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

Overview

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.

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.

Interventions

• 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

Primary outcome measures

• Percentage of cycles with two mature follicles (total of two ovaries) at the stage of triggering ovulation [Time frame: up to 9 months]

Secondary outcome measures (12)

• Number of follicles ≥14 mm on the day of trigger [Time frame: 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 [Time frame: 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 [Time frame: up to 9 months]
• Presence or absence of dose adjustment in subsequent cycles [Time frame: up to 9 months]
• E2 level on the day of trigger [Time frame: Up to Day 15 of the cycle (each cycle is 28 days)]
• Dose adjustment on subsequent cycle(s) : quantity of mcg [Time frame: up to 9 months]
• PG level on the day of trigger [Time frame: Up to Day 15 of the cycle (each cycle is 28 days)]
• LH level on the day of trigger [Time frame: Up to Day 15 of the cycle (each cycle is 28 days)]
• Frequency of spontaneous LH surge by cycle , at the end of stimulation [Time frame: up to 9 months]
• Cycle cancellation rate [Time frame: up to 9 months]
• Pregnancy loss rate [Time frame: up to 9 months]
• Rate of Biochemical pregnancy (βhCG test) by initiated cycle [Time frame: From enrollment to 2 weeks after IUI]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

France · 5 centers

• Cabinet Dr Elodie Descat-Polyclinique Jean Villar — Bruges
• Chi Creteil — Créteil
• Cabinet Dr Géraldine PORCU-Institut de Médecine de la Reproduction — Marseille
• Cabinet Dr Nicolas Chevalier-Centre AMP Saint Roch — Montpellier
• Cabinet Dr Nathalie Massin- Hôpital Américain De Paris — Neuilly-sur-Seine

Identifiers

NCT: NCT07153367 · RISE

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