Impact of Blastocyst Morphological Development and Blastocoele Re-expansion on Pregnancy Outcome After Using REKOVELLE®

The Impact of Frozen - Thawed Blastocyst Morphological Development and Blastocoele Re-expansion on Clinical Pregnancy Outcome After One Controlled Ovarian Stimulation Cycle Using REKOVELLE®

The purpose of this observational study is to examine the development and appearance of embryos before and after freezing following a single controlled ovarian stimulation cycle using REKOVELLE® (follitropin delta) as the recombinant follicular stimulating hormone (rFSH) for controlled ovarian stimulation. The primary objective of the study is to examine how specific factors of embryo development or appearance are related to the chance of becoming pregnant.

The ovarian stimulation protocol with REKOVELLE®, a new rFSH prescribed for ovarian stimulation, is individualised with a dosing regimen that is based on two parameters: the body weight and the level of a hormone, the anti-Müllerian hormone, (AMH), a parameter used to predict how the ovaries will respond to the ovarian stimulation.

Study Overview

• Status: Terminated
• Conditions: Controlled Ovarian Stimulation
• Intervention / Treatment: Drug: Follitropin Delta

• Study Type: Observational
• Enrollment (Actual): 362

Contacts and Locations

Study Locations

• Denmark
  • Højbjerg, Denmark
    • Ciconia, VivaNeo (there may be other sites in this country)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The study aims to enroll between 1200 and 1500 cycles which is estimated to be sufficient for observing 616 single frozen-thawed blastocyst transfers. Patients can contribute data from one or more frozen-thawed blastocyst transfers. Further, the patient cohort will be recruited among the patient population of 8-10 public and private in vitro fertilization (IVF) clinics in Denmark.

Description

Inclusion Criteria:

• Patients undergoing elective single embryo transfer (e-SET) in a frozen embryo replacement (FER) treatment where the frozen blastocyst was obtained from an IVF or intracytoplasmic sperm injection (ICSI) cycle following controlled ovarian stimulation with REKOVELLE® .
• Women are prescribed REKOVELLE® for their IVF or ICSI according to the approved label.
• Morphological measurements and clinical outcomes are available for the fresh embryos obtained from the IVF or ICSI cycle.
• Willing and able to understand Danish or English patient information.
• Willingness and ability to provide written informed consent.

Exclusion Criteria:

• Patients with any contraindication for treatment with REKOVELLE® for controlled ovarian stimulation.
• Patients with contraindication for undergoing assisted reproductive technologies (ART) such as an IVF or ICSI cycle.
• Oocyte donors.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

REKOVELLE®; Follitropin Delta

Drug: Follitropin Delta; The Intervention (solution for injection) is delivered with an injection pen. For women with AMH <15 pmol/L the daily dose is 12 micrograms, irrespective of body weight. For women with AMH ≥15 pmol/L the daily dose decreases from 0.19 to 0.10 micrograms/kg by increasing AMH concentration. The maximum daily dose for the first treatment cycle is 12 micrograms. For subsequent treatment cycles, the daily dose of REKOVELLE® should be maintained or modified according to the patient's ovarian response in the previous cycle. Based on the ovarian hypo/hyper-response in the previous cycle, the daily dose in the subsequent cycle should be increased (by 25% or 50%) or decreased (by 20% or 33%). The maximum daily dose is 24 micrograms.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical pregnancy rate	Clinical pregnancy is defined as at least one intrauterine gestational sac with fetal heart beat at week 7, from frozen thawed blastocysts. The correlation between morphological parameters (blastocyst score, timelapse score, blastocoele re-expansion) and clinical pregnancy rate will be assessed.	7 weeks after each embryo transfer

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of days of treatment with REKOVELLE®		From day 1 up to day 20 of REKOVELLE® stimulation
Cumulative clinical pregnancy rate	The cumulative clinical pregnancy rate will be calculated based on all participants included in the study and all clinical pregnancies recorded from fresh and frozen-thawed blastocyst transfers as the fraction of participants with at least one positive clinical pregnancy. The cumulative pregnancy rate will be plotted versus transfer number and versus time from start of REKOVELLE® treatment.	Up to 24 months
Positive βhCG result (blood or urinary pregnancy test)		Up to 24 months
Use of the algorithm-based individualized dosing regimen with REKOVELLE®	Use of the Ferring developed dosing app for the daily dose calculation. The daily dose is calculated with body weight in kilograms or pounds and AMH serum level in pmoL/L or ng/ml to define the daily dose of REKOVELLE® in micrograms.	At the day of the consultation visit where the daily dose of REKOVELLE® is decided
Daily dose of REKOVELLE® administered	Daily dose of REKOVELLE® in micrograms is recorded.	From day 1 up to day 20 of REKOVELLE® stimulation
Day of REKOVELLE® stimulation start	The time point of the start of the stimulation is decided at the discretion of the investigator.	At the day of the first REKOVELLE® injection during the ovarian stimulation treatment
Day of REKOVELLE® stimulation end	The time point of the end of the stimulation is decided at the discretion of the investigator.	At the day of the last REKOVELLE® injection during the ovarian stimulation treatment
Any deviation in REKOVELLE® administration	REKOVELLE® should be used according to the approved label, any possible deviations such as different starting dose or dose adjustment during stimulation will be recorded and analyzed.	From day 1 up to day 20 of REKOVELLE® stimulation

Collaborators and Investigators

• Sponsor: Ferring Pharmaceuticals
• Investigators: Study Director: Global Clinical Compliance, Ferring Pharmaceuticals

Publications and helpful links

General Publications

• Gabrielsen A, Iversen LH, Fedder J, Eskildsen TV, Englund AL, Hansen SR, Pinton P. Pre-Vitrification and Post-Warming Variables of Vitrified-Warmed Blastocysts That Are Predictable for Implantation. J Clin Med. 2023 Oct 6;12(19):6389. doi: 10.3390/jcm12196389.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2018
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: September 14, 2018
• First Submitted That Met QC Criteria: October 4, 2018
• First Posted (Actual): October 5, 2018

Study Record Updates

• Last Update Posted (Estimated): December 12, 2023
• Last Update Submitted That Met QC Criteria: December 5, 2023
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Follicle Stimulating Hormone
• Other Study ID Numbers: 000317

Drug and device information, study documents

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