Why Do Some Normal Embryos Fail to Implant?

One of the hardest questions to answer for a fertility specialist is, “Why did a genetically normal embryo fail to implant?”.  With the increased use of preimplantation genetic screening on embryos, couples often have very high hopes of achieving a pregnancy when a genetically normal is obtained from an in vitro fertilization cycle. Unfortunately, not all genetically normal embryos will create a pregnancy.

When it comes to the embryo, it’s not only the genetics that determine implantation potential.  The health of the sperm and egg even prior to fertilization play an important role in embryo growth and development.  For instance, we know that women who experience severe stress during or preceding their IVF cycles have worse embryo quality than patients with less stress.  Stress and other lifestyle factors (smoking, illicit drug use, etc.) can influence the quality of sperm and egg, so that even if they create a genetically normal embryo, it may not be healthy enough to implant.

Newer testing looking at mitochondrial DNA expression may give us some insight into how stressed an embryo is and what it’s implantation potential may be.  Stressed embryos seem to compensate by increasing their mitochondrial DNA expression.  The mitochondrial energy is needed for chromosome and cell division, so stressed embryos have to increase their mitochondrial DNA to get the job done.  Quantifying the amount of mitochondrial DNA expression of genetically normal embryos gives us more information about the quality of each embryo.

Uterine factors also play a role in implantation failure.  For patients who don’t conceive with a genetically normal embryo, it’s important to take a close look at the uterine cavity.  I often recommend a hysteroscopy, which is a simple outpatient procedure, to get a clear look at the uterine cavity.  This allows us to make sure there are no lesions, such as polyps or intrauterine fibroids, that prevented implantation.  A biopsy of the uterine lining also allows us to look for underlying inflammation (chronic endometritis) that may not be visible to the naked eye.

Lastly, synchronizing the uterine lining to the developmental stage of the embryo is important.  An endometrial receptivity test allows us to know if we have timed the embryo transfer appropriately.  For some patients, the uterine lining may be slower to “mature” than others, which shifts their implantation window to a later time.  If this is not identified, even the best embryos won’t be able to stick because the uterine lining won’t be at the right stage for implantation.

There are many possible reasons why an embryo may fail to implant, but for some patients, the cause may never be determined.  Although our testing has come a long way, there is still a lot we don’t know about embryo implantation.  I can only hope that over time, our technology and testing will become even better, so that we can increase implantation potential and provide more answers to patients who don’t conceive.

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