IVF Failure: Common Reasons & Next Steps

In vitro fertilisation (IVF) failure can be a heartbreaking experience for couples trying to conceive. Understanding the IVF failure reasons is crucial for guiding future treatment strategies and improving the chances of success. As a fertility specialist practising across multiple locations in Chennai, including Mylapore and Chetpet, I often see patients struggling with this issue. This blog post aims to shed light on the common causes of IVF failure and provide guidance on what to do next.

What Is IVF and How Does It Work

IVF is a complex series of procedures used to help with fertility or prevent genetic problems and assist with the conception of a child. During IVF, mature eggs are collected (retrieved) from your ovaries and fertilised by sperm in a lab. Then the fertilised egg (embryo) or eggs are transferred to your uterus. One full cycle of IVF takes about three weeks.

The IVF process typically involves these steps:

1. Ovarian Stimulation: Medications are used to stimulate the ovaries to produce multiple eggs.
2. Egg Retrieval: Eggs are retrieved from the ovaries using a needle guided by ultrasound.
3. Fertilisation: The eggs are fertilised with sperm in a laboratory setting. Intracytoplasmic sperm injection (ICSI) is sometimes used to inject a single sperm directly into each egg.
4. Embryo Culture: Fertilised eggs (embryos) are monitored for several days to assess their development.
5. Embryo Transfer: One or more embryos are placed into the uterus.
6. Pregnancy Test: A blood test is performed about two weeks after the embryo transfer to determine if pregnancy has occurred.

Common Reasons for IVF Failure

IVF failure can be attributed to a variety of factors, which can be broadly categorised into embryo-related, uterine-related, and other contributing factors. According to recent studies, chromosomal abnormalities in the embryo are a significant reason, with 25% to 40% of oocytes being chromosomally abnormal. Here are some of the most common reasons:

Embryo Quality

• Chromosomal Abnormalities: The most frequent cause of IVF failure is chromosomal abnormalities (aneuploidy) in the embryo. As women age, the risk of these abnormalities increases. Preimplantation genetic testing for aneuploidy (PGT-A) can screen embryos for chromosomal abnormalities before transfer.
• Embryo Development: Even if embryos appear morphologically normal, they may have underlying developmental issues that prevent successful implantation. As someone with direct IVF lab expertise, I personally work in the IVF laboratory, selecting and grading embryos under magnification.
• Egg Quality: Egg quality declines with age, affecting the embryo's potential for implantation. Factors such as oxidative stress and mitochondrial dysfunction can also impact egg quality.
• Sperm Quality: Sperm quality is another contributing factor. Poor sperm motility, morphology, or DNA fragmentation can affect fertilisation and embryo development. A semen analysis can evaluate sperm health.

Uterine Factors

• Endometrial Receptivity: The endometrium (uterine lining) must be receptive for the embryo to implant. Endometrial receptivity can be affected by factors such as endometrial thickness, uterine abnormalities, and hormonal imbalances.
• Uterine Abnormalities: Conditions such as uterine polyps, fibroids, or adhesions can interfere with implantation. A hysteroscopy or saline sonogram can help identify these issues.
• Adenomyosis: Adenomyosis, a condition where the endometrial tissue exists within and grows into the uterine wall, can significantly reduce the chances of successful implantation. The presence of adenomyosis can lead to chronic inflammation and structural changes in the uterus, making it difficult for the embryo to attach and thrive.
• Endometritis: Chronic endometritis, an inflammation of the uterine lining, can also lead to IVF failure. A systematic review and meta-analysis concluded that women with endometrial polyps exhibit a higher prevalence of chronic endometritis.

Lifestyle and Other Factors

• Age: Maternal age is a significant factor affecting IVF success rates. As women age, egg quality declines, and the risk of chromosomal abnormalities increases.
• Lifestyle Factors: Smoking, excessive alcohol consumption, obesity, and stress can negatively impact fertility and IVF outcomes.
• Underlying Medical Conditions: Conditions such as polycystic ovary syndrome (PCOS), endometriosis, thyroid disorders, and autoimmune diseases can affect IVF success.
• Immunological Factors: In some cases, immunological factors can contribute to IVF failure. These factors involve the maternal immune system rejecting the embryo.
• Unexplained Infertility: Sometimes, despite thorough investigations, the cause of IVF failure remains unexplained.

IVF Failure Investigation: Diagnostic Tests

After a failed IVF cycle, it's essential to conduct a thorough investigation to identify potential underlying issues. Here are some common diagnostic tests:

Semen Analysis

A semen analysis evaluates sperm count, motility, and morphology. Abnormalities in sperm parameters can affect fertilisation and embryo development.

Ovarian Reserve Testing

Ovarian reserve testing assesses the quantity and quality of a woman's eggs. Common tests include:

• Anti-Müllerian Hormone (AMH): AMH levels indicate the number of remaining eggs in the ovaries.
• Follicle-Stimulating Hormone (FSH): FSH levels can provide information about ovarian function.
• Antral Follicle Count (AFC): AFC measures the number of follicles in the ovaries using ultrasound.

Uterine Evaluation

Uterine evaluation assesses the uterine cavity for abnormalities that may interfere with implantation. Common tests include:

• Hysteroscopy: A hysteroscopy involves inserting a thin, lighted scope into the uterus to visualise the uterine lining.
• Saline Sonogram (Saline Infusion Sonohysterography - SIS): A saline sonogram uses ultrasound to examine the uterine cavity after injecting saline solution.
• 3D Ultrasound: ESHRE recommends 3D ultrasound for investigations.

Blood Tests

Blood tests can help identify hormonal imbalances, thyroid disorders, and autoimmune diseases. Common tests include:

• Thyroid-Stimulating Hormone (TSH): TSH levels assess thyroid function.
• Prolactin: Elevated prolactin levels can interfere with ovulation.
• Antiphospholipid Antibodies (APL): APL testing screens for antiphospholipid syndrome, an autoimmune disorder that can affect pregnancy.

Endometrial Biopsy

An endometrial biopsy involves taking a small sample of the uterine lining to assess its receptivity. The Endometrial Receptivity Analysis (ERA) test can help determine the optimal timing for embryo transfer.

Genetic Testing

Genetic testing can screen embryos for chromosomal abnormalities before transfer.

• Preimplantation Genetic Testing for Aneuploidy (PGT-A): PGT-A screens embryos for chromosomal abnormalities.
• Karyotyping: Karyotyping analyzes chromosomes to identify any abnormalities.

Next Steps After a Failed IVF Cycle

After a failed IVF cycle, it's essential to take a step back and reassess the situation. Here are some next steps to consider:

Review the IVF Cycle

Carefully review the IVF cycle with your fertility specialist to identify any potential issues with ovarian stimulation, egg retrieval, fertilisation, embryo development, or embryo transfer.

Consider Additional Testing

Based on the initial investigations, consider additional testing to identify any underlying conditions that may be contributing to IVF failure. Diagnostic reassessment is often recommended after IVF failure to identify missed factors.

Lifestyle Modifications

Make lifestyle modifications to improve fertility and overall health. These include:

• Healthy Diet: Follow a balanced diet rich in fruits, vegetables, lean proteins, and healthy fats. Consider a Mediterranean-style diet. Ensure adequate intake of folic acid, iron, and calcium. A balanced diet during IVF should consist of approximately 40-50% healthy carbohydrates, 25-35% lean protein, and 20-30% healthy fats.
• Weight Management: Maintain a healthy weight.
• Stop Smoking: Stop smoking at least three months before starting IVF.
• Limit Alcohol and Caffeine: Reduce alcohol and caffeine intake.
• Stress Reduction: Reduce stress through exercise, yoga, or meditation.

Adjust Treatment Protocol

Based on the findings of the investigations, adjust the treatment protocol for future IVF cycles. This may involve:

• Medication Adjustments: Adjusting the medications used for ovarian stimulation.
• ICSI: Using ICSI to improve fertilisation rates.
• Assisted Hatching: ASRM guidelines suggest that assisted hatching may be useful in patients with a poor prognosis.
• PGT-A: Using PGT-A to screen embryos for chromosomal abnormalities.

Explore Alternative Options

If multiple IVF cycles have failed, consider exploring alternative options such as:

• Donor Egg IVF: Using donor eggs can improve success rates for women with poor egg quality.
• Donor Sperm IVF: Using donor sperm can improve success rates for men with poor sperm quality.
• Surrogacy: Surrogacy involves another woman carrying and delivering the baby.

Data Table on Lifestyle Factors and IVF Outcomes

When to Seek Professional Help

Experiencing IVF failure can be emotionally and physically challenging. It's crucial to seek professional help from a fertility specialist to investigate the underlying causes and develop a personalized treatment plan. According to an ESHRE survey, recurrent implantation failure is defined after three consecutive embryo transfers. For personalised guidance, book a consultation with Dr. Rukkayal Fathima. Remember that with the right approach and support, many couples can achieve their dream of parenthood.