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Fauser's late start mild stimulation IVF cycle

One of the best established practitioners of minimal stimulation is Fauser from Utrecht in the Netherlands.   His approach should best be termed a “late start mild stimulation IVF cycle". Based on his earlier basic science research, the plan behind this cycle was to utilize  less gonadotropins by waiting to start them with the objective of avoiding the natural drop in FSH that occurs mid-cycle.  He did that to cut the cost of the cycle and to theoretically improve embryo quality by using less gonadotropins and being more like a natural cycle.

 

With his protocol the patient waits until day 5 before starting gonadotropins and then uses an antagonist (like ganirelix) once the follicle begins to grow to avoid a premature LH surge.  Avoiding a premature LH surges is a major problem in natural cycle IVF which can damage the eggs.   If LH started to rise before the follicle was ready to respond to it, it would doom the success of the IVF cycle.  Fauser's usual gonadotropin starting dose is 150 units. Simply starting gonadotropins on day 5 instead of day 1 reduces gonadotropin use by 50%.  The aim of the ovulation induction is to produce two good follicles (as opposed to a large number as in traditional IVF).  Fauser's pregnancy rate was approximately the same as for a higher dose regimen in his program, but his cancellation rate (40%) was higher than for a higher dose regimen (25% one study).  The higher dose regimen in his program was gentler than what is commonly used in the US for IVF.  Their ongoing pregnancy rates of 16-25% is lower than the average in the US (about 35%) and the cycle cancellation rates (25%) are higher than in the US for routine IVF in good prognosis patients (about 14%).

One study by the Fauser group is especially worth discussing.  In this 2007 study, the objective was to look at how the stimulation protocol affected chromosomal abnormality.  He compared good prognosis patients undergoing his late start mild stimulation protocol to a higher dose protocol.  The high dose regimen used mid-luteal suppression with Lupron and a starting dose of 225 units day (not very high).  Patients were randomized to high dose or mild dose stimulations.  On day three after fertilization, all embryos were biopsied and PGD for 10 chromosomes was performed.  More eggs and embryos were obtained with the higher dose regimen, but the number of normal embryos was the same in each treatment group.  Fauser speculated that the increased percentage rate of abnormalities with the high dose group was caused by the higher gonadotropin stimulation levels.  If confirmed, this is an important observation.  However, other logical explanations could be that higher dose gonadotropins only rescues and develops abnormal embryos or that the increased cancellation rate in the minimal stimulation cycles created a selection bias for embryos to provide this result. 

If this Fauser observation of decreased aneuploidy with mild stimulations is correct, it is a benefit that is present in all types of these lower stimulation IVF cycles.