Infertility, FemalePhase 4NCT06701071
Evaluation of a Long Versus Short Clomid Protocol for Controlled Ovarian Stimulation
A Phase 4 study testing Clomiphene Citrate in people with Infertility, Female, run by University of Southern California at 1 site in United States.
Trial summary
The goal of this clinical trial is to evaluate a long Clomid protocol as compared to a 5-day Clomid protocol for ovarian stimulation in patients with diminished ovarian reserve undergoing ovarian stimulation for in-vitro fertilization. Read more about this study
- Who is it for?
- Ages 18 to 44 years, women only
- Conditions the study is for
- Infertility, Female
- What is being tested?
- Clomiphene Citrate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2025to Jun 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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 44 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Undergoing IVF
- Must meet POSEIDON criteria based on clinic evaluation
- Female partner: Antral follicle count of 2 or more and age <45 at time of stimulation start
- Male partner/sperm source: Cannot be azoospermic
- Planning freeze-all cycle (regardless of blastocyst or cleavage stage culture) or fresh transfer if randomized to short Clomid group
- Planning 36-hour trigger window
Who cannot join
- Normal ovarian reserve or good response
- Allergy or adverse reaction to Clomid
- Minimal stimulation protocols
- History of prior premature ovulation
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
HRC Fertility
Pasadena, California, 91101
Bonnie Song, MD, 866-472-4483, bonnie.song@med.usc.edu
Richard Paulson, MD, 866-472-4483, paulsonivf@havingbabies.com
About this study
Official title: Evaluation of a Long Versus Short Clomid Protocol for Controlled Ovarian Stimulation in Patients With Diminished Ovarian Reserve Undergoing In-vitro Fertilization: a Randomized Controlled Trial
The goal of this clinical trial is to evaluate a long Clomid protocol as compared to a 5-day Clomid protocol for ovarian stimulation in patients with diminished ovarian reserve undergoing ovarian stimulation for in-vitro fertilization. The aim of the long Clomid protocol is to intensify stimulation of the ovaries and reduce both cost and injection burden for patients. Participants will be randomized to receive the long Clomid protocol vs. the typical protocol involving Clomid only for 5 days followed by growth hormone-releasing hormone (GnRH) antagonist. The primary outcome the investigators will evaluate will be the number of mature eggs retrieved.
Read the detailed description
Clomiphene citrate (Clomid) is often used for assisted reproductive technologies and may be used to augment ovarian stimulation with exogenous gonadotropins by stimulating pituitary follicle-stimulating hormone (FSH) release in addition. The mechanism of action of Clomid is antagonism at the estrogen receptor, and this stimulates FSH release from the pituitary. The typical Clomid-based protocol has involved clomid only given for the first five days of stimulation to allow for endometrial development later in the cycle for a fresh embryo transfer following the oocyte retrieval. This protocol involves the addition of a GnRH antagonist medication later in the cycle to prevent premature ovulation. Recent national trends in IVF, however, have moved towards frozen embryo transfers and use of preimplantation genetic testing, which obviates any concerns regarding the endometrium. Recent experience in our clinic has suggested that Clomid may also prevent premature ovulation by antagonizing the positive feedback that is responsible for the luteinizing hormone (LH) surge and ovulation. Given in this manner, Clomid can be given throughout the duration of an ovarian stimulation cycle, achieve higher FSH levels and degree of ovarian stimulation in patients with diminished ovarian reserve, and obviate the need for GnRH antagonist medication (another expensive subcutaneous injection). The objective of this study is to compare a "long Clomid protocol" (i.e. using Clomid throughout the entire duration of the IVF cycle) as compared to the typical 5-day clomid protocol. The investigators hypothesize that the long Clomid protocol will be non-inferior to the typical five-day course and obviate the need for GnRH antagonist by preventing premature ovulation. Patients with diminished ovarian reserve and anticipated poor response to ovarian stimulation will be randomized to the long Clomid protocol vs. a 5-day Clomid with GnRH antagonist protocol. The primary outcome will be oocyte yield. Secondary outcome will be premature ovulation, embryo development, and pregnancy outcomes.
Please note that participants are responsible for treatment costs if they take part in this study. Our clinic Financial Team will be happy to discuss treatment costs and determine your insurance coverage at your initial consultation.
- Conditions
- Infertility, Female
- Being tested
- Clomiphene Citrate
- Medical subject headings
- Infertility, Female
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Clomiphene CitrateDrug
Clomiphene citrate is an estrogen receptor antagonist that leads to pituitary FSH release and prevention of the LH surge.
| Study group | Role | What they receive |
|---|---|---|
| Long Clomid | Experimental | Clomid with gonadotropins throughout the entire duration of ovarian stimulation without addition of GnRH antagonist Receives: Drug: Clomiphene Citrate |
| 5-day Clomid | Active comparator | Clomid only for 5 days at beginning of ovarian stimulation with gonadotropins, with GnRH antagonist added when the lead follicle reaches ~14mm. Receives: Drug: Clomiphene Citrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of mature oocytes
The number of mature oocytes retrieved at oocyte retrieval
Measured: Up to 1 month after study completion
Secondary outcomes (3)
Number of participants that experience premature ovulation
Premature LH surge, progesterone rise and estradiol decrease, or evidence of premature ovulation (no oocytes on retrieval or free fluid and follicular collapse on ultrasound)
Measured: Up to 1 month after study completion
Number of oocytes that get fertilized and grow to the blastocyst stage
Fertilization rate and blastulation
Measured: Up to 1 month after study completion
Pregnancy outcomes
Clinical pregnancy rate, ongoing pregnancy rate, live birth rate
Measured: Up to 3 years after study completion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2024
- Study start1 Jun 2025
- Primary completionJun 2028 (estimated)
- Study completionJun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Infertility, FemaleStudies 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
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients will be randomized to the two treatment arms
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Southern California
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Richard Paulson, University of Southern California
- Investigators
- Richard Paulson, Principal investigator, paulsonivf@havingbabies.com
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06701071
- Sponsor's protocol ID
- HS-23-00039
- Status last verified
- Jun 2026
- First submitted
- 13 Jun 2024
- Last updated
- 4 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of a Long Versus Short Clomid Protocol for Controlled Ovarian Stimulation in Patients With Diminished Ovarian Reserve Undergoing In-vitro Fertilization: a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT06701071
- Acronym / sponsor ID
- HS-23-00039
- Conditions
- Infertility, Female
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- University of Southern CaliforniaUniversity, hospital or other
- Study start
- 1 Jun 2025 (actual)
- Primary completion
- Jun 2028 (estimated)
- Study completion
- Jun 2028 (estimated)
- First posted
- 22 Nov 2024 (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.
The goal of this clinical trial is to evaluate a long Clomid protocol as compared to a 5-day Clomid protocol for ovarian stimulation in patients with diminished ovarian reserve undergoing ovarian stimulation for in-vitro fertilization. The aim of the long Clomid protocol is to intensify stimulation of the ovaries and reduce both cost and injection burden for patients. Participants will be randomized to receive the long Clomid protocol vs. the typical protocol involving Clomid only for 5 days followed by growth hormone-releasing hormone (GnRH) antagonist. The primary outcome the investigators will evaluate will be the number of mature eggs retrieved.
Detailed description
Clomiphene citrate (Clomid) is often used for assisted reproductive technologies and may be used to augment ovarian stimulation with exogenous gonadotropins by stimulating pituitary follicle-stimulating hormone (FSH) release in addition. The mechanism of action of Clomid is antagonism at the estrogen receptor, and this stimulates FSH release from the pituitary. The typical Clomid-based protocol has involved clomid only given for the first five days of stimulation to allow for endometrial development later in the cycle for a fresh embryo transfer following the oocyte retrieval. This protocol involves the addition of a GnRH antagonist medication later in the cycle to prevent premature ovulation. Recent national trends in IVF, however, have moved towards frozen embryo transfers and use of preimplantation genetic testing, which obviates any concerns regarding the endometrium. Recent experience in our clinic has suggested that Clomid may also prevent premature ovulation by antagonizing the positive feedback that is responsible for the luteinizing hormone (LH) surge and ovulation. Given in this manner, Clomid can be given throughout the duration of an ovarian stimulation cycle, achieve higher FSH levels and degree of ovarian stimulation in patients with diminished ovarian reserve, and obviate the need for GnRH antagonist medication (another expensive subcutaneous injection). The objective of this study is to compare a "long Clomid protocol" (i.e. using Clomid throughout the entire duration of the IVF cycle) as compared to the typical 5-day clomid protocol. The investigators hypothesize that the long Clomid protocol will be non-inferior to the typical five-day course and obviate the need for GnRH antagonist by preventing premature ovulation. Patients with diminished ovarian reserve and anticipated poor response to ovarian stimulation will be randomized to the long Clomid protocol vs. a 5-day Clomid with GnRH antagonist protocol. The primary outcome will be oocyte yield. Secondary outcome will be premature ovulation, embryo development, and pregnancy outcomes.
Please note that participants are responsible for treatment costs if they take part in this study. Our clinic Financial Team will be happy to discuss treatment costs and determine your insurance coverage at your initial consultation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Patients will be randomized to the two treatment arms
| Arm | Type | Receives |
|---|---|---|
| Long Clomid | Experimental | Drug: Clomiphene CitrateClomid with gonadotropins throughout the entire duration of ovarian stimulation without addition of GnRH antagonist |
| 5-day Clomid | Active comparator | Drug: Clomiphene CitrateClomid only for 5 days at beginning of ovarian stimulation with gonadotropins, with GnRH antagonist added when the lead follicle reaches ~14mm. |
Who may qualify
- Ages
- 18 to 44 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Undergoing IVF
- Must meet POSEIDON criteria based on clinic evaluation
- Female partner: Antral follicle count of 2 or more and age <45 at time of stimulation start
- Male partner/sperm source: Cannot be azoospermic
- Planning freeze-all cycle (regardless of blastocyst or cleavage stage culture) or fresh transfer if randomized to short Clomid group
Key exclusion criteria (4 listed)
- Normal ovarian reserve or good response
- Allergy or adverse reaction to Clomid
- Minimal stimulation protocols
- History of prior premature ovulation
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 |
|---|---|---|
| Clomiphene CitrateClomiphene citrate is an estrogen receptor antagonist that leads to pituitary FSH release and prevention of the LH surge. | Drug | 5-day Clomid, Long Clomid |
Primary outcome
Number of mature oocytes
Time frame: Up to 1 month after study completion
The number of mature oocytes retrieved at oocyte retrieval
3 secondary outcomes
Number of participants that experience premature ovulation
Time frame: Up to 1 month after study completion
Number of oocytes that get fertilized and grow to the blastocyst stage
Time frame: Up to 1 month after study completion
Pregnancy outcomes
Time frame: Up to 3 years after study completion
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2026.
- 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.
Richard Paulson principal investigator
paulsonivf@havingbabies.com
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 Clomiphene Citrate in people with Infertility, Female, run by University of Southern California at 1 site in United States.
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 6 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: looking for participants now, as of the sponsor's last update on 4 Aug 2026. 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 United States. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Bonnie Song, MD (323-409-3026, Bonnie.Song@med.usc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of mature oocytes (time frame: Up to 1 month after study completion). 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 4 Aug 2026.