Contact information
Type
Scientific
Primary contact
Prof R. Homburg
ORCID ID
Contact details
VU University Medical Center
Department of Obstetrics and Gynaecology Division of Reproductive Medicine
P.O. Box 7057
Amsterdam
1007 MB
Netherlands
+31 (0)20 4440070
R.homburg@vumc.nl
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
NTR545; 04.165
Study information
Scientific title
Acronym
COFFI study
Study hypothesis
We hypothesize that the use of low dose gonadotrophin therapy, will prove to be more efficient than CC when used as first line treatment.
Ethics approval
Received from local medical ethics committee
Study design
Multicentre randomised open label active controlled parallel group prospective study and cost effective analysis
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
Polycystic Ovary Syndrome (PCOS)
Intervention
Medications:
Patients will be randomised to receive either clomiphene citrate or Puregon (Follitropine/ recombinant - Follicule Stimulating Hormone [r-FSH]) for ovulation induction (a maximum of 3 cycles of treatment will be given for the purposes of this study).
Clomiphene citrate will be given starting on day 4 of the cycle for 5 days. If no response is seen by day 17 of the cycle, it should be abandoned.
Puregon (follitropine) will be given, starting from day 4 of the cycle, until the criteria for human Choionic Gonadotropin (hCG) administration are achieved. If these criteria are not reached following 35 days of stimulation, the cycle should be abandoned.
Monitoring:
An U/S examination of follicle number and size and endometrial thickness will be performed. HCG will be given when at least 1 follicle of >17 mm is seen on U/S examination. This applies to both treatment protocols. HCG will be withheld if a total of >3 follicles >15 mm diameter are seen on U/S.
Intervention type
Other
Phase
Not Specified
Drug names
Primary outcome measures
1. Pregnancy rate - per patient, per cycle, cumulative over 3 cycles (hCG measurement 15 days after ovulation)
2. Miscarriage rate - embryonic, fetal (diagnosed with ultrasound)
3. Multiple pregnancy rate (number of gestational sacs measured with ultrasound)
4. Live birth rate
5. Ovulation rate (followed with ultrasound)
6. Initiation of treatment to pregnancy interval
Secondary outcome measures
1. Number and size of follicles >10 mm on day of hCG
2. Endometrial thickness on day of hCG
3. Estradiol and progesterone concentrations on day of hCG
4. Number of abandoned cycles (hCG withheld) due to overstimulation or lack of response
5. Ovarian hyperstimulation
6. Correlation of basal hormone concentrations with pregnancy and miscarriage rates
7. Number of units of Puregon used per cycle and per pregnancy achieved
Overall trial start date
01/11/2004
Overall trial end date
01/11/2008
Reason abandoned
Eligibility
Participant inclusion criteria
1. The diagnosis of PCOS will be made when a history of at least 6 months inability to conceive is accompanied by at least 2 of the following:
1.1. Irregular menstruation (oligo- or amenorrhea) (>35 days)
1.2. Clinical or biochemical evidence of hyperandrogenism (hirsutism, acne, raised TT or FAI)
1.3. Typical features of PCO on ultrasound (U/S) examination (see The Rotterdam Consensus for further details)
2. All women desiring pregnancy who conform to the definition of PCOS cited above and who have had no fertility treatment in the preceding year
3. Age <40 years
4. Patients who have previously conceived either spontaneously or on CC therapy may also be included
5. Patients with a previous history of pregnancy, whether resulting in a delivery or spontaneous abortion, a previous history of gynecological or abdominal surgical intervention or pelvic inflammatory disease, should have a normal uterine cavity and tubal patency demonstrated by radiological (HSG), laparoscopic or ultrasonic means before entering the study
6. A mandatory sperm count deemed normal by the treating physician is acceptable for inclusion. Intrauterine insemination may be employed at the discretion of the treating physician.
Participant type
Patient
Age group
Not Specified
Gender
Not Specified
Target number of participants
320
Participant exclusion criteria
1. Age >39 years
2. An obvious mechanical or male factor
3. Co-existing conditions such as overt diabetes mellitus, oestrogen dependent tumours, ovarian cysts, hypertension, thyroid disease, Cushings syndrome or congenital adrenal hyperplasia
Recruitment start date
01/11/2004
Recruitment end date
01/11/2008
Locations
Countries of recruitment
Netherlands
Trial participating centre
VU University Medical Center
Amsterdam
1007 MB
Netherlands
Funders
Funder type
Charity
Funder name
Gynaecology Research Foundation (Stichting Wetenschappelijk Onderzoek Gynaecologie [SWOG]) (Netherlands)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary