Another possible cause of miscarriage not related to chromosomes or to the biological clock is thrombophilia. The most common form of thrombophilia is the MTHFR defect, which impairs folic acid metabolism. This defect is a bit controversial and often misrepresented. A large percentage of any normal population (10 percent) are genetic carriers of this defect. These carriers have only a mild reduction in their ability to metabolize folic acid, and these individuals are called heterozygotic MTHFR carriers. The MTHFR defect acts the same as other autosomalrecessive gene defects such as cystic fibrosis. If one of your two genes is normal and the other of the two genes is defective, you are a carrier but do not have the disease. If, however, you have a defect in both MTHFR genes (which would be the case in 1 out of every 400 women), you have a risk of hypercoagulability of the blood, an increased risk of heart disease later in life, and a higher risk of miscarriage. When both MTHFR genes are mutated (not just one), they are called “homozygous.” This gene defect causes an increased level of the amino acid homocysteine in your blood because the MTHFR enzyme is necessary to process homocysteine in your body.

Taking folic acid along with vitamins B 6 and B 12 corrects this imbalance. Folic acid is abundantly present in dark-green leafy vegetables, several cereal grains, and citrus fruits. Therefore, women who eat lots of broccoli are very unlikely to have a problem even if they carry this gene defect. Some patients with MTHFR homozygous gene defects are fertile and have had no problem with miscarriages, and others with the same gene defect have had great difficulties. It is clear that heterozygous MTHFR defects cause no problem, and even homozygous defects only cause miscarriage late in pregnancy, if at all. The MTHFR defect is never the cause of early miscarriage or failure to get pregnant.

MTHFR is just one of several so-called thrombophilias, all of which can be screened for routinely with a blood sample. If such a screen is positive, you can simply take folic acid and vitamin B replacements and conscientiously change your diet. In some cases, your doctor may want to put you on tiny doses of aspirin to protect against the higher risk of clotting in the developing placenta.

However, some of these thrombophilias have been vastly exaggerated, and such diagnoses have often been abused and overused to the patient’s detriment. Some thrombophilias have been alleged to be caused by so-called antiphospholipid syndrome, which causes the body’s immune system to attack itself. In fact, there are labs and doctors who have made huge amounts of money pushing antiphospholipid defects as a cause of failure to get pregnant or maintain a pregnancy in many infertile women. In the 1990s, the American Society for Reproductive Medicine undertook a massive review of all of the studies evaluating treatment of this condition; they found the diagnosis to be irrelevant, and the treatment worthless.

With antiphospholipid syndrome, your immune system fails to recognize self from not-self. This is a relatively rare autoimmune disease whereby your body’s immune system attacks your own body as though it were a foreign invader. These rare conditions are characterized by joint pains, fatigue, and, among other things, higher coagulability of the blood. Autoimmune diseases are slowly progressive and debilitating for the rare patients that have them. However, patients with severe autoimmune diseases are not infertile. They have no difficulty getting pregnant, but they simply have a higher rate of late miscarriage than a normal population. Therefore, their pregnancies are treated with aspirin and sometimes heparin (a much stronger and potentially dangerous anticoagulant) to protect the placental blood flow and allow the pregnancy to go to term.

Some years ago it was speculated that women who failed to get pregnant or women with recurrent miscarriage might have some sort of subtle, subclinical, undetected version of autoimmune disease. A huge battery of expensive tests were concocted to attempt to define these autoimmune diseases that were not clinically apparent in any way other than infertility. An extremely expensive form of treatment was then devised called intravenous immunoglobulin (IVIG) therapy, in which the patient’s blood was sent to an out-of-town laboratory that developed antibodies to that patient’s antibodies. The blood was then sent back to the infertility clinic and administered to the patient, supposedly to block her body’s antibody attack on her uterus. These so-called IVIG infusions were extremely expensive and appeared, to some in the field, to be a money spinner that lacked merit. Carefully controlled studies and reviews of these studies have now been published in scientific journals demonstrating the complete lack of effectiveness of this expensive therapy.

Many years ago, we treated a woman in her late thirties with multiple <a href="https://glowing.com/glow-fertility-program">IVF</a> attempts, each one resulting either in failure to get pregnant or in an early miscarriage. On her own, she consulted an outside laboratory that we would have nothing to do with, and she had a detailed autoimmune evaluation costing several thousand dollars. It supposedly revealed that she had these so-called antiphospholipid antibodies, and she insisted on being treated with heparin, baby aspirin, and even IVIG infusions for her next <a href="https://glowing.com/glow-fertility-program">IVF</a> cycle. But when the chromosome test came back from her miscarried pregnancy, it demonstrated that the fetus had trisomy 16, a chromosomal error that was clearly incompatible with life, and this was the true cause of her miscarriage. She finally decided to try donor eggs from a younger woman, without any heparin, aspirin, IVIG, or any other antithrombophilia treatment, and this time she delivered a healthy baby girl without any problems. Slick marketing from one of these autoimmune thrombophilia labs had convinced her that her miscarriages, and her failure to get pregnant, were caused by her being immune to her own tissue, and they had recommended worthless treatment that was very profitable for them. But her problem was clearly her aging eggs, which were prone to chromosomal errors.

Another couple came to us from the East Coast because the husband had azoospermia, and a TESE attempt back home revealed no sperm in the testes. The couple wanted to try again to see whether there were just a few sperm that had somehow or other been missed in his previous TESE procedure at a different institution. We did find enough sperm in his testes (very few) to perform ICSI with her eighteen eggs. We transferred three beautiful-appearing embryos, and she became pregnant. However, she miscarried in the first three months. Devastated by this, she sought another opinion from a well-known infertility doctor on the East Coast. His routine testing for “thrombophilia screen” revealed a positive Leiden factor in her blood, which could have been implicated as a possible cause of miscarriage. In fact, this doctor told her he was certain this was the problem. He recommended doing her next <a href="https://glowing.com/glow-fertility-program">IVF</a> cycle taking heparin and baby aspirin. However, when the chromosomal testing (karyotyping) of her miscarried fetus came back a week later, it revealed trisomy 16, clearly a chromosomal error in the embryo and a very common cause of miscarriage. She then underwent another TESE-ICSI procedure with us, without using any heparin or anticoagulant therapy, and she became pregnant again, but this time she delivered a healthy baby boy.

Thus, even when it was thought that a subtle thrombophilia was found to be the cause of her miscarriage, the true cause was a chromosomal error originating in her eggs. Although we have to be aware of these thrombophilias, nutritional defects, or possible antibody causes for miscarriage, these are generally overstated conditions. The wholesale administration of aspirin and anticoagulation regimens to infertile women, or to women with recurrent miscarriages, is certainly ill-advised and, in most cases, not likely to solve the problem. Nonetheless, there is a great deal of controversy on this subject, and many patients will say to their doctor, “Why not try it if there’s nothing to lose?”

Deficiencies in factor V Leiden are commonly found in up to 4 percent of the population, and further studies have failed to find any increased incidence of this defect in women with recurrent early miscarriage. However, other thrombophilias, such as protein C deficiency, have been shown to be increased in women with recurrent miscarriage. There is still great controversy and uncertainty surrounding the contribution of thrombophilia to recurrent miscarriage, and many infertility physicians do not even recommend routine testing for these defects.

Nonetheless, we do endorse treating MTHFR defects with vitamin supplementation. It was well established as early as 1992 in England that folic acid deficiency in the early embryo results in neural-tube defects, which are among the most common and heartbreaking congenital birth defects in children. One of the biggest fears of expectant mothers (completely unrelated to the biological clock or to the woman’s aging) involves these neural-tube defects, which cause meningomyocele, hydrocephalus (enlarged head), or even anencephaly, when a child is born without a brain and dies immediately upon birth. Around 1992, it was discovered that putting women on folic acid vitamin supplements during early pregnancy dramatically reduced the incidence of these terrifying neural-tube defects. Since then, women who are attempting to get pregnant anywhere in the modern world are routinely placed on folic acid supplements to protect against these birth defects. If a woman has an MTHFR defect, she will merely need to be on higher doses of folic acid supplements, or on a diet even richer in folic acid. We see no problem associated with routinely administering this increased folic acid, vitamin B 6 , vitamin B 12 regimen, since it is almost a routine part of proper pregnancy management in the current era. But it is not likely to solve the problem of recurrent miscarriage.

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