Using a Fixed Dosage of Follitropin Delta for Ovarian Stimulation for Intrauterine Insemination: Rekovelle for Intrauterine Successful Experience (RISE) (RISE)

The aim of this study is to evaluate the use of a fixed dose of 3.66 mcg of follitropin delta (Rekovelle) on ovarian response during ovarian stimulation for intrauterine insemination (IUI). The assumption is that this fixed dose will be effective while minimizing the risk of multiple pregnancies. A recent study demonstrated the efficacy of follitropin delta for ovarian stimulation in IUI, and it has been approved in France for controlled ovarian stimulation in assisted reproductive techniques such as in vitro fertilization (IVF) and IVF with intracytoplasmic sperm injection (ICSI). With an adapted dose of Rekovelle for patients with regular menstrual cycles, ovarian stimulation is optimized from the first attempt, promoting the development of two follicles to improve pregnancy chances while reducing the risk of multiple pregnancies. This approach aims to achieve pregnancy faster and provide a more comfortable treatment experience.

Study Overview

• Status: Recruiting
• Conditions: Infertility; Insemination
• Intervention / Treatment: Drug: REKOVELLE (Follitropin Delta)

Detailed Description

Intrauterine insemination (IUI) is a frequently used step in the management of unexplained infertility or mild fertility disorders. In normal-weight patients, the main objective of ovarian stimulation in IUI is to obtain a controlled ovarian response, ideally bifollicular.

Moreover, the main risks currently associated with IUI are multiple pregnancies and iatrogenic complications (cycle cancellation due to insufficient response or excessive response to stimulation more than 3 follicles). It is therefore essential to optimize stimulation treatment protocols to ensure IUI under the best possible conditions.

Due to a precise dose adjustment with Follitropin Delta, the product used in the study (REKOVELLE), for normo-ovulatory patient, an optimal response (bifollicular response) is expected for the majority of patients from the first stimulation. This goal will also facilitate quicker pregnancy attainment and reduce the risk of drop-out and insémination annulation The hypothesis is that this dosage would be efficient and also minimize the risk of multiple pregnancies During the screening visit, the investigator checks the patient's eligibility and informs her about the RISE study. At the inclusion visit, written informed consent is obtained, and the Rekovelle® treatment is explained and initiated. Monitoring visits start on day 9 and then every 2 days until two mature follicles develop. Ovocyte maturation is triggered with an hCG injection, followed by insemination 24 to 36 hours later, performed according to routine care. Follow-up visits occur at 6-8 weeks and 13 weeks post-insemination.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Aroua Ben Guirat; Phone Number: +33157023710; Email: aroua.benguirat@chicreteil.fr

Study Locations

• France
  • Bruges, France, 33520
    • Recruiting
    • Cabinet Dr Elodie Descat-Polyclinique Jean Villar
    • Contact: Elodie Descat, Dr; Email: elodie.descat@gmail.com
    • Principal Investigator: Elodie Descat, Dr
  • Créteil, France, 94000
    • Recruiting
    • CHI créteil
    • Contact: Maud Pasquier, Dr; Phone Number: 0033 1 57 02 24 70; Email: Maud.Pasquier@chicreteil.fr
    • Principal Investigator: Maud Pasquier, Dr
  • Marseille, France, 13008
    • Recruiting
    • Cabinet Dr Géraldine PORCU-Institut de Médecine de la Reproduction
    • Contact: Géraldine Porcu-Buisson, Dr; Email: geraldine.porcu-buisson@hotmail.fr
    • Principal Investigator: Géraldine Porcu-Buisson, Dr
  • Montpellier, France, 34070
    • Recruiting
    • Cabinet Dr Nicolas Chevalier-Centre AMP Saint Roch
    • Contact: Nicolas Chevalier, Dr; Email: nicolas.chevalier.doc@hotmail.fr
    • Principal Investigator: Nicolas Chevalier, Dr
  • Neuilly-sur-Seine, France, 92200
    • Suspended
    • Cabinet Dr Nathalie Massin- Hôpital Américain De Paris

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Normo-ovulatory patients
• 18 - 38 included years old
• BMI between 18 and 29 included kg/m²
• Regular menstrual cycles
• At least one healthy Fallopian tube
• Normal uterus cavity
• First treatment for IUI
• Affiliation to the social security

Exclusion Criteria:

• Endometriosis Stage III
• Total mobile sperm count <1 million
• Severe spermatogenesis disorders
• Women with Poly Cystic Ovary Syndrom
• History of OHSS or excessive response to gonadotrophins
• Chronic disease with contraindication to ovarian stimulation with gonadotrophins
• Known genetic disease
• Hypothalamus or pituitary tumors
• Ovarian hypertrophy or ovarian cyst not due to polycystic ovary syndrome
• Gynecological bleeding of unknown etiology
• Ovarian, uterine or breast carcinoma
• Primary ovarian failure
• Genital malformations incompatible with pregnancy
• Uterine fibroids incompatible with pregnancy
• Protected persons (pregnant women, nursing mothers, person under guardianship, minors, persons deprived of liberty, and persons unable to give consent)
• Tumors (including meningioma) whose development is known or suspected to be progesterone-dependent
• History of hepatic dysfunction
• Have been receiving progestogen therapy for more than 6 months
• Known contraindication to hormonal treatments (progestogens or oestrogens), or with a history of adverse events related to their use
• Previous thromboembolism events during or following the use of gonadotrophins or with high risk factors for thromboembolic events (venous or arterial)
• Previous or current treatment with gonadotrophins
• Hypersensitivity to the active substance or to any of the excipients
• High risk of OHSS such as women with AMH ≥ 35 pmol/L
• History of severe uterine malformation (unicornuate or bicornuate uterus),
• Past history of ovarian torsion
• Uncontrolled thyroid dysfunction
• Uncontrolled adrenal dysfunction
• Hydrosalpynx
• Breast pathologies not compatible with gonadotrophin stimulation
• Use of infertility medications that could affect follicle stimulation and maturation such as GH
• Participation in other interventional research
• Not able to understand and sign the written informed consent form

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rekovelle Arm	Drug: REKOVELLE (Follitropin Delta); Each patient will start the ovarian stimulation with a fixed dose of 3,66 mcg of Rekovelle ® on day 4 of the natural cycle (Stimulation day 1-S1). The stimulation period will last a maximum of 13 days. Patients will be regularly evaluated to monitor the response to stimulation with ultrasound scan and blood sampling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of cycles with two mature follicles (total of two ovaries) at the stage of triggering ovulation	Percentage of cycles with two mature follicles (total of two ovaries) at the stage of triggering ovulation (follicles diameter ≥14 mm) and no follicles between 10 et 13 mm.	up to 9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of follicles ≥14 mm on the day of trigger	Number of follicles ≥14 mm on the day of trigger ( by cycle)	Up to Day 15 of the cycle (each cycle is 28 days)
Number of follicles between 10 et 13 mm on the day of trigger	Number of follicles between 10 et 13 mm on the day of trigger (by cycle)	Up to Day 15 of the cycle (each cycle is 28 days)
Percentage of cycles with two mature follicles (total of two ovaries) at the stage of triggering ovulation (follicles diameter ≥14 mm) and no follicles between 10 et 13 mm for each cycle and according to dose adjustment	Percentage of cycles with two mature follicles (total of two ovaries) at the stage of triggering ovulation (follicles diameter ≥14 mm) and no follicles between 10 et 13 mm for each cycle and according to dose adjustment	up to 9 months
Presence or absence of dose adjustment in subsequent cycles	Presence or absence of dose adjustment in subsequent cycles	up to 9 months
E2 level on the day of trigger	E2 level on the day of trigger (pg/ml)	Up to Day 15 of the cycle (each cycle is 28 days)
Dose adjustment on subsequent cycle(s) : quantity of mcg	Dose adjustment on subsequent cycle(s) : quantity of mcg	up to 9 months
PG level on the day of trigger	PG level on the day of trigger (ng/ml)	Up to Day 15 of the cycle (each cycle is 28 days)
LH level on the day of trigger	LH level on the day of trigger (UI/L)	Up to Day 15 of the cycle (each cycle is 28 days)
Frequency of spontaneous LH surge by cycle , at the end of stimulation	Frequency of spontaneous LH surge by cycle , at the end of stimulation (last day of stimulation)	up to 9 months
Cycle cancellation rate	Cycle cancellation rate (by cycle) . The Cycle is cancelled when more than 2 follicles ≥ 14mm or 4 follicles ≥ 10mm, or if there is no response to treatment.	up to 9 months
Pregnancy loss rate	Pregnancy loss rate	up to 9 months
Rate of Biochemical pregnancy (βhCG test) by initiated cycle	Rate of Biochemical pregnancy (βhCG test) by initiated cycle	From enrollment to 2 weeks after IUI
Rate of Clinical pregnancy by initiated cycle	Rate of Clinical pregnancy by initiated cycle	From enrollment to 8 weeks after IUI
Rate of Ongoing pregnancy by initiated cycle	Rate of Ongoing pregnancy by initiated cycle	From enrollment to 13 weeks after IUI
Pregnancy rate with one follicle or two follicles diameter ≥14 mm	Pregnancy rate with one follicle or two follicles diameter ≥14 mm	up to 9 months
Multiple pregnancy rate	Multiple pregnancy rate	up to 9 months
Time to pregnancy	Time to pregnancy (time between 1st stimulation and date of pregnancy)	From first stimulation until pregnancy confirmed by HCG > 100 UI/L, assessed up to 6 months.
The number of stimulation days.	The number of stimulation days.	up to 9 months
Unexpected and related Events	Unexpected and related Events	up to 9 months
Duration in days between each cycle	Duration in days between each cycle	up to 9 months
Dose adjustment on subsequent cycle(s) : number of cycles	Dose adjustment on subsequent cycle(s) : number of cycles	up to 9 months
Dose adjustment on subsequent cycle(s) : percentage of cycles	Dose adjustment on subsequent cycle(s) : percentage of cycles	up to 9 months
Rate of Biochemical pregnancy (βhCG test) by insemination	Rate of Biochemical pregnancy (βhCG test) by insemination	From enrollment to 2 weeks after IUI
Rate of Biochemical pregnancy (βhCG test):cumulative rates	Rate of Biochemical pregnancy (βhCG test) : cumulative rates	From enrollment to 2 weeks after IUI
Rate of Clinical pregnancy by insemination	Rate of Clinical pregnancy by insemination	From enrollment to 8 weeks after IUI
Rate of Clinical pregnancy (cumulative rates)	Rate of Clinical pregnancy (cumulative rates)	From enrollment to 8 weeks after IUI
Rate of Ongoing pregnancy by insemination	Rate of Ongoing pregnancy by insemination	From enrollment to 13 weeks after IUI
Rate of Ongoing pregnancy: cumulative rates	Rate of Ongoing pregnancy: cumulative rates	From enrollment to 13 weeks after IUI
The duration of stimulation for each cycle	The duration of stimulation for each cycle	up to 9 months
Endometrial thickness	Endometrial thickness	up to 9 months
Pregnancy outcome according to the cycle rank	Pregnancy outcome according to the cycle rank	up to 9 months
Cumulative pregnancy outcome up to 3 cycles	Cumulative pregnancy outcome up to 3 cycles	up to 9 months
Number of OHSS	Number of OHSS	up to 9 months
Number of ectopic pregnancy	Number of ectopic pregnancy	up tp 9 months
Number of ovarian torsion	Number of ovarian torsion	up to 9 months
Number of thromboembolic events	Number of thromboembolic events	up to 9 months
Causes of cycle cancellation	Causes of cycle cancellation	up to 9 months

Collaborators and Investigators

• Sponsor: Centre Hospitalier Intercommunal Creteil
• Collaborators: Ferring Pharmaceuticals
• Investigators: Principal Investigator: Nicolas Chevalier, Centre AMP Saint Roch

Study record dates

Study Major Dates

• Study Start (Actual): December 17, 2025
• Primary Completion (Estimated): December 17, 2027
• Study Completion (Estimated): March 17, 2028

Study Registration Dates

• First Submitted: July 3, 2025
• First Submitted That Met QC Criteria: August 29, 2025
• First Posted (Actual): September 4, 2025

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: April 3, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Infertility; follitropin delta
• Other Study ID Numbers: RISE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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