Could bacteria in the uterine lining be one piece of the puzzle when embryos don’t implant? Dr Natalia Szlarb, Fertility Specialist, explains what is known about the uterine microbiome, how it can be assessed, and why embryo quality, lining and timing still come first.
The uterine microbiome is one part of the implantation picture worth considering after failed IVF transfers, but embryo quality remains central, says Dr Natalia Szlarb.
When an embryo transfer fails, it is natural to look for a single explanation. The uterine lining and its microorganisms may be part of the answer, but they are not the only factors to consider. Embryo genetics, the thickness and structure of the lining, the timing of transfer and hormone support all contribute to the assessment.
The microbiome is the collection of microorganisms present in an environment. In the uterus, some bacteria are considered favourable for implantation, while others may interfere with it. Lactobacillus species are among those associated with a favourable environment because they lower the pH of the lining.
That does not mean the goal is a completely bacteria-free uterus. The more useful question is which organisms are present and whether a finding calls for treatment. A biopsy result also needs interpretation: bacteria picked up from the vagina or cervix as the sample is collected can complicate the picture.
An endometrial biopsy, also called a uterine lining biopsy, collects a sample of the lining for analysis. In Dr Natalia Szlarb’s practice, it is often considered after the second failed transfer rather than waiting for three unsuccessful transfers. The assessment can bring together microbiology with other questions about whether the lining is ready for an embryo.
A very thin catheter is passed through the cervix to collect the sample. The same biopsy sample can be used to assess the microbiome and receptivity—the timing of the period when the lining is considered ready for implantation. Immunological factors may also be assessed as part of the same visit.
For microbiology, a genetic laboratory can use DNA amplification and sequencing to identify bacteria in the sample. This approach is more sensitive than classical culture for detecting bacteria in the uterine lining. A clinic arranging the test may work with a genetic laboratory that can interpret the result and recommend treatment.
A biopsy finding is not always straightforward, however. Because the catheter travels through the cervix, it can pick up vaginal or cervical bacteria on the way. Patients can ask how the laboratory distinguishes a potentially relevant uterine finding from contamination and what the result would mean for the next transfer.
The vaginal and uterine microbiomes are assessed differently. A vaginal evaluation uses swabs and can include testing for yeast. It can also look for other organisms assessed in general gynaecology.
A vaginal swab does not replace a uterine lining biopsy when the aim is to assess microorganisms inside the uterine cavity. The cervix separates the vagina from the cavity, so a uterine sample requires a catheter. That distinction matters when discussing a test: “microbiome testing” can refer to samples from different places.
The results can also lead to different treatment decisions. Some bacteria found in the vagina are not considered appropriate in the uterine environment, and a laboratory must consider whether bacteria in a biopsy reflect the uterine lining or contamination during collection. Knowing exactly which area is being tested helps patients understand what a result can—and cannot—address.
Treatment depends on the organism identified and the laboratory’s recommendation. If a harmful bacterium is found in a uterine biopsy, targeted antibiotics may be used. Oral or vaginal probiotics may also be recommended for certain patients, with the choice guided by the biopsy and laboratory advice rather than a specific brand.
Finding bacteria does not automatically mean another biopsy is needed after treatment. For example, after a small amount of streptococcus is found, a repeat biopsy is usually not needed if the organism is sensitive to the prescribed antibiotic and the recommended course has been completed. The treating clinic should make this decision, taking the result and treatment into account.
There is also a distinction between a biopsy finding and an acute infection. Acute uterine inflammation can spread to the tubes and cause a tubo-ovarian abscess. This requires hospital treatment with intravenous antibiotics, followed by oral antibiotics for at least three weeks if inflammatory markers improve and CRP goes down.
After acute tubal inflammation, hydrosalpinx may develop. In this condition, fluid from the affected tube can flow into the uterus and make implantation impossible, so it must be addressed before embryo transfer. Chronic uterine inflammation can also persist after an acute infection and may contribute to repeated implantation failure.
A microbiome result is most useful when it is considered alongside the rest of the IVF history. For recurrent implantation failure, the first step in the approach described is to re-examine embryo genetics. Even younger patients may have embryos with chromosomal abnormalities, particularly when there have been multiple failed cycles or a balanced translocation.
PGT-A is a way of checking embryos for chromosomal abnormalities. The decision to consider embryo testing depends on the individual history, rather than the uterine biopsy result alone. If a genetically normal embryo is available, the next question is whether the lining and transfer conditions are suitable.
The structure of the uterus and lining matters too. Hysteroscopy can be used to look for adhesions, polyps and fibroids, while lining thickness is another part of transfer preparation. A thin lining can reduce the chance of implantation and may be difficult to grow after miscarriages or several D&C.
For patients whose lining does not respond as hoped, the preparation protocol can be revisited. Some patients who do not grow the lining with oral or transdermal estrogen do respond to vaginal estrogen, and some may need a longer protocol. A previously successful protocol can also be part of the discussion when planning another attempt.
The implantation window is the period when the lining is considered receptive to an embryo. Receptivity testing aims to determine how many hours a patient needs before that window opens, so a transfer can be timed accordingly. It may be considered when indicated, including as part of a broader biopsy assessment.
