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Assisted Reproduction with Clomiphene Citrate

7/5/2020

Hello. I am a professor of medical science at Brown University and an author of the paper “Clomiphene Citrate at 50, the Dawning of Assisted Reproduction”, Alley Adashi. My own first paper on Clomiphene Citrate was published in 1979 in “Fertility and Sterility”.

The focus was the gestational outcomes of ovulation induction with the drug. In the subsequent three years we published three additional papers on more basic aspects. The real story, however, begins in 1967, when Clomiphene Citrate was approved by the FDA for the purpose of inducing ovulation in women, who were infertile.

In hindsight, this was a breakthrough by any measure. At the time, in general, there was very little one that could be offered. There were infertile couples, who were seeking to build a family. There was certainly nothing of consequence that could be offered to women.

To physicians, who care for patients with infertility, Clomiphene Citrate was literally a panacea at the time. There was simply nothing quite like it up to that point.

The drug itself was synthesized in 1956 by Frank Paula Pauline, who was a chemist with William’s Merrill Company in Cincinnati. Frank Paula Pauline regrettably passed away last year. His obituary was carried by the “New York Times”, he was 94. At the time he was the son of Italian immigrants, born and raised in Pittsburgh. His father was a steel worker.

Assisted Reproduction with Clomiphene Citrate

An American dream, if there ever was one, the company considered multiple applications. Ovulation induction was one of them, but contraception was also on the table, as was the possibility of using Clomiphene to antagonize estrogen dependent endometrial hyperplasia or even breast cancer.

Ultimately, the successful studies focused on ovulation induction and began with a series of consultations in 1960 at the annual meeting of a predecessor Society to the American Society for Reproductive Medicine. It was only a year later, when Dr. Robert Greenblatt from the Medical College of Georgia in Augusta Georgia reported on the pages of “JAMA”, the successful induction of ovulation in a substantial number of patients, who presented with a policy ovary syndrome. Several of them were, in fact, successful in conceiving. Many others resumed normal auditory function, while on the drug.

The final point I will make is that if there was ever a downside to Clomiphene Citrate, it was, of course, it's propensity to bring about multiple birth. And Clomiphene is by definition a contributor to the so-called mad pervert epidemic. We are all contending with it falls largely under the category of non IVF induced multiple birth, about which we have relatively little hard data. But we know that the multiple births that are attributable to non IVF technologies, unfortunately, continue to plague us, whereas IVF driven multiple births, are on a decline.

One way or the other, this is a remarkably important story that is useful to reiterate on this important occasion, which is the 50th anniversary of this drug.

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