Clinical trial NCT01046032: Metformin Treatment Before in Vitro Fertilization (IVF) in Women With Ultrasound Evidence of Polycystic Ovaries
Official title: Metformin Treatment Before IVF in Women With Ultrasound Evidence of Polycystic Ovaries; a Prospective, Randomised, Double Blind, Placebo Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Polycystic Ovary Syndrome
Keywords: Polycystic ovaries
Ovarian stimulation
IVF
Ovarian hyperstimulation
Metformin
Lead sponsor: University of Oxford
Sponsor class: OTHER
Collaborators: name: Imperial College London
name: University of Nottingham
First posted: 2010-01-11
Enrollment: 134
Sex: FEMALE
Maximum age (years): 38
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Live birth rate
timeFrame: End of pregnancy
Secondary outcomes:
measure: Severe ovarian hyperstimulation syndrome
timeFrame: 2 months
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: IVF Hammersmith
city: Nottingham
country: United Kingdom
facility: Nuture IVF Unit
city: Oxford
country: United Kingdom
facility: Oxford Fertility Unit
Study officials:
affiliation: University of Oxford
name: Tim J Child, MA MD MRCOG
role: STUDY_DIRECTOR
affiliation: University of Oxford
name: Alexander G Swanton, MBBS MRCOG
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.1093/humrep/del025. Epub 2006 Feb 24.
citation: 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.
citation: 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.