Association of the probability of pregnancy with exposure to progesterone and LH between the end of menstruation and the day of hCG administration in patients treated by IVF.

Introduction: The exposure of endometrium to supraphysiological steroid levels
during the follicular phase of an IVF cycle results in histological abnormalities
and subsequently affects pregnancy rates. It has been demonstrated that
prolonged duration of stimulation after the end of menstruation and until the
day of hCG administration (menstruation-free interval) is associated with a decreased
probability of ongoing pregnancy in GnRH antagonist/rec-FSH cycles
(Kolibianakis et al., 2006). This study investigated the association between the
hormonal exposure during the menstruation free interval with the probability of
pregnancy achievement.
Material and Methods: One hundred women (age ? 39 years) participated in
this prospective trial. Patients were stimulated with a fixed dose of rec-FSH
(200 IU) starting on day 2 of the cycle and they were asked to report the first
day they were completely free of menstruation. The menstruation free interval
was calculated from that day until the day of hCG.
To inhibit premature LH surge, daily GnRH antagonist (0.25 mg) was used
from the day 6 of stimulation onwards. Final oocyte maturation was triggered
by administration of 10000 IU of hCG as soon as ? 3 follicles ? 17 mm were
present. Hormonal assessment was performed at initiation of stimulation, on the
1st day after the menstruation had stopped, on day of antagonist initiation and
on the day of hCG administration. Oocyte retrieval was carried out 36 hours
after hCG administration and conventional IVF/ICSI was performed. One or
two embryos were transferred on day 3 after oocyte retrieval. The luteal phase was supplemented with vaginal administration of 600 mg natural micronized
progesterone in three separate doses.
The hormonal exposure during the menstruation free interval was assessed
for each patient by using the area under the curve (AUC). The predictive value
of this exposure for the probability of pregnancy was assessed by receiver operating
characteristic (ROC) curve analysis and by performing binary logistic
regression. All tests were two tailed with a confidence level of 95% (p <0.05).
Values are expressed as mean ± standard deviation (SD).
Results: The exposure to progesterone (P) during the menstruation-free interval
(AUC P) was significantly lower in patients who achieved an ongoing
pregnancy compared with those who did not (3.13 ± 1.14 vs. 4.20 ± 2.54, respectively
p = 0.004).
ROC curve analysis of the exposure to P during the menstruation-free interval
(AUC P) showed that this parameter could distinguish between patients
who achieved an ongoing pregnancy and those who did not. (AUC P = 0.636;
95% CI:0.528-0.745, p = 0.031).
Binary forward logistic regression using as dependent variable the achievement
of ongoing pregnancy and as independent variables the AUC P, AUC LH,
AUC FSH, AUC E2, the number of COCs, the number of embryos transferred,
the number of cryopreserved embryos and the menstruation free interval confirmed
the negative effect of the increased exposure to P for the achievement
of pregnancy {exp (B) 0.541,95% CI:0. 353-0.851, p = 0.005}. In addition, the
exposure to endogenous LH during the menstruation free interval was also predictive
for the achievement of pregnancy. A higher exposure to endogenous LH
during the menstruation free interval was associated with an increased chance
of pregnancy {exp (B) 1.088,95% CI: 1.014-1.168, p = 0.019}.
Conclusions: The current study provides evidence that in recFSH/GnRH antagonist
cycles, an increased probability of ongoing pregnancy is associated
with a lower exposure to P and a higher exposure to endogenous LH during the
menstruation free interval.