The Brussels in vivo clomiphene test: a randomised controlled trial.

Introduction: Chronic anovulation is a frequent infertility cause in women,
and approximately 80% of these patients present with irregular menstrual cycles,
but serum FSH and estradiol levels within the normal range (World Health
Organisation (WHO) group2). Whereas, clomiphene citrate (CC) remains the
first line treatment choice for these normogonadotropic anovulatory patients, 20
to 25% of anovulatory women with normal FSH concentrations, do not respond
to CC. The aim of the study was to prospectively analyse whether patients failing
to respond to CC may experience different ovulation rates with highly purified
hMG or an increased dose of during the same treatment cycle.
Materials and Methods: This prospective randomised trial was conducted in
73 normogonadotrophic anovulatory infertile women seeking infertility treatment.
The trial was set up to compare two protocols for ovulation induction. In
both groups of patients, a standard protocol was applied and a dose of 50 mg
clomiphene citrate (Clomid®) was administered from day 3 until day 7 of the
cycle. If no reaction was found on day 13, patients were randomly allocated
to one of the two study groups. In the CC group, an increased dose of 100
mg clomiphene citrate was administered from day 13 until day 17 of the cyle,
whereas in the hMG group, human menopausal gonadotropins (hMG, Menopur
®) was administered at a dose of 75 IU from day 13 until day 17. Folliculogenesis
was checked, and afterwards final oocyte maturation was induced by the administration
of 10,000 IU of hCG when a follicle of 17 mm in diameter
was visualised on ultrasonography.
The primary endpoint was the presence of folliculogenesis in each treatment
group. Secondary outcome measure was the pregnancy rate in each treatment
group.
Results: Demographic characteristics, such as female age, BMI and basal
hormonal values, did not significantly differ among compared groups. There
was no difference between both groups regarding folliculogenesis (83,5% in
the CC group vs 88% in hMG group, p = 0.38). A positive hCG was seen in
2/40 patients (5%)in group A versus 5/33 patients (15%) in group B (p = 0.14).
However, the ongoing pregnancy rate was 5% (2/40) in the CC group and 9.1%
(3/33%) in the hMG group (p = 0.40).
Discussion: To our knowledge, this is the first randomised trial was performed
comparing CC with hMG for ovulation induction, when no initial reaction was
obtained after a standard dose of CC (50 mg). The rationale for this study was
that time to achieving ovulation would be greatly reduced; even if no follicular
reaction was demonstrated on day 13 of the cycle, this treatment cycle could
be saved.