InfertilityNCT03300518
Effectiveness of Estradiol Valerate Pretreatment in Antagonist Protocol for Poor Ovarian Response Patient
A study testing Follitropin Beta;MSD, Ganirelix and hCG in people with Infertility, run by Reproductive & Genetic Hospital of CITIC-Xiangya at 1 site in China.
Trial summary
The purpose of study is to assess the efficacy of add-on estrogen pretreatment in GnRH antagonist protocol on oocyte retrieval as compared with GnRH antagonist protocol for patients with poor ovarian response Add-on estrogen pretreatment protocol is superior to none pretreatment GnRH antagonist protocol for the number… Read more about this study
- Who is it for?
- Ages 40 to 45 years, women only
- Conditions the study is for
- Infertility
- What is being tested?
- Follitropin Beta;MSD, Ganirelix and hCG
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 552 participants
- Where
- 1 siteChina
- Study dates
- 15 Nov 2017to 18 Aug 2021
- Phase
- Interventional
- 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 40 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- At least two of the following three features must be present:
- Advanced maternal age (≥40 years) or any other risk factor for POR
- A previous POR (≤3 oocytes with a conventional stimulation protocol)
- An abnormal ovarian reserve test (i.e. antral follicle count < 5-7 follicles or AMH< 0.5 - 1.1 ng/mL)
Who cannot join
- Age ≥45 years,
- Patients who conducted PGD/PGS, and donor egg cycles were excluded.
- Presence of unilateral ovary absence
- Abnormal uterine deformity or structure.
- Spontaneous abortion patients with three or more (including biochemical pregnancy abortion)
- With other endocrine disease, ovulation disorders such as adrenal cortex function or thyroid dysfunction
- Have assisted reproductive technology contraindications or pregnancy contraindication of patients
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized Study to Analysis the Effectiveness of Estradiol Valerate Pretreatment in Antagonist Protocol for Poor Ovarian Response Patient
The purpose of study is to assess the efficacy of add-on estrogen pretreatment in GnRH antagonist protocol on oocyte retrieval as compared with GnRH antagonist protocol for patients with poor ovarian response Add-on estrogen pretreatment protocol is superior to none pretreatment GnRH antagonist protocol for the number of oocytes retrieval
Read the detailed description
Women of advanced maternal age seeking ART treatment are characterized as poor ovarian responders in the process of ovarian simulation. Poor response to ovarian stimulation causes high cycle cancellation rate and extremely low pregnancy rate.
More attention has been paid to the potential interest of steroid pretreatments in GnRH antagonist cycles; not only for scheduling the GnRH antagonist cycles, but also for synchronizing the follicular growth which may result in more oocytes retrieved. But available clinical results are controversial.
Previous studies have shown that utilizing the natural negative feedback of the hypothalamus-pituitary-ovary axis induced by estradiol valerate pretreatment effectively prevented inter-cycle increases in follicle-stimulating hormone, improved follicle synchronization, and resulted in a more coordinated follicular development, leading to the recovery of more mature oocytes. However none of the randomized controlled studies compared estradiol valerate pretreatment or not on treatment outcomes, ongoing pregnancy rate, directly on poor response patients using estradiol valerate pretreatment in GnRH antagonist protocol.
- Conditions
- Infertility
- Being tested
- Follitropin Beta;MSD, Ganirelix, hCG, estradiol valerate
- Keywords
- GnRH antagonist, Estrogen pretreatment, Poor response patient
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Follitropin Beta;MSDDrug
Also called Puregon
Patients will start stimulation with a daily s.c. injection of follitropin beta( 300IU Puregonon;MSD) menstrual cycle day 2 or 3.
GanirelixDrug
Also called Orgalutran
A daily administration of ganirelix (0.25 mg Orgalutran; MSD) was introduced when the leading follicle is near 13mm, and was repeated up to the time of hCG administration.
hCGDrug
Also called Ovidrel
Ovulation was triggered when the leading follicles reach 18-20mm and at least two follicles 17-18mm , HCG 10000 IU is used to trigger
estradiol valerateDrug
Also called progynova
Estradiol valerate (progynova,Schering) daily dose of 4 mg (2 mg twice a day) was given orally, started 7 days before the presumed onset of menses and administered up to 2 days of the next menstrual cycle
| Study group | Role | What they receive |
|---|---|---|
| pretreatment group | Other | the pretreatment group underwent a modified treatment protocol with pretreatment with estogen administering during the cycle preceding the IVF/ICSI cycle. daily dose of 4 mg (2 mg twice a day) estradiol valerate was given orally in the middle luteal phase which is confirmed seven days after ovulation monitoring by the ultrasound up to 2 days of the next menstrual cycle.Recombinant FSH (Puregon) was initiated on menstrual cycle day 2- 3 at an initial dose of 300 IU/day.A daily administration of ganirelix (0.25 mg Orgalutran; Organon) was introduced when the leading follicle is near 13mm, and was repeated up to the time of hCG administration.Ovulation was triggered when the leading follicles reach 18-20mm and at least two follicles 17-18mm , HCG 10000 IU is used to trigger. Receives: Drug: Follitropin Beta;MSD; Drug: Ganirelix; Drug: hCG; Drug: estradiol valerate |
| control groups | Other | In the control groups standard GnRH-antagonist protocol was applied.Recombinant FSH (Puregon) was initiated on menstrual cycle day 2- 3 at an initial dose of 300 IU/day.A daily administration of ganirelix (0.25 mg Orgalutran; Organon) was introduced when the leading follicle is near 13mm, and was repeated up to the time of hCG administration.Ovulation was triggered when the leading follicles reach 18-20mm and at least two follicles 17-18mm , HCG 10000 IU is used to trigger. Receives: Drug: Follitropin Beta;MSD; Drug: Ganirelix; Drug: hCG |
What is being measured
The primary outcome is the main question the study is designed to answer.
The number of oocytes retrieved by the IVG 36 hours after hCG administration
The total MII oocytes retrievedd
Measured: 36 hours after hCG administration
Secondary outcomes (3)
Clinical pregnancy rate
clinical pregnancy, defined as intrauterine pregnancy with a positive heartbeat at 6 weeks of gestation.Clinical pregnancy rate:Number of clinical pregnancies expressed per 100 initiated cycles, aspiration cycles, or embryo transfer cycles. When clinical pregnancy rates are given, the denominator must be specified.
Measured: 6weeks
ongoing pregnancy rate
ongoing pregnancy defined as an intact pregnancy at 12 weeks of gestation
Measured: 12weeks
Optimal number of embryo
According to the embryonic developmental rate and morphology, the high quality embryos were defined as the next day (D2) transplanted embryos reached 3 or 4 cells and the third day (D3) transplanted embryos reached 6 to 8 cells with morphological grade 1 or 2
Measured: 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2017
- Study start15 Nov 2017
- Primary completion18 Jun 2021
- Study completion18 Aug 2021
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 InfertilityStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 552 participants (actual)
Sponsor and investigators
- Lead sponsor
- Reproductive & Genetic Hospital of CITIC-Xiangya
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Fei Gong, Doctor, Study director, Reproductive & Genetic Hospital of CITIC-Xiangya
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03300518
- Sponsor's protocol ID
- MSD-MISP-ZX-01
- Status last verified
- Jan 2022
- First submitted
- 28 Sep 2017
- Last updated
- 11 Jan 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Zhang S, Tang Y, Wang X, Zong Y, Li X, Cai S, Ma H, Guo H, Song J, Lin G, Lu G, Gong F. Estrogen valerate pretreatment with the antagonist protocol does not increase oocyte retrieval in patients with low ovarian response: a randomized controlled trial. Hum Reprod. 2022 Jun 30;37(7):1431-1439. doi: 10.1093/humrep/deac081.
PubMed 35460400
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Study to Analysis the Effectiveness of Estradiol Valerate Pretreatment in Antagonist Protocol for Poor Ovarian Response Patient
- ClinicalTrials.gov ID
- NCT03300518
- Acronym / sponsor ID
- MSD-MISP-ZX-01
- Conditions
- Infertility
- Keywords
- GnRH antagonist, Estrogen pretreatment, Poor response patient
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 552 participants (actual)
- Lead sponsor
- Reproductive & Genetic Hospital of CITIC-XiangyaUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 15 Nov 2017 (actual)
- Primary completion
- 18 Jun 2021 (actual)
- Study completion
- 18 Aug 2021 (actual)
- First posted
- 3 Oct 2017 (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 purpose of study is to assess the efficacy of add-on estrogen pretreatment in GnRH antagonist protocol on oocyte retrieval as compared with GnRH antagonist protocol for patients with poor ovarian response Add-on estrogen pretreatment protocol is superior to none pretreatment GnRH antagonist protocol for the number of oocytes retrieval
Detailed description
Women of advanced maternal age seeking ART treatment are characterized as poor ovarian responders in the process of ovarian simulation. Poor response to ovarian stimulation causes high cycle cancellation rate and extremely low pregnancy rate.
More attention has been paid to the potential interest of steroid pretreatments in GnRH antagonist cycles; not only for scheduling the GnRH antagonist cycles, but also for synchronizing the follicular growth which may result in more oocytes retrieved. But available clinical results are controversial.
Previous studies have shown that utilizing the natural negative feedback of the hypothalamus-pituitary-ovary axis induced by estradiol valerate pretreatment effectively prevented inter-cycle increases in follicle-stimulating hormone, improved follicle synchronization, and resulted in a more coordinated follicular development, leading to the recovery of more mature oocytes. However none of the randomized controlled studies compared estradiol valerate pretreatment or not on treatment outcomes, ongoing pregnancy rate, directly on poor response patients using estradiol valerate pretreatment in 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 |
|---|---|---|
| pretreatment group | Other | Drug: Follitropin Beta;MSD, Drug: Ganirelix, Drug: hCG, Drug: estradiol valeratethe pretreatment group underwent a modified treatment protocol with pretreatment with estogen administering during the cycle preceding the IVF/ICSI cycle. daily dose of 4 mg (2 mg twice a day) estradiol valerate was given orally in the middle luteal phase which is confirmed seven days after ovulation monitoring by the ultrasound up to 2 days of the next menstrual cycle.Recombinant FSH (Puregon) was initiated on menstrual cycle day 2- 3 at an initial dose of 300 IU/day.A daily administration of ganirelix (0.25 mg Orgalutran; Organon) was introduced when the leading follicle is near 13mm, and was repeated up to the time of hCG administration.Ovulation was triggered when the leading follicles reach 18-20mm and at least two follicles 17-18mm , HCG 10000 IU is used to trigger. |
| control groups | Other | Drug: Follitropin Beta;MSD, Drug: Ganirelix, Drug: hCGIn the control groups standard GnRH-antagonist protocol was applied.Recombinant FSH (Puregon) was initiated on menstrual cycle day 2- 3 at an initial dose of 300 IU/day.A daily administration of ganirelix (0.25 mg Orgalutran; Organon) was introduced when the leading follicle is near 13mm, and was repeated up to the time of hCG administration.Ovulation was triggered when the leading follicles reach 18-20mm and at least two follicles 17-18mm , HCG 10000 IU is used to trigger. |
Who may qualify
- Ages
- 40 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- At least two of the following three features must be present:
Key exclusion criteria (7 listed)
- Age ≥45 years,
- Patients who conducted PGD/PGS, and donor egg cycles were excluded.
- Presence of unilateral ovary absence
- Abnormal uterine deformity or structure.
- Spontaneous abortion patients with three or more (including biochemical pregnancy abortion)
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 |
|---|---|---|
| Follitropin Beta;MSDAlso: PuregonPatients will start stimulation with a daily s.c. injection of follitropin beta( 300IU Puregonon;MSD) menstrual cycle day 2 or 3. | Drug | control groups, pretreatment group |
| GanirelixAlso: OrgalutranA daily administration of ganirelix (0.25 mg Orgalutran; MSD) was introduced when the leading follicle is near 13mm, and was repeated up to the time of hCG administration. | Drug | control groups, pretreatment group |
| hCGAlso: OvidrelOvulation was triggered when the leading follicles reach 18-20mm and at least two follicles 17-18mm , HCG 10000 IU is used to trigger | Drug | control groups, pretreatment group |
| estradiol valerateAlso: progynovaEstradiol valerate (progynova,Schering) daily dose of 4 mg (2 mg twice a day) was given orally, started 7 days before the presumed onset of menses and administered up to 2 days of the next menstrual cycle | Drug | pretreatment group |
Primary outcome
The number of oocytes retrieved by the IVG 36 hours after hCG administration
Time frame: 36 hours after hCG administration
The total MII oocytes retrievedd
3 secondary outcomes
Clinical pregnancy rate
Time frame: 6weeks
ongoing pregnancy rate
Time frame: 12weeks
Optimal number of embryo
Time frame: 1 week
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 11 Jan 2022.
- Derived from this study: PubMed 35460400Zhang S, Tang Y, Wang X, Zong Y, Li X, Cai S, Ma H, Guo H, Song J, Lin G, Lu G, Gong F. Estrogen valerate pretreatment with the antagonist protocol does not increase oocyte retrieval in patients with low ovarian response: a randomized controlled trial. Hum Reprod. 2022 Jun 30;37(7):1431-1439. doi: 10.1093/humrep/deac081.
- Individual participant dataSharing planned: Undecided
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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.
Fei Gong, Doctor study director
Reproductive & Genetic Hospital of CITIC-Xiangya
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Follitropin Beta;MSD, Ganirelix and hCG in people with Infertility, run by Reproductive & Genetic Hospital of CITIC-Xiangya at 1 site in China.
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 4 inclusion and 7 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 11 Jan 2022. 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 China. 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.
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?
The number of oocytes retrieved by the IVG 36 hours after hCG administration (time frame: 36 hours after hCG administration). 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 NCT03300518, 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 11 Jan 2022.