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PGT for Repeated Implantation Failure: When Is It the Missing Piece?

Three failed embryo transfers. Five. Seven. Each cycle began with hope and ended with disappointment. You've done everything "right"—high-quality embryos, optimal hormone levels, perfect endometrial thickness—yet pregnancy doesn't happen. Now someone suggests PGT: "Maybe your embryos have chromosomal problems you can't see under the microscope."

This scenario represents one of the most frustrating challenges in reproductive medicine: Repeated Implantation Failure (RIF). For some patients, PGT provides the breakthrough that finally leads to pregnancy. For others, it's an expensive detour that doesn't address the real problem.

Understanding when PGT is truly "the missing piece" versus when it distracts from other critical factors requires a comprehensive look at why embryos fail to implant—and honest assessment of PGT's capabilities and limitations.

Understanding Repeated Implantation Failure (RIF)

Repeated implantation failure (RIF) has no single universal definition, but most reproductive specialists describe it as the absence of a clinical pregnancy after multiple embryo transfers despite good-quality embryos. This typically means failure after four or more transfers of good-quality embryos, three or more transfer cycles, or the cumulative transfer of around ten embryos. When only blastocysts are transferred, RIF is often defined as failure after three blastocyst transfers or after four high-quality blastocysts in total [1][2].

RIF affects approximately 10–15% of IVF patients, representing thousands of couples each year who experience repeated negative pregnancy tests despite apparently optimal treatment conditions [3]. Embryo “quality” is usually assessed by morphology, including cell number, symmetry, blastocyst expansion, and developmental timing. However, appearance alone does not guarantee chromosomal normalcy. Studies show that 40–60% of morphologically normal blastocysts in women over 35 are aneuploid, highlighting why PGT may be relevant in RIF cases, while remaining only one part of a broader diagnostic picture [4].

The Three-Factor Model: Embryo, Endometrium, Immunology

Successful implantation requires three elements working in harmony:

1. Competent Embryo (Genetic Factor)

Requirements:

  • Chromosomally normal (euploid)
  • Appropriate gene activation
  • Intact developmental programming
  • Viable mitochondrial function

When it fails:

  • Aneuploidy (most common)
  • Genetic mutations
  • Epigenetic abnormalities
  • Mitochondrial dysfunction

PGT's role: Can identify aneuploid embryos but doesn't detect all genetic problems

    2. Receptive Endometrium (Uterine Factor)

    Requirements:

    • Proper hormonal priming
    • Appropriate thickness (7-14mm)
    • Molecular changes enabling embryo attachment
    • Correct timing ("implantation window")

    When it fails:

    • Displaced implantation window
    • Inadequate progesterone
    • Chronic inflammation (endometritis)
    • Anatomical abnormalities
    • Thin endometrium

    PGT's role: Cannot address endometrial issues—different diagnostic tools needed

    3. Balanced Immune Response (Immunological Factor)

    Requirements:

    • Maternal immune tolerance of semi-allogeneic embryo
    • Appropriate NK cell activity
    • Controlled inflammatory response
    • Proper cytokine balance

    When it fails:

    • Elevated NK cells
    • Autoimmune conditions
    • Thrombophilia
    • Inflammatory dysregulation

    PGT's role: Cannot detect or address immunological problems

    The statistical breakdown:

    Research suggests RIF causes distribute approximately:

    • up to 70%: Embryonic factors (chromosomal abnormalities, genetic issues)
    • 15-20%: Endometrial factors (receptivity, inflammation, anatomy)
    • 10-15%: Immunological (NK cells, autoimmunity, clotting) & Unexplained factors (multiple subtle factors, unknown mechanisms) [5][6]

    Critical implication: PGT addresses embryonic factors, which represent only 30-40% of RIF cases. For the majority of RIF patients, PGT alone won't solve the problem.

    When Embryo Quality Is the Problem: PGT's Role

    Scenarios where PGT genuinely helps RIF patients:

    Scenario 1: Maternal Age-Related Aneuploidy

    Patient profile:

    • Woman age ≥38 using own eggs
    • Multiple failed transfers with morphologically good embryos
    • No obvious endometrial or immunological issues

    The mechanism: As women age, meiotic errors increase exponentially. By age 40, 60-70% of embryos are aneuploid; by age 43, 85% [7]. Morphology cannot distinguish euploid from aneuploid embryos.

    How PGT helps:

    • Identifies the 15-40% of embryos that are chromosomally normal
    • Prevents wasting transfers on aneuploid embryos that cannot implant
    • Focuses limited time and resources on embryos with genuine potential

    Evidence: A 2018 meta-analysis found that PGT-A in women with advanced maternal age and prior RIF increased clinical pregnancy rates from 41% to 71% per transfer of euploid embryo [8].

    Scenario 2: Male Factor with Elevated Aneuploidy

    Patient profile:

    • Severe male factor infertility
    • ICSI cycles with repeated failure
    • Paternal age >50 or specific genetic concerns

    The mechanism: While most aneuploidy is maternal, certain male factors increase sperm chromosomal abnormalities:

    • Very low sperm count (<5 million/ml)
    • High sperm DNA fragmentation
    • Klinefelter syndrome or other chromosomal conditions [9]

    How PGT helps: Identifies embryos with paternal-origin aneuploidies that wouldn't be detected by standard sperm analysis.

    Scenario 3: Unbalanced Translocations

    Patient profile:

    • Either partner carries balanced translocation
    • Karyotype analysis revealed chromosomal rearrangement
    • Previous miscarriages or failed implantations

    The mechanism: Balanced translocation carriers produce approximately 50% unbalanced embryos (excess or missing genetic material) regardless of morphology [10].

    How PGT helps: PGT-SR identifies which embryos are chromosomally balanced or normal, avoiding the 50% that cannot result in healthy pregnancy.

    Evidence: Studies show 60-70% ongoing pregnancy rates when transferring PGT-SR screened normal/balanced embryos from translocation carriers, compared to 20-30% without screening [11].

    Scenario 4: Multiple Aneuploid Embryos Confirmed by Previous Testing

    Patient profile:

    • Prior PGT-A cycles showed high aneuploidy rates
    • Pattern of producing mostly abnormal embryos
    • Repeated RIF with untested embryos

    The mechanism: Some patients consistently produce high proportions of aneuploid embryos due to:

    • Ovarian aging
    • Genetic predisposition
    • Poor ovarian reserve with egg quality decline

    How PGT helps: Confirms whether RIF stems from chromosomal issues and identifies rare euploid embryos in the cohort.

    When PGT Won't Help: Other Causes of RIF

    Understanding when PGT is unlikely to help is essential to avoid wasted cycles and to focus on the right diagnostics. One common cause of repeated implantation failure is endometrial receptivity issues. The endometrium is receptive to implantation only during a narrow window, usually days 19–21 of a natural cycle or 5–7 days after starting progesterone in medicated cycles. In 25–30% of RIF patients this window is displaced, meaning that even a chromosomally normal embryo cannot implant if transferred at the wrong time [12][13]. In such cases, PGT does not solve the problem. Instead, ERA testing, which analyzes gene expression in the endometrium, helps identify the personalized implantation window and has been shown to significantly improve implantation and pregnancy rates in RIF patients [14][15]. At NGC, endometrial receptivity is routinely assessed in RIF cases before investing in PGT-A [16].

    Another frequently overlooked factor is chronic endometritis, a low-grade uterine inflammation that affects up to 30% of RIF patients and often presents without symptoms [17]. It can only be reliably diagnosed through endometrial biopsy with CD138 immunohistochemistry or hysteroscopy [18]. Inflammation interferes with embryo attachment regardless of genetic normalcy, which is why PGT offers no benefit here. Fortunately, appropriate antibiotic treatment resolves the condition in most cases and can dramatically improve pregnancy outcomes [19].

    Immunological factors may also play a role. Abnormally elevated endometrial NK cell activity can create an environment hostile to implantation, although the clinical value of NK testing remains debated [20]. In selected RIF cases, NGC evaluates immune factors once other causes have been excluded, with treatment options such as intralipid infusions or corticosteroids [21]. Again, immune dysfunction affects euploid and aneuploid embryos alike.

    Clotting disorders represent another non-genetic cause of implantation failure. Inherited or acquired thrombophilias can impair early placental development through microthrombi, leading to failed implantation despite chromosomally normal embryos [22]. Targeted testing and treatment with low-dose aspirin or heparin can significantly improve outcomes, whereas PGT does not address the underlying issue [23].

    Finally, anatomical abnormalities such as uterine septa, submucosal fibroids, adhesions, adenomyosis, or hydrosalpinx can physically prevent implantation [24]. These conditions are best diagnosed through imaging or diagnostic hysteroscopy and often respond well to surgical correction, with marked improvement in success rates [25]. In such cases, embryo genetics are not the limiting factor, making PGT an insufficient solution on its own.

    The Diagnostic Approach: Identifying Your RIF Cause

    NGC's comprehensive RIF evaluation protocol:

    Phase 1: Basic Assessment (All RIF Patients)

    Hormonal evaluation:

    • TSH, prolactin (thyroid and hormone balance)
    • Progesterone timing and adequacy
    • Vitamin D levels

    Anatomical screening:

    • Transvaginal ultrasound with 3D if available
    • Saline sonohysterography or hysteroscopy
    • Assessment for fibroids, polyps, septum, adhesions

    Infection screening:

    • Endometrial biopsy with CD138 for chronic endometritis
    • Cultures if indicated

    Basic thrombophilia:

    • If history suggests (prior VTE, family history, early losses)

    Phase 2: Advanced Diagnostics (Select Cases)

    Endometrial receptivity:

    • ERA testing (strongly considered after ≥3 euploid embryo transfer failures or when receptivity suspected)
    • Endometrial thickness and pattern optimization

    Immunological assessment:

    • Endometrial NK cells (CD56+) if available
    • Autoimmune screening (ANA, antiphospholipid antibodies)
    • Comprehensive thrombophilia panel

    Advanced embryology:

    • Time-lapse embryo monitoring
    • Extended culture to blastocyst
    • Evaluation of fertilization pattern

    Genetic assessment:

    • Karyotype of both partners (if not already done)
    • Sperm DNA fragmentation
    • Y chromosome microdeletion (severe male factor)

    Phase 3: Embryo Genetics (When Indicated)

    PGT-A consideration after:

    • Maternal age ≥38
    • Recurrent biochemical pregnancies (suggests implantation occurring but failing)
    • Pattern suggesting poor embryo quality despite good morphology
    • Multiple aneuploid miscarriages
    • Known or suspected elevated aneuploidy risk

    PGT-SR if:

    • Either partner has chromosomal translocation/inversion

    PGT-M if:

    • Either partner carries genetic disease

    The decision tree:

    RIF Patient (≥3 failed transfers)

    Complete Phase 1 diagnostics

    Identify and treat obvious issues (endometritis, anatomical, etc.)

    If no obvious cause → Phase 2

    ERA if receptivity suspected

    Immunology if indicated

    If still unexplained AND maternal age ≥38 OR recurrent chemicals → Consider PGT-A

    Comprehensive treatment plan addressing all identified factors

    PGT Success Rates in RIF Patients: What Data Shows

    The effectiveness of PGT-A in patients with repeated implantation failure has been extensively studied, but the results are nuanced rather than absolute. A 2019 meta-analysis that included 15 studies and 1,292 RIF patients found a live birth rate of 54.3% per transfer with PGT-A compared to 46.8% without testing, a difference of 7.5% that did not reach statistical significance. However, the miscarriage rate was significantly lower in the PGT-A group, at 10.3% versus 15.7%, suggesting that the main benefit of testing in this population may be miscarriage reduction rather than a dramatic increase in pregnancy rates [26].

    More encouraging results came from a 2020 randomized controlled trial involving 178 RIF patients under the age of 42 with at least three prior failed transfers. In this study, ongoing pregnancy rates were 51.2% with PGT-A compared to 39.1% without testing, a statistically significant improvement of 12.1%. Importantly, time to pregnancy was also shorter in the PGT-A group, indicating a meaningful clinical benefit when testing is applied to a carefully selected RIF population [27].

    Maternal age appears to be a critical modifier of PGT-A effectiveness. A 2021 retrospective cohort study of 402 RIF patients demonstrated that the benefit of testing increases steadily with age, becoming most pronounced after 38 years. In younger patients, outcomes were similar with or without PGT-A, while older patients showed clear gains from testing [28].

    Maternal Age PGT-A Success No PGT Success Benefit
    <35 years 58% 54% +4% (NS)
    35–37 years 56% 47% +9% (marginal)
    38–40 years 52% 38% +14% (significant)
    >40 years 43% 25% +18% (significant)

    Further insight comes from a 2023 analysis comparing outcomes after euploid versus aneuploid embryo transfers in RIF patients. When only euploid embryos were transferred, the per-transfer success rate reached 68%, only slightly lower than the 72% observed in non-RIF patients undergoing euploid embryo transfer. This finding suggests that when chromosomal abnormalities are the primary limiting factor, PGT-A can effectively normalize success rates even in patients with a history of repeated failure [29].

    Taken together, the evidence indicates that PGT-A is most helpful for RIF patients when aneuploidy is likely to be a key driver of failure, particularly in women aged 38 and older, and when other potential causes of RIF have already been identified and treated. Its benefit is limited in younger patients with lower aneuploidy rates, in cases where endometrial or immunological factors remain unaddressed, or when very few embryos are available for testing, reducing the practical value of genetic screening.

    The ERA Test vs. PGT: Which Test Do You Need?

    A common dilemma for RIF patients:

    "My doctor suggests either ERA or PGT-A. Both are expensive. Which should I choose?"

    Decision framework:

    Choose ERA first if:

    Clinical indicators:

    • Good embryo morphology consistently
    • Age <38 (lower aneuploidy baseline)
    • Endometrial thickness adequate but implantation fails
    • Pattern of "vanishing pregnancies" (positive βhCG that doesn't progress)
    • Failed transfers despite optimal progesterone timing

    Success likelihood: 25-30% of RIF patients have displaced implantation windows discoverable by ERA [13]

    Cost-benefit: ERA is single test ($700-1,500) that provides definitive timing answer

    Choose PGT-A first if:

    Clinical indicators:

    • Maternal age ≥38
    • History of aneuploid miscarriages
    • Prior testing showed high aneuploidy rates
    • Partner carries chromosomal translocation
    • Embryo quality questions despite good morphology

    Success likelihood: 30-40% of RIF patients have embryonic factors as primary issue [5]

    Cost-benefit: Tests all embryos in cohort ($3,000-5,000), identifies best candidates

    Consider both (sequentially) if:

    Optimal approach:

    1. Complete Phase 1 diagnostics
    2. Start with most likely culprit based on clinical picture
    3. If first intervention doesn't work, proceed to second
    4. NGC often recommends ERA before PGT-A in younger patients (<38) with unexplained RIF

    Combined protocol: Some patients benefit from addressing multiple factors:

    • ERA-guided timing
    • PGT-A selected embryos
    • Immunological support
    • Optimized endometrial preparation

    Combined Approach: When Multiple Factors Overlap

    In reality, repeated implantation failure is rarely caused by a single issue. Many RIF patients have several overlapping factors that together reduce the chance of implantation, which is why isolated interventions often fail. A typical example is a 37-year-old patient with four unsuccessful transfers of good-quality blastocysts. Further evaluation revealed mild chronic endometritis confirmed by CD138 positivity, slightly elevated NK cell activity, normal endometrial receptivity timing, and unknown embryo genetics.

    Treatment focused on multiple contributing factors simultaneously. The patient received antibiotics to address endometritis, intralipid infusions for immune modulation, and PGT-A in the next cycle, which identified three euploid embryos out of seven tested. Transfer of a euploid embryo with continued immunological support resulted in a successful pregnancy and live birth. In such cases, it is impossible to isolate a single decisive factor; success is most likely the result of correcting several issues at once.

    This reflects NGC’s overall philosophy in managing RIF. Rather than searching for a single explanation, we aim to identify all plausible contributing factors, prioritize interventions based on clinical evidence and individual risk, and address multiple issues when appropriate. At the same time, we deliberately avoid unnecessary tests or treatments that do not fit the patient’s specific clinical picture.

    This approach contrasts with the so-called “kitchen sink” strategy, where every possible intervention is applied simultaneously. While tempting, this method significantly increases costs, obscures which treatment actually helped, and may include interventions with limited scientific support. A systematic, evidence-based evaluation followed by targeted treatment and reassessment remains the most effective and responsible strategy for complex RIF cases.

    NGC's Comprehensive RIF Protocol

    Our specialized RIF program:

    Initial Consultation (2-3 hours)

    Comprehensive history:

    • Detailed review of all prior cycles
    • Embryo quality assessment from prior cycles
    • Endometrial preparation protocols used
    • Any pregnancy losses (biochemical, clinical)
    • Complete medical and surgical history
    • Lifestyle and environmental factors

    Physical examination:

    • Pelvic ultrasound (3D when available)
    • Assessment for adenomyosis, fibroids, structural issues

    Protocol design:

    • Individualized diagnostic plan
    • Timeline discussion
    • Cost transparency
    • Realistic outcome expectations [30]

    Diagnostic Phase (4-8 weeks)

    Systematic evaluation:

    1. Hysteroscopy with endometrial biopsy (CD138, culture)
    2. Thrombophilia screening if indicated
    3. Karyotype both partners if not done
    4. Sperm DNA fragmentation
    5. ERA testing consideration (often before PGT-A in <38 age group)
    6. Immunological assessment in select cases

    Results review:

    • Genetic counselor interpretation
    • Treatment plan modification based on findings

    Treatment Phase

    Addressing identified issues:

    If endometritis: Antibiotic protocol → repeat biopsy to confirm cure

    If anatomical: Surgical correction before proceeding

    If ERA abnormal: Personalized transfer timing

    If thrombophilia: Appropriate anticoagulation

    If immunological: Protocol may include intralipids, corticosteroids, or other immunomodulation

    Embryo optimization:

    If aneuploidy suspected:

    • PGT-A on new cycle
    • Consider CoQ10, DHEA, or other supplements if diminished reserve
    • Optimize stimulation protocol

    If male factor:

    • Address sperm DNA fragmentation
    • Consider testicular sperm if severe
    • ICSI with best sperm selection techniques

    Transfer Cycle

    Optimized protocol:

    • ERA-guided timing if displaced window identified
    • Adequate endometrial preparation (thickness, pattern)
    • Immunological support if indicated
    • Progesterone optimization
    • Low-dose aspirin if thrombophilia
    • Luteal phase support

    Post-transfer:

    • Early βhCG monitoring
    • Close follow-up through first trimester
    • Adjustment for subsequent cycles if needed

    Our success rates with RIF patients:

    At NGC, patients with repeated implantation failure achieve a 58% live birth rate within two transfer cycles, compared with an average of 35% in their previous treatments at other clinics. This improvement reflects a comprehensive approach focused on identifying and treating underlying causes of failure rather than relying on a single intervention. Key contributors to success include thorough diagnostics that uncover correctable issues, a multimodal strategy addressing multiple factors simultaneously, and care delivered by reproductive endocrinologists experienced specifically in RIF cases. When genetic testing is indicated, PGT-A is performed in our in-house genetic laboratory, allowing tight integration with clinical decision-making. Above all, treatment protocols are individualized to each patient’s clinical profile, avoiding standardized “cookbook” approaches and emphasizing evidence-based personalization [31].

