PCO - Polycystic OvariesPhase 4NCT04157725
Mild Stimulation Protocol Using Clomiphene Citrate for Women With PCOS Undergoing in Vitro Fertilization
A Phase 4 study testing mild stimulation protocol: oral Clomiphene Citrate and Conventional Stimulation Protocol: will receive FSH/HMG in people with PCO - Polycystic Ovaries and Infertility, run by American University of Beirut Medical Center at 1 site in Lebanon.
Trial summary
Infertility is of increasing significance affecting almost 48.5 million couples around the world. Anovulation is a major cause of infertility in women with polycystic ovary syndrome (PCOS) accounting for about 80% of women with anovulatory infertility. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- PCO - Polycystic Ovaries, Infertility
- What is being tested?
- mild stimulation protocol: oral Clomiphene Citrate and Conventional Stimulation Protocol: will receive FSH/HMG
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 154 participants
- Where
- 1 siteLebanon
- Study dates
- 1 Jun 2023to 1 Jul 2025
- Phase
- Phase 4
- 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 18 to 40 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Female patients between 18-40 years of age
- Antral follicle count exceeding 16 and/or AMH exceeding 3.5 ng/dl
- PCOS features as per Rotterdam criteria: 2 of 3 criteria: a. Ultrasound morphology; b. Oligo/amenorrhea; c. Hyperandrogenism (clinical or chemical).
Who cannot join
- Recurrent implantation failure
- Recurrent pregnancy loss
- Congenital uterine anomalies
- Untreated maternal medical conditions (Diabetes, thyroid disease…)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Mild Stimulation Protocol Using Clomiphene Citrate / Gonadotropins Versus Conventional Stimulation Protocol for Women With PCOS Undergoing in Vitro Fertilization (IVF): a Prospective Non-randomized Controlled Trial
Infertility is of increasing significance affecting almost 48.5 million couples around the world. Anovulation is a major cause of infertility in women with polycystic ovary syndrome (PCOS) accounting for about 80% of women with anovulatory infertility. Ultrasound morphological features of PCOS include the presence of 16 or more follicles measuring 2-9 mm in diameter, and/or an overall large ovarian volume of >10mm3. Women with PCOS ultrasound features exhibit an exaggerated response to controlled ovarian stimulation.
Controlled ovarian hyperstimulation is an established prerequisite to assisted reproductive techniques with the aim of obtaining a higher yield of oocytes and ultimately increasing success rates. According to the ESHRE/ASRM consensus on infertility treatment related to polycystic ovary syndrome, IVF seems to represent a reasonable treatment option as the risks of multiple pregnancies and ovarian hyper-stimulation syndrome may be kept to a minimum. The optimal stimulation protocol however is still debatable. Recently, patient-friendly stimulation protocols for assisted reproductive technology were introduced aiming at minimizing overall treatment costs and health hazards to the patient. Mild stimulation protocols are considered relatively novel protocols. They consist of combining oral stimulation agents (clomiphene citrate or letrozole) with low-dose gonadotropins as effective alternatives to conventional gonadotropin-only stimulation protocols. Mild stimulation protocol has been associated with better tolerance, ease of use, and comparable livebirth outcomes. The investigators aim to test the hypothesis that mild stimulation protocols could produce a similar proportion of term livebirths to conventional treatment, while reducing treatment costs and health hazards.
This is a prospective non-randomized controlled trial comparing a mild ovarian stimulation protocol to conventional treatment for assisted reproductive technology at the Division of Reproductive Endocrinology and Infertility - Haifa Idriss Fertility Center - American University of Beirut Medical Center.
Read the detailed description
Infertility is a medical condition of increasing significance with an estimated 48.5 million affected couples around the world . Anovulation is a major cause of infertility in women with polycystic ovary syndrome (PCOS) accounting for about 80% of women with anovulatory infertility. The prevalence of PCOS varies widely among different ethnic populations and is highest in the Middle East. One way to diagnose PCOS is on the basis of the Rotterdam criteria, according to which women should satisfy 2 of 3 criteria including anovulation, polycystic ovarian morphology on ultrasound and hyperandrogenism (either clinical or biochemical). Trans-vaginal ultrasound evaluation is an important tool to assess ovarian features and determine the risk for ovarian hyper-response to follicle stimulation.
Ultrasound morphological features of polycystic ovary syndrome (PCOS) include the presence of 16 or more follicles measuring 2-9mm in diameter, and/or an overall large ovarian volume of >10mm3. Women with PCOS ultrasound features exhibit an exaggerated response to controlled ovarian stimulation . It was demonstrated that the number of baseline follicles seen on ultrasound strongly correlates with the number of recovered oocytes, and that was especially documented in women with a baseline number of pre-antral follicles exceeding 15 who were found to be at increased risk for ovarian hyper-stimulation syndrome .
Controlled ovarian hyperstimulation is an established prerequisite to assisted reproductive techniques with the aim of obtaining a higher yield of oocytes and ultimately increasing success rates. According to the ESHRE/ASRM consensus on infertility treatment related to polycystic ovary syndrome (2008), IVF seems to represent a reasonable treatment option as the risks of multiple pregnancies and ovarian hyper-stimulation syndrome may be kept to a minimum. The optimal stimulation protocol however is still debatable.
The investigators plan to conduct a prospective non-randomized controlled trial comparing a mild ovarian stimulation protocol to conventional treatment for assisted reproductive technology at the Division of Reproductive Endocrinology and Infertility - Haifa Idriss Fertility Center - American University of Beirut Medical Center.
Interest in embryo cryopreservation will be discussed with candidates before the start of IVF treatment. Women meeting the inclusion criteria who show no interest in embryo cryopreservation and in obtaining supernumerary embryos will be allocated to the mild stimulation (group A) protocol. Alternatively, women interested in obtaining a high number of embryos for the purpose of cryopreservation will be allocated to the conventional stimulation (group B) protocol.
- Conditions
- PCO - Polycystic Ovaries, Infertility
- Being tested
- mild stimulation protocol: oral Clomiphene Citrate, Conventional Stimulation Protocol: will receive FSH/HMG
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
mild stimulation protocol: oral Clomiphene CitrateDrug
Group A (mild stimulation protocol) will receive oral Clomiphene Citrate (Clomid®) 150 mg/day for 5 days (starting on the 2nd of menses), followed by FSH/HMG (human menopausal gonadotropins) at a daily dose of 150-225 IU starting from the 6th day of the menstrual cycle. GnRH antagonist (Cetrotide®, Merck-Serono, Switzerland) 0.25 mg subcutaneously daily will be started once a dominant follicle becomes ≥14 mm until the day of final follicle maturation. Once 3 leading follicles reach 18mm in diameter, final follicle maturation will be triggered using HCG (Choriomon® 10,000 IU) in the presence of 14 or less pre-ovulatory follicles or GnRH agonist (Triptorelin-Gonapeptyl® 0.3mg single dose) in the presence of 15 or more follicles. The choice of the starting FSH/HMG daily dose will be tailored to BMI: 150 IU/d for BMI less than 25 and 225IU/d for BMI 25 and above.
Conventional Stimulation Protocol: will receive FSH/HMGDrug
Group B (conventional stimulation protocol) will receive FSH/HMG (human menopausal gonadotropins) at a daily dose of 150-225 IU starting on the 2nd day of menses. GnRH antagonist (Cetrotide®, Merck-Serono, Switzerland) 0.25 mg subcutaneously daily will be started once a dominant follicle becomes ≥14 mm until the day of final follicle maturation. Once 3 leading follicles reach 18mm in diameter, final follicle maturation will be triggered using HCG (Choriomon® 10,000 IU) in the presence of 14 or less pre-ovulatory follicles or GnRH agonist (Triptorelin-Gonapeptyl® 0.3mg single dose) in the presence of 15 or more follicles. The choice of the starting FSH/HMG daily dose will be tailored to BMI: 150 IU/d for BMI less than 25 and 225IU/d for BMI 25 and above.
| Study group | Role | What they receive |
|---|---|---|
| Group A (mild stimulation protocol) | Experimental | Not described Receives: Drug: mild stimulation protocol: oral Clomiphene Citrate |
| Group B (conventional stimulation protocol) | Active comparator | Not described Receives: Drug: Conventional Stimulation Protocol: will receive FSH/HMG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Live birth rate
Defined as number of viable fetuses above 24 weeks of gestation per number of embryos transferred
Measured: more than 24 weeks of gestation
Secondary outcomes (11)
Total number of gonadotropins
Measured: up to 2 weeks
Duration of stimulation
Measured: up to 2 weeks
total number of developing follicles
Measured: up to 2 weeks
Rate of GnRHa trigger of final follicle maturation, endometrial thickness and pattern.
Measured: up to 2 weeks
Fertilization rate
Measured: up to 1 week
Cleavage rate
Measured: up to 1 week
Number of transferred embryos
Measured: up to 1 week
Quality of transferred embryos
Embryo grading as assessed on day 3 or day 5 (day of transfer)
Measured: up to 1 week
Number of supernumerary embryos suitable for cryopreservation
Measured: up to 1 week
Treatment emergent adverse effects
headaches, hot flushes, irritability, visual changes, injection site discomfort, abdominal discomfort, and clinically significant OHSS (moderate and severe)
Measured: up to 2 weeks
Cost
Direct and indirect costs of treatment will be recorded (ovarian stimulation agents, luteal support medications, OPU, ET, physician fees, monitoring)
Measured: up to 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2019
- Study start1 Jun 2023
- Primary completion1 Jan 2025 (estimated)
- Study completion1 Jul 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PCO - Polycystic OvariesStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 154 participants (estimated)
Sponsor and investigators
- Lead sponsor
- American University of Beirut Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Johnny Awwad, American University of Beirut Medical Center
- Investigators
- Johnny T Awwad, M.D, Principal investigator, American University of Beirut Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04157725
- Sponsor's protocol ID
- AmericanUBMC-MS
- Status last verified
- Jul 2023
- First submitted
- 17 Jul 2019
- Last updated
- 20 Jul 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mild Stimulation Protocol Using Clomiphene Citrate / Gonadotropins Versus Conventional Stimulation Protocol for Women With PCOS Undergoing in Vitro Fertilization (IVF): a Prospective Non-randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT04157725
- Acronym / sponsor ID
- AmericanUBMC-MS
- Conditions
- PCO - Polycystic Ovaries, Infertility
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 154 participants (estimated)
- Lead sponsor
- American University of Beirut Medical CenterUniversity, hospital or other
- Study start
- 1 Jun 2023 (actual)
- Primary completion
- 1 Jan 2025 (estimated)
- Study completion
- 1 Jul 2025 (estimated)
- First posted
- 8 Nov 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.
Infertility is of increasing significance affecting almost 48.5 million couples around the world. Anovulation is a major cause of infertility in women with polycystic ovary syndrome (PCOS) accounting for about 80% of women with anovulatory infertility. Ultrasound morphological features of PCOS include the presence of 16 or more follicles measuring 2-9 mm in diameter, and/or an overall large ovarian volume of >10mm3. Women with PCOS ultrasound features exhibit an exaggerated response to controlled ovarian stimulation.
Controlled ovarian hyperstimulation is an established prerequisite to assisted reproductive techniques with the aim of obtaining a higher yield of oocytes and ultimately increasing success rates. According to the ESHRE/ASRM consensus on infertility treatment related to polycystic ovary syndrome, IVF seems to represent a reasonable treatment option as the risks of multiple pregnancies and ovarian hyper-stimulation syndrome may be kept to a minimum. The optimal stimulation protocol however is still debatable. Recently, patient-friendly stimulation protocols for assisted reproductive technology were introduced aiming at minimizing overall treatment costs and health hazards to the patient. Mild stimulation protocols are considered relatively novel protocols. They consist of combining oral stimulation agents (clomiphene citrate or letrozole) with low-dose gonadotropins as effective alternatives to conventional gonadotropin-only stimulation protocols. Mild stimulation protocol has been associated with better tolerance, ease of use, and comparable livebirth outcomes. The investigators aim to test the hypothesis that mild stimulation protocols could produce a similar proportion of term livebirths to conventional treatment, while reducing treatment costs and health hazards.
This is a prospective non-randomized controlled trial comparing a mild ovarian stimulation protocol to conventional treatment for assisted reproductive technology at the Division of Reproductive Endocrinology and Infertility - Haifa Idriss Fertility Center - American University of Beirut Medical Center.
Detailed description
Infertility is a medical condition of increasing significance with an estimated 48.5 million affected couples around the world . Anovulation is a major cause of infertility in women with polycystic ovary syndrome (PCOS) accounting for about 80% of women with anovulatory infertility. The prevalence of PCOS varies widely among different ethnic populations and is highest in the Middle East. One way to diagnose PCOS is on the basis of the Rotterdam criteria, according to which women should satisfy 2 of 3 criteria including anovulation, polycystic ovarian morphology on ultrasound and hyperandrogenism (either clinical or biochemical). Trans-vaginal ultrasound evaluation is an important tool to assess ovarian features and determine the risk for ovarian hyper-response to follicle stimulation.
Ultrasound morphological features of polycystic ovary syndrome (PCOS) include the presence of 16 or more follicles measuring 2-9mm in diameter, and/or an overall large ovarian volume of >10mm3. Women with PCOS ultrasound features exhibit an exaggerated response to controlled ovarian stimulation . It was demonstrated that the number of baseline follicles seen on ultrasound strongly correlates with the number of recovered oocytes, and that was especially documented in women with a baseline number of pre-antral follicles exceeding 15 who were found to be at increased risk for ovarian hyper-stimulation syndrome .
Controlled ovarian hyperstimulation is an established prerequisite to assisted reproductive techniques with the aim of obtaining a higher yield of oocytes and ultimately increasing success rates. According to the ESHRE/ASRM consensus on infertility treatment related to polycystic ovary syndrome (2008), IVF seems to represent a reasonable treatment option as the risks of multiple pregnancies and ovarian hyper-stimulation syndrome may be kept to a minimum. The optimal stimulation protocol however is still debatable.
The investigators plan to conduct a prospective non-randomized controlled trial comparing a mild ovarian stimulation protocol to conventional treatment for assisted reproductive technology at the Division of Reproductive Endocrinology and Infertility - Haifa Idriss Fertility Center - American University of Beirut Medical Center.
Interest in embryo cryopreservation will be discussed with candidates before the start of IVF treatment. Women meeting the inclusion criteria who show no interest in embryo cryopreservation and in obtaining supernumerary embryos will be allocated to the mild stimulation (group A) protocol. Alternatively, women interested in obtaining a high number of embryos for the purpose of cryopreservation will be allocated to the conventional stimulation (group B) protocol.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A (mild stimulation protocol) | Experimental | Drug: mild stimulation protocol: oral Clomiphene Citrate |
| Group B (conventional stimulation protocol) | Active comparator | Drug: Conventional Stimulation Protocol: will receive FSH/HMG |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Female patients between 18-40 years of age
- Antral follicle count exceeding 16 and/or AMH exceeding 3.5 ng/dl
- PCOS features as per Rotterdam criteria: 2 of 3 criteria: a. Ultrasound morphology; b. Oligo/amenorrhea; c. Hyperandrogenism (clinical or chemical).
Key exclusion criteria (4 listed)
- Recurrent implantation failure
- Recurrent pregnancy loss
- Congenital uterine anomalies
- Untreated maternal medical conditions (Diabetes, thyroid disease…)
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 |
|---|---|---|
| mild stimulation protocol: oral Clomiphene CitrateGroup A (mild stimulation protocol) will receive oral Clomiphene Citrate (Clomid®) 150 mg/day for 5 days (starting on the 2nd of menses), followed by FSH/HMG (human menopausal gonadotropins) at a daily dose of 150-225 IU starting from the 6th day of the menstrual cycle. GnRH antagonist (Cetrotide®, Merck-Serono, Switzerland) 0.25 mg subcutaneously daily will be started once a dominant follicle becomes ≥14 mm until the day of final follicle maturation. Once 3 leading follicles reach 18mm in diameter, final follicle maturation will be triggered using HCG (Choriomon® 10,000 IU) in the presence of 14 or less pre-ovulatory follicles or GnRH agonist (Triptorelin-Gonapeptyl® 0.3mg single dose) in the presence of 15 or more follicles. The choice of the starting FSH/HMG daily dose will be tailored to BMI: 150 IU/d for BMI less than 25 and 225IU/d for BMI 25 and above. | Drug | Group A (mild stimulation protocol) |
| Conventional Stimulation Protocol: will receive FSH/HMGGroup B (conventional stimulation protocol) will receive FSH/HMG (human menopausal gonadotropins) at a daily dose of 150-225 IU starting on the 2nd day of menses. GnRH antagonist (Cetrotide®, Merck-Serono, Switzerland) 0.25 mg subcutaneously daily will be started once a dominant follicle becomes ≥14 mm until the day of final follicle maturation. Once 3 leading follicles reach 18mm in diameter, final follicle maturation will be triggered using HCG (Choriomon® 10,000 IU) in the presence of 14 or less pre-ovulatory follicles or GnRH agonist (Triptorelin-Gonapeptyl® 0.3mg single dose) in the presence of 15 or more follicles. The choice of the starting FSH/HMG daily dose will be tailored to BMI: 150 IU/d for BMI less than 25 and 225IU/d for BMI 25 and above. | Drug | Group B (conventional stimulation protocol) |
Primary outcome
Live birth rate
Time frame: more than 24 weeks of gestation
Defined as number of viable fetuses above 24 weeks of gestation per number of embryos transferred
11 secondary outcomes
Total number of gonadotropins
Time frame: up to 2 weeks
Duration of stimulation
Time frame: up to 2 weeks
total number of developing follicles
Time frame: up to 2 weeks
Rate of GnRHa trigger of final follicle maturation, endometrial thickness and pattern.
Time frame: up to 2 weeks
Fertilization rate
Time frame: up to 1 week
Cleavage rate
Time frame: up to 1 week
Number of transferred embryos
Time frame: up to 1 week
Quality of transferred embryos
Time frame: up to 1 week
Number of supernumerary embryos suitable for cryopreservation
Time frame: up to 1 week
Treatment emergent adverse effects
Time frame: up to 2 weeks
Cost
Time frame: up to 2 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2023.
- Individual participant dataSharing planned: No
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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.
Johnny T Awwad, M.D principal investigator
American University of Beirut Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing mild stimulation protocol: oral Clomiphene Citrate and Conventional Stimulation Protocol: will receive FSH/HMG in people with PCO - Polycystic Ovaries and Infertility, run by American University of Beirut Medical Center at 1 site in Lebanon.
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 3 inclusion and 4 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: status not confirmed, as of the sponsor's last update on 20 Jul 2023. 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 Lebanon. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Live birth rate (time frame: more than 24 weeks of gestation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Jul 2023.