The Impact of Assisted Hatching on Pregnancy Outcomes After Vitrified-Warmed Embryo Transfer in Advanced-age Patients

Official title

The Impact of Laser-Assisted Hatching on Pregnancy Outcomes After Vitrified-Warmed Embryo Transfer in Advanced-age Patients: A Randomized Controlled Trial

Overview

The goal of this clinical trial is to evaluate the effect of laser assisted hatching (LAH) on pregnancy outcomes, with live birth rate as the primary outcome, in advanced age infertile women aged ≥35 years who are undergoing non-donor IVF/ICSI cycles and planning vitrified-warmed embryo transfer. It also aims to monitor the safety of LAH and assess various secondary pregnancy and neonatal outcomes. The main questions it aims to answer are: Does laser assisted hatching improve the live birth rate in advanced age women undergoing vitrified-warmed embryo transfer? Does laser assisted hatching affect secondary outcomes including implantation rate, biochemical pregnancy rate, clinical pregnancy rate, ectopic pregnancy rate, ongoing pregnancy rate, miscarriage rate, multiple pregnancy rate, preterm birth rate, and rates of obstetric and neonatal complications as well as congenital anomalies? Researchers will compare the Laser Assisted Hatching (LAH) Group to the Control Group (without LAH) to see if LAH can improve pregnancy outcomes in the study population. Participants will: * Be randomly assigned to either the LAH Group or the Control Group at a 1:1 ratio, stratified by age (\<40 years/≥40 years) and embryo stage (cleavage stage/blastocyst) using stratified block randomization. * Undergo the first or second frozen-thawed embryo transfer cycle, with transferred embryos meeting the quality criteria (cleavage-stage embryos: Grade I, Grade II, or CP and above; blastocysts: 4BC/CB and above). * Receive embryo vitrification and warming after routine fertilization and culture; LAH Group will undergo LAH (thinning zona pellucida for cleavage-stage embryos, removing 1/4-1/3 of zona pellucida circumference for blastocysts) in G2 medium after embryo thawing, while Control Group will not receive assisted hatching. * Have endometrial preparation by natural, ovulatory, or hormone replacement cycles as appropriate, and 1-2 viable embryos will be transferred under ultrasound guidance within 3 hours after thawing, followed by routine luteal support after transfer. * Complete follow-up at multiple time points: 12-15 days after embryo transfer (serum β-hCG test), 28 days after embryo transfer (transvaginal ultrasound), 12 weeks of gestation (ultrasound), 28 weeks of gestation (ultrasound), and 1 month after delivery (collection of delivery and neonatal information). * Provide demographic, clinical, and embryological baseline data, as well as various outcome data during the study period. * Undergo regular monitoring of vital signs, laboratory test results, and adverse events, with key prevention and control of specific risks related to LAH such as embryo damage and multiple pregnancy.

Interventions

• Procedure Laser assisted hatching
  Laser assisted hatching will be performed on vitrified-warmed embryos prior to embryo transfer according to standard laboratory procedures. For cleavage-stage embryos, the zona pellucida will be thinned; for blastocysts, 1/4-1/3 of the zona pellucida circumference will be removed, and the operation will be performed in G2 medium after embryo thawing.

Primary outcome measures

• Live birth rate [Time frame: From enrollment to the delivery (≥28 weeks of gestation)]

Secondary outcome measures (12)

• Ongoing pregnancy rate [Time frame: From enrollment to 12 weeks of gestation]
• Biochemical pregnancy rate [Time frame: From enrollment to 12 days (blastocyst), 14 days (D3), or 15 days (D2) after embryo transfer]
• Ectopic pregnancy rate [Time frame: From enrollment to 28 days after embryo transfer]
• Neonatal complication rate [Time frame: From enrollment to 1 month after delivery]
• Macrosomia rate [Time frame: From enrollment to the delivery]
• Low birth weight rate [Time frame: From enrollment to the delivery]
• Miscarriage rate [Time frame: From enrollment to 28 weeks of gestation]
• Clinical pregnancy rate [Time frame: From enrollment to 28 days after embryo transfer]
• Preterm birth rate [Time frame: From enrollment to the delivery]
• Implantation rate [Time frame: From enrollment to 28 days after embryo transfer]
• Congenital malformation rate [Time frame: From enrollment to 1 month after delivery]
• Multiple pregnancy rate [Time frame: From enrollment to 28 days after embryo transfer]

Eligibility criteria

Inclusion criteria

• 1: Female age ≥ 35 years
• 2: First or second vitrified-warmed embryo transfer cycle
• 3: Quality of embryos for transfer meeting the criteria: Grade I, II, CP or above (cleavage-stage embryos); Grade 4BC/CB or above (blastocysts)
• 4: Provide written informed consent

Exclusion criteria

• 1: Use of donor oocytes or sperm, or planned preimplantation genetic testing (PGT)
• 2: Severe immune or chromosomal abnormalities
• 3: Uterine cavity abnormalities (i.e., adenomyosis, submucous uterine fibroids, hydrosalpinx, uterine septum, and endometrial polyps)
• 4: Embryos with an abnormal zona pellucida
• 5: Complicated with severe underlying diseases (e.g., uncontrolled hypertension/diabetes mellitus, active malignant tumors)
• 6: A history of recurrent implantation failure (≥2 cycles) or recurrent miscarriage (≥2 episodes)

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: NCT07490561 · SH9H-2026-T42-2

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