Efficacy of a Non-Invasive Endometrial Receptivity Prediction Model Based on Peripheral Blood miRNA Signatures During the Peri-Implantation Period in Improving IVF Outcomes in Patients With Unexplained RIF

Official title

Efficacy of a Non-Invasive Endometrial Receptivity Prediction Model Based on Peripheral Blood miRNA Signatures During the Peri-Implantation Period in Improving IVF Outcomes in Patients With Unexplained Recurrent Implantation Failure: A Prospective, Single-Blind, Two-Arm, Parallel Randomized Controlled Trial

Overview

The goal of this clinical trial aims to investigate whether a non-invasive implantation window prediction model, constructed based on characteristic changes in peripheral blood miRNAs during the peri-implantation period, can improve pregnancy outcomes in patients with unexplained recurrent implantation failure undergoing frozen embryo transfer. Researchers will compare the clinical pregnancy outcomes between individualized embryo transfer guided by implantation window results and conventional embryo transfer, to observe whether implantation window-guided individualized embryo transfer can improve the clinical efficacy for patients with recurrent implantation failure (RIF). Participants will complete implantation window testing as required by the study protocol, undergo randomization and blinding, and proceed with embryo transfer according to their assigned group.

Interventions

• Diagnostic test Non-invasive endometrial receptivity prediction model guides personalized embryo transfer for patients with recurrent implantation failure (RIF).
  Participants will undergo personalized embryo transfer based on the detection results of the window of implantation (WOI) via peripheral blood miRNA analysis. For subjects whose WOI results indicate that Day 5 (D5) is non-receptive, the embryo transfer timing will be appropriately advanced or delayed by 24 or 48 hours relative to the standard time. For subjects whose WOI results indicate that D5 is receptive, embryo transfer will be performed at the standard time (the fifth day after ovulation).

Primary outcome measures

• Implantation rate per embryo transferred, assessed by counting gestational sacs on ultrasound. [Time frame: From the day of embryo transfer until the completion of the first ultrasound assessment (typically at 35 days ± 7 days after transfer).]

Secondary outcome measures (3)

• Proportion of patients with abnormal endometrial receptivity, as assessed by dynamic changes in peripheral blood microRNA levels 5 days after ovulation. [Time frame: From the day of ovulation trigger until the completion of microRNA sample collection and analysis (within 5 to 7 days post-trigger).]
• Clinical pregnancy rate per embryo transfer, confirmed by ultrasound visualization of gestational sac and fetal heartbeat. [Time frame: From the day of embryo transfer until the confirmation of clinical pregnancy by ultrasound (assessed at approximately 35 days ± 7 days after embryo transfer).]
• Ongoing Pregnancy Rate per embryo transfer, confirmed by ultrasound after 12 weeks of gestation. [Time frame: From the day of embryo transfer until the confirmation of fetal viability at or after 12 weeks of gestation (typically up to 14 weeks of gestation).]

Eligibility criteria

Inclusion criteria

• Patients with unexplained recurrent implantation failure (RIF) meeting the diagnostic criteria for RIF: adult women under 40 years old who have failed to achieve clinical pregnancy after 3 embryo transfer cycles; or after transferring at least 3 high-quality embryos.

Definition of high-quality embryos: Day 3 embryos (with a cell count ≥7 and fragmentation rate <10%) and blastocysts (≥3BB).

• Female BMI: 18.5-25 kg/m².
• Endometrial thickness ≥7 mm during the embryo transfer cycle.
• Women planning to undergo frozen-thawed embryo transfer (FET) of blastocysts following in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI).
• Signed informed consent form.

Exclusion criteria

• Known causes of embryo implantation failure, such as infections, reproductive tract malformations, uterine cavity factors, adenomyosis or endometriosis, autoimmune system diseases (diagnosed by immunology department), hydrosalpinx, etc.
• Couples with chromosomal abnormalities (excluding chromosomal polymorphisms) or familial genetic disorders in either or both partners.
• Women with a history of recurrent miscarriage.
• Women with contraindications to pregnancy or assisted reproductive technology.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07363018 · 20251123

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