E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Polycystic ovary syndrome (PCOS) is a disorder characterized by polycystic ovaries, oligo-amenorrea and hyperandogenism. It is the most common endocrine disorder in women of fertile age. PCOS women are an- or oligoovulatory and often suffer from infertility or subfertility. Prevalence estimates vary between three and twenty percent depending on the diagnostic criteriae used, and the population studied. A prevalence of five to seven percent has been reprted in Caucasian women. |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Does Metformin treatment before IVF/ICSI in non obese (BMI below 28 kg/m2) women with polycystic ovarian syndrome increase clinical pregnancy rate in IVF/ICSI? Clinical pregnancy rate is defined as a verified intrauterine gestational sack by ultrasound week seven of pregnancy. |
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E.2.2 | Secondary objectives of the trial |
-Number of oocytes collected and embryo quality -Dose of gonadotrophin, both daily and total used in IVF/ICSI cycle (ie costs of treatment) Also number of days of gonadotrophin treatment. -s-Estradiol on day of hCG-injection, and occurrence of ovarian hyperstimulation syndome (OHSS) -Spontaneous pregnancy rates during pretreatment period (ie before IVF/ICSI) -Spontaneous abortion rates and finally live birth rates.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
--PCOS diagnosis based on the ESHRE/ASRM (Rotterdam may 03) criteria;-fulfilling at least two of the following three criteria - Oligo-amenorrea, hyperandrogenism and/or PCO-ovaries by ultrasound. -More than one year of infertility in PCOS women planned for IVF or ICSI -First or second cycle of IVF or ICSI-treatment -Age below 38 years at inclusion -BMI below 28 kg/m2 at inclusion -Patient willing to be randomised for 4 months treatment with metformin or placebo -If previously on metformin, a one month wash-out period is required. |
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E.4 | Principal exclusion criteria |
-More than one previous IVF-cycle -Patients not suitable for starting dose 112.5 IE of Gonal F -Basal-FSH above 10 IE -Known liver disease or s-ALAT above 80 IU/L -Known renal disease or s-Creatinine above above 110 mmol/l -Known alcoholism or drug abuse -Known diabetes mellitus, or fasting plasma-glucose above 7.0 mmol/L (= fasting whole blood glucose above 6.1 mmol/L) -Peroral steroid hormone treatment -Treatment with cimetidin, anticoaguantia, erythromycin or other macrolides -Hyperprolactinemia or s-PRL above 700 IE/L -Abnormal thyroid function tests -Congenital adrenal hyperplasia -Androgen secreting tumours -Cushing disease -Unfit to participate of any other reason |
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E.5 End points |
E.5.1 | Primary end point(s) |
Clinical pregnancy rate following IVF or ICSI treatment in non obese PCOS women. Clinical pregnancy rate defined by an intrauterine gestational sack week 7 in pregnancy |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit in the IVF-unit will be ultrasound week seven in pregnancy. In addition live birth rates, birth weight, gestational week (premature births), late abortions and both major and minor malformations diagnosed at birth will be reported. So the study is not finished until the last pregnant patient has given birth. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |