Female InfertilityEarly Phase 1NCT06778733
Effectiveness of Low Dose Gonadotropin Stimulation Protocol Vs High Dose Gonadotropin Protocol in Poor Responders
A Early Phase 1 study testing Clomiphane citrate and recombinant human Follicle-Stimulating Hormone (r-FSH-alfa) in people with Female Infertility, run by University of Athens at 2 sites in Greece.
Trial summary
In the present study we examined the effect of addition of CC to a low dose gonadotropin (150 IU/day) / GnRH antagonist protocol in comparison to a high gonadotropin dose (300 IU/day) regiment (short protocol) in women with poor ovarian responce (POR). Read more about this study
- Who is it for?
- Ages 30 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Female Infertility
- What is being tested?
- Clomiphane citrate and recombinant human Follicle-Stimulating Hormone (r-FSH-alfa)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 2 sitesGreece
- Study dates
- 1 Jan 2022to 30 Apr 2024
- Phase
- Early Phase 1
- 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 30 to 45 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
None listed.
Who cannot join
- The succesful ongoing pregnancy after the first stimulation.
Trial locations and contacts
2 sites in 1 country.
Greece2 sites
Aretaieion University Hospital
Athens, Attica
Aretaieion University Hospital
Athens
About this study
Official title: The Effect of Clomiphene Citrate Administration in Combination with Low Dose (150 IU) of Gonadotropins Vs High Dose Gonadotropin Protocol in Poor Responders. Impact on Stimulation Characteristics and Pregnancy Outcome.
In the present study we examined the effect of addition of CC to a low dose gonadotropin (150 IU/day) / GnRH antagonist protocol in comparison to a high gonadotropin dose (300 IU/day) regiment (short protocol) in women with poor ovarian responce (POR).
Read the detailed description
22 patients diagnosed with poor ovarian response, aged 35-43 years, were enrolled in the study. The definition of poor response was based on the presence of at least one of the following criteria: Age equal or over 40 years old or other cause of subfertility, AFC less than 5-7, AMH 0.5-1,1ng/ml , a previous POR (≤3 oocytes with a conventional stimulation protocol or cancellation due to poor response) . All patients received appropriate counselling . Early follicular phase FSH and estradiol (E2) were measured prior to the initiation of treatment. All women had measurements of serum FSH and estradiol and a pelvic sonogram on the second day of their cycle. Providing that serum FSH level was less than 16 mIU/ml and estradiol level less than 70 pg/ml on cycle day2 , ovarian stimulation was initiated with 300 IU of gonadotropins either in the form of a combination of highly purified urinary FSH and LH or with a combination of recombinant FSH and recombinant LH. All patients were re-evaluated on day 5 of the stimulation, and dosage adjustments were made and the antagonists (Cetrorelix or ganirelix 0.25 mg/day) were initiated when at least one follicle reached a diameter of 14mm . When at least 2 follicles reached an average diameter of 18 mm, final oocyte maturation was triggered with 10,000IU of hCG ( Ovitrelle, Greece Inc.). Oocyte retrieval was performed 34 to 36 hours later. All patients underwent ICSI. Patients with successful fertilization underwent embryo transfer under sonographic guidance on day 5 after retrieval. Serum β-hCG levels were measured 12 days after oocyte retrieval, and clinical pregnancy was confirmed by transvaginal ultrasound 14 days later. Ongoing pregnancy was confirmed at 12 weeks by ultrasound. In case of negative pregnancy test result the same participants received CC (100 mg/day) from day 3 to day 7 of the menstrual cycle, in combination with low-dose gonadotropins (150 IU/day) until the day of hCG administration. The primary outcome measure was ongoing pregnancy rates. Secondary outcomes included the number of follicles, the number of mature oocytes, fertilization rate, total number of embryos and embryo quality in each group. Furthermore, we included biochemical pregnancy rates and miscarriage as secondary outcomes as well.
- Conditions
- Female Infertility
- Being tested
- Clomiphane citrate, recombinant human Follicle-Stimulating Hormone (r-FSH-alfa)
- Keywords
- Clomiphene Citrate, IVF, Gonadotrophins, pregnancy rates, ovarian reserve, Low-dose gonadotrophins
- Medical subject headings
- Infertility, Female
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Clomiphane citrateDrug
Also called Clomiphene citrate 50mg/tab, Serpafar 50mg/tab
Clomiphene citrate 100mg/day from day 3 to day 7 of the cycle (5 days) will be added to the low-dose (150 IU) short GnRh antagonist protocol (recombinant human Follicle-Stimulating Hormone (r-FSH-alfa) (Gonal-f; Merck Serono Hellas AE))
recombinant human Follicle-Stimulating Hormone (r-FSH-alfa)Drug
Also called Gonal-f 150 Iu/day, Gonal-f 300 IU/day
All patients will undergo ovarian stimulation with the standard-dose GNRH-antagonist protocol.
Ovarian stimulation will be initiated with 150 IU of of recombinant human Follicle-Stimulating Hormone (r-FSH-alfa) (Gonal-f; Merck Serono Hellas AE)
| Study group | Role | What they receive |
|---|---|---|
| Clomiphene Citrate (CC)/r-FSH | Active comparator | Administration of 100mg/day Clomiphene citrate (CC) from day 3 to day 7 of the cycle (5 days) in combination with low-dose gonadotropins (150IU) according to a short stimulation GnRh antagonists protocol.
Treatment schedule:
Serum AMH levels were measured before the stimulation began. Estradiol and FSH levels were measured on the third day of the participants' menstrual cycle. Ovarian stimulation started on the same day with 150 IU of recombinant human Follicle-Stimulating Hormone (r-FSH) after a transvaginal ultrasound was performed, provided that serum FSH levels were below 16 mIU/ml and estradiol levels were under 70 pg/ml (r-FSH group). All patients underwent routine monitoring with transvaginal ultrasound. The GnRH antagonist cetrorelix acetate, at a dose of 0.25 mg/day was given when a dominant follicle reached 14 mm in diameter. Oocyte retrieval (OPU) was performed 34-36 hours after hCG administration followed by IVF/ICSI and embryo transfer on day 3 after OPU Receives: Drug: Clomiphane citrate; Drug: recombinant human Follicle-Stimulating Hormone (r-FSH-alfa) |
| High-dose Gonadotropins (r-FSH) | Active comparator | Patients in this group will be stimulated according to the high-dose short r-FSH antagonist protocol.
Treatment schedule:
Ovarian stimulation started on day 3 with 300 IU of recombinant human Follicle-Stimulating Hormone (r-FSH) after a transvaginal ultrasound was performed, provided that serum FSH levels were below 16 mIU/ml and estradiol levels were under 70 pg/ml (r-FSH group). All patients underwent routine monitoring with transvaginal ultrasound and serum estradiol measurements. The GnRH antagonist cetrorelix acetate, at a dose of 0.25 mg/day, was given when a dominant follicle reached 14 mm in diameter. Oocyte retrieval (OPU) was performed 34-36 hours after hCG administration, followed by IVF/ICSI and embryo transfer on day 3 after OPU. Receives: Drug: recombinant human Follicle-Stimulating Hormone (r-FSH-alfa) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ongoing pregnancy rates
succesfull clinical pregnancy after performing ultrasound on 12 weeks of pregnancy
Measured: 28 months from start of study
Secondary outcomes (6)
Number of follicles
Calculated on the day of triggering
Measured: 24 months from start of study
Number of mature oocytes
MII
Measured: 24 months from start of study
Fertilization rate
Percentage
Measured: 24 months from start of study
Total number of embryos in each group
Total number of embryos
Measured: 24 months from start of study
Biochemical pregnancy rates
Absence of clinical pregnancy
Measured: 24 months from start of study
Miscarriage rates
Percentage of pregnancies that did not reach viability
Measured: 28 months from start of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2025
- Study start1 Jan 2022
- Primary completion1 Jan 2024
- Study completion30 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Female InfertilityStudies 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Prospective cohort study
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Athens
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nikos Vlahos, Aretaieion University Hospital
- Investigators
- Olga Triantafyllidou, MD,, Principal investigator, University of Athens School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06778733
- Sponsor's protocol ID
- ARETAIEION IVF UNIT
- Status last verified
- Jan 2025
- First submitted
- 5 Oct 2024
- Last updated
- 16 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Pilehvari S, ShahrokhTehraninejad E, Hosseinrashidi B, Keikhah F, Haghollahi F, Aziminekoo E. Comparison Pregnancy Outcomes Between Minimal Stimulation Protocol and Conventional GnRH Antagonist Protocols in Poor Ovarian Responders. J Family Reprod Health. 2016 Mar;10(1):35-42.
PubMed 27385972Moffat R, Hansali C, Schoetzau A, Ahler A, Gobrecht U, Beutler S, Raggi A, Sartorius G, De Geyter C. Randomised controlled trial on the effect of clomiphene citrate and gonadotropin dose on ovarian response markers and IVF outcomes in poor responders. Hum Reprod. 2021 Mar 18;36(4):987-997. doi: 10.1093/humrep/deaa336.
PubMed 33367742Liu S, Liu X, Li H, Liu M, Lv Y, Li Y. Clomiphene citrate priming increases sensitivity during ovarian stimulation in poor ovarian responders undergoing in vitro fertilization treatment: a retrospective cohort study. Hum Fertil (Camb). 2023 Dec;26(5):1080-1086. doi: 10.1080/14647273.2022.2109069. Epub 2022 Aug 11.
PubMed 35950570
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Clomiphene Citrate Administration in Combination with Low Dose (150 IU) of Gonadotropins Vs High Dose Gonadotropin Protocol in Poor Responders. Impact on Stimulation Characteristics and Pregnancy Outcome.
- ClinicalTrials.gov ID
- NCT06778733
- Acronym / sponsor ID
- ARETAIEION IVF UNIT
- Conditions
- Female Infertility
- Keywords
- Clomiphene Citrate, IVF, Gonadotrophins, pregnancy rates, ovarian reserve, Low-dose gonadotrophins
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- University of AthensUniversity, hospital or other
- Study start
- 1 Jan 2022 (actual)
- Primary completion
- 1 Jan 2024 (actual)
- Study completion
- 30 Apr 2024 (actual)
- First posted
- 16 Jan 2025 (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.
In the present study we examined the effect of addition of CC to a low dose gonadotropin (150 IU/day) / GnRH antagonist protocol in comparison to a high gonadotropin dose (300 IU/day) regiment (short protocol) in women with poor ovarian responce (POR).
Detailed description
22 patients diagnosed with poor ovarian response, aged 35-43 years, were enrolled in the study. The definition of poor response was based on the presence of at least one of the following criteria: Age equal or over 40 years old or other cause of subfertility, AFC less than 5-7, AMH 0.5-1,1ng/ml , a previous POR (≤3 oocytes with a conventional stimulation protocol or cancellation due to poor response) . All patients received appropriate counselling . Early follicular phase FSH and estradiol (E2) were measured prior to the initiation of treatment. All women had measurements of serum FSH and estradiol and a pelvic sonogram on the second day of their cycle. Providing that serum FSH level was less than 16 mIU/ml and estradiol level less than 70 pg/ml on cycle day2 , ovarian stimulation was initiated with 300 IU of gonadotropins either in the form of a combination of highly purified urinary FSH and LH or with a combination of recombinant FSH and recombinant LH. All patients were re-evaluated on day 5 of the stimulation, and dosage adjustments were made and the antagonists (Cetrorelix or ganirelix 0.25 mg/day) were initiated when at least one follicle reached a diameter of 14mm . When at least 2 follicles reached an average diameter of 18 mm, final oocyte maturation was triggered with 10,000IU of hCG ( Ovitrelle, Greece Inc.). Oocyte retrieval was performed 34 to 36 hours later. All patients underwent ICSI. Patients with successful fertilization underwent embryo transfer under sonographic guidance on day 5 after retrieval. Serum β-hCG levels were measured 12 days after oocyte retrieval, and clinical pregnancy was confirmed by transvaginal ultrasound 14 days later. Ongoing pregnancy was confirmed at 12 weeks by ultrasound. In case of negative pregnancy test result the same participants received CC (100 mg/day) from day 3 to day 7 of the menstrual cycle, in combination with low-dose gonadotropins (150 IU/day) until the day of hCG administration. The primary outcome measure was ongoing pregnancy rates. Secondary outcomes included the number of follicles, the number of mature oocytes, fertilization rate, total number of embryos and embryo quality in each group. Furthermore, we included biochemical pregnancy rates and miscarriage as secondary outcomes as well.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Prospective cohort study
| Arm | Type | Receives |
|---|---|---|
| Clomiphene Citrate (CC)/r-FSH | Active comparator | Drug: Clomiphane citrate, Drug: recombinant human Follicle-Stimulating Hormone (r-FSH-alfa)Administration of 100mg/day Clomiphene citrate (CC) from day 3 to day 7 of the cycle (5 days) in combination with low-dose gonadotropins (150IU) according to a short stimulation GnRh antagonists protocol. Treatment schedule: Serum AMH levels were measured before the stimulation began. Estradiol and FSH levels were measured on the third day of the participants' menstrual cycle. Ovarian stimulation started on the same day with 150 IU of recombinant human Follicle-Stimulating Hormone (r-FSH) after a transvaginal ultrasound was performed, provided that serum FSH levels were below 16 mIU/ml and estradiol levels were under 70 pg/ml (r-FSH group). All patients underwent routine monitoring with transvaginal ultrasound. The GnRH antagonist cetrorelix acetate, at a dose of 0.25 mg/day was given when a dominant follicle reached 14 mm in diameter. Oocyte retrieval (OPU) was performed 34-36 hours after hCG administration followed by IVF/ICSI and embryo transfer on day 3 after OPU |
| High-dose Gonadotropins (r-FSH) | Active comparator | Drug: recombinant human Follicle-Stimulating Hormone (r-FSH-alfa)Patients in this group will be stimulated according to the high-dose short r-FSH antagonist protocol. Treatment schedule: Ovarian stimulation started on day 3 with 300 IU of recombinant human Follicle-Stimulating Hormone (r-FSH) after a transvaginal ultrasound was performed, provided that serum FSH levels were below 16 mIU/ml and estradiol levels were under 70 pg/ml (r-FSH group). All patients underwent routine monitoring with transvaginal ultrasound and serum estradiol measurements. The GnRH antagonist cetrorelix acetate, at a dose of 0.25 mg/day, was given when a dominant follicle reached 14 mm in diameter. Oocyte retrieval (OPU) was performed 34-36 hours after hCG administration, followed by IVF/ICSI and embryo transfer on day 3 after OPU. |
Who may qualify
- Ages
- 30 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (0 listed)
Key exclusion criteria (1 listed)
- The succesful ongoing pregnancy after the first stimulation.
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 |
|---|---|---|
| Clomiphane citrateAlso: Clomiphene citrate 50mg/tab, Serpafar 50mg/tabClomiphene citrate 100mg/day from day 3 to day 7 of the cycle (5 days) will be added to the low-dose (150 IU) short GnRh antagonist protocol (recombinant human Follicle-Stimulating Hormone (r-FSH-alfa) (Gonal-f; Merck Serono Hellas AE)) | Drug | Clomiphene Citrate (CC)/r-FSH |
| recombinant human Follicle-Stimulating Hormone (r-FSH-alfa)Also: Gonal-f 150 Iu/day, Gonal-f 300 IU/dayAll patients will undergo ovarian stimulation with the standard-dose GNRH-antagonist protocol. Ovarian stimulation will be initiated with 150 IU of of recombinant human Follicle-Stimulating Hormone (r-FSH-alfa) (Gonal-f; Merck Serono Hellas AE) | Drug | Clomiphene Citrate (CC)/r-FSH, High-dose Gonadotropins (r-FSH) |
Primary outcome
Ongoing pregnancy rates
Time frame: 28 months from start of study
succesfull clinical pregnancy after performing ultrasound on 12 weeks of pregnancy
6 secondary outcomes
Number of follicles
Time frame: 24 months from start of study
Number of mature oocytes
Time frame: 24 months from start of study
Fertilization rate
Time frame: 24 months from start of study
Total number of embryos in each group
Time frame: 24 months from start of study
Biochemical pregnancy rates
Time frame: 24 months from start of study
Miscarriage rates
Time frame: 28 months from start of study
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 16 Jan 2025.
- Background: PubMed 27385972Pilehvari S, ShahrokhTehraninejad E, Hosseinrashidi B, Keikhah F, Haghollahi F, Aziminekoo E. Comparison Pregnancy Outcomes Between Minimal Stimulation Protocol and Conventional GnRH Antagonist Protocols in Poor Ovarian Responders. J Family Reprod Health. 2016 Mar;10(1):35-42.
- Background: PubMed 33367742Moffat R, Hansali C, Schoetzau A, Ahler A, Gobrecht U, Beutler S, Raggi A, Sartorius G, De Geyter C. Randomised controlled trial on the effect of clomiphene citrate and gonadotropin dose on ovarian response markers and IVF outcomes in poor responders. Hum Reprod. 2021 Mar 18;36(4):987-997. doi: 10.1093/humrep/deaa336.
- Background: PubMed 35950570Liu S, Liu X, Li H, Liu M, Lv Y, Li Y. Clomiphene citrate priming increases sensitivity during ovarian stimulation in poor ovarian responders undergoing in vitro fertilization treatment: a retrospective cohort study. Hum Fertil (Camb). 2023 Dec;26(5):1080-1086. doi: 10.1080/14647273.2022.2109069. Epub 2022 Aug 11.
- Related InfoLink provided by the sponsor.
- 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.
Olga Triantafyllidou, MD, principal investigator
University of Athens School of Medicine
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Clomiphane citrate and recombinant human Follicle-Stimulating Hormone (r-FSH-alfa) in people with Female Infertility, run by University of Athens at 2 sites in Greece.
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 0 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 16 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Greece. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Ongoing pregnancy rates (time frame: 28 months from start of study). 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 NCT06778733, which also lists 3 linked publications.
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 16 Jan 2025.