In vitro fertilization (IVF) is the last opportunity for countless individuals and couples struggling with infertility. For over 40 years, IVF has stood as a beacon of hope for its ability to facilitate conception outside the body. It has revolutionized reproductive medicine and has given rise to new possibilities for starting or expanding families. However, despite its increasing success rates over the years, IVF remains a complex and intricate procedure, fraught with challenges and uncertainties. It still only has an average success rate of 56% for women under 35 and lower for those older. Emotionally, one of the most disheartening outcomes for those undergoing IVF is the failure to achieve a successful pregnancy. The causes of IVF failure are multifaceted, encompassing a myriad of biological, technical, and environmental factors that interplay in intricate ways. We start by describing and summarizing these general factors and then provide some actionable options available to solve the root causes. Some of these actions or options will be offered to you but for others, you may need to advocate. 

IVF Failure Caused by Biological Factors 

Biological factors are perhaps the most fundamental contributors to IVF failure. While IVF techniques have advanced significantly, they still cannot entirely compensate for certain underlying biological issues that hinder successful implantation and pregnancy. 

Advanced Maternal Age: One of the primary biological factors linked to IVF failure is the age of the woman undergoing the procedure. As women age, the quality and quantity of their eggs decrease, leading to a higher likelihood of chromosomal abnormalities in embryos. These abnormalities can result in failed implantation, early miscarriage, or developmental issues in the fetus.

Genetic Abnormalities: Genetic factors play a pivotal role in the success of IVF. Both partners contribute genetic material to the embryo, and if either or both partners carry genetic mutations or anomalies, the chances of IVF failure increase. These genetic factors can result in implantation failure or early pregnancy loss.

Action: Preimplantation Genetic Testing (PGT) can uncover many of these abnormalities increasing the probability that the embryo that is being used will result in a successful live birth.

Endometrial Receptivity: The receptivity of the uterine lining to the embryo, known as endometrial receptivity, is a critical factor in IVF success. Hormonal imbalances, anatomical abnormalities, or inflammatory conditions such as endometriosis can compromise the receptive environment of the uterus, leading to failed embryo implantation.

Action: IVF centers use ultrasound, blood tests and hormone injections as standard protocols for many conditions affecting endometrial receptivity. In addition, a relatively new test called ReceptivaDx is now available using an endometrial biopsy to help detect endometriosis and other inflammatory conditions.

Technical Factors

The technical aspects of IVF, including laboratory procedures and embryo manipulation, are vital in determining the outcome of the procedure. A slight misstep in any of these processes can lead to IVF failure.

Embryo Selection: Embryo selection is a crucial step in IVF. Not all embryos have the same potential for successful implantation. While pre-implantation genetic testing (PGT) can help identify chromosomally normal embryos, the process is not foolproof, and some embryos may still fail to implant despite appearing healthy.

Cryopreservation Challenges: Freezing embryos for future transfer, known as cryopreservation, is a common practice in IVF. However, the freezing and thawing processes can sometimes damage the embryos, affecting their viability and reducing the chances of successful implantation. Thankfully this technology has improved tremendously in the last 10 years making this a less likely cause of IVF failure.

Laboratory Conditions: The conditions within the IVF laboratory are pivotal. Fluctuations in temperature, humidity, or air quality can impact embryo development. Additionally, errors in embryo handling or culture medium composition can lead to poor embryo quality and subsequent implantation failure.

Action: Reviewing the success rates of an IVF center you are interested in will help uncover poor quality control. Do they have their own on-site embryo lab or is this outsourced? What is the experience of the personnel working at these labs?

Environmental and Lifestyle Factors Impacting IVF Failure

IVF failure can also be influenced by external factors that may not be directly related to the medical procedures but can still impact the success of the treatment.

Stress: The emotional and psychological stress of undergoing IVF can have physiological effects on the body. Chronic stress can disrupt hormonal balance, potentially affecting egg quality, embryo development, and uterine receptivity.

Lifestyle Choices: Lifestyle factors such as diet, exercise, and substance use can impact IVF outcomes. Poor diet, excessive caffeine or alcohol consumption, and smoking can all contribute to lower fertility and reduced chances of successful IVF.

Environmental Toxins: Exposure to environmental toxins and pollutants has been linked to fertility issues. These toxins can affect both egg and sperm quality, leading to decreased chances of successful fertilization and implantation.

Underlying Health Conditions

Certain underlying health conditions can significantly impact IVF success rates.

Polycystic Ovary Syndrome (PCOS): Women with PCOS often have irregular menstrual cycles and hormonal imbalances, which can make it more challenging to predict ovulation and time the IVF procedures accurately.

Endometriosis: Endometriosis, a condition in which tissue similar to the uterine lining grows outside the uterus, can lead to inflammation and scarring, potentially affecting egg quality, embryo development, and implantation. For more than half the women with endometriosis going through fertility treatment, their endometriosis is “silent” meaning no obvious symptoms.

Action: A relatively new test called ReceptivaDx is now available using an endometrial biopsy to help detect endometriosis (including silent endometriosis) and other inflammatory conditions. If found positive, treatment options are available to resolve this common underlying issue.

Immunological Factors: In some cases, the body’s immune response may recognize embryos as foreign entities and attack them. This immunological response can result in failed implantation or early pregnancy loss.

Action: There are several tests that look for the relative amounts of T-cells, B-cells, and NK cells in the bloodstream. This is known as the immunophenotype and there are dedicated labs focused on these immunological issues in women who have had multiple failed IVFs.

The causes of IVF failure are intricate and interconnected, spanning biological, technical, and environmental realms. As our understanding of reproductive medicine continues to evolve, researchers and clinicians are continuously working to identify and address these factors to improve IVF success rates. While IVF failure can be devastating, it’s essential to recognize that each case is unique. Advances in technology, coupled with personalized treatment plans, offer renewed hope for individuals and couples facing IVF challenges. Educating and advocating for yourself is critical to maximizing your options for resolving IVF failure. 

Share this article: