The effect of laser-assisted hatching on vitrified/warmed blastocysts: the ALADDIN randomized controlled trial.

ABSTRACT

OBJECTIVE: To evaluate whether laser-mediated assisted hatching (AH) performed on vitrified/warmed blastocysts before embryo transfer can improve live birth rate. DESIGN: The "pArtiaL zonA pelluciDa removal by assisteD hatchINg of blastocysts (ALADDIN)" is a 2-center comparative study with a parallel randomized controlled design. SETTING: University hospital. PATIENTS Participants were recruited between September 2018 and November 2021. They were aged 18-39 years, underwent nondonor in vitro fertilization cycles, and were scheduled for elective single embryo transfer with vitrified/warmed blastocysts. Those with uterine abnormalities, body mass index of >35 kg/m2, severe male factor infertility, or performing preimplantation genetic testing were excluded. INTERVENTION Assisted hatching was performed using a 1,480 nm diode laser, removing approximately one-third of the zona pellucida with continuous 0.2 ms pulses applied from the 1-5 o'clock positions. MAIN OUTCOME MEASURES: The primary outcome was the live birth rate. Secondary end points included clinical pregnancy, miscarriage, multiple pregnancies, preterm births, obstetric and neonatal complications, and congenital anomalies. RESULTS: Overall, 698 participants met the inclusion criteria and were randomized 352 patients were assigned to the AH arm and 346 to the control arm. Of the participants, 105 (29.8%) and 101 (29.2%), respectively, achieved a live birth after treatment. The relative risk of live birth in patients with vitrified/warmed blastocysts treated with AH was 1.02 (95% confidence interval, 0.86-1.19). Exploratory subgroup analyses for women's age, recruiting centers, indications for in vitro fertilization, method of insemination, blastocyst quality, and days of blastocyst development failed to highlight any clinical situation that could benefit from AH in thawed blastocysts. CONCLUSION: In patients undergoing frozen embryo transfer with vitrified/warmed blastocysts, laser AH does not improve the live birth rate. Further studies are required to rule out milder but potentially interesting benefits in specific subgroups of patients. TRIAL REGISTRATION ClinicalTrials.gov NCT03623659.