How to avoid oocyte retrievals during weekend days using a GnRH antagonist protocol? A randomised controlled trial.

Introduction: GnRH antagonist protocols are associated with a reduction of
treatment duration and a reduced risk for ovarian hyperstimulation syndrome.
Nevertheless, the long GnRH agonist protocol remains highly popular in many
centers, because of the flexibility of its schedule; the GnRH antagonist protocol
is more patient-friendly but less amenable to organise gonadotrophin stimulation
so as to minimise weekend oocyte retrievals. The aim of this study is to
prospectively analyse the ability to control the scheduling of GnRH antagonist
cycles by the administration of estradiol valerate during the luteo-follicular
transition period prior to the initiation of ovarian stimulation.
Material and Methods: We conducted a randomised controlled trial. Patients
fulfilling the following inclusion criteria were enrolled in the trial: 1. normal
FSH on cycle day 3 (<12 IU/L), 2. age ? 36 years, 3. first or second attempt
of ICSI, 4. normal ultrasound scan and 5. a regular menstrual cycle (i.e. 22-35
days), presumed to be ovulatory. Patients were randomised into two groups:
the control group and the pretreatment group. In the control group, patients
received a standard GnRH antagonist protocol, in which rFSH 150 IU/L was
applied from day 2 of the cycle onwards. On day 6 of the stimulation, subcutaneous
administration of the GnRH antagonist ganirelix (Orgalutran®) was
started at a daily dose of 0.25 mg. In the pretreatment group, patients were
administered a pretreatment with estradiol valerate (Progynova®) at a daily dose
of 2 x 2 mg (2 mg in the morning, 2 mg in the evening) from day 25 of the
menstrual cycle onwards, during 6 to 10 consecutive days, depending on the
day of the week (if day 25 is Monday, Saturday or Sunday: 6 days, Tuesday: 10
days, Wednesday: 9 days, Thursday: 8 days, Friday: 7 days). After discontinuation
of the estradiol valerate administration, ovarian stimulation with recombinant
FSH (rFSH, Puregon®) at a dose of 150 IU/L was started. In both groups,
final oocyte maturation was triggered by the administration of 10,000 IU hCG
(Pregnyl®), as soon as three follicles of 17 mm diameter were observed on ultrasonography.
Oocyte retrieval took place 36 h after triggering. The primary
endpoint was the proportion of patients undergoing oocyte retrieval during a
weekend day (i.e. Saturday or Sunday).
Results: Since May 2010, 56 patients have been included in the trial so far.
Both groups had comparable baseline characteristics. The duration of rFSH
stimulation and consumption of gonadotrophins were also comparable: 9.5 (SD 1.2) versus 8.8 (SD 1.6) days, and 1454 (SD 230) versus 1320 (SD 284) IU in
the pretreatment and control group respectively. The number of cumulus oocyte
complexes did not differ significantly in the pretreatment group (12.5, SD 6.4)
compared to the control group (11.5, SD 10.5). The proportion of patients
undergoing oocyte retrieval during a weekend day was lower in the pretreatment
group (1/19 or 5.3%) compared to the control group (5/24 or 20.8%),
although this decrease was not statistically significant (absolute between-group
difference of -15.5%, 95% confidence interval -34.7 to + 3.5%, P = 0.205).
The ongoing pregnancy rates per started cycle were similar in the pretreatment
group (8/22 or 36%) compared to the control group (9/27 or 33%).
Conclusions: The results of this randomised trial suggest that pretreatment
with estradiol valerate can act as a planning tool to schedule GnRH antagonist
cycles. Pretreatment with estradiol valerate results in a trend towards a lower
proportion of patients undergoing oocyte retrieval during a weekend day and
can assist the organisation of an ART centre.