Successful embryo implantation depends on three basic factors – embryo quality, receptive endometrium, and synchronized dialogue between the maternal tissue and blastocyst. But how to determine the optimal duration of progesterone administration before transferring an embryo?
Progesterone is an endocrine hormone, but when it starts acting on the endometrium, both on the epithelium and the stromal cells, it acts in paracrine and autocrine mechanisms. Hence, there is a shift from endocrine action to paracrine and autocrine action at the level of the endometrium. If there is no shift or any disruption in the shifting from endocrine action to the paracrine and autocrine actions, then there is P-resistance.
That means, there will not be any deficiency in progesterone, and the hormone will be sufficient but when it starts acting, there will be some defect at the paracrine and autocrine level, and that is how the p-resistance will start evolving.
Surprisingly, there has not been any meta-analysis that gave strong evidence to say that we need to give 4 days of progesterone for day 3 embryo and 6 days progesterone for day 5 embryo. However, the concept of P-resistance and Successful embryo implantation has evolved only after observing the natural cycles.
The Macklon triangle says that the majority of the conceptions, say around 70 – 75%, are of no use, and more than 60% will go to waste even before this concept’s importance is noted. That is, the P-resistance and implantation failure or the early pregnancy losses will go much before its clinical recognition.
However, many recent technologies and studies have shown that we are slowly progressing towards understanding the interaction between the endometrium and the embryo.
The implantation rates have been relatively stagnant over the past 10 years and that implies that the studies on implantation have really slowed down. More than half of all these cases seem to be concentrated in specific subgroups of patients including those with unexplained causes.
A recent study published in Journal of Assisted Reproduction and Genetics, in January 2019, revealed that after correcting the endometriosis either by not correcting may be controlling the endometriosis by either giving two doses of depot injections or by laparoscopy. It also courted that a good clinical pregnancy and live birth rate can be achieved.
On the other hand, many studies have also shown that 40 – 50% of the euploid embryos fail to implant and it is extremely likely that there are implantation related abnormalities not measured by ERA (Endometrial Receptivity Analysis) test alone.
More prospective studies using pregnancy outcome endpoints are certainly needed before we can overcome Edward’s last barrier to the ART (Assisted Reproductive Technology) success. In the future, our goal should be to make receptive implantation failure an exceedingly rare occurrence.
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