My Embryo Transfer Failed … What Happened?

Most clinics will (offer to) schedule what's informally known among IVF patients as a "WTF appointment", though sometimes you may need to request having it.

Yes, that's really what patients call it, “WTF call”. Whether it truly means “why transfer failed” or … the other one, is still a mystery to me, though I find both equally appropriate.

That is a follow-up consultation after a failed transfer to discuss what happened and what might be done differently for the next transfer (if there will be one).

This meeting is critical. Do not skip it. Even if you have to wait a few weeks until it happens, you are better off “losing” a cycle than losing precious embryos. And do not go in unprepared.

Here's what you need to know:

In many cases, your clinic will say something like “we can’t really know why it didn’t work”, “sometimes it just doesn't work" or “it’s a numbers game, you gotta keep trying”

While that is technically true (implantation is never guaranteed, even with a perfect embryo and a perfect lining), it should not be the end of the conversation.

If your clinic shrugs and says "let's just try again with the same protocol" with no further explanation, you absolutely need to ask: "What are you going to investigate or change?"

You do not have to ask all those questions. But you can.

Whatever questions you ask your clinic, make sure you write down the answers, and that you are satisfied with how they answered.

Do not dismiss your inner voice if it feels like the answer you received was too vague or dismissive. It is your body, your loss, your money: you are entitled to a thoughtful discussion and a clear explanation.

Here's the difficult truth: in many cases, the exact reason for a failed transfer cannot be definitively determined.

Implantation is an incredibly complex process that requires a chromosomally normal embryo, a receptive uterine lining, precise hormonal timing, an appropriate immune response, adequate blood supply, and probably factors we haven't even identified yet.

In fact, research shows that approximately 65% of patients will achieve a live birth after their first euploid embryo transfer, and more than 90% will achieve a live birth after up to three consecutive euploid transfers. Some studies have reported cumulative implantation or pregnancy rates approaching 95% after three euploid transfers.

That’s right: for about a third of women, it will take 2, if not 3 cumulative euploid transfers to have a baby. And for 5-8% of them, it will take more than 3 cumulative euploid embryo transfers and very thorough investigations before they can have a live birth.

But just because we can't always pinpoint THE reason why it failed, it doesn't mean we can't investigate and optimize for next time.

Failed transfers generally fall into a few broad categories:

• Chromosomal abnormalities: even PGT-A "normal" embryos can have issues
  • see our Egg Quality article for a detailed discussion of PGT-A limitations
• Sperm DNA fragmentation affecting embryo competence
  • see our Egg Quality article section on sperm factors
  • Similarly, sperm bacterial infections (or genital-tract inflammation) may increase oxidative stress, impair sperm quality, and contribute to sperm DNA fragmentation.
• Poor embryo quality/grade at transfer: the biology behind an embryo development is extremely complex, requires a ton of energy, and thousands of cellular and molecular processes have to occur correctly. Sometimes, some embryos just don’t have the necessary cellular energy to allow them to develop; or something happens during their cells’ development, that make them arrest or fail.
• Damage during the freeze-thaw process: while it is increasingly rare with the vitrification process, it remains possible. Freezing and thawing embryos does involve human action, which means human error may happen.

It is important to remember that even a chromosomally normal embryo transferred into a normal uterus under ideal conditions is not guaranteed to implant.

Human reproduction remains surprisingly inefficient compared with what many patients expect, and one single failed transfer does not necessarily indicate that something is wrong.

• Polyps, fibroids, adhesions distorting the uterine cavity
• Adenomyosis: often underdiagnosed, it may contribute to inflammation, altered uterine contractility, and reduced implantation rates.
• Chronic endometritis: a low-grade uterine infection detected via CD138 immunostaining biopsy, treatable with antibiotics. It creates an unfavorable uterine environment for the embryo.
• Lining issues: thin endometrial lining (<7mm), poor lining pattern, and/or sub-optimal blood perfusion and flow.
• Endometriosis can affect uterine receptivity, even as it is physically located outside the uterus
• Uterine septum or structural anomalies (e.g. bicornuate or very small uterus)

See our Causes of Infertility article for more information on these uterine/anatomical factors.

• Progesterone timing mismatch: in some women, the "window of implantation" may be shifted, meaning that some women may need a longer or shorter exposure to progesterone before transfer
• Inadequate progesterone support:
• Thyroid dysfunction: TSH should ideally be <2.5 mIU/ml for fertility purposes; sometimes, TSH does creep up post ovulation or around transfer, and poorly controlled thyroid dysfunction has been associated with miscarriage and adverse pregnancy outcomes.
• Elevated prolactin, insulin, glucose, or androgen levels may negatively affect endometrial receptivity – see below section “What Tests Should Be Done After a Failed Transfer?”, sub-section “Bloodwork – hormonal” for further explanation.

This is a deep and sometimes controversial area. We will cover it extensively in our upcoming companion article "Recurrent Implantation Failure & Recurrent Pregnancy Loss: The Complete Investigation Guide".

We also recommend referencing the book “Is Your Body Baby Friendly?: Unexplained Infertility, Miscarriage and IVF Failure Successfully Treated with Immunotherapy” by the reproductive immunology pioneer Alan E. Beer, for a full review of the factors considered by “reproductive immunologists” (aka, “RI”) to help some women achieve pregnancy.

The most common immune-related factors that can prevent an embryo from implanting, or lead to a pregnancy loss, include:

• Elevated NK cell activity: natural killer (NK) cells are normal and necessary immune cells in the uterine lining, and they help with early placental development. However, when they are too activated or sending overly inflammatory signals, the uterus may be less receptive to implantation. The clinical significance of NK-cell testing remains debated, particularly outside specialized reproductive-immunology practices.
• Th1/Th2 cytokine imbalance: cytokines are “immune-system messenger signals”, which need to be well balanced to deliver the appropriate signals. Embryo implantation needs a carefully timed immune response: if the balance tips too far toward inflammation, the embryo may have a harder time attaching and developing normally.
• Antiphospholipid antibodies: these are immune proteins that can increase clotting risk and interfere with early placental blood flow. They are most clearly linked with recurrent pregnancy loss (RPL), but may be considered after failed transfers when the history suggests clotting or autoimmune involvement.
• Possible HLA-related immune compatibility issues: HLA markers help the immune system recognize and communicate with pregnancy tissue. Some theories suggest that certain partner/embryo immune-marker combinations may make it harder for the uterus to develop the right tolerance signals for implantation.
• Autoimmune conditions affecting implantation: autoimmune conditions can create background inflammation, abnormal antibodies, or clotting risks that may affect the uterine environment. The key issue is usually whether the condition is active or well-controlled around the time of transfer.

• Antiphospholipid syndrome or APS. It is an autoimmune clotting disorder involving “antibodies”, such as lupus anticoagulant, anticardiolipin, and anti-β2-glycoprotein I. It is one of the better-established immune/clotting conditions linked to recurrent pregnancy loss and placental blood-flow problems.
• Factor V Leiden mutation: this is an inherited clotting mutation that can make blood more likely to clot. In fertility contexts, the concern is whether tiny clots could interfere with early placental blood flow, especially in patients with prior losses or personal/family clotting history.
• Prothrombin gene mutation: this inherited mutation can increase prothrombin, a clotting protein, and raise the tendency toward blood clots. Like Factor V Leiden, it is usually interpreted in the context of the whole history rather than treated as a stand-alone explanation for every failed transfer.
• MTHFR mutations: these affect how the body metabolizes folate, but common variants are not usually considered a major cause of implantation failure by themselves. The more relevant question is whether homocysteine is elevated, or whether folate/B-vitamin metabolism needs support - either could in turn be a cause for implantation failure via increasing clotting risks.
• Elevated Factor VIII, Factor XI, or PAI-1: Factors VIII and XI are clotting factors; when persistently elevated, they may contribute to a more clot-prone state. PAI-1 affects the body’s ability to break down clots, so high PAI-1 activity may theoretically make early placental circulation less stable.
• Protein C or S deficiency: Protein C and S are natural anticoagulants, meaning they help keep clotting in check. If levels are truly low, clotting risk may be higher. Timing matters in terms of testing, because pregnancy, estrogen levels, and acute illness can affect results.

• Difficult or traumatic transfer (catheter issues, cervical stenosis): a difficult transfer can happen if the catheter has trouble passing through the cervix (= cervical stenosis, the narrowing of the canal), or the procedure causes bleeding or uterine irritation. This can matter because a smooth, gentle transfer is generally associated with better conditions for embryo placement.
• Uterine contractions during transfer: the uterus can contract in response to catheter manipulation, stress, irritation, or underlying conditions like adenomyosis. Strong contractions around transfer may theoretically move the embryo away from the ideal implantation area. Some clinics will administer medication such as Valium to help reduce contractions.
• Suboptimal embryo placement: embryos are usually placed in a specific area of the uterine cavity, often the upper-middle region, under ultrasound guidance. If placement is too high, too low, or technically unclear, it may reduce the chance that the embryo lands in the most receptive spot.

Sometimes, despite thorough investigation, no clear cause is found. This does NOT mean "nothing can be done", and empiric treatments may still be considered.

Oftentimes, some clinics will, for instance, opt for a “kitchen sink protocol” or for a 2- to 3-month hormonal down-regulation as a “preventive precaution” to attempt to reduce any possible inflammation, even if tests results came back negative or inconclusive.

Beyond genetic testing of the embryo itself, testing both intended parents’ DNA can sometimes be useful after repeated implantation failure or pregnancy loss, especially if it was not done before treatment.

These tests look for inherited genetic risks that could affect embryo development, miscarriage risk, or future child health.

• Karyotyping is a chromosome analysis for both partners, looking for structural rearrangements such as “balanced translocations”. A person with a balanced translocation is usually healthy, but their embryos may inherit missing or extra chromosomal material, which can lead to failed implantation, miscarriage, or an affected pregnancy. If found, options may include genetic counseling, PGT-SR testing, or adjusted embryo-selection strategy.
• Genetic carrier screening checks whether one or both partners carry inherited genetic conditions that could be passed to a child. If both partners carry the same recessive condition, or one partner carries certain X-linked conditions, there may be a risk of creating an affected embryo. Carrier screening does not explain most failed transfers, but it can guide decisions about PGT-M, donor gametes, prenatal testing, or which embryos are safest to transfer.

It may sound silly to say, however, in order for an embryo to successfully implant and grow in the uterus, the uterus needs to be normal in shape, size, appearance, texture etc..

Just like a house with weak or crooked foundations will possibly collapse, an embryo will struggle to develop if the uterus has structural issues or is not hospitable.

Visualizing the inside of the uterine cavity is therefore a simple, yet very important, step in uncovering why an embryo transfer failed or pregnancy was lost.

• Hysteroscopy: this is the gold standard for directly visualizing the uterine cavity, and will normally be done under light anesthesia.
  • This is a short surgical procedure whereby the doctor will insert a tiny probe equipped with a camera through the cervix and in the uterus, in order to have a clear visual of the uterine cavity.
  • It can identify (and treat) polyps, adhesions, fibroids, and septum in the same procedure.
  • If you haven't had one, this should be strongly considered after a failed transfer.
• Saline sonohysterogram (SIS/SHG): this procedure aims to evaluate the uterine cavity via ultrasound, and is usually done in minutes as a simple office procedure, without anesthesia.
  • It is less invasive than a hysteroscopy, but can miss smaller issues that would be seen by hysteroscopy.
  • During an SIS/SHG, the doctor will insert a catheter through the cervix and into the uterus, release some saline solution in the uterus, and look at the uterus’ structure, shape and form on an ultrasound machine, while the uterus is filled with the saline.
• MRI: it can be particularly useful for adenomyosis diagnosis (better than ultrasound in many cases).

Similarly, for an embryo to successfully implant and grow in the uterus, the uterus needs to be hospitable and receptive. Some conditions or pathologies may make the uterus insufficiently hospitable and receptive, making an embryo implantation difficult or impossible.

The main ones are diagnosed with the following tests:

• CD138 immunostaining: this is a biopsy of the uterus lining, which detects chronic endometritis aka “CE” (labs will indicate a number of “plasma cells in the endometrium”). This is a low-grade infection of the uterus, caused by the presence of certain bacteria and pathogens.
  • If positive, treatment is typically 1-2 courses of antibiotics (often doxycycline ± metronidazole), followed by a repeat biopsy to confirm clearance.
  • CE can sometimes be resistant to antibiotics, depending on the type of pathogens causing it. For instance, existence of biofilm-forming organisms (such as E. coli, Ureaplasma spp., and some Streptococcus species) can render treatment difficult, as they shield the pathogen from the antibiotics. Further testing and/or very specific antibiotics, sometimes, even an antimicrobial protocol, may be necessary to fully eliminate this infection in such cases.
  • Some other biopsies offer chronic endometritis detection. CD138 immunostain is however the gold standard, as the other tests may have different, more forgiving thresholds.
• ReceptivaDx biopsy: it tests for what is called the BCL6 protein, to identify uterine inflammation most often associated with "silent endometriosis”.
  • The most common cause of the presence of the BCL6 protein is “silent” endometriosis (e.g., endometriosis without symptoms), however it is not the only cause.
  • Hydrosalpinx, chronic endometritis, progesterone resistance and others can also explain the presence of the BCL6 protein marker, and therefore, this biopsy is not 100% reliable for endometriosis diagnosis.
  • It can however be a useful tool, as it is a less invasive screening before laparoscopy (which is the gold standard for endometriosis diagnosis and treatment).
• EMMA/ALICE and other microbiome testing: these biopsies or uterine tissue tests evaluate the uterine microbiome and detect specific infections (such as chronic endometritis), but also identify the actual bacteria (good and bad) and pathogens that may be present in the uterus.
  • The EMMA/ALICE biopsy is often done together with ERA, in a “mock cycle”. This is when the patient follows a normal embryo transfer cycle protocol, but instead of transferring an embryo at the appropriate time, a uterine biopsy is then done, to then analyse the tissues and determine whether the uterine environment, at presumed time of transfer, is adequate.
  • Other similar microbiome tests are available, such as the Fertilysis Female Microbiome “at home” test, which analyses tissues sampled from menstruation and vaginal swabs.
  • There is growing interest in the role of the uterine and reproductive-tract microbiome in implantation and fertility, with the presence of certain good bacteria (Lactobacillus-dominant flora, incl. L. crispatus, L. jensenii, L. gasseri) being generally considered more favorable for implantation. These bacteria help maintain a low-inflammatory, acidic environment that discourages overgrowth of potentially harmful bacteria.
  • Microbiome testing is promising, but still not as settled as something like hysteroscopy or CD138 testing for chronic endometritis.
• ERA (Endometrial Receptivity Analysis): it determines your personal "window of implantation". Some patients are pre-receptive or post-receptive, meaning standard progesterone timing is off for them. Evidence is quite debated, but it can be useful in specific cases, and some clinicians still consider it in selected patients with recurrent implantation failure, despite mixed evidence.

Diagnostic laparoscopy is a minimally invasive surgery where a camera is inserted through small abdominal incisions to look at the pelvis from the outside of the uterus.

Unlike hysteroscopy, which evaluates the uterine cavity from the inside, laparoscopy can identify problems that imaging and uterine biopsies may miss: endometriosis lesions, endometriomas, pelvic adhesions, scar tissue from prior infection or surgery, distorted pelvic anatomy, fibroids on the outer uterine wall, ovarian cysts, blocked or damaged tubes, and hydrosalpinx (a fluid-filled fallopian tube). It can also include “chromopertubation”, where dye is passed through the tubes to assess whether they are open.

• Important point: laparoscopy is not only diagnostic. In the right hands, it can be therapeutic in the same procedure. A surgeon may excise or ablate endometriosis, remove endometriomas or selected fibroids, release adhesions, restore distorted anatomy, or remove/clip a hydrosalpinx before transfer. That last one matters even in IVF: fluid from a hydrosalpinx can leak back into the uterus and reduce implantation, so salpingectomy or tubal occlusion is often recommended before embryo transfer when a communicating hydrosalpinx is present.
• When to consider it and why:
  • Women with: significant pelvic pain, severe cramps, painful sex, bowel/bladder symptoms around periods, known or suspected endometriosis, endometrioma visible on ultrasound, prior pelvic infection, prior abdominal/pelvic surgery, abnormal HSG/hysteroscopy, or persistent suspicion despite all other exams being normal.
  • It can also be therapeutic for suspected endometriosis, endometriomas, pelvic adhesions, scar tissue, fibroids outside the uterine cavity, distorted pelvic anatomy, or tubal disease. Depending on what is found, the surgeon may indeed excise endometriosis, release adhesions, remove selected fibroids/cysts, restore anatomy, or treat a damaged tube.
  • Note on tubal removal or occlusion: if hydrosalpinx is present. Even when using IVF, fluid from a hydrosalpinx can leak into the uterus, reduce receptivity, and be toxic to the embryo. Removing or blocking the affected tube before transfer can improve outcomes for women with hydrosalpinx.
• When to be cautious: while minimally invasive and typically quick, laparoscopy is still surgery, not a casual add-on.
  • It entails anesthesia and surgical risks; and some therapeutic interventions can bear serious long-terms effects (like, surgery on ovarian endometriomas that can sometimes reduce ovarian reserve if healthy ovarian tissue is damaged). It is also low-yield as a purely exploratory procedure in asymptomatic patients with normal imaging.
  • The decision should be individualized and, ideally, performed by a surgeon experienced in fertility-preserving endometriosis and reproductive surgery.

When completing initial “preconception” tests with a fertility clinic, some basic bloodwork is usually done, and includes things such as STDs, CMP (complete metabolic panel) and some hormonal testing.

However, most clinics do not always (or sufficiently) test the below hormones, which are important to monitor in the context of fertility.

Indeed, any surge or deficit of those could potentially disrupt embryo implantation, and so, clinics should review results of all these hormones’ testing with care.

• Estradiol and progesterone must be at appropriate levels at different cycle points. Most clinics will check those at a given point in time; fewer clinics will monitor those at all necessary cycle points.
  • Estradiol (bloodwork usually tests for “E2”) helps build and thicken the uterine lining before transfer. Too little estrogen may lead to a thin or poorly developed lining, while excessive or poorly timed estrogen exposure may disrupt the uterus lining’s readiness for progesterone.
  • Progesterone (bloodwork usually tests for “P4”) transforms the lining from “growing mode” into “receptive mode.” If progesterone exposure is too short, too long, too low, or mistimed, the embryo and endometrium may be out of sync during the implantation window.
  • Minimum progesterone levels vary depending on the type of transfer/pregnancy. They also fluctuate within the day, and levels in blood will vary depending on the source of progesterone.

Note: progesterone thresholds remain somewhat controversial and vary between studies, transfer types, laboratories, and progesterone formulations. Clinical decisions should always be individualized and interpreted in the context of the transfer protocol being used.

• In the context of embryo transfers, E2 and P4 levels should ideally be tested several times during prep phase, on trigger or ovulation day, on transfer day, and then at each beta testing.

• Thyroid panel (TSH, free T3, free T4, thyroid antibodies):
  • Thyroid hormones help regulate metabolism, ovulation, endometrial receptivity, and early pregnancy development. If thyroid function is too high or too low, implantation and miscarriage risk may be affected.
  • While many fertility clinics monitor TSH closely before and after transfer, not all do. It is strongly advised to ask for your clinic to check and monitor your thyroid hormones.
  • For fertility purposes, TSH should generally remain below 2.5 mIU/L when attempting conception or during early pregnancy; some clinics may target the lower portion of the normal range.
  • Thyroid antibodies can also independently affect implantation: excessive TPOs for instance are an indicator of possible Hashimoto’s disease, an autoimmune disorder affecting the thyroid that can impair implantation.
• AMH and FSH while not implantation hormones in the direct sense, they mainly reflect ovarian reserve and how the ovaries may respond to stimulation. Abnormal patterns can point to egg/embryo-quality issues or broader hormonal imbalance, which may indirectly affect transfer outcomes
• Prolactin: normally a hormone produced towards the end of pregnancy ahead of lactation and breastfeeding, elevated prolactin levels may interfere with ovulation, luteal function, and reproductive outcomes in some patients
• Vitamin D behaves more like a hormone than a simple vitamin, and it plays roles in immune regulation, inflammation, and endometrial function.
  • Low vitamin D has been associated with poorer reproductive outcomes in some studies, and is known to be associated with poorer IVF outcomes.
  • Evidence is not strong enough to treat it as a stand-alone explanation for transfer failure, but many women in reproductive age are actually significantly deficient in vitamin D – and it is a very easy issue to solve with proper supplementation.
• Fasting insulin and glucose: insulin resistance and high glucose can create a more inflammatory, metabolically stressed environment. This may affect egg quality, endometrial receptivity, hormone signaling, and early placental development.
• Androgens such as testosterone are needed in small amounts, but excess levels can disrupt ovulation, follicle development, and endometrial signaling. In conditions like PCOS, high androgens often travel with insulin resistance and inflammation, which may further affect implantation.

Completing these tests often requires getting under the care of a reproductive immunologist (RI), although some REs can sometime offer these – or some of them. Some independent companies also offer immune testing (e.g., Pregmune, Fertilysis).

Tests commonly completed include:

• Natural Killer (NK) cell assay: this measures NK cell activity (not just count)
• Th1/Th2 cytokine ratio: an elevated Th1 response may create a hostile implantation environment
• TNF-α, IFN-γ and similar: those are called “pro-inflammatory cytokines”. Their presence may indicate an overly active immune system.
• Immunoglobulin levels (IgG, IgM, IgA): where these levels are off, this may indicate an immune imbalance or active infection that needs correcting
• ANA (antinuclear antibody) ratio: this can indicate autoimmune activity that needs curbing.
• HLA-DQ alpha genotyping (for both partners): this assesses immunologic compatibility

Not all REs agree on the role of immune testing or treatment, and evidence varies considerably between specific tests and therapies. However, the interaction between the immune system and reproduction has been well established scientifically for decades. The controversy largely centers on which abnormalities are clinically meaningful, which patients should be tested, and which treatments provide meaningful benefit.

Typical clotting panel tests will include the below. Many of these tests are NOT part of standard fertility workups. You may need to specifically request them, and some may require a reproductive immunologist or a hematologist.

• Lupus anticoagulant
• Anticardiolipin antibodies (IgG and IgM)
• Anti-β2-glycoprotein I antibodies (IgG and IgM)
• Factor V Leiden mutation
• Prothrombin gene mutation (G20210A)
• MTHFR mutations (C677T and A1298C)
• Protein C and Protein S (functional)
• Antithrombin III
• Factor VIII and XI activity
• PAI-1 (4G/5G polymorphism)
• Homocysteine
• Beta-fibrinogen polymorphism
• Lipoprotein(a)

The below tests can also be done (if not already the case during pre-conception testing), to rule out any issue on the sperm side, that could lead to embryo genetics issues or implantation issues.

• Sperm DNA fragmentation tests (with SCSA or TUNEL assay) are NOT included in a standard semen analysis and must be specifically ordered.
  • High sperm DNA fragmentation can impair embryo development and “genomic stability” after fertilization, contributing to implantation failure or early miscarriage even when a standard semen analysis looks normal. It is more commonly associated with recurrent pregnancy loss and poor embryo development, than with a single isolated failed transfer.
  • see our Egg Quality article for a detailed discussion.
• Sperm bacterial infections (or genital-tract inflammation) may increase oxidative stress, impair sperm quality, and contribute to sperm DNA fragmentation. Semen culture or urology evaluation for possible genital-tract infection/inflammation, especially if there are symptoms, high round cells/white blood cells, recurrent abnormal semen results, or elevated sperm DNA fragmentation.
• Hormonal panel for male partner (testosterone, FSH, LH)

• Change of transfer type: switch from medicated (hormone-supplemented) to natural or modified natural cycle, or vice versa.
  • For example, in patients with endometriosis and/or adenomyosis, a full medicated transfer may not be optimal, as it entails heavy estrogen supplementing, whereas estrogens may contribute to disease activity and inflammation in some women with endometriosis or adenomyosis.
• Adjust progesterone timing: based on ERA results or clinical judgment
• Add or adjust progesterone delivery: vaginal or rectal suppositories, intramuscular injections, oral supplementation, or all of the above.
  • For example, in natural or modified natural protocols, progesterone supplementing is usually very limited or non-existent. For some patients, however (e.g., progesterone resistance, or insufficient corpus luteum support), progesterone supplementation may be necessary.
• Add estrogen support: patches, pills (oral or vaginal), or injections can help improve lining
• Endometrial scratch: a deliberate, light "scratching" of the uterine lining in the cycle before transfer, is thought to trigger an inflammatory response that may improve receptivity. While evidence is still mixed, some recent studies have demonstrated notable benefit, particularly after unexplained implantation failure.

Those therapies are often used empirically in RIF/RPL patients, particularly by reproductive immunologists. Their goal is to modulate your immune system, to reach a more balanced immune response in your body and uterus after embryo transfer. The below are commonly found in the RI world, although each practitioner will have their own favorites and “no go” treatments:

• Prednisone, Medrol, Dexamethasone and similar: those are corticosteroids whose goal is to suppress immune overactivity.
• Hydroxychloroquine (Plaquenil): an anti-inflammatory often used in autoimmune-related implantation failure.
• Tacrolimus (Prograf): an immunosuppressant initially formulated for organ transplant patients, it is sometimes used in reproductive immunology protocols for patients with elevated Th1 cytokines.
• LDN (Low-Dose Naltrexone): a pharmaceutical drug initially developed to help remedy drug addictions, at a low dose (typically, less than 4.5mg daily), it is used by Res/RIs to reduce inflammation (esp. adenomyosis) and modulate immune tolerance. While research remains inconclusive, it is increasingly discussed and used in RIF contexts.
• Intralipids: it is an intravenous fat emulsion infusion, thought to modulate NK cell activity. It is relatively low-cost and low-risk.
• IVIg (Intravenous Immunoglobulin) infusions: a blood product that broadly modulates immune function. Very expensive and harder to access, but supported by some studies for patients with elevated NK cells or Th1/Th2 imbalance. It is also used by RIs in early pregnancy, in presence of SCH – sub-chorionic hematomas. Evidence remains mixed, and outcomes may depend heavily on the patient's underlying immune profile.
• Neupogen (G-CSF/Filgrastim): a growth factor sometimes used as a uterine wash 24-48hrs before transfer, or daily subcutaneous injections post transfer, to improve endometrial thickness, and receptivity.
• Lymphocyte infusion therapy (LIT): a treatment intended to promote maternal immune tolerance using paternal and/or donor lymphocytes. It remains controversial and is unavailable or restricted in some countries, such as in the US.

• Low-dose aspirin (baby aspirin, 81mg): commonly added for blood flow and mild anti-inflammatory effect
• Lovenox (Enoxaparin) or Heparin: injectable blood thinners used at a prophylactic dose (oftentimes, 30 or 40mg daily), for diagnosed or suspected thrombophilia/clotting disorders
• Combination protocols: aspirin + Lovenox is common for antiphospholipid syndrome

• Hysteroscopic polypectomy:  which can grow from the uterine lining into the cavity and interfere with implantation or increase abnormal bleeding.
• Hysteroscopic adhesiolysis: removal of intrauterine scar tissue/adhesions, which can develop after D&C, miscarriage with retained tissue, infection, uterine surgery, or sometimes C-section-related trauma, and may prevent the lining from developing normally or the embryo from implanting.
• Hysteroscopic septum resection / metroplasty: correction of a uterine septum or other significant cavity-distorting structural abnormality.
  • A septum is a congenital band of tissue that divides part of the uterine cavity and can be associated with miscarriage, malpresentation, and sometimes implantation problems.
  • Cavity abnormalities are sometimes very difficult to identify, even to the eye of specialists, and yet, can be a long-time cause of infertility. You can find a very telling example on Dr. Victory’s YouTube channel: see this video, at ~10’ in, where he explains what the issue was for his patient Stephanie, and how he helped her out.
• Myomectomy: removal of fibroids located in or on the uterus, especially submucosal fibroids or intramural fibroids that distort the uterine cavity, interfere with lining development, cause heavy bleeding, or are very painful.
• Tubal removal, if hydrosalpinx is present. Fluid from a damaged, fluid-filled tube can leak back into the uterus and may be embryo-toxic or reduce implantation; removing or blocking the affected tube before transfer can improve IVF outcomes.
• Laparoscopic surgery: used to diagnose and treat pelvic disease outside the uterine cavity, including endometriosis, endometriomas, adhesions, scar tissue, distorted pelvic anatomy, some fibroids, ovarian cysts, and tubal disease. Some procedures can be done during the same laparoscopy, such as endometriosis excision, adhesiolysis, cystectomy, salpingectomy, or selected fibroid removal. Hysteroscopic procedures may also be combined in the same surgical session when needed.
• C-section scar niche / isthmocele repair: in selected patients, repair of a symptomatic or fluid-collecting C-section scar defect that may interfere with the uterine cavity environment, cause abnormal bleeding, or complicate embryo transfer planning.

• Varicocele repair: in male partners with a clinically significant varicocele, and abnormal semen parameters and/or elevated sperm DNA fragmentation, surgical “varicocele” repair may improve sperm quality in some cases.
• TESE or micro-TESE: this is surgical sperm retrieval from the testicle, sometimes considered when sperm DNA fragmentation remains high despite other interventions. Indeed, retrieving sperm directly in the testicle may lead to sperm with less DNA damage than ejaculated sperm - in some cases.

• Acupuncture and other supportive care: some studies suggest modest benefit of acupuncture around transfer time. It is however fairly low-risk, and may help some patients with pain, anxiety, sleep, and nervous system regulation around transfer. It should be framed as supportive care rather than a proven implantation treatment.
• Uterine PRP (platelet-rich plasma): typically used for thin lining or recurrent implantation failure. The patient’s blood is centrifuged to extract the PRP, which is then deposited in the uterine cavity – in some cases, in the uterus lining. Evidence is still emerging, but some clinics use it when lining growth or receptivity remains poor despite standard treatment.
• Sildenafil (Viagra), Pentoxifylline and other blood-flow support: vaginal sildenafil, pentoxifylline, vitamin E, or similar blood-flow strategies may be used for thin lining or suspected poor uterine perfusion. Evidence is mixed, but it is sometimes tried when the lining remains thin despite estrogen optimization.
• Intrauterine hCG infusion: hCG placed into the uterus before transfer is proposed to support embryo-endometrium signaling. Evidence is mixed and protocol-dependent, with some clinics proposing it more easily than others.
• Hormonal suppression with GnRH agonist depot medication: Lupron Depot, Zoladex, Decapeptyl, or similar may be used before embryo transfers, when endometriosis, adenomyosis, elevated BCL6, or other inflammatory implantation dysfunction is suspected. The goal is to suppress estrogen-driven disease activity and calm the uterine/pelvic environment before transfer, though it can delay treatment and cause temporary menopause-like side effects.
• Weight loss and metabolic optimization, with or without GLP-1 medication: in patients with obesity or overweight, insulin resistance, PCOS/PMOS, or metabolic inflammation, pre-transfer metabolic optimization may improve overall IVF and pregnancy conditions. GLP-1 medications can be helpful in selected patients before conception, but must be stopped before embryo transfer/pregnancy under medical guidance.

• Using a different embryo (if available):
  • Sometimes it really is about that specific embryo, and the next transferred embryo will be the one leading to a live birth.
  • For older women, transferring day-3 embryo(s) instead of a blastocyst (day 5, 6 or 7) can sometimes make a difference. While research isn’t yet very solid, the theory is that older women’s embryos are more fragile, and can perform better in utero vs. in vitro. While incubators in labs replicate very well the female uterus in terms of temperature, climate control, medium (substance) in which embryos are, and (near) sterility, only the uterus is (in principle) “100% perfect” for embryos – especially weaker ones.
  • Some clinics/practitioners will also transfer 2+ embryos (usually untested embryos), on the assumption that transferring multiple embryos increases the chance that at least one implants, but also increases the risk of multiple pregnancy. Research is very limited, but from a statistics’ standpoint, success rates can indeed be higher. Note: your clinic will likely follow the ASRM’s guidelines (or similar for non-US countries) in terms of the maximum number of embryos to be transferred, keeping in mind the higher risks pertaining to multiples’ pregnancies.
• Consider transferring a mosaic embryo: if all euploid transfers have failed, and you have some mosaic embryos, these can absolutely be worth transferring - discuss with your clinic!
  • see our Egg Quality article for a detailed discussion of PGT-A limitations
• Do another retrieval with optimized protocol: particularly if sperm or egg quality optimization hasn't been attempted before, this could make a difference on an embryo’s quality and euploidy.
  • see our Egg Quality article for a detailed discussion around how to try and optimize egg and sperm quality
• Consider assisted hatching: hatching is the process whereby the embryo, in advanced blastocyst stage, starts breaking open its “zona pellucida” (its shell), in order to then find and attach to its implantation spot in the uterus lining. The embryology lab can “accelerate” the implantation process by performing “assisted hatching”, which entail the embryologist making a small opening of the zona pellucida before transfer. If not already used, it may improve implantation potential in selected situations, though evidence varies by patient population.
• Consider EmbryoGlue: used by default by a number of clinics nowadays, this is hyaluronan-enriched transfer medium that may improve embryo-endometrial interaction during transfer.

• A reproductive immunologist (RI): these are specialists who focus specifically on immune-mediated implantation failure. Most REs are not trained in or receptive to reproductive immunology, and working with an RI may be necessary for some IVF patients with RIF (recurrent implantation failure)
  • In the US, there are a handful of dedicated RIs, most of whom consult almost entirely remotely. Each one has a fairly strict intake/onboarding procedure to get under their care, with 3-6+ months wait list in some cases. The list of RIs includes:
    • Dr. A.E. Derbala at the Derbala Institute for Reproductive Immunology (Harper Woods, MI)
    • Dr Giovanni Jubiz at the Center for Reproductive Immunology & Infertility (Orlando, FL)
    • Dr. Joanne Kwak-Kim and Dr. Luu at the Rosalind Franklin University / RFU Clinics (Chicago, IL)
    • Dr Raphael Stricker at the Alan E. Beer Medical Center for Reproductive Immunology
    • (Los Gatos, CA)
  • In and outside the US, a number of fertility clinics include some professionals trained in reproductive immunology. Consult the American Society for Reproductive Immunology (ASRI) or the International Society for Immunology of Reproduction (ISIR) for broader resources and to verify certified professionals.
  • Even if you do not have fertility insurance, it is likely your plan will cover at least some testing and/or consultation, and of course, prescription medications. Do not necessarily assume that you’ll be fully out of pocket if you have no fertility benefits.
• A high-complexity IVF clinic: some patients also seek a second opinion from high-complexity IVF clinics or specialist implantation/RPL programs. Those are centers that routinely see patients after multiple failed transfers, recurrent miscarriage, poor ovarian response, suspected endometriosis, immune/clotting complexity, or difficult prior cycles.
• A maternal-fetal medicine specialist and/or hematologist, for clotting factor evaluation and other more complex issues.

• A reason to investigate
• A reason to ask better or harder questions
• A reason to advocate fiercely for yourself
• Sometimes, a stepping stone to the answer that finally makes the difference

• Evidence that your body is broken
• Evidence that it is your fault
• A sign that you should give up