When IVF doesn’t work, it can feel discouraging — but it’s not the end of the road. With the right care, science, and support, there are always new paths to parenthood.
In this webinar, Dr Athanasios Pantelis, PhD – Obstetrician-Gynaecologist, Infertility Specialist & Scientific Director at NewLife Greece – explains what Recurrent Implantation Failure (RIF) is, why it happens, and what can be done to improve outcomes.
Dr Pantelis also shares 3 real-life IVF success stories after RIF, giving patients hope and practical insights into treatment strategies that can make a difference.
Recurrent implantation failure (RIF) is one of the most emotionally and clinically challenging situations in assisted reproduction. During this educational webinar, Dr Athanasios Pantelis shared his clinical experience, scientific evidence, and real-life IVF cases to explain why implantation sometimes fails and what can be done when it does.
The discussion focused on understanding the causes of RIF, how it is properly diagnosed, and how personalised treatment strategies can still lead to successful pregnancies—even after multiple failed IVF attempts.
Dr Pantelis explained that recurrent implantation failure refers to repeated failure of embryos to implant into the uterus after several IVF attempts. Although definitions can vary, RIF is commonly described as:
• Three or more failed embryo transfers
• Transfer of good-quality blastocyst-stage embryos
• Often after IVF cycles that appear technically correct
He emphasised that defining RIF correctly is essential. Clinicians must consider:
• The developmental stage of embryos (blastocyst stage is key)
• Whether embryos were genetically tested
• Embryo morphology and quality
• Exclusion of other factors such as uterine abnormalities or severe egg quality issues
RIF affects a significant proportion of IVF patients—estimated at around 20–25%—and often leads to emotional distress, financial strain, and frustration for patients and clinicians alike.
According to Dr Pantelis, RIF is multifactorial. In most cases, more than one factor contributes to implantation failure.
Embryonic causes account for the largest proportion of implantation failures. These include:
• Chromosomal abnormalities (aneuploidy)
• Poor embryo quality
• Developmental arrest or slow embryo growth
• Genetic mutations
Dr Pantelis noted that embryos may appear morphologically normal but still be genetically abnormal, which explains why implantation can fail despite “good-looking” embryos.
The uterine environment plays a crucial role in implantation. Potential maternal causes include:
• Submucosal fibroids
• Endometrial polyps
• Uterine septum
• Thin endometrium
• Poor blood flow to the uterus
• Non-receptive endometrium
• Chronic endometrial inflammation
He highlighted that although embryonic factors account for roughly 80% of implantation success, endometrial receptivity still contributes around 20%, making uterine assessment essential.
Immune system dysregulation may prevent implantation or lead to very early pregnancy loss. These include:
• Elevated natural killer (NK) cells
• Antiphospholipid syndrome
• Autoimmune conditions such as lupus or Hashimoto’s thyroiditis
Dr Pantelis explained that immune-related implantation failure is increasingly recognised and, in selected cases, can be treated effectively.
Genetic abnormalities in either partner may affect embryo development. These may include:
• Chromosomal rearrangements
• Balanced translocations
• Other inherited genetic conditions
In such cases, advanced genetic testing becomes essential.
Dr Pantelis stressed that a thorough and structured investigation is critical. Current evidence supports a comprehensive approach that may include:
• Parental karyotyping from peripheral blood
• Preimplantation Genetic Testing (PGT-A, PGT-M, or PGT-SR)
• Diagnostic hysteroscopy to assess the uterine cavity
• Endometrial biopsies for:
– CD138 (chronic inflammation)
– Natural killer cells
• Autoimmune blood testing
• Endometrial receptivity testing (ERA)
This personalised diagnostic pathway allows clinicians to target the underlying cause rather than repeating unsuccessful treatments.
Dr Pantelis outlined several evidence-based interventions depending on diagnostic results:
• PGT-A, PGT-M or PGT-SR for genetic abnormalities
• Antibiotic therapy and probiotics for chronic endometritis
• Operative hysteroscopy to remove fibroids, polyps, or septa
• Immune-modulating treatments such as:
– Corticosteroids
– Intralipid infusions
– Low-dose aspirin
He also discussed emerging techniques such as embryo–endometrial co-culture and mesenchymal stem cell therapies, noting that while early data are promising, larger trials are still needed.
The first case involved a 38-year-old woman and her 42-year-old partner with male factor infertility. IVF resulted in five blastocysts, but three consecutive single embryo transfers failed.
Further investigation revealed chronic inflammation of the endometrium through hysteroscopy and CD138 biopsy. After targeted antibiotic treatment and proper recovery time, a subsequent embryo transfer resulted in a successful pregnancy and live birth.
The second case involved a 45-year-old woman undergoing IVF with donor eggs due to menopause. Despite high-quality donor embryos, multiple transfers failed.
Advanced testing revealed that her endometrium was receptive 24 hours later than expected. Adjusting embryo transfer timing based on the ERA test led to a successful pregnancy.
A 42-year-old single woman with low AMH underwent multiple IVF cycles with her own eggs. Despite repeated attempts and normal endometrial conditions, all embryos tested genetically abnormal.
