ENDOMETRIAL RECEPTIVITY IN AN IN VITRO FERTILIZATION PROGRAM IN RELATION TO PROGESTERONE CONCENTRATION ON THE DAY OF ADMINISTRATION OF AN OVULATION TRIGGER

Objective. To evaluate the impact of serum progesterone concentrations on the day of administration of an ovulation trigger on endometrial receptivity in an in vitro fertilization (IVF) program. Subjects and methods. A total of274patients with tuboperitoneal and/or mate factor infertility and in 19 oocyte donors treated in accordance with an IVF program were examined. Pipelle endometrial biopsy was performed on the day of oocyte aspiration in 36 women in whom embryo transfer had been cancelled. Histological (endometrial dating in accordance with the Noyes criteria; determination ofpinopodia), immunohistochemical (expression of estrogen receptor (ER), progesterone receptor (PR), and leukemia inhibitory factor (LIE)), and molecular genetic (mRNA expression of the genes IL1B, IL2, LIF, LIFR, IL8, IL1S, IL18, HBEGF, IGFBP1, IGF1, VEGFA, VEGFA isoform 189, TNFA, MMP11, PTGS2, CD56, CD 68, ESR1, PGR, MSXl(HOXT), HOXAