AzTrials
AzTrials

Polycystic Ovary SyndromePhase 3NCT03086005

Study to Assess the Effect of Metformin Supplementation on IVF Outcome in Patients With Polycystic Ovarian Syndrome.

A Phase 3 study testing Metformin in people with Polycystic Ovary Syndrome, run by Chung-Hoon Kim at 1 site in South Korea.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study was performed to investigate the effects of metformin on controlled ovarian stimulation (COS), in vitro fertilization (IVF) outcomes, pregnancy outcomes, and comparison of serum and follicular fluid cytokines and hormones in patients with polycystic ovary syndrome (PCOS) undergoing IVF using… Read more about this study

Who is it for?
Ages 20 to 40 years, women only
Conditions the study is for
Polycystic Ovary Syndrome
What is being tested?
Metformin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
24 participants
Where
1 siteSouth Korea
Study dates
12 Oct 2011to 23 Jul 2015
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 20 to 40 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

  • PCOS diagnostic criteria
  • 2003 American Society for Reproductive Medicine(ARSM)/European Society of Human Reproduction and Embryology(ESHRE) consensus meeting guideline
  • include two out of three
  • Oligo - or anovulation
  • Clinical or/and biochemical hyperandrogenism
  • Polycystic ovaries on ultrasound, exclusion of other etiologies( ≥ 12 follicles(2-9 mm diameter) in each ovary or ovarian volume(0.5 x length x width x thickness) ≥ 10cm3)
  • Anatomical normal uterus
  • Normal level of thyroid hormone

Who cannot join

  • Severe endometriosis(stageIII, IV)
  • Endometrial thickness less than 7mm in late follicular phase
  • Severe male infertility factor, non-obstructive azoospermia
  • History of ectopic pregnancy or abortion over the last 3 months
  • Unexplained abnormal uterine bleeding
  • Congenital adrenal hyperplasia
Show all 13Show fewer
  • Androgen secreting tumor
  • Cushing syndrome
  • Concurrent administration of metformin, ovulation induction drugs, oral contraceptives within previous 3 months
  • Chronic disease(liver, kidney, severe heart failure, DM)
  • Any pathology of genital tract
  • History of alcohol abuse
  • Refuse of study participate consent

Trial locations and contacts

1 site in 1 country.

South Korea1 site

  • Asan Medical Center

    Seoul, Songpa-gu, 05505

Other trials in South Korea

About this study

Official title: A Multicenter, Prospective, Randomized Study to Assess the Effect of Metformin Supplementation on IVF Outcome and Intrafollicular Environment in Patients With Polycystic Ovarian Syndrome Undergoing In Vitro Fertilization/Embryo Transfer

This study was performed to investigate the effects of metformin on controlled ovarian stimulation (COS), in vitro fertilization (IVF) outcomes, pregnancy outcomes, and comparison of serum and follicular fluid cytokines and hormones in patients with polycystic ovary syndrome (PCOS) undergoing IVF using gonadotropin-releasing hormone(GnRH) antagonist protocol.

Read the detailed description

Polycystic ovary syndrome is the common cause of the female infertility that features insulin resistance and hyperinsulinemia participate in the reproductive as well as metabolic disturbances.

In many studies, metformin treatment reduces androgen levels and attenuates hyperinsulinemia in women with PCOS. This favorable effect on insulin and androgens levels, justifies the use of metformin in reproductive disturbances in PCOS women. Metformin treatment was shown to diminish ovarian androgen secretion, while lowering insulin levels in women with PCOS.

In women with PCOS, metformin treatment may increase ovulation, improve menstrual cyclicity, and reduce seum androgen levels. Metformin has direct effects on the ovary and also reduces the level of insulin that act upon the ovary. It has been indicated that metformin has direct, insulin-independent actions on theca cell steroidogenesis, because in human ovarian theca-like tumor cells, metformin suppressed androstenedione production. Metformin also exert a direct effect on granulosa cells and subsequent reduction of steroid production.

Metformin was shown to improve endothelium dependent vasodilation in insulin resistant patients and potentially protect against atherogenesis and cardiovascular disease.

Considering gonadotropin ovulation induction or IVF in women with PCOS, metformin coadministration improves the pregnancy outcome and reduces the risk of ovarian hyperstimulation syndrome. Metformin therapy throughout pregnancy can reduce the risk of early miscarriage or the incidence of gestational diabetes.

All patients were pretreated for 3 weeks with monophasic oral contraceptive (OC)(Yasmin; Bayer Schering Pharma, Berlin, Germany) before COS. Five days after OC discontinuation, COS for IVF/ICSI was commenced. GnRH antagonist protocol was used for COS in all subjects. Patients were randomly allocated into the metformin or control groups, using sealed envelopes.

Being tested
Metformin
Keywords
Metformin
Medical subject headings
Polycystic Ovary Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MetforminDrug

    Also called Glucophage Tab 500mg, National Drug Code(NDC) 0087-6060-05

Study groups in NCT03086005
Study groupRoleWhat they receive
MetforminExperimentalMetformin 500mg tablet by mouth, every 12 hours, from the first day of oral contraceptive pills taken to the day of oocyte retrieval
Receives: Drug: Metformin
PlaceboPlacebo comparatorPlacebo(identical in appearance to metformin), every 12 hours, from the first day of oral contraceptive pills taken to the day of oocyte retrieval
Receives: Drug: Metformin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of mature(MII) oocyte

    using polarized light microscopy

    Measured: Day1(from the day of oocyte retrieval to fertilization confirmation)

Secondary outcomes (8)

  1. Clinical pregnancy rate in %

    Clinical pregnancy was defined as a viable pregnancy beyond 12 weeks gestation by ultrasonographic visualization.

