Why Do Good Embryos Not Implant?

One of the most frustrating aspects of the IVF journey can be the failure of good-quality embryos to implant, even after multiple attempts. Boston IVF reproductive endocrinologist, Dr. Pietro Bortoletto, dives deep into why this happens and explores the complex, multifaceted process of implantation to shed light on potential reasons for implantation failure—and what can be done about it.

What is Recurrent Implantation Failure (RIF)?
Recurrent implantation failure (RIF) refers to the repeated failure of embryos to implant in the uterus after multiple IVF cycles. According to Dr. Bortoletto, implantation is confirmed by detecting a specific level of HCG (pregnancy hormone) in the blood. When this level remains below the threshold, it is considered a failed implantation. RIF is typically diagnosed after several failed attempts using high-quality embryos.

The definition of RIF is still evolving, but generally, if a patient has transferred two or more high-quality embryos across multiple cycles and fails to achieve a pregnancy, it may be considered recurrent implantation failure. Understanding why this happens requires exploring the intricacies of the implantation process.

The Complexity of Embryo Implantation
The process of implantation is far from straightforward. It involves a "battle," as Dr. Bortoletto puts it, between the embryo and the uterus. The uterus must evaluate the quality of the embryo and decide whether to support its growth, while the embryo works to establish itself in the uterine lining. This process consists of three key stages:

1. Embryo Opposition: The embryo first gets close to the uterine lining.
2. Embryo Adhesion: The embryo adheres to the uterine lining.
3. Embryo Invasion: The embryo invades the uterine lining, establishing a connection with the mother's blood supply.

Each of these stages must go perfectly for successful implantation, but there are many variables—both with the embryo and the uterus—that can go wrong. Even "good" embryos may fail to implant if there is a problem with the uterine environment, timing, or communication between the two.

Factors Leading to Implantation Failure

1. Embryo Quality
   • Even high-quality embryos may not always implant due to chromosomal abnormalities that can't be seen through routine observation. Preimplantation genetic testing (PGT) can help identify embryos with a higher likelihood of success.
   • Poor communication between the embryo and the uterus can result in failure, as good-quality embryos release certain molecular signals that help facilitate implantation.
2. Uterine Issues
   • Anatomical problems like polyps, fibroids, or scar tissue inside the uterus can prevent successful implantation. Even issues like adenomyosis, where tissue from the uterine lining invades the muscular walls of the uterus, can negatively impact implantation.
   • The window of implantation is a critical period when the uterus is most receptive to an embryo. If this timing is off, even the best embryos may not implant.
3. Immune System Factors
   • The immune system plays a role in deciding whether the uterus will accept or reject an embryo. Sometimes, an overly active immune response can reject an embryo, treating it as a foreign body. The presence of immune cells like natural killer cells and T cells can affect this process, although further research is needed to determine how much of an impact these immune factors have.
4. Genetic Factors
   • Sometimes, the problem lies with the parents' genetics. Inherited conditions can affect how embryos develop, even if they appear to be of good quality.

How Can We Improve Implantation Success?
While implantation is a complex process, there are several ways to improve the chances of success:

1. Preimplantation Genetic Testing (PGT): PGT allows doctors to screen embryos for chromosomal abnormalities, helping to ensure only genetically normal embryos are transferred, increasing the chance of implantation.
2. Uterine Evaluation: Before beginning another IVF cycle, doctors may recommend evaluating the uterus using a hysteroscopy or saline sonogram to check for polyps, fibroids, or scar tissue that may interfere with implantation. Removing these abnormalities can create a more hospitable environment for the embryo.
3. Optimizing the Uterine Lining: Timing is everything. Doctors may perform tests to ensure the window of implantation is properly timed. If the window is off, medications can be used to adjust the timing to better support the embryo.
4. Addressing Immune and Clotting Issues: In cases where immune factors are suspected to be an issue, treatments such as blood thinners, low-dose aspirin, or even immune-modulating therapies may be used to improve the chances of implantation.
5. Lifestyle Adjustments: Lifestyle factors like smoking, stress, and weight can also impact the chances of successful implantation. Behavioral changes, such as quitting smoking and managing weight, can improve the overall chances of success.

Conclusion
Embryo implantation is a complex, highly orchestrated process, and when good embryos fail to implant, it can be frustrating and emotionally exhausting. However, by understanding the potential causes of failure and working closely with your fertility team, steps can be taken to improve the likelihood of success. Whether it's through genetic testing, uterine evaluation, or immune system management, there are many ways to increase the chances of a successful pregnancy.