Evidence that failure to conceive despite apparent correction of ovulatory defects by follicle-maturing drugs may be related to premature trophoblast invasion

There is evidence that follicle-maturing drugs, especially when used for controlled ovarian hyperstimulation for in vitro fertilization–embryo transfer (IVF–ET) purposes, may be associated with lower pregnancy rates following ET related to a hostile uterine environment. It was assumed that this was related to implantation failure of the embryos. However, there is a possibility that the embryo may implant too soon into a uterine environment not ready for the invading trophoblast. To test this hypothesis a 34kDa protein known as the progesterone-induced blocking factor (PIBF), which only rises after trophoblast invasion, was measured at the peri-implantation time 3 days after ET. The results showed a marked reduction in pregnancy rates per transfer in those positive for PIBF at this time especially in those receiving controlled ovarian hyperstimulation. Thus, these data suggested that premature trophoblast invasion rather than failure for embryos to implant may be the etiologic factor responsible for the adverse effect of controlled ovarian stimulation in the uterine environment.