InfertilityICENCT02148393
Implantation Enhancement by Elective Cryopreservation of All Viable Embryos
A study testing Vitrification with subsequent-cycle embryo thawing/transfer, Intensified luteal phase support for fresh embryo transfer and Pregnyl® in people with Infertility and OHSS, run by Universitair Ziekenhuis Brussel at 1 site in Belgium.
Trial summary
A randomised controlled open-label clinical trial to compare the clinical pregnancy rates between fresh embryo transfer and elective all-embryo vitrification with thawing and transfer in a subsequent cycle in high-responders Read more about this study
- Who is it for?
- Ages 18 to 40 years, women only
- Conditions the study is for
- Infertility, OHSS
- What is being tested?
- Vitrification with subsequent-cycle embryo thawing/transfer, Intensified luteal phase support for fresh embryo transfer and Pregnyl®
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 212 participants
- Where
- 1 siteBelgium
- Study dates
- May 2014to 28 Feb 2017
- 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
- First or second IVF/ICSI cycle
- High response to ovarian stimulation (defined as presence of ≥18 follicles of ≥11 mm on the day of GnRH triggering)
- GnRH antagonist down-regulation
- Signed informed consent
- Patients can be included only once in the trial
- Planned replacement of 1 or 2 blastocysts
Who cannot join
- Other known reasons for impaired implantation (i.e. hydrosalpinx, fibroid distorting the endometrial cavity, Asherman's syndrome, thrombophilia or endometrial tuberculosis)
- Oocyte/embryos donation acceptors
- Embryos planned to undergo preimplantation genetic diagnosis/screening
- Body mass index ≥35 or ≤18
- Women who have previously enrolled in the trial
- Those unable to comprehend the investigational nature of the proposed study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Elective Blastocyst Vitrification for Endometrial Receptivity Enhancement in High-responder Patients Undergoing in Vitro Fertilisation/Intracytoplasmatic Sperm Injection (IVF/ICSI)
A randomised controlled open-label clinical trial to compare the clinical pregnancy rates between fresh embryo transfer and elective all-embryo vitrification with thawing and transfer in a subsequent cycle in high-responders
Read the detailed description
Two-arm randomised, single-centre, controlled open-label trial. Summarily, women undergoing exogenous gonadotropin ovarian stimulation for ART in a gonadotropin-releasing hormone (GnRH) antagonist down-regulated cycle and at high risk for ovarian hyperstimulation syndrome (OHSS) will be included in either the control ("fresh embryo transfer") or intervention ("subsequent vitrified-warmed embryo transfer") groups. Women in the control group will undergo GnRH agonist triggering followed by intensified luteal phase support while the intervention group will electively vitrify all viable embryos after GnRH triggering and perform the embryo transfer (ET) in a subsequent unstimulated cycle.
Ovarian stimulation, ultrasound and hormonal monitoring, ovulation induction, oocyte retrieval, embryology procedure, IVF and luteal support will be according to how they are normally performed in our centre.
All women included will undergo artificial ovarian stimulation with GnRH antagonist down-regulation with daily injections of either ganirelix (Orgalutran®) or cetrorelix (Cetrotide®). Treating physicians will opt on which exogenous gonadotropins should be used according to the patient's profile and preference and can include either recombinant follicle stimulating hormone (FSH) or highly purified urinary human menopausal gonadotropin (HP-HMG). Ovarian stimulation will commence after it is confirmed that the patient is not pregnant and has basal levels of oestradiol, progesterone, FSH and luteinising hormone (LH). The stimulation will be monitored simultaneously by pelvic ultrasound and hormonal analyses (oestradiol, progesterone), starting on day 7 of stimulation and then every 1 to 3 days, according to the individual endocrine profile and follicular development.
Final oocyte maturation will be triggered with 0.2 mg triptorelin (Decapeptyl®, Gonapeptyl®) as soon as 3 follicles of ≥17 mm are observed. A GnRH agonist will be the preferred triggering agent for both groups to reduce the risk of severe OHSS associated with human chorionic gonadotropin (hCG) triggering in high-responders. Oocyte retrieval will be performed 36 hours after hCG administration under either local anaesthesia with analgesic premedication or general anaesthesia, according to patient preference.
IVF/ICSI will be performed, using the specimen of sperm made available by the male progenitor on the day of oocyte retrieval.
The choice to transfer one or two embryos will be decided by the clinician at consultation mainly depending on the patient's age and the number of embryos replaced in the previous treatment cycles, according to Belgian law.
- Conditions
- Infertility, OHSS
- Being tested
- Vitrification with subsequent-cycle embryo thawing/transfer, Intensified luteal phase support for fresh embryo transfer, Pregnyl®, Utrogestan®, Progynova®
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitrification with subsequent-cycle embryo thawing/transferProcedure or surgery
The vitrification process will be performed under the same conditions of all other vitrification procedures usually performed in our centre. In summary, vitrification will be accomplished using closed high security straws (CryoBioSystem®) in combination with dimethylsulfoxide, ethylene glycol and sucrose as cryoprotectants (Irvine ScientificR Freeze Kit®).
In the meantime, patients will wait for a subsequent cycle before starting exogenous hormone therapy for endometrial preparation.
Intensified luteal phase support for fresh embryo transferProcedure or surgery
A single administration of 1500 IU of exogenous hCG (Pregnyl®) 1 hour after oocyte retrieval followed by daily vaginally-administered progesterone 200 mg tid (Utrogestan®) and oestradiol valerate 2 mg bid (Progynova®).
Pregnyl®Drug
Also called hCG
1500 IU
Utrogestan®Drug
Also called Vaginal progesterone
200 mg tid
Progynova®Drug
Also called Estradiol valerate
2 mg bid
CryoBioSystem®Device
CryoBioSystem® in combination with dimethylsulfoxide, ethylene glycol and sucrose as cryoprotectants (Irvine ScientificR Freeze Kit®) closed in high security straws
| Study group | Role | What they receive |
|---|---|---|
| Control | Active comparator | In the control group, following oocyte retrieval, intensified luteal phase support for fresh embryo transfer (with Pregnyl®, Utrogestan® and Progynova®) will be performed. Fresh ET in the uterine cavity will be performed on the 5th day of embryo development at blastocyst stage under ultrasound guidance whenever possible. Receives: Procedure: Intensified luteal phase support for fresh embryo transfer; Drug: Pregnyl®; Drug: Utrogestan®; Drug: Progynova® |
| Intervention | Experimental | Elective vitrification with subsequent-cycle embryo thawing/transfer (CryoBioSystem®) will be performed. Hence, no luteal phase support will be provided immediately after oocyte retrieval. Instead, patients will wait for a subsequent cycle before starting exogenous hormone therapy for endometrial preparation.
On the day of embryo transfer, blastocyst(s) will be warmed one by one until one or two blastocysts are suitable for transfer. ET to the uterine cavity will be performed under ultrasound guidance whenever possible. Receives: Procedure: Vitrification with subsequent-cycle embryo thawing/transfer; Device: CryoBioSystem® |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical pregnancy rates
Pregnancy visible under transvaginal pelvic ultrasound
Measured: 7 weeks
Secondary outcomes (1)
Ovarian hyperstimulation syndrome incidence
Observation of early-onset ovarian hyperstimulation syndrome
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2014 (estimated)
- Study startMay 2014
- Primary completion28 Feb 2017
- Study completion28 Feb 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for InfertilityStudies of the same condition, open and under way.
- More trials run by Universitair Ziekenhuis BrusselThe 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
- None (open label)
- Enrolment
- 212 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitair Ziekenhuis Brussel
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Samuel Santos-Ribeiro, Universitair Ziekenhuis Brussel
- Investigators
- Samuel Santos-Ribeiro, MD, Principal investigator, Universitair Ziekenhuis BrusselChristophe Blockeel, PhD, Principal investigator, Universitair Ziekenhuis Brussel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02148393
- Sponsor's protocol ID
- 2014-128
- Other IDs
- 2014-001480-12, 2014
- Acronym
- ICE
- Status last verified
- Mar 2018
- First submitted
- 16 May 2014
- Last updated
- 9 Mar 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Zaat T, Zagers M, Mol F, Goddijn M, van Wely M, Mastenbroek S. Fresh versus frozen embryo transfers in assisted reproduction. Cochrane Database Syst Rev. 2021 Feb 4;2(2):CD011184. doi: 10.1002/14651858.CD011184.pub3.
PubMed 33539543Santos-Ribeiro S, Mackens S, Popovic-Todorovic B, Racca A, Polyzos NP, Van Landuyt L, Drakopoulos P, de Vos M, Tournaye H, Blockeel C. The freeze-all strategy versus agonist triggering with low-dose hCG for luteal phase support in IVF/ICSI for high responders: a randomized controlled trial. Hum Reprod. 2020 Dec 1;35(12):2808-2818. doi: 10.1093/humrep/deaa226.
PubMed 32964939
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Elective Blastocyst Vitrification for Endometrial Receptivity Enhancement in High-responder Patients Undergoing in Vitro Fertilisation/Intracytoplasmatic Sperm Injection (IVF/ICSI)
- ClinicalTrials.gov ID
- NCT02148393
- Acronym / sponsor ID
- ICE / 2014-128
- Conditions
- Infertility, OHSS
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 212 participants (actual)
- Lead sponsor
- Universitair Ziekenhuis BrusselUniversity, hospital or other
- Study start
- May 2014
- Primary completion
- 28 Feb 2017 (actual)
- Study completion
- 28 Feb 2017 (actual)
- First posted
- 28 May 2014 (estimated)
- 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.
A randomised controlled open-label clinical trial to compare the clinical pregnancy rates between fresh embryo transfer and elective all-embryo vitrification with thawing and transfer in a subsequent cycle in high-responders
Detailed description
Two-arm randomised, single-centre, controlled open-label trial. Summarily, women undergoing exogenous gonadotropin ovarian stimulation for ART in a gonadotropin-releasing hormone (GnRH) antagonist down-regulated cycle and at high risk for ovarian hyperstimulation syndrome (OHSS) will be included in either the control ("fresh embryo transfer") or intervention ("subsequent vitrified-warmed embryo transfer") groups. Women in the control group will undergo GnRH agonist triggering followed by intensified luteal phase support while the intervention group will electively vitrify all viable embryos after GnRH triggering and perform the embryo transfer (ET) in a subsequent unstimulated cycle.
Ovarian stimulation, ultrasound and hormonal monitoring, ovulation induction, oocyte retrieval, embryology procedure, IVF and luteal support will be according to how they are normally performed in our centre.
All women included will undergo artificial ovarian stimulation with GnRH antagonist down-regulation with daily injections of either ganirelix (Orgalutran®) or cetrorelix (Cetrotide®). Treating physicians will opt on which exogenous gonadotropins should be used according to the patient's profile and preference and can include either recombinant follicle stimulating hormone (FSH) or highly purified urinary human menopausal gonadotropin (HP-HMG). Ovarian stimulation will commence after it is confirmed that the patient is not pregnant and has basal levels of oestradiol, progesterone, FSH and luteinising hormone (LH). The stimulation will be monitored simultaneously by pelvic ultrasound and hormonal analyses (oestradiol, progesterone), starting on day 7 of stimulation and then every 1 to 3 days, according to the individual endocrine profile and follicular development.
Final oocyte maturation will be triggered with 0.2 mg triptorelin (Decapeptyl®, Gonapeptyl®) as soon as 3 follicles of ≥17 mm are observed. A GnRH agonist will be the preferred triggering agent for both groups to reduce the risk of severe OHSS associated with human chorionic gonadotropin (hCG) triggering in high-responders. Oocyte retrieval will be performed 36 hours after hCG administration under either local anaesthesia with analgesic premedication or general anaesthesia, according to patient preference.
IVF/ICSI will be performed, using the specimen of sperm made available by the male progenitor on the day of oocyte retrieval.
