Clinical trial NCT03623659: pArtiaL zonA pelluciDa Removal by assisteD hatchINg of Blastocysts
Official title: Does Partial Zona Pellucida Removal From Vitrified-warmed Human Blastocysts Improve Delivery Rate in IVF? A Multicentric RCT on Laser Assisted Hatching
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Infertility
Keywords: Assisted hatching
Zona pellucida
Implantation failure
Blastocyst
Cryopreservation
Lead sponsor: IRCCS San Raffaele
Sponsor class: OTHER
First posted: 2018-08-09
Enrollment: 700
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of study is to assess the possible impact of assisted hatching on delivery rate after transfer of vitrified-warmed human blastocysts.

Detailed description: Zona pellucida (ZP) manipulation, termed "assisted hatching" (AH), has been introduced in order to favor embryo hatching and ultimately improve assisted reproductive technology success but with poor proofs of safety and biological plausibility.

Vitrifying and warming of blastocysts may impair the successful hatching process of the embryo out of its ZP and its following implantation into the uterus. Theoretically, AH may facilitate the hatching process and subsequently increase implantation rates.

In this prospective randomized controlled trial (RCT), the hypothesis is to test whether the application of a partial AH to vitrified/warmed blastocysts might affect patients' delivery rate.

Patients with vitrified blastocysts will be randomized at the time of blastocyst warming to a study group (with AH) or a control group (without AH). AH will be performed at the expanded blastocyst stage using a laser technique and a laser opening will be initiated at the 1 o'clock position. Consecutive laser shots will be applied to reach the 5 o'clock position of the blastocyst. The blastocysts will then be cultured at least 2 h and subsequently transferred into the patient's uterus.

Eligibility criteria: Inclusion Criteria:

* single embryo transfer of vitrified/warmed blastocyst (SET)
* first or second frozen IVF (with or without Intracytoplasmic Sperm Injection) cycle of blastocysts
* first or second oocyte retrieval

Exclusion Criteria:

* Preimplantation Genetic Testing (PGT) cycle
* BMI \> 35 kg/m2
* severe male factor
* abnormal uterine cavity

Primary outcomes:
measure: Delivery rate
timeFrame: 38 weeks after embryo transfer
Secondary outcomes:
measure: Implantation rate
timeFrame: 6-7 weeks after transfer
measure: Clinical Pregnancy rate
timeFrame: 4 weeks after transfer
measure: Biochemical pregnancy rate
timeFrame: 4 week after transfer
measure: Ongoing pregnancy rate
timeFrame: 20 weeks after transfer
measure: Multiple pregnancy rate
timeFrame: 4 week after transfer
measure: obstetrical and neonatal complication rate
timeFrame: after birth; 9-10 months after transfer
measure: congenital anomalies rate
timeFrame: after birth, 9-10 months after transfer
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
city: Milan
country: Italy
facility: IRCCS San Raffaele
Study officials:
affiliation: IRCCS San Raffaele
name: Alessandra Alteri, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Alteri A, Vigano P, Maizar AA, Jovine L, Giacomini E, Rubino P. Revisiting embryo assisted hatching approaches: a systematic review of the current protocols. J Assist Reprod Genet. 2018 Mar;35(3):367-391. doi: 10.1007/s10815-018-1118-4. Epub 2018 Jan 19.
citation: Alteri A, Guarneri C, Corti L, Restelli L, Reschini M, Giardina P, Papaleo E, Somigliana E, Vigano P, Paffoni A. ALADDIN study: does assisted hatching of vitrified/warmed blastocysts improve live birth rate? Protocol for a multicentric randomised controlled trial. BMJ Open. 2020 Jul 19;10(7):e031544. doi: 10.1136/bmjopen-2019-031544.