ICE: Implantation Enhancement by Elective Cryopreservation of All Viable Embryos

Sponsor

Universitair Ziekenhuis Brussel (Other)

Overall Status

Completed

CT.gov ID

NCT02148393

Collaborator

(none)

212

Enrollment

Location

Arms

Duration (Months)

6.2

Patients Per Site Per Month

Study Details

Study Description

Brief 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

Condition or Disease	Intervention/Treatment	Phase
Infertility OHSS	Procedure: Vitrification with subsequent-cycle embryo thawing/transfer Procedure: Intensified luteal phase support for fresh embryo transfer Drug: Pregnyl® Drug: Utrogestan® Drug: Progynova® Device: CryoBioSystem®	N/A

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

Study Type:

Interventional

Actual Enrollment :

212 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Elective Blastocyst Vitrification for Endometrial Receptivity Enhancement in High-responder Patients Undergoing in Vitro Fertilisation/Intracytoplasmatic Sperm Injection (IVF/ICSI)

Study Start Date :

May 1, 2014

Actual Primary Completion Date :

Feb 28, 2017

Actual Study Completion Date :

Feb 28, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Control 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.	Procedure: Intensified luteal phase support for fresh embryo transfer 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®). Drug: Pregnyl® 1500 IU Other Names: hCG Drug: Utrogestan® 200 mg tid Other Names: Vaginal progesterone Drug: Progynova® 2 mg bid Other Names: Estradiol valerate
Experimental: Intervention 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.	Procedure: Vitrification with subsequent-cycle embryo thawing/transfer 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. Device: CryoBioSystem® CryoBioSystem® in combination with dimethylsulfoxide, ethylene glycol and sucrose as cryoprotectants (Irvine ScientificR Freeze Kit®) closed in high security straws

Arm

Intervention/Treatment

Active Comparator: Control

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.

Procedure: Intensified luteal phase support for fresh embryo transfer

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®).

Drug: Pregnyl®

1500 IU

Other Names:

hCG

Drug: Utrogestan®

200 mg tid

Other Names:

Vaginal progesterone

Drug: Progynova®

2 mg bid

Other Names:

Estradiol valerate

Experimental: Intervention

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.

Procedure: Vitrification with subsequent-cycle embryo thawing/transfer

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.

Device: CryoBioSystem®

CryoBioSystem® in combination with dimethylsulfoxide, ethylene glycol and sucrose as cryoprotectants (Irvine ScientificR Freeze Kit®) closed in high security straws

Outcome Measures

Primary Outcome Measures

Clinical pregnancy rates [7 weeks]
Pregnancy visible under transvaginal pelvic ultrasound

Secondary Outcome Measures

Ovarian hyperstimulation syndrome incidence [8 weeks]
Observation of early-onset ovarian hyperstimulation syndrome

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 40 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Universitair Ziekenhuis Brussel	Brussels	Lisboa	Belgium	1600-548

Sponsors and Collaborators

Universitair Ziekenhuis Brussel

Investigators

Principal Investigator: Samuel Santos-Ribeiro, MD, Universitair Ziekenhuis Brussel
Principal Investigator: Christophe Blockeel, PhD, Universitair Ziekenhuis Brussel