The choice to transfer one or two embryos will be decided by the clinician at consultation mainly depending on the patient's age and the number of embryos replaced in the previous treatment cycles, according to Belgian law.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control | Active comparator | Procedure: Intensified luteal phase support for fresh embryo transfer, Drug: Pregnyl®, Drug: Utrogestan®, Drug: Progynova®In the control group, following oocyte retrieval, intensified luteal phase support for fresh embryo transfer (with Pregnyl®, Utrogestan® and Progynova®) will be performed. Fresh ET in the uterine cavity will be performed on the 5th day of embryo development at blastocyst stage under ultrasound guidance whenever possible. |
| Intervention | Experimental | Procedure: Vitrification with subsequent-cycle embryo thawing/transfer, Device: CryoBioSystem®Elective vitrification with subsequent-cycle embryo thawing/transfer (CryoBioSystem®) will be performed. Hence, no luteal phase support will be provided immediately after oocyte retrieval. Instead, patients will wait for a subsequent cycle before starting exogenous hormone therapy for endometrial preparation. On the day of embryo transfer, blastocyst(s) will be warmed one by one until one or two blastocysts are suitable for transfer. ET to the uterine cavity will be performed under ultrasound guidance whenever possible. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- First or second IVF/ICSI cycle
- High response to ovarian stimulation (defined as presence of ≥18 follicles of ≥11 mm on the day of GnRH triggering)
- GnRH antagonist down-regulation
- Signed informed consent
- Patients can be included only once in the trial
Key exclusion criteria (6 listed)
- Other known reasons for impaired implantation (i.e. hydrosalpinx, fibroid distorting the endometrial cavity, Asherman's syndrome, thrombophilia or endometrial tuberculosis)
- Oocyte/embryos donation acceptors
- Embryos planned to undergo preimplantation genetic diagnosis/screening
- Body mass index ≥35 or ≤18
- Women who have previously enrolled in the trial
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 |
|---|---|---|
| Vitrification with subsequent-cycle embryo thawing/transferThe vitrification process will be performed under the same conditions of all other vitrification procedures usually performed in our centre. In summary, vitrification will be accomplished using closed high security straws (CryoBioSystem®) in combination with dimethylsulfoxide, ethylene glycol and sucrose as cryoprotectants (Irvine ScientificR Freeze Kit®). In the meantime, patients will wait for a subsequent cycle before starting exogenous hormone therapy for endometrial preparation. | Procedure or surgery | Intervention |
| Intensified luteal phase support for fresh embryo transferA single administration of 1500 IU of exogenous hCG (Pregnyl®) 1 hour after oocyte retrieval followed by daily vaginally-administered progesterone 200 mg tid (Utrogestan®) and oestradiol valerate 2 mg bid (Progynova®). | Procedure or surgery | Control |
| Pregnyl®Also: hCG1500 IU | Drug | Control |
| Utrogestan®Also: Vaginal progesterone200 mg tid | Drug | Control |
| Progynova®Also: Estradiol valerate2 mg bid | Drug | Control |
| CryoBioSystem®CryoBioSystem® in combination with dimethylsulfoxide, ethylene glycol and sucrose as cryoprotectants (Irvine ScientificR Freeze Kit®) closed in high security straws | Device | Intervention |
Primary outcome
Clinical pregnancy rates
Time frame: 7 weeks
Pregnancy visible under transvaginal pelvic ultrasound
1 secondary outcome
Ovarian hyperstimulation syndrome incidence
Time frame: 8 weeks
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 9 Mar 2018.
- Derived from this study: PubMed 33539543Zaat T, Zagers M, Mol F, Goddijn M, van Wely M, Mastenbroek S. Fresh versus frozen embryo transfers in assisted reproduction. Cochrane Database Syst Rev. 2021 Feb 4;2(2):CD011184. doi: 10.1002/14651858.CD011184.pub3.
- Derived from this study: PubMed 32964939Santos-Ribeiro S, Mackens S, Popovic-Todorovic B, Racca A, Polyzos NP, Van Landuyt L, Drakopoulos P, de Vos M, Tournaye H, Blockeel C. The freeze-all strategy versus agonist triggering with low-dose hCG for luteal phase support in IVF/ICSI for high responders: a randomized controlled trial. Hum Reprod. 2020 Dec 1;35(12):2808-2818. doi: 10.1093/humrep/deaa226.
- Individual participant dataSharing planned: Undecided
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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.
Samuel Santos-Ribeiro, MD principal investigator
Universitair Ziekenhuis Brussel
Christophe Blockeel, PhD principal investigator
Universitair Ziekenhuis Brussel
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Vitrification with subsequent-cycle embryo thawing/transfer, Intensified luteal phase support for fresh embryo transfer and Pregnyl® in people with Infertility and OHSS, run by Universitair Ziekenhuis Brussel at 1 site in Belgium.
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 6 inclusion and 6 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 9 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. 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?
Clinical pregnancy rates (time frame: 7 weeks). 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 NCT02148393, which also lists 2 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 9 Mar 2018.