HCG; IVF; Pregnancy Rates; ART; Chorionic GonadotropinPhase 3HCGNCT03423537
Low-dose HCG as an Adjunct to Ovarian Stimulation in Subfertile Women Undergoing ART
A Phase 3 study testing hCG in people with HCG; IVF; Pregnancy Rates; ART; Chorionic Gonadotropin, run by National and Kapodistrian University of Athens at 1 site in Greece.
Trial summary
The objective of this prospective randomized clinical trial is to investigate whether the addition of low-dose hCG to a short GnRH-agonist protocol for IVF and ovarian stimulation with rFSH from the onset of the follicular phase and throughout stimulation in sub fertile women undergoing IVF, improves pregnancy rates. Read more about this study
- Who is it for?
- Ages 35 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- HCG; IVF; Pregnancy Rates; ART; Chorionic Gonadotropin
- What is being tested?
- hCG
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteGreece
- Study dates
- 1 Jun 2018to 30 Apr 2019
- Phase
- Phase 3
- 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 35 to 40 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age: between 35 and 40 years of age,
- Physiological menstrual cycles (24-35 day cycle),
- Normal endocrine function (normal PRL and TSH, FSH ≤ 15 IU / ml),
- Transvaginal ultrasound (TVS) without pathological findings,
- Free personal medical history,
- Indication for IVF / ICSI (NICE, 2016)
- 1st or 2nd IVF / ICSI cycle
Who cannot join
- Endocrine or metabolic disorders, e.g. PCO (S)
- Pathology of the uterus and / or endometrium,
- Pelvic inflammatory disease (PID),
- Basal FSH levels> 15 IU / ml,
- Surgery in the ovaries,
- Body Mass Index (BMI) ≥ 35 kg / m2,
- Age: <35 years \&> 41 years old
Trial locations and contacts
1 site in 1 country.
Greece1 site
3rd Department of Obstetrics and Gynecology, Assisted Reproduction Unit
Athens, Chaidari, 12462
About this study
Official title: A Prospective, Multicenter, Double-blind, Placebo-controlled, Phase III Clinical Study, on the Efficacy and Safety of Low-dose hCG in a Short Protocol With GnRH Agonist and Ovarian Stimulation With Recombinant FSH (rFSH) During the Follicular Phase in Subfertile Women Undergoing ART
The objective of this prospective randomized clinical trial is to investigate whether the addition of low-dose hCG to a short GnRH-agonist protocol for IVF and ovarian stimulation with rFSH from the onset of the follicular phase and throughout stimulation in sub fertile women undergoing IVF, improves pregnancy rates.
Read the detailed description
This is a prospective, multicenter, randomized, double-blind, placebo-controlled, two parallel group of patients, Phase IIIb clinical study to test the efficacy and safety of adding low-dose hCGs in a short protocol with GnRH agonist and ovarian stimulation with recombinant FSH (rFSH) from the onset of the follicular phase and throughout the duration of stimulation in enrolled women to the increase in the rate of clinical pregnancies.
Main end point will be the rate of clinical pregnancy (positive heart rate at 7 weeks of gestation in the ultrasound), while secondary endpoints will be
- The number of follicles (> 11,> 14,> 18 mm) on the day of triggering with hCG
- The thickness of the endometrium on the day of follicular maturation
- Live birth rates
- Automatic abortion rates (loss of pregnancy after positive heart function up to 20 weeks of gestation)
- The rate of ongoing pregnancy (positive heart function after 12 weeks of gestation),
- The percentage of ovarian hyperstimulation syndrome (after triggering) with hCG for the next 2 weeks
- The rate of multiple pregnancy.
Participants will be randomly divided into two groups: the intervention group (Group 1) and the control group (Group 2). Randomization will be done using sealed envelopes marked "Group 1" and "Group 2". The randomization list will be prepared centrally for the four participating clinics (research centers) and there will be a "stratification" per center, per 30, respectively, and will be shared among the participants.
