Clinical trial NCT02148393: Implantation Enhancement by Elective Cryopreservation of All Viable Embryos
Official title: Elective Blastocyst Vitrification for Endometrial Receptivity Enhancement in High-responder Patients Undergoing in Vitro Fertilisation/Intracytoplasmatic Sperm Injection (IVF/ICSI)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Infertility
OHSS
Lead sponsor: Universitair Ziekenhuis Brussel
Sponsor class: OTHER
First posted: 2014-05-28
Enrollment: 212
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Clinical pregnancy rates
timeFrame: 7 weeks
Secondary outcomes:
measure: Ovarian hyperstimulation syndrome incidence
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Universitair Ziekenhuis Brussel
state: Lisboa
Study officials:
affiliation: Universitair Ziekenhuis Brussel
name: Samuel Santos-Ribeiro, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitair Ziekenhuis Brussel
name: Christophe Blockeel, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Santos-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.