What Should Be Investigated After Two Failed Embryo Transfers?

Estimated reading time: 8 minutes

Last updated: June 2026

Medically reviewed by Dr Ahmed Elgheriany

Consultant in Fertility & IVF

When Two Embryo Transfers Fail, Should You Simply Try Again?

One unsuccessful embryo transfer is unfortunately common and often reflects the natural biological limitations of human reproduction. However, when implantation repeatedly fails despite apparently reassuring treatment, many couples begin asking an important question:

“Are we missing something?”

In many situations, the answer is yes.

Repeated implantation failure should not automatically lead to repeating exactly the same treatment protocol. Instead, it should prompt a structured reassessment to identify potentially correctable factors before proceeding with another transfer.

Figure 1. A personalised framework for investigating recurrent implantation failure.

The goal is not to order every available investigation. Rather, it is to determine whether the previous treatment strategy overlooked important biological or clinical factors.

Step 1. Re-evaluate the Embryo

Successful implantation begins with the embryo.

Questions to consider include:

• Was the embryo transferred at the blastocyst stage?

• What was its morphological quality?

• Was preimplantation genetic testing (PGT-A) appropriate in this situation?

• Could laboratory culture conditions have influenced embryo development?

• Were there repeated fertilisation or blastulation problems suggesting poor gamete quality?

Even chromosomally normal embryos cannot implant if other components of implantation are not functioning optimally.

Step 2. Assess the Uterine Environment

A receptive uterus is essential.

Assessment should include:

• Three-dimensional ultrasound

• Careful assessment for adenomyosis

• Endometrial thickness and appearance

• Fibroids affecting the uterine cavity

• Endometrial polyps

• Congenital uterine abnormalities

• Intrauterine adhesions when suspected

Depending on the clinical history, hysteroscopy may also be appropriate.

Step 3. Consider Endometrial Health

The endometrium is far more than a tissue lining. Its function changes dramatically during the implantation window.

Important questions include:

• Is chronic endometritis suspected?

• Is implantation timing appropriate?

• Are there features suggesting impaired decidualisation?

• Has previous surgery altered endometrial function?

Structural normality does not always guarantee functional receptivity.

Step 4. Evaluate Male Factors Beyond Routine Semen Analysis

A normal semen analysis does not necessarily indicate normal sperm function.

In selected patients, further assessment may include:

• Sperm DNA fragmentation

• Oxidative stress assessment

• Detailed lifestyle review

• Medical conditions affecting sperm quality

• Previous chemotherapy or systemic illness

Male factors remain under-recognised contributors to repeated implantation failure.

Figure 2. Advanced laboratory investigations may identify underlying factors contributing to repeated implantation failure and help guide personalised IVF treatment.

Step 5. Review Ovarian Response

Rather than focusing solely on AMH levels, clinicians should ask:

• Was stimulation appropriate?

• Were sufficient mature oocytes obtained?

• Was egg maturity optimal?

• Was trigger timing appropriate?

• Was embryo development consistent with ovarian reserve?

Each stimulation cycle provides valuable biological information that should guide future treatment.

Step 6. Assess Systemic Medical Conditions

Several common medical conditions may influence implantation or early pregnancy.

Examples include:

• Thyroid disorders

• Diabetes

• Obesity

• Vitamin deficiencies

• Autoimmune diseases

• Coagulation disorders in carefully selected patients

Optimising general health should always accompany fertility treatment.

Step 7. Consider Immunological Assessment Carefully

Reproductive immunology remains one of the most debated areas in fertility medicine.

Current evidence does not support routine immune testing or empirical immunosuppressive treatment for every patient.

However, carefully selected individuals, particularly those with recurrent implantation failure, recurrent pregnancy loss, autoimmune disease, or previous abnormal immune investigations, may benefit from a personalised assessment performed within the context of their overall clinical picture.

Interpretation is often more important than the test itself.

No single immune marker should determine treatment in isolation.

Step 8. Review Previous Treatment Decisions

Sometimes the investigation lies not in new testing but in understanding what has already happened.

Important questions include:

• Was progesterone adequate?

• Was embryo transfer technically straightforward?

• Was the timing of transfer appropriate?

• Were medications individualised?

• Were previous cycles repeated without meaningful changes?

Every unsuccessful cycle should provide information that shapes the next one.

Figure 3. Successful fertility care depends not only on performing the right investigations, but also on interpreting them in the right clinical context.

A Personalised Approach Matters

Repeated implantation failure rarely has a single cause. Instead, it often reflects the interaction of several small factors involving the embryo, the uterus, hormonal environment, sperm quality, and maternal physiology.

The most effective investigation is therefore not necessarily the largest panel of tests, but a structured clinical assessment that identifies which investigations are genuinely relevant for each individual patient.

Key Takeaway

After two failed embryo transfers, the next step should not simply be another transfer using the same protocol.

Instead, treatment should begin with a careful reassessment of the embryo, uterus, endometrium, male factors, ovarian response, general health, and, where appropriate, selected immunological considerations.

Personalised fertility care aims to understand why implantation has not occurred before deciding how to proceed.

About the Author

Ahmed Elgheriany, MSc, MRCOG

Consultant in Fertility & IVF

Dedicated to evidence-based, personalised fertility care with a specialist interest in recurrent implantation failure, reproductive immunology, endometriosis, adenomyosis, recurrent pregnancy loss, and complex IVF treatment.

This article is intended for educational purposes only and should not replace personalised medical advice.