The efficacy of GnRH antagonists in cycles with mild ovarian hyperstimulation with recFSH in an intrauterine insemination program.
A randomised placebo-controlled double-blinded investigator initiated study.

Accurate timing of insemination is one of the most important variables that affect the result of intrauterine insemination (IUI).
The onset of the preovulatory luteinizing hormone (LH) surge is one of the best indicators of the initiation of ovulation.
The LH rise can be detected in blood. In cycles with ovarian stimulation spontaneous LH surges occur in 25% of the cases, hardly resulting in any pregnancy and are therefore useless.

Luteinizing hormone surges can be prevented by administering a GnRH-antagonist. When used from a mean diameter of 14 mm of the dominant follicle(s) onwards, it has to be applied for a few days.
Preventing LH surges with administering an effective drug might be cost-effective.
It seems therefore logical to perform a large multicentre randomised controlled trial to investigate the efficacy of applying a GnRH-antagonist in MOH/IUI programs.
The results of a multi-centre trial were presented at the ESHRE 2004, showing effective suppression of LH surges by the antagonist, but no significant differences in pregnancy rates.
The authors stated that larger multi-centre double-blinded placebo-controlled trials are mandatory.


The aim of the study is to examine the efficacy of GnRH-antagonists in cycles with ovarian stimulation with recombinant Follicle Stimulating Hormone (FSH) combined with IUI.


This will be done in a prospectively randomised placebo controlled trial in couples with unexplained and mild male subfertility for at least 2 years.


Use will be made of recombinant FSH (Gonal-F, Serono Benelux). 75 IU Gonal-F will be administered daily subcutaneously. Gonal-F stimulation will start on cycle day 2 to 4.

From a follicle size of at least 14 mm onwards Cetrorelix (Cetrotide, Serono Benelux) 0.25 mg will be administered subcutaneously or an equal volume equivalent of placebo.

Rec-hCG (250 μg Ovitrelle, Serono Benelux) will be administered on the day that the size of the largest follicle is at least 18 mm. Once-only insemination will take place 38-40 hours after administration of Ovitrelle.


Live birth rates will be treated as primary end points. Pregnancy rates per couple, the occurrence of spontaneous LH surges and premature luteinization, multiple pregnancy rates, miscarriage rates and rates of ectopic pregnancies, total costs and cost-effectiveness will be secondary end-points.


Because this study will be the same as the standard treatment the patients will not be exposed to additional risks. Except the injection of cetrorelix for a couple of days and the withdrawal of blood on the day of hCG no extra events will take place compared to the standard treatment.

We hypothesize that the use of a GnRH-antagonist in cycles with Mild Ovarian Hyperstimulation (MOH) combined with Intrauterine insemination (IUI) programs significantly improves live birth rates compared with MOH and a placebo.

The research group of patients will consist of two arms:
one group will receive ovarian stimulation with recFSH combined with placebo (the recFSH group)
and one group will receive recFSH combined with a GnRH-antagonist (the recFSH-anta group).
Both ovarian stimulation protocols will be followed by intrauterine insemination.