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To determine whether estradiol-to-progesterone (E2/P) ratios at the time of embryo …

Biology Articles » Reproductive Biology » Serum estradiol/progesterone ratio on day of embryo transfer may predict reproductive outcome following controlled ovarian hyperstimulation and in vitro fertilization » Discussion

- Serum estradiol/progesterone ratio on day of embryo transfer may predict reproductive outcome following controlled ovarian hyperstimulation and in vitro fertilization

For normal endometrial morphology to occur, an E2 priming phase is required followed by P. In the pre-GnRH agonist era, the alteration of the E2/P ratio was considered a main cause of luteal-phase inadequacy and IVF failure, possibly mediated by the luteolytic action of E2 [12]. The action of estrogen is required for up-regulation of P receptors. In the follicular and early luteal phases of a normal menstrual cycle, both E2and P receptors are found in glandular and stromal compartements [13]. P antagonizes the proliferative effects of E2 on the endometrial glands by down-regulating estrogen receptors and is followed by a subsequent disappearance of P receptors [14].

Many stimulation cycles in assisted reproduction are associated with failed pregnancy despite the transfer of apparently healthy and morphologically normal embryos. This suggests impairment of endometrial differentiation or receptivity in response to E2 and P may also warrant consideration [15]. In our study, the role of the E2/P ratio at the time of embryo transfer was compared with the pregnancy outcome. Our working hypothesis of this investigation is that a high P level in combination with a low E2 level in the early luteal phase could presage failed implantation. These data suggest that the E2/P ratio on OI +4 days, OI +5 days and OI +7 days are significantly associated with clinical pregnancy rate. Interestingly, a significant higher clinical pregnancy rate could be achieved if blastocysts on OI +7 days were transferred. It seems that, blastocyst transfer allowed the identification of embryos with very high implantation potential [16], and probably a better blastocyst-endometrial epithelium interaction. The behaviour of the blastocyst may be influenced by signals from the endometrium which has been primed with preimplantation ovarian steroids [17].

Specifically, we identified no differences in peak E2 and P on day of oocyte retrieval or in the early luteal (on OI +4 days, OI +5 days and OI +7 days) E2 and P concentrations between pregnant and non-pregnant women. The use of a single luteal E2 and P measurement to predict endometrial receptivity was not useful, although at our center the early detection of a low E2 level did help identify those who were then given supplementary hCG support for corpus luteum rescue. Additionally, a single P value in the early luteal phase was not informative for diagnosing luteal phase defect. Assessment of the E2/P ratio in the early luteal phase provided better prognostic information with relatively higher values of this ratio being associated with a healthy corpus luteum activity and successful implantation.

In this study, patients received both GnRH-agonist and GnRH-antagonist stimulated cycles for controlled ovarian hyperstimulation to prevent premature LH surge. Uniform luteal support consisting of vaginal micronized progesterone starting on the day of ET was given to all patients in order to compensate for possible iatrogenic luteal phase defect [18]. GnRH- agonists are associated with persistent blockage of LH output for at least 10 days following the final dose [2,19]. Prolonged administration of GnRH agonists may also affect ovarian steroidgenesis directly because of the presence of GnRH receptors in the ovary [20]. In contrast, an inhibitory effect of GnRH-antagonist on steroidgenesis may also be postulated [21,22]. Here, we confirmed the present hormonal profile dynamics, and the calculated E2/P ratio was not affected by the treatment protocol used (GnRH agonist vs. antagonist), findings that agree with previous work [23].

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