A failed embryo transfer does not necessarily mean the next one will fail, and Dr Natalia Szlarb, Fertility Specialist, offers a step-by-step approach to looking at the embryo, the uterine lining and other factors before another attempt.
Hosted by: Clara Toombs, Founder of Fertilia AI.
Start With What the Embryo Can—and Cannot—Tell You
After a failed transfer, it is natural to focus on whether the embryo looked healthy. But an embryo’s appearance, or morphology, does not tell the whole story. An embryo that looks good can still have a genetic abnormality that affects its chance of implanting.
Preimplantation genetic testing can help identify embryos that are euploid, meaning genetically normal, before transfer. Testing at the day-five blastocyst stage can give patients and clinicians more information about embryo quality. It can also help guide a decision about whether to continue trying with the patient’s own eggs or consider egg donation.
Age affects the likelihood of obtaining a genetically normal embryo. At age 35 to 36, 50% to 60% of embryos are expected to be genetically normal and healthy. Between ages 38 and 40, the figure is 20% to 30%; older than 42 to 43, it is less than 10%.
Those figures describe the likelihood of finding a healthy embryo, not a guarantee about any individual cycle. Once an embryo has been tested and found to be euploid, its implantation potential is described as similar whether the patient is 35, 40 or 45. The challenge at older ages is often obtaining enough euploid embryos to transfer.
Does a day-six embryo have a poorer chance?
An embryo that reaches the blastocyst stage on day six should not automatically be dismissed as the reason a transfer failed. In Dr Natalia Szlarb’s view, day-six embryos are as good as day-five embryos, and developing more slowly is not, by itself, a cause of implantation failure. The broader assessment still matters: how the embryo looks is only one part of understanding its potential.
Testing may also raise questions about mosaic embryos, which contain genetically abnormal cells. Laboratories classify them as high or low mosaic, depending on how many abnormal cells are present, and the chromosome involved matters when considering transfer. This is a decision to discuss with the genetic laboratory and fertility team rather than one to make from the embryo’s grade alone.
When Is It Time to Investigate?
Recurrent implantation failure generally refers to embryos failing to implant after at least three transfer cycles during IVF or egg donation treatment. That definition can provide a starting point, but it does not mean every patient must wait through three unsuccessful transfers before asking questions. Earlier evaluation of the lining may be appropriate when genetically normal embryos or embryos created with donor eggs have already been transferred.
A useful review considers several possible contributors together. These include the embryo, the anatomy and condition of the uterus, immune factors, and hormones. Looking at only one part of that picture can leave a patient repeating a transfer without understanding what else might be relevant.
The review can also include the sperm and the genetic background of both partners. Abnormal sperm parameters can reduce the number of good-quality embryos produced, while DNA fragmentation is another factor that can affect embryo quality and development. A karyotype, a test that looks at chromosomes, may identify an issue such as a balanced translocation that changes how embryo results are interpreted.
Check the Uterus and Its Lining
Even when an embryo is suitable for transfer, the uterus needs to offer the best possible conditions for implantation. A review can look at the shape of the uterine cavity, the thickness of its lining and whether there is evidence of infection. It can also consider whether the lining is ready at the time the embryo is transferred.
Endometrial thickness is one part of that assessment. The recommended range before progesterone is 8 to 12 millimetres. After progesterone is introduced, the lining usually decreases by one millimetre or less.
Thickness alone does not describe the whole uterine cavity. Polyps and fibroids can occupy space and negatively affect implantation, and removal may be considered when they are present. For a fibroid that grows into the cavity, an operative hysteroscopy may be used to remove it.
Clinics can assess the cavity in different ways. Hysteroscopy allows the cavity to be examined directly, while hydrosonography uses fluid introduced through a thin catheter to expand the womb for imaging. Hydrosonography can identify anatomical problems that may interfere with implantation, with sensitivity comparable to diagnostic hysteroscopy.
Other findings may also change the plan. A hydrosalpinx, involving fluid in a fallopian tube, is a concern because infected tubal fluid can interfere with implantation. Adenomyosis may be addressed with medication before transfer, while endometriosis can affect ovarian reserve.
