Clinical trial NCT05815719
Conditions: Fertility Issues
Keywords: OVARIAN STIMULATION
Sponsor: Instituto Bernabeu
Start date: 2022-11-17; Completion date: 2023-05-30
Enrollment: 30 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
To evaluate the efficacy of the weekly use of corifollitropin alfa in double ovarian stimulation process and to compare it to the conventional protocol with daily medication administration.

Detailed description:
The purpose of this pilot study is to evaluate the efficacy of the weekly use of corifollitropin alfa in terms of ovarian stimulation results and its biological outcomes (total number of oocytes retrieved) in case of ovarian stimulation cycles in double stimulation modality (DUOSTIM) and in comparison with the conventional DUOSTIM protocol: daily administration of gonadotropins.

Arms: arm 1: Patients to carry out an experimental double ovarian stimulation and to receive 4 weekly injections of Corifollitropin alfa. Prospective group. arm 2: Patients to carry out a conventional double ovarian stimulation and to receive daily injections of gonadotropins. Retrospective group (data retrieved from strictly selected treatments carried out in our institution within the 24 months prior to the inclusion of the first patient in the study group and according to the standard guideline of the clinic).
Interventions: intervention 1: Corifollitropin Alfa intervention 2: Follitropin Alfa intervention 3: Follitropin Alfa Biosimilar intervention 4: Urinary Human follicle stimulating hormone
Intervention descriptions: intervention 1: 150 micrograms per dose intervention 2: Variable dose. intervention 3: Variable dose. intervention 4: Variable dose.

Protocol documents:
Prot_SAP_000.pdf: 
PROTOCOL 
“Continuous ovarian stimulation in DUOSTIM cycles” 
Date: May 7, 2022 
 
 
Despite its growing popularity, ovarian stimulation over prolonged periods involves the 
application of a large number of injectable medications, resulting in an increased 
therapeutic burden for the patient. Therefore, there is a need for research into simplified 
protocols to guarantee optimal patient outcomes not affecting the DuoStim treatment 
efficiency. At present, we have the physiological basis and optimal drugs to achieve this 
objective. 
1. Objectives 
The present study aims to explore the progesterone and Corifolitropin alpha 
application in DuoStim cycles, following the follicular surges concept, in order to alleviate 
treatment burden in patients indicated for DuoStim cycles and without diminishing the 
technique’s efficacy or safety. Could continuous weekly dosing constitute a viable 
alternative to daily FSH administration, to obtain a comparable oocyte yield? 
2. Materials and methods 
2.1. Study design and Patients 
From November 2022 to May 2023, an observational cohort study was conducted at 
Instituto Bernabeu Alicante to assess non-inferiority. All procedures were performed in a 
single laboratory and the study was registered (NCT05815719) and validated by the 
Instituto Bernabeu review committee (IBMR31/01-06-2022). All subjects provided 
informed consent prior to participation.  
The cohort included patients under the DuoStim protocol at the beginning of the 
stimulation process. Patients with ovarian pathology (e.g., cysts or tumours, with the 
exception of endometriomas <4 cm) at the time of stimulation initiation were not included. 
Baseline determination included age, AMH levels and body mass index (BMI) 
measurements. 
2.2. Procedures 


On the one hand, the study group (n=15) received subcutaneous injections of 150 µg 
Corifolitropin alpha (Elonva®) consecutively for eight days, together with oral 
administration of micronized natural progesterone 200 mg/day (to prevent LH peak) 
during follicular and luteal phase. 
On the other hand, the control group (n=15) was formed from historical records of 
patients undergoing DuoStim over the course of 2021 to 2022, following a standard daily 
FSH/flexible GnRH antagonist protocol. Controls were matched 1 to 1 for age and AMH 
values (± 0,4 pmol/l). 
During follicular phase, the GnHR agonist was administered as trigger, whilst the use 
of hCG or GnHR agonist in luteal phase was permitted. 
2.3. Result measurements 
The study’s main objective was to study the total number of obtained oocytes and the 
metaphase II stage oocytes rate (stimulation in follicular phase + luteal phase). 
Secondary objectives included: total number of required injectable and the duration of 
ovarian stimulation (total days of follicular and luteal phases): 
 
Stimulation in follicular phase: from the day of the first injectable administration 
in follicular phase and up to (inclusive) trigger day.  
 
Stimulation in luteal phase: starting from the day after the first punction up to and 
including trigger day in luteal phase. 
 
2.4. Statistical analysis 
A non-inferiority trial was planned with a minimum sample size of 13 patients per 
group, based on a tolerated difference of ± 1, a standard deviation of 1, a statistical power 
of 80%, and a type 1 error of 5%.   
Data were presented as mean ± standard deviation (SD). As our data are not random 
but come from chosen cases and controls with similar age and AMH levels, the 
samples would be matched. Therefore, differences were analysed using Student’s t-
test for paired simples if variables had a normal distribution or, the Wilcoxon sign-rank 
test if a non-normal distribution was assumed.