New solution to repeated embryo transfer failures in surrogate mothers
Human Reproduction 2025 heavyweight study: no difference in live birth rates for surrogate mothers using atosiban in routine frozen embryo cycles
I. The Clinical Mystery of Atosiban: From Preterm Labor Treatment to Cross-border Applications in Reproduction
1. Analysis of the essence of the drug
Mechanism of action: selective oxytocin receptor antagonist, inhibits contractions by blocking OXTR receptors in the myometrium.
Original indication: FDA-approved for preterm labor interruption at 24-33 weeks of gestation (intravenous infusion regimen).
Basis of application in the field of reproduction:
Ventilator manipulation triggers the release of prostaglandins, with contractions reaching a frequency of 4-6 contractions/minute.
Serum oxytocin levels are 2 to 8 times higher in RIF (Repeated Implantation Failure) than those of patients with a primary diagnosis. 2.8 times
2. The theory-to-practice gap
Dr. Emma Wilson of the Cambridge Center for Reproductive Medicine states:
“Atosiban is less than 30% bioavailable in the resting uterus and its efficacy is highly dependent on the threshold of contraction activity – it is only efficacious if the underlying contractions are >3 per minute”
II. Top publication evidence: disruptive findings from 1100 frozen embryo transfers
ralph lauren polo ralph lauren pas cher Study design milestones
| parameters | Atosiban Group (n=549) | Placebo group (n=551) | P-value |
|---|---|---|---|
| live birth rate | 49.5% | 44.7% | 0.10 |
| Clinical pregnancy rate | 58.1% | 53.6% | 0.12 |
| abortion rate | 12.3% | 14.2% | 0.38 |
In-depth subgroup analysis
High-contraction population (>3 contractions/min):
Live birth rate 51.9% in the atosiban group vs 39.3% in the placebo group (*P=0.11*)
Core findings:
“For surrogate mothers who fail their first transfer, there is no significant benefit from the routine use of atosiban for secondary frozen embryo transfers”
– -Human Reproduction 2025;40(7):dae107
Additional trial at University College London: contraction inhibition decreased from 78% to 12% 2 hours after intravenous injection, confirming that the short half-life (t1/2=1.7h) was the main cause of failure
III. the precise benefit of the population: the four clinical scenarios of the breakthrough strategy
▶ Scenario 1: endometriosis
Pathological features:
Serum contractile hormone: 1.89±0.33ng/L (significantly higher than tubal infertility 1.66±0.32ng/L)
Frequency of uterine contractions: 2.5±1.2 contractions/minute (40% above the normal threshold)
Intervention effect:
A single intravenous infusion of 6.75mg → Clinical pregnancy rate increased from 38.3% to 58.3% (P<0.01)
▶ Scenario 2: Fresh embryo transfer cycle
High-risk triple factor:
Supraphysiologic estrogen (>5000 pmol/L) activates OXTR expression
Cervical manipulation causes mechanical irritation
Peak prostaglandin release is 300% higher than in frozen embryo cycles
Multicenter data:
Live birth rate in the atosiban group 53.17% vs. 41.01% in the control group (*P=0.002*)
▶ Scenario 3: High-aged obese multiple failed surrogate mothers
Fertility Center Subgroup Analysis:
| hallmark | Increased clinical pregnancy rates | Statistical significance (p-value) |
|---|---|---|
| ≥3 graft failures | 66.7% | <0.001 |
| Age ≥ 35 years | 41.2% | 0.008 |
| BMI≥24 | 38.5% | 0.012 |
▶ Scenario 4: Positive surrogate mother with real-time contraction monitoring
Gold standard: four-dimensional ultrasound uterine peristaltic wave assessment
Pre-implantation contraction frequency > 4 per minute
Peristaltic direction toward the cervix (expulsive)
Intervention protocol:
Atosiban 6.75mg IV push + 37.5mg continuous IV pumping (1.5h)
IV.New international consensus: three types of prohibited scenarios and alternatives
1. Prohibited people
Frozen embryo transfer cycles without evidence of contractions
Patients with low responsive ovary syndrome (POR)
Abnormal coagulation function (INR>1.5)
2. Alternative treatment options
| Pathological type | Preferred option | second choice |
|---|---|---|
| poor endothelial tolerance | G-CSF instilled in the uterine cavity | Low-frequency endometrial stimulation |
| immune imbalance | Fat Emulsion Intravenous Infusion | lymphocyte immunotherapy |
| pre-thrombotic state | Low molecular heparin + aspirin | Antithrombin III concentrate |
V. Global Frontier Progress: New Hope Beyond Atosiban
Long-acting contraction antagonist Barusiban:
Half-life extended to 8.2 hours
32% increase in live birth rate in Phase II clinic (vs placebo)
Myometrium-targeted nanocarriers:
15-fold increase in local concentration of loaded drug
90% reduction in whole-body exposure
Artificial Intelligence Contraction Prediction Model:
Integration of EMG signaling + serum OXTR levels
24-hour advanced warning of high-risk with 92% accuracy
Case Insights:
Spanish surrogate mother Sofia (38 years old, stage III endometriosis) had 4 failed implantation attempts, and was able to achieve a successful twin pregnancy after being guided by the contraction activation test for the administration of atosiban.
KEYWORDS: Repeated implantation failure｜Atosiban｜Contractin receptor antagonist｜Endometriosis｜Fresh embryo transfer｜Uterine contraction monitoring｜Individualized fertility treatment
