By Anja Stojsin Carter, PhD.
For a pregnancy to occur, an embryo travels to the uterus via the fallopian tubes and arrives around Day 5 or 6 post-fertilization. At this stage, the embryo is a blastocyst and is made of two layers; the inner layer (Inner Cell Mass) forms the fetus/baby and the outer layer (trophectoderm) forms the placenta. The embryo then hatches through the glycoprotein shell known as Zona Pellucida (ZP) and is ready to make a contact with endometrium (the first layer of the uterine lining).
In an IVF cycle, the embryo is placed into the uterus directly by the fertility physician using a specialized catheter. Once in the uterus, the embryo must still hatch from the ZP shell and begin implantation.
The stages of implantation are attachment, when proteins on the surface of the embryo and the endometrium link and anchor the embryo; invasion, where the embryo starts to “dig” into the lining; and decidualization, where blood flow and immune changes occur in the endometrium, ultimately assuring that the embryo does not get rejected as a foreign body (since it is genetically unique from the uterine cells).
By 10 to 12 days of development, the embryo is completely embedded into the endometrium and ready to start developing into the fetus and placenta.
The presence of the embryo in the endometrium induces production of the human chorionic gonadotropin (hCG) hormone. hCG gets released into the blood and urine and therefore can be detected by the pregnancy tests. Growth of the embryo and secretion of hCG further signals the ovarian follicle that released the oocyte to begin the production of progesterone, a hormone crucial for further thickening of the endometrium and proper progression of the pregnancy.
There are some things that we can do to help determine if an IVF embryo and the uterine lining are suitable and increase the chance of a successful implantation! With the current scientific knowledge, it is highly recommended that both embryo health and endometrial receptivity is checked in every patient going through the IVF.
The embryo needs to be a euploid, meaning that it has the proper genetic compliment (46 chromosomes). In a spontaneous pregnancy this cannot be tested, but in IVF, the embryo trophectoderm can be biopsied and the cells tested to make sure it is euploid (Pre-Implantation Genetic Testing; PGT). If an embryo is aneuploid, meaning it doesn’t have the proper number of chromosomes, then it is very unlikely to result in a pregnancy or could produce a miscarriage.
The endometrial receptivity assay (ERA) tests the endometrial lining in order to determine the moment when the embryo is most likely to implant. In most people, this is Day 5 of embryo development (5 days post-ovulation) but in approx. 30% of people, this window is shifted earlier or later. If this is known, the day of embryo transfer can be adjusted so it happens during the optimal time.
Last but not least, immunological status of the endometrium can be assessed. More specifically, the increased presence of the Natural Killer (NK) cells could be increasing the risk of the implantation failure. These cells are naturally present at the site of implantation, however, if in high numbers can lead to pregnancy rejection. It has been showed that something as simple as intravenous intralipid injections can be used to decrease the potency of these cells and increase implantation success.
In summary, PGT and ERA are becoming the standard of care prior to an embryo transfer. These tests give us information to select the best embryo and transfer it on the optimal day, providing a patient the best chance of becoming pregnant and minimizing risk of implantation failure.