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

Study Overview
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Brief Summary
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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).

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

Conditions
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Polycystic Ovary Syndrome

Intervention / Treatment
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* Drug: Metformin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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: 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). Abnormal thyroid function tests (TSH outside of laboratory normal range). Congenital adrenal hyperplasia.

Ages Eligible for Study
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Maximum Age: 38 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Metformin<br>Drug (including placebo) | Drug: Metformin<br>* 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.<br>|
| Placebo Comparator: Sugar pill<br>Drug (including placebo) | Drug: Placebo<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Live birth rate |  | End of pregnancy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severe ovarian hyperstimulation syndrome |  | 2 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Polycystic ovaries, Ovarian stimulation, IVF, Ovarian hyperstimulation, Metformin