Can we prevent premature luteinization in IVF cycles?

From 1991 there is a long-lasting discussion on a possible detrimental effect of premature increase of progesterone levels during ovarian stimulation in IVF. A recent meta-analysis of more than 60,000 cycles states that premature progesterone increase reduces pregnancy rates starting from P4 values of 0.8 ng/ml. The detrimental effect seems to be related to endometrial receptivity impairment according to lack of detrimental effect on oocytes competence in ovodonation. Embryo freezing and deferred embryo transfer on artificial endometrium permits to avoid this detrimental effect but the cycle has to be segmented in two phases. Moreover embryo freezing is an extra burden for IVF lab and could induce embryo damage. So the implementation of an effective pharmacological treatment to prevent premature luteinization could be very interesting for our daily ART practice. On the basis of so far available literature data and our preliminary proof of concept experience we suggest that metformin (1000-1500 mg daily) from first monitoring until ovulation triggering could be suitable for this purpose irrespective of ovarian reserve of the patient.