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
Protocol serial number	NTR545; 04.165
Sponsor	VU University Medical Centre (VUMC) (Netherlands)
Funder	Gynaecology Research Foundation (Stichting Wetenschappelijk Onderzoek Gynaecologie [SWOG]) (Netherlands)

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

Primary study design	Interventional
Study design	Multicentre randomised open label active controlled parallel group prospective study and cost effective analysis
Secondary study design	Randomised controlled trial
Scientific title
Study acronym	COFFI study
Study objectives	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(s)	Received from local medical ethics committee
Health condition(s) or problem(s) studied	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
Primary outcome measure(s)	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
Key secondary outcome measure(s)	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
Completion date	01/11/2008

Eligibility

Participant type(s)	Patient
Age group	Not Specified
Sex	Not Specified
Target sample size at registration	320
Key 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.
Key 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
Date of first enrolment	01/11/2004
Date of final enrolment	01/11/2008

Locations

Countries of recruitment

Netherlands

Study participating centre

VU University Medical Center

Amsterdam
1007 MB
Netherlands

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan