Implantation Enhancement by Elective Cryopreservation of All Viable Embryos

Infertility Clinical Trial

— ICE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02148393
• Other study ID #: 2014-128
• Secondary ID: 2014-001480-12
• Status: Completed
• Phase: N/A
• First received: May 16, 2014
• Last updated: March 8, 2018
• Start date: May 2014
• Est. completion date: February 28, 2017

Study information

• Verified date: March 2018
• Source: Universitair Ziekenhuis Brussel
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 212
• Est. completion date: February 28, 2017
• Est. primary completion date: February 28, 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Infertility
• OHSS

Intervention

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.
• 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
• Utrogestan®
200 mg tid
• Progynova®
2 mg bid

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

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Brussel	Brussels	Lisboa

Sponsors (1)

Lead Sponsor	Collaborator
Universitair Ziekenhuis Brussel

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical pregnancy rates	Pregnancy visible under transvaginal pelvic ultrasound	7 weeks
Secondary	Ovarian hyperstimulation syndrome incidence	Observation of early-onset ovarian hyperstimulation syndrome	8 weeks

External Links

•   Centre for Reproductive Medicine