💙 What You Need to Know
- RIF affects up to 5% of IVF patients—you're not alone
- More than 50% of cases are "unexplained," but investigation is still worthwhile
- Treatable causes include uterine issues, untested embryos, and chronic endometritis
- PGT-A testing often reveals that embryo genetics were the issue all along
- Many RIF patients eventually succeed—persistence matters
Few things in fertility treatment are as emotionally devastating as watching transfer after transfer fail. You've done everything right. Your embryos looked good. But still—no pregnancy, or early losses. The repeated hope and disappointment is exhausting.
If you're experiencing recurrent implantation failure (RIF), know this: there's often something that can be done. Let's explore what might be happening and how to move forward.
What Is Recurrent Implantation Failure?
There's debate about the exact definition, but the most commonly used criteria is:
- Traditional definition: Failure of 3 or more transfers of good-quality embryos in women under 40
- ESHRE 2023 definition: Transfer of viable embryos failed "sufficiently often" to warrant investigation (acknowledging that the threshold varies by patient)
The ESHRE definition recognizes that a 25-year-old with excellent embryos failing twice may warrant investigation, while a 42-year-old may need more attempts before concluding something is wrong.
💡 The Statistical Reality
IVF success rates are 40-60% per transfer for young women with good embryos. That means even in ideal circumstances, failure happens 40-60% of the time. Three failures in a row can happen by chance alone. RIF is "real" when the pattern exceeds what statistics would predict.
Potential Causes of RIF
When implantation fails repeatedly, the issue may lie with the embryo, the uterus, or factors we don't fully understand. Here's what can go wrong:
🧬 Embryo Factors
- Chromosomal abnormalities (most common)
- Sperm DNA fragmentation
- Poor embryo quality despite appearance
- Genetic issues in either parent
🏠 Uterine Factors
- Uterine polyps or fibroids
- Uterine septum or anomalies
- Thin endometrial lining
- Intrauterine adhesions (Asherman's)
- Hydrosalpinx (fluid-filled tube)
🔬 Immunological/Blood
- Thrombophilia (clotting disorders)
- Antiphospholipid syndrome
- Immune factors (controversial)
- Chronic endometritis (infection)
❓ Other Factors
- Endometriosis/adenomyosis
- Non-receptive endometrium
- Transfer technique issues
- Lifestyle factors (smoking, BMI)
The Most Common Culprit: Embryo Genetics
Here's the uncomfortable truth: the majority of RIF cases are ultimately due to embryo chromosomal abnormalities—even when embryos looked "perfect."
Embryo grading (those "AA" or "5BA" scores) assesses appearance, not genetics. An embryo can look textbook-perfect and still be chromosomally abnormal. This is especially true for women over 35.
of embryos from women 40+ are chromosomally abnormal—regardless of how they look
When RIF patients who haven't done PGT-A testing finally test their embryos, they often discover they've been transferring aneuploid embryos all along. The "failure" wasn't really failure—it was the embryos.
The RIF Workup: What to Test
After 2-3 failed transfers, a systematic investigation is warranted:
| Test | What It Checks | When to Do It |
|---|---|---|
| Hysteroscopy | Direct visualization of uterine cavity—polyps, fibroids, adhesions, septum | After 2-3 failures; gold standard |
| 3D Ultrasound/SIS | Uterine shape, cavity abnormalities, lining | Non-invasive first step |
| PGT-A | Embryo chromosomes—if not done previously | Essential if untested embryos have failed |
| Thrombophilia Panel | Clotting disorders (Factor V Leiden, MTHFR, etc.) | Especially if family/personal history of clots |
| Antiphospholipid Antibodies | Lupus anticoagulant, anticardiolipin, beta-2 glycoprotein | Should be done in RIF workup |
| Endometrial Biopsy | Chronic endometritis (CD138 staining) | Increasingly recommended for RIF |
| HSG/HyCoSy | Tubal patency, hydrosalpinx | If not done recently |
| Karyotyping | Parental chromosomes | If recurrent loss or abnormal PGT results |
| Sperm DNA Fragmentation | Sperm genetic integrity | If male factor suspected or unexplained |
⚠️ Tests to Be Cautious About
ERA (Endometrial Receptivity Analysis): Despite heavy marketing, randomized trials show no benefit. It's expensive, delays treatment, and evidence doesn't support routine use. NK cell testing: Natural killer cell levels don't predict IVF success, and treatments based on them are unproven.
Treatments That Actually Help
🔧 Treating Uterine Abnormalities Strong Evidence
If hysteroscopy reveals issues, treating them improves outcomes:
- Polyp removal: Quick procedure with proven benefit
- Fibroid removal: If submucosal (protruding into cavity)
- Septum resection: Associated with improved pregnancy rates
- Adhesion lysis: Restores normal cavity
- Hydrosalpinx removal: Tubal fluid is toxic to embryos—removal or clipping helps significantly
🧬 PGT-A Testing Strong Evidence
If you've been transferring untested embryos, PGT-A can be transformative:
- Identifies euploid (chromosomally normal) embryos
- Prevents transfer of embryos destined to fail
- Per-transfer success rates with euploid embryos are excellent, even in RIF patients
- Often reveals that "RIF" was really just bad luck with aneuploidy
💊 Treating Chronic Endometritis Moderate Evidence
Chronic endometritis (CE) is a low-grade uterine infection that's often silent:
- Found in 30-60% of RIF patients (much higher than general population)
- Diagnosed by biopsy looking for CD138+ plasma cells
- Treated with antibiotics (usually 2-week course of doxycycline or similar)
- Studies show improved pregnancy rates after treatment
💉 Anticoagulation for Thrombophilia Moderate Evidence
If clotting disorders are identified:
- Low-dose aspirin: Often started before transfer
- Heparin/Lovenox: For confirmed thrombophilia or antiphospholipid syndrome
- Benefits are clearer for recurrent pregnancy loss than for implantation failure
- Treatment should be based on actual positive test results, not empirically
🔄 Protocol Adjustments Moderate Evidence
Sometimes the approach itself needs changing:
- Fresh → Frozen: FET may give better endometrial environment
- Medicated → Natural FET: Some patients do better with natural cycles
- Different stimulation protocol: May improve egg/embryo quality
- Different clinic: Lab quality and transfer technique matter
Treatments with Limited Evidence
Some treatments are offered for RIF but lack robust evidence:
- IVIg (intravenous immunoglobulin): Expensive, theoretical benefit, needs more research
- Intralipid infusions: Limited evidence, unproven
- Endometrial scratching: Major RCT showed no benefit—skip it
- ERA testing: Sounds logical, but trials show it doesn't help
- PRP (platelet-rich plasma): Promising small studies, but not proven
💚 A Practical Approach
Focus resources on proven interventions: fix structural issues, test embryos, treat infections, address clotting disorders if present. Save money on unproven add-ons for additional transfer attempts—which have better evidence than most extras.
The Role of Lifestyle Factors
While not the primary cause of most RIF, modifiable factors can affect success:
- Smoking: Significantly reduces IVF success—quit completely
- BMI: Both very high and very low BMI associated with worse outcomes
- Stress: Studies show high cortisol may increase miscarriage risk; stress management is worthwhile
- Vitamin D: Deficiency is common; optimize levels (>30 ng/mL)
- Sleep: Poor sleep quality associated with worse outcomes
When RIF Is Really Just Statistics
An important perspective: not all repeated failures indicate a problem. IVF has inherent failure rates.
With a 45% per-transfer success rate:
- ~55% chance of first transfer failing
- ~30% chance of first two failing
- ~17% chance of first three failing
In other words, roughly 1 in 6 patients with "average" prognosis will fail three transfers by chance alone—not because anything is wrong. This is why even "unexplained" RIF often succeeds with persistence.
of RIF patients eventually achieve pregnancy with continued treatment
The Second Opinion Question
After multiple failures, seeking a second opinion is reasonable and often valuable:
- Fresh eyes may spot something missed
- Different protocols may be suggested
- Lab quality varies significantly between clinics
- Validation that current approach is appropriate—or not
You're not being disloyal to your doctor by getting another perspective. Good doctors understand and support this.
Questions to Ask Your RE After Failed Transfers
- "What do you think went wrong, and why?"
- "What testing do you recommend before we try again?"
- "Should we do hysteroscopy to check my uterus?"
- "Should we consider PGT-A testing our embryos?"
- "Do you recommend checking for chronic endometritis?"
- "Would you change anything about our protocol?"
- "At what point should we consider donor eggs or other options?"
- "What are my realistic chances going forward?"
RIF Treatment in Colombia
Colombian clinics offer comprehensive RIF evaluation and treatment:
- Hysteroscopy: Diagnostic and operative, at a fraction of US cost
- PGT-A testing: Available with significant savings
- Complete workup: Thrombophilia panels, endometrial biopsies, imaging
- Protocol expertise: Experience with complex cases
- Cost advantage: Allows for more attempts, which may matter most
For patients who've spent significant resources without success, Colombia's lower costs can enable the additional cycles that often make the difference.
Ready for a Fresh Perspective?
Our partner clinics specialize in complex cases and offer thorough RIF workups. Get a second opinion and learn what options remain.
Request a Free ConsultationHope After Repeated Failure
RIF is heartbreaking, but it's not a verdict. Many patients with multiple failures eventually succeed because:
- Treatable causes get identified and addressed
- PGT-A reveals the embryo issue all along
- Statistics eventually work in your favor
- Protocol changes make a difference
- A different clinic gets better results
Your journey isn't over. There's more to try. And for many, the next transfer—informed by what you've learned—finally works. 💙