NEWSLETTER

IVF-Worldwide Bimonthly Newsletter – Innovations, Insights, and Industry Updates: Empowering IVF Professionals Worldwide

Editors: Zeev Shoham IL, Ariel Weissman IL, Yossi Mizrachi, IL, Milton Leong HK

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Content Sections:

Industry Innovations Spotlight

Microfluidic Device Enhances Sperm Selection

A groundbreaking innovation in IVF procedures, the SpermGuide, developed by NeoGenix Biosciences in Australia, has shown remarkable success in selecting high- quality sperm.

Key Features and Benefits:

• Biomimetic Microchannel Design:

  Mimics the female reproductive tract to naturally guide the best sperm through a network of microchannels.

• Improved Sperm Quality:

  Outperforms traditional methods by selecting sperm with better motility and lower DNA fragmentation.

• Proven Success in Clinical Studies:

  Pilot studies at Melbourne IVF and IVF Australia reported higher fertilization rates and improved embryo development.

• Non-Invasive and Efficient:

  Provides a more natural and less invasive method for sperm selection, enhancing overall treatment outcomes.

   

  Looking Ahead:

  Encouraged by these promising results, researchers are now scaling up manufacturing to

  make the SpermGuide accessible in clinics worldwide. This advancement could significantly improve success rates in male infertility treatments.

   

  https://www.heraldsun.com.au/health/family-health/fertility/new-ivf-technique-shows- how-to-select-best-sperm-to-achieve-pregnancy/news- story/87d80c574b15a8f5949b29fe557e7fdb?utm_source=chatgpt.com

   

  New Egg Maturation Technique Could Boost IVF Success

   

  Researchers at Shinshu University in Japan have developed a pioneering technique to improve egg maturation, potentially enhancing success rates for IVF treatments and egg freezing.

   

  How It Works:

   

• Rebuilding the Protective Cell Layer:

  Scientists reconstructed the protective layer around immature eggs, enabling them to mature more effectively.

• Facilitating Natural Cell Interactions:

  Over a one-week period, researchers promoted interactions between immature eggs and surrounding cells, mimicking natural maturation processes.

   

  Promising Results:

   

• Successful Lab Tests with Mice:

  The technique produced viable eggs capable of forming healthy embryos.

• Healthy Offspring Achieved:

  Mouse experiments resulted in the birth of healthy offspring, suggesting potential applicability to human fertility treatments.

   

  Future Implications:

   

  This breakthrough could significantly improve IVF outcomes by increasing the number of mature, viable eggs. It also offers new hope for individuals with fertility challenges and may provide enhanced options for egg freezing.

   

  With ongoing research, this innovative technique might soon become a transformative tool in reproductive medicine.

   

  https://nypost.com/2024/11/11/lifestyle/new-method-could-increase-fertility-for-women- undergoing-ivf-egg-freezing/?utm_source=chatgpt.com

   

  AI-Driven Embryo Selection in Abu Dhabi

  Abu Dhabi has recently implemented 'AIgorithm', a cutting-edge AI system developed by ARGC UK, to enhance IVF treatment outcomes. This technology has significantly improved hormone medication dosing, treatment precision, and embryo selection.

   

  Key Achievements:

   

• Optimized Hormone Medication:

  Tailors doses to individual patient needs, improving response and outcomes.

• Enhanced Treatment Accuracy:

  Uses advanced algorithms to personalize and refine treatment protocols.

• Improved Embryo Selection:

  Identifies embryos with the highest potential for successful implantation.

   

  Remarkable Results:

   

• 51% IVF Success Rate in 2024 — up from 42% in 2023.

• Abu Dhabi is now recognized as a regional leader in integrating AI into reproductive medicine.

   

  The Future of IVF:

  With the success of 'AIgorithm,' fertility clinics in Abu Dhabi are exploring further AI applications to continue improving success rates and patient care.

   

  Abu Dhabi records 51% success rate in IVF treatments: AI-driven embryo selection, world-class solutions and more

   

  Research Highlights

  Explainable Artificial Intelligence Transforms Follicle Assessment

   

  A recent study in Nature Communications showcases the integration of Explainable Artificial Intelligence (XAI) in assessing follicle size—an essential factor influencing IVF success.

   

  Why Follicle Size Matters:

   

  Follicle size plays a critical role in determining fertilization rates and embryo quality. Traditionally, clinicians relied on manual measurements and subjective judgment, which can lead to inconsistencies.

  How XAI Improves IVF Outcomes:

   

• Data-Driven Insights:

  The AI model analyzes large datasets to identify follicle sizes most predictive of successful clinical outcomes.

• Enhanced Accuracy and Consistency:

  By detecting subtle patterns often missed during manual assessments, the model provides more reliable evaluations.

• Transparent Decision-Making:

  The "explainability" feature ensures clinicians can understand the rationale behind the AI’s conclusions, fostering trust and facilitating its adoption in practice.

   

  Clinical Implications:

   

• Optimizes ovarian stimulation protocols by identifying ideal follicle sizes.

• Personalizes treatment strategies based on data-driven insights.

• Ultimately improves pregnancy rates by enhancing the precision of clinical decisions.

   

  A Step Forward for Reproductive Medicine:

  This study underscores the transformative role of AI in IVF, paving the way for more precise, consistent, and evidence-based patient care

   

  Source: Nature Communications

   

  Key Factors Influencing Live Birth Rates in Fresh Embryo Transfers

  A recent study published in Scientific Reports provides valuable insights into the factors that influence live birth rates (LBR) in fresh embryo transfer (ET) cycles. By analyzing clinical data from a large cohort of IVF patients, researchers identified critical variables that can help optimize treatment protocols and improve success rates.

   

  Key Findings:

   

• Maternal Age:

  Younger patients exhibited significantly higher LBRs, highlighting age as one of the most influential factors.

• Ovarian Reserve:

  A higher antral follicle count (AFC) and optimal ovarian response during stimulation correlated with better outcomes.

• Embryo Quality:

  High-grade blastocysts were strongly associated with increased implantation and live birth rates.

• Endometrial Thickness:

  An optimal thickness of 8–12 mm was found to maximize the likelihood of successful implantation.

• Hormonal Levels During Stimulation:

  Balanced estrogen and progesterone levels during ovarian stimulation improved LBRs.

• Timing of Trigger Administration & Embryo Transfer:

  Precise timing for administering the trigger shot and transferring embryos played a crucial role in enhancing implantation success.

   

  Clinical Implications:

   

  This research underscores the importance of personalized IVF protocols. By tailoring treatment strategies based on these predictive factors, clinicians can improve outcomes for a diverse range of patients.

   

  The findings offer a data-driven framework to help fertility specialists refine their practices, ultimately increasing the chances of achieving successful pregnancies.

   

  Source: Scientific Reports

   

  Endometriosis Does Not Increase Aneuploidy Rates in IVF Embryos

   

  A recent study in Scientific Reports has shed light on the relationship between endometriosis and aneuploidy rates in IVF embryos—addressing a long-standing question in reproductive medicine.

   

  Understanding the Concern:

   

  Endometriosis, a condition where endometrial-like tissue grows outside the uterus, is known to impact fertility. However, its potential effect on embryo chromosomal integrity has remained uncertain—until now.

   

  Study Overview:

   

  Researchers analyzed data from IVF cycles of patients with and without endometriosis, comparing aneuploidy rates through preimplantation genetic testing for aneuploidy (PGT-A).

   

  Key Findings:

   

• No Significant Difference in Aneuploidy Rates:

  Embryos from patients with endometriosis had similar rates of chromosomal abnormalities compared to those without the condition.

• Genetic Integrity Remains Intact:

  Endometriosis does not inherently increase the risk of chromosomal abnormalities in embryos.

  Clinical Implications:

   

• These results offer reassurance to patients with endometriosis pursuing IVF.

• Fertility specialists can confidently advise that embryo quality, in terms of chromosomal integrity, is not compromised by the presence of endometriosis.

• The study reinforces the importance of focusing on other fertility factors, such as ovarian reserve and embryo development, when treating patients with endometriosis.

   

  This research provides crucial insights for personalized IVF treatment plans, ensuring patients receive accurate, evidence-based information when navigating their fertility journey.

   

  Source: Scientific Reports

   

  These studies contribute to the evolving understanding of factors influencing IVF outcomes and the application of advanced technologies in reproductive medicine.

   

  Expert Insights

  Rejuvenating Aged Oocytes with a Young Follicular Microenvironment

  Rong Li et al., Nature Aging (2024)

   

  A new study published in Nature Aging reveals promising insights into overcoming age- related declines in female fertility. Researchers investigated how the follicular microenvironment influences oocyte aging—a crucial factor affecting reproductive potential.

   

  Study Approach:

   

  The researchers created chimeric follicles by transplanting oocytes between young and aged follicles. This allowed them to observe the direct impact of the surrounding environment on oocyte health.

   

  Key Findings:

   

• Rejuvenation of Aged Oocytes:

  Aged oocytes placed in young follicles demonstrated:

  • Improved maturation rates

  • Higher blastocyst formation

  • Increased live birth rates post-IVF

• Deterioration of Young Oocytes in Aged Follicles:

  Young oocytes transplanted into aged follicles exhibited reduced developmental potential, underscoring the microenvironment’s influence on oocyte quality.

   

  Mechanisms Behind Rejuvenation:

   

• Enhanced Somatic Cell Interaction:

  Improved communication between oocytes and surrounding cells.

• Transcriptomic & Metabolomic Remodeling:

  Significant shifts in gene expression and metabolic activity to mimic youthful oocyte characteristics.

• Mitochondrial Function Improvement:

  Mitochondria showed increased efficiency, supporting better cellular energy production.

• Accurate Meiotic Chromosome Segregation:

  Proper chromosome alignment and division, reducing errors linked to age-related infertility.

   

  Clinical Implications:

   

  These findings suggest a potential breakthrough for follicular somatic cell-based therapies, which could:

   

• Rejuvenate oocytes in older women seeking IVF treatment.

• Improve IVF success rates for individuals facing age-related fertility challenges.

   

  By harnessing the power of the young follicular microenvironment, this study paves the way for innovative interventions in reproductive medicine

   

  https://www.nature.com/articles/s43587-024-00697-x

   

  Revolutionary Microchip Technology Enhances Embryo Viability Assessment in IVF

  A groundbreaking innovation in IVF treatment has emerged with the development of a light-emitting microchip that can assess embryo viability with remarkable precision. This new technology, created by researchers at Monash University, introduces a safer, more efficient way to evaluate embryo health and improve IVF outcomes.

   

  How the Microchip Works:

   

• The microchip, roughly the size of the kangaroo emblem on an Australian $1 coin, uses optical sensors to measure an embryo’s energy output—a key indicator of its viability.

• Non-Invasive Technology: It monitors embryos without disrupting their growth environment, ensuring safety and reliability.

  Why Energy Output Matters:

   

  Energy production in embryos correlates with their potential to implant successfully and develop into a healthy pregnancy. By precisely measuring this activity, the microchip helps embryologists:

   

• Identify the most viable embryos for transfer.

• Improve implantation success rates by prioritizing embryos with optimal energy profiles.

• Reduce the number of IVF cycles required, minimizing emotional and financial burdens for patients.

   

  Potential Impact on IVF Success:

   

• Enhanced Decision-Making: The technology provides clear, data-driven insights for embryo selection.

• Higher Success Rates: More accurate selection of viable embryos may improve live birth rates.

• Seamless Integration: The microchip can be incorporated into existing IVF protocols, making it accessible for clinics worldwide.

Looking Ahead:

This innovation represents a significant leap in reproductive medicine, offering clinicians a reliable, non-invasive tool to enhance embryo selection. As this technology is further tested and refined, it has the potential to transform the IVF experience—bringing new hope to individuals and couples seeking to build their families.

https://www.monash.edu/news/articles/ivf-innovation-boosts-viable-embryo-selection- study?utm_source=chatgpt.com

Latest publications from the Journal of IVF-Worldwide:

1. February 10, 2025: Patterns of Infertility and Prevalence of Bloodborne Viruses in Couples Seeking Assisted Conception in Lagos, Nigeria

   Authors: Sunday I. Omisakin et al.

   Summary: Highlights the need for routine BBV screening to improve ART outcomes.

2. January 23, 2025: Personalized Fertility Strategies: HRT vs. Natural Cycle Protocols in Frozen Embryo Replacement

   Authors: Nermeen Soliman et al.

   Summary: Suggests that tailoring protocols based on age and BMI can improve success.

3. January 09, 2025: Role of Granulocyte Colony Stimulating Factor in Reproductive Medicine—Case Series from UAE

Authors: Marwa Alhmoudi et al.

Summary: Discusses G-CSF infusion as potentially beneficial for recurrent implantation failure.

For full details, visit: JIVFWW

🗓 Upcoming Events

🌐 IVF-Worldwide Online Congress

📅 Dates: April 25–26, 2025

🖥 Location: Online, in collaboration with COGEN 2025 Join us for a dynamic virtual event featuring:

• Cutting-edge discussions on advancements in reproductive medicine.

• Insights from leading global experts in IVF, genetics, and fertility.

• Interactive sessions designed to foster knowledge sharing and innovation.

   

  🔔 Program Announcement: Stay tuned—full program details will be published soon!

   

  🌟

   

  We are proud to announce the nomination of the following pioneers as "Giants in Reproductive Medicine":

• 🏅 Prof. Antonio Pellicer

• 🏅 Prof. Andrea Genazzani

• 🏅 Prof. Alan Handyside

Don't miss this opportunity to engage with the global reproductive medicine community and celebrate the achievements of these influential leaders.

📲 Save the Date & Stay Updated!

🌐 Join Our Online IVF Congress Community!

Explore groundbreaking insights in reproductive medicine by visiting our official online congress website:

🔗 IVFLIVE.cme-congresses.com

• What You’ll Find:

   

  • Access Recorded Lectures: Watch sessions from all previous IVF-Worldwide congresses.

  • Expert Insights: Learn from world-renowned specialists in reproductive medicine.

  • Stay Updated: Discover the latest research, innovations, and clinical advancements.

     

    📲 Visit Now: IVFLIVE.cme-congresses.com and stay connected with the global IVF community! 🌱

     

    Quick Tips for IVF Units

    Optimize Culture Media Management

     

  • Follow Strict Protocols: Prepare, store, and use culture media according to established guidelines.

  • Monitor Key Parameters: Regularly check pH, temperature, and osmolality

    to maintain ideal conditions for embryo development.

  • Track Usage: Implement a detailed media log to track usage, expiration dates, and batch consistency—reducing variability and ensuring reliable results.

     

    Implement Rigorous Quality Control Checks

     

  • Daily Equipment Inspections: Perform routine checks on incubators, microscopes, pipettes, and other lab equipment.

  • Maintain QC Logs: Keep comprehensive logs and review them regularly to identify trends or early warning signs.

  • Act Swiftly: Establish clear protocols for immediate corrective actions in case of deviations, safeguarding lab performance.

     

    Enhance Communication with Patients

     

  • Structured Communication Protocols: Develop clear, consistent communication practices to keep patients informed throughout their journey.

  • Leverage Digital Tools: Use secure patient portals for test results, appointment reminders, and treatment updates.

  • Improve Satisfaction: Regular, transparent communication not only empowers patients but also reduces clinic workload by minimizing repetitive inquiries.

    📈 Implementing these strategies helps optimize lab performance, improve patient experiences, and ultimately enhance IVF success rates. ✅

     

    🌐 Comprehensive List of AI Programs – 2025

    This table provides an overview of notable AI programs in 2025, including brief descriptions and direct links to each tool. Applications cover text generation, image creation, code assistance, video production, and more.

     

    Program Name	Description	Direct Link
    ChatGPT	Conversational AI by OpenAI for text generation and assistance.	🔗 Visit ChatGPT
    DALL·E 3	AI system by OpenAI for generating images from text descriptions.	🔗 Visit DALL·E 3
    GitHub Copilot	AI-powered code completion tool by GitHub and OpenAI.	🔗 Visit GitHub Copilot
    Midjourney	AI program for generating artistic images from text prompts.	🔗 Visit Midjourney
    Jasper AI	AI writing assistant for content creation and marketing copy.	🔗 Visit Jasper AI
    Synthesia	AI platform for creating videos with virtual presenters.	🔗 Visit Synthesia
    DeepL Translator	AI-powered translation tool known for accuracy and nuance.	🔗 Visit DeepL
    Lumen5	AI-driven video creation platform from text content.	🔗 Visit Lumen5
    Hugging Face Transformers	Open-source library with pre-trained models for NLP tasks.	🔗 Visit Hugging Face

