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The Four Methods of Ovarian Stimulation in Patients With Polycystic Ovarian Syndrome

Primary Purpose

Polycystic Ovary Syndrome, Ovarian Hyperstimulation Syndrome

Status
Completed
Phase
Not Applicable
Locations
Iran, Islamic Republic of
Study Type
Interventional
Intervention
Minimal ovarian stimulation
Sponsored by
Royan Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Polycystic Ovary Syndrome

Eligibility Criteria

20 Years - 38 Years (Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

  1. Infertile women with polycystic ovary syndrome based on Rotterdam criterion
  2. 20<Age<38
  3. BMI<30
  4. Non recurrent miscarriage
  5. Non endocrine, hematologic and autoimmune disorders
  6. Non chromosomal and genetic abnormalities
  7. Non uterine anomalies, surgical history, endometriosis, adenomyosis, hydrosalpinx, uterine fibroids
  8. Non azoospermia

Exclusion Criteria:

1. Patient's tendency for withdrawal

Sites / Locations

  • Royan Institute

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

No Intervention

No Intervention

Arm Label

Minimal ovarian stimulation with rec-FSH

Minimal ovarian stimulation with HMG

Mild ovarian stimulation with rec-FSH

Mild ovarian stimulation with HMG

Arm Description

The group of minimal ovarian stimulation that will receive 100 mg clomiphene citrate every day from Day 3 to Day 7 of the menstrual cycle and then will be treated with 150 International Unit (IU) Gonal-f (Follitropin alfa, Merck Serono, Germany) after the seventh day.

The group of minimal ovarian stimulation that will receive 100 mg clomiphene citrate every day from Day 3 to Day 7 of the menstrual cycle and then will be treated with 150 IU Merional (Highly Purified Menotropin، IBSA، Switzerland) after the seventh day.

The group of mild ovarian stimulation that will receive 150 IU Gonal-f (Follitropin alfa, Merck Serono, Germany) daily from Day 3 of the menstrual cycle.

The group of mild ovarian stimulation that will receive 150 IU Merional (Highly Purified Menotropin، IBSA، Switzerland) daily from Day 3 of the menstrual cycle.

Outcomes

Primary Outcome Measures

Fertilization rate
The ratio of 2 pronuclear to total number of injected oocytes.
Implantation rate
The ratio of total number of observed gestational sacs to total number of transferred embryos.
Clinical pregnancy rate
The observation of gestational sac with heart beat by using trans-vaginal ultrasound.

Secondary Outcome Measures

ovarian hyper stimulation syndrome (OHSS) rate
Total number of cases with symptoms of ovarian hyper-stimulation syndrome.
Total number of retrieved oocytes
Total number of obtained oocytes which reported by embryologist.
Quality of retrieved oocytes
Total number of Meta-phase II oocytes which reported by embryologist.

Full Information

First Posted
February 25, 2019
Last Updated
April 18, 2021
Sponsor
Royan Institute
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1. Study Identification

Unique Protocol Identification Number
NCT03876145
Brief Title
The Four Methods of Ovarian Stimulation in Patients With Polycystic Ovarian Syndrome
Official Title
A Comparison of Four Methods of Ovarian Stimulation With GnRH Antagonist in Patients With Polycystic Ovarian Syndrome in Royan Institute; A Randomized Controlled Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
November 12, 2016 (Actual)
Primary Completion Date
May 5, 2019 (Actual)
Study Completion Date
November 20, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Royan Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study is a randomized controlled clinical trial to compare the pregnancy outcomes of mild and minimal stimulation in infertile women with polycystic ovarian syndrome. The study population consisted of all infertile women with polycystic ovary syndrome based on Rotterdam criteria who have not succeed to achieve fertility despite multiple treatments such as drug therapy, laparoscopic surgery, and the frequent failure of induction therapy using gonadotropins and are now candidate for in vitro fertilization (IVF) or intra cytoplasmic sperm injection (ICSI) in Reproductive Biomedicine Research Center, Royan institute, Tehran Iran.
Detailed Description
An overview of the history of assisted reproductive technologies such as IVF and ICSI that are based on the process of ovulation stimulation, suggests that although this process was initially welcomed with the aim of achieving a large number of oocytes and embryos, consequences such as low quality of obtained oocytes and embryos, failure in achieving the desired results in fertility of treated patients, and the incidence of adverse effects such as ovarian hyper stimulation syndrome have made researchers re-examine the process of ovulation stimulation. Hence, mild ovulation stimulation method has been introduced to the field of assisted reproductive techniques (ART) in recent years. This method includes the prescription of low doses of gonadotropins or shorter duration of its administration in the ovulation stimulation cycle. Mild ovulation method has advantages such as reduction of the physical, mental, and financial risks of treatment which can improve the quality assisted reproductive services provided for infertile couples. Several studies have confirmed the efficiency of this method of ovulation stimulation as a way for improving the quality of the ovulation process and achieving desirable results in fertility. However, the important and interesting point in studies conducted in this area, particularly on IVF and ICSI cycles, is that the application of this method has been mostly investigated in normal populations and, after the approval of its efficiency, it has been recommended to be used in patients with poor or high ovarian response. It should be also mentioned that efficiency of this method in patients with poor ovarian response has been evaluated in a few studies, while in patients with high ovarian response such as those suffering from polycystic ovary syndrome, only few studies have been conducted in patients with a history of ovarian hyper stimulation syndrome. On the other hand, in many cases, the efficiency of mild ovulation stimulation, in which lower doses or shorter durations of gonadotropin administration are desired, has been investigated, and the application of minimal ovulation stimulation method, in which the use of clomiphene citrate is also included besides lower doses or shorter durations of gonadotropin administration, has been studied in a few cases. In addition to the dose and duration of gonadotropin administration, another important point in achieving the desired results of treatment using the ovulation stimulation cycles is the type of gonadotropin. The studies conducted on the comparison of recombinant-FSH (rec-FSH) and Human Menopausal Gonadotropin (HMG) types of gonadotropin indicate the superiority of HMG gonadotropins, as the results show that the administration of HMG gonadotropins will lead to achieving fewer but high quality oocytes and embryos. By contrast, rec-FSH application puts the patients at increased risk of ovarian hyper stimulation syndrome. However, the interesting and important point in most of these studies is that this comparison has been drawn in long-term treatment cycles, while few studies have been conducted on antagonist treatment cycles which do not fully corroborate the results obtained from long-term cycles. According to what mentioned above, the present research aims to study the efficiency of minimal ovulation stimulation method in the treatment of infertile patients with poly cystic ovarian syndrome (PCOS) and also the effect of gonadotropin type on treatment cycles with antagonist gonadotropin-releasing hormone (GnRH). It is hoped that the findings of the present research provide solutions for improving the quality of infertility treatment in PCOS patients, who currently undergo IVF or ICSI as a last resort.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polycystic Ovary Syndrome, Ovarian Hyperstimulation Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Minimal ovarian stimulation with rec-FSH
Arm Type
Experimental
Arm Description
The group of minimal ovarian stimulation that will receive 100 mg clomiphene citrate every day from Day 3 to Day 7 of the menstrual cycle and then will be treated with 150 International Unit (IU) Gonal-f (Follitropin alfa, Merck Serono, Germany) after the seventh day.
Arm Title
Minimal ovarian stimulation with HMG
Arm Type
Experimental
Arm Description
The group of minimal ovarian stimulation that will receive 100 mg clomiphene citrate every day from Day 3 to Day 7 of the menstrual cycle and then will be treated with 150 IU Merional (Highly Purified Menotropin، IBSA، Switzerland) after the seventh day.
Arm Title
Mild ovarian stimulation with rec-FSH
Arm Type
No Intervention
Arm Description
The group of mild ovarian stimulation that will receive 150 IU Gonal-f (Follitropin alfa, Merck Serono, Germany) daily from Day 3 of the menstrual cycle.
Arm Title
Mild ovarian stimulation with HMG
Arm Type
No Intervention
Arm Description
The group of mild ovarian stimulation that will receive 150 IU Merional (Highly Purified Menotropin، IBSA، Switzerland) daily from Day 3 of the menstrual cycle.
Intervention Type
Other
Intervention Name(s)
Minimal ovarian stimulation
Intervention Description
After obtaining informed consent to participate in the study, the subjects will be randomly divided into the following 4 groups: The group of minimal ovarian stimulation with rec-FSH or HMG. The group of mild ovarian stimulation with rec-FSH or HMG. In all 4 experimental groups, after reaching at least three follicles the size of 12 millimeters (mm), daily administration of 0.25 milligram (mg) Cetrotide (antagonist GnRH) will be started and after reaching at least three follicles the size of 17 mm, 500 microgram Ovitrelle (recombinant Human curionic gonadotropin) will be prescribed. 36 hours later, ovulation process will be done. On the day of Ovitrelle administration, serum levels of estradiol and progesterone will be also evaluated. Based on the patient's condition and the quality of obtained oocytes and embryos, 2 embryos will be transferred.
Primary Outcome Measure Information:
Title
Fertilization rate
Description
The ratio of 2 pronuclear to total number of injected oocytes.
Time Frame
16-18 hours after start of IVF or ICSI, which occurs on day of oocyte pick-up (34-36 hours after hCG administration [approximately Stimulation Day 10]).
Title
Implantation rate
Description
The ratio of total number of observed gestational sacs to total number of transferred embryos.
Time Frame
4 weeks after embryo transfer
Title
Clinical pregnancy rate
Description
The observation of gestational sac with heart beat by using trans-vaginal ultrasound.
Time Frame
4 weeks after embryo transfer
Secondary Outcome Measure Information:
Title
ovarian hyper stimulation syndrome (OHSS) rate
Description
Total number of cases with symptoms of ovarian hyper-stimulation syndrome.
Time Frame
Up to approximately 2 month after oocyte pick-up (34-36 hours after hCG administration [approximately Stimulation Day 10]).
Title
Total number of retrieved oocytes
Description
Total number of obtained oocytes which reported by embryologist.
Time Frame
Day of oocyte pick-up, 34-36 hours after human curionic gonadotropin (hCG) administration (approximately Stimulation Day 10).
Title
Quality of retrieved oocytes
Description
Total number of Meta-phase II oocytes which reported by embryologist.
Time Frame
Day of oocyte pick-up, 34-36 hours after hCG administration (approximately Stimulation Day 10).

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
38 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Infertile women with polycystic ovary syndrome based on Rotterdam criterion 20<Age<38 BMI<30 Non recurrent miscarriage Non endocrine, hematologic and autoimmune disorders Non chromosomal and genetic abnormalities Non uterine anomalies, surgical history, endometriosis, adenomyosis, hydrosalpinx, uterine fibroids Non azoospermia Exclusion Criteria: 1. Patient's tendency for withdrawal
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Firoozeh Ghaffari, M.D.
Organizational Affiliation
Department of Endocrinology and Female Infertility, ACECR, Tehran, Iran.
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Azar Yahyaei, M.Sc.
Organizational Affiliation
Department of Endocrinology and Female Infertility, ACECR, Tehran, Iran.
Official's Role
Principal Investigator
Facility Information:
Facility Name
Royan Institute
City
Tehran
ZIP/Postal Code
16635-148
Country
Iran, Islamic Republic of

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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The Four Methods of Ovarian Stimulation in Patients With Polycystic Ovarian Syndrome

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