Q.
I’ve noticed that there are FSH urine test kits for sale over-the-counter to help women confirm the onset of menopause. Since FSH testing is involved in determining fertility reserve, can I use this over-the-counter FSH test to help realize my fertility potential?

A.
It appears as if a fair number of over-the-counter FSH test kits are indeed sold in drug stores and over the Internet. I am not going to comment on their efficacy for measuring hormonal changes that the pre menopausal body starts to undergo. But I can answer your question. These test kits are not useful tools to help you determine your fertility potential.

By way of background, human follicle stimulating hormone (FSH) produced by the pituitary gland stimulates primordial follicular growth and estrogen production by the emerging follicle that will mature into an egg.

The urine test kits provide a black or white – yes or no answer, not a glimpse of your FSH level in the context of a gray scale range of indicators. For accurate fertility potential diagnosis, we analyze FSH level in much more detail. On day two or day three of your cycle (following menses) we test your FSH level in conjunction with other tests including estradiol (E2) and an antral follicle count.

Most home urine tests, such as for pregnancy tests and ovulation predictor tests, use a threshold level of the hormone in the urine to detect a positive. With FSH test kits, only when the level reaches menopausal levels of FSH, equivalent to around 40-50 mIU/mL or higher in the bloodstream, will the test turn “positive.” For most women interested in testing for ovarian reserve, we would be looking for levels equivalent to 5-20 mIU/mL. So the sensitivity of the testing is set for menopausal and post-menopausal levels, not the levels seen in women with regular menstrual cycles. By the same token, they will not be able to discriminate normal from decreased ovarian reserve.

– Carolyn Givens, MD

To the immune system of a pregnant woman, there is no doubt that a baby is a temporary graft of foreign tissue. A baby and its placenta express proteins on its cell surfaces that come from the father, and therefore are “foreign” and could potentially be rejected by a woman’s immune system.

Like all living species that gestate their young within the mother’s body, humans have evolved mechanisms to protect the baby from rejection by the host mother’s system. The last few years has seen an increased interest in the subject of the role of the immune system in implantation of embryos and maintenance of pregnancy. The clinical relevance of perceived abnormalities in the immune system of women with unexplained infertility, unexplained implantation failure and recurrent miscarriage is a controversial topic. Elaborate theories to explain these failures have been proposed but most have not yet stood up to the test of good science. One of the latest theories to lay blame is that of a class of immune cells (lymphocytes) known as “natural killer” cells. Natural killer (NK) cells are responsible for killing certain types of foreign cells. In the current theory, increased NK cell activity potentially leads to attack of placental cells and therefore rejection of the fetus. But NK cells will only kill lab-cultured placental cells in the presence of another protein, called interleukin-2. Yet interleukin-2 is not present in the uterine lining of the uterus at the time of implantation. NK cells are found in both the bloodstream and in the uterine lining. NK cells are present in the uterus only during the second half of the cycle and can be found concentrated at the site of implantation. In mice that have been genetically altered to no longer make NK cells, successful reproduction will only occur if NK cells are given back to these mice. This suggests that, at least for these mice, NK cells may be necessary for implantation. So are NK cells there to inhibit or promote embryo implantation? The answer is not clear. Further complicating the NK cell story is the fact that there are several kinds of specific NK cells. These types can be classified by the expression of specific receptor proteins on the surface of NK cells. As it turns out, NK cells in the uterus are different from the NK cells that circulate in the bloodstream. Therefore, using blood tests to determine if there are too many circulating NK cells would bear little reflection on what is going on within the population of uterine NK cells. Other blood tests have been devised to assess whether these uterine-specific NK cells are being over-produced, such as tests for Tumor Necrosis Factor a (TNF-a), and Interferon g (IFN-g). These are proteins secreted by a particular class of NK cells found in the uterus. Women identified by these blood tests as having elevated NK activity or increased levels of TNF-a or IFN-g have been told that they will never successfully conceive unless they receive treatment with various immune suppressing agents such as intravenous immunoglobulin infusions (IVIG), glucocorticoid (prednisone) medications or anti-TNFa medications. But these treatments are not free from risk. Anti-TNFa medications have been implicated in several serious diseases such as lymphomas and lupus-like syndromes. Glucocorticoids during pregnancy can be associated with an increased risk of pre-term rupture of the fetal membranes, increased risk of pre-eclampsia (high blood pressure during pregnancy) and gestational diabetes. Immunoglobulin infusion (IVIG) is the use of infusions of a pooled blood production (immune proteins) and can be associated with anaphylactic (shock) response, and a host of side effects. This is why the vast majority of reproductive endocrinologists do not support administration of these drugs to women, even if they have been told they have increased NK cell activity in their blood stream. Unfortunately, our understanding of the role of the immune system in implantation and pregnancy is very rudimentary at this point. Trying to take this limited knowledge and develop tests to predict who may or may not be experiencing abnormalities of the immune system is akin to going out on a long limb of unproven possibilities. Furthermore, determining that women with supposed abnormalities in their NK cell activity be treated with anti-TNFa medications, steroids or immunoglobulin infusions to globally suppress the immune system is akin to going out even further on a flimsy stem. These treatments can be expensive and potentially harmful. The good news in all of this is that there is extensive research under way to try to better understand the very complex nature of embryo implantation and the immune privilege of the fetus within the womb. The bad news is that we are still a long way from understanding whether or not there truly are immune system malfunctions that occur which could potentially block implantation or directly cause repeated miscarriage. To therefore say that we can run a clinical test on a woman or furthermore, develop a rational mode to safely treat a woman for such a syndrome is going way beyond the bounds of good clinical medicine.

– Carolyn Givens, MD

Many people who get pregnant easily but have experienced recurrent miscarriages may not realize that they may actually have an “infertility” problem. The rubric of infertility includes not only helping couples establish a pregnancy but also achieving a viable pregnancy, which will grow to full term. So the diagnosis and treatment of recurrent miscarriages is indeed an area that is managed by infertility experts.

Recurrent Miscarriages, also called recurrent pregnancy loss (RPL), is diagnosed after at least 2 or 3, or more, consecutive pregnancy losses in the first or early second trimester (less than 15 weeks gestation). It is one of the most common clinical problems in reproduction, yet a definite cause can be established in only about 50% of the cases, often leaving patients distraught and frustrated. Consequently, some patients will turn to alternative therapies of unproven benefit. Medically known causes and treatments are described in this article.

Egg Quality Factor
The normal biological aging process of the egg causes the egg to function less accurately during the fertilization process at the critical time of chromosomal duplication and pairing. The resulting chromosomally abnormal embryos have a lower chance of implanting in the uterine lining. If implantation does occur, these embryos have a higher chance of leading to a first trimester miscarriage. We test for egg quality by performing a blood test for the FSH and Estradiol hormones on menstrual cycle day 2 or 3. For some patients we may recommend a more extensive test called a Clomid Challenge Test.

Other Hormonal Factors
Other hormonal abnormalities that result in miscarriage must be very subtle because the cycle is normal enough to allow egg development, ovulation, fertilization, and implantation, yet the pregnancy is lost at a later time. The amount of progesterone produced by the follicle after ovulation and the effect of that progesterone on the lining of the uterus may be of importance. A low progesterone level or an inadequate maturation of the uterine lining is called a luteal phase defect.

Abnormalities of other metabolic hormones can cause a luteal phase defect. If the prolactin level is elevated, it is important to evaluate for prolactin-elevating drugs, hypothyroidism (check the TSH), and pituitary tumors. The prolactin level can be lowered to a normal range with medications.

Women who have polycystic ovary syndrome (PCOS) are at higher risk of miscarriages because of an intraovarian hormonal imbalance. If PCOS is suspected, checking for LH, androgens and insulin resistance can be helpful in discussing treatment with insulin-sensitizing agents (metformin).

Anatomical factors
The anatomical factors are a variety of structural abnormalities of the cervix and uterus that are found in about 15% of women with recurrent pregnancy loss. These factors are diagnosed by performing a hysterosalpingogram (HSG), mid-cycle ultrasound or saline hysterogram, with attention directed to the shape or contour of the uterine cavity.

Potential abnormalities that may be found and associated with recurrent miscarriages are polyps, fibroids, and uterine septums. These anatomical abnormalities can lead to an unfavorable uterine environment for the embryo at the time of implantation and early embryo development. These can lead to early pregnancy loss. All of these abnormalities can usually be corrected with minor surgery.

Chromosomal Factor
There are 2 types of chromosomal factors. One is a random event; the other is genetically inherited by the fetus. At least 60% of all miscarriages are chromosomally abnormal embryos that arose from sporadic, random genetic defects in the sperm or the egg. These are defects that would not have been detected by analysis of the couple’s chromosomes (karyotype). However, these defects become more common as the woman ages. The miscarriage risk increases from about 15% of pregnancies before age 35, to 35% by age 40 and to 50% by age 45. About 99% of the time a chromosomally abnormal embryo will be miscarried. Because perhaps 1% will continue to develop, amniocentesis or chorionic villus sampling, which determine the genetic makeup of the fetus, is suggested for women over 35. When the genetic makeup of the fertilized egg is very abnormal, no embryo forms. On ultrasound examination an empty sac or a “blighted ovum” is seen in the uterus.

Some patients have chromosomal abnormalities in each cell, including eggs and sperm, which place them at greater risk of making a larger proportion of abnormal embryos. The fetus then genetically inherits this abnormality. Every cell in our body other than eggs and sperm has 46 chromosomes arranged in 23 pairs. It is possible that between the two chromosomes of a designated pair there could be a mix-up in the sequence of genes that make up these chromosomes, but the total number of genes is still normal. This mix-up is called a “balanced translocation” and causes no symptoms, diseases, or abnormalities in the patient or partner. However, if this genetic rearrangement occurs in a sperm or egg, the embryo will be chromosomally abnormal, and a miscarriage will follow. Balanced translocations can be detected by performing a chromosomal analysis. Chromosomal analysis requires a blood sample from both partners. The white blood cells are cultured to produce an analysis, or karyotype, of the chromosome pairs. The karyotype will be abnormal in about 5% of cases of couples that have suffered from three or more miscarriages. It is difficult to say what the risk of repeated miscarriages will be with a balanced translocation, however a normal full term pregnancy is still possible.

Immunologic factors
The immune system protects our bodies against foreign micro-organisms by recognizing any cells that are different from our own and making antibodies that attack and destroy those cells. Some women with recurrent pregnancy loss have autoantibodies. These are antibodies in their blood vessels that are made to attack their own tissues (e.g., antiphospholipid (anticardiolipin), antinuclear, or antithyroid antibodies). Antiphospholipid antibodies, along with lupus anticoagulant, may interfere with the formation of a normal placenta early in pregnancy and increase the risk of abnormal blood clotting in the placenta later in the pregnancy. This compromised placenta will lead to compromised growth of the fetus and an eventual miscarriage. If one has a positive antibody test, the test should be repeated 6-8 weeks later. If both sets of tests are positive, the recommended treatment may include one “baby” aspirin tablet per day, and sometimes the addition of daily heparin.

Thrombophilia Factors
Various enzymes regulate effective flow and clotting of blood. If there is a deficiency in some of the clotting enzymes, then small blood vessels of the placenta may be at greater risk of forming clots. Clots of the placenta will compromise blood flow to the growing embryo, placing the pregnancy at greater risk of a miscarriage. There are now a number of clotting enzymes that are recommended to be tested for in patients with recurrent miscarriages. If specific combinations of these enzymes are found to be in an abnormal range, then recommended treatment is a “Baby” aspirin per day with the possible addition of heparin.

Most miscarriages are the result of a random genetic defect leading to abnormal chromosomes for that particular fetus. This random event is unlikely to recur. For patients who have had three consecutive first-trimester miscarriages, and normal results after full evaluation, the chance of the next pregnancy leading to the delivery of a child is approximately 65%. Therefore, despite having had three recurrent miscarriages, the odds are still in favor of the next pregnancy being a normal pregnancy. While it can be incredibly frustrating both for patient and physician, to face repetitive failed pregnancies, it is still important to understand that the odds are still in the patient’s favor of eventual success. This may require fertility treatment, from low-tech intervention such as Clomid to high tech intervention such as IVF with preimplantation genetic screening (PGS), but in general, success is in our favor. If you are, or know someone who is experiencing recurrent miscarriages, please discuss this with a fertility specialist who may be able to recommend treatment options.

– Isabelle Ryan MD

Some patients might have noticed claims that an Inhibin B blood test can better help determine her egg quality. We at Pacific Fertility Center have examined this topic carefully and have chosen not to incorporate this test as a routine procedure.

