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Why Mini-IVF is Not as Successful as Standard Cycle IVF

A new kind of mild-stimulation "mini-IVF" performed with Clomid has recently become popular at many clinics around the world. In this video, Dr. Gleicher debunks claims that these cycles are more effective and less expensive than standard IVF cycles that utilize Gonadotropin.

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Hi, I'm Norbert Gleicher MD and I'm the medical director and chief scientist here at the Center for Human Reproduction in New York City. I want to talk to you today about something that is widely called mini IVF. One of many different ways how in-vitro fertilization can be conducted. The difference between mini IVF and the standard IVF cycle is in principle how the ovaries are stimulated. And the concept of mini IVF is that, as the name says, that kind of stimulation be kept to a minimum. In practical terms, that means that most mini IVF cycles either are conducted in so-called natural cycles (meaning in cycles where women are still counting on their own cyclicity) or in cycles where the ovaries are relatively mildly stimulated with a medication called clomiphene citrate or a similar drug. In other words, oral medications rather than the injectable gonadotropins, which have become a mainstay of in-vitro fertilization. That is important for everybody to understand. But, IVF when it started, it started in natural cycles. The first experiments in IVF by British investigators were indeed done in natural cycles, and they were so unsuccessful that after a while they switched to the use of clomiphene citrate or "clomid." And the first IVF baby, about 40 years ago, was conceived with help of clomiphene citrate. But that's when the action started moving from the UK to the United States because at that time, there was an IVF Center in the US that was run by a couple of very prominent but retired colleagues by the name of "the Joneses." And they found that clomid stimulation was really highly inefficient, and it was their idea to replace clomid stimulation in IVF (and this was in the very early years of IVF in the 1980s). It was their idea to replace clomiphene with gonadotropin stimulation. And as they did that, suddenly pregnancy rates in ivf greatly improved. And IVF went from being an experimental, very inefficient treatment, to having rapidly improving treatment with better and better pregnancy chances. Now, sometimes we don't remember history, but in many ways it, therefore, seems rather paradoxical that we would now, 40 years later, return to clomiphene citrate as the principal drug for stimulation. We didn't like it then. Patients didn't like it then because of the side effects on the psyche. We didn't like it that because it didn't stimulate very well and it causes very thin and endometrium that is often too thin to allow embryos to implant. Yet, clomiphene citrate, by proponents of mild stimulation, has again become the go-to drug in those cycles. So, we here at CHR don't believe that this makes much sense simply because of those historical experiences. But there's maybe an even more important reason why it doesn't make any sense, and that more important reason is that after female age, the number of eggs and embryos that an IVF cycle produces is the second most important predictor of how well this IVF cycle will do what the pregnancy chances will be that that idea of cycle produces. And believe me, clomid never comes even close to producing how many eggs you can get in the same patient with gonadotropin stimulation. Therefore, it never made sense to us here at CHR why colleagues would from the beginning, give up on producing more eggs and embryos in a cycle. The rationale that was given for a long time was that the mildest stimulation produces better quality eggs. In other words, the more aggressive stimulation with gonadotropin produces poorer quality eggs. And then, meanwhile, that argument has to be shown to be completely bogus, simply not true. There is no decline in quality if your stimulate harder, indeed (and this needs to be repeated), after female age, the number of eggs and embryos a cycle produces is the most important predictor of pregnancy chance. And therefore, we here at CHR, are really not big fans of mild stimulation. We do offer mild stimulation cycles, but we offer them only to very select patients and really only for financial reasons because obviously clomid is a much cheaper medication than the gonadotropins. And if patients are young, and want to save money, then indeed they may still have a very decent chance with a clomid stimulated cycle, but that's the exception. It shouldn't be the rule. And the best evidence for that is that the country where those mild stimulations have become most popular is Japan. That country, since those mild stimulation cycles became the rule, lost two-thirds of its live birth chances. Imagine that! Two-thirds of life births disappeared when our Japanese colleagues started switching from standard stimulation to clomid cycles. In the same time period, they started three times as many cycles. So, in other words, our Japanese colleagues after 10 years of mild stimulations now must perform three times as many IVF cycles than they did at the beginning of that change in practice just to maintain the same live birthrate. And that demonstrates that the last argument in favor of mild stimulation is also bogus. And that argument has been that mild stimulation is cheaper. Of course, on a per-cycle basis it is cheaper, but if the live birth rate is only 1/3 or less of a regular cycle, then in terms of having a baby at home, it is anything but cheaper. Thank you very much for listening.

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