Posted By Fiona McCulloch, ND,
Thursday, February 7, 2013
Updated: Wednesday, January 29, 2014
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This article was published in the March 2011 NDNR Journal
Infertility is a reproductive disease which has an enormous impact on
the quality of life for millions of patients. It affects 1 in 5 of all
couples, and most patients undergo extensive diagnostic and treatment
interventions on their journey to create a family. Infertility has a
myriad of causes including endocrine disorders, gynecological disease,
infectious disease, circulatory disease and aging and cellular health.
Autoimmune disorders are also implicated in reproductive disorders and
may especially play a role in unexplained cases of infertility.
It is known that autoimmune diseases such as diabetes, autoimmune
thyroiditis and systemic lupus erythematosis are linked to decreased
fertility. Other causes of infertility such as premature ovarian
insufficiency, endometriosis and polycystic ovarian syndrome include
autoimmune components. In many unexplained cases of infertility,
inflammatory processes may be involved or antibodies may be directed
against hormones, clotting factors, or reproductive tissues such as the
ovaries or testes. The research into autoimmune infertility is just in
its beginning, but as naturopathic physicians there are valuable tests
and treatments we can provide to our patients who present either with
known autoimmune disorders and difficulty conceiving, or with the ever
enigmatic diagnosis of "unexplained infertility”.
The biological factors involved in autoimmune infertility are
various. These include a multitude of cellular and inflammatory changes.
Some of the most common factors are discussed below.
Endometriosis has many autoimmune components including elevated
levels of cytokines, and T- and B-cell abnormalities. Peripheral
monocytes are more active, and peritoneal macrophages are present in
higher numbers with higher activity levels. This causes increased
inflammatory cytokine release.
There are alterations in B-cell activity and an increased incidence
of autoantibodies in women with endometriosis. Like classical autoimmune
diseases, endometriosis has been associated with polyclonal B-cell
activation, immunological abnormalities in T- and B-cell functions,
increased apoptosis, tissue damage, multiorgan involvement, familial
occurrence, possible genetic basis, involvement of environmental
cofactors, and association with other autoimmune diseases. TNF-a, levels
are elevated in the peritoneal fluid of patients with endometriosis. In
women with endometriosis, TH2 mediated immunity humoral responses are
A 2001 study found that 50% of endometriosis patients had
autoantibodies to candida enolase. The same study found increased levels
of these antibodies in patients with a list of other autoimmune
Autoimmune thyroid disease and infertility.
Thyroid diseases involving antithyroid antibodies have been
correlated to infertility and increased pregnancy loss. Autoimmune
thyroid disease, even in the absence of hypothyroidism has been
associated with infertility and reduced response to fertility treatment.
It has also been associated with gluten related autoimmunity.
Autoimmune thyroid disease can lead to hypo or hyperthyroidism which can
impact fertility and cause miscarriage.
Other Autoimmune Diseases and Fertility
Antinuclear antibodies (ANAs ) which have been associated with
infertility can be present in conditions such as SLE, Sjogren’s
syndrome, Raynaud’s syndrome, and can also be detected in women with a
history of exposure to chemicals such as bisphenol-A.
Addison’s disease is associated with anti-ovarian antibodies which
can reduce ovulatory function and cause premature ovarian failure in
Patients with celiac disease may have multiple nutritional
deficiencies that can lead to infertility. Celiac disease has been
linked to recurrent miscarriage, pregnancy complication and infertility.
A 2010 study found that between 5-10% of women with a history of
stillbirth, recurrent miscarriage, intrauterine growth restriction, and
infertility were seropositive for transglutaminase IgA compared to 1% of
the control group. Latent celiac disease may be a major cause of
In approximately 20% of women with premature ovarian
insufficiency(POI), autoimmune factors can be found. POI can be linked
to autoimmune thyroid disease, Addison’s disease, or SLE or may have
unknown etiology. Women may have antibodies against the ovarian tissues,
or reproductive hormones such as FSH.
Antisperm antibodies are another cause of infertility. These can be
present in either male or female patients. They are commonly found in
males after vasectomy procedures, and their presence can make vasectomy
difficult to reverse. Antisperm antibodies affect the ability of the
sperm to penetrate the egg or reduce motility by attaching to the tail
of the sperm . They have also been associated with antiphospholipid
antibodies. Antisperm antibodies are generally produced by CD19+/5+ B
cells and are associated with elevated natural killer cells and anti-dna
Autoimmune blood clotting disorders
Disorders with increased antiphospholipid antibodies( APAs) including
anti-cardiolipin antibodies cause a hypercoagulatory state in the blood
and can be associated with reproductive failure and recurrent
miscarriage. These antibodies can be found in systemic diseases such as
SLE, or on their own.
Immunological Considerations for Patients with Reproductive Challenges
A condition of TH1 cytokine dominance can be associated with the
inability to conceive or maintain a pregnancy. In women with high
TH1/TH2 ratios there is an increased incidence of pregnancy loss and
infertility however for different autoimmune conditions the predominant
immune pathway may differ.
Natural killer(NK) cells
Elevated peripheral NK cells are associated with many systemic
autoimmune diseases but can also be found in women with unexplained
infertility conditions. NK cells produce TH1 cytokines including
TNF-alpha and Interferon gamma. These cytokines are normally involved in
cellular toxicity directed at cancerous cells and viruses . If
increased in early pregnancy, the presence of NK cells and their
cytokines can disrupt the growth and development of the embryo.
TNF-alpha works as a signal to other immune cells which then migrate to
the uterus to attack the non-self invader which has been immunologically
detected. A 1999 study found that in women who had repeated
miscarriage, there was markedly increased NK cell cytotoxicity
associated with a rise in CD56+CD16+ and a drop in CD56+ cells. Another
special type of NK cell called uterine NK (uNK) cells have a protective
immunosuppressive effect locally in the endometrium. Dysfunction of
these cells has been associated with pregnancy loss
Homocysteine and Folate Metabolism
folate deficiency and hyperhomocysteinemia are known to be risk factors
for infertility and pregnancy complications. Errors in these pathways
caused by genetic mutations have been associated with autoimmune
diseases Patients with a mutation of the MTHFR gene have difficulty
reducing 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. 5-
methyltetrahydrofolate is used to convert homocysteine to methionine by
the enzyme methionine synthase. A 2010 study on a group of 71 Swedish
and Finnish female patients with unexplained infertility found a higher
incidence of folate metabolism polymorphisms compared to women in the
general population. Folate receptor blocking autoantibodies have also
been related to subfertility
Folate metabolism disorders can can lead to reduced cell division,
inflammatory cytokine production, altered nitric oxide metabolism,
increased oxidative stress, abnormal methylation reactions and
thrombosis. This causes problems with folliculogenesis and implanting or
maintaining a healthy pregnancy. In males, defects in this pathway can
Diagnostic testing in the naturopathic clinic
In addition to general and endocrine panels for infertility, consider
testing for homocysteine, CRP, ESR, ANA panels, APA panels, PTT,
Partial PTT, DHEA-S, TSH, Antithyroglobulin, Antithyroid peroxidase,
HBA1C, CBC, diurnal cortisol, assessments for candida, and gluten
Clinically, I have found that optimal homocysteine levels should be
8mmol/L or below in patients with autoimmune infertility factors.
TH1 to TH2 ratios can be a very helpful tool for designing treatment
plans. NK assays and testing for genetic variants of MTHFR are also
These vary depending on results found and can include low dose
aspirin, anti-coagulants, corticosteroids, IVIG, Lymphocyte immunization
therapy (LIT) and TNF-alpha blockers. These are often combined with IVF
or other assisted reproductive technologies.
Treatments in the naturopathic clinic
Some of the following treatment options may be considered after a thorough assessment determines specific autoimmune factors.
- To reduce TH1 dominant inflammatory responses in patients who
require it, maritime pine extract (100mg bid), resveratrol ,(100mg bid) ,
and green tea EGCG (300mg catechins bid), . Maritime pine, and
resveratrol also inhibit platelet aggregation and thrombosis,,. The
antioxidant effects of these substances are also beneficial.
- Proline rich polypeptides such as those found in bovine colostrum
may favour a shift towards TH1 and downregulate overactive TH2
- High quality omega 3 fish oil. 2 – 3g of EPA and DHA daily to aid
with inflammatory and thrombotic disorders . A 2007 study on mice found
that a ratio of 23:14 EPA to DHA decreased tnf alpha in 8 hours. EPA
also regulates autoimmune markers in endometriosis
- L-5-methyltetrahydrofolate 5mg daily, vitamin B12 1000mcg qd and
vitamin B6 75mg qd to improve homocysteine and folate metabolism. Screen
for history of cancer before using high dose folate. Trimethylglycine
1000mg qd may also be used to lower homocysteine levels in selected
- N-Acetyl Cysteine 600mg bid. Reduces inflammatory cytokines.
Improves autoimmune thyroid disease NAC also enhances semen parameters
and the oxidative status and quality of the endometrium . NAC also
protects the integrity of ovaries subjected to physical and oxidative
damage, and aids liver detoxifcation pathways.
- For patients with thyroid antibodies, l-selenomethionine 200mcg
daily,,,. If hypothyroid, use of bio-identical hormone therapy may be
indicated to prevent miscarriage. Trace minerals for thyroid function
are also be beneficial.
- Thyroid protomorphogen may be useful for patients with antithyroid
antibodies to act as a decoy. Increase dosage slowly to 1 tablet tid.
- Elimination of gluten should be implemented as required for patients with positive serology.
- Probiotics 20 billion CFUs daily. Rotate strains monthly to modulate immunity and repair gut lining. Treat candida if present.
- Support liver detoxification pathways.
- Bio-identical progesterone is a potent immunosuppressive agent
capable of blocking both cytokine release and action . May be used in
the luteal phase of the cycle to support early pregnancy.
- DHEA – can be useful in premature ovarian insufficiency and to
improve pregnancy rate and reduce miscarriage in advanced maternal age.
It has also been found to be beneficial in the treatment of autoimmune
disease,, and to reduce NK cell activity. DHEA should only be used after
serum DHEA-S and androgen evaluation. Dose adjusted according to
patient need but is often 25mg tid or less.
- Addressing stress is very important in all patients suffering from
the effects of reproductive challenges. Autoimmune diseases are
aggravated by stress as it can increase humoral immunity and shift
TH1:TH2 ratios. Adrenal therapies, sufficient sleep, yoga, meditation,
movement therapy, and prayer can all positively effect patients in this
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pathway genes are associated with unexplained female infertility. Fertil Steril. 2010;94(1):130-7.
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with multiple sclerosis in a German case-control study. Neurosci Lett. 2010; 468(3):183-5.
- Safarinejad MR, Shafiei N, Safarinejad S. Relationship Between
Genetic Polymorphisms of Methylenetetrahydrofolate Reductase (C677T,
A1298C, and G1793A) as Risk Factors for Idiopathic Male Infertility. Reprod Sci. 2010 Oct 26 [Epub ahead of print]
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the bark of Pinus maritime on the expression of pro inflammatory
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consumption of the green tea polyphenol EGCG in a murine model for human
Sjogren’s syndrome, an autoimmune disease. Life Sci. 2008 Oct 24;83(17-18):581-8.
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thrombosis and thrombophlebitis in long-haul flights with pycnogenol. Clin Appl Thromb Hemost. 2004 Oct;10(4):373-7
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effect of fish oil intake in humans: modulation of fibrinogen level and
thrombin generation. Arterioscler Thromb Vasc Biol. 2004 Sep;24(9):1734-40.
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supplementation improves vascular function and reduces inflammation in
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- Netsu S, Konno R, Odagiri K, Soma M, Fujiwara H, Suzuki M. Oral
eicosapentaenoic acid supplementation as possible therapy for
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ameliorates the inflammatory disease process in experimental autoimmune
encephalomyelitis in Lewis rats. J Autoimmune Dis. 2005 May 3;2(1):4.
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Posted By ona McCulloch, BSc, ND,
Wednesday, August 3, 2011
Updated: Tuesday, February 4, 2014
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The American Thyroid Association has updated their guidelines for the
management of thyroid concerns in pregnancy, the details of which were
published in the journal Thyroid this past month. Many of us who work
in the field of fertility have long been aware of research suggesting
that ranges for TSH should be lower in pregnancy. It is truly great to
see that this has been formally recognized. Although these guidelines
were written for pregnancy, I also apply these to women with fertility
concerns who are preparing for pregnancy. Prevention is always best
when it comes to avoiding miscarriage.
Thyroid disease is very common in pregnancy. One of the reasons is thatone of the main thyroid hormones (free T4) decreases in pregnancy.Another
reason is that TBG (thyroxine binding globulin) increases during
pregnancy – TBG is a hormone that binds to the circulating thyroid
hormone, making it unavailable to act on receptors. This aggravates
cases of hypothyroidism by binding up the thyroid hormone that would
normally be available to work in the body.
hCG, the pregnancy hormone, has a profound effect on thyroid function too. Normally in pregnancy, hCG causes TSH (Thyroid stimulating hormone) to decrease.
TSH is produced by the pituitary gland and causes the thyroid gland to
make thyroid hormones. So in a healthy pregnancy, we expect a woman to
have a lower TSH than she usually would . This makes high levels of
TSH in pregnancy to be of even more concern and gives us a lower
"normal” reference range for pregnancy. When TSH levels are high, this
indicates that the thyroid function is low, as the pituitary is
attempting to stimulate more thyroid hormone production from the thyroid
Autoimmune thyroiditisis very common in
pregnancy as well. 1 in 10 pregnant women will develop antibodies to
the thyroid. Hypothyroidism develops in 16% of women with thyroid
antibodies. Thyroid antibodies are also associated with lower success
rates in IVF cycles, and increased miscarriage rates, even if there is
no hypothyroidism in the patient. Postpartum thyroiditis can occur in
around 50% of women who develop antibodies during pregnancy.
As you can see, thyroid conditions are a very common health problem,
and have great impact on pregnancies and fertility. Not only is thyroid
disease related to miscarriage, but subclinical hypothyroidism or
positive thyroid antibodies can impact the brain development of the
fetus and have been linked to poor intellectual development in the baby.
Hyperthyroidism is related to miscarriage and a host of problems such
as intrauterine growth restriction. So this is an issue we must take
The new guidelines suggest the following:
- Trimester specific tighter ranges for TSH:
|First trimester normal range
||0.1 to 2.5 mIU/L
||0.2 to 3.0 mIU/L
||0.3 to 3.0 mIU/L
- Women who are already receiving thyroid replacement therapy should increase their dose by 25% to 30% when they become pregnant.
- The total amount of iodine should be 250 ug from all dietary and supplemental sources.
- Monitoring is important to ensure that women with hypothyroidism or
subclinical hypothyroidism are not at risk. TSH should be measured once
every 4 weeks until 16 to 20 weeks’ gestation and at least once between
26 and 32 weeks’ gestation.
Basic nutrition for thyroid in pregnancy
Of note,although our salt is iodized in developed countries, there is a growing deficiency of iodine.This
is because the iodine in our salt supply is not well absorbed and
utilized. In pregnancy, there is a 50% increase in iodine requirements.
So, choose a prenatal with some iodine content, usually around
150-200ug per day. Do not exceed 500mcg total intake daily, as this can
pose an increased risk for hypothyroidism.
Selenium should be part of a prenatal vitamin.
Several studies have shown that selenium decreases the levels of
thyroid antibodies (anti thyroglobulin (anti TG) and anti
thyroidperosidase (anti TPO). A randomized controlled trial found
that supplementing with 200mcg of selenium daily during pregnancy and
the post partum period reduced the incidence of postpartum thyroiditis
in women who were positive for thyroid antibodies. 55 mcg should
suffice as prevention in healthy women.
Perinatal thyroid disease is very common and new research is rapidly
emerging on this topic. Thyroid disease affects fertility, pregnancy,
maternal and fetal health. Women should optimally try to establish
healthy thyroid function before conceiving: this way many concerns can
be prevented, and the health of both moms and babies will be protected.
- Selenium Supplementation in Patients with Autoimmune
Thyroiditis Decreases Thyroid Peroxidase Antibodies Concentrations JCEM
2002 87: 1687-1691
- Guidelines of the American Thyroid Association for the
Diagnosis and Management of Thyroid Disease During Pregnancy and
Postpartum. The American Thyroid Association Taskforce on Thyroid
Disease During Pregnancy and Postpartum. THYROID Volume 21, Number 10,
- Dietary Iodine: Why Are So Many Mothers Not Getting Enough? Renner R 2010. Environ Health Perspect 118:a438-a442.
prevalence of thyroid antibodies in euthyroid women with a history of
recurrent in-vitro fertilization failure Hum. Reprod. (2000) 15(3):
Posted By Administration,
Monday, August 30, 2010
Updated: Friday, April 18, 2014
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by Fiona McCulloch, ND
Top Fertility tests : A Quick Reference for Women from an Integrative Medicine Perspective
FSH – Follicle Stimulating Hormone
Day 3 FSH can indicate how hard the pituitary is working to stimulate the ovaries. Though traditionally a higher FSH is given a poor prognosis, I don’t always see it this way clinically. The FSH can very much change depending on the quality of the antral follicles, which depends on ovarian health over the previous months as well as ovarian reserve. The poorer the quality of the eggs, the more free radical damage they have accumulated and the poorer ovarian blood flow is, the more FSH the pituitary will have to put out in order to stimulate the antral follicles. Healthy follicles are responsive to lower amounts of FSH. If treatments are started to enhance ovarian health over 120 days of folliculogenesis prior to ovulation, the lowered FSH that can result can indeed indicate that the quality of the eggs in the ovaries has increased. Please keep in mind that I have seen many women with high FSH become pregnant when egg quality and ovarian health is worked on so having a high FSH is not untreatable.
|FSH Levels (Day 3)
||less than 6 mIU/mL
||above 13 mIU/mL
LH – Luteinizing Hormone
This is a test which is often done on day 3 of the cycle. If higher than the FSH, especially if higher than a 2:1 ratio, it can indicate polycystic ovarian syndrome. Having a high LH level will result in increased ovarian testosterone production, altered estrogen production, and abnormalities with ovulation. Normal day 3 range : <7 mIU/mL
Measured on day 3 of the cycle. If elevated, estradiol can lower the fsh, thereby masking elevated fsh levels. This can happen in cases of low ovarian reserve or functional cysts. Estradiol can be low in conditions of low ovarian reserve. Women who have estradiol over 294 pmol/L (or 80 pg/ml) have a lower chance of success with an IVF cycle since they will not respond to stimulation as well.
This is often measured on day 21. This is used to determine whether ovulation has occurred as a healthy corpus luteum produces progesterone. It is important to measure progesterone 7 days after your ovulation, measuring on day 21 only applies to women who ovulate on day 14. Levels higher than 16 nmol/L strongly suggest an ovulatory cycle.
Often measured in the morning can indicate the impact of stress on the reproductive system. Elevated cortisol can affect ovarian circulation and function. Normal levels : 250 – 850 nmol/L taken between 6-8am. Low cortisol can be found in congenital adrenal hyperplasia. Normal levels for am cortisol 101-536 nmol/L
The total level of testosterone in the system. If elevated this can indicate polycystic ovarian syndrome. High testosterone can interfere with normal ovulation often causing delayed ovulation or anovulation. Levels can also be low around which can negatively affect ovarian function. Normal levels for females 0.3- 4.0 nmol/L
The amount of testosterone that is not bound to carriers and is available to stimulate tissues. The higher this is, the more androgenic effect on the tissues. This can be elevated in PCOS and specific adrenal conditions such as non-classical congenital adrenal hyperplasia (non classical CAH). Normal levels for females 0.1-8.9 pmol/L
A hormone normally elevated in nursing and pregnancy. If elevated in other situations it can interfere with ovulation and fertility. It can be elevated due to stress, medications such as antidepressants or painkillers, thyroid disease, or pituitary conditions such as microadenomas. normal levels in women 3.3 – 26.7 ug/l.
DHT – Dihydrotestosterone
A form of testosterone which is very potent. DHT Can be elevated in pcos or enzyme conversion disorders resulting in androgen excess signs and symptoms. Serum testing for DHT is often unreliable.
Sex hormone binding globulin
Can be low in patients with androgen excess conditions such as pcos or in hypothyroidism. Can be high in non classical CAH, hyperthyroidism. Normal levels : Follicular phase 24 – 200 nmol/L, Luteal phase 48 – 185 nmol/L
A long termarker of insulin resistance and blood glucose control. Can be elevated in pcos. Marks the previous 3 months of blood glucose control. Normal levels 0.040 – 0.060
DHEA – S
A precursor to hormones, most especially androgens. DHEA is made by the adrenal gland. Levels tend to reduce with age and can be reduced in low ovarian reserve. Levels can be elevated in PCOS. Normal range for women 0-11 µmol/liter
A marker for stored iron. Levels can be low in patients with infertility. I recommend patients to achieve ferritin levels of above 50.
TSH - thyroid stimulating hormone
I like to achieve levels of approximately 2 – 2.5. Levels above this can put the patient at risk for early miscarriage. Normal Ranges are : 0.4 – 4 mIU/L. If levels are above 3, and especially if thyroid antibodies such as antithyroglobulin and anti-thyroid peroxidase are present with signs and symptoms of hypothyroidism, this and may present risks for fertility.
Important for overall health, hormone balance, and stress levels. Normal levels of 1, 25 Hydroxy Vitamin D 40 -150 pmol/L
A marker of inflammation and circulatory health. This test is only recently being found to be important for ovarian health. Elevated levels can be found in autoimmune conditions, ovarian aging and endometriosis. Normal range : 4.7 – 14.1 umol/L
A measure of blood clotting. Blood which clots excessively may interfere with implantation. Can also elevated in endometriosis or fibroids. Normal value for INR 0.9 – 1.2
Anti sperm antibodies
The presence of anti- sperm antibodies in women can destroy or damage the sperm before they have the chance to fertilize the egg. Around 5% of infertile women have these antibodies in their bloodstreams.
Anti thyroid antibodies
These include antithyroid peroxidase and antithyroglobulin. These antibodies, if present will reduce fertility by 13%, even if thyroid function is normal. These antibodies can cause alterations in thyroid function and also can be cross reactive with ovarian tissue. Women with PCOS who don’t respond to clomid have a higher liklihood of having antithyroid antibodies.
Anti nuclear antibodies
These antibodies are present in autoimmune disease such as Lupus and Sjogrens syndrome.
