Understanding IVF Failure, Investigative Strategies, and Ways to Improve IVF Success

Empowering Patients on Their Fertility Journey

Introduction

Embarking on the journey of in vitro fertilization (IVF) can be both hopeful and challenging. IVF is a highly advanced assisted reproductive technology that has helped millions achieve their dream of starting or growing a family. However, it is important to know that not every IVF cycle results in a pregnancy. 

Just like every seed that is planted in soil doesn’t become a plant, owing to either seed or soil or environment problems, similarly when IVF fails we need to determine if the issue is in the seed (embryo), the soil (uterus) or in the environment (mother’s body).  This leaflet is designed to help you understand possible reasons for IVF failure, the tests doctors may recommend to first determine the cause, and then help choose strategies to improve your chances in future attempts.

Why Does IVF Sometimes Fail?

IVF is a complex process involving many steps, and there are several reasons why it may not lead to a successful pregnancy. Understanding these factors can help you and your healthcare team make informed decisions as you move forward.

• Maternal Age: As women age, egg quality and quantity naturally decline. Older age can make it harder to achieve pregnancy through IVF, as eggs may be fewer and less likely to fertilize or develop into healthy embryos.
• Embryo Quality: High-quality embryos have a better chance of implanting and developing into a healthy pregnancy. Embryos may not develop properly due to genetic issues or problems during fertilization.
• Implantation Challenges: Even healthy embryos sometimes do not implant in the uterine lining. Issues such as a thin endometrium (uterine lining), uterine polyps, fibroids, or scar tissue can affect implantation.
• Genetic Factors: Genetic abnormalities in the embryos or the parents themselves can reduce the chances of a successful pregnancy and may result in miscarriage or unsuccessful implantation.
• Lifestyle and Health Factors: Habits like smoking, heavy alcohol use, or being overweight can influence IVF outcomes. Health conditions such as polycystic ovary syndrome (PCOS), endometriosis, and thyroid disorders may also impact success rates.
• Sperm Issues: Male fertility factors, including low sperm count, poor motility (movement), or abnormal sperm shape, may indicate a chromosomal issue in the sperm which can in turn can affect the ability to fertilize an egg or lead to problems in embryo development.
• Immunological and Blood Clotting Problems: Sometimes, the mother's immune system or blood clotting tendencies may interfere with embryo implantation or early development.

Investigative Strategies: Tests to Find Out Why IVF Failed

If an IVF cycle fails, your doctor may recommend additional tests to help understand the reasons and guide future treatment. These tests aim to identify any underlying problems that can be addressed to increase your chances of success.

1. Hormone Assessment

Blood tests can check levels of hormones such as FSH (follicle-stimulating hormone), LH (luteinizing hormone), Anti-mullerian hormone (AMH), oestradiol, testosterone and progesterone. These tell your doctor about ovarian reserve (the number and quality of eggs remaining) and whether your hormones are well-balanced for conception.

2. Advanced Genetic Testing

• Preimplantation Genetic Testing (PGT-A):  PGT screens embryos for chromosomal abnormalities and can help select embryos with the best chance of resulting in a successful pregnancy. For PGT-A, embryo cells are obtained via a biopsy from the outer shell of the blastocyst (embryo). The DNA of these cells is then extracted and analysed.  (LINK to PGT-A page)
• Parental Genetic Testing: Blood tests for both partners can detect inherited genetic conditions that might affect embryo health or development.

3. Uterine Evaluation

Procedures such as ultrasound, hysteroscopy (using a small camera to look inside the uterus), or saline sonography can reveal physical abnormalities inside the uterus, such as polyps, fibroids, scar tissue, or septum, any of which may hinder implantation.

4. Endometrial Receptivity Testing (ERA)

Rarely there is a mismatch between the seed and soil ie the embryo and endometrium development. ERA is a specialized test that assesses whether the lining of your uterus is prepared to accept an embryo by analysing molecular markers. It helps determine the best timing for embryo transfer, maximizing the chance that the embryo and uterus are in sync. This is especially relevant if using medicated cycles for embryo preparation.

5. Semen Analysis and Sperm Quality Testing

A detailed semen analysis evaluates sperm count, motility, shape, and DNA integrity. Advanced tests such as sperm DNA fragmentation can detect deeper issues not seen on a standard analysis.

6. Immunological Tests

1. Immunological tests assess factors such as antiphospholipid antibodies and natural killer (NK) cells, which can influence implantation success. Higher-than-normal NK cell activity can raise the likelihood of the mother's immune system rejecting the foetus. Specialized tests—including blood panels and NK cell assays—help evaluate these risks by measuring antibody levels and cellular activity. When abnormalities are detected, treatment strategies are tailored to address the specific immunological issues. In cases of heightened NK cell activity, treatments might include corticosteroids or intravenous intralipid infusion or immunoglobulin (IVIG) to help modulate immune responses. 

7. Thrombophilia (Blood Clotting) Screening

Thrombophilia refers to an increased tendency for blood to clot. When a patient has thrombophilia, tiny blood clots may form in the blood vessels of the uterus, which can reduce oxygen and nutrient flow to the growing embryo. This may increase the risk of failed implantation or even early pregnancy loss. Thrombophilia can be inherited (passed down in families) or acquired later in life. Common thrombophilia tests include screening for genetic mutations such as Factor V Leiden and prothrombin gene mutation, as well as measuring levels of proteins that help control blood clotting, like antithrombin, protein C, and protein S. Tests may also check for antiphospholipid antibodies, which are linked to a higher risk of blood clots and have been associated with repeated implantation failure or miscarriage.

If a thrombophilia condition is detected, your fertility specialist may recommend specific treatments or changes to your IVF plan to help reduce the risk of clotting and support healthy implantation. This could include medications that thin the blood, such as low-dose aspirin tablets or heparin injections, or closer monitoring during your cycle.

What Happens After These Tests?

The results of these investigations help your fertility team identify specific barriers to success. In many cases, these findings can lead to targeted treatments or adjustments to your IVF plan, including:

• Changing medication protocols to better support egg development or better endometrium for implantation
• Scheduling embryo transfer at a time when the uterus is most receptive – using Natural cycle preparation for frozen embryo transfer may help
• Treating uterine abnormalities such as polyps or fibroids through minor surgical procedures
• Addressing immune system issues with medications such as corticosteroids, intralipid infusions, or intravenous immunoglobulin (IVIG)
• Managing blood clotting disorders with blood-thinning medications like low-dose aspirin tablets or heparin injections.
• Selecting genetically healthy embryos for transfer to reduce the risk of miscarriage
• Improving sperm quality through lifestyle changes, supplements, or advanced sperm selection techniques

Strategies to Improve IVF Outcomes

Alongside targeted medical treatments, there are many steps you can take to improve your chances of IVF success:

• Adopt a Healthy Lifestyle: Eating a balanced diet, exercising regularly, stopping smoking, limiting alcohol and caffeine, and maintaining a healthy weight all contribute positively to fertility.
• Manage Stress: Infertility treatment can be emotionally challenging. Seeking counselling, support groups, or stress-reduction techniques such as mindfulness or yoga can be beneficial.
• Address Underlying Health Conditions: Managing conditions such as diabetes, thyroid disease, or high blood pressure before and during IVF can help improve outcomes.
• Medication and Supplement Adherence: Take all medications and supplements as prescribed by your fertility team.
• Maintain Open Communication: Keep in close contact with your healthcare team and ask questions about your treatment plan and test results.

Looking Ahead: Your Fertility Journey

It’s natural to feel disappointed after an unsuccessful IVF cycle, but each cycle provides valuable information that can inform future success. Advances in reproductive medicine mean that new solutions and tailored approaches become available all the time. By understanding your individual circumstances and working closely with your fertility team, you can move forward with a renewed and more personalized approach.

Conclusion

While IVF failure can be a difficult setback, it is not the end of the journey. With the help of investigative tests and personalized treatment strategies, many people achieve successful pregnancies in future cycles. Your fertility specialists will be with you every step of the way, offering guidance, support, and hope for what comes next.

If you have questions or concerns, don’t hesitate to reach out to your fertility clinic. Remember, you are not alone—and with knowledge, support, and advanced care, the dream of building your family remains within reach.