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Tan Xiaojun
·Senior reproductive medicine expert
·Postdoctoral fellow at Peking University
·PhD candidate at Xiangya School of Medicine, Central South
University
·Master’s tutor at Central South University
· Master's degree candidate in reproductive
medicine at the University of South China
· Professional training at Huazhong University
of Science and Technology and Tongji
Hospital Reproductive Center
Expertise:
diagnosis and treatment of infertility, first/second/third generation IVF (including
egg/sperm donation), microsperm retrieval, embryo freezing and resuscitation, artificial
insemination (including husband's sperm and sperm donation), paternity testing, chromosomal
disease
diagnosis, high-throughput gene sequencing, endometrial receptivity gene testing and other
clinical
technology applications. Many of these technologies are at the leading level both domestically
and
internationally.
There are four common reasons behind the failure of continuous transplantation: embryo problem or uterine environment problem? A paper clarifies the key points of investigation
Is the failure of continuous transplantation an embryo problem or a uterine environment problem? Clinically, it is often not a choice, but the result of the joint action of embryo quality, endometrium, hormone support and operation process. This paper combs the inspection ideas, common technologies and inspection procedures.
What is "continuous transplant failure"?
"Continuous transplant failure" in the field of assisted reproduction usually corresponds to the clinical discussion scope of "repeated implantation failure" or "repeated implantation failure". However, it is necessary to point out a common misunderstanding first: it does not mean that there must be a problem with the uterus, nor does it mean that the embryo must not work.
The European Society for Human Reproduction and Embryology (ESHRE) pointed out in its good practice suggestion on repeated implantation failure in 2023 that this situation is more suitable to be understood as a "result phenomenon" in the process of assisted reproduction than a disease with a completely unified definition and a single cause; Whether to enter further examination should be judged according to the individual success probability of patients. In other words, the clinical focus is not simply labeling, but finding the key link that leads to failure.
From the first principle, embryo implantation must meet at least two conditions:
Embryos have the ability to continue to develop.
Endometrium has the ability to accept embryos in a suitable time window.
As long as there is deviation in any link, it may lead to transplant failure. Therefore, a more accurate understanding of the failure of continuous transplantation is the performance of the mismatch between "embryo-end factor" and "maternal-end factor".
Experts suggest that the failure of continuous transplantation is not simply to ask "whose problem is it", but to judge "which link has the main contradiction and which link is only the secondary interference". This is more important than simply additional inspection.
What technical judgments are often involved in the failure of continuous transplantation?
Embryo evaluation: first look at "can you get into bed"
The first common clinical judgment is whether the embryo itself has sufficient development potential. Even if the morphological score is good, it does not mean that the chromosome must be normal. The 2024 document of the American Society of Reproductive Medicine (ASRM) mentioned that the proportion of embryo aneuploidy will increase obviously with age; In its cited research, the proportion of aneuploidy in embryos of people under 35 years old is 52.0%, and that of people aged 35-40 years old is 64.5%. This means that the weight of embryonic factors in continuous failure usually increases with age.
Therefore, the following situations often suggest that we should focus on the embryonic end:
The woman is older.
Fewer eggs and fewer high-quality embryos were obtained.
Repeatedly only biochemical pregnancy or no implantation at all
The risk of severe oligospermia and sperm DNA damage is higher in men.
The proportion of blastocysts from previous embryo culture is low.
But we should also look at PGT-A objectively. The updated draft of NICE 2025/2026 is cautious about PGT-A, suggesting that PGT-A should not be generally provided as a routine addition; ASRM 2024 also pointed out that PGT-A did not improve the outcome in all people, and some age groups may benefit, but it is not necessarily better if they do it.
Conclusion: PGT-A is more suitable for people with clear medical indications to discuss, and it is not suitable to be packaged as the standard answer for all patients with continuous failure.
2. Evaluation of uterine environment: Look at "Can you catch an embryo?"
The uterine environment mainly includes:
Is the shape of uterine cavity normal?
Is endometrial thickness and classification appropriate?
Is there chronic endometritis?
Whether there are polyp, adhesion, submucosal myoma, adenomyosis and other factors that affect implantation.
Do luteal support and hormone exposure time match?
ESHRE suggests that chronic endometritis can be considered for evaluation, and if it is diagnosed, antibiotic treatment can be considered; The cited systematic review shows that patients who have been "cured" after treatment have a better outcome of live birth/persistent pregnancy than those with persistent chronic endometritis.
For hysteroscopy, it is also necessary to avoid excessive examination. NICE's evidence on screening hysteroscopy recalls that screening hysteroscopy is not recommended unless there is clinical suspicion of uterine or endometrial abnormality. This shows that hysteroscopy is valuable, but it should be based on reasonable indications, rather than "everyone does it after several failures."
3. Intima receptivity test: There is room for discussion, but the evidence is inconsistent.
Many patients will pay attention to "endometrial receptivity test" such as ERA after continuous transplantation failure. It needs to be pointed out directly here that the current evidence of this kind of testing does not support conventional screening.
