In what can only be described as the drug industries’ version of the shell game, over the past three decades the manufacturers of fertility drugs have demonstrated with exquisite skill that what you don’t see may as well not exist.
In 1972 it was reported in a scientific journal that in a combined study involving Clomid (clomiphene citrate) and Pergonal (human menopausal gonadotropin/hMG), there was twice the expected frequency of Down syndrome in the offspring of women using those drugs. The subject birth defect, which is usually caused by an abnormal chromosome (trisomy 21) in older women, could not be attributed to the average age of the study populations. The following year, another published study concluded that there was an increased incidence of abnormal chromosomes in first trimester spontaneous abortions (miscarriages) in women conceiving with fertility drugs, including clomiphene and hMG, when compared to the general population and women who naturally conceived two or more cycles after using drugs to induce ovulation. In yet another published paper during the same year (1973), scientists described a study establishing that clomiphene was capable of causing abnormal chromosomes in the endometrium (lining of the uterus) of women using the drug.
Yet, even though this evidence was presented to the FDA over 3 decades earlier, the current labeling (package inserts) for these drugs make absolutely no reference to these studies.
But it doesn’t stop there. In 1983, a scientific article appearing in the International Journal of Epidemiology, reported on a study in which they found a significant increase in the incidence of limb reduction defects (absence of limbs) following the use of fertility drugs, including clomiphene citrate. And beginning in late 1987, a series of published scientific studies began appearing in medical journals in which the researchers reported on an increased incidence of neural tube defects (NTDs) following use of fertility drugs, including their use during in vitro fertilization (IVF). An NTD results when the neural tube fails to fully close during the 4th week of pregnancy, leaving an open cranium (anencephaly) and/or spinal column (spina bifida). One scientist, after combining the results of 3 of these studies in a meta-analysis, stated that “the three studies, when combined, do indicate that the association between ovulation induction and NTD is real.” He calculated that the odds of the combined statistics (a 194 percent increased risk) occurring by chance was only 4 in a thousand (P = 0.004). In still another NTD study published in 1991, the authors commented that “these data (a 136 percent increased risk), combined with those previously published, indicate an association between stimulation of ovulation and increased rate of NTD.”
Yet, in spite of this knowledge, the FDA took no steps to insure that the users of fertility drugs and their doctors were aware of these studies. To the contrary, between 1967 and 1995, the Clomid package insert assured prescribing physicians that “no causative evidence of a deleterious effect of Clomid therapy on the human fetus (had) been seen.”
During the mid-1990s it was determined that NTDs and other specific congenital anomalies can occur when the early embryo is denied an adequate supply of cholesterol. In addition to being an important constituent of the human cell, it has been discovered that a gene (Sonic hedgehog/Shh), which dictates how certain organs are to form during early pregnancy, must bind with cholesterol to properly function. Absent a sufficient level of cholesterol, Shh cannot effectively communicate and malformations occur.
The discovery about the importance of cholesterol in the development of embryonic organs was a major breakthrough toward understanding how fertility drugs can malform a human embryo. Although not widely known, clomiphene citrate is a cholesterol inhibiting drug — it inhibits the function of an enzyme in the body that normally converts desmosterol to cholesterol. The suppression of cholesterol during the critical first few weeks of pregnancy can also occur as a consequence of another function of fertility drugs; namely, their demonstrated ability to significantly elevate normal levels of estrogen. It has been established that there is an inverse correlation between the level of estrogen and the level of cholesterol: the higher the estrogen, the lower the cholesterol.
A recent published study (January 2008) demonstrated this very subject. The researchers found that when women, who did not develop ovarian follicular cysts, were exposed to clomiphene during the first 2 months of pregnancy, they had a 350 percent increased risk of having a baby with a neural tube defect. However, if the fertility drug also caused the development of ovarian cysts — which contain high levels of estrogen — the incidence of NTDs shot even higher to a 540 percent increased risk. The authors concluded that when accompanied by follicular cysts, the “treatment with clomiphene may have a role in the genesis of NTD.” Although administered prior to conception, clomiphene can be biologically active up to 54 days after ingestion, and is thus present during early pregnancy in every woman who conceives during a treatment cycle.
The real tragedy about withholding this information from users of fertility drugs and their doctors is that there currently exists a simple means to substantially reduce or eliminate the risk of birth defects while continuing to take these drugs.