InfertilityPhase 4NCT01233206
Metformin in High Responder Polycystic Ovary Syndrome (PCOS) Patients Undergoing IVF Cycles
A Phase 4 study testing Metformin in people with Infertility and Polycystic Ovary Syndrome (PCOS), run by University Magna Graecia at 1 site in Italy.
Trial summary
The use of metformin pre-treatment and co-administration was recently proposed in infertile women affected by polycystic ovary syndrome (PCOS) treated with gonadotropins. Data from meta-analyses showed that metformin administration significantly reduced the stimulation length and the total dose of gonadotropins used… Read more about this study
- Who is it for?
- Ages 18 to 35 years, women only
- Conditions the study is for
- Infertility, Polycystic Ovary Syndrome (PCOS)
- What is being tested?
- Metformin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteItaly
- Study dates
- May 2009to Jan 2011
- 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 35 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- History of one previous cancelled cycle for high-risk of OHSS, or history of moderate/severe OHSS during their previous IVF cycle
- Infertility
- Polycystic ovary syndrome (PCOS)
- insulin resistance
- hyperandrogenism
Who cannot join
- BMI>30 kg/m2
- age >35 years
- FSH>9UI/L
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Metformin Addition to Gonadotropins Ovarian Stimulation in High Responder Patients With PCOS Undergoing In-vitro Fertilization
The use of metformin pre-treatment and co-administration was recently proposed in infertile women affected by polycystic ovary syndrome (PCOS) treated with gonadotropins.
Data from meta-analyses showed that metformin administration significantly reduced the stimulation length and the total dose of gonadotropins used in PCOS women undergoing gonadotropins stimulation for non in-vitro fertilization (IVF) cycles. On the other hand, in IVF cycles metformin was demonstrated to significantly reduce the ovarian hyperstimulation syndrome (OHSS) rate in infertile patients with PCOS treated with gonadotropins.
Read more
The metformin regulating effect on the ovarian response was also observed in a randomized controlled trial (RCT) on young non-obese insulin-resistant women with PCOS receiving gonadotropins for mono-ovulation induction. In particular, metformin increased the mono-ovulatory cycles, the duration of stimulation and the amount of gonadotropins used, while it reduced the number of dominant follicles and the estradiol (E2) levels.
The aim of the present study was to evaluate the effect of metformin administration in high responder PCOS patients undergoing gonadotropins ovarian stimulation for IVF cycles.
Read the detailed description
Infertile young non-obese insulin-resistant patients with PCOS who had a background of the first IVF treatment cycle cancelled because of high risk for OHSS will be enrolled and randomized in two treatment arms.
In their second IVF attempt, the experimental group will receive metformin (500 mg, 3 times daily) pre-treatment for two weeks and co-administration during gonadotropins ovarian stimulation; the control group will be treated with placebo (2 cps daily) pre-treatment and co-administration by using the same schedule of the experimental group. In all patients, ovarian stimulation will be carried out with a personalized step-down gonadotropin in association with a minidose flare-up GnRH agonist protocol.
- Conditions
- Infertility, Polycystic Ovary Syndrome (PCOS)
- Being tested
- Metformin, Placebo administration
- Keywords
- PCOS, Polycystic ovary syndrome, Cancelled cycles, OHSS, Infertility
- Medical subject headings
- Infertility, Polycystic Ovary Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Metformin pre-treatment and co-administration
Placebo administrationDrug
Placebo pre-treatment and co-administration
| Study group | Role | What they receive |
|---|---|---|
| Experimental group | Experimental | Patients receiving metformin pretreatment and co-administration Receives: Drug: Metformin |
| Control group | Placebo comparator | Placebo Receives: Drug: Placebo administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of OHSS
Measured: one month
Secondary outcomes (9)
Stimulation length
Measured: one month
Gonadotropins dose
Measured: one month
Dominant follicles on day of ovulation triggering
Measured: one month
Ovulation rate
Measured: one month
Peak estradiol levels on day of ovulation triggering
Measured: one month
Embryo quality
Measured: one month
pregnancy rate
Measured: one month
multiple pregnancy rate
Measured: one month
Live birth rate
Measured: ten months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2010 (estimated)
- Study startMay 2009
- Primary completionNov 2010
- Study completionJan 2011
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 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
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Magna Graecia
- Sponsor type
- University, hospital or other
- Investigators
- Stefano Palomba, Principal investigator, University Magna GraeciaFulvio Zullo, Study chair, University Magna Graecia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01233206
- Sponsor's protocol ID
- 04/2010
- Status last verified
- Jun 2011
- First submitted
- 8 Oct 2010
- Last updated
- 10 Jun 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Palomba S, Falbo A, Orio F Jr, Manguso F, Russo T, Tolino A, Annamaria C, Dale B, Zullo F. A randomized controlled trial evaluating metformin pre-treatment and co-administration in non-obese insulin-resistant women with polycystic ovary syndrome treated with controlled ovarian stimulation plus timed intercourse or intrauterine insemination. Hum Reprod. 2005 Oct;20(10):2879-86. doi: 10.1093/humrep/dei130. Epub 2005 Jun 15.
PubMed 15958399Tso LO, Costello MF, Albuquerque LET, Andriolo RB, Macedo CR. Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2020 Dec 21;12(12):CD006105. doi: 10.1002/14651858.CD006105.pub4.
PubMed 33347618Palomba S, Falbo A, Carrillo L, Villani MT, Orio F, Russo T, Di Cello A, Cappiello F, Capasso S, Tolino A, Colao A, Mastrantonio P, La Sala GB, Zullo F, Cittadini E; METformin in High Responder Italian Group. Metformin reduces risk of ovarian hyperstimulation syndrome in patients with polycystic ovary syndrome during gonadotropin-stimulated in vitro fertilization cycles: a randomized, controlled trial. Fertil Steril. 2011 Dec;96(6):1384-1390.e4. doi: 10.1016/j.fertnstert.2011.09.020. Epub 2011 Oct 7.
PubMed 21982727
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metformin Addition to Gonadotropins Ovarian Stimulation in High Responder Patients With PCOS Undergoing In-vitro Fertilization
- ClinicalTrials.gov ID
- NCT01233206
- Acronym / sponsor ID
- 04/2010
- Conditions
- Infertility, Polycystic Ovary Syndrome (PCOS)
- Keywords
- PCOS, Polycystic ovary syndrome, Cancelled cycles, OHSS, Infertility
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- University Magna GraeciaUniversity, hospital or other
- Study start
- May 2009
- Primary completion
- Nov 2010 (actual)
- Study completion
- Jan 2011 (actual)
- First posted
- 3 Nov 2010 (estimated)
- 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 use of metformin pre-treatment and co-administration was recently proposed in infertile women affected by polycystic ovary syndrome (PCOS) treated with gonadotropins.
Data from meta-analyses showed that metformin administration significantly reduced the stimulation length and the total dose of gonadotropins used in PCOS women undergoing gonadotropins stimulation for non in-vitro fertilization (IVF) cycles. On the other hand, in IVF cycles metformin was demonstrated to significantly reduce the ovarian hyperstimulation syndrome (OHSS) rate in infertile patients with PCOS treated with gonadotropins.
The metformin regulating effect on the ovarian response was also observed in a randomized controlled trial (RCT) on young non-obese insulin-resistant women with PCOS receiving gonadotropins for mono-ovulation induction. In particular, metformin increased the mono-ovulatory cycles, the duration of stimulation and the amount of gonadotropins used, while it reduced the number of dominant follicles and the estradiol (E2) levels.
The aim of the present study was to evaluate the effect of metformin administration in high responder PCOS patients undergoing gonadotropins ovarian stimulation for IVF cycles.
Detailed description
Infertile young non-obese insulin-resistant patients with PCOS who had a background of the first IVF treatment cycle cancelled because of high risk for OHSS will be enrolled and randomized in two treatment arms.
In their second IVF attempt, the experimental group will receive metformin (500 mg, 3 times daily) pre-treatment for two weeks and co-administration during gonadotropins ovarian stimulation; the control group will be treated with placebo (2 cps daily) pre-treatment and co-administration by using the same schedule of the experimental group. In all patients, ovarian stimulation will be carried out with a personalized step-down gonadotropin in association with a minidose flare-up GnRH agonist protocol.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental group | Experimental | Drug: MetforminPatients receiving metformin pretreatment and co-administration |
| Control group | Placebo comparator | Drug: Placebo administrationPlacebo |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- History of one previous cancelled cycle for high-risk of OHSS, or history of moderate/severe OHSS during their previous IVF cycle
- Infertility
- Polycystic ovary syndrome (PCOS)
- insulin resistance
- hyperandrogenism
Key exclusion criteria (3 listed)
- BMI>30 kg/m2
- age >35 years
- FSH>9UI/L
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 |
|---|---|---|
| MetforminMetformin pre-treatment and co-administration | Drug | Experimental group |
| Placebo administrationPlacebo pre-treatment and co-administration | Drug | Control group |
Primary outcome
Rate of OHSS
Time frame: one month
9 secondary outcomes
Stimulation length
Time frame: one month
Gonadotropins dose
Time frame: one month
Dominant follicles on day of ovulation triggering
Time frame: one month
Ovulation rate
Time frame: one month
Peak estradiol levels on day of ovulation triggering
Time frame: one month
Embryo quality
Time frame: one month
pregnancy rate
Time frame: one month
multiple pregnancy rate
Time frame: one month
Live birth rate
Time frame: ten months
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 10 Jun 2011.
- Background: PubMed 15958399Palomba S, Falbo A, Orio F Jr, Manguso F, Russo T, Tolino A, Annamaria C, Dale B, Zullo F. A randomized controlled trial evaluating metformin pre-treatment and co-administration in non-obese insulin-resistant women with polycystic ovary syndrome treated with controlled ovarian stimulation plus timed intercourse or intrauterine insemination. Hum Reprod. 2005 Oct;20(10):2879-86. doi: 10.1093/humrep/dei130. Epub 2005 Jun 15.
- Derived from this study: PubMed 33347618Tso LO, Costello MF, Albuquerque LET, Andriolo RB, Macedo CR. Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2020 Dec 21;12(12):CD006105. doi: 10.1002/14651858.CD006105.pub4.
- Derived from this study: PubMed 21982727Palomba S, Falbo A, Carrillo L, Villani MT, Orio F, Russo T, Di Cello A, Cappiello F, Capasso S, Tolino A, Colao A, Mastrantonio P, La Sala GB, Zullo F, Cittadini E; METformin in High Responder Italian Group. Metformin reduces risk of ovarian hyperstimulation syndrome in patients with polycystic ovary syndrome during gonadotropin-stimulated in vitro fertilization cycles: a randomized, controlled trial. Fertil Steril. 2011 Dec;96(6):1384-1390.e4. doi: 10.1016/j.fertnstert.2011.09.020. Epub 2011 Oct 7.
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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.
Stefano Palomba principal investigator
University Magna Graecia
Fulvio Zullo study chair
University Magna Graecia
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 Metformin in people with Infertility and Polycystic Ovary Syndrome (PCOS), run by University Magna Graecia at 1 site in Italy.
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 5 inclusion and 3 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 10 Jun 2011. 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 Italy. 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 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?
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?
Rate of OHSS (time frame: one month). 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 NCT01233206, 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 10 Jun 2011.