InfertilityPhase 4NATOSNCT02892942
NATural Ovarian Stimulation
A Phase 4 study testing Gonal-F® and Cetrotide® in people with Infertility, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
To overcome unsuitable effects of controlled ovarian hyperstimulation (COH )while maintaining large oocyte availability, investigators elaborated an innovative protocol (NATural Ovarian Stimulation) that dissociates E2 production from multiple follicle development. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women only
- Conditions the study is for
- Infertility
- What is being tested?
- Gonal-F® and Cetrotide®
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 129 participants
- Where
- 1 siteFrance
- Study dates
- 13 Jan 2017to 8 Feb 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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
- IVF-ET candidates (excluding PGD and oocyte donor);
- Body mass index from 18 to 30 kg/m2;
- Non smokers;
- Regular menstrual cycles (25-35 days);
- Presence of both ovaries;
- Antral follicle count (follicles measuring from 3 to 10 mm in diameter) ranging from 10 to 30 on cycle days 2 to 4;
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- Serum AMH levels ranging from 0.5 to 5.0 ng/mL;
- Normal endometrium at ultrasound (US) and/or hysteroscopy;
- Informed consent signed
Who cannot join
- Iatrogenic ovarian insufficiency (surgery, radiotherapy, chemotherapy);
- Uterine abnormalities as demonstrated by pelvic US and/or hysteroscopy;
- Usual contra-indications for COH (cancer risk, blood coagulation disorders, etc)
- Renal insufficiency
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Innovative Controlled Ovarian Hyperstimulation (COH) Protocol That Combines Large Oocyte Availability and Physiologic Estrogenic Environment for Good Prognosis In Vitro Fertilization and Embryo Transfer (IVF-ET) Patients
To overcome unsuitable effects of controlled ovarian hyperstimulation (COH )while maintaining large oocyte availability, investigators elaborated an innovative protocol (NATural Ovarian Stimulation) that dissociates E2 production from multiple follicle development.
The purpose of this prospective, randomized trial is to demonstrate that, in a good prognosis IVF-ET population, the physiological E2 environment resulting from NATOS significantly improves IVF-ET outcome when compared to the conventional GnRH antagonist protocol.
Read the detailed description
Controlled ovarian hyperstimulation (COH) seeks to improve IVF-ET results by increasing per-cycle oocyte and embryo availability. Yet, the coexistence of multiple preovulatory follicles engenders compulsory alterations in the endocrine milieu of the follicular phase. The most evident of them are the extremely high serum estradiol (E2) levels. The 10 to 15-fold increase in E2 levels as a result of COH has been shown to provoke unwanted consequences in both embryo quality and uterine receptivity.
Therefore, investigators elaborated an innovative COH protocol (NATural Ovarian Stimulation) that aimed at dissociating E2 production from multiple follicle development. To obtain this effect, they virtually curtailed endogenous LH production by using GnRH antagonist doses as strong and frequent enough to maintain E2 levels around the physiological range during standard exogenous FSH-only administration. Given that high E2 levels are commonly reached in patients having a normal follicle endowment, NATOS should target this group of good prognosis IVF-ET candidates. Indeed, this new COH approach was first tested in a pilot study that included 15 good prognosis IVF-ET candidates, aged 25-35 years, who volunteered to undergo NATOS. 11 out of 15 patients achieved a pregnancy. These pilot results spurred them to conduct a prospective, randomized trial to demonstrate that, in a good prognosis IVF-ET population, the physiological E2 environment resulting from NATOS significantly improves IVF-ET outcome when compared to the conventional GnRH antagonist protocol.
- Conditions
- Infertility
- Being tested
- Gonal-F®, Cetrotide®
- Keywords
- Controlled ovarian hyperstimulation, Estradiol, Embryo implantation, Endometrial receptivity, Fertility preservation
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gonal-F®Drug
225 to 450 IU/d; from day 2 of menstrual cycle onward
Cetrotide®Drug
0.25 mg/day, starting on day 6 of Gonal-F®.
Cetrotide®Drug
1.5 mg/day (6 ampoules of 0.25 mg), starting on day 1 (S1) of Gonal-F® treatment until dhCG
| Study group | Role | What they receive |
|---|---|---|
| Control Group | Active comparator | Background therapy which is the usual COH treatment:
* Recombinant FSH (Gonal-F®, 225 to 450 IU/d; MerckSerono Pharmaceuticals) from day 2 of their menstrual cycle onward,
* GnRH antagonist (Cetrotide®, MerckSerono Pharmaceuticals) 0.25 mg/day, S.C., starting on day 6 of Gonal-F®. Receives: Drug: Gonal-F®; Drug: Cetrotide® |
| NATOS Group | Experimental | Background therapy which is the usual COH treatment:
* Recombinant FSH (Gonal-F®, 225 to 450 IU/d; MerckSerono Pharmaceuticals) from day 2 of their menstrual cycle onward,
* GnRH antagonist (Cetrotide®, MerckSerono Pharmaceuticals) 0.25 mg/day, S.C., starting on day 6 of Gonal-F®.
GnRH antagonist treatment (Cetrotide®, MerckSerono Pharmaceuticals) will be reinforced and patients will receive 1.5 mg/day (6 ampoules of 0.25 mg), S.C., starting on day 1 (S1) of Gonal-F® treatment until dhCG Receives: Drug: Gonal-F®; Drug: Cetrotide® |
What is being measured
The primary outcome is the main question the study is designed to answer.
Live birth obtained after IVF-ET
Live birth defined as delivery ≥ 22 weeks of amenorrhea
Measured: 1 month post-partum
Secondary outcomes (1)
Number of oocytes obtained
Measured: At oocyte retrieval (14±8 days after start of treatment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2016 (estimated)
- Study start13 Jan 2017
- Primary completion8 Feb 2019
- Study completion8 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for InfertilityStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 129 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- MerckSerono Pharmaceuticals, URC-CIC Paris Descartes Necker Cochin
- Responsible party
- Sponsor
- Investigators
- RENATO FANCHIN, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02892942
- Sponsor's protocol ID
- P150947
- Acronym
- NATOS
- Status last verified
- Mar 2026
- First submitted
- 25 Aug 2016
- Last updated
- 3 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Innovative Controlled Ovarian Hyperstimulation (COH) Protocol That Combines Large Oocyte Availability and Physiologic Estrogenic Environment for Good Prognosis In Vitro Fertilization and Embryo Transfer (IVF-ET) Patients
- ClinicalTrials.gov ID
- NCT02892942
- Acronym / sponsor ID
- NATOS / P150947
- Conditions
- Infertility
- Keywords
- Controlled ovarian hyperstimulation, Estradiol, Embryo implantation, Endometrial receptivity, Fertility preservation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 129 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- MerckSerono Pharmaceuticals, URC-CIC Paris Descartes Necker Cochin
- Study start
- 13 Jan 2017 (actual)
- Primary completion
- 8 Feb 2019 (actual)
- Study completion
- 8 Feb 2019 (actual)
- First posted
- 8 Sep 2016 (estimated)
- 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.
To overcome unsuitable effects of controlled ovarian hyperstimulation (COH )while maintaining large oocyte availability, investigators elaborated an innovative protocol (NATural Ovarian Stimulation) that dissociates E2 production from multiple follicle development.
The purpose of this prospective, randomized trial is to demonstrate that, in a good prognosis IVF-ET population, the physiological E2 environment resulting from NATOS significantly improves IVF-ET outcome when compared to the conventional GnRH antagonist protocol.
Detailed description
Controlled ovarian hyperstimulation (COH) seeks to improve IVF-ET results by increasing per-cycle oocyte and embryo availability. Yet, the coexistence of multiple preovulatory follicles engenders compulsory alterations in the endocrine milieu of the follicular phase. The most evident of them are the extremely high serum estradiol (E2) levels. The 10 to 15-fold increase in E2 levels as a result of COH has been shown to provoke unwanted consequences in both embryo quality and uterine receptivity.
Therefore, investigators elaborated an innovative COH protocol (NATural Ovarian Stimulation) that aimed at dissociating E2 production from multiple follicle development. To obtain this effect, they virtually curtailed endogenous LH production by using GnRH antagonist doses as strong and frequent enough to maintain E2 levels around the physiological range during standard exogenous FSH-only administration. Given that high E2 levels are commonly reached in patients having a normal follicle endowment, NATOS should target this group of good prognosis IVF-ET candidates. Indeed, this new COH approach was first tested in a pilot study that included 15 good prognosis IVF-ET candidates, aged 25-35 years, who volunteered to undergo NATOS. 11 out of 15 patients achieved a pregnancy. These pilot results spurred them to conduct a prospective, randomized trial to demonstrate that, in a good prognosis IVF-ET population, the physiological E2 environment resulting from NATOS significantly improves IVF-ET outcome when compared to the conventional GnRH antagonist protocol.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control Group | Active comparator | Drug: Gonal-F®, Drug: Cetrotide®Background therapy which is the usual COH treatment: * Recombinant FSH (Gonal-F®, 225 to 450 IU/d; MerckSerono Pharmaceuticals) from day 2 of their menstrual cycle onward, * GnRH antagonist (Cetrotide®, MerckSerono Pharmaceuticals) 0.25 mg/day, S.C., starting on day 6 of Gonal-F®. |
| NATOS Group | Experimental | Drug: Gonal-F®, Drug: Cetrotide®Background therapy which is the usual COH treatment: * Recombinant FSH (Gonal-F®, 225 to 450 IU/d; MerckSerono Pharmaceuticals) from day 2 of their menstrual cycle onward, * GnRH antagonist (Cetrotide®, MerckSerono Pharmaceuticals) 0.25 mg/day, S.C., starting on day 6 of Gonal-F®. GnRH antagonist treatment (Cetrotide®, MerckSerono Pharmaceuticals) will be reinforced and patients will receive 1.5 mg/day (6 ampoules of 0.25 mg), S.C., starting on day 1 (S1) of Gonal-F® treatment until dhCG |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- IVF-ET candidates (excluding PGD and oocyte donor);
- Body mass index from 18 to 30 kg/m2;
- Non smokers;
- Regular menstrual cycles (25-35 days);
- Presence of both ovaries;
Key exclusion criteria (4 listed)
- Iatrogenic ovarian insufficiency (surgery, radiotherapy, chemotherapy);
- Uterine abnormalities as demonstrated by pelvic US and/or hysteroscopy;
- Usual contra-indications for COH (cancer risk, blood coagulation disorders, etc)
- Renal insufficiency
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 |
|---|---|---|
| Gonal-F®225 to 450 IU/d; from day 2 of menstrual cycle onward | Drug | Control Group, NATOS Group |
| Cetrotide®0.25 mg/day, starting on day 6 of Gonal-F®. | Drug | Control Group, NATOS Group |
| Cetrotide®1.5 mg/day (6 ampoules of 0.25 mg), starting on day 1 (S1) of Gonal-F® treatment until dhCG | Drug | NATOS Group |
Primary outcome
Live birth obtained after IVF-ET
Time frame: 1 month post-partum
Live birth defined as delivery ≥ 22 weeks of amenorrhea
1 secondary outcome
Number of oocytes obtained
Time frame: At oocyte retrieval (14±8 days after start of treatment)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2026.
- 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. This study is not recruiting at the moment.
RENATO FANCHIN, MD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Gonal-F® and Cetrotide® in people with Infertility, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 9 inclusion and 4 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: finished, as of the sponsor's last update on 3 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Live birth obtained after IVF-ET (time frame: 1 month post-partum). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Apr 2026.