Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03086005
Recruitment Status : Completed
First Posted : March 22, 2017
Last Update Posted : May 11, 2017
Sponsor:
Information provided by (Responsible Party):
Chung-Hoon Kim, Asan Medical Center

Brief 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 gonadotropin-releasing hormone(GnRH) antagonist protocol.

Condition or disease Intervention/treatment Phase
Polycystic Ovary Syndrome Drug: Metformin Phase 3

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : October 12, 2011
Actual Primary Completion Date : May 4, 2015
Actual Study Completion Date : July 23, 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Metformin
Metformin 500mg tablet by mouth, every 12 hours, from the first day of oral contraceptive pills taken to the day of oocyte retrieval
Drug: Metformin
Other Name: Glucophage Tab 500mg, National Drug Code(NDC) 0087-6060-05

Placebo Comparator: Placebo
Placebo(identical in appearance to metformin), every 12 hours, from the first day of oral contraceptive pills taken to the day of oocyte retrieval
Drug: Metformin
Other Name: Glucophage Tab 500mg, National Drug Code(NDC) 0087-6060-05




Primary Outcome Measures :
  1. Number of mature(MII) oocyte [ Time Frame: Day1(from the day of oocyte retrieval to fertilization confirmation) ]
    using polarized light microscopy


Secondary Outcome Measures :
  1. Clinical pregnancy rate in % [ Time Frame: 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. ]
    Clinical pregnancy was defined as a viable pregnancy beyond 12 weeks gestation by ultrasonographic visualization.

  2. Miscarriage rate in % [ Time Frame: 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. ]
    Miscarriage was defined as a early loss of a pregnancy before 20 weeks of pregnancy.

  3. Total dose of follicle-stimulating hormone(FSH) used(IU) [ Time Frame: average of 10 days, From the day of stimulation start with FSH to the day of oocyte retrieval ]
    compare the ovarian response to controlled ovarian stimulation between two groups

  4. Total duration of FSH used(day) [ Time Frame: average of 10 days, From the day of stimulation start with FSH to the day of oocyte retrieval ]
    compare the ovarian response to controlled ovarian stimulation between two groups

  5. Number of oocytes retrieved [ Time Frame: Day1(the day of oocyte retrieval) ]
    using polarized light microscopy

  6. Number of frozen 2 pronucleus(2PN) embryos [ Time Frame: Day1((from the day of oocyte retrieval to fertilization confirmation) ]
    using polarized light microscopy

  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 [ Time Frame: Day 1 ]
    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.

  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 [ Time Frame: Day 1 ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   20 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

      1. Oligo - or anovulation
      2. Clinical or/and biochemical hyperandrogenism
      3. 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

Exclusion Criteria:

  • 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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03086005


Locations
Layout table for location information
Korea, Republic of
Asan Medical Center
Seoul, Songpa-gu, Korea, Republic of, 05505
Sponsors and Collaborators
Chung-Hoon Kim
Investigators
Layout table for investigator information
Study Chair: CHUNG-HUN KIM, Professor Asan Medical Center
Publications:

Layout table for additonal information
Responsible Party: Chung-Hoon Kim, Asan Medical Center
ClinicalTrials.gov Identifier: NCT03086005    
Other Study ID Numbers: 2010-Metformin for PCOS
First Posted: March 22, 2017    Key Record Dates
Last Update Posted: May 11, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Chung-Hoon Kim, Asan Medical Center:
Metformin
Additional relevant MeSH terms:
Layout table for MeSH terms
Polycystic Ovary Syndrome
Syndrome
Disease
Pathologic Processes
Ovarian Cysts
Cysts
Neoplasms
Ovarian Diseases
Adnexal Diseases
Gonadal Disorders
Endocrine System Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs