IVFPhase 2MARCS 2NCT06997900
Menopur And Rekovelle Combination Study Version 2.0
A Phase 2 study testing Combination therapy : Follitropin delta and HP-hMG in people with IVF and Controlled Ovarian Simulation, run by Clinique Ovo at 2 sites in Canada.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 to 40 years, women only
- Conditions the study is for
- IVF, Controlled Ovarian Simulation, Fertility Disorders
- What is being tested?
- Combination therapy : Follitropin delta and HP-hMG
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 2 sitesCanada
- Study dates
- 4 Jul 2025to Aug 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Canada2 sites, 2 recruiting
- Recruiting
Clinique ovo
Montreal, Quebec, H4P 2S4
Isaac-Jacques Kadoch, MD
- Recruiting
Ottawa fertility centre
Ottawa, Ontario
Jenna Gale, MD
About this study
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 ?
Read more
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
Read the detailed 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.
- Conditions
- IVF, Controlled Ovarian Simulation, Fertility Disorders
- Being tested
- Combination therapy : Follitropin delta and HP-hMG
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Combination therapy : Follitropin delta and HP-hMGDrug
Follitropin delta dose will be determined by age. Highly purified human menopausal gonadotrophin will be determined by follitropin delta dose and body weight.
| Study group | Role | What they receive |
|---|---|---|
| Follitropin delta and HP-hMG | Experimental | Not described Receives: Drug: Combination therapy : Follitropin delta and HP-hMG |
What is being measured
The primary outcome is the main question the study is designed to answer.
number of good quality (>3BB) or utilizable blastocysts per treatment cycle at day 5 or 6 of embryo culture
Measured: 5 to 6 days after egg retrieval (up to 1 to 2 months after enrollment)
Secondary outcomes (1)
Safety profile of follitropin delta + HP-hMG mixed protocol
Patient rate that will develop ovarian hyperstimulation syndrome (OHSS)
Measured: up to 15 days after egg retrieval
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2025
- Study start4 Jul 2025
- Primary completionAug 2026 (estimated)
- Study completionAug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for IVFStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Clinique Ovo
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Ferring Pharmaceuticals
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06997900
- Sponsor's protocol ID
- IIS-1056
- Acronym
- MARCS 2
- Status last verified
- Jul 2025
- First submitted
- 21 May 2025
- Last updated
- 31 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 33267959
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Menopur And Rekovelle Combination Study Version 2.0
- ClinicalTrials.gov ID
- NCT06997900
- Acronym / sponsor ID
- MARCS 2 / IIS-1056
- Conditions
- IVF, Controlled Ovarian Simulation, Fertility Disorders
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Clinique OvoIndustry (pharma, biotech, devices)
- Collaborators
- Ferring Pharmaceuticals
- Study start
- 4 Jul 2025 (actual)
- Primary completion
- Aug 2026 (estimated)
- Study completion
- Aug 2027 (estimated)
- First posted
- 31 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Follitropin delta and HP-hMG | Experimental | Drug: Combination therapy : Follitropin delta and HP-hMG |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Combination therapy : Follitropin delta and HP-hMGFollitropin delta dose will be determined by age. Highly purified human menopausal gonadotrophin will be determined by follitropin delta dose and body weight. | Drug | Follitropin delta and HP-hMG |
Primary outcome
number of good quality (>3BB) or utilizable blastocysts per treatment cycle at day 5 or 6 of embryo culture
Time frame: 5 to 6 days after egg retrieval (up to 1 to 2 months after enrollment)
1 secondary outcome
Safety profile of follitropin delta + HP-hMG mixed protocol
Time frame: up to 15 days after egg retrieval
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2025.
- Results publication: PubMed 33267959Bissonnette 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Combination therapy : Follitropin delta and HP-hMG in people with IVF and Controlled Ovarian Simulation, run by Clinique Ovo at 2 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 31 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Marya Far (514-798-2000 ext. 759, m.far@cliniqueovo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
number of good quality (>3BB) or utilizable blastocysts per treatment cycle at day 5 or 6 of embryo culture (time frame: 5 to 6 days after egg retrieval (up to 1 to 2 months after enrollment)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06997900, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2025.