Implantation failure of endometrial origin: what is new?

To review recent findings related to possible causes of recurrent implantation failure of endometrial origin in normal uterus.

Recent evidences suggest that in apparently normal endometria, RIF may associate with molecular and functional changes in the uterus such as abnormal endometrial microbiota, including the presence of chronic endometritis, poor synchronization between the blastocyst and endometrium, and/or excessive uterine peristalsis. An altered endometrial microbiota detected by molecular techniques has been recently related to poorer embryo implantation, even in apparently normal endometria. The use of the endometrial receptivity analysis test to obtain an objective signature of endometrial receptivity has shown to improve the reproductive performance in RIF patients. The diagnosis of uterine peristalsis, however, remains challenging since the usual evaluation by transvaginal ultrasound is not accurate, and drugs tested to reduce uterine peristalsis and enhance embryo implantation have not been clearly beneficial. Finally, endometrial injury to improve implantation rates remains controversial being definitive well-designed trials needed to assess its benefit, if any.

In recurrent implantation failure of endometrial origin an altered pattern of the microbial endometrial ecosystem, a displaced window of implantation leading to desynchronization between the blastocyst and the endometrium, or an altered pattern of uterine contractions during embryo transfer may be factors to consider in our attempt to solve this clinical issue. New diagnostics for assessing these conditions and new therapies to improve these dysfunctional situations are currently under investigation to be presumably included in the near future in the work-up of affected patients.