Special Ovarian Reserve Markers:
Antimullerian hormone is produced by growing follicles and prevents premature recruitment of primordial follicles. This value generally correlates with the number of functional primordial and antral follicles remaining in the ovary. Generally, the higher the AMH, the more healthy follicles are in the ovary. Antimullerian hormone can predict the age of onset of menopause with some degree of accuracy. Low AMH often does not give a good prognosis for IVF because IVF is based on the stimulation of multiple follicles – women with lower AMH tend to get fewer follicles during IVF stimulation. However, even if AMH is low, conception is possible. Even if there are not many follicles remaining in the ovary, their quality can be improved with treatments including antioxidants and circulatory enhancing therapies. Natural conception with low AMH can and does happen. Normal ranges :
||28.6 pmol/L – 48.5 pmol/L or over 1.0 ng/ml
||15.7 pmol/L – 28.6 pmol/L or over 1.0 ng/ml
||2.2 pmol/L – 15.7 pmol/L or 0.3 – 0.9 ng/ml
||0.0 pmol/L – 2.2 pmol/L or less than 0.3 ng/ml
|High Level found in PCOS
||> 48.5 pmol/L or over 3 ng/ml
A marker of ovarian function and reserve, this protein is secreted by small developing follicles and works to inhibit FSH levels, hence the name inhibin. This test is completed on day 3 of the cycle. As inhibin is secreted by the follicles, it can indicate the number of and function of the remaining folliciles. This test is not widely available. Normal = above 45 pg/ml Low = below 45 pg/mL Inhibin B is a spectrum however, and this line is a general guideline not a strict cutoff. Like with AMH even if inhibin B is low, conception is possible if the health of the remaining follicles is enhanced.
Mosby’s Manual of Diagnostic and Laboratory Tests. 4th Ed. 2010
Speroff, Clinical Gynecologic Endocrinology and Infertility. 7th Edition 2005.
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Tuesday, July 27, 2010
Updated: Friday, April 18, 2014
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by Hyla Cass, MD
Our mothers once called them "women's problems." Now we know that these mood swings and physical changes, from PMS to menopause, are all part of a delicate balance among our various hormones. In my years of practicing integrative medicine, I have helped hundreds of women overcome PMS and menopausal symptoms naturally, and here's how.
Let's start by defining hormones. They are chemical messengers secreted by any one of the body's endocrine (ductless) glands. They travel through the bloodstream, telling various systems what to do. Besides reproductive functions, hormones affect virtually every body system from digestion to metabolism to hair growth.
All women have the same hormones but in varying quantities, making your own hormonal profile as unique as your fingerprint. When your hormones are in harmony, you will have predictable menstrual cycles --and moods. When out of balance, you will have irregular cycles and a host of symptoms, from bloating, cramps, weight gain and acne to food cravings, irritability and depression. Perimenopause, the transition to menopause, which can start as early as your late 30's, often causes an increase in PMS. In fact, many women report experiencing PMS for the first time at that point. Also common in peri-menopausal women, is a loss of libido, due to a dip in testosterone which governs sexual desire, and of course, those hot flashes and night sweats, which make sex the last thing on your mind!
For a full picture of your hormonal status, we need to check levels of estrogen, progesterone, DHEA-S and testosterone in blood, saliva, or urine, taken on day 19-21 of the cycle. For perimenopausal women, I also order FSH (follicule stimulating hormone) and LH (luteinizing hormone) blood tests to assess ovarian function. I will check cortisol levels (saliva test) and thyroid hormones (blood test), too, since they are a part of the overall hormone symphony.
You can find home testing kits online. Take these tests on days 19-21 of your cycle, with day one being the first day of your period. If you are post-menopausal, it won't matter when you take the tests. If you're irregular, do your best to estimate the appropriate date.
If testing reveals that your hormone levels to be below the normal range, it may be due to perimenopause or other physiological factors. Faced with fluctuating hormones, doctors have traditionally prescribed synthetic hormone replacement therapy (HRT), such as Premarin (from pregnant mares' urine) and Prempro (Premarin plus synthetic progesterone), to correct imbalances. The recent Women's Health Initiative study showed that women taking this form of HRT had 27 percent more heart attacks, a higher rate of breast cancer, 38 percent more strokes and double the number of blood clots. There are safer ways to balance hormones successfully, ranging from supplements and herbs to bio-identical hormone therapy.
Natural Ways to Balance Sex Hormones
The first step to balancing your hormones is a clean diet:
• Eat fewer animal products, with lots of vegetables, including raw broccoli and other
• Reduce or eliminate caffeine, alcohol, nicotine and sugar.
• Reduce or eliminate high-fat dairy products.
• Eliminate as much processed food as possible
• Reduce salt intake.
• Eat small, regular meals.
Yoga and meditation are helpful for PMS sufferers because they work on the nervous system to help balance hormones.
Supplements for PMS:
I give my patients magnesium (100 mg two to three times daily) and vitamin B6 (25-100 mg) to relieve irritability and tight muscles as well as premenstrual water retention.
Another important nutrient is GLA, an omega-6 fatty acid which also helps reduce the water retention, breast tenderness and moodiness associated with PMS, likely by it's action on the hormone prolactin. GLA is found in borage oil (1500 mg of borage twice daily), black currant seed or evening primrose oils.
The herb, Chasteberry (Vitus Agnus Castus), helps to balance the hormone, progesterone, relieving symptoms of PMS and heavy or irregular periods as well. Dose is 50-200 mg daily depending on symptoms. Do not take if you're pregnant.
The herb, Dong Quai, helps to balance the hormone estrogen. Like Vitex, the dose is 50-200 mg daily depending on symptoms and also do not take if you're pregnant.
Another useful nutrient is the amino acid, 5-HTP (5-hydroxytryptophan) 500-200 mg daily, depending on your individual needs. It helps to raise levels of the feel-good and calming brain chemical, serotonin, which is often low in PMS sufferers.
These nutrients plus wild yam a source of natural hormone production, can all be found in the formulation, PMS Balance. I have had many women report almost immediate relief upon taking this or a similar formula. Others may take a month or two to feel the full effects.