"Group 1" will indicate the application of the protocol by adding hCG with the initiation of controlled ovarian stimulation protocol for IVF / ICSI with rFSH, and "Group 2" will indicate the application of the conventional protocol without the addition of hCG .
Each patient's assignment to a treatment group will be made by calling the unit's midwife who will have 2 envelopes with the above indications and who will not be present when the pair is informed by 2 members of the research team.
- Being tested
- hCG, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
hCGDrug
Also called Pregnyl
the addition of hCG (Pregnyl®, MSD Greece) will begin with the administration of gonadotrophin at a dose of 100 IU per day, administered subcutaneously, and will continue until the administration of hCG for follicular maturation.
PlaceboDrug
100IU per day containing N/S 0.9% will be injected
| Study group | Role | What they receive |
|---|---|---|
| Group 1 [HCG (+) group] | Experimental | "Group 1" will indicate the application of the protocol by adding hCG with the initiation of standard GnRH agonist protocol for IVF / ICSI with rFSH Receives: Drug: hCG |
| Group 2 [placebo] | Placebo comparator | "Group 2" will indicate the application of the standard GnRH agonist protocol without the addition of hCG, but placebo, instead Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
number of transferred embryos
number of high quality transferred embryos at day 3
Measured: 21 days after the beginning of ovarian stimulation
The rate of clinical pregnancy
Positive heart rate at 7 weeks of gestation in ultrasound
Measured: 7 weeks after the initiation of treatment
Secondary outcomes (4)
Number of follicles
(> 11,> 14,> 18 mm) on the day of triggering with hCG
Measured: 2 weeks after the initiation of treatment
The thickness of the endometrium
On the day of follicular maturation (triggering) with hCG
Measured: 2 weeks after the initiation of treatment
Automatic abortion rates - miscarriage
(Lss of pregnancy after positive heart function up to 20 weeks of gestation
Measured: up to 20 weeks of gestation
The percentage of ovarian hyperstimulation syndrome
After triggering with hCG
Measured: 2 weeks after the hCG triggering
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2018
- Study start1 Jun 2018
- Primary completion30 Apr 2019
- Study completion30 Apr 2019
Why it stopped: Inability for further recruitment, change of position of the principal investigator, COVID-19 pandemic
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for HCG; IVF; Pregnancy Rates; ART; Chorionic GonadotropinStudies of the same condition, open and under way.
- More trials run by National and Kapodistrian University of AthensThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- National and Kapodistrian University of Athens
- Sponsor type
- University, hospital or other
- Collaborators
- University of Thessaly
- Responsible party
- Principal investigator, Siristatidis Charalampos, MD, PhD, National and Kapodistrian University of Athens
- Investigators
- Charalampos Siristatidis, Ass Prof, Principal investigator, National and Kapodistrian University of Athens
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03423537
- Sponsor's protocol ID
- hCG-GR-001-2016
- Other IDs
- 2016-005208-24, 2016
- Acronym
- HCG
- Status last verified
- Sep 2020
- First submitted
- 21 Jan 2018
- Last updated
- 30 Mar 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Drakakis P, Loutradis D, Beloukas A, Sypsa V, Anastasiadou V, Kalofolias G, Arabatzi H, Kiapekou E, Stefanidis K, Paraskevis D, Makrigiannakis A, Hatzakis A, Antsaklis A. Early hCG addition to rFSH for ovarian stimulation in IVF provides better results and the cDNA copies of the hCG receptor may be an indicator of successful stimulation. Reprod Biol Endocrinol. 2009 Oct 13;7:110. doi: 10.1186/1477-7827-7-110.
PubMed 19825188Gomaa H, Casper RF, Esfandiari N, Chang P, Bentov Y. Addition of low dose hCG to rFSh benefits older women during ovarian stimulation for IVF. Reprod Biol Endocrinol. 2012 Aug 6;10:55. doi: 10.1186/1477-7827-10-55.
PubMed 22866896Martins WP, Vieira AD, Figueiredo JB, Nastri CO. FSH replaced by low-dose hCG in the late follicular phase versus continued FSH for assisted reproductive techniques. Cochrane Database Syst Rev. 2013 Mar 28;2013(3):CD010042. doi: 10.1002/14651858.CD010042.pub2.
PubMed 23543584Beretsos P, Partsinevelos GA, Arabatzi E, Drakakis P, Mavrogianni D, Anagnostou E, Stefanidis K, Antsaklis A, Loutradis D. "hCG priming" effect in controlled ovarian stimulation through a long protocol. Reprod Biol Endocrinol. 2009 Aug 31;7:91. doi: 10.1186/1477-7827-7-91.
PubMed 19719843
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Multicenter, Double-blind, Placebo-controlled, Phase III Clinical Study, on the Efficacy and Safety of Low-dose hCG in a Short Protocol With GnRH Agonist and Ovarian Stimulation With Recombinant FSH (rFSH) During the Follicular Phase in Subfertile Women Undergoing ART
- ClinicalTrials.gov ID
- NCT03423537
- Acronym / sponsor ID
- HCG / hCG-GR-001-2016
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Inability for further recruitment, change of position of the principal investigator, COVID-19 pandemic
- Enrolment
- 80 participants (actual)
- Lead sponsor
- National and Kapodistrian University of AthensUniversity, hospital or other
- Collaborators
- University of Thessaly
- Study start
- 1 Jun 2018 (actual)
- Primary completion
- 30 Apr 2019 (actual)
- Study completion
- 30 Apr 2019 (actual)
- First posted
- 6 Feb 2018 (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 objective of this prospective randomized clinical trial is to investigate whether the addition of low-dose hCG to a short GnRH-agonist protocol for IVF and ovarian stimulation with rFSH from the onset of the follicular phase and throughout stimulation in sub fertile women undergoing IVF, improves pregnancy rates.
Detailed description
This is a prospective, multicenter, randomized, double-blind, placebo-controlled, two parallel group of patients, Phase IIIb clinical study to test the efficacy and safety of adding low-dose hCGs in a short protocol with GnRH agonist and ovarian stimulation with recombinant FSH (rFSH) from the onset of the follicular phase and throughout the duration of stimulation in enrolled women to the increase in the rate of clinical pregnancies.
Main end point will be the rate of clinical pregnancy (positive heart rate at 7 weeks of gestation in the ultrasound), while secondary endpoints will be
- The number of follicles (> 11,> 14,> 18 mm) on the day of triggering with hCG
- The thickness of the endometrium on the day of follicular maturation
- Live birth rates
- Automatic abortion rates (loss of pregnancy after positive heart function up to 20 weeks of gestation)
- The rate of ongoing pregnancy (positive heart function after 12 weeks of gestation),
- The percentage of ovarian hyperstimulation syndrome (after triggering) with hCG for the next 2 weeks
- The rate of multiple pregnancy.
Participants will be randomly divided into two groups: the intervention group (Group 1) and the control group (Group 2). Randomization will be done using sealed envelopes marked "Group 1" and "Group 2". The randomization list will be prepared centrally for the four participating clinics (research centers) and there will be a "stratification" per center, per 30, respectively, and will be shared among the participants.
"Group 1" will indicate the application of the protocol by adding hCG with the initiation of controlled ovarian stimulation protocol for IVF / ICSI with rFSH, and "Group 2" will indicate the application of the conventional protocol without the addition of hCG .
Each patient's assignment to a treatment group will be made by calling the unit's midwife who will have 2 envelopes with the above indications and who will not be present when the pair is informed by 2 members of the research team.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 [HCG (+) group] | Experimental | Drug: hCG"Group 1" will indicate the application of the protocol by adding hCG with the initiation of standard GnRH agonist protocol for IVF / ICSI with rFSH |
| Group 2 [placebo] | Placebo comparator | Drug: Placebo"Group 2" will indicate the application of the standard GnRH agonist protocol without the addition of hCG, but placebo, instead |
Who may qualify
- Ages
- 35 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Age: between 35 and 40 years of age,
- Physiological menstrual cycles (24-35 day cycle),
- Normal endocrine function (normal PRL and TSH, FSH ≤ 15 IU / ml),
- Transvaginal ultrasound (TVS) without pathological findings,
- Free personal medical history,
Key exclusion criteria (7 listed)
- Endocrine or metabolic disorders, e.g. PCO (S)
- Pathology of the uterus and / or endometrium,
- Pelvic inflammatory disease (PID),
- Basal FSH levels> 15 IU / ml,
- Surgery in the ovaries,
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 |
|---|---|---|
| hCGAlso: Pregnylthe addition of hCG (Pregnyl®, MSD Greece) will begin with the administration of gonadotrophin at a dose of 100 IU per day, administered subcutaneously, and will continue until the administration of hCG for follicular maturation. | Drug | Group 1 [HCG (+) group] |
| Placebo100IU per day containing N/S 0.9% will be injected | Drug | Group 2 [placebo] |
Primary outcome
number of transferred embryos
Time frame: 21 days after the beginning of ovarian stimulation
number of high quality transferred embryos at day 3
The rate of clinical pregnancy
Time frame: 7 weeks after the initiation of treatment
Positive heart rate at 7 weeks of gestation in ultrasound
4 secondary outcomes
Number of follicles
Time frame: 2 weeks after the initiation of treatment
The thickness of the endometrium
Time frame: 2 weeks after the initiation of treatment
Automatic abortion rates - miscarriage
Time frame: up to 20 weeks of gestation
The percentage of ovarian hyperstimulation syndrome
Time frame: 2 weeks after the hCG triggering
Results and safety
The study was stopped early (reason given: Inability for further recruitment, change of position of the principal investigator, COVID-19 pandemic). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2021.
- Results publication: PubMed 19825188Drakakis P, Loutradis D, Beloukas A, Sypsa V, Anastasiadou V, Kalofolias G, Arabatzi H, Kiapekou E, Stefanidis K, Paraskevis D, Makrigiannakis A, Hatzakis A, Antsaklis A. Early hCG addition to rFSH for ovarian stimulation in IVF provides better results and the cDNA copies of the hCG receptor may be an indicator of successful stimulation. Reprod Biol Endocrinol. 2009 Oct 13;7:110. doi: 10.1186/1477-7827-7-110.
- Results publication: PubMed 22866896Gomaa H, Casper RF, Esfandiari N, Chang P, Bentov Y. Addition of low dose hCG to rFSh benefits older women during ovarian stimulation for IVF. Reprod Biol Endocrinol. 2012 Aug 6;10:55. doi: 10.1186/1477-7827-10-55.
- Results publication: PubMed 23543584Martins WP, Vieira AD, Figueiredo JB, Nastri CO. FSH replaced by low-dose hCG in the late follicular phase versus continued FSH for assisted reproductive techniques. Cochrane Database Syst Rev. 2013 Mar 28;2013(3):CD010042. doi: 10.1002/14651858.CD010042.pub2.
- Results publication: PubMed 19719843Beretsos P, Partsinevelos GA, Arabatzi E, Drakakis P, Mavrogianni D, Anagnostou E, Stefanidis K, Antsaklis A, Loutradis D. "hCG priming" effect in controlled ovarian stimulation through a long protocol. Reprod Biol Endocrinol. 2009 Aug 31;7:91. doi: 10.1186/1477-7827-7-91.
- Current guidelinesLink provided by the sponsor.
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.
Charalampos Siristatidis, Ass Prof principal investigator
National and Kapodistrian University of Athens
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing hCG in people with HCG; IVF; Pregnancy Rates; ART; Chorionic Gonadotropin, run by National and Kapodistrian University of Athens at 1 site 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 7 inclusion and 7 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: stopped early, as of the sponsor's last update on 30 Mar 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 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 was stopped early (reason given: Inability for further recruitment, change of position of the principal investigator, COVID-19 pandemic). 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?
number of transferred embryos (time frame: 21 days after the beginning of ovarian stimulation). The study lists 2 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 NCT03423537, which also lists 4 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 30 Mar 2021.