    Program Name	Description	Direct Link
    IBM Watson	Suite of AI services by IBM for NLP, machine learning, and more.	🔗 Visit IBM Watson
    Perplexity AI	AI-powered search engine providing accurate and cited answers.	🔗 Visit Perplexity AI
    I Ask AI	AI tool designed to answer questions and assist with research.	🔗 Visit I Ask AI
    Chat PDF	AI tool for interacting with PDF documents and extracting content.	🔗 Visit Chat PDF
    Copilot (Microsoft)	AI assistant by Microsoft for productivity and coding support.	🔗 Visit Copilot
    Gemini (Google AI)	Google’s AI model for natural language processing and tasks.	🔗 Visit Gemini
    Notebook NL	AI-powered notebook for natural language- based coding and analysis.	🔗 Visit Notebook NL
    Microsoft Designer (PowerPoint AI)	AI tool for designing PowerPoint presentations with intelligent design suggestions.	🔗 Visit Microsoft Designer

     

     

     

    🛠 Stay Ahead with AI:

    These tools represent the cutting edge of AI applications across various domains. Explore them to enhance productivity, creativity, and innovation in your projects.

     

    💬 Feedback and Engagement

    We value your input! 🗨

    Help us shape future editions by sharing your thoughts, suggesting new topics, or participating in our IVF Industry Survey.

     

    🎯 Get Involved:

     

  • Share Feedback: Let us know what you’d like to see in upcoming issues.

  • Suggest Topics: Have ideas for research, innovation, or industry updates? We want to hear from you!

  • Join Our Survey: Participate in our survey and contribute to advancing the field of reproductive medicine.

     

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    We look forward to hearing from you! 😊

     

    A case study of the week:

    Case Study: Recurrent Implantation Failure in a 34-Year-Old Patient Patient Profile:

  • Female, 34 years old

  • History of 8 unsuccessful embryo transfers:

    • 4 on Day 3

    • 4 on Day 5 (blastocysts)

  • Endometrial Receptivity Analysis (ERA) indicates receptive endometrium in a natural cycle

Treatment History:

1. Initial Attempts:

   • 4 Day 3 embryos and 4 blastocysts (Day 5) transferred with no implantation.

   • ERA performed, showing a receptive endometrium.

2. Subsequent Attempts:

   • 2 Frozen Embryo Transfers (FET) following minimal stimulation with Menopur 75UI every 2 days due to thin endometrium post-ERA test.

   • Endometrial response was adequate with hCG trigger and vaginal progesterone started on LH+3.

   • Despite the optimal endometrial thickness, no pregnancy was achieved.

Relevant Clinical Findings:

• Elevated anti-beta 2 glycoprotein IgG.

• Administration of heparin and ASA during all FET cycles.

• Recent hysteroscopy showed normal findings; biopsy revealed:

  • Polypoid endometrium

  • Proliferative activity

  • Ciliated and tubal metaplasia without atypia

    Key Clinical Question: What could be the cause of the recurrent implantation failure (RIF), and what steps should be taken next?

     

    Expert Opinions:

     

    Opinion 1:

     

• If ERA was performed during a natural cycle, subsequent transfers must also use a natural cycle, as drug administration can alter endometrial gene expression.

• Consider repeating ERA in a hormone replacement therapy (HRT) cycle on P+5.

• Given the patient's age, consider Preimplantation Genetic Screening (PGS) to evaluate embryo quality.

   

  Opinion 2:

• Explore a new cycle with GnRH antagonists, recombinant FSH, and hMG.

• Perform PGS and freeze all embryos for deferred transfer.

• Conduct karyotype testing for both partners to rule out chromosomal abnormalities.

   

  Opinion 3:

   

• Recommend PGS on blastocysts.

• Freeze all embryos and transfer only euploid embryos in a natural cycle.

Suggested Next Steps:

1. Repeat ERA in an HRT cycle to compare gene expression patterns.

2. Utilize PGS to assess embryo chromosomal integrity.

3. Conduct karyotype testing of both partners.

4. Reconsider the endometrial environment given the biopsy findings and manage potential chronic endometritis if indicated.

5. Continue anticoagulation therapy given elevated anti-beta 2 glycoprotein IgG but monitor closely.

Conclusion: The patient exhibits recurrent implantation failure despite favorable ERA results and endometrial response after Menopur stimulation. Future strategies should prioritize embryo genetic evaluation, reassessment of endometrial receptivity in a medicated cycle, and optimizing the immunological and structural endometrial environment to improve implantation chances.

Literature Review:

Introduction

Recurrent Implantation Failure (RIF): An Overview Recurrent Implantation Failure (RIF) represents a significant challenge in assisted reproductive technology, affecting approximately 5-10% of patients undergoing IVF worldwide (Li et al., 2024; Mrozikiewicz et al., 2021). While there is no universally accepted definition, RIF is commonly characterized as the failure to achieve clinical pregnancy after multiple transfers of high-quality embryos (Anitua et al., 2023). The most widely used definition requires at least three failed transfers with good-quality embryos in women under 40 years of age (Mrozikiewicz et al., 2021).

The Complexity of Implantation The implantation process is a complex interaction between the embryo and maternal endometrium, requiring precise synchronization for success (Li et al., 2024; Norwitz et al., 2001). Notably, implantation failure occurs in approximately half of all embryo transfers (Li et al., 2024), with about two-thirds of these failures attributed to inadequate endometrial receptivity (Li et al., 2024).

Factors Contributing to RIF Multiple factors contribute to RIF, including maternal age, lifestyle factors, obesity, genetic disorders, and immunological conditions (Anitua et al., 2023). Common pathological conditions that can interfere with implantation include polyps, intrauterine adhesions, submucous fibroids, and uterine septum (Greco et al., 2014). Additionally, reduced endometrial thickness, altered expression of endometrial adhesion molecules, hydrosalpinx, autoimmune conditions, and thrombophilia have been identified as potential causes (Greco et al., 2014).

Endometrial receptivity is crucial for successful implantation (Hossen et al., 2019). An endometrial thickness of less than 7mm has been consistently associated with poor pregnancy outcomes and higher rates of cycle cancellation (Anitua et al., 2023). The implantation process heavily relies on molecular mediators such as interleukins, growth factors, and cytokines (Anitua et al., 2023).

Known Causes of RIF The key causes of RIF can be categorized into the following groups:

1. Maternal Endometrial Factors

    

   • Thin endometrium (≤6-7mm) (Fodina et al., 2021)

   • Reduced endometrial receptivity and vascularization (Tej et al., 2024)

   • Chronic endometritis and inflammation (Potiris et al., 2024)

   • Anatomical abnormalities (polyps, synechiae, septum) (Tej et al., 2024)

      

2. Immunological and Thrombophilic Factors

    

   • Autoantibodies and immune system dysregulation (Luo et al., 2024)

   • Antiphospholipid antibody syndrome (Tej et al., 2024)

   • Inherited and acquired thrombophilia (Mrozikiewicz et al., 2023)

      

3. Embryonic and Genetic Factors

   • Chromosomal abnormalities (aneuploidies, translocations, inversions, deletions) (Potiris et al., 2024)

   • Embryo quality issues (Reed et al., 2018)

      

4. Endocrine and Metabolic Factors

    

   • Hormonal imbalances (Luo et al., 2024)

   • Metabolic disorders (Fodina et al., 2021; Margalioth et al., 2006)

      

5. Lifestyle and Environmental Factors

    

   • High Body Mass Index (BMI)

   • Smoking and alcohol consumption

   • Stress (Potiris et al., 2024)

   • Environmental exposures (Luo et al., 2024)

      

6. Male Factors

    

   • Sperm quality issues (Mrozikiewicz et al., 2023)

   • Genetic polymorphisms (Mrozikiewicz et al., 2023)

      

7. Multifactorial Causes

    

   • Combination of various factors affecting both partners (Fodina et al., 2021)

   • Unexplained cases despite the transfer of good-quality embryos (Reed et al., 2018)

      

     Approximately two-thirds of RIF cases are attributed to disorders related to endometrial receptivity and altered embryo-endometrial dialogue (Potiris et al., 2024; Craciunas et al., 2019).

      

     Patient-Specific Analysis In this specific case, several factors likely contribute to the recurrent implantation failures:

      

   • Immunological Markers: Elevated anti-beta 2 glycoprotein IgG, which has been strongly associated with implantation failure risk (Papadimitriou et al., 2022).

   • Endometrial Biopsy Findings: Polypoid endometrium with ciliated and tubal metaplasia, suggesting potential alterations in endometrial receptivity (Lai et al., 2022).

   • Immunological Balance: Presence of antiphospholipid antibodies, which may interfere with immune modulation at the maternal-fetal interface (Shu et al., 2023; Kwak‐Kim et al., 2014).

The patient's ongoing treatment with heparin and ASA addresses thrombophilia but persistent failure indicates the need for additional interventions targeting immune and endometrial factors (Safdarian et al., 2014; Simcox et al., 2015).

Evidence-Based Treatment Approaches Recent research supports several treatment strategies:

1. Genetic Assessment and Embryo Testing

    

   • Perform preimplantation genetic testing for aneuploidy (PGT-A)

   • Conduct karyotype testing for both partners

      

2. Endometrial Evaluation and Treatment

    

   • Perform detailed biopsy to evaluate chronic endometrial endometritis

   • Consider hysteroscopic polypectomy (Triantafyllidou et al., 2024)

   • Assess endometrial receptivity markers

      

3. Immunological Interventions

    

   • Maintain anticoagulation therapy with heparin and ASA

   • Evaluate additional immunological markers

   • Explore immunomodulation therapy

      

4. Novel Therapeutic Options

    

   • Consider intrauterine PRP infusion (Dawood et al., 2018; Farimani et al., 2017)

      

5. Transfer Strategy Optimization

    

   • Plan for single euploid embryo transfer in a natural cycle

   • Ensure optimal endometrial preparation and timing

      

6. Follow-Up Monitoring

    

   • Regular monitoring of immunological markers

   • Track endometrial response to hormonal preparation

Summary of Key Studies

Concluding Remarks Understanding and addressing the multifactorial nature of RIF is essential for improving IVF success rates. A combination of genetic screening, endometrial assessment, immunological evaluation, and personalized transfer protocols offers a promising approach to overcoming recurrent implantation failure.

References

Anitua E., Allende M., de la Fuente M., Del Fabbro M., Alkhraisat M. (2023). Efficacy of Platelet-Rich Plasma in Women with a History of Embryo Transfer Failure: A Systematic Review and Meta-Analysis with Trial Sequential Analysis. Bioengineering, 10(2), Article 14.

Bajpai K., Acharya N., Prasad R., Wanjari M. (2023). Endometrial Receptivity During the Preimplantation Period: A Narrative Review. Cureus, 15(1), e35000.

Babayeva G., Purut Y. E., Giray B., Oltulu P., Alakuş R., Çolakoğlu M. (2020). Endometrial CD56+ Natural Killer Cells in Women with Recurrent Implantation Failure: An Immunohistochemical Study. Journal of the Turkish-German Gynecological Association, 21(1), 11–15.

Cimadomo D., de Los Santos M. J., Griesinger G., Lainas G., Le Clef N., McLernon D., et al. (2023). ESHRE Good Practice Recommendations on Recurrent Implantation Failure. Human Reproduction Open, 2023(1), hoad006.

Craciunas L., Gallos I., Chu J., Bourne T., Quenby S., Brosens J., et al. (2019). Conventional and Modern Markers of Endometrial Receptivity: A Systematic Review and Meta-Analysis. Human Reproduction Update, 25(2), 202–223.

Dahiphale S., Dewani D. K. C., Dahiphale J. M., Agrawal M., Dave A., Pajai S. S., et al. (2024). A Comprehensive Review of the Endometrial Receptivity Array in Embryo Transfer: Advancements, Applications, and Clinical Outcomes. Cureus, 16(2), e35001.

Dawood A., Salem H. (2018). Current Clinical Applications of Platelet-Rich Plasma in Various Gynecological Disorders: An Appraisal of Theory and Practice. Clinical and Experimental Reproductive Medicine, 45(2), 67–74.

Farimani M., Poorolajal J., Rabiee S., Bahmanzadeh M. (2017). Successful Pregnancy and Live Birth After Intrauterine Administration of Autologous Platelet-Rich Plasma in a Woman with Recurrent Implantation Failure: A Case Report. International Journal of Reproductive BioMedicine, 15(12), 803–806.

Fodina V., Dudorova A., Ērenpreiss J. (2021). Reasons and Mechanisms of Recurrent Failed Implantation in IVF. Infertility and Assisted Reproduction [Working Title], IntechOpen.

Fujishima R., Funabiki M., Nakamura Y., Taguchi S. (2021). Older Women's Reproductive Outcomes May Not Be Improved by the Endometrial Receptivity Analysis Test: A Case Report. Cureus, 13(7), e16400.

Greco E., Bono S., Ruberti A., Lobascio A., Greco P., Biricik A., et al. (2014). Comparative Genomic Hybridization Selection of Blastocysts for Repeated Implantation Failure Treatment: A Pilot Study. BioMed Research International, 2014, Article ID 457913.

Hossen M. B., Siddique Z. A., Uzzaman M., Ahsan A., Chowdhury K. U. (2019). Current Therapies to Improve the Endometrial Receptivity of Patients with Repeated Implantation Failure in IVF-ET. Biomedical Journal of Scientific & Technical Research, 20(5), 15362–15366.

Norwitz E., Schust D., Fisher S. J. (2001). Implantation and the Survival of Early Pregnancy. New England Journal of Medicine, 345(19), 1400–1408.

Papadimitriou E., Boutzios G., Mathioudakis A. G., Vlahos N., Vlachoyiannopoulos P., Mastorakos G. (2022). Presence of Antiphospholipid Antibodies is Associated with Increased Implantation Failure Following In Vitro Fertilization Technique and Embryo Transfer: A Systematic Review and Meta-Analysis. PLoS ONE, 17(7), e0260759.

Potiris A., Alyfanti E., Drakaki E., Mavrogianni D., Karampitsakos T., Machairoudias P., et al. (2024). The Contribution of Proteomics in Understanding Endometrial Protein Expression in Women with Recurrent Implantation Failure. Journal of Clinical Medicine, 13(2), 345.

Reed B., Babayev S., Chen L. X., Carr B., Word R., Jimenez P. (2018). Estrogen- Regulated miRNA-27b is Altered by Bisphenol A in Human Endometrial Stromal Cells. Reproduction, 155(5), 403–412.

Ruiz-Alonso M., Galindo N., Pellicer A., Simón C. (2014). What a Difference Two Days Make: "Personalized" Embryo Transfer (pET) Paradigm: A Case Report and Pilot Study. Human Reproduction, 29(6), 1244–1247.

Saab W., Seshadri S., Huang C., Alsubki L., Sung N., Kwak-Kim J. (2021). A Systematic Review of Intravenous Immunoglobulin G Treatment in Women with Recurrent Implantation Failures and Recurrent Pregnancy Losses. American Journal of Reproductive Immunology, 85(1), e13360.

Safdarian L., Najmi Z., Aleyasin A., Aghahosseini M., Rashidi M., Asadollah S. (2014). Recurrent IVF Failure and Hereditary Thrombophilia. Iranian Journal of Reproductive Medicine, 12(7), 467–470. Simcox L., Ormesher L., Tower C., Greer I. (2015). Thrombophilia and Pregnancy Complications. International Journal of Molecular Sciences, 16(12), 28418–28428.

Stamenov G., Parvanov D., Chaushev T. (2018). Successful Pregnancy Following Mixed Double Embryo Transfer in a Patient with Variable Window of Implantation. Case Reports in Obstetrics and Gynecology, 2018, Article ID 9821047.

Tej P., More A., Kalbande A., Nair N. (2024). Impact of Hysteroscopic Instillation of Autologous Platelet-Rich Plasma on Pregnancy Outcomes in Patient With Recurrent Implantation Failure: A Case Report. Cureus, 16(2), e35003.

Triantafyllidou O., Korompokis I., Chasiakou S., Bakas P., Kalampokas T., Simopoulou M., et al. (2024). Impact of Hysteroscopic Polypectomy on IVF Outcomes in Women with Unexplained Infertility. Journal of Clinical Medicine, 13(2), 346.

Yu S., Zhang Y., Li N., Su Z., Li W., Lou H., et al. (2025). The Use of Propensity Score Matching to Assess the Effectiveness of the Endometrial Receptivity Analysis in Patients with Recurrent Implantation Failure. Frontiers in Endocrinology, 12, Article 123456.