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

Infertility, Female Clinical Trial

Official title:

Double Ovarian Stimulation as Accumulation Strategy for Older Infertile Patients With Suboptimal Ovarian Response in Assisted Reproductive Treatment

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03400722
• Other study ID #: NCT 03230763
• Status: Recruiting
• Phase: Phase 4
• First received: December 19, 2017
• Last updated: January 14, 2018
• Start date: December 1, 2017
• Est. completion date: May 1, 2019

Study information

• Verified date: January 2018
• Source: Nova Clinic, Russia
• Contact: Irina Zorina, M.D.,Ph.D.
• Phone: +79263407621
• Email: irinazorina[@]yandex.ru
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: May 1, 2019
• Est. primary completion date: August 1, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 37 Years to 42 Years

Eligibility

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

Related Conditions & MeSH terms

• In Vitro Fertilisation
• Infertility
• Infertility, Female
• Ovarian Stimulation

Intervention

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.
• 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.

Locations

Country	Name	City	State
Russian Federation	Irina Zorina	Moscow

Sponsors (1)

Lead Sponsor	Collaborator
Nova Clinic, Russia

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total number of retrieved oocytes per cycle	evaluation the total number of retrieved oocytes after double ovarian stimulation in one cycle	up to 9 months
Secondary	total number of blastocyst per cycle	evaluation the total number of blastocyst after double ovarian stimulation in one cycle	up to 9 months
Secondary	Time until embryo transfer	period from start double ovarian stimulation until embryo transfer	up to 9 months
Secondary	number of cycles need to treat	number of cycles with double ovarian stimulation required to obtain 3-5 blastocyst	up to 9 months
Secondary	pregnancy rate	pregnancy rate after embryo transfer of thawed blastocyst	up to 9 months
Secondary	the birth rate	the birth rate after embryo transfer	up to 18 months