After extensive counselling, she proceeded with embryo donation. The first transfer resulted in a successful pregnancy and live birth.
Dr Pantelis emphasised that RIF places a heavy psychological burden on patients. Feelings of stress, anxiety, depression, and hopelessness are common.
He encouraged patients to seek:
• Psychological counselling
• Support groups
• Open communication with their fertility team
Patients must understand that they are not alone.
He explained that even after multiple failures, success is still possible.
Recurrent implantation failure is complex, multifactorial, and highly individual. However, advances in:
• Genetic testing
• Immune assessment
• Personalised embryo transfer timing
• Patient-centred care
are improving outcomes for many patients who once had limited options.
Dr Pantelis concluded that continued research, personalised treatment strategies, and emotional support are essential to help patients move forward on their fertility journey—even after IVF failure.
These tests were widely recommended in the past for many patients with recurrent implantation failure. However, in the last one and a half years, a large randomised controlled trial showed that identifying a “window of implantation” in one specific cycle does not mean that the same window applies every month for the same woman. Based on recent literature, most clinicians have significantly reduced their recommendations for these tests, as they do not appear to benefit the majority of patients.
When transferring one genetically tested (euploid) embryo, the chance of pregnancy is approximately 55–60%. When a woman has three genetically normal embryos available, the cumulative chance of pregnancy rises to approximately 92–93%. According to recent evidence and professional recommendations, transferring up to three euploid embryos significantly increases the likelihood not only of pregnancy but also of a viable pregnancy carried to term.
Adenomyosis is a common condition and is associated with reduced implantation rates. Current guidelines recommend freezing embryos and performing downregulation with appropriate injections to suppress adenomyosis before embryo transfer. The transfer should then be done in a medicated cycle. When adenomyosis is properly suppressed, pregnancy rates can become similar to those of women without this condition.
In the past, treatment mainly focused on supplements and vitamins. Over the last three to three and a half years, embryology laboratories have increasingly used sperm sorting devices that function as filters on the day of sperm collection. These devices allow embryologists to select sperm that are motile, morphologically normal, and have lower DNA fragmentation. At our clinic, we have used these techniques for approximately two and a half to three years and have largely overcome issues related to high DNA fragmentation.
Genetically abnormal embryos often fail to implant or result in miscarriage, usually before the ninth week. Late miscarriages, especially after the ninth week, are frequently associated with thrombophilias, including antiphospholipid syndrome. These conditions involve antibodies such as lupus anticoagulant or anticardiolipin antibodies. In such cases, a thorough investigation of the endometrial cavity is essential. If IVF continues, preimplantation genetic testing of embryos is recommended.
Blastocyst-stage embryos (day 5 or 6) have approximately double the chance of implantation compared to day 3 embryos. Until day 3, embryo development is mainly driven by maternal genetic material. From day 4 onward, paternal genetics begin to play a significant role. Embryos that cannot reach the blastocyst stage in the laboratory are also unlikely to survive in the uterus.
For women over 42–43, approximately 20 mature eggs are often needed to obtain one chromosomally normal embryo. Some women may achieve this in one attempt, others in multiple attempts. The key factor is collecting as many eggs as possible to increase the likelihood of finding a euploid embryo.
If endometriosis has been properly treated and both fallopian tubes are open, spontaneous conception should be attempted for 6–9 months, even with low AMH. If pregnancy does not occur, IVF should then be considered.
Yes. Combining embryos from a fresh cycle with frozen embryos can increase the overall chance of pregnancy.
Elevated NK cells in blood are not reliable, as they may indicate various autoimmune conditions. NK cells should only be evaluated within the uterine cavity through biopsy. If elevated NK cells are found in the endometrium, treatment includes oral corticosteroids and intralipid infusions. Typically, 4 intralipid infusions are given: on embryo transfer day, on positive pregnancy test day, at 8 weeks, and at 12 weeks of pregnancy.
No. Cryopreservation does not reduce embryo quality.
After approximately six stimulated cycles, the chances of success with a woman’s own eggs are usually maximised. Regarding cancer risk, earlier theories suggested estrogen exposure could increase cancer risk, but evidence from the last 10–15 years has shown this is not the case. Estrogen exposure during pregnancy is significantly higher and longer than during IVF stimulation. IVF does not increase cancer risk, and cancer patients are routinely advised to undergo stimulation before chemotherapy.
Based on current knowledge, chemotherapy does not destroy the endometrium’s ability to accept an embryo.
AMH reflects the number of remaining follicles, not egg quality. Age is the most important factor. A young woman with low AMH has better chances than an older woman with the same AMH level.
When all investigations have been completed and only one euploid embryo remains, sometimes changing the transfer approach—such as using a natural cycle instead of a medicated one—may help. However, in some cases, no additional interventions can be identified.
Supplements may slightly improve motility or DNA integrity, but cannot significantly improve low sperm concentration or morphology. In cases of severe male factor infertility, ICSI is required.
Yes. Low AMH reflects quantity, not quality. A 28-year-old woman with low AMH can still achieve pregnancy with her own eggs.
