InfertilityNCT03623659
pArtiaL zonA pelluciDa Removal by assisteD hatchINg of Blastocysts
A study testing Laser assisted hatching in people with Infertility, run by IRCCS San Raffaele at 2 sites in Italy.
Trial summary
The aim of study is to assess the possible impact of assisted hatching on delivery rate after transfer of vitrified-warmed human blastocysts. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women only
- Conditions the study is for
- Infertility
- What is being tested?
- Laser assisted hatching
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 700 participants
- Where
- 2 sitesItaly
- Study dates
- 5 Sep 2018to 20 Jan 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- Preimplantation Genetic Testing (PGT) cycle
- BMI > 35 kg/m2
- severe male factor
- abnormal uterine cavity
Trial locations and contacts
2 sites in 1 country.
Italy2 sites
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Milan, 20122
IRCCS San Raffaele
Milan, 20132
About this study
Official title: Does Partial Zona Pellucida Removal From Vitrified-warmed Human Blastocysts Improve Delivery Rate in IVF? A Multicentric RCT on Laser Assisted Hatching
The aim of study is to assess the possible impact of assisted hatching on delivery rate after transfer of vitrified-warmed human blastocysts.
Read the 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.
- Conditions
- Infertility
- Being tested
- Laser assisted hatching
- Keywords
- Assisted hatching, Zona pellucida, Implantation failure, Blastocyst, Cryopreservation
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laser assisted hatchingProcedure or surgery
After warming, blastocysts are subjected to laser assisted hatching (LAH) following the standard procedure.The LAH procedure lasts one minute per blastocyst.
| Study group | Role | What they receive |
|---|---|---|
| AH group | Active comparator | Subjects whose vitrified/warmed blastocysts will be subjected to the treatment of laser assisted hatching Receives: Procedure: Laser assisted hatching |
| Control group | No intervention | Subjects whose vitrified/warmed blastocysts will be subjected to the same procedures except for the treatment of laser assisted hatching |
What is being measured
The primary outcome is the main question the study is designed to answer.
Delivery rate
Number of deliveries, that result in a live birth, per transferred blastocyst
Measured: 38 weeks after embryo transfer
Secondary outcomes (7)
Implantation rate
the number of gestational sacs observed at echographic screening at 6 weeks of pregnancy divided by the number of transferred embryos
Measured: 6-7 weeks after transfer
Clinical Pregnancy rate
the ultrasonographic demonstration of an intrauterine gestational sac divided by the number of included women
Measured: 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
Measured: 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
Measured: 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
Measured: 4 week after transfer
obstetrical and neonatal complication rate
condition that adversely affects women and their foetal health during delivery
Measured: 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
Measured: after birth, 9-10 months after transfer
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2018
- Study start5 Sep 2018
- Primary completion20 Jan 2023
- Study completion20 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for InfertilityStudies of the same condition, open and under way.
- More trials run by IRCCS San RaffaeleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 700 participants (actual)
Sponsor and investigators
- Lead sponsor
- IRCCS San Raffaele
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Alessandra Alteri, IRCCS San Raffaele
- Investigators
- Alessandra Alteri, PhD, Principal investigator, IRCCS San Raffaele
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03623659
- Sponsor's protocol ID
- ALADDIN
- Status last verified
- Jan 2023
- First submitted
- 3 Aug 2018
- Last updated
- 23 Jan 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 29350315Alteri A, Reschini M, Guarneri C, Bandini V, Bertapelle G, Pinna M, Rabellotti E, Ferrari S, Papaleo E, Paffoni A, Vigano P, Somigliana E. The effect of laser-assisted hatching on vitrified/warmed blastocysts: the ALADDIN randomized controlled trial. Fertil Steril. 2024 Jul;122(1):106-113. doi: 10.1016/j.fertnstert.2024.02.010. Epub 2024 Feb 9.
PubMed 38342371Alteri 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.
PubMed 32690492
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Does Partial Zona Pellucida Removal From Vitrified-warmed Human Blastocysts Improve Delivery Rate in IVF? A Multicentric RCT on Laser Assisted Hatching
- ClinicalTrials.gov ID
- NCT03623659
- Acronym / sponsor ID
- ALADDIN
- Conditions
- Infertility
- Keywords
- Assisted hatching, Zona pellucida, Implantation failure, Blastocyst, Cryopreservation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 700 participants (actual)
- Lead sponsor
- IRCCS San RaffaeleUniversity, hospital or other
- Study start
- 5 Sep 2018 (actual)
- Primary completion
- 20 Jan 2023 (actual)
- Study completion
- 20 Jan 2023 (actual)
- First posted
- 9 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AH group | Active comparator | Procedure: Laser assisted hatchingSubjects whose vitrified/warmed blastocysts will be subjected to the treatment of laser assisted hatching |
| Control group | No intervention | –Subjects whose vitrified/warmed blastocysts will be subjected to the same procedures except for the treatment of laser assisted hatching |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (4 listed)
- Preimplantation Genetic Testing (PGT) cycle
- BMI > 35 kg/m2
- severe male factor
- abnormal uterine cavity
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Laser assisted hatchingAfter warming, blastocysts are subjected to laser assisted hatching (LAH) following the standard procedure.The LAH procedure lasts one minute per blastocyst. | Procedure or surgery | AH group |
Primary outcome
Delivery rate
Time frame: 38 weeks after embryo transfer
Number of deliveries, that result in a live birth, per transferred blastocyst
7 secondary outcomes
Implantation rate
Time frame: 6-7 weeks after transfer
Clinical Pregnancy rate
Time frame: 4 weeks after transfer
Biochemical pregnancy rate
Time frame: 4 week after transfer
Ongoing pregnancy rate
Time frame: 20 weeks after transfer
Multiple pregnancy rate
Time frame: 4 week after transfer
obstetrical and neonatal complication rate
Time frame: after birth; 9-10 months after transfer
congenital anomalies rate
Time frame: after birth, 9-10 months after transfer
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2023.
- Background: PubMed 29350315Alteri 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.
- Derived from this study: PubMed 38342371Alteri A, Reschini M, Guarneri C, Bandini V, Bertapelle G, Pinna M, Rabellotti E, Ferrari S, Papaleo E, Paffoni A, Vigano P, Somigliana E. The effect of laser-assisted hatching on vitrified/warmed blastocysts: the ALADDIN randomized controlled trial. Fertil Steril. 2024 Jul;122(1):106-113. doi: 10.1016/j.fertnstert.2024.02.010. Epub 2024 Feb 9.
- Derived from this study: PubMed 32690492Alteri 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alessandra Alteri, PhD principal investigator
IRCCS San Raffaele
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Laser assisted hatching in people with Infertility, run by IRCCS San Raffaele at 2 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Delivery rate (time frame: 38 weeks after embryo transfer). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03623659, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2023.