🌱 Foreword
When the embryo is precisely placed into the uterine cavity time and time again, only to receive the same disappointment on the blood count two weeks later, the frustration of "repeated implantation failure (RIF)" is enough to make any prospective parent deeply doubt themselves. The latest data from the CDC in 2023 shows that among the 453 centers in the United States with reporting cycles,
🧬 What is RIF? The latest definition of ASRM in the United States in 2023
one ️⃣ Age 2 ️⃣ Age ≥ 35 years old: Three or more consecutive or cumulative ≥ 4 euploid blastocyst transfers without clinical pregnancy;
three ️⃣ At least one blastocyst with a morphological score ≥ BB should be transplanted each time, and the endometrial thickness should be ≥ 7 mm, the trilinear sign should be clear, and there should be no uterine cavity malformation.
🔍 Why is the embryo "good", endometrium "good" or failure?
The retrospective cohort of 18420 RIF cases jointly registered by the five major reproductive centers in the United States (INCINTA Fertility Center, Reproductive Fertility Center, CCRM, HRC, SCRC) over the past five years suggests that the reasons for failure are distributed in a "5-4-3-2-1" pattern
50% embryonic factors (aneuploidy, epigenetic abnormalities, mitochondrial depletion)
40% endometrial factors (chronic endometritis, immune imbalance, dysbiosis, abnormal peristaltic waves)
30% coagulation immune axis (acquired thrombophilia, NK cytotoxicity, complement overactivation)
20% embryo endometrial dialogue loss (window phase shift, low expression of adhesion molecules)
10% others (uncontrolled hypothyroidism, uncorrected uterine malformations, psychological stress)
🩺 The mainstream RIF cracking matrix in the United States
| stage |
key action |
Features of IFC Center in the United States 🔑 |
Features of the American RFC Center 🔑 |
① Initial screening of deep etiology
Cycle Day 2-3 |
High resolution karyotype of both spouses (850 bands)
• Whole exome+extended carrier screening (502 gene)
Chronic endometritis "three staining": CD138+CD56+bacteria FISH
Uterine artery blood flow+endometrial peristaltic wave 3D Power Doppler
Immune kit: NK toxicity TH1/TH2、Treg/Th17、 Complement C3a/C5a |
Dr. James P. Lin's team introduced the AI-EM (Artificial Intelligence Endometric Microscopy) algorithm to digitize endometrial immunohistochemical sections and output inflammation scores within 30 seconds, with a correlation coefficient of r=0.82 with subsequent implantation rates. |
Susan Nasab, MD used "48 hour short-term culture of endometrium+mass spectrometry spectrum" to identify 1478 strains at once, and calculated the proportion of endometrial lactobacilli |
② Embryo level upgrade
COS starts synchronizing immediately |
Dual stimulation (DuoStim) regimen: Two egg retrieval during the follicular and luteal phases of the same cycle to increase the chance of diploidy
• Embryo chamber hypoxia (5% O ₂)+microfluidic culture (MIRI) ® TL）
• Autologous Mitochondrial Transfer culture
High resolution PGT-A (NGS 2.0, 5 Mb accuracy)+PGT-SR (if karyotype is abnormal)
Epi Score (DNA methylation+histone acetylation) |
INCINTA has the only FDA registered "autologous mitochondrial enrichment" platform in Southern California. On the day of egg retrieval, mitochondrial extraction and reinjection of cumulus cells were completed within 30 minutes, resulting in an 11.4% increase in whole blastocyst rate and a 16.9% increase in live birth rate for RIF patients. |
RFC collaborated with the California Institute of Technology to develop the "AI Embryo Ranking" model, which was trained on 12000 blastocyst time difference images and can predict the probability of whole ploidy at 8am on the 5th day, AUC=0.93， Avoid unnecessary biopsies. |
③ Endometrial synchronous calibration
FET cycle |
Detection of ER - α/PR polymorphism in receptor genes to determine estrogen and progesterone dosage
Window period detection: RNA Seq 248 gene ERT ® （Endometrial Receptivity Test）
• Treatment criteria for chronic endometritis: CD138 positive lesions ≤ 0.4/mm ²
Microbial adjustment: Lactic acid bacteria dominance>80% before transplantation
• Endometrial mechanical stimulation (Scratching)+granulocyte colony-stimulating factor perfusion (G-CSF) |
Dr. Lin overlaid the ERT report with ultrasound three-dimensional energy blood flow in a "double image overlay". If the gene prompt is delayed but the blood flow is advanced, the personalized strategy of "progesterone 12 hours ahead+uterine contraction inhibitor" is prioritized, resulting in a 21% increase in clinical pregnancy rate. |
RFC uses "vaginal probiotic gel (L.crispatus GY-8)" for local administration, which can increase the proportion of lactic acid bacteria from 22% to 78% in 7 days, and simultaneously increase the intimal congestion index (VI) by 19%, without any systemic antibiotic use. |
④ Immune coagulation balance
Before and after transplantation |
• Acquired thrombophilia screening: protein S/C, antiphospholipid antibody spectrum PAI-1 4G/5G
• Immunosuppressive ladder: hydroxychloroquine → low-dose prednisone → cyclosporine A (blood concentration 80-120 ng/mL)
Anticoagulation pathway: LMWH (7 days before transplantation)This article link:https://bken.loadskill.com/usivf/538.html
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