Currently we use a number of parameters to determine egg quality, or ovarian reserve. For most patients this includes review of:

1. The female partner’s age,
2. Results of cycle day 3 FSH and
3. Estradiol (estrogen) testing or
4. A complete clomid challenge test (CCCT), and
5. Ultrasound to determine basal antral follicle count (AFC).

With these parameters we can help determine chances of success with each treatment modality.

We are constantly looking for ways to better determine ovarian reserve. One proposed adjunct is a blood test for Inhibin B. Inhibin B is a protein secreted by the resting antral follicles in the ovary, and is responsible for inhibiting the secretion of FSH in the early part (follicular phase) of the menstrual cycle. There is also a second inhibin called Inhibin A. This inhibin is secreted by the selected and growing follicle in the second (luteal phase) part of the menstrual cycle.

Inhibin B is secreted by the group of small, resting follicles in the ovary and indicates a woman’s ovarian reserve. The higher the Inhibin B level, the more ovarian follicles are present in the ovary, the greater the chance of growing a number of follicles with stimulation medications, the greater the chance of achieving a pregnancy. Most studies indicate that an Inhibin B level = 45 pg/ml would indicate adequate ovarian reserve. Inhibin B levels decrease as women age and total follicle numbers decline. Women with very low Inhibin B levels (<20 pg/ml) have such poor ovarian reserve that they have a very high chance of cancellation in an IVF cycle.

Inhibin B is a direct measurement of the hormonal dynamics of the ovarian follicles. FSH testing is an indirect measure of ovarian reserve, but the FSH test is readily available at most reference laboratories. Inhibin B testing is more laborious, and few labs offer this test. Additionally, numerous studies have shown that doing an Inhibin B test alone does not provide more accurate information nor better predict one’s ovarian reserve, compared to an FSH test alone. Therefore, these 2 limitations have not allowed for the incorporation of routine Inhibin B testing in a fertility evaluation.

– Isabelle Ryan, MD

Prolactin is a protein hormone produced in the pituitary gland that controls lactation. This hormone in women is normally produced at low levels except after birth, when suckling at the breast stimulates secretion of breast milk. Prolactin inhibits reproductive hormones and during breast-feeding is responsible for decreasing the chances of conception during the postpartum period.

A relatively common benign tumor of the pituitary can result in the over-secretion of prolactin. If this happens, a woman may develop galactorrhea, or inappropriate secretion of breast milk when not in the postpartum (after birth) period. If the levels of prolactin are high, she may develop a short luteal phase (second half of the menstrual cycle) or even stop ovulating altogether.

There are many causes of high prolactin levels, such as diet, stress, breast stimulation, and exercise. Occasionally, a small growth, or tumor, of the pituitary can be responsible. If the levels of prolactin are high, a woman will be advised to undergo an MRI of the pituitary gland to determine whether a tumor is present, and, if so, its size. If it is less than one centimeter in diameter, it is called a microadenoma. If it is greater than one centimeter, it is called a macroadenoma. Macroadenomas can cause pressure on the optic nerve, leading to headaches and partial visual loss in some cases.

Most of the time, high prolactin levels can be treated with either bromocriptine (Parlodel) or cabergoline (Dostinex). These medications will usually shrink the tumor size and restore the prolactin levels to the normal range. If the medications do not shrink the tumor and symptoms persist, a surgical procedure to remove the tumor known as a “trans-sphenoidal resection” will be advised. Surgery today is rarely performed.

Many women will be found to have mildly elevated levels of prolactin with no apparent symptoms. At these levels, there are rarely symptoms of galactorrhea, anovulation or headaches and visual changes and an MRI is not necessary. However, if the woman is trying to conceive, it is recommended that she start medication to restore the prolactin levels to the normal range. Even mild elevations of prolactin can be associated with infertility. Usually, the medications are discontinued once pregnancy occurs. The only women that are advised to continue Parlodel or Dostinex during pregnancy are those with confirmed macroadenomas (large pituitary tumors), as they can grow in pregnancy and cause optic nerve compression.

There are some things that can result in mild and transient elevations of prolactin. These include nipple stimulation, a high protein meal, birth control pills (sometimes) and some psychiatric medications such as phenothiazines for psychosis. These should be avoided just prior to having prolactin levels drawn.

