This is a very interesting study that relates to recurrent pregnancy loss patients. This is a very early phase study just basically raising the idea that this drug may be of benefit and needs much more study before application patient care. The study makes the point that with higher order loss numbers, 4 or greater, the chance of having “normal genetic testing” increases. A caution, however relates to how normal is defined in genetic testing and certainly applies to our fertility patients undergoing embryo testing. Even with “whole genome sequencing,” the entire genetic picture is not tested. Therefore, normal only relates to the limits of testing which to date is limited to large changes in chromosomal structure and completely excludes single gene problems that could result in death of the embryo or abnormal development. The lining changes referred to in this study were linked also to progesterone levels, that can be related to ovulatory dysfunction and this was not addressed in this study. Our thoughts regarding subtle ovulation defects as a cause of a significant percentage of losses certainly could be supported by this studies’ findings. A caveat of this study revealed in the disclosures is the author is submitting patents for the test looking at the tissue changes associated in the changes studied in the endometrial lining. This always raises a red flag. A very interesting aspect though relates to the incretin pathway that is affected beneficially by the drug Sitagliptin is useful in the treatment of later phase insulin resistance and early type II DM. We know that this dysfunction is intimately associated with ovulation defects, progesterone secretion defects from the follicle and hence recurrent pregnancy loss. Further elucidation of these mechanisms and possibly the correlation of ovulation problems with these structural changes in the endometrial lining could prove very helpful in better understanding the basis of recurrent pregnancy loss.
Michael D. Fox, MD
Advanced Reproductive Specialists