    Measured: Pregnancy test was carried out at 11 days after embryo transfer and was classified as positive when the serum beta-human chorionic gonadotropin(hCG) level was over 5 IU/L. Than follow up to 12 weeks of gestation.

  2. Miscarriage rate in %

    Miscarriage was defined as a early loss of a pregnancy before 20 weeks of pregnancy.

    Measured: Pregnancy test was carried out at 11 days after embryo transfer and was classified as positive when the serum beta-human chorionic gonadotropin(hCG) level was over 5 IU/L. Than follow up to 20 weeks of gestation.

  3. Total dose of follicle-stimulating hormone(FSH) used(IU)

    compare the ovarian response to controlled ovarian stimulation between two groups

    Measured: average of 10 days, From the day of stimulation start with FSH to the day of oocyte retrieval

  4. Total duration of FSH used(day)

    compare the ovarian response to controlled ovarian stimulation between two groups

    Measured: average of 10 days, From the day of stimulation start with FSH to the day of oocyte retrieval

  5. Number of oocytes retrieved

    using polarized light microscopy

    Measured: Day1(the day of oocyte retrieval)

  6. Number of frozen 2 pronucleus(2PN) embryos

    using polarized light microscopy

    Measured: Day1((from the day of oocyte retrieval to fertilization confirmation)

  7. Follicular fluid Tumor necrosis factor(TNF)-α level in pg/ml and follicular fluid Adiponectin level in pg/ml and follicular fluid Interleukin-6 level in pg/ml and follicular fluid Anti-mullerian hormone(AMH) level in pg/ml

    At the day of oocyte retrieval, follicular fluids were collected from the follicles with a diameter over than 15mm. The fluids were frozen within 4 hours for the future analysis. All the samples were stored at -20℃ and were analysed in the biochemistry department of the study centre.

    Measured: Day 1

  8. Serum TNF-α level in pg/ml and serum Adiponectin level in pg/ml and serum Interleukin-6 level in pg/ml and serum AMH level in pg/ml and serum Testosterone level in pg/ml and serum Estradiol level in pg/ml

    Serum samples were obtained on the day of Metformin commencement and ovum pick up. Levels are measured by means of solid-phase enzyme-linked immunosorbent assay.

    Measured: Day 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Mar 2017
  2. Study start12 Oct 2011
  3. Primary completion4 May 2015
  4. Study completion23 Jul 2015

Resources

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
Double blind
Who is masked
Participant, Investigator
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03086005
Sponsor's protocol ID
2010-Metformin for PCOS
Status last verified
May 2017
First submitted
15 Feb 2017
Last updated
11 May 2017
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Consensus on infertility treatment related to polycystic ovary syndrome. Hum Reprod. 2008 Mar;23(3):462-77. doi: 10.1093/humrep/dem426.

    PubMed 18308833

  • Diamanti-Kandarakis E, Economou F, Palimeri S, Christakou C. Metformin in polycystic ovary syndrome. Ann N Y Acad Sci. 2010 Sep;1205:192-8. doi: 10.1111/j.1749-6632.2010.05679.x.

    PubMed 20840272

  • Doldi N, Persico P, Di Sebastiano F, Marsiglio E, Ferrari A. Gonadotropin-releasing hormone antagonist and metformin for treatment of polycystic ovary syndrome patients undergoing in vitro fertilization-embryo transfer. Gynecol Endocrinol. 2006 May;22(5):235-8. doi: 10.1080/14767050600761893.

    PubMed 16785142

  • Farrell K, Antoni MH. Insulin resistance, obesity, inflammation, and depression in polycystic ovary syndrome: biobehavioral mechanisms and interventions. Fertil Steril. 2010 Oct;94(5):1565-74. doi: 10.1016/j.fertnstert.2010.03.081. Epub 2010 May 14.

    PubMed 20471009

  • Katsiki N, Hatzitolios AI. Insulin-sensitizing agents in the treatment of polycystic ovary syndrome: an update. Curr Opin Obstet Gynecol. 2010 Dec;22(6):466-76. doi: 10.1097/GCO.0b013e32833e1264.

    PubMed 20724929

  • Toulis KA, Goulis DG, Farmakiotis D, Georgopoulos NA, Katsikis I, Tarlatzis BC, Papadimas I, Panidis D. Adiponectin levels in women with polycystic ovary syndrome: a systematic review and a meta-analysis. Hum Reprod Update. 2009 May-Jun;15(3):297-307. doi: 10.1093/humupd/dmp006. Epub 2009 Mar 4.

    PubMed 19261627

  • Ardawi MS, Rouzi AA. Plasma adiponectin and insulin resistance in women with polycystic ovary syndrome. Fertil Steril. 2005 Jun;83(6):1708-16. doi: 10.1016/j.fertnstert.2004.11.077.

    PubMed 15950640

  • Tso 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 33347618

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Metformin in people with Polycystic Ovary Syndrome, run by Chung-Hoon Kim at 1 site in South Korea.

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 8 inclusion and 13 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 11 May 2017. 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 South Korea. 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 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?

Number of mature(MII) oocyte (time frame: Day1(from the day of oocyte retrieval to fertilization confirmation)). 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 NCT03086005, which also lists 8 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 11 May 2017.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in