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Double Ovarian Stimulation as Accumulation Strategy for Older Infertile Patients With Suboptimal Ovarian Response

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ClinicalTrials.gov Identifier: NCT03400722
Recruitment Status : Unknown
Verified January 2018 by Nova Clinic, Russia.
Recruitment status was:  Recruiting
First Posted : January 17, 2018
Last Update Posted : January 17, 2018
Sponsor:
Information provided by (Responsible Party):
Nova Clinic, Russia

Brief 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. 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.


Condition or disease Intervention/treatment Phase
Infertility, Female Ovarian Stimulation In Vitro Fertilisation Drug: Pergoveris Drug: Clomiphene Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Double Ovarian Stimulation as Accumulation Strategy for Older Infertile Patients With Suboptimal Ovarian Response in Assisted Reproductive Treatment
Actual Study Start Date : December 1, 2017
Estimated Primary Completion Date : August 1, 2018
Estimated Study Completion Date : May 1, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Infertility
Drug Information available for: Clomifene

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.
Drug: Pergoveris
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:
  • antagonist of gonadotropin releasing hormone
  • agonist of gonadotropin releasing hormone

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.
Drug: Clomiphene
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:
  • Pergoveris
  • agonist of gonadotropin releasing hormone




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. total number of blastocyst per cycle [ Time Frame: up to 9 months ]
    evaluation the total number of blastocyst after double ovarian stimulation in one cycle

  2. Time until embryo transfer [ Time Frame: up to 9 months ]
    period from start double ovarian stimulation until embryo transfer

  3. number of cycles need to treat [ Time Frame: up to 9 months ]
    number of cycles with double ovarian stimulation required to obtain 3-5 blastocyst

  4. pregnancy rate [ Time Frame: up to 9 months ]
    pregnancy rate after embryo transfer of thawed blastocyst

  5. the birth rate [ Time Frame: up to 18 months ]
    the birth rate after embryo transfer



Information from the National Library of Medicine

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Ages Eligible for Study:   37 Years to 42 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 37 - 42 years of age
  2. BMI 18-30 kg\m2
  3. 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
  4. Informed consent

Exclusion Criteria:

  1. Medical contraindications for IVF
  2. Basal follicle stimulating hormone (FSH) more 15 IU/L
  3. Severe mail factor

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03400722


Contacts
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Contact: Irina Zorina, M.D.,Ph.D. +79263407621 irinazorina@yandex.ru
Contact: Irina Zorina, M.D.,Ph.D. +74952211188 i.zorina@nova-clinic.ru

Locations
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Russian Federation
Irina Zorina Recruiting
Moscow, Russian Federation, 119048
Contact: Irina Zorina, M.D.,Ph.D    +74992210688    irinazorina@yandex.ru   
Contact: Yulia Tsoraeva, M.D.    +74992210688    tsoraevadz@mail.ru   
Sponsors and Collaborators
Nova Clinic, Russia
Investigators
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Study Director: Konstantin Dancheev MEDINSERVIS LLC NOVA CLINIC
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Responsible Party: Nova Clinic, Russia
ClinicalTrials.gov Identifier: NCT03400722    
Other Study ID Numbers: NCT 03230763
First Posted: January 17, 2018    Key Record Dates
Last Update Posted: January 17, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Nova Clinic, Russia:
Suboptimal ovarian response
Ovarian Stimulation
Infertility, Female
In Vitro Fertilisation
Additional relevant MeSH terms:
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Infertility
Infertility, Female
Clomiphene
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Estrogen Antagonists
Hormone Antagonists
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators