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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.
Embryo quality is good but it has not been implanted, Guangzhou IVF, embryo transfer, investigation process of implantation failure, reasons for repeated implantation failure, endometrial receptivity, frozen embryo transfer failure, assisted reproductive science
The embryo quality is good but it has not been implanted, which does not necessarily mean that the embryo is fine. Clinical evaluation is usually combined with uterine environment, tubal factors, chronic endometritis, intima thickness, transplantation process and individual basis.
What do you mean, "the embryo is of good quality but never gets into bed"?
In the assisted reproductive scene, "embryo quality is good" usually means that the morphological score is good, and in some cases, the chromosome test results are ideal. However, it needs to be clear in medicine: good shape does not mean that you can be implanted; Even if it is an aneuploid embryo, not every transplant can be successful. ESHRE pointed out that repeated implantation failure should not be simply attributed to a single problem, but should be comprehensively judged by combining the cumulative pregnancy opportunity of the individual patient, the number of previous transplants and the basic cause; At the same time, many tests and treatments are still insufficient at the evidence level, which is not suitable for routine generalization. ASRM also mentioned that even if embryos with normal chromosomes are transferred, there will still be non-implantation.
Which groups of people are more likely to encounter this situation?
From the perspective of reproductive medicine, the following people need to pay more attention to systematic investigation:
Those who have had two or more transplant failures: ESHRE believes that when individuals have a high cumulative predicted chance of implantation after several transplants and are still not pregnant, they should consider further examination instead of just repeating the original plan.
Older people: the embryo has a good appearance and cannot completely cover the changes in oocyte quality brought about by age. According to the opinions of the ASRM 2024 Committee, in the relevant research, the proportion of aneuploidy in embryos of women younger than 35 years old is about 52.0%, and that of women aged 35-40 years old is about 64.5%, indicating that age still affects the level of embryo genetics.
Those who have basic problems of uterus, fallopian tube or endometrium, such as abnormal uterine cavity, hydrosalpinx, endometriosis/adenomyosis, thin endometrium, etc., are listed as related factors that need to be paid attention to in clinic by ESHRE.
From a technical point of view, what six types of reasons may be concentrated?
1. The embryo "looks good", but it does not mean that the development potential is completely normal.
Morphology mainly reflects appearance and cannot completely replace genetics and developmental potential evaluation. Even if PGT-A is done, the medical community does not think that it can steadily improve the cumulative live birth outcome for all people; It is more like a screening tool than a "guarantee of success".
2. Insufficient endometrial receptivity
Implantation is essentially a "time window matching" between embryo and endometrium. ESHRE pointed out that many additional tests on endometrial receptivity have not been fully verified, and "doing a certain endometrial test" cannot be regarded as the standard answer. In other words, endometrial problems may exist, but they cannot be simply defined by a popular test.
3. Abnormal uterine structure
Intrauterine adhesion, submucosal myoma, uterine malformation, polyps, etc., may affect the implantation position and endometrial environment of embryos. ESHRE suggested that hysteroscopy should be further considered when ultrasound indicates abnormal uterine cavity, instead of all losers doing the same set of examinations mechanically.
4. Hydrosalpingitis is neglected
Hydrosalpingitis is one of the factors easily missed in clinic. ESHRE clearly listed it as an anatomical problem related to repeated implantation failure; If ultrasound suspects hydrops, fallopian tube imaging can be further evaluated.
5. Chronic endometritis
Chronic endometritis sometimes has no obvious symptoms, but it may reduce the pregnancy rate. ESHRE's suggestion is: * * Consider evaluating chronic endometritis; If the diagnosis is definite, antibiotic treatment can be considered. * * This shows that it is not necessary for all patients to be screened, but it has practical significance in people who have repeatedly failed.
6. Thin intima or insufficient preparation for transplantation cycle.
ESHRE review mentioned that endometrial thickness less than 7 mm in late follicular phase was associated with lower live birth rate, and OR was about 0.47 in related studies. This does not mean that "it is absolutely impossible to transplant under 7 mm", but it suggests that there is a statistical correlation between intima thickness and outcome, and it is often necessary to combine estrogen exposure, intima morphology and previous cycle performance in clinic.
Expert tip: The embryo quality is good, but it has never been implanted. The more common clinical idea is not to "constantly change the remedies", but to judge whether the problem is more like embryo potential, intrauterine environment, fallopian tube factors, or transplantation process matching. Additional treatment with insufficient evidence should not be tried repeatedly.
Frequently asked questions
Q: Why don't you get into bed after PGT-A?
Because PGT-A mainly screens for abnormal chromosome number, it cannot cover all factors that affect implantation. ASRM pointed out that PGT-A could not steadily improve the cumulative live birth outcome in all populations. ESHRE also stressed that the failure to implant an aneuploid embryo does not automatically mean that there must be something wrong with the endometrium.
Q: Is it possible to find the reason just by checking immunity?
I can't understand it that way. ESHRE is cautious about a variety of "immune-related" tests and treatments, pointing out that many projects lack sufficient high-quality evidence; For example, blood cytokine assessment, G-CSF, intravenous fat emulsion, IVIG, LMWH, etc., are not recommended as routine methods to improve pregnancy or live birth rate.
Q: Should everyone do hysteroscopy?
No. The existing suggestions are more inclined to do hysteroscopy when there are abnormal images, rather than taking it as a fixed action for all patients who have repeatedly failed.
Common clinical investigation process
Investigation direction, common clinical concerns, next step
Is the embryo factor only good in morphology or combined with genetic information? Review fertilization, blastocyst formation and previous embryo outcomes.
Image evaluation of tubal factors for hydrosalpinx, and transplantation after treatment if necessary.
Whether the thickness, shape and cycle preparation of intima fully optimize the intima preparation scheme?
Whether there is chronic endometritis due to inflammatory factors; Biopsy/pathological evaluation if necessary.
Process factors, transplant timing, luteal support, laboratory strategy, the whole process of the last cycle
The core of this kind of process is not to "do more tests", but to conduct hierarchical investigation according to evidence and medical history. ESHRE particularly emphasized that the treatment after repeated failures should focus on projects that are biologically reasonable and supported by certain evidence.
Summary:
Embryo quality is good but it has not been implanted, and the reason is often not single.
The more common explanations include: the true developmental potential of the embryo is not completely consistent with the appearance, the endometrial receptivity is insufficient, the uterine cavity structure is abnormal, hydrosalpinx, chronic endometritis, thin endometrium or insufficient cycle preparation.
superiority
Adopting the idea of "hierarchical investigation" is closer to the real clinical logic.
Can reduce the time and cost consumption caused by unfounded additional treatment.
It helps to locate the problem to the embryo, endometrium, uterine cavity or the process itself.
Disadvantage (risk)
Part of the reason is that there is still a lack of a single, accurate and one-time confirmation method.
Some popular tests or treatments have limited evidence, which easily leads to over-medical treatment.
Even if the standard investigation is completed, the results of the next transplant cannot be simply regarded as inevitable improvement.
Conclusion: When "good embryos don't implant repeatedly" appears, it is more reasonable not to blindly add items, but to make evidence-based re-examination around embryos, uterine cavity, fallopian tubes, intima and transplantation process.
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