Implantation Enhancement by Elective Cryopreservation of All Viable Embryos (ICE)

Universitair Ziekenhuis Brussel

Status: Completed

Conditions: Infertility; OHSS

Treatments: Device: CryoBioSystem®; Procedure: Vitrification with subsequent-cycle embryo thawing/transfer; Drug: Progynova®; Drug: Utrogestan®; Drug: Pregnyl®; Procedure: Intensified luteal phase support for fresh embryo transfer

Study type: Interventional

Funder types: Other

Identifiers

NCT02148393

2014-001480-12 (EudraCT Number)

2014-128

Details and patient eligibility

About

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

Full 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.

Enrollment: 212 patients

Sex: Female

Ages: 18 to 40 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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212 participants in 2 patient groups

Control

Active Comparator group

Description:

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.

Treatment:

Drug: Utrogestan®

Drug: Pregnyl®

Procedure: Intensified luteal phase support for fresh embryo transfer

Drug: Progynova®

Intervention

Experimental group

Description:

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.

Treatment:

Procedure: Vitrification with subsequent-cycle embryo thawing/transfer

Device: CryoBioSystem®