Condition category
Urological and Genital Diseases
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information



Primary contact

Prof R. Homburg


Contact details

VU University Medical Center
Department of Obstetrics and Gynaecology Division of Reproductive Medicine
P.O. Box 7057
1007 MB
+31 (0)20 4440070

Additional identifiers

EudraCT number number

Protocol/serial number

NTR545; 04.165

Study information

Scientific title


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


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet


Polycystic Ovary Syndrome (PCOS)


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.

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



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


Overall trial end date


Reason abandoned


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


Age group

Not Specified


Not Specified

Target number of participants


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, Cushing’s syndrome or congenital adrenal hyperplasia

Recruitment start date


Recruitment end date



Countries of recruitment


Trial participating centre

VU University Medical Center
1007 MB

Sponsor information


VU University Medical Centre (VUMC) (Netherlands)

Sponsor details

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

Sponsor type

Hospital/treatment centre



Funder type


Funder name

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

Alternative name(s)

Funding Body Type

Funding Body Subtype


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

Publication citations

Additional files

Editorial Notes