As they always say, “That which you don’t see, does not exist.” For more than 30 years, fertility drug manufacturers have established this saying with superb skill. This is what is described by the drug manufacturer’s form of the shell game. In the year 1972, there was a combined study that involved human menopausal gonadotropin/hMG (Pergonal) and clomiphene citrate (Clomid). The results were published in a scientific journal, indicating that the Down syndrome in the children of women that used those drugs was 2x the estimated frequency. Talking about a birth defect that is normally caused by trisomy 21 (an abnormal chromosome), in older women, cannot be ascribed to the normal population study age.

In the subsequent year, another report was published indicating more and more incidences of abnormal chromosomes.  It showed miscarriages (spontaneous abortions) in women that made use of fertility drugs with hMG and clomiphene. This was in comparison with the overall population and women that conceived naturally in two or more cycles having used the medication to induce ovulation. In the same year, another paper was yet again published. In this publication, the scientist made descriptions of the study. It established that clomiphene had the potential to cause abnormal chromosomes in the lining of the uterus (endometrium) of women that took the medication. Though this evidence has been known to the FDA for more than 30 years, the recent package inserts (labelling) for these medications has totally omitted these studies.

However, it doesn’t end there. : In 1983, a scientific article appeared in the International Journal of Epidemiology. The report was on a study in which a substantial rise in the occurrence of limb reduction defects (deficiency of limbs) was found. This was from the use of fertility medications that included clomiphene citrate.  And from late 1987, a series of published scientific reports started appearing in medical journals.

In these studies, researchers reported on the rise of occurrences of neural tube defects (NTDs) from the use of fertility medication, even in vitro fertilization (IVF).  An NTD occurs when the neural tube does not close fully in the fourth week of pregnancy thus leading to anencephaly (an open cranium) and/or spina bifida (spinal column). A scientist had combined the results of three studies in a meta-analysis.

He specified that the three studies if put together shows that there is a real relationship between inducing ovulation and NTD. From his estimation, the odds of the joined statistics (a 194 % increase in risk) happening by chance was P = 0.004 i.e. 4 in a 1,000.

In 1991, another NTD study was published.

The authors mentioned that the data (a 136 % increase in risk), joined with the earlier published, show a relationship between stimulated ovulation and increase in NTD rate. Despite all this available knowledge, the FDA is yet to take any necessary step to make sure that those that use these fertility medications are informed of these studies. They need to ensure that their doctors too, are aware of these studies.


On the contrary, from 1967 and 1995, the Clomid package insert guaranteed prescribing doctors that they were no causative proof of a damaging effect of Clomid treatment on the human fetus.  In the mid-1990s it was established that NTDs and other particular natural anomalies can happen when the early embryo is starved of a sufficient cholesterol supply. Apart from it being an essential constituent of the human cell, there is more. It was found out that a gene which dictates how some organs form during the early pregnancy period must combine with cholesterol for it to work properly.

This gene is the sonic hedgehog/Shh.

Without an adequate level of cholesterol, Shh cannot communicate properly and defects will occur. Finding out about the significance of cholesterol was a huge breakthrough in the development of embryonic organs. It has helped to understand more how a human embryo can become defect because of fertility drugs. It is yet to be vastly known that clomiphene citrate is a drug that inhibits cholesterol. It hinders the functioning of a certain body enzyme that changes desmosterol to cholesterol.  Fertility drugs have a demonstrated ability to considerably raise normal estrogen levels.  This is another suppressing of cholesterol in the critical beginning few weeks of pregnancy. The inverse correlation between estrogen and cholesterol level has been proven. Hence, the more the estrogen level, the lesser the cholesterol.

In the beginning of 2008, a study was published to demonstrate this. The researchers discovered that women that did not develop ovarian follicular cysts were open to clomiphene in the beginning 2 months of pregnancy. These women had a 350 % risk increase of conceiving a baby with an NTD.  In addition, if the fertility drug had caused the development of ovarian cysts, that contains high estrogen levels, the occurrence of NTDs went higher up to a 540 % increase in risk.

The authors came to the conclusion that when complemented by follicular cysts, treating with clomiphene might have a hand in the creation of NTD.  However, if it is administered before conception, it can be biologically active for about 54 days after consumption. Hence, it will be present in early pregnancy in every woman that conceives in the course of a treatment cycle. The sad thing about hiding this info from users of fertility drugs and their physician is that there presently exists a modest means to minimize birth defects risks while using these medications. Follow posts from Medicine Direct to be more informed .