Q.
My friend was tested with a high FSH of 10 and she still got pregnant, naturally! Now I’m confused – I have a low FSH of 7 and have not been able to conceive, even with IVF.

A.
It is true that the follicle stimulating hormone (FSH) test can be a useful indicator of a woman’s ovarian reserve (egg quality/quantity) but it is by no means a perfect screening for egg quality and/or quantity.

FSH, a hormone produced by the pituitary gland in the brain, is released into the bloodstream and travels to the ovary where it stimulates immature follicles containing microscopic oocytes to eventually develop a mature oocyte (egg). Early in the menstrual cycle, if the blood level of FSH is high, it indicates that the pituitary is working hard to stimulate the ovaries, therefore, the number and perhaps quality of the remaining eggs is decreased.

FSH is tested on day 2 or 3 of your cycle to provide a baseline measurement. An elevated FSH level above 8 might suggest that a woman is starting to experience the loss of her ovarian reserve. Menopausal women show FSH levels that are above 40. However, there are several variables, and as with many issues surrounding infertility, it has much to do with age.

Proper interpretation of FSH levels requires a simultaneous measurement of blood estrogen (estradiol) levels. Estradiol is made by the ovary, enters the blood stream and travels back to the brain (pituitary) to help regulate FSH release. Early in the cycle, day 2 or 3, it should be less than 60. A high level of estradiol, above 80, indicates that estradiol is suppressing the pituitary and providing an inaccurate FSH reading.

Several studies have set out to determine whether women with elevated basal FSH levels should be excluded from fertility treatment. A comprehensive study in the United Kingdom analyzed over 2000 patients for four years undergoing IVF treatment. Although it found no significant correlation between FSH levels and fertilization rates or miscarriage rates, the pregnancy rates and live birth rates were lower among women with higher FSH levels. Elevated FSH levels were also associated with more frequent cycle cancellation, need for larger amounts of stimulation medication, and lower numbers of eggs and embryos with fewer embryos transferred. However younger women, even with high FSH levels, had significantly greater live birth rates compared to older women with normal FSH levels. Again, age matters, despite a normal FSH value.

A normal FSH reading, although reassuring, may be indicative of egg quantity but not necessarily quality. The follicles may be producing mature eggs, however, the quality of those eggs may not be adequate. This is especially true for women over 40 years old.

Another caveat is that most women have variable FSH readings from one cycle to another. The best indicator of treatment response, however, is typically the highest FSH reading. There is no benefit, therefore, in repeated testing of FSH over several cycles and choosing to undergo an IVF cycle when the FSH is normal.

In last month’s Fertility Flash, we introduced readers to the controversy of implicating the immune system in response to repeated IVF failure. In Immunology PART 2 we further describe the types of testing and treatment scenarios that, for the most part, are considered non-evidence-based medical practice.

The majority of reproductive endocrinologists in the U.S. and Europe do not recommend an extensive battery of immunological tests nor is there “immune system” specific treatment after repeated and/or unexplained IVF failures. To clarify, IVF failure is defined as IVF that does not result in a pregnancy.

Because it is frustrating to patients to experience repeated conception failures with no apparent explanation, it is only natural for them to continue seeking answers.

Unfortunately, patients find information on the Internet, which prompts them to seek various tests and treatments, despite the lack of scientific basis. In some cases, these treatment options have been shown to be of no benefit, but patients still seek these in the hope that they might be successful.

It is important to understand that physicians have a limited number of valid tests to perform in these situations. As we continue to understand the biology of embryo development and implantation, we may be able to identify other “valid tests” in the future.

Most of the tests that are included in a typical “immunology” work-up are listed in Table 1. It is important to note that of the battery of tests that purportedly determine immune deficiencies related to infertility, several are standardized for recurrent pregnancy loss (RPL). RPL is defined as three or more consecutive pregnancy losses before 20 weeks gestation. We have noted the tests that are valuable in assessing RPL.

Below are descriptions of the questionable tests and additional treatment options that are administered by a handful of practitioners at great expense to patients. These tests are controversial not only because of their poor predictive value, but also because these laboratory assays are not standardized; the threshold between normal and abnormal/positive and negative differs from one laboratory to another.

The following research studies and medical association positions have negated further consideration of such treatments by the majority of reproductive endocrinologists worldwide.

Antiphospholipid Antibodies (APAs)
Because antiphospholipid antibodies (APAs) have been tied to recurrent pregnancy loss (RPL), particularly anticardiolipin antibodies (ACAs) and the lupus anticoagulant (LAC), medical researchers have investigated the role these antibodies may play in unexplained infertility.

This area has been the focus of several well-conducted studies. Infertile women do show an increased prevalence of phospholipid antibodies. Whether these autoantibodies cause infertility or IVF failure, or are present due to other issues related to infertility, has been the critical question studied.

The controversy surrounding this topic has prompted professional organizations to convene committees to examine the research. The American Society for Reproductive Medicine (ASRM), the world’s largest professional body of reproductive endocrinology and infertility specialists, issued a statement in October 1999 reaffirming that the presence of APA does not affect IVF success.

Anti-sperm antibodies
Reproductive scientists continue to debate whether or not antibodies bound to sperm cause infertility. Fortunately, effective treatments for male factor infertility include intrauterine insemination, IVF, and ultimately intracytoplasmic sperm injection.

Anti-thyroid antibodies
Currently no compelling research data supports the use of routine antithyroid antibody testing in women undergoing assisted reproduction. Data reveals that the prevalence of thyroid antibodies is similar in fertile women and women with unexplained infertility.

Other autoantibodies
There is a lack of compelling evidence that testing for anti-nuclear and anti-smooth muscle antibodies in routine clinical practice is relevant to the diagnosis or treatment of unexplained infertility.

Leukocyte testing (immunophenotyping) for NK Cells
Immunophenotyping for the diagnosis of unexplained infertility or failed IVF lacks strong scientific support. Treatments to correct any presumed leukocyte dysfunction have not demonstrated efficacy in the treatment of infertility, nor for RPL. Very simply, the clinical use of leukocyte testing in fertility practice is not supported by current data.

Treatments
Treatment approaches following such “immunology tests” are similarly of unconfirmed benefit and some may cause harm.

Lymphocyte immune therapy (LIT)
This is a broad-based yet very controversial treatment purporting to improve a woman’s maternal immune tolerance towards her fetus, which necessarily carries dissimilar paternal proteins on the surface of fetal cells. Not only is this therapy expensive, it also has potential serious adverse effects including transfusion reaction, anaphylactic shock and transmission of infection. The US Food and Drug Administration has issued restrictions against transfusion of women with their partner’s white blood cells or cellular products.

Intravenous immune globulin (IVIG)
Intravenous immune globulin treatment has been the subject of several studies. Those by Coulam and DePlacido suggested that women receiving IVIG had improved implantation rates, yet they were too small to be conclusive. A later randomized, controlled study demonstrated that IVIG added no benefit in unexplained recurrent IVF failure.

Steroids
This treatment based on steroids’ immunosuppressive effects has been linked to significant maternal and fetal morbidity. Two randomized, controlled studies revealed that the routine use of steroids was of no benefit to women undergoing IVF treatment. Two additional randomized, controlled studies concluded that steroid therapy in women with RPL did not improve the live birth rate when compared with aspirin or aspirin plus heparin

Aspirin
Treating infertile women with aspirin continues to be debated due to conflicting studies. One randomized, controlled trial found that aspirin did not improve implantation and pregnancy rates in selected women undergoing IVF + ICSI. Yet another randomized, controlled study reported that aspirin significantly improved implantation and pregnancy rates in women undergoing IVF.

Low-dose aspirin is frequently prescribed in IVF cycles to enhance blood flow to the uterus. This is not seen as an immunological issue. The use of low-dose aspirin during pregnancy in cases of RPL has also been shown to improve pregnancy outcome for women with hereditary or acquired blood clotting problems.

Heparin
The therapeutic benefits of heparin are one of the most vociferously debated topics in ART. Some physicians believe that heparin facilitates implantation. Two prospective studies, one randomized and another non-randomized, both showed that combination treatment with aspirin and heparin significantly improved the live birth rate in women with antiphospholipid antibody (APL) syndrome. Antiphospholipid antibody syndrome is a specific entity where the patient has a clinical history with miscarriages (usually second trimester), abnormal clotting events (DVT), various pregnancy complications and various systemic disorders (lupus). A prospective cohort study concluded that aspirin and heparin therapy was of no benefit in APA-positive women undergoing IVF.

Summary
Women suffering from the anguish of unexplained IVF failure may be compelled to take action, even turning to treatment that is not widely accepted in the medical community. These women continue to be presented with testing and treatment cycles by non-specialists as well as a handful of practicing reproductive endocrinologists who appear to be on a mission to defy sound science.

The majority of reproductive endocrinologists worldwide believe the evidence confirms immunology treatments are not valid for unexplained and/or repeated IVF failures. Currently the FDA has issued statements indicating that IVIG and LIT treatment are invalid in the treatment of infertility, unless administered in the context of a randomized study, supervised by clinical researchers. We at PFC concur and do not recommend this form of testing or treatment, even if a woman’s options are narrowing.

Note:
This article presents a basic summation of controversial testing and treatment options related to the topic of reproductive failure and immunology. An extensive packet of information, which includes copies of scientific studies and position papers compiled by our team of physicians at Pacific Fertility Center is available upon request. Call 888-834-3095.

Q.
I’m strongly considering an IVF cycle. Is there any way to know how productive my ovaries are likely to be besides blood tests? I’m 38 years old.

A.
There is no reliable screening test that peeks into your ovaries to determine your “ovarian reserve”, that is, how many eggs you might have available for fertilization. However, one good measuring method that we use is to count your antral follicles, which are tiny resting sacs containing immature eggs that are waiting to develop.

Active ovaries continuously form these follicles – they bubble up or percolate from microscopic immature eggs to the antral follicles that are visible on ultrasound. As ovaries age, fewer of these antral follicles are visible. The antral follicle count is a powerful method of predicting the numbers of eggs; it is not quite so good at predicting embryo quality.

The test is usually done early in the menstrual cycle. Ideally, we like to see 6-8 follicles per ovary, although women have been known to get pregnant even with low antral follicle counts.

The marketplace offers a dizzying selection of devices to help women predict ovulation to increase their odds of conceiving. Collectively, these products are called ovulation predictor kits (OPKs) or fertility monitoring devices.

They are broadly grouped into two main types: those that gauge a woman’s Luteinizing hormone (LH) surge and those that monitor one’s estrogen level. The LH surge is tracked with urine testing strips, which are then discarded. Estrogen can be tracked with longer-use fertility monitoring devices that check saliva or other bodily fluids.

When under-going artificial insemination (AI) and intrauterine insemination (IUI), women need a very precise measurement of ovulation. Single-use OPKs that require urine testing first thing in the morning or after 2-4 hours of “holding it” are ideal for this. They react when a woman’s pituitary gland sends out an LH surge, directing the egg to leave the ovary in 24-36 hours, like clockwork. The egg then spends the next 6-12 hours sliding down the fallopian tube where it must be fertilized before implanting into the uterus. This critical window requires sperm to be on the spot, ready to fertilize.

For LH testing, PFC recommends ClearPlan/ClearBlue Easy and Ovu-Kit One-Step because, in our experience, they tend to give the most unambiguous results. The kits that are not as highly recommended are Answer, First Response and generics; they appear to be more prone to false negative results.

For couples timing pregnancy to the LH surge, natural intercourse is recommended both on the day that the kit changes, and the next day. If a couple is going through IUI with fresh sperm, the insemination will be timed the day after the kit shows ovulation. If frozen sperm is being used, many times two inseminations take place: one on the day of change and another the following day.

The longer-use ovulation monitors that use saliva to measure estrogen levels typically identify a 72 hour peak “zone” of fertility. Tracking estrogen levels can be a fascinating process, although patients may need additional time to train their eye to spot the critical pattern that appears in saliva with elevated estrogen. Curiously, the salt content in body fluids increases with a rise in estrogen. Once dried in a magnified setting, the saliva reveals a distinct crystallization, or “ferning” from the salt level (see illustration on left), similar to ice patterns on a frosty window.

Some name brands include Fertile Focus, the Donna and Lady-Q. These devices are useful if couples can have frequent intercourse during their 3-6 day zone of fertility.

A brand new product that also tracks ovulation via estrogen levels uses a wrist watch-like calculator that must be worn every night. This device makes direct contact with one’s skin, and uses a sensor that contains a non-allergenic gel released to detect one’s estrogen from the moisture released off the wrist.

Since PFC has not reviewed the estrogen-monitoring products and their efficacy, patients are strongly advised to do their own research.

*Reproduced with permission: www.maybeit.com