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

NCT01046032 | Completed DMC

• 1 other identifier: 05/Q1605/87
• Study Type: interventional
• Target: 134
• Locations: 1 country
• Sites: 3

Brief 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).

Conditions

Polycystic Ovary Syndrome

Keywords

Polycystic ovaries; Ovarian stimulation; IVF; Ovarian hyperstimulation; Metformin

Outcome Measures

Primary Outcomes (1)

• Live birth rate

  End of pregnancy

Secondary Outcomes (1)

• Severe ovarian hyperstimulation syndrome

  2 months

Study Arms (2)

Metformin

ACTIVE COMPARATOR

Drug (including placebo)

Drug: Metformin

Sugar pill

PLACEBO COMPARATOR

Drug (including placebo)

Drug: Placebo

Interventions

Metformin DRUG

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.

Metformin

Placebo DRUG

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.

Sugar pill

Eligibility Criteria

• Age: Up to 38 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• Clinical manifestations of PCOS, including any of the following:
• Oligo- or amenorrhoea with cycles ≥42 days apart.
• Anovulation with mid-luteal progesterone \<16 nmol/L.
• Biochemical hyperandrogenism with serum testosterone ≥3.5 nmol/L and/or free androgen index \>5 (FAI = \[total testosterone/SHBG\] x 100).
• 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).

Sponsors & Collaborators

• University of Oxford: lead
• Imperial College London: collaborator
• University of Nottingham: collaborator

Study Sites (3)

IVF Hammersmith

London, United Kingdom

Location

Nuture IVF Unit

Nottingham, United Kingdom

Location

Oxford Fertility Unit

Oxford, OX39DU, United Kingdom

Location

Related Publications (3)

• 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. doi: 10.1093/humrep/del025. Epub 2006 Feb 24.

  PMID: 16501038 BACKGROUND

• Kjotrod SB, von During 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. doi: 10.1093/humrep/deh248. Epub 2004 Apr 29.

  PMID: 15117902 BACKGROUND

• Swanton A, Lighten A, Granne I, McVeigh E, Lavery S, Trew G, Talmor A, Raine-Fenning N, Jayaprakasan K, Child T. Do women with ovaries of polycystic morphology without any other features of PCOS benefit from short-term metformin co-treatment during IVF? A double-blind, placebo-controlled, randomized trial. Hum Reprod. 2011 Aug;26(8):2178-84. doi: 10.1093/humrep/der120. Epub 2011 May 18.

  PMID: 21593045 DERIVED

MeSH Terms

Conditions

Polycystic Ovary Syndrome

Interventions

Metformin

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Tim J Child, MA MD MRCOG

  University of Oxford

  STUDY DIRECTOR

• Alexander G Swanton, MBBS MRCOG

  University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 3, 2010
• First Posted: January 11, 2010
• Study Start: December 1, 2005
• Primary Completion: May 1, 2009
• Study Completion: May 1, 2009
• Last Updated: January 11, 2010

Record last verified: 2010-01

Locations

GB (3)