CuMulativE Live bIrth Rate of Patients at High Risk of OHSS After Freeze-all Embryos at Cleavage or blAstocyst Stage (MELISSA)

CuMulativE Live bIrth Rate of Patients at High Risk of OHSS After Freeze-all Embryos at Cleavage or blAstocyst Stage in a Single Embryo Transfer Setting (MELISSA)

Ovarian stimulation for the induction of multifollicular growth by gonadotrophins represents an important part of In Vitro Fertilization (IVF). However, the use of these drugs can be associated with side effects, from which the most common is the Ovarian Hyperstimulation Syndrome (OHSS). Stimulation with gonadotrophins in a Gonadotropin-releasing hormone (GnRH) antagonist cycle rather than a GnRH agonist cycle reduces significantly the risk of OHSS. During stimulation, the best predictor of severe OHSS is the number of follicles >10mm on the day of triggering final oocyte maturation, with the threshold at ≥16 follicles. When this occurs, final oocyte maturation can be induced with a GnRH agonist, reducing further the risk the syndrome. To perform a fresh embryo transfer, 1500 IU human Chorionic Gonadotropin (hCG) can be administered on the day of oocyte retrieval for the luteal support. However, with this procedure there are still some cases of OHSS. To overcome this, it is suggested to combine GnRH agonist triggering with a freeze-all embryos strategy and perform embryo replacement in subsequent frozen-thawed embryo transfer (FET) cycles. Different cryopreservation strategies are been performed according to the procedure of each fertility center, such as cryopreservation at 2 pronuclear (2PN), cleavage or blastocyst stage. The aim of this study is to determine the optimal strategy for the freeze-all cycles and particularly the optimal day for freezing, thawing and transferring the embryos. The hypothesis is that there will increased cumulative live birth rates per started cycle in blastocyst compared to cleavage stage FET cycles.

Study Overview

• Status: Unknown
• Conditions: Infertility
• Intervention / Treatment: Procedure: cryopreservation of embryos at cleavage stage; Procedure: cryopreservation of embryos at blastocyst stage

• Study Type: Interventional
• Enrollment (Anticipated): 128
• Phase: Not Applicable

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Patients <40 years old
• Indication for In Vitro Fertilisation (IVF)/Intracytoplasmic sperm injection (ICSI)
• No more than 2 previous failed IVF/ICSI cycles
• Stimulation in GnRH antagonist cycle
• Presence of ≥16 follicles of >10mm on the day of triggering of final oocyte maturation
• GnRH agonist trigger (triptorelin 0.2mg)

Exclusion Criteria:

• Cycles with testicular sperm extraction
• Preimplantation genetic diagnosis
• Patients with uterine malformations
• Patients with infectious diseases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cleavage; Embryos cryopreserved with vitrification at the cleavage stage (day 3) of embryo development	Procedure: cryopreservation of embryos at cleavage stage; cryopreservation of embryos at cleavage stage (day 3) of embryo development
Active Comparator: Blastocyst; Embryos cryopreserved with vitrification at the blastocyst stage (day 5 or 6)	Procedure: cryopreservation of embryos at blastocyst stage; cryopreservation of embryos at blastocyst stage (day 5 or 6) of embryo development

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative live birth	Cumulative live birth rate per oocyte retrieval	within one year of randomisation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frozen thawed embryo transfer cycles needed to achieve live birth	Number of frozen thawed embryo transfer cycles needed to achieve live birth	within one year of randomisation

Collaborators and Investigators

• Sponsor: Université Libre de Bruxelles
• Collaborators: Aristotle University Of Thessaloniki

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2019
• Primary Completion (Anticipated): February 1, 2020
• Study Completion (Anticipated): February 1, 2021

Study Registration Dates

• First Submitted: December 7, 2018
• First Submitted That Met QC Criteria: January 23, 2019
• First Posted (Actual): January 25, 2019

Study Record Updates

• Last Update Posted (Actual): January 25, 2019
• Last Update Submitted That Met QC Criteria: January 23, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: blastocyst; OHSS; Agonist trigger; freeze-all; cleavage
• Additional Relevant MeSH Terms: Infertility
• Other Study ID Numbers: SRB_201807_150

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No