Menopur And Rekovelle Combination Study Version 2.0 (MARCS 2)

Ovo Clinic

Status and phase

Enrolling

Phase 2

Conditions

Fertility Disorders

IVF

Controlled Ovarian Simulation

Treatments

Drug: Combination therapy : Follitropin delta and HP-hMG

Study type

Interventional

Funder types

Industry

Identifiers

NCT06997900

IIS-1056

Details and patient eligibility

About

The goal of this clinical trial is to evaluate the safety and effectiveness of a personalized ovarian stimulation regimen in women aged 18 to 40 undergoing in vitro fertilization (IVF). The main question it aims to answer is:

Does personalizing the starting doses of follitropin delta (REKOVELLE) and HP-hMG (MENOPUR) based on both age and body lead to similar results as anti-Müllerian hormone (AMH) and weight based dosing ?

Researchers will compare the new dosing regimen to the MARCS study results to see if this new approach leads to similar outcomes

Participants will:

Receive ovarian stimulation using a personalized dose of REKOVELLE aND MENOPUR based on age and weight
Be monitored through ultrasound imaging and blood tests to measure estradiol (E2) levels
Undergo standard IVF procedures including egg retrieval and embryo assessment

Full description

In vitro fertilization (IVF) is a multi-step process that includes controlled ovarian stimulation, oocyte retrieval, fertilization, and embryo transfer. Success in IVF largely depends on how the ovaries respond to stimulation using exogenous gonadotropins. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are key to folliculogenesis and oocyte maturation, and are central to ovarian stimulation protocols. Physicians typically determine the appropriate stimulation regimen by considering clinical factors such as age, body weight, and ovarian reserve, and choosing the type and dose of gonadotropins accordingly. The combined use of FSH and LH, such as in protocols incorporating both recombinant FSH and human menopausal gonadotropin (hMG), has shown improvements in ART outcomes.

Among gonadotropins, follitropin delta (REKOVELLE) is a recombinant FSH with allowing for individualized dosing based on anti-Müllerian hormone (AMH) levels and body weight. The ESTHER-1 trial demonstrated its safety and efficacy when personalized using this algorithm. Furthermore, the MARCS study showed that combining REKOVELLE with highly purified hMG (MENOPUR) led to higher number of retrieved oocytes and improved blastulation rate compared to REKOVELLE alone.

However, in some regions, AMH is not routinely used to personalize FSH dosing. Other trials, such as RITA-1 and RITA-2, demonstrated the potential of adjusting REKOVELLE doses based solely on age and body weight. Inspired by these findings, this study seeks to evaluate dosing based on age and weight for combination therapy with REKOVELLE and MENOPUR.

This is a prospective, interventional, phase II clinical trial enrolling 200 participants across two fertility centers in Canada. The objective is to determine whether individualizing the starting doses of REKOVELLE and MENOPUR based on age and body weight results in similar clinical outcomes to those achieved when dosing is based on AMH and weight, as per the standard REKOVELLE dosing algorithm.

Unlike the original MARCS protocol, which used a fixed dose of REKOVELLE and variable MENOPUR, this study will apply an adjustable REKOVELLE dose and a fixed MENOPUR dose. The study aims to assess ovarian response, blastulation, embryo quality, pregnancy rates, and safety outcomes, particularly the risk of ovarian hyperstimulation syndrome (OHSS).

This research will contribute valuable data on the feasibility and effectiveness of an age- and weight-based dosing regimen for REKOVELLE and MENOPUR mixed protocol ovarian stimulation, especially in clinical environments where AMH measurement is less accessible.

Enrollment

200 estimated patients

Sex

Female

Ages

18 to 40 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Women aged 18 to 40 years inclusively at the time of consent form signature
Diagnosis of unexplained infertility, tubal infertility, endometriosis stage I/II or male factor infertility
Regular menstrual cycles of 24-35 days
Presence of both ovaries
Early follicular phase FSH serum concentration <10 IU/L measured between Day 2 and Day 5 of menstrual cycle within the previous 24 months
First IVF/ICSI cycle
IVF antagonist protocol prescribed
Partner or donor ejaculated sperm (fresh or frozen) used for fertilization

Exclusion criteria

Women undergoing oocyte donation
Endometriosis stage III/IV
High risk of OHSS (AMH ≥ 35 pmol/L)
Body Mass Index (BMI) > 40 kg/m2 Protocol number: IIS-1056 MARCS 2.0 Study Version: 1.1 - Date : 14 APR 2025 Page 12 of 28
Gynaecological haemorrhages of unknown aetiology
History of recurrent miscarriages defined as ≥ 3 consecutive losses
Renal or hepatic impairment
Hypersensitivity to any active ingredient or excipients in follitropin delta and/or HP-hMG
Tumours of hypothalamus or pituitary gland
Ovarian enlargement or ovarian cyst not due to polycystic ovarian syndrome
Current or history of ovarian, uterine or mammary carcinoma
History of thrombophilia
Use of hormonal preparations (except for 17β-estradiol, testosterone gel, DHEA and thyroid medication) during the last menstrual cycle
Women participating in any other interventional research project