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The relationship between premature progesterone rise with serum Estradiol levels and number of follicles in GnRH antagonist/recFSH stimulated cycles

Journal Contribution - Journal Article Conference Contribution

Introduction: The stimulation protocols in IVF treatment cycles induce supraphysiological
serum concentrations of oestradiol (E2) during the follicular phase. Despite the use of GnRH analogues, there is a risk of premature progesterone
(P) rise jeopardizing the pregnancy outcome. To the best of our knowledge,
this is the first study to investigate the relationship between premature
P rise and serum E2 levels and the number of follicles in GnRH antagonist/
rec-FSH stimulated cylces.
Material and Methods: Two hundreds and seven patients treated by IVF/ICSI at
the Centre for Reproductive Medicine of Dutch-Speaking Brussels Free University
were included in this observational study. Recombinant FSH (Puregon; NV
Organon, OSS, The Netherlands) was started on Day 2 of the menstrual cycle at
a dose of 200 IU/day in all patients. GnRH antagonist (Orgalutran; NV Organon)
was started day 6 of rFSH stimulation. Triggering of final oocyte maturation was
performed using 10000 IU hCG (Pregnyl; Organon, Oss, The Netherlands) as
soon as at least three follicles ? 17 mm were present on ultrasound scan.
Hormonal assessment was performed at the initiation of stimulation, on
Day 6 of rec-FSH stimulation, on Day 8 and on the day of hCG administration.
Ultrasound scan was performed on Day 6 and thereafter as necessary in order
to ensure that hCG would be injected as soon as the patient had ? 3 follicles
of ? 17 mm.
Results: A logestic regression model was performed to assess the relationship
between E2 and number of follicles of ? 11 mm of the trigger day with progesterone
rise (over 1.5 ng/ml). A significant effect on progesterone rise was
observed for both E2 (p <0.001) and the number of follicles (p = 0.041).
The maximum accuracy calculated via the ROC curve was employed in
order to estimate a cut-off for E2 and number of follicles on day of trigger when
progesterone is > 1.5 ng/ml. A serum E2 on day of hCG > 2428 pg/ml and more
than 12 follicles of ? 11 mm in diameter were found to have a 0.1793 and 0.3655
specificity, 0.4355 and 0.5484 sensitivity, a positive predictive value 27% and
34% and negative predictive value 92% and 117% respectively for progesterone
rise over 1.5 ng/mi. The AUC was 0.62547 and 0.60845 respectively.
Conclusions: These data demonstrate a significant effect on progesterone rise
by E2 (P <0.001) and number of follicles (P = 0.041) in GnRH antagonist/rec-
FSH stimulated cycles.
Premature progesterone rise during GnRH antagonist IVF cycles is a frequent
phenomenon which is associated with lower pregnancy and implantation
rates. With this knowledge, an upcoming progesterone rise during follicular
phase can be anticipated and prevented.
Journal: Hum Reprod
ISSN: 0268-1161
Volume: 26
Pages: 324, 526
Publication year:2011
Keywords:Progesterone, Estradiol