Progesterone is another part of transfer preparation. A level can be checked on the day of transfer to assess whether there is enough support, although there is no single good answer for the level that is sufficient for implantation. A vaginal dose alone does not necessarily establish what the measured level will be.
If the level is considered inadequate on transfer day, injectable progesterone may be added. The dose and route are decisions for the treating team, alongside the timing of the transfer. For patients, it is reasonable to ask whether progesterone will be checked and how the result would change the plan.
Recurrent urinary tract infections are another issue patients may raise while preparing for IVF. They are separate from the question of what is present in a uterine biopsy, so the two should not be treated as interchangeable test results. A patient with recurring symptoms can discuss their history and management with their clinician.
Recurrent UTIs can occur after sexual intercourse, and emptying the bladder after intercourse was suggested as a preventive measure. Management may also include antibiotics or products combining cranberry, lactobacillus and mannose. The choice depends on the patient’s situation, rather than on a uterine microbiome result alone.
The uterine microbiome may offer a useful avenue to investigate, especially after unsuccessful transfers or a history of uterine inflammation. It is one part of a wider assessment that starts with the embryo and also considers the lining, transfer timing and hormone support.
Before agreeing to a biopsy, patients can ask what the clinic hopes to learn, how it will interpret possible contamination and whether the result would change treatment. For those facing repeated unsuccessful cycles, a second opinion can help bring the different pieces of the implantation picture together and identify what might be done differently.
First, assess whether embryos should be genetically tested, especially after repeated failed transfers. Endometrial thickness is also important. Natural cycles should generally be avoided except in estrogen-resistant patients. Most patients are downregulated and prepared in an artificial cycle so that transfer occurs without hormonal bias.
Receptivity testing can be done when indicated. If a biopsy is performed, microbiology should also be assessed. In very complicated cases, immunological preparation is added after transfer.
No specific brands are recommended. A biopsy can identify which types of Lactobacillus are present and which antibiotics are recommended in different parts of the world. Have the biopsy performed through a clinic that has an agreement with a genetic laboratory, as the result can help identify the best medication for that setting.
Recurrent UTIs are especially common after sexual intercourse. Emptying the bladder after intercourse can help. Wet bathing suits can also contribute to UTIs in summer.
Management may include antibiotics or repeated antibiotic treatment. Cranberry pills with lactobacillus can favour a lower pH, while combinations of cranberry, lactobacillus, and mannose may help prevent UTIs.
An in-person discussion is needed to review age, AMH, antral follicle count, and euploidy rate. If good embryos are available, the lining, immunology, and other factors can be addressed. A second opinion by phone or consultation can also be helpful.
Yes. The vagina contains many bacteria that should not be in the womb, so the uterine cavity should be assessed differently.
In general gynaecology, cervical and vaginal swabs are used to test for chlamydia, mycoplasma, trichomonas, yeast, and other classical organisms. In reproductive medicine, uterine lining biopsies are sent to genetic laboratories for DNA amplification testing. Treatment depends on whether the organisms are considered part of the uterine environment or contamination.
Start with the embryo, because a genetically normal embryo is the main factor. At age 43, fewer than 10% of embryos are genetically normal, so having one healthy embryo is a blessing. If the embryo is fit, it should be transferred into a womb that is free of infection. If there are no genetically healthy embryos, seek a second opinion to discuss egg donation.
Usually not. If the Streptococcus is sensitive, especially to penicillin and second-generation cephalosporins, you should be fine after completing the antibiotic course recommended by the laboratory.
These are 2 different tests. For the uterine microbiome, an endometrial biopsy with DNA amplification testing is recommended. The biopsy can be sent to Spain, Valencia, or Asia. For the vaginal microbiome, vaginal swabs with different media are used, and yeast testing is part of the evaluation.
There is no good answer. Vaginal micronised progesterone has been used at 800, then 1,200, and later as 200-mg pessaries. In general gynaecology, the dose is 200 in the morning and 200 in the evening.
In reproductive medicine, even 1,200 daily may leave the progesterone level under 12 on the day of transfer. Injectable progesterone at 25 mg a day may then need to be added. Do not rely on the vaginal dose alone; double-check the level on transfer day.
The most common way is sexual intercourse. People are not born with uterine infections. Very rarely, infection can be acquired through water exposure, including saunas and swimming pools.
Recommendations for vaginal and oral probiotics should come from the biopsy results and the genetic laboratory, rather than a general brand recommendation.
A reproductive immunology specialist should manage this, and the immunologist’s recommendation should be followed. Options mentioned include immunisation with partner lymphocytes and vaccines with men’s leukocytes. There is a strong school in Poland and a very good school in Germany.
If the immunologist says the crossmatch is not okay, the patient needs to do the “lid.” The answer also stated that “in Charlotte it will not solve it”; these terms were not clarified.
Repeat protocols that have already been successful. Some patients do not grow the lining with oral or transdermal estrogens but do with vaginal estrogens. The protocol may need to be extended to 20 or 25 days. If the doctor is not happy with the lining, the protocol should be stopped and repeated.
The lining can be trained, and some patients have grown it over six months. A lining of 6 mm is not thick enough for implantation because adding progesterone may reduce it to 5 mm, so the cycle should be repeated once more.