ESHRE's good practice recommendations clearly mention that the evidence at this stage is not enough to support the routine use of commercial endometrial receptivity testing to diagnose the causes of repeated implantation failure. The review of NICE-related evidence also shows that the existing research evidence is unstable, and many studies even exclude people who have failed to plant repeatedly, so the extrapolation is limited.
Experts suggest that the value of endometrial receptivity testing is more in "specific individualized discussion" than "necessary items after repeated failures" The level of evidence is still treated with caution.
Which groups of people need to be investigated more?
Different people have different contradictions. Attributing all failures to "uterine environment" or "embryo quality" may lead to direction deviation.
The crowd characteristics are more common, and the direction of priority investigation is explained.
The age-related egg quality of women aged ≥35 years, especially ≥38 years, is decreased, and the weight of embryo tip is usually increased.
The uterine environment, transplantation window and inflammatory factors of repeated high-quality blastocyst transplantation without implantation need to re-examine the endometrial, uterine cavity, corpus luteum support and operation details.
The previous history of intrauterine surgery, abortion and curettage, intrauterine adhesion and endometrial damage should be vigilant.
The uterine environment and inflammatory microenvironment associated with adenomyosis and endometriosis may affect endometrial receptivity and uterine contraction.
The sperm quality and related laboratory strategies need to be evaluated for the embryo potential of the man with severe oligozoospermia.
The combination of multiple biochemical pregnancies or early abortion embryos and maternal factors can not only focus on the bed itself.
Core judgment principles:
Old age, few embryos and low blastocyst rate, pay attention to the embryonic end first;
High-quality embryos fail repeatedly and the history of uterine cavity is complicated, so the uterine end should be paid attention to first;
There are risk factors on both sides, so it is necessary to make a joint assessment instead of a single bet.
How to check it in clinic? A relatively clear process
Step 1: Review the previous cycle data first.
Many consecutive failures are not due to "not doing high-end inspection", but because the basic medical records are not fully duplicated. The contents of the duplicate include:
Every ovulation promotion scheme and the number of eggs obtained
Fertilization rate, excellent embryo rate and blastocyst formation rate
Have frozen embryos been compared with fresh embryos?
Intima thickness and hormone value on the day of transplantation
Are luteal support programs consistent?
Are there any operational problems such as difficult transplantation, uterine contraction and bleeding?
Advantages: low cost, large amount of information, and frequent discovery of real problems.
Disadvantages (risks): If the medical records are incomplete, it is easy to miss details.
Confidence rating: high. Because this is the basic step of clinical decision-making and the logic is the most stable.
Step 2: Distinguish between the embryonic end and the uterine end.
If the following manifestations occur, it is often suggested that the embryonic end is preferred:
Available embryos are few.
Cliff-like decline of embryonic development
advanced/venerable age
The male factor is obvious
If the following manifestations occur, it is often suggested that the uterine end is preferred:
Many high-quality embryo transfer failures
History of intrauterine surgery
Repeated thinning of intima
Ultrasound prompts polyps, adenomyosis or hydrops.
Suspected chronic endometritis
Step 3: Select the examination according to the indication, instead of "adding all items"
Common items that can be discussed include:
Ultrasound and evaluation of uterine cavity
Hysteroscopy if necessary
Review of intimal thickness and morphology
Related examination of chronic endometritis
Embryo culture and laboratory link resumption
Genetic evaluation when necessary
Advantages: reduce invalid inspections and improve pertinence.
Disadvantages (risks): Doctors are required to have strong integrated judgment ability.
Confidence rating: high. In line with the current evidence-based medicine and guidelines.
Frequently asked questions
Q: Is the failure of continuous transplantation more common, embryo problem or uterine environment problem?
Conclusion: Embryonic problems are often more common in clinic, but we can't ignore the uterine environment.
The reason is simple: embryo chromosome abnormality itself is an important source of failure, and it is more obvious with age. On the other hand, if the transfer of high-quality embryos has failed for many times, especially for aneuploid embryos, we must seriously consider the uterine cavity, endometrium, inflammation and support programs.
Q: Does PGT-A basically eliminate the embryo problem?
I can't.
PGT-A mainly solves the screening of chromosome number, which does not mean that it fully represents the embryonic development ability, nor does it mean that it will definitely improve the cumulative live birth rate of all people. Laboratory conditions, biopsy strategies and chimera interpretation will also affect the results.
Q: Is endometrial receptivity testing a necessary step after continuous failure?
Not a routine necessary step.
At present, mainstream evidence supports "selective use and careful interpretation" rather than taking it as a standard process.
Q: Is hysteroscopy safer?
Not everyone needs it.
If the imaging findings are abnormal, the history of uterine cavity is complicated, or the clinical problems of uterine cavity are highly suspected, hysteroscopy is of high value; However, as a routine screening for all failed patients, the evidence is not sufficient.
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