Could a uterine scar be involved?
A scar is worth discussing as part of an anatomical assessment, particularly if there is a niche or if the scar is very thin. One recommendation is to consider surgical repair before another transfer when there is a niche or the scar measures less than half a centimetre. A consultation can help determine the best approach to the individual uterine structure.
The condition of the surrounding lining also matters. If there is an area of good lining, transfer can be directed toward the part that looks best using transvaginal ultrasound guidance. Repairing a scar or choosing a better-looking area does not eliminate the need to consider the other possible reasons for a failed transfer.
Understanding Biopsy and Timing Tests
A transfer has to be coordinated with the time when the lining is receptive to an embryo. This period is often called the implantation window. For patients who have had repeated failures, assessing the lining’s timing may be part of planning the next transfer.
One proposed way to do this is an endometrial biopsy during a mock, or rehearsal, cycle. The sample can be used for receptivity testing, including ERA testing, and can also be sent for microbiology and Lactobacillus testing. Discussing these possibilities before a biopsy can help patients understand what the sample will be used to investigate.
A biopsy may also be used to look for infection in the uterine lining. Bacteria in the cervix are not necessarily the same as those in the endometrium, so a cervical swab alone does not answer the same question. Microbiologic testing and DNA amplification can be used to examine the lining itself.
If bacteria are identified, the laboratory can provide an antibiogram showing which are sensitive or resistant to antibiotics. Some biopsies use immunohistochemistry to assess inflammatory cells, while another approach focuses on identifying bacteria directly. The results and any proposed treatment should be reviewed with the fertility team in the context of the patient’s transfer history.
What About Hormones and the Immune System?
The embryo and uterus are central to the discussion, but they are not the only considerations. Thyroid function, prolactin and blood clotting are also part of the wider assessment. Elevated prolactin can be treated, so checking it can identify an issue to address before a further transfer.
Immunology may enter the discussion even when an embryo has been found to be genetically normal. The proposed concern is that the immune system may recognise an embryo as foreign, and some approaches investigate compatibility between partners. Some clinics may discuss immunological protocols or immunisation using a partner’s lymphocytes as possible treatments.
These investigations and treatments are part of an individualised approach, not proof that an immune issue caused a particular failed transfer. Patients considering them can ask what a proposed test is intended to identify, how the result would change treatment and what alternatives would be considered. A step-by-step plan can help keep the investigation connected to decisions about the next cycle.
Planning the Transfer and the Wait Afterwards
Transfer preparation may take place in a natural cycle or an artificial cycle. In an artificial cycle, estrogen is used to prepare the lining, followed by progesterone before transfer. The timing is designed to coordinate the lining with the embryo.
A transfer may also use a fresh or frozen embryo. In a good laboratory, implantation rates after freezing and thawing are described as comparable. For patients considering surrogacy, the fresh-versus-frozen question should be discussed with the treating team; the source did not establish a clear advantage for one approach in that setting.
After transfer, the advice presented is to continue normal life, including walking, while avoiding hard work. It also recommends showers rather than bathing or swimming, and avoiding sexual intercourse until the pregnancy test. These are practical precautions to discuss with the clinic providing treatment.
Progesterone can be checked on the day of transfer to see whether the level is suitable for implantation. The recommended approach also includes continuing medication until twelve weeks of pregnancy. Patients should confirm their own medication plan with their fertility team rather than stopping or changing treatment on their own.
Final Thoughts
A failed transfer can leave patients wondering whether the embryo, the uterus or something else was responsible. The next step does not have to be another identical attempt: it can be a review of embryo genetics, the uterine cavity and lining, transfer timing, hormones and any other factors relevant to the individual. Even when testing or treatment identifies something to address, another transfer is not guaranteed to succeed.
The aim is to make the next decision with a clearer picture. For some patients, that may mean adjusting the transfer plan or treating a uterine problem. For others, genetic results may make a conversation about egg donation the next step.
