Infertility, OHSS
Conditions
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.
Interventions
DRUGUtrogestan®
200 mg tid
DRUGProgynova®
2 mg bid
PROCEDUREVitrification 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.
PROCEDUREIntensified 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®).
DRUGPregnyl®
1500 IU
DEVICECryoBioSystem®
CryoBioSystem® in combination with dimethylsulfoxide, ethylene glycol and sucrose as cryoprotectants (Irvine ScientificR Freeze Kit®) closed in high security straws
Sponsors
Universitair Ziekenhuis Brussel
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical pregnancy rates | 7 weeks | Pregnancy visible under transvaginal pelvic ultrasound |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ovarian hyperstimulation syndrome incidence | 8 weeks | Observation of early-onset ovarian hyperstimulation syndrome |
Countries
Belgium
Outcome results
None listed