Mini-IVF: Minimal Stimulation IVF Technique

In addition to IVF with conventional stimulation, we also offer IVF with minimal stimulation (mini-IVF), which is a new, dramatically lower cost option with comparable results.

When patients contemplate IVF, their first reaction is often the fear of daily injections of hormones for months, the incredibly high cost of the drugs, the risk of multiple pregnancy and consequent prematurity, side effects related to high levels of estrogen resulting from large numbers of eggs, hyperstimulation syndrome, and the prospect of painful daily progesterone injections for a full ten weeks even after the IVF procedure. Mini-IVF is a very unique approach developed by our colleagues in Japan (and then perfected in our clinic) to circumvent these problems and to simplify IVF for patients, reducing the cost while maintaining the same success rates. For older patients, the success rate is even higher than with conventional IVF. With the refinements we have added to mini-IVF, the pregnancy rates are startlingly high.

Mini-IVF is designed to recruit only a few (but high quality) eggs, thus avoiding the risks of hyperstimulation, reducing the number of injections and dramatically reducing the cost of medications. In many patients who had very poor quality embryos with conventional IVF stimulation protocols, mini-IVF dramatically improved their embryo quality and resulted in pregnancy in otherwise "useless cases." This approach is not just a simple-minded reduction in hormonal stimulation. It is an ingeniously conceived and completely different approach to IVF that saves the patient much of the complexity and cost associated with more conventional IVF protocols. Here is how it works:

On Day 3 of the menstrual cycle, you start on a low dose of Clomid (50mg), but you don’t stop the Clomid in five days as is usually the custom. You just keep taking the Clomid until ultrasound monitoring shows the follicles to be ready for ovulation. A very low “booster” dose of gonadotropin (just 150 iu of FSH), is added on Days 8, 10, and 12. Clomid not only stimulates your own pituitary to release FSH naturally (by blocking estrogen’s suppressing effect), but also staying on the Clomid (a unique new approach) blocks estrogen’s stimulation of LH release, and so also prevents premature ovulation. Thus, with this simple change in protocol, the old-fashioned, cheap Clomid is able to stimulate the development of smaller number of better quality eggs for IVF.

Another advantage of this protocol is that you did not have to go on Lupron first to suppress the pituitary. Staying on Clomid blocks estrogen from stimulating your pituitary to release LH, and this prevents premature ovulation without your having to be suppressed. This means that you can be induced to ovulate with just a simple injection or nasal sniff of Lupron. This causes a more natural LH surge, and avoids the luteal phase defect caused by HCG that would otherwise require months of progesterone injections.

The next step is to recognize that Clomid has a negative effect on the uterine lining (because it prevents estrogen from stimulating the endometrium). That is one reason why results in the past have been so poor with the use of Clomid for ovarian stimulation. The embryos are less likely to implant in such endometrium. But that problem is solved by using the Japanese protocol for embryo freezing, “vitrification.” Using this approach, we can now very safely freeze embryos with virtually no risk of loss. Frozen embryo transfers can then be performed in later natural cycles.

Even for poor prognosis cases of older women with low ovarian reserve, there is an advantage to mini-IVF over high dose stimulation. Such patients normally yield very few eggs even with huge megadoses of gonadotropin. Mini-IVF is just as likely to yield as many eggs (very few, of course) as giving huge megadoses of gonadotropin. But the egg quality is better and they can afford to do more cycles if that is what is required. Even in the worst case scenario, when there are no eggs left at all, then at least the patients can discover this with only $300 spent on drugs instead of $7,000 (cost of maximum dosage).

Think of this simple parable: If you are sitting under an apple tree, and wish to eat the most ripe and ready apples, you have a choice. You can chop down the tree, and look at every apple on the fallen tree to see which ones were ready. Or you can simply try to shake the lower branches and eat the one or two that have fallen. That is the idea of mini-IVF. For many patients, it will remove much of the aggravation and complexity associated with IVF, and also dramatically reduce the cost. But it requires a great deal of sophisticated ability to do well.

Mini-IVF is tricky to perform well and many centers which try it are deficient. There is no margin for error. There are several reasons for the success we have with these much lower cost mini-IVF techniques which we have pioneered in the U.S. Firstly, it is hard to overstate how crucial the purity of air quality in the lab as well as the operating room is. There are organic volatile toxins in the air everywhere in microscopic quantities that don't seem to affect our well being. But they do dramatically affect the well being of these highly exposed embryos. Secondly, the very clever Japanese approach to minimal stimulation allows us to retrieve smaller numbers of better quality eggs than the more expensive massive dosing of conventional IVF protocols, better quality eggs at lower cost. Finally, the ability to freeze the embryos with impunity and then transfer in a later cycle where the uterine lining is more perfectly synchronized to the stage of embryo development than during a stimulated cycle, all add up to high success rates at lower cost.