm agglutination
assay or the Immunobead Binding Test (IBT), to name a few. At
the Sher institute For Reproductive Medicine (SIRM), the Indirect
Immunobead Binding Test (IBT) is used to detect antibodies present
in the blood serum, in cervical mucus or on the sperm surface.
All patients at SIRM are screened for sperm antibodies in the
blood serum. If that test is positive (that is, antibodies are
present), a second direct test is sometimes recommended to determine
if antibodies are present on the surface of male's sperm or in
the secretions of the female's cervix. As mentioned earlier, certain
antibodies are more likely to be found in some parts of the body
than in others. The presence of high levels of antibodies in the
serum does not invariable mean that they will find their way to
the semen or cervix. Antibodies present in the serum will have
little effect on fertility if they are not also present where
sperm are manufactured (testes) or deposited (cervix).
IgA is the
most common antibody in secretions of the cervix, uterus and fallopian
tubes. IgG may also be present, but IgM is found only rarely.
In the male, IgA and IgG are found in the semen although there
is controversy as to whether they originate locally (secreted
by testicular cells) or cross over from the circulation. Antibodies
of the IgM class are not found in semen.
Like the source
of some antibodies, the question of the critical levels of sperm
antibodies is also hotly debated among clinicians. There seems
to be general agreement that blood serum levels above 40% by the
IBT are associated with significant fertility problems.
Once an
antibody problem has been identified, there are generally 3 options:
- In some
patients, the administration of corticosteroids (prednisone)
to temporarily suppress antibody production. Pregnancy rates
are poor and steroid treatment carries with it the risk
of significant side effects. Spontaneous fractures have been
reported in 2 - 4% of cases. As such, we do not routinely recommend
this treatment.
- The
best option is a form of in vitro fertilization (IVF) known
as intracytoplasmic sperm injection (ICSI) where each egg is
injected with a single sperm), high pregnancy and birth rates
have been reported.
Other treatments
for sperm antibodies such as prolonged use of condoms or antibiotic
therapy have also proven to be of no value in increasing the chances
of pregnancy in antibody-positive couples.
Sperm antibodies
occur in about 7% of infertile women and are even more common
in men, especially those who have previously undergone reproductive
surgery such as vasectomy or vasectomy reversal. In fact, when
vasectomy has been performed more than ten years prior, more than
was >70% of such men will have high concentrations of sperm
antibodies representing a severe form of male infertility.
ICSI, has optimized IVF pregnancy in cases of male
immunologic infertility, to the point that success rates are virtually
unaffected by the presence or concentration of antisperm antibodies.
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