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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Infertility

Intervention / Treatment
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* Procedure: cryopreservation of embryos at cleavage stage
* Procedure: cryopreservation of embryos at blastocyst stage


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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OHSS, Agonist trigger, freeze-all, blastocyst, cleavage