Continuous use of Oral contraceptives as an alternative for long term Pituitary down-regulation with a GnRH agonist prior to IVF/ICSI in Endometriosis patients: a randomised controlled trial and prospective cohort study

It is shown in a number of publications that long term pituitary
down-regulation for three to six months prior to IVF/ICSI improves clinical
pregnancy rates in patients suffering from endometriosis. However, discussion
about this treatment strategy exists, as both the Cochrane and ESHRE
recommendation are based on only three small studies. These studies are
executed in a different IVF/ICSI treatment era in which more aggressive
stimulation was used followed by transferring two or more embryos instead of
single embryo transfer which is the current standard. Being afraid that
prolonged down-regulation with a GnRH agonists may lower the response to
ovarian stimulation (especially in patient with a poor response in previous
IVF/ICSI treatments), it is conceivable that clinicians nowadays may be
sceptical about this treatment regime. In addition, uncomfortable side effects,
such as vasomotor instability, are often related to this treatment regime,
which make patients frequently unwilling to use GnRH agonists for a longer
period of time. Alternatively, the effect of continued use of oral
contraceptives (OCs) for six to eight weeks prior to IVF/ICSI has also been
investigated. These observational data show that this treatment might be
beneficial in patients with severe endometriosis undergoing IVF/ICSI, as
clinical pregnancy rates were improved compared to endometriosis patient
treated without OCs and similar to that of control patients without
endometriosis. Those results in combination with the direct costs of GnRH
agonists (¤ 370,- per 3 months) versus oral contraceptives (¤ 41,- per 3
months) and indirect costs (higher loss of productivity during GnRH agonist
treatment) makes it interesting to investigate whether the outcome of
continuous use of OCs is as effective as long term pituitary down-regulation
with a GnRH agonist prior to IVF/ICSI, which has not been investigated yet.

To show a non-inferiority of continuous use of oral contraceptives for three
months to long term pituitary down-regulation with a GnRH agonist for three
months prior to present-day IVF/ICSI protocols in patients with severe
endometriosis (ASRM stages III and IV).

Prospective randomised controlled, parallel two-arm study and a prospective
cohort

Continuous use of oral contraceptives for three months (intervention group)
versus long term pituitary down-regulation with a GnRH agonist for three months
(reference group) prior to IVF/ICSI.

As both treatment protocols are not experimental and already used in daily
practice, no additional risks or burdens are expected from the study. All
measurements will be combined as much as possible with routine investigations.
All possible sides effects and severe adverse events will be monitored and
evaluated. No untoward effects of continuous use of oral contraceptives prior
to IVF/ICSI on treatment outcome (i.e. ongoing pregnancy) are expected. Non
inferiority of continuous use of oral contraceptives can improve patients
comfort by eliminating the side effects related to long term pituitary
down-regulation with a GnRH agonist. An IVF/ICSI treatment strategy with
continuous use of oral contraceptives holds promise to be more patient friendly
as well as cost-effective compared with long term pituitary down-regulation
with a GnRH agonist.
Participants will be asked to complete questionnaires every three months. Women
who participate in the cohort study, will receive the same questionnaires
except for the questionnaire on cost effectiveness.