Should clomiphene citrate (CC) or low-dose gonadotrophin therapy be the first-line treatment for anovulatory infertility associated with polycystic ovary syndrome (PCOS)? A multicentre, randomised, prospective study and cost effective analysis.

ISRCTN ISRCTN41865643
DOI https://doi.org/10.1186/ISRCTN41865643
Secondary identifying numbers NTR545; 04.165
Submission date
14/02/2006
Registration date
14/02/2006
Last edited
25/08/2009
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Urological and Genital Diseases
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof R. Homburg
Scientific

VU University Medical Center
Department of Obstetrics and Gynaecology Division of Reproductive Medicine
P.O. Box 7057
Amsterdam
1007 MB
Netherlands

Phone +31 (0)20 4440070
Email R.homburg@vumc.nl

Study information

Study designMulticentre randomised open label active controlled parallel group prospective study and cost effective analysis
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Scientific title
Study acronymCOFFI study
Study objectivesWe 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(s)Received from local medical ethics committee
Health condition(s) or problem(s) studiedPolycystic Ovary Syndrome (PCOS)
InterventionMedications:
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 typeOther
Primary outcome measure1. 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 measures1. 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 study start date01/11/2004
Completion date01/11/2008

Eligibility

Participant type(s)Patient
Age groupNot Specified
SexNot Specified
Target number of participants320
Key inclusion criteria1. 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.
Key exclusion criteria1. 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, Cushing’s syndrome or congenital adrenal hyperplasia
Date of first enrolment01/11/2004
Date of final enrolment01/11/2008

Locations

Countries of recruitment

  • Netherlands

Study participating centre

VU University Medical Center
Amsterdam
1007 MB
Netherlands

Sponsor information

VU University Medical Centre (VUMC) (Netherlands)
Hospital/treatment centre

Department of Obstetrics and Gynaecology
Division of Reproductive Medicine
P.O. Box 7057
Amsterdam
1007 MB
Netherlands

ROR logo "ROR" https://ror.org/00q6h8f30

Funders

Funder type

Charity

Gynaecology Research Foundation (Stichting Wetenschappelijk Onderzoek Gynaecologie [SWOG]) (Netherlands)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan