immunologicalinfertility

Traditional Chinese
Medicine Articles

The articles below are for educational purposes and not for self
diagnosis and treatment. Please see a professional for a
proper assessment and treatment.

Immunological Infertility - An Integrative Approach
Recently, there has been a lot of discussion about the role that the immune system plays in
fertility. The immune system generally works to protect the body from foreign cells and bacteria.
Sometimes though, problems within the immune system prevent it from working properly. Many
couples facing infertility issues may actually have immune system dysfunction, which is
preventing them from conceiving. Up to 20% of couples with unexplained infertility are
actually suffering from an immune system dysfunction.
In the infertile population as a whole, antisperm antibodies (ASAB) occurs in 5–10% of
individuals (men more than women), but they are also present in about 2% of fertile men,
most commonly IgG and IgA. IgM antibodies, because of their size, are rarely found in semen
and if present may be associated with infection. Sperm bound IgA antibodies are associated with
poor cervical mucous penetration, but this is not the case with sperm bound IgG antibodies. The
presence of sperm antibody in the serum of either partner is probably associated with impaired
fertility, but the case has not been proved, so that routine testing for serum ASAB, although
widely practiced, is not recommended. Immunobead testing (IBT), however, against IgA and
IgG in semen is recommended, although differences in analytical practice render comparisons of
test results between centers unreliable. Assays that only identify serum ASAB may not be
optimal, because antibodies, in the male genital tract, may be of primary importance. Semen
screening for antibodies is performed on fresh samples and makes use of either the IBT method
or the mixed antiglobulin reaction (MAR) test. The sample must contain at least 100
spermatozoa with progressive motility and the mucous, debris, and bacteria content must not be
so high as to interfere with these tests. There is no gold standard for the diagnosis of
immunological infertility but the mixed antiglobulin reaction test (MAR test) is probably the
first method of choice. This test identifies IgG on the spermatozoa. This is considered to be an
adequate routine screening test because IgA antibodies almost never occur without IgG
antibodies. Severely oligozoospermic and/or samples with greatly reduced motility are unsuitable
for testing. The test is considered positive if 50% or more sperm have blood cells attached and
weakly positive if 10–50% of the sperm have blood cells attached. In a negative test the sperm
should swim freely between the aggregation of red cells. If the red cells do not
aggregate together, then the test is invalid and should be repeated. The test is considered of
clinical relevance when 50% agglutination is present. The IBT is one of the most widely used
tests to detect ASAB, directly on sperm or indirectly in seminal plasma, cervical mucous,
follicular fluid, and serum. The presence of IgG, IgA, and IgM antibodies on the sperm surface
can be assessed simultaneously with this test. The test is considered to be positive when 20% or
more of motile spermatozoa have immunobead binding, but only clinically relevant when 50%
or more of the motile spermatozoa have antibody bound to them [1].
Antisperm antibodies are one immune factor, which could be involved in infertility. Antisperm
antibodies are cells that fight against normal, healthy sperm. If antisperm antibodies are
present, instead of seeing sperm as natural cells, the immune system fights against the sperm and
destroys them. This prevents the production of any viable sperm. Though still to be proven, there
is evidence that antibodies against sperm can result in male infertility. Antisperm antibodies can

really impair the function of healthy sperm. These antibodies attach to sperm, reducing motility
and making it more difficult for sperm to pass through cervical mucus. Antisperm antibodies
can also force sperm to clump together, making it difficult for sperm to fertilize an egg.
Laboratory studies have shown that sperm density, sperm mobility, the number of while cells,
and pyocytes are closely related to the positive rate of antisperm antibodies, the lower the

sperm density and sperm motility are the more white cells and pyocytes there are, the higher the
positive rate of antisperm antibodies. The male gonadal inflammation and urethra infection are
the most common causes that lead to the positive rate of antisperm antibodies. Men who have
experienced the following are at increased risk for developing antisperm antibodies: vasectomy
reversal, testicular cancer, testicular biopsy, varicocele, testicular torsion, and infections [2].
Ejaculate quality may limit male reproductive success, and consequently, sperm quality is of
importance. Spermatozoa are perceived as "non-self" by the immune system and are exposed to
immunological attacks in the male reproductive tract. To reduce immunological reactions
against their own sperm, males are dependent on the testis being an immunoprivileged site.
Immunoprivilege is obtained by the blood-testis barrier and by local immunosuppression by
androgens. Despite this testicular immunosuppression, an influx of leukocytes may occur in
testes. The condition in which males have a heightened level of leukocytes in semen is called
leukocytospermia, and it is associated with reduced fertility. As the ability of
immunosuppression by androgens may depend on current intensities of infectious organisms in
the extratesticular soma, only males with high parasite resistance may be able to bear the cost of
immunosuppression and consequently produce high quality ejaculates. This issue is addressed by
a meta-analysis on the effects of broad-spectrum antibiotic treatment of male leukocytospermia-
associated infertility. The analysis showed that antibiotic treatment of leukocytospermic men,
without diagnosed genital tract infections, resulted in a significant improvement of ejaculate
quality, that is, an increase in ejaculate volume, sperm concentration, number of motile
spermatozoa, and number of spermatozoa with normal morphology. Moreover, the amount of
leukocytes in semen was also reduced. This suggests that broad-spectrum treatment targeted
toward bacterial infections reduces the density of leukocytes in semen and, at the same time,
improves the quality of ejaculates produced. Our results emphasize the importance of parasitic
resistance and immunity as factors that cause variations in ejaculate quality [3].
Sometimes, women can develop antisperm antibodies. About 5% of women with unexplained
infertility have these antibodies in their blood stream, As a result, sperm are killed before they
have chance to fertilize the egg. When a woman becomes pregnant, her body is being invaded by
something foreign. Alloimmune origins of pregnancy loss occur when the mother rejects fetal
tissue a foreign. Nature has devised schemes whereby the mother produces antibodies to the
fetus and miscarriage, can follow [4].

In some cases, the woman actually produces antisperm cells, which attack the sperm as it enters
the vagina in the same way T cells attack germs in the bloodstream. For any woman to
conceive and carry a fetus to term, there must be a natural suppression of her T-helper immune
response. However, overriding this suppression can cause the embryo or fetus to abort. In the
abnormal cases the immune system has lost it’s ability to discriminate between what is safe and
what is harmful, in this case the sperm, the foreign invader. In some cases, a woman’s cells
produce a kind of cytokine protein that literally kills the developing embryo. Antibodies
attacking the hormones and neurotransmitters, elevated FSH, natural killer cells, lupus
anticoagulant, and other clotting factors causing vascular and blood flow abnormalities are
other markers. Nearly half of the women who have experienced three or more miscarriages are
found to be manufacturing a group of antibodies called antiphosholipid antibody (aPL), or
lupus anticoagulant, lupus inhibitor or anticardiolipin antibody. Women with these antibodies
are prone to blood clotting in the placenta, creating a high risk of fetal death, especially later
on in the pregnancy [4].

Premature ovarian failure or POF is another hormonal disturbance due to the presence of anti-
thyroid antibodies in the bloodstream, which is an indication of hypothyroidism, and accounts
for 23 to 35 percent of recurrent miscarriages. Endrometrial glandular development arrest is
another immunlogic reproductive response, which the uterine lining fails to respond adequately

to the signals of the rising progesterone. In order to prepare for ovulation and implantation,
inflammatory cells are needed to help prepare the endometrial lining for implantation. Without
a working immune system, normal reproduction can be affected, preventing pregnancy. Women
who often present with migraine headaches associated with endometriosis indicate an
autoimmune reaction within the blood vessels [5].

The female’s inflammation of the genital duct, increase in local exudates, the immune correlated
cells enter the genital duct, and at the changes of mucosal osmosis of the genital duct enhances
the absorption of spermia antibody, and as natural adjuvants, the infective agents like bacteria
and viruses, strengthen the immune response of the human body to antibodies. Therefore,
antisperm antibodies appear in the local area of the genital duct and the in the serum, which
affects the activity of the spermia, and interferes with fertilization, and infertility occurs. Zona
pellucid immunology is the human body is invaded by an antigen which cross reacts with
pellucid zone, or the degeneration of pellucid zone caused by infective agents stimulate the body
to produce anti-pellucid zone, and blocks the fertilizing process, and results in infertility [6].

Any man can potentially develop antisperm antibodies, as can any woman, so couples facing
infertility should be tested for the antibodies. However, certain people are more at risk of
developing these antibodies. There are a variety of tests that can detect the presence of
antisperm antibodies in the body. In women, blood tests are commonly used to detect the
antibody. The post-coital test can detect the presence of antisperm antibodies in a woman's
cervical mucus. In men, sperm testing is the best way to analyze for antisperm antibodies. The
immunobead assay and the mixed agglutination reaction test are both used. There are a variety
of treatments available to help couples struggling with antisperm antibodies to conceive.
Corticosteroids help to decrease the production of antisperm antibodies. Unfortunately,
corticosteroids are associated with side effects, including hipbone damage. IUI can help
couples to overcome antisperm antibodies as it allows sperm to bypass the cervical mucus.
Fertility drugs can also be used.   IVF is the most successful treatment for couples with
antisperm antibodies. This allows the sperm to be directly injected into the egg, without having
to travel through the uterus and fallopian tubes [7].

Research
Receptors for the Fc region of the immunoglobulin G (IgG)(Fc gamma R) have been recognized
as a link between humoral and cellular immune responses. A soluble form of Fc-yRlII (CD16)
has been found in seminal plasma (SP), which may modulate immunosuppression of antisperm
immune responses in the male and female reproductive tracts. SP from some individuals
apparently have lower levels of Fc’yRlIl, but it is not known whether the diminished activities
are due to low receptor concentration or steric interference from IgG. To test the hypothesis that
different levels are due to steric interference, relative levels of Fc’yRlII were measured in SP
using monoclonal antibody 3G8 in an amplified enzyme-linked immunosorbent assay (ELISA)
system. Men who were positive for antisperm antibodies (ASA) by Sperm Mar and direct
immunobead assay(N= 26)and negative for ASA(N= 26)were tested. Individuals who were ASA
positive had lower detectable levels than those who were ASA negative (t = 1 .99, P = 0.05).
Therefore, variation in Fc’yRlll levels may be due to steric interference from IgG. IgG subclass
concentrations in SP of both groups were determined using an ELISA method and compared to
Fc-yRIIl levels. Slight correlations were seen for IgG1 (tı = 0.237, P < 0.001), IgG2 (tı =
0.204, P < 0.001), and total IgG (tQ = 0.299, P < 0.001) in relation to Fc-yRIII levels in ASA-
negative SP specimens. We conclude that ASA-positive SP has lower detectable levels of Fc’
yRIlI and that some variability in ASA-negative SP can be attributed to variance in IgG
subclass levels, especially IgGi and lgG2. Therefore, we can conclude that lower levels of
FcıyRlIl in some SP specimens are due to steric interference from IgG8.

Male immunological infertility was diagnosed when mixed antiglobulin reaction to IgG was
positive. IUI is significantly better than limited intercourse with prednisolone (11). IUI is an
effective method, results are obtained rapidly & steroid side effects can be avoided. IUI
significantly improved pregnancy rate (PR) when used as an adjuvant therapy to cyclical dose
steroid therapy [9].
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TCM Point of View
In TCM Wei Qi is inadequate in people with weak immune system, and is often related to Kidney
Yang deficiency. Sleep is of utmost importance in nourishing the blood and yin of the liver,
kidney yin, yang, and jing. The body and mind must at complete rest to restore the essential
energy. Other factors such as a poor diet, excessive stress, too little or excessive physical
activity all effect the immune system. Practices such as Tai Ji Chuan and Qi Gong strengthen
the Yuan Source Qi, and relax the mind, regulate the qi and blood, as well as the regulating all

the internal organ functions, and boost the immune system. Poor diet damages the spleen, and
the spleen is the source of the qi, and blood. If spleen qi is damaged, it cannot perform T&T
leading to damp accumulation, and furthermore is unable to produce the material for the
production of blood. Too many sweet, spicy, greasy, fat, fried foods can also lead to damp
accumulation and damaging the spleen.
In TCM what matters is the process which results in problems with the immune system, and focus
on treating the root problem and treating the body as a whole, which will cause the
immunological markers to correct themselves.
According to Randine Lewis, in the TCM point of view immunological factors hostile to
pregnancy may be caused by imbalances in levels of heat and or damp, blood flow, ying and
yang disharmony or in the level of qi energy. TCM differential diagnosis is used to diagnose
excesses and deficiencies, and a treatment plan based on the diagnosis is chosen to balance the
body as a whole. Lewis further states that our immune system originates in the kidneys and the
liver, therefore basic tonification of the immune system must begin with the kidneys with such
points as Kid 3, Kid 7, Liv 14, Ub 23, Ub 52, and Du 4. The Chong meridian is responsible for
circulation of the elements of the immune system circulation and points such as St 30, Sp 4, and
Pc 6 can activate the immune cells. The nourishment of the immune system is the spleen’s
responsibility and points such as St 36, Ren 6, and Ren 12, can achieve this purpose. The
immune cells disrupting, and creating energetic blockages in the uterus normal function of
receiving the embryo can be neutralized and be moved out by using points such as Ub 23, Kid
16 and St 30, along with other points based on pattern differentiation. Herbs such as Dang Gui
(Angelica) and Chuan Xiong (Ligusticum) are indicated in cases with blood stasis in the uterus
in early pregnancy.
Other autoimmune reactions and patterns according to Lewis include antibodies affecting the
seritonin circulating in the blood, and common signs and symptoms associated with this
imbalance include body aches, increasing depression, irritability and PMS, early morning
insomnia, night sweat especially of the breast bone area, panic attacks, thin uterine lining of
less than 8mm on days 13 or 14, poor response to high levels of FSH, and hormone levels
crashing

in mid cycle. These symptoms are translated into liver qi stagnation, and yin deficiency with

heat in the heart and liver in TCM. These symptoms are further complicated by irregular
menstruation, and a sawtoothed, erratic BBT graph. Women with this condition should pay
special attention in practices to calm the shen, along with the same focus with acupuncture and
herbs, diet, and lifestyle changes.
Lastly Lewis states that any immunological issue regardless of the physical or symptomatic
manifestations requires the tonification of the spleen qi. Immunological functions are attributes
of Wei Qi in TCM, which is incorporates the functions of the spleen and lungs. Herbs such as

Huang Qi (Astragalus), Bai Zhu (Atractylodes), Dang Shen (Codonopsis), and Shan Yao
(Dioscorea) can strengthen the Wei Qi. Again, Qi Gong, and diet, and shen calming techniques.
Diest is the most important raw, cold, sweet and fatty foods, wheat, fruit juices, and dairy
products which damage the spleen and produce damp should be avoided.
Pattern Identification In Women
Kidney yin deficiency - the excessive consumption of kidney yin leads jing and blood deficiency
and the imbalance between chong and the ren, and finally the poor nourishment of the uterine
collaterals, causing infertility. Yin deficiency fire leads to heat accumulation in the chong and
the uterous, dysfunction of sexual gland axis and hypophsis-adrenal cortex system. This results
in immune test being positive and no pregnancy long after miscarriage. Deficiency of kidney
yin results in interior heat accumulation disturbing the chong channel and forces the blood to
move, and resulting in menstruation [10]. Other symptoms may include short cycles, profuse

menstrual bleeding, tidal fever, dry mouth, sore throat, constipation, red eyes, dizziness, tinnitus,
low back pain, easily angered. The pulse is thready and rapid, with a thin, red and dry tongue.
Blood Stagnation due to cold – residual blood during menstruation, and in fetal abortion,
infected with pathogenic cold, blood stasis due to cold accumulation, and obstruction of the
uterine collaterals and blood stops at the uterous with pathogenic cold, and the dysfunction of
the body’s sexual glandular axis and hypophsis-adrenocortical system. It results in immune test
being positive, and non-pregnancy occurs [10].
Phlegm Obstruction – Main symptoms include the inability to conceive after one of unprotected
intercourse, generally overweight, fatigue, general feeling of heaviness, profuse sticky vaginal
discharge. There could also be no other signs and symptoms except this vaginal discharge and
positive sperm antibodies. The tongue will present with a thin white coating and pulse slippery
and fine.
Liver qi and blood stagnation – Infertility after trying for several years, abdominal pain
associated with menstrual flow accompanied by dark clots. Tongue may or may not be dark
with purple spots, and a wiry and choppy pulse
Damp heat – Signs and symptoms may include infertility after one year of unprotected
intercourse, profuse, yellow vaginal discharge, possibly with foul odor, amenorrhea or early
menstruation with irregular flow, and sometime with clots. Other symptoms may include vaginal
or rectal itching, chronic lower abdominal pain which is worse at menstruation, low back pain
with a red tongue and yellow tongue coating, with a thready, slippery and rapid pulse.
________________________________________________________________________

Pattern Identification In Men

Kidney yang deficiency – this gives rise to the hypofunction of the sex gland axis and pituitary
gland-adrenocortical system, which affects the mormal function of organic cellular immunity,
humoral immunity, and reticuloendothelial system, this leading to abnormality of immunoligic
function, along with general kidney yang deficiency signs and symptoms [10].
Kidney yin deficiency – gives rise to abnormalities of the body’s gonad axis and hyophysis-

adrenal gland cortex system can result in hyperimmunologic function, and immunologic test is
positive, along with general kidney yin deficiency signs and symptoms
Damp heat in the liver channel - hyperactivity of body’s immune system or the decrease of the
function of reticuloendothelial system result in immunologic abnormality, and positive
immunologic test. The downward flow of damp heat steaming the sperm storing organs leads to
abnormal spermia, high abnormality rate, or non liquefaction of seminal fluid, these along with
general liver channel damp heat signs and symptoms [10].

Mechanism of Action of Herbs
The mechanism of action of the herbs is not known precisely, and undoubtedly varies according
to the type of infertility problem being treated and the herb formula that is used. The traditional
Chinese views are that infertility tends to arise from one or more of three prominent causes:
1.        A "deficiency" syndrome prevents the hormonal system from properly influencing the
sexual and reproductive functions. This is said to be a weakness of the "kidney and liver" which
may influence various body functions producing symptoms such as frequent urination, weakness
and aching of the back and legs, impotence, irregular menstruation, and difficulties with
regulation of body temperature. Deficiency syndromes are treated with tonic herbs that are said
to nourish qi (e.g., ginseng, codonopsis, atractylodes, astragalus), blood (e.g., tang-kuei, peony
,
ho-shou-wu, gelatin), yin (e.g., lycium fruit, ligustrum, eclipta, ophiopogon), or yang (e.g.,
epimedium, cistanche, cuscuta, eucommia), and are selected according to the overall evaluation
of symptoms.
2.        A "stagnancy" syndrome prevents the sexual and reproductive organs from functioning
despite normal hormone levels and normal ability to respond to hormones. This is said to
involve a stagnancy of "qi and blood," which has the impact of restricting circulation to the
tissues involved. Qi stagnation is often noted by tense muscles, restrained anger, and digestive
disorders; herbs for resolving the stagnancy include bupleurum, cyperus, lindera, and various
citrus products. Other symptoms that might arise include abdominal pain or bloating, chronic
inflammation, and formation of lumps (including cysts and tumors). Blood stagnation often
occurs following childbirth, surgery, injury, or severe infection and is typically noted when there
is severe pain (such as dysmenorrhea), or hard swellings and obstructions; abnormal cell
growth, including dysplasia and cancer, are thought to involve blood stagnation. Herbs such as
salvia, red peony, persica, and carthamus may be used.
3.        A "heat" syndrome, which causes the affected organs to function abnormally. Heat
syndromes may be associated with an infection or inflammatory process. This type of syndrome
can produce abnormal semen quality leading to male infertility, while gynecologic infections
can maintain female infertility by blocking the passages, altering the mucous membrane
conditions, or influencing the local temperature. Herbs that inhibit infections and reduce
inflammation are used, including gardenia, phellodendron, patrinia, and lonicera.
In each case, the purpose of the Chinese herbs is to rectify the underlying imbalance to restore
normal functions. Western medicine can diagnose tubal blockage (which usually corresponds to
blood stagnancy in Chinese medicine) and infection (which corresponds to heat syndromes of
Chinese medicine) and in many cases can successfully treat these causes of infertility. However,
Western medicine often fails to diagnose deficiency syndromes and most of the stagnancy
syndromes. Therefore, the majority of Chinese herb formulas to be applied in the U.S. are those
that counteract the deficiency (called tonics) and those that resolve the stagnancy (called
regulators). A description of Chinese herb formulas used for infertility is presented in the
appendix to Chinese Herbology, a training manual produced by the Institute for Traditional
Medicine [11].

Research
The hormonal effects of Chinese herbs used to treat impotence and infertility and to prevent
miscarriage have been demonstrated in laboratory experiments. For example, the laboratory
evaluation of Huanjing Decoction (composed of rehmannia, ho-shou-wu, ligustrum, morus fruit,
achyranthes, dipsacus, cynomorium, astragalus seed, and cuscuta) was administered to senile
mice for four months, two weeks treatment, and one week of break. Estradiol and
dihydrotestosterone receptors in the nucleus of thymic cells were decreased to levels found in
young mice; cytosol estradiol receptors increased. Also, the formula influenced the immune
system: it increased thymus weight, thymic index, and prevented atrophic changes in the
ultrastructures of thymic lymphocytes and epithelial reticular cells[11].

Dietary and Lifestyle Recommendations
Some health care professionals recommend the use of 300-400mg of para-aminobenzoic acid
(PABA) for the treatment of immunological infertility. PABA has an effect on the production
of red blood cells, protein metabolism, and folic acid in the intestines, and often used in cases
with folic acid production disorders. PABA is found naturally in foods such as liver, eggs, rice,
wheat germ, bran, molasses and dark green vegetables. Antioxidants such as vitamin E, C,
Betacarotene, selenium and zinc, as well as super-antioxidants such as pycnogenol (OPC) found
in extracts such as grapeseed, pine bark, bilberry and red wine. Fish oil keeps the blood clear,
and moderates NK cell activity. The bulk of the patients diet should include whole, organic
foods, including greens, wheatgrass, spirulina, bee pollen, and royal jelly.   Blue green algae
triggers the movement of NK cells from the blood into the tissues. Reishi, and shiitake
mushrooms, and kombucha tea are also effective [12].

The Effects of Medications
Glucocorticoid medications such as cortisone, prednisone, prednisolone, dexamethasone, and
methylprenisolone, inhibit immunologic reactions within the body. These medications are
considered as release the exterior medicinals according to TCM, which can deplete the essence if
used in excess. They cause disturbances in the yang qi, and exacerbate the kidney and spleen qi
deficiency conditions. They lead to water retention, anxiety and insomnia. Long term use of
these drugs may damage the ability to conceive. Long term use of antibiotics, glucocorticoids,
and birth control pills lead to yeast proliferation, which enters the blood and cause endocrine
and immunological problems. In TCM spleen is involved. The consumption of organic
vegetables, brown rice, tofu and tempeh, organic and hormone free meats are dietary
recommendations for yeast overgrowth. Yeast breads, alcohol, vinegar, fermented beverages,
sugar including sugary fruits such as grapes, oranges, strawberries, bananas and fruit juices
should be avoided. Apples and pears are permissible [12].

The Flip Side
At the present growth rate, the world population is estimated to reach a phenomenal 8.9 billion
people by the year 2050, posing a great risk of overpopulation. Therefore, new strategies of
contraception are required. A novel contraceptive strategy that is receiving considerable
attention is that of immuno-contraception. Spermatozoa have proteins that are unique, cell
specific, immunogenic and accessible to antibodies. The targeting of antibodies to gamete-
specific antigens implicated in sperm function, sperm–egg binding and fertilization could block
sperm binding and thus fertilization. The present review highlights the current status, relative
merits and future directions for various sperm-based candidate antigens with regard to the
development of a contraceptive vaccine [13].

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