Menopur And Rekovelle Combination Study Version 2.0

Обзор

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

Подробное описание

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.

Вмешательства

• Препарат Combination therapy : Follitropin delta and HP-hMG
  Follitropin delta dose will be determined by age. Highly purified human menopausal gonadotrophin will be determined by follitropin delta dose and body weight.

Первичные конечные точки

• number of good quality (>3BB) or utilizable blastocysts per treatment cycle at day 5 or 6 of embryo culture [Срок оценки: 5 to 6 days after egg retrieval (up to 1 to 2 months after enrollment)]

Вторичные конечные точки (1)

• Safety profile of follitropin delta + HP-hMG mixed protocol [Срок оценки: up to 15 days after egg retrieval]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Канада · 2 центра

• Ottawa fertility centre — Ottawa
• Clinique ovo — Montreal

Публикации

• Bissonnette F, Minano Masip J, Kadoch IJ, Librach C, Sampalis J, Yuzpe A. Individualized ovarian stimulation for in vitro fertilization: a multicenter, open label, exploratory study with a mixed protocol of follitropin delta and highly purified human menopausal gonadotropin. Fertil Steril. 2021 Apr;115(4):991-1000. doi: 10.1016/j.fertnstert.2020.09.158. Epub 2020 Nov 30. PMID 33267959

Идентификаторы

NCT: NCT06997900 · IIS-1056

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