IVF Failure after IVF Failure – Is There Still a Chance?
Repeated IVF failure is one of the most emotionally and medically challenging experiences for patients and fertility specialists alike. In this expert-led webinar, Prof. Evangelos Papanikolaou, Founder and Reproductive Medicine Specialist at Assisting Nature, addressed one of the most difficult questions in reproductive medicine: what happens when IVF fails again and again, and whether pregnancy is still possible.
Speaking openly and realistically, Prof. Papanikolaou explained why repeated failure occurs, how it should be defined, and which diagnostic and treatment approaches may still offer hope.
When Is IVF Failure Considered “Repeated”?
Prof. Papanikolaou explained that defining repeated IVF failure is not straightforward, even within the scientific community. There is no universally accepted definition, and opinions differ on how many unsuccessful attempts should be considered “recurrent.”
However, he noted that a commonly accepted definition today is the failure to achieve a live birth after the transfer of four good-quality embryos in women under the age of 40. In his words, after transferring 4 good-quality embryos, “you should have at least 1 genetic embryo.” When this does not happen, the situation requires deeper investigation.
This definition helps clinicians decide when it is time to move beyond standard approaches and reconsider the entire diagnostic and treatment strategy.
The Central Role of the Embryo
One of the most important messages from Prof. Papanikolaou’s presentation was that the embryo itself accounts for the vast majority of IVF failures.
He emphasised that approximately 90% of implantation failures are due to embryonic factors, with only about 10% related to other causes. This is why, in his view, discussing repeated IVF failure without having assessed embryo genetics may not be meaningful.
He explained that in the era of advanced reproductive medicine, failing to evaluate embryo chromosomal status can lead to unnecessary treatments and prolonged emotional distress for patients.
Why Preimplantation Genetic Testing Matters
According to Prof. Papanikolaou, preimplantation genetic testing plays a crucial role when IVF fails repeatedly. Without it, clinicians may be overlooking the most likely cause of failure.
He highlighted that many patients undergo multiple embryo transfers without knowing whether the embryos are chromosomally normal. In such cases, repeated failure may not reflect a problem with the uterus or treatment protocol, but rather the genetic competence of the embryos themselves.
At the same time, he cautioned that genetic testing does not explain everything. Even if embryos are genetically normal, implantation may still fail, which is why the remaining 10% of potential causes must be carefully evaluated.
Uterine and Anatomical Factors
Among non-embryonic causes, anatomical abnormalities of the uterus are a key consideration. Prof. Papanikolaou discussed conditions such as congenital uterine septum, fibroids, and endometrial polyps, all of which can interfere with implantation.
These factors are often treatable, but only if they are properly identified. He stressed the importance of thorough imaging and, when necessary, hysteroscopic evaluation to ensure that the uterine cavity is suitable for embryo implantation.
Hormonal and Endocrine Influences
Endocrine factors may also play a role in repeated IVF failure. Even when basic hormone levels appear normal, fluctuations can occur over time.
Prof. Papanikolaou explained that thyroid function, prolactin levels, and progesterone absorption should be carefully monitored. He noted that some patients do not adequately absorb vaginal progesterone, which is why measuring progesterone levels before embryo transfer is essential. If levels are insufficient, additional subcutaneous progesterone may be required.
Immunological and Thrombophilic Factors
Immunological issues are among the most complex and controversial areas in reproductive medicine. Prof. Papanikolaou acknowledged that it is difficult to clearly define autoimmune causes of implantation failure, but he also stated that some patients struggle to accept the embryo as a “foreign body,” particularly in cases involving egg donation.
Thrombophilia was also discussed as a contributing factor in a small percentage of cases. While more commonly associated with recurrent miscarriage, clotting disorders can also affect implantation. He emphasised the importance of early pregnancy monitoring, including early pregnancy hormone testing after embryo transfer.
The Importance of the Microbiome and Endometrial Health
Prof. Papanikolaou addressed emerging evidence around the endometrial microbiome, explaining that it may influence implantation and should not be dismissed as a marketing trend.
At the same time, he expressed caution regarding the overdiagnosis of chronic endometritis, suggesting that while it may be relevant in certain cases, it should not be assumed to be the cause of failure without clear evidence.
Male Factor: An Often Overlooked Contributor
A key part of the discussion focused on male factor infertility, which Prof. Papanikolaou believes is frequently underestimated.
He explained that the use of ICSI does not eliminate all sperm-related issues. DNA fragmentation in sperm can significantly affect embryo development and implantation, even when sperm count appears acceptable.
He strongly recommended DNA fragmentation testing, particularly in cases of repeated IVF failure. Additionally, he stated that karyotyping both partners should ideally be performed early in the fertility journey, rather than after multiple failed cycles, as chromosomal abnormalities may otherwise remain undetected.
Personalised Treatment Is More Than a Buzzword
While “personalised treatment” is often used as a marketing phrase, Prof. Papanikolaou stressed that true personalisation requires experience and critical thinking.
He pointed out that lifestyle advice alone is not sufficient if patients are unwilling or unable to implement meaningful changes, such as smoking cessation. Similarly, supplements cannot compensate for unresolved underlying problems.
Personalisation also involves knowing when to seek input from other specialists, including endocrinologists, haematologists, and experienced endoscopic surgeons.
The more eyes, the better the outcome, he explained.
The Role of the IVF Laboratory Environment
The quality of the IVF laboratory was another area of strong emphasis. Prof. Papanikolaou explained that patients often have no way of knowing whether a clinic’s laboratory environment is optimal.
He expressed concern about large corporate-owned clinics where decision-making may be driven by financial considerations rather than clinical expertise. In contrast, he argued that clinics led by physicians and embryologists are more likely to maintain the highest laboratory standards, because “the baby is your IVF clinic.”
Supportive Care and Maintaining Hope
Finally, Prof. Papanikolaou addressed the emotional dimension of repeated IVF failure. He emphasised the importance of supportive care, both medical and psychological, and encouraged patients not to lose courage.
Repeated failure does not mean that pregnancy is impossible. Rather, it signals the need for deeper investigation, careful reassessment, and, in many cases, a change in strategy.
Is There Still a Chance?
According to Prof. Papanikolaou, the answer is often yes—but only when repeated IVF failure is approached with honesty, scientific rigour, and individualised care. Understanding that most failures are embryo-related, while still addressing uterine, hormonal, immunological, male, and laboratory factors, allows patients and clinicians to move forward with clearer expectations and renewed direction.
