- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03400722
Double Ovarian Stimulation as Accumulation Strategy for Older Infertile Patients With Suboptimal Ovarian Response
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.
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.
Study Overview
Status
Intervention / Treatment
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 Type
Enrollment (Anticipated)
Phase
- Phase 4
Contacts and Locations
Study Contact
- Name: Irina Zorina, M.D.,Ph.D.
- Phone Number: +79263407621
- Email: irinazorina@yandex.ru
Study Contact Backup
- Name: Irina Zorina, M.D.,Ph.D.
- Phone Number: +74952211188
- Email: i.zorina@nova-clinic.ru
Study Locations
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Moscow, Russian Federation, 119048
- Recruiting
- Irina Zorina
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Contact:
- Irina Zorina, M.D.,Ph.D
- Phone Number: +74992210688
- Email: irinazorina@yandex.ru
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Contact:
- Yulia Tsoraeva, M.D.
- Phone Number: +74992210688
- Email: tsoraevadz@mail.ru
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- Medical contraindications for IVF
- Basal follicle stimulating hormone (FSH) more 15 IU/L
- Severe mail factor
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: DUOSTIM group
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.
|
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.
Other Names:
|
Experimental: Modified Shanghai Protocol group
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.
|
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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Total number of retrieved oocytes per cycle
Time Frame: up to 9 months
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evaluation the total number of retrieved oocytes after double ovarian stimulation in one cycle
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up to 9 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
total number of blastocyst per cycle
Time Frame: up to 9 months
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evaluation the total number of blastocyst after double ovarian stimulation in one cycle
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up to 9 months
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Time until embryo transfer
Time Frame: up to 9 months
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period from start double ovarian stimulation until embryo transfer
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up to 9 months
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number of cycles need to treat
Time Frame: up to 9 months
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number of cycles with double ovarian stimulation required to obtain 3-5 blastocyst
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up to 9 months
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pregnancy rate
Time Frame: up to 9 months
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pregnancy rate after embryo transfer of thawed blastocyst
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up to 9 months
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the birth rate
Time Frame: up to 18 months
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the birth rate after embryo transfer
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up to 18 months
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Konstantin Dancheev, MEDINSERVIS LLC NOVA CLINIC
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Infertility
- Infertility, Female
- Physiological Effects of Drugs
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Hormone Antagonists
- Estrogen Antagonists
- Reproductive Control Agents
- Fertility Agents, Female
- Fertility Agents
- Selective Estrogen Receptor Modulators
- Estrogen Receptor Modulators
- Hormones
- Clomiphene
Other Study ID Numbers
- NCT 03230763
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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