Infertility, FemalePhase 4NCT03400722
Double Ovarian Stimulation as Accumulation Strategy for Older Infertile Patients With Suboptimal Ovarian Response
A Phase 4 study testing Pergoveris and Clomiphene in people with Infertility, Female and Ovarian Stimulation, run by Nova Clinic, Russia at 1 site in Russia.
Trial summary
Patients with infertility of the older age group of 37-42 years - a large cohort of patients of reproductive medicine. Two possible causes reduce their probability of pregnancy - an increasing age and a decrease of the ovarian reserve. Read more about this study
- Who is it for?
- Ages 37 to 42 years, women only
- Conditions the study is for
- Infertility, Female, Ovarian Stimulation, In Vitro Fertilisation
- What is being tested?
- Pergoveris and Clomiphene
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteRussia
- Study dates
- 1 Dec 2017to 1 May 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 37 to 42 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 37 - 42 years of age
- BMI 18-30 kg\m2
- Suboptimal ovarian responders with normal ovarian reserve: the number of antral follicles greater than 5 and AMH greater than 1.2 ng / ml, resulting in 4-9 oocytes after a standard ovarian stimulation, according Poseidon classification - group 2b
- Informed consent
Who cannot join
- Medical contraindications for IVF
- Basal follicle stimulating hormone (FSH) more 15 IU/L
- Severe mail factor
Trial locations and contacts
1 site in 1 country.
Russia1 site, 1 recruiting
- Recruiting
Irina Zorina
Moscow, 119048
Irina Zorina, M.D.,Ph.D, +74992210688, irinazorina@yandex.ru
Yulia Tsoraeva, M.D., +74992210688, tsoraevadz@mail.ru
About this study
Official title: Double Ovarian Stimulation as Accumulation Strategy for Older Infertile Patients With Suboptimal Ovarian Response in Assisted Reproductive Treatment
Patients with infertility of the older age group of 37-42 years - a large cohort of patients of reproductive medicine. Two possible causes reduce their probability of pregnancy - an increasing age and a decrease of the ovarian reserve. In these conditions, the early receipt of embryos for future transfer can serve as a correct strategy for treating infertility in this category of patients. According to statistical data, patients of the 37-42-year-old age group need 3-5 blastocysts, out of them 1-2 euploid to achieve pregnancy.
The POSEIDON group of researchers identified a group of 2b patients with a suboptimal response to the induction of superovulation in IVF programs - patients older than 35 years with a normal ovarian reserve (the number of antral follicles greater than 5 and Anti-Müllerian hormone (AMH) greater than 1.2 ng / ml), resulting in 4-9 oocytes after a standard ovarian stimulation.
Read more
In this situation standard stimulation protocols can stretch the process of obtaining embryos indefinitely, during which the patient will move to another age category with a decrease in the likelihood of pregnancy.
Thus, these patients are shown the fastest reception of oocytes and the accumulation of embryos, which can be done using double ovarian stimulation in the same menstrual cycle.
The aim of the study is to compare the different schemes of double stimulation in patients with infertility of the older age group of 37-42 years with the preceding suboptimal response.
Group 1 - patients of the DUOSTIM group. Group 2 - Patients of the Shanghai Protocol.
The investigated parameters - primary outcome measures: total number of retrieved oocytes per cycle, secondary outcome measures: total number of blastocyst per cycle, number of cycles with double ovarian stimulation required to obtain 3-5 blastocyst, time until embryo transfer, pregnancy rate and birth rate This is a prospective randomized non-blinded clinical study.
Read the detailed description
The aim of the study is to compare the different schemes of double stimulation in patients with infertility of the older age group of 37-42 years with the preceding suboptimal response.
Materials and methods. Patients with preserved ovarian reserve of 37-42 years old, who had the history of standard stimulation in IVF programs, which produce less 4-7 oocytes. Patients will be randomised in two groups. Group 1 - patients of the double ovarian stimulation in the same cycle with recombinant gonadotropin (DUOSTIM group). Group 2 - patients of the double ovarian stimulation in the same cycle with clomifen and recombinant gonadotropin (modified Shanghai Protocol).
The stimulation protocol in the Group 1 - Follitropin and Lutropin Alfa (Pergoveris) 150 -300 IU start from day 2 of the cycle up to the day of trigger, gonadotropin-releasing hormone (GnRH) antagonist 0,25 mg start from day 7-8 of the cycle up to the day of trigger, final trigger of ovarian stimulation - gonadotropin-releasing hormone agonist (GnRH-a) 0,2 mg, oocyte retrieval 35 hours after trigger, stop period for 5 days, after stop period start Pergoveris 150 - 300 IU start up to the day of trigger, GnRH antagonist 0,25 mg start from day 6 of ovarian stimulation up to the day of trigger, final trigger of ovarian stimulation - GnRH-a 0,2 mg, oocyte retrieval 35 hours after trigger.
After oocyte retrieval fertilization will be carried out by invitro insemination (IVI) or intracytoplasmic sperm injection (ICSI), the development of embryos will be carried out up to blastocyst stage, then blastocyst vitrification will be performed. The cycles of double ovarian stimulation will be performed until the patient will have not less than 3-5 blastocysts. Then the embryo accumulation process will be completed and the unfrozen embryos transferred in the hormonal replacement cycle or natural ovulatory cycle.
The stimulation protocol in the Group 2 - Clomiphene 50 mg start from day 2-3 of the cycle up to the day of trigger, Pergoveris 150 IU - 6,8, 10 days of the cycle, final trigger of ovarian stimulation - GnRH-a 0,2 mg, oocyte retrieval 35 hours after trigger, after stop period for 2-3 days start Pergoveris 150 - 300 IU up to the day of trigger, final trigger of ovarian stimulation - GnRH-a 0,2 mg, oocyte retrieval 35 hours after trigger. After oocyte retrieval fertilization will be carried out by IVI or ICSI, the development of embryos will be carried out up to blastocyst stage, then blastocyst vitrification will be performed. The cycles of double ovarian stimulation will be performed until the patient will have not less than 3-5 blastocysts. Then the embryo accumulation process will be completed and the unfrozen embryos transferred in the hormonal replacement cycle or natural ovulatory cycle.
- Being tested
- Pergoveris, Clomiphene
- Keywords
- Suboptimal ovarian response, Ovarian Stimulation, Infertility, Female, In Vitro Fertilisation
- Medical subject headings
- Infertility, Female
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PergoverisDrug
Also called antagonist of gonadotropin releasing hormone, agonist of gonadotropin releasing hormone
Two controlled ovarian stimulation within the same menstrual cycle. It will be followed by ovarian puncture, fertilisation of oocyte by IVI or ICSI, blastocyst vitrification. If there are 3-5 blastocysts, the embryo accumulation process will be completed and the unfrozen embryos transferred.
ClomipheneDrug
Also called Pergoveris, agonist of gonadotropin releasing hormone
Two controlled ovarian stimulation within the same menstrual cycle. It will be followed by ovarian puncture, fertilisation of oocyte by IVI or ICSI, blastocyst vitrification. If there are 3-5 blastocysts, the embryo accumulation process will be completed and the unfrozen embryos transferred.
| Study group | Role | What they receive |
|---|---|---|
| DUOSTIM group | Experimental | Pergoveris 150 -300 IU start from day 2 of the cycle up to the day of trigger, GnRH antagonist 0,25 mg start from day 7-8 of the cycle up to the day of trigger, final trigger of ovarian stimulation - GnRH-a 0,2 mg, oocyte retrieval 35 hours after trigger, stop period for 5 days, after stop period start Pergoveris 150 - 300 IU start up to the day of trigger, GnRH antagonist 0,25 mg start from day 6 of ovarian stimulation up to the day of trigger, final trigger of ovarian stimulation - GnRH-a 0,2 mg, oocyte retrieval 35 hours after trigger. After oocyte retrieval fertilization will be carried out by IVI or ICSI, the development of embryos will be carried out up to blastocyst stage, then blastocyst vitrification will be performed. Receives: Drug: Pergoveris |
| Modified Shanghai Protocol group | Experimental | Clomiphene 50 mg start from day 2-3 of the cycle up to the day of trigger, Pergoveris 150 - 300 IU - 6,8, 10 days of the cycle, final trigger of ovarian stimulation - GnRH-a 0,2 mg, oocyte retrieval 35 hours after trigger, after stop period for 2-3 days start Pergoveris 150 - 300 IU up to the day of trigger, final trigger of ovarian stimulation - GnRH-a 0,2 mg, oocyte retrieval 35 hours after trigger. After oocyte retrieval fertilization will be carried out by IVI or ICSI, the development of embryos will be carried out up to blastocyst stage, then blastocyst vitrification will be performed. Receives: Drug: Clomiphene |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total number of retrieved oocytes per cycle
evaluation the total number of retrieved oocytes after double ovarian stimulation in one cycle
Measured: up to 9 months
Secondary outcomes (5)
total number of blastocyst per cycle
evaluation the total number of blastocyst after double ovarian stimulation in one cycle
Measured: up to 9 months
Time until embryo transfer
period from start double ovarian stimulation until embryo transfer
Measured: up to 9 months
number of cycles need to treat
number of cycles with double ovarian stimulation required to obtain 3-5 blastocyst
Measured: up to 9 months
pregnancy rate
pregnancy rate after embryo transfer of thawed blastocyst
Measured: up to 9 months
the birth rate
the birth rate after embryo transfer
Measured: up to 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jan 2018
- Study start1 Dec 2017
- Primary completion1 Aug 2018 (estimated)
- Study completion1 May 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Infertility, FemaleStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nova Clinic, Russia
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Konstantin Dancheev, Study director, MEDINSERVIS LLC NOVA CLINIC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03400722
- Sponsor's protocol ID
- NCT 03230763
- Status last verified
- Jan 2018
- First submitted
- 19 Dec 2017
- Last updated
- 17 Jan 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 17 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double Ovarian Stimulation as Accumulation Strategy for Older Infertile Patients With Suboptimal Ovarian Response in Assisted Reproductive Treatment
- ClinicalTrials.gov ID
- NCT03400722
- Acronym / sponsor ID
- NCT 03230763
- Keywords
- Suboptimal ovarian response, Ovarian Stimulation, Infertility, Female, In Vitro Fertilisation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Nova Clinic, RussiaUniversity, hospital or other
- Study start
- 1 Dec 2017 (actual)
- Primary completion
- 1 Aug 2018 (estimated)
- Study completion
- 1 May 2019 (estimated)
- First posted
- 17 Jan 2018 (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.
Patients with infertility of the older age group of 37-42 years - a large cohort of patients of reproductive medicine. Two possible causes reduce their probability of pregnancy - an increasing age and a decrease of the ovarian reserve. In these conditions, the early receipt of embryos for future transfer can serve as a correct strategy for treating infertility in this category of patients. According to statistical data, patients of the 37-42-year-old age group need 3-5 blastocysts, out of them 1-2 euploid to achieve pregnancy.
The POSEIDON group of researchers identified a group of 2b patients with a suboptimal response to the induction of superovulation in IVF programs - patients older than 35 years with a normal ovarian reserve (the number of antral follicles greater than 5 and Anti-Müllerian hormone (AMH) greater than 1.2 ng / ml), resulting in 4-9 oocytes after a standard ovarian stimulation.
In this situation standard stimulation protocols can stretch the process of obtaining embryos indefinitely, during which the patient will move to another age category with a decrease in the likelihood of pregnancy.
Thus, these patients are shown the fastest reception of oocytes and the accumulation of embryos, which can be done using double ovarian stimulation in the same menstrual cycle.
The aim of the study is to compare the different schemes of double stimulation in patients with infertility of the older age group of 37-42 years with the preceding suboptimal response.
Group 1 - patients of the DUOSTIM group. Group 2 - Patients of the Shanghai Protocol.
The investigated parameters - primary outcome measures: total number of retrieved oocytes per cycle, secondary outcome measures: total number of blastocyst per cycle, number of cycles with double ovarian stimulation required to obtain 3-5 blastocyst, time until embryo transfer, pregnancy rate and birth rate This is a prospective randomized non-blinded clinical study.
Detailed description
The aim of the study is to compare the different schemes of double stimulation in patients with infertility of the older age group of 37-42 years with the preceding suboptimal response.
Materials and methods. Patients with preserved ovarian reserve of 37-42 years old, who had the history of standard stimulation in IVF programs, which produce less 4-7 oocytes. Patients will be randomised in two groups. Group 1 - patients of the double ovarian stimulation in the same cycle with recombinant gonadotropin (DUOSTIM group). Group 2 - patients of the double ovarian stimulation in the same cycle with clomifen and recombinant gonadotropin (modified Shanghai Protocol).
The stimulation protocol in the Group 1 - Follitropin and Lutropin Alfa (Pergoveris) 150 -300 IU start from day 2 of the cycle up to the day of trigger, gonadotropin-releasing hormone (GnRH) antagonist 0,25 mg start from day 7-8 of the cycle up to the day of trigger, final trigger of ovarian stimulation - gonadotropin-releasing hormone agonist (GnRH-a) 0,2 mg, oocyte retrieval 35 hours after trigger, stop period for 5 days, after stop period start Pergoveris 150 - 300 IU start up to the day of trigger, GnRH antagonist 0,25 mg start from day 6 of ovarian stimulation up to the day of trigger, final trigger of ovarian stimulation - GnRH-a 0,2 mg, oocyte retrieval 35 hours after trigger.
After oocyte retrieval fertilization will be carried out by invitro insemination (IVI) or intracytoplasmic sperm injection (ICSI), the development of embryos will be carried out up to blastocyst stage, then blastocyst vitrification will be performed. The cycles of double ovarian stimulation will be performed until the patient will have not less than 3-5 blastocysts. Then the embryo accumulation process will be completed and the unfrozen embryos transferred in the hormonal replacement cycle or natural ovulatory cycle.
The stimulation protocol in the Group 2 - Clomiphene 50 mg start from day 2-3 of the cycle up to the day of trigger, Pergoveris 150 IU - 6,8, 10 days of the cycle, final trigger of ovarian stimulation - GnRH-a 0,2 mg, oocyte retrieval 35 hours after trigger, after stop period for 2-3 days start Pergoveris 150 - 300 IU up to the day of trigger, final trigger of ovarian stimulation - GnRH-a 0,2 mg, oocyte retrieval 35 hours after trigger. After oocyte retrieval fertilization will be carried out by IVI or ICSI, the development of embryos will be carried out up to blastocyst stage, then blastocyst vitrification will be performed. The cycles of double ovarian stimulation will be performed until the patient will have not less than 3-5 blastocysts. Then the embryo accumulation process will be completed and the unfrozen embryos transferred in the hormonal replacement cycle or natural ovulatory cycle.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DUOSTIM group | Experimental | Drug: PergoverisPergoveris 150 -300 IU start from day 2 of the cycle up to the day of trigger, GnRH antagonist 0,25 mg start from day 7-8 of the cycle up to the day of trigger, final trigger of ovarian stimulation - GnRH-a 0,2 mg, oocyte retrieval 35 hours after trigger, stop period for 5 days, after stop period start Pergoveris 150 - 300 IU start up to the day of trigger, GnRH antagonist 0,25 mg start from day 6 of ovarian stimulation up to the day of trigger, final trigger of ovarian stimulation - GnRH-a 0,2 mg, oocyte retrieval 35 hours after trigger. After oocyte retrieval fertilization will be carried out by IVI or ICSI, the development of embryos will be carried out up to blastocyst stage, then blastocyst vitrification will be performed. |
| Modified Shanghai Protocol group | Experimental | Drug: ClomipheneClomiphene 50 mg start from day 2-3 of the cycle up to the day of trigger, Pergoveris 150 - 300 IU - 6,8, 10 days of the cycle, final trigger of ovarian stimulation - GnRH-a 0,2 mg, oocyte retrieval 35 hours after trigger, after stop period for 2-3 days start Pergoveris 150 - 300 IU up to the day of trigger, final trigger of ovarian stimulation - GnRH-a 0,2 mg, oocyte retrieval 35 hours after trigger. After oocyte retrieval fertilization will be carried out by IVI or ICSI, the development of embryos will be carried out up to blastocyst stage, then blastocyst vitrification will be performed. |
Who may qualify
- Ages
- 37 to 42 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 37 - 42 years of age
- BMI 18-30 kg\m2
- Suboptimal ovarian responders with normal ovarian reserve: the number of antral follicles greater than 5 and AMH greater than 1.2 ng / ml, resulting in 4-9 oocytes after a standard ovarian stimulation, according Poseidon classification - group 2b
- Informed consent
Key exclusion criteria (3 listed)
- Medical contraindications for IVF
- Basal follicle stimulating hormone (FSH) more 15 IU/L
- Severe mail factor
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 |
|---|---|---|
| PergoverisAlso: antagonist of gonadotropin releasing hormone, agonist of gonadotropin releasing hormoneTwo controlled ovarian stimulation within the same menstrual cycle. It will be followed by ovarian puncture, fertilisation of oocyte by IVI or ICSI, blastocyst vitrification. If there are 3-5 blastocysts, the embryo accumulation process will be completed and the unfrozen embryos transferred. | Drug | DUOSTIM group |
| ClomipheneAlso: Pergoveris, agonist of gonadotropin releasing hormoneTwo controlled ovarian stimulation within the same menstrual cycle. It will be followed by ovarian puncture, fertilisation of oocyte by IVI or ICSI, blastocyst vitrification. If there are 3-5 blastocysts, the embryo accumulation process will be completed and the unfrozen embryos transferred. | Drug | Modified Shanghai Protocol group |
Primary outcome
Total number of retrieved oocytes per cycle
Time frame: up to 9 months
evaluation the total number of retrieved oocytes after double ovarian stimulation in one cycle
5 secondary outcomes
total number of blastocyst per cycle
Time frame: up to 9 months
Time until embryo transfer
Time frame: up to 9 months
number of cycles need to treat
Time frame: up to 9 months
pregnancy rate
Time frame: up to 9 months
the birth rate
Time frame: up to 18 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jan 2018.
- 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.
Konstantin Dancheev study director
MEDINSERVIS LLC NOVA CLINIC
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 Pergoveris and Clomiphene in people with Infertility, Female and Ovarian Stimulation, run by Nova Clinic, Russia at 1 site in Russia.
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 3 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: status not confirmed, as of the sponsor's last update on 17 Jan 2018. 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 Russia. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Irina Zorina, M.D.,Ph.D. (+79263407621, irinazorina@yandex.ru), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total number of retrieved oocytes per cycle (time frame: up to 9 months). 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 17 Jan 2018.