|- candidate number||15066|
|- NTR Number||NTR4057|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||1-jul-2013|
|- Secondary IDs||2013_021 METC AMC|
|- Public Title||Superovulation in intra uterine insemination: FSH or clomifene citrate?|
|- Scientific Title||Superovulation in intra uterine insemination: FSH or clomifene citrate?|
|- Healt Condition(s) or Problem(s) studied||Intra-uterine insemination (IUI), Clomiphene , Unexplained infertility, FSH|
|- Inclusion criteria||-At least 12 months of unprotected intercourse without conception.|
-At least one sided tubal patency, which is established according to local protocol.
-The male partner or semen-donor has normal semen quality or mild impairment of semen quality. Mild male subfertility is defined as abnormal semen parameters according to the WHO but an average total motile sperm account before processing of at least 10 million based on the average of two semen analyses.
-The 12-month prognosis for the couple to conceive naturally has to be below 30%
according to the model of Hunault.
|- Exclusion criteria||-Double sided tubal pathology|
-Women with irregular cycles, PCOS or other endocrine disorders
-Impaired semen quality: pre-wash TMC<10 million
-Women younger than 18 or older than 43 years.
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-mei-2013|
|- planned closingdate||1-apr-2017|
|- Target number of participants||382|
|- Interventions||4 cycles IUI-FSH or 4 cycles IUI-clomifene citrate |
|- Primary outcome||Cumulative ongoing pregnancy rate |
|- Secondary outcome||1. Number of cycles with monofollicular growth|
2. Number of cycles with multiple follicle growth
3. Number of cancelled cycles due to the occurrence of >3 follicles >15 mm
4. Difference in severity of known adverse effects
5. Time to ongoing pregnancy rate
6. Clinical pregnancy
7. Miscarriage rate
8. Live birth rate
9. Multiple pregnancies
10. Patients preference by DCE
11. Direct and indirect costs
|- Timepoints||6 months after randomisation |
|- Trial web site||http://www.studies-obsgyn.nl/super|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES||MD. M.H. Mochtar|
|- CONTACT for SCIENTIFIC QUERIES||MD. M.H. Mochtar|
|- Sponsor/Initiator ||Academic Medical Center (AMC)|
(Source(s) of Monetary or Material Support)
|ZON-MW, The Netherlands Organization for Health Research and Development|
|- Brief summary||Rationale |
In The Netherlands, the first line treatment for patients diagnosed with unexplained subfertility or mild male factor is intrauterine insemination with ovarian stimulation. Ovarian stimulation can be achieved with follicle stimulating hormone (FSH) or with Clomifene citrate (CC).
Through ovarian superstimulation multiple follicles are recruited, which increases pregnancy
chances. A Cochrane meta-analysis pooling the evidence of 7 studies including 566 subfertile couples suggests a favor for FSH compared to CC and most clinics in The Netherlands use FSH. The downside of the use of ovarian superstimulation is the increased
risk of multiple pregnancies. In an effort to reduce multiple pregnancy rates but maintain an
acceptable pregnancy rate at the same time, one aims to recruit only two dominant follicles.
Only one study comparing FSH to CC, while aiming to recruit two follicles, showed equal
pregnancy results. This study however was underpowered and the vast majority of Dutch
clinics continue to stimulate with FSH, resulting in an annual cost of 11 million euro for
medication costs alone.
To determine which ovarian superstimulation regimen (FSH or CC) aiming to recruit only two
dominant follicles should be applied in IUI in couples with unexplained subfertility or mild male factor subfertility.
Nationwide parallel multicenter randomized clinical trial, comparing FSH with CC as ovarian
stimulation in IUI and an economic analysis alongside it.
Women diagnosed with unexplained or mild male factor subfertility according to Dutch
guidelines and an unfavorable prognosis according to the model of Hunault on the
occurrence of a spontaneous pregnancy within one year.
A maximum of 4 cycles of IUI with ovarian stimulation. In the first cycle one group receives
daily 75 IU FSH subcutaneously form cycle day 3 until ovulation triggering, The other group
receives oral tablets CC 100 mg daily from cycle day 3 until cycle day 7. The next cycles,
dosages may be adjusted appropriately. The time horizon will be 6 months.
Main study parameters/endpoints
Primary outcome is ongoing pregnancy rate defined as a positive heartbeat at 12 weeks
gestation determined by transvaginal ultrasound. Secondary endpoints are multiple
pregnancy rates, miscarriage rate, live birth rate and patients' preference and costs.
Nature and extent of the burden and risks associated with participation, benefit and
The strategies compared are already broadly applied in current practice. No additional risks
are expected. Patients will be asked to fill in a questionnaire to compare the severity of the
already know side effects of both medications. There is no benefit for participants, but the
results may benefit future subfertile couples
|- Main changes (audit trail)|
|- RECORD||1-jul-2013 - 15-jul-2013|