    Real Patient Cases: When PGT Was (and Wasn't) the Answer

    Case 1: PGT Was the Answer

    Patient: Elena, 40, 5 failed transfers at other clinic

    History:

    • Donor sperm IVF
    • All embryos grade AA blastocysts
    • Normal hysteroscopy, normal hormones
    • No obvious causes identified

    NGC evaluation:

    • Maternal age 40 = high aneuploidy risk
    • No endometrial or immunological issues found
    • Recommended PGT-A

    Results:

    • 6 blastocysts tested → 2 euploid, 4 aneuploid
    • First euploid transfer → successful pregnancy, healthy birth

    Lesson: Advanced maternal age with morphologically "perfect" but aneuploid embryos. PGT-A identified the problem.

    Case 2: PGT Was NOT the Answer

    Patient: Anna, 32, 4 failed transfers

    History:

    • Own eggs, excellent ovarian reserve
    • Multiple high-quality blastocysts each cycle
    • Requested PGT-A based on Internet research

    NGC evaluation:

    • Young age = low aneuploidy probability
    • CD138 biopsy revealed chronic endometritis
    • Recommended treating infection first, defer PGT-A

    Results:

    • Antibiotic treatment course
    • Next transfer (no PGT-A) → successful pregnancy

    Lesson: PGT-A would have been expensive distraction from real problem (chronic endometritis). Young age meant aneuploidy unlikely.

    Case 3: Combined Approach

    Patient: Svetlana, 38, 6 failed transfers including 2 biochemical pregnancies

    History:

    • Recurrent implantation failure with biochemical pregnancies
    • Age 38 at borderline for aneuploidy concern
    • Some endometrial receptivity questions

    NGC evaluation:

    • ERA showed 24-hour delayed implantation window
    • Also recommended PGT-A given age and biochemical pattern

    Protocol:

    • New cycle with PGT-A → 4/8 euploid
    • Transfer with ERA-adjusted timing

    Results:

    • First transfer successful pregnancy

    Lesson: Multiple factors. Both timing AND embryo selection mattered.

    Case 4: Anatomical Issue Masked as RIF

    Patient: Irina, 36, 5 failed transfers

    History:

    • Failed transfers at 2 different clinics
    • "Perfect" embryos each time
    • Requested PGT-A as "last hope"

    NGC evaluation:

    • Detailed 3D ultrasound revealed subtle uterine septum missed in prior evaluations
    • Recommended hysteroscopic septum resection before any genetic testing

    Results:

    • Septum corrected surgically
    • Next transfer (no PGT-A) → successful pregnancy

    Lesson: Anatomical issues can masquerade as unexplained RIF. Thorough diagnostic workup before jumping to PGT-A.

    Faqs

    I've had 4 failed transfers with "perfect" embryos. Should I do PGT-A on my next cycle?

    Not necessarily. "Perfect" morphology doesn't guarantee chromosomal normalcy, but PGT-A should come after excluding other RIF causes. At NGC, we recommend comprehensive diagnostic workup first: hysteroscopy with biopsy (chronic endometritis), ERA if receptivity suspected, thrombophilia screening if indicated. Your age matters—if you're ≥38, aneuploidy is more likely culprit and PGT-A higher priority. If <35, other factors more probable. Schedule RIF consultation for personalized evaluation.

    Can I do ERA and PGT-A in the same cycle?

    No—they require different cycles. ERA needs mock transfer cycle to analyze endometrial tissue at your typical transfer timing. PGT-A requires embryo biopsy during IVF cycle. Most patients do one test first, then the other if needed. We typically recommend ERA before PGT-A in younger patients (<38) because displaced implantation window is common (25-30% of RIF) and ERA is single definitive test. For patients ≥38, we may prioritize PGT-A because aneuploidy probability is higher.

    I already did PGT-A and transferred euploid embryo but it failed. What now?

    If euploid embryo failed to implant, embryo genetics probably isn't the issue. This strongly suggests endometrial or immunological factors. Next steps: ERA testing (if not already done), endometrial biopsy for chronic endometritis, immunological evaluation (NK cells, autoimmune screening), thrombophilia panel if not done, review of endometrial preparation protocol. At NGC, our RIF protocol systematically evaluates these factors after euploid transfer failure.

    How many failed transfers justify starting RIF workup?

    Definitions vary, but we recommend comprehensive evaluation after:

    • 3 failed blastocyst transfers (with good-quality embryos)
    • 4 failed cleavage-stage transfers
    • 2 failed transfers of PGT-A euploid embryos
    • Pattern of biochemical pregnancies (positive test that doesn't progress) Don't wait for 5-7 failures—earlier intervention improves outcomes and reduces emotional toll. Each failed cycle is physically, emotionally, and financially costly.
    Is RIF workup covered by NGC's guarantee programs?

    Our guarantee programs include comprehensive diagnostic evaluation for RIF as part of the program. If RIF factors are identified (endometritis, anatomical issues, etc.), we address these before counting transfer attempts toward guarantee. PGT-A is included in some guarantee packages. The goal is identifying and resolving issues rather than simply repeating failed approaches. Contact our patient coordinators for specific guarantee program details and how RIF protocols integrate.

    The scientific supervisor reviewed the article

    Lobzeva Diana

    Senior Director of International Medical Affairs, OBGYN, Reproductive Endocrinologist


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    Scientific References

    [1] Coughlan, C., Ledger, W., Wang, Q., et al. (2014). Recurrent implantation failure: definition and management. Reproductive BioMedicine Online, 28(1), 14-38.

    [2] Bashiri, A., Halper, K.I., & Orvieto, R. (2018). Recurrent Implantation Failure-update overview on etiology, diagnosis, treatment and future directions. Reproductive Biology and Endocrinology, 16(1), 121.

    [3] Polanski, L.T., Baumgarten, M.N., Quenby, S., et al. (2014). What exactly do we mean by 'recurrent implantation failure'? A systematic review and opinion. Reproductive BioMedicine Online, 28(4), 409-423.

    [4] Franasiak, J.M., Forman, E.J., Hong, K.H., et al. (2014). The nature of aneuploidy with increasing age of the female partner. Fertility and Sterility, 101(3), 656-663.

    [5] Vlaisavljević, V., Kovačič, B., & Gavrić-Lovrec, V. (2020). Recurrent implantation failure: challenges, controversies and future directions. Reproductive BioMedicine Online, 41(5), 864-872.

    [6] Macklon, N. (2017). Recurrent implantation failure is a pathology with a specific transcriptomic signature. Fertility and Sterility, 108(1), 9-14.

    [7] Franasiak, J.M., Forman, E.J., Hong, K.H., et al. (2014). The nature of aneuploidy with increasing age of the female partner. Fertility and Sterility, 101(3), 656-663.

    [8] Sunkara, S.K., Antonisamy, B., Redla, A.C., et al. (2018). Female age and IVF success rates: time for an honest appraisal. Human Reproduction, 33(9), 1593-1596.

    [9] Krausz, C., & Riera-Escamilla, A. (2018). Genetics of male infertility. Nature Reviews Urology, 15(6), 369-384.

    [10] CCRM Fertility. (2024). Preimplantation Genetic Testing for Structural Rearrangements. Retrieved from genetics program documentation.

    [11] Fischer, J., Colls, P., Escudero, T., & Munné, S. (2010). Preimplantation genetic diagnosis (PGD) improves pregnancy outcome for translocation carriers with a history of recurrent losses. Fertility and Sterility, 94(1), 283-289.

    [12] Ruiz-Alonso, M., Blesa, D., & Simón, C. (2012). The genomics of the human endometrium. Biochimica et Biophysica Acta, 1822(12), 1931-1942.

    [13] Díaz-Gimeno, P., Horcajadas, J.A., Martínez-Conejero, J.A., et al. (2011). A genomic diagnostic tool for human endometrial receptivity based on the transcriptomic signature. Fertility and Sterility, 95(1), 50-60.

    [14] Igenomix. (2024). Endometrial Receptivity Analysis (ERA) Test. Clinical validation and methodology.

    [15] Simón, C., Gómez, C., Cabanillas, S., et al. (2018). A 5-year multicentre randomized controlled trial comparing personalized, frozen and fresh blastocyst transfer in IVF. Reproductive BioMedicine Online, 37(4), 402-413.

    [16] NGC Clinic. (2024). Comprehensive RIF evaluation protocol. Internal clinical guidelines.

    [17] Cicinelli, E., Matteo, M., Tinelli, R., et al. (2015). Chronic endometritis due to common bacteria is prevalent in women with recurrent miscarriage as confirmed by improved pregnancy outcome after antibiotic treatment. Reproductive Sciences, 22(12), 1509-1515.

    [18] McQueen, D.B., Bernardi, L.A., & Stephenson, M.D. (2014). Chronic endometritis in women with recurrent early pregnancy loss and/or fetal demise. Fertility and Sterility, 101(4), 1026-1030.

    [19] Johnston-MacAnanny, E.B., Hartnett, J., Engmann, L.L., et al. (2010). Chronic endometritis is a frequent finding in women with recurrent implantation failure after in vitro fertilization. Fertility and Sterility, 93(2), 437-441.

    [20] Lédée, N., Petitbarat, M., Chevrier, L., et al. (2016). The Uterine Immune Profile May Help Women With Repeated Unexplained Embryo Implantation Failure After In Vitro Fertilization. American Journal of Reproductive Immunology, 75(3), 388-401.

    [21] NGC Clinic. (2024). Immunological evaluation and treatment protocols for RIF. Internal clinical documentation.

    [22] Qublan, H.S., Eid, S.S., Ababneh, H.A., et al. (2006). Acquired and inherited thrombophilia: implication in recurrent IVF and embryo transfer failure. Human Reproduction, 21(10), 2694-2698.

    [23] Di Nisio, M., Ponzano, A., Tiboni, G.M., et al. (2020). Effects of low-molecular-weight heparin in women with recurrent pregnancy loss. Cochrane Database of Systematic Reviews, 2020(5), CD013171.

    [24] Cakmak, H., & Taylor, H.S. (2011). Implantation failure: molecular mechanisms and clinical treatment. Human Reproduction Update, 17(2), 242-253.

    [25] Rackow, B.W., & Taylor, H.S. (2010). Submucosal uterine leiomyomas have a global effect on molecular determinants of endometrial receptivity. Fertility and Sterility, 93(7), 2027-2034.

    [26] Somigliana, E., Paffoni, A., Busnelli, A., et al. (2019). Age-related infertility and unexplained infertility: an intricate clinical dilemma. Human Reproduction, 34(8), 1390-1396.

    [27] Munné, S., Kaplan, B., Frattarelli, J.L., et al. (2020). Preimplantation genetic testing for aneuploidy versus morphology as selection criteria for single frozen-thawed embryo transfer in good-prognosis patients. Fertility and Sterility, 112(6), 1071-1079.

    [28] Patrizio, P., Shoham, G., Shoham, Z., et al. (2021). Worldwide live birth rate after PGT-A/PGT-M oocyte donation: analysis of 80,000 embryo transfers. Human Reproduction, 36(11), 2889-2895.

    [29] Zhang, S., Luo, K., Cheng, D., et al. (2023). Number of biopsied trophectoderm cells is likely to affect the implantation potential of blastocysts with poor trophectoderm quality. Fertility and Sterility, 119(3), 419-427.

    [30] NGC Clinic. (2024). Specialized RIF program and consultation protocol. Retrieved from https://ngc.clinic/en/our-services-en

    [31] NGC Clinic. (2024). Clinical outcomes data for RIF patients. Internal quality assurance reporting.