pArtiaL zonA pelluciDa Removal by assisteD hatchINg of Blastocysts

Study Overview
=================
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.

Official Title
-----------------
Does Partial Zona Pellucida Removal From Vitrified-warmed Human Blastocysts Improve Delivery Rate in IVF? A Multicentric RCT on Laser Assisted Hatching

Conditions
-----------------
Infertility

Intervention / Treatment
-----------------
* Procedure: Laser assisted hatching


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: AH group<br>Subjects whose vitrified/warmed blastocysts will be subjected to the treatment of laser assisted hatching | Procedure: Laser assisted hatching<br>* After warming, blastocysts are subjected to laser assisted hatching (LAH) following the standard procedure.The LAH procedure lasts one minute per blastocyst.<br>|
| No Intervention: Control group<br>Subjects whose vitrified/warmed blastocysts will be subjected to the same procedures except for the treatment of laser assisted hatching | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delivery rate | Number of deliveries, that result in a live birth, per transferred blastocyst | 38 weeks after embryo transfer | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Implantation rate | the number of gestational sacs observed at echographic screening at 6 weeks of pregnancy divided by the number of transferred embryos | 6-7 weeks after transfer | 
| Clinical Pregnancy rate | the ultrasonographic demonstration of an intrauterine gestational sac divided by the number of included women | 4 weeks after transfer | 
| Biochemical pregnancy rate | Pregnancies failing to progress to the point of ultrasound confirmation divided by the number of women with a positive pregnancy test on blood | 4 week after transfer | 
| Ongoing pregnancy rate | the ultrasonographic demonstration of an intrauterine gestational sac with fetal hearth divided by the number of included women | 20 weeks after transfer | 
| Multiple pregnancy rate | a pregnancy in which more than one fetus develops in the uterus at the same time divided by the number of women with a clinical pregnancy | 4 week after transfer | 
| obstetrical and neonatal complication rate | condition that adversely affects women and their foetal health during delivery | after birth; 9-10 months after transfer | 
| congenital anomalies rate | birth defects, congenital disorders, congenital malformations, or congenital abnormalities, are conditions of prenatal origin that are present at birth, potentially impacting an infant's health, development and/or survival divided by the number of livebirths | after birth, 9-10 months after transfer | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Assisted hatching, Zona pellucida, Implantation failure, Blastocyst, Cryopreservation