Metformin Treatment Before in Vitro Fertilization (IVF) in Women With Ultrasound Evidence of Polycystic Ovaries

Polycystic Ovary Syndrome Clinical Trial

Official title:

Metformin Treatment Before IVF in Women With Ultrasound Evidence of Polycystic Ovaries; a Prospective, Randomised, Double Blind, Placebo Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01046032
• Other study ID #: 05/Q1605/87
• Status: Completed
• Phase: N/A
• First received: January 3, 2010
• Last updated: January 8, 2010
• Start date: December 2005
• Est. completion date: May 2009

Study information

• Verified date: January 2010
• Source: University of Oxford
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

The aim of study was to investigate whether pre-treatment with metformin before and during IVF increases the live birth rate compared to placebo in women with sonographic evidence of polycystic ovaries (PCO), but without any clinical manifestations of polycystic ovary syndrome (PCOS).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 134
• Est. completion date: May 2009
• Est. primary completion date: May 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: N/A to 38 Years

Eligibility

Inclusion Criteria:

• Women attending with ovulatory PCO due to undergo IVF/ICSI treatment.

• First or second cycle of IVF/ICSI.

• If previously on metformin, a minimum one month washout period was required.

• Polycystic ovaries diagnosed by ultrasound presence of =12 follicles measuring 2-9 mm in diameter in at least one ovary and/or increased ovarian volume (=10 ml).

• Written informed consent.

Exclusion Criteria:

• Clinical manifestations of PCOS, including any of the following:

1. Oligo- or amenorrhoea with cycles =42 days apart.

2. Anovulation with mid-luteal progesterone <16 nmol/L.

3. Biochemical hyperandrogenism with serum testosterone =3.5 nmol/L and/or free androgen index >5 (FAI = [total testosterone/SHBG] x 100).

4. Clinical hyperandrogenism with hirsutism or acne requiring treatment at least weekly.

• Age >38 years.

• BMI >35 kg/m2.

• Basal FSH >12 IU/L.

• Liver disease or ALT >80 IU/L.

• Renal disease, or creatinine >130 nmol/L.

• Alcoholism or drug abuse.

• Diabetes mellitus (evaluated by fasting glucose >6.7mmol/L).

• Per oral steroid treatment in last month.

• Cimetidine, anticoagulation, erythromycin, or other macrolides in last month.

• Hyperprolactinemia (Prolactin >700 mIU/L).

• Abnormal thyroid function tests (TSH outside of laboratory normal range).

• Congenital adrenal hyperplasia.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Polycystic Ovary Syndrome

Intervention

Drug:
• Metformin
Women were randomised to receive either metformin or placebo starting three weeks before initiation of a GnRH agonist during an IVF treatment cycle (seven weeks prior to oocyte collection and then stopped at oocyte collection). Seventy identical packs of metformin and 70 identical packs of placebo were supplied by DHP Ltd, Crickhowell, Powys (UK) a commercial clinical trial supplier. The randomisation service was provided by DHP Ltd.
• Placebo
Women were randomised to receive either metformin or placebo starting three weeks before initiation of a GnRH agonist during an IVF treatment cycle (seven weeks prior to oocyte collection and then stopped at oocyte collection). Seventy identical packs of metformin and 70 identical packs of placebo were supplied by DHP Ltd, Crickhowell, Powys (UK) a commercial clinical trial supplier. The randomisation service was provided by DHP Ltd.

Locations

Country	Name	City	State
United Kingdom	IVF Hammersmith	London
United Kingdom	Nuture IVF Unit	Nottingham
United Kingdom	Oxford Fertility Unit	Oxford

Sponsors (3)

Lead Sponsor	Collaborator
University of Oxford	Imperial College London, University of Nottingham

Country where clinical trial is conducted

United Kingdom, 

References & Publications (2)

Kjøtrød SB, von Düring V, Carlsen SM. Metformin treatment before IVF/ICSI in women with polycystic ovary syndrome; a prospective, randomized, double blind study. Hum Reprod. 2004 Jun;19(6):1315-22. Epub 2004 Apr 29. — View Citation

Tang T, Glanville J, Orsi N, Barth JH, Balen AH. The use of metformin for women with PCOS undergoing IVF treatment. Hum Reprod. 2006 Jun;21(6):1416-25. Epub 2006 Feb 24. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Live birth rate		End of pregnancy	No
Secondary	Severe ovarian hyperstimulation syndrome		2 months	No