With menopausal symptoms, I may also add black cohosh and red clover extract. While there was a recent study that claimed that black cohosh didn't work, it was in fact, flawed, and contradicted numerous well-done studies that found it to be very effective. I have also discovered a remarkable new product called FemmePhase. Even the majority of my hard-core hot flashers have found relief with it.
When the nutrients aren't quite doing the job, you can add over-the-counter natural progesterone cream (up to 30 mg daily) for one week prior to your period. This is a maximum of 3 percent progesterone, or 30 mg per 1 gram dose.
I may also prescribe higher dose bio-identical hormones for my patients. The progesterone is often 10 percent, which is three times as strong as the over-the counter dose. Made from highly purified derivatives of soy and wild yams, these formulas are carbon copies of your own natural hormones. Prescription strength bio-identical hormones are available only from compounding pharmacies, and are prescribed by your doctor. Doses are based on your individual hormonal needs as determined by your lab tests.
As I say repeatedly - "you don't have to live with PMS/peri-menopausal symptoms." This applies to both the woman herself and her long-suffering loved ones. This information should help you take care of most cases of PMS and peri-menopausal symptoms. I have many grateful women, and their partners, for whom PMS has truly become a thing of the past.
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Friday, July 2, 2010
Updated: Friday, April 18, 2014
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by Fiona McCulloch, ND
Polycystic ovarian syndrome is the number one reproductive disease in women. This disease disrupts normal ovulatory cycles which can result in heartbreaking infertility for millions of women. Known hormonal changes in PCOS include excess androgens (ie: testosterone), and insulin resistance. Most thought now is leaning towards insulin resistance being the primary cause of PCOS, with genetic factors playing a role, but once the cycle of anovulation begins it feeds back on itself, causing the condition to remain in a vicious cycle. Women with PCOS have not only insulin resistance, but also have neuroendocrine imbalances, resulting in elevated LH (lutenizing hormone) levels. Having a high LH to FSH ratio is one of the hallmarks of polycystic ovarian syndrome or persistent anovulation. In response to a combination of high LH and insulin resistance, the follicles in the ovary will begin to secrete too many male hormones (androgens) which then inhibit the hormonal pathways that are needed to stimulate ovulation.
Various medications are traditionally used to induce ovulation in women with PCOS. A growing body of evidence now exists indicating that low-frequency electroacupuncture is as effective as commonly used medications in inducing ovulation. Furthermore, this form of acupuncture can benefit many of the hormonal imbalances seen in polycystic ovarian syndrome. Thousands of women worldwide use acupuncture therapy for PCOS and so I’d like to discuss how it works, and why it is so beneficial to induce ovulation.
General principles of how electroacupuncture stimulates the ovaries through the nervous system
Electroacupuncture has been found to profoundly effect the reproductive organs, through mechanisms in the sympathetic nervous system, endocrine system, and neuroendocrine system. When needles are inserted into certain points and stimulated in a specific manner, this produces a neurological reflex transmitted to the organ correlated with that nerve pathway. For example, needles inserted into the leg muscles below the knee, lower back, or abdomen in specific regions cause a response which measurably affects the ovary. In addition, the nervous system will transmit a signal to the brain, and the brain then emits a response which affects the organ from a central mechanism. These effects have been investigated through measurements of hormones, neuropeptides, and circulatory changes on both animals and humans receiving this specific type of electroacupuncture.
Nervous system alterations in PCOS
Evidence indicates that women with pcos have abnormal circulating levels of a neurohormone called β-endorphin. β-endorphin is known to increase insulin production and reduce insulin excretion by the liver, which is very much implicated in PCOS. It has also been found that women with PCOS have unusually high amounts of sympathetic nerve fibres in their ovaries. These nerve fibres cause unusual stimulation of the ovary by the sympathetic nervous system (the part of the nervous system associated with “flight or fight” responses in the body, among other processes). Stimulation of these nerve fibres can cause the ovaries to produce androgens, which then impair normal ovulation. Women with PCOS have also been found to have high amounts of nerve growth factors in their ovaries, something which is associated with high levels of sympathetic nervous system activity. Disturbances in central and peripheral β-endorphin release, high androgens, insulin resistance, abdominal obesity, and cardiovascular disease are associated with increased sympathetic nervous system activity, and all of these are also associated with the pathology of PCOS. In a recent study by Elizabet Stener-Vitorin in Sweden, direct intraneural testing found a strong correlation between levels of sympathetic nervous system activity and testosterone levels in women with PCOS. Those who had the highest amounts of sympathetic nervous system activity were found to have the highest testosterone levels and the most severe PCOS conditions.
What evidence exists for acupuncture inducing ovulation?
Several studies exist on low frequency electroacupuncture and ovulation induction. In one trial, the effect of a series of 14 electroacupuncture treatments on 24 anovulatory women with pcos was investigated. In 38% of these women, regular ovulation was induced. Three months after the last treatment, LH/FSH ratios and testosterone levels were significantly decreased, a sign of improvement in PCOS pathology. In another study done on a group of women given human menopausal gonadotrophin (a commonly used drug in the treatment of infertility), acupuncture was compared to hCG injections in order to assess its effect on ovulation. Traditionally hCG is given to stimulate ovulation during medicated cycles at fertility clinics. It was found that a single acupuncture treatment induced ovulation as effectively as the as the hCG injection and reduced the incidence of ovarian hyperstimulation syndrome, a painful side effect of medicated cycles. Other studies have also indicated enhanced ovarian response when acupuncture is added to medicated cycles. Female rats with PCOS induced by chronic exposure to DHT (a form of testosterone) were given low frequency electroacupuncture and physical exercise. The treatment increased the amount of healthy follicles in the ovaries, and significantly normalized cycles.
Effects of electroacupuncture on nervous system changes in PCOS
It has also been found that electro-acupuncture can regulate parts of the central nervous system related to dysfunction in PCOS. Specifically, beneficial effects on neurohormones such as GnRH(Gonadotropin releasing hormone) and androgen receptor proteins, indicate that electro-acupuncture significantly benefits the hypothalamic-pituitary-ovarian axis and through this can help to restore normal cycling. Electroacupuncture was also found in 3 recent studies to increase ovarian blood flow through effects on sympathetic nervous system pathways. In addition, it has been found in two studies to reduce high peripheral circulating β-endorphins in women with PCOS, and thereby improve insulin resistance. As sympathetic nerve activity appears to contribute to the development and maintenance of PCOS, the beneficial effects of electroacupuncture, and also exercise, may be mediated by nervous system modulation to the ovaries.
Electro-acupuncture appears to work through multiple pathways to disrupt the “vicious cycle” of PCOS. Even though much more research needs to be done to determine all of the mechanisms involved, its safety and low incidence of side effects makes it an excellent therapy to stimulate ovulation naturally for the many women who suffer with this disease.
Andersson, S., Lundeberg, T., 1995. Acupuncture — from empiricism to science:functional background to acupuncture effects in pain and disease. Med. Hypotheses 45, 271–281.
Cai, X., 1997. Substitution of acupuncture for HCG in ovulation induction. J. Tradit. Chin. Med. 17, 119–121.
Carmina, E., Ditkoff, E.C., Malizia, G., Vijod, A.G., Janni, A., Lobo, R.A., 1992. Increased circulating levels of immunoreactive beta-endorphin in polycystic ovary syndrome is not caused by increased pituitary secretion. Am. J. Obstet. Gynecol. 167,
Chen, B.Y., Yu, J., 1991. Relationship between blood radioimmunoreactive beta-endorphin and hand skin temperature during the electro-acupuncture induction of ovulation. Acupunct. Electrother.
Lobo, R.A., Granger, L. R., Paul, W.L., Goebelsmann, U., Mishell Jr., D.R., 1983. Psychological stress and increases in urinary norepinephrine metabolites, platelet serotonin, and adrenal androgens in women with polycystic ovary syndrome. Am. J. Obstet. Gynecol. 145, 496–503.
Feng, Y., Johansson, J., Shao, R., Manneras, L., Fernandez-Rodriguez, J., Billig, H., Stener-Victorin, E., 2009. Hypothalamic neuroendocrine functions in rats with dihydrotestosterone-induced polycystic ovary syndrome: effects of low-frequency electroacupuncture. PLoS ONE 4, e6638. produces skeletal muscle vasodilation following antidromic stimulation of unmyelinated afferents in the dorsal root in rats. Neurosci. Lett. 283, 137–140.
Jin, C.L., Tohya, K., Kuribayashi, K., Kimura, M., Hirao, Y.H., 2009. Increased oocyte production after acupuncture treatment during superovulation process in mice. J. of Reprod. & Conception 20, 35–44.
Manneras, L., Cajander, S., Lonn, M., Stener-Victorin, E., 2009. Acupuncture and exercise restore adipose tissue expression of sympathetic markers and improve ovarian morphology in rats with dihydrotestosterone-induced PCOS. Am. J. Physiol. Regul. Integr. Comp. Physiol. 296, R1124–R1131.
Stener-Victorin, E., Wu, X., Effects and mechanisms of acupuncture in the reproductive system, Auton. Neurosci.(2010)
Stener-Victorin, E., Lindholm, C., 2004. Immunity and beta-endorphin concentrations in hypothalamus and plasma in rats with steroid-induced polycystic ovaries: effect of low-frequency electroacupuncture. Biol. Reprod. 70, 329–333.
Stener-Victorin, E., Waldenstrom, U., Tagnfors, U., Lundeberg, T., Lindstedt, G., Janson, P.O., 2006. Effects of electro-acupuncture on anovulation in women with polycystic ovary syndrome. Acta Obstet. Gynecol. Scand.
Stener-Victorin, E., Lundeberg, T., Waldenstrom, U., Manni, L., Aloe, L., Gunnarsson, S., Janson, P.O., 2000a. Effects of electro-acupuncture on nerve growth factor and ovarian morphology in rats with experimentally induced polycystic ovaries. Biol. Reprod. 63, 1497–1503.
Stener-Victorin, E., Lundeberg, T., Waldenstrom, U., Bileviciute-Ljungar, I., Janson, P.O., 2001. Effects of electro-acupuncture on corticotropin-releasing factor in rats with experimentally-induced polycystic ovaries. Neuropeptides 35, 227–231.
Stener-Victorin, E., Kobayashi, R., Kurosawa, M., 2003a. Ovarian blood ﬂow responses to electro-acupuncture stimulation at different frequencies and intensities in anaesthetized rats. Auton. Neurosci.: Basic and Clin. 108, 50–56.
Stener-Victorin, E., Lundeberg, T., Cajander, S., Aloe, L., Manni, L., Waldenstrom, U., Janson, P.O., 2003b. Steroid-induced polycystic ovaries in rats: effect of electro- acupuncture on concentrations of endothelin-1 and nerve growth factor (NGF), and expression of NGF mRNA in the ovaries, the adrenal glands, and the central nervous system. Reprod. Biol. Endocrinol. 1, 33.
Stener-Victorin, E., Fujisawa, S., Kurosawa, M., 2006. Ovarian blood ﬂow responses to electroacupuncture stimulation depend on estrous cycle and on site and frequency of stimulation in anesthetized rats. J. Appl. Physiol. 101, 84–91.
Stener-Victorin, E., Jedel, E., Manneras, L., 2008. Acupuncture in polycystic ovary syndrome: current experimental and clinical evidence. J. Neuroendocrinol. 20, 290–298.
Stener-Victorin, E., Jedel, E., Janson, P.O., Sverrisdottir, Y.B., 2009. Low-frequency electro-acupuncture and physical exercise decrease high muscle sympathetic nerve activity in polycystic ovary syndrome. Am.J.Physiol.Regul.Integr.Comp.Physiol. 297 (2), R387R395.
Zhao, H., Tian, Z.Z., Chen, B.Y., 2003a. An important role of corticotropin-releasing hormone in electroacupuncture normalizing the subnormal function of hypothalamus–pituitary–ovary axis in ovariectomized rats. Neurosci. Lett. 349, 25–28.
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Wednesday, January 20, 2010
Updated: Friday, April 18, 2014
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Thyroid problems are extremely common, and because they can be asymptomatic, it can be difficult to know if a condition is present. The thyroid is absolutely essential for healthy fertility. Dysfunction can cause ovulatory disorders, menstrual irregularity, and recurrent miscarriage. The thyroid gland is key to support ovarian function. If thyroid function is low, the eggs will not mature fully and, ovulation can be either delayed or prevented. Surprisingly, 5-20 percent of women in their reproductive years have a thyroid condition.
Autoimmune thyroid disease is one major cause of many thyroid conditions. Women who test positive for thyroid antibodies will generally develop hypothyroidism at a rate of 20% per year. Often times, when a fertility general health screening is done, the only test completed for the thyroid is TSH (Thyroid Stimulating Hormone). TSH is a useful test to screen for hypo or hyperthyroidism, however it does not detect autoimmune conditions. Autoimmune thyroid antibodies can be present with no symptoms of hypothyroidism at all. In autoimmune thyroiditis, TSH levels are often normal so it is important to complete a full thyroid panel. This can determine if there is a risk of developing hypothyroidism which could threaten a pregnancy. When a woman becomes pregnant, there are widespread hormonal changes in the body, including an increased demand for thyroid function. If autoimmune antibodies are present, this can trigger miscarriage due to inability of the thyroid to compensate normally for pregnancy. Many cases of recurrent miscarriage or premature birth are related to thyroid disease so this is a very important part of fertility screening in those who suffer from miscarriages. One of the protective functions of pregnancy is a decrease in immunity, so it is unlikely that a new flare up of Grave’s disease (an autoimmune disease which causes symptoms of hyperthyroidism and goitre) will occur during pregnancy, however often we see worsening of hypothyroidism.
Another condition which can be present in those with thyroid disease is primary ovarian failure. This is caused by autoantibodies to the ovary and is associated with autoantibodies to the thyroid. This condition, although not common, can be devastating for women.
In men, hypo- or hyper- thyroidism can cause poor development of sperm, so for all men with sperm quality concerns, the thyroid should be screened. Although thyroid disease is more common in women, it can still happen for many men and go undetected.
Symptoms of Hypothyroidism:
fatigue, weakness, weight gain, dry skin or hair, feeling cold, constipation, irritability, depression, muscle cramps, menstrual irregularities.
Symptoms of Hyperthyroidism:
anxiety, feeling hot, insomnia, heart palpitations, weight loss, hunger, sweating, trembling
To optimize fertility the following lab testing for thyroid should be done. Explanation of thyroid lab values and normal ranges are included.
TSH – Thyroid Stimulating Hormone.
This is a hormone released by the pituitary gland (in the brain) which stimulates the thyroid to release thyroid hormones. It is controlled by feedback mechanisms, when thyroid hormone is low in the bloodstream, the pituitary gland will increase its output of TSH to stimulate more release of thyroid hormones.
Normal Levels : 0.4 – 4 mIU/L. If levels are above 2, and especially if thyroid antibodies are present with signs and symptoms of hypothyroidism, this is suspect of “subclinical hypothyroidism” and may present risks for fertility.
Free T4 – Thyroxine.
A thyroid hormone produced by the thyroid gland. This is the most abundant thyroid hormone in the body. It is also the weaker of the thyroid hormones. It represents 80% of the thyroid hormones in the body, and its major function is to be converted into the stronger T3 hormone. This is a measure of the T4 which is not bound to carrier proteins.
Normal Levels: 8.5-15.2 pmol/L
Free T3 – Triiodothyronine.
A thyroid hormone produced from the conversion of T4 by enzymes. This is a much stronger thyroid hormone and has powerful effects on the body’s metabolism. It represents 20% of the total thyroid hormones in the body. The conversion of T4 into T3 can also be impaired, so this is important to investigate. This is a measure of the T3 which is not bound to carrier proteins.
Normal Levels: 3.5 – 6.5 pmol/L
When there is sufficient T3, the body will convert excess T4 into a compound known as reverse T3. This compound is inactive, and serves to protect the body from excessive overstimulation by thyroid hormone. It can bind to receptors where T3 would normally bind, however it does not stimulate the receptor as T3 would. In some cases, the body may actually convert T4 excessively into reverse T3, which can result in metabolic abnormalities. This condition should be screened for whenever signs and symptoms (including low body temperature) are present in fertility patients.
Normal Levels: 200-300 pmol/L
Thyroid peroxidase antibodies
These are antibodies against an enzyme known as Thyroid Peroxidase. Thyroid peroxidase is involved in the conversion of T4 to T3. If antibodies exist, this can cause a conversion disorder which results in hypothyroidism.
Normal Levels: <35
These are antibodies directed against a protein known as Thyroglobulin. Thyroglobulin is present in the thyroid gland and is essential for the production of thyroid hormones. These antibodies can trigger destruction of the thyroid gland.
Normal Levels: <20
Treatment for thyroid conditions can involve thyroid hormones, nutritional supplements, amino acids and herbal medicines, depending on which type of thyroid condition is present. Naturopathic treatment for thyroid is often integrated with conventional thyroid medications when needed to optimize response for fertility concerns.
- Dr. Fiona McCulloch
Reference: Mosby’s Manual of Diagnostic and Laboratory Tests