Polycystic Ovary SyndromeNCT03876145
The Four Methods of Ovarian Stimulation in Patients With Polycystic Ovarian Syndrome
A study testing Minimal ovarian stimulation in people with Polycystic Ovary Syndrome and Ovarian Hyperstimulation Syndrome, run by Royan Institute at 1 site in Iran.
Trial 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… Read more about this study
- Who is it for?
- Ages 20 to 38 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Polycystic Ovary Syndrome, Ovarian Hyperstimulation Syndrome
- What is being tested?
- Minimal ovarian stimulation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteIran
- Study dates
- 12 Nov 2016to 20 Nov 2020
- Phase
- Interventional
- 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 20 to 38 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 1. Patient's tendency for withdrawal
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Being tested
- Minimal ovarian stimulation
- Medical subject headings
- Polycystic Ovary Syndrome, Ovarian Hyperstimulation Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Minimal ovarian stimulationOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Minimal ovarian stimulation with rec-FSH | Experimental | 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. Receives: Other: Minimal ovarian stimulation |
| Minimal ovarian stimulation with HMG | Experimental | 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. Receives: Other: Minimal ovarian stimulation |
| Mild ovarian stimulation with rec-FSH | No intervention | 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. |
| Mild ovarian stimulation with HMG | No intervention | 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fertilization rate
The ratio of 2 pronuclear to total number of injected oocytes.
Measured: 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]).
Implantation rate
The ratio of total number of observed gestational sacs to total number of transferred embryos.
Measured: 4 weeks after embryo transfer
Clinical pregnancy rate
The observation of gestational sac with heart beat by using trans-vaginal ultrasound.
Measured: 4 weeks after embryo transfer
Secondary outcomes (3)
ovarian hyper stimulation syndrome (OHSS) rate
Total number of cases with symptoms of ovarian hyper-stimulation syndrome.
Measured: Up to approximately 2 month after oocyte pick-up (34-36 hours after hCG administration [approximately Stimulation Day 10]).
Total number of retrieved oocytes
Total number of obtained oocytes which reported by embryologist.
Measured: Day of oocyte pick-up, 34-36 hours after human curionic gonadotropin (hCG) administration (approximately Stimulation Day 10).
Quality of retrieved oocytes
Total number of Meta-phase II oocytes which reported by embryologist.
Measured: Day of oocyte pick-up, 34-36 hours after hCG administration (approximately Stimulation Day 10).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2019
- Study start12 Nov 2016
- Primary completion5 May 2019
- Study completion20 Nov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Polycystic Ovary SyndromeStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Royan Institute
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Firoozeh Ghaffari, M.D., Study director, Department of Endocrinology and Female Infertility, ACECR, Tehran, Iran.Azar Yahyaei, M.Sc., Principal investigator, Department of Endocrinology and Female Infertility, ACECR, Tehran, Iran.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03876145
- Sponsor's protocol ID
- Royan-Female Infertility
- Status last verified
- Feb 2019
- First submitted
- 25 Feb 2019
- Last updated
- 20 Apr 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Yahyaei A, Vesali S, Ghaffari F. Introduce an optimal method of ovarian stimulation in the polycystic ovarian syndrome affected: a randomized controlled trial. BMC Womens Health. 2023 Jun 20;23(1):323. doi: 10.1186/s12905-023-02473-2.
PubMed 37340371
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03876145
- Acronym / sponsor ID
- Royan-Female Infertility
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Royan InstituteOther government
- Study start
- 12 Nov 2016 (actual)
- Primary completion
- 5 May 2019 (actual)
- Study completion
- 20 Nov 2020 (actual)
- First posted
- 15 Mar 2019 (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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Minimal ovarian stimulation with rec-FSH | Experimental | Other: Minimal ovarian stimulationThe 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. |
| Minimal ovarian stimulation with HMG | Experimental | Other: Minimal ovarian stimulationThe 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. |
| Mild ovarian stimulation with rec-FSH | No intervention | –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. |
| Mild ovarian stimulation with HMG | No intervention | –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. |
Who may qualify
- Ages
- 20 to 38 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Infertile women with polycystic ovary syndrome based on Rotterdam criterion
- 20<Age<38
- BMI<30
- Non recurrent miscarriage
- Non endocrine, hematologic and autoimmune disorders
Key exclusion criteria (1 listed)
- 1. Patient's tendency for withdrawal
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 |
|---|---|---|
| Minimal ovarian stimulationAfter 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. | Other | Minimal ovarian stimulation with HMG, Minimal ovarian stimulation with rec-FSH |
Primary outcome
Fertilization rate
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]).
The ratio of 2 pronuclear to total number of injected oocytes.
Implantation rate
Time frame: 4 weeks after embryo transfer
The ratio of total number of observed gestational sacs to total number of transferred embryos.
Clinical pregnancy rate
Time frame: 4 weeks after embryo transfer
The observation of gestational sac with heart beat by using trans-vaginal ultrasound.
3 secondary outcomes
ovarian hyper stimulation syndrome (OHSS) rate
Time frame: Up to approximately 2 month after oocyte pick-up (34-36 hours after hCG administration [approximately Stimulation Day 10]).
Total number of retrieved oocytes
Time frame: Day of oocyte pick-up, 34-36 hours after human curionic gonadotropin (hCG) administration (approximately Stimulation Day 10).
Quality of retrieved oocytes
Time frame: Day of oocyte pick-up, 34-36 hours after hCG administration (approximately Stimulation Day 10).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2021.
- Derived from this study: PubMed 37340371Yahyaei A, Vesali S, Ghaffari F. Introduce an optimal method of ovarian stimulation in the polycystic ovarian syndrome affected: a randomized controlled trial. BMC Womens Health. 2023 Jun 20;23(1):323. doi: 10.1186/s12905-023-02473-2.
- 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.
Firoozeh Ghaffari, M.D. study director
Department of Endocrinology and Female Infertility, ACECR, Tehran, Iran.
Azar Yahyaei, M.Sc. principal investigator
Department of Endocrinology and Female Infertility, ACECR, Tehran, Iran.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Minimal ovarian stimulation in people with Polycystic Ovary Syndrome and Ovarian Hyperstimulation Syndrome, run by Royan Institute at 1 site in Iran.
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 8 inclusion and 1 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: finished, as of the sponsor's last update on 20 Apr 2021. 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 Iran. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fertilization rate (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]).). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03876145, which also lists 1 linked publication.
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 20 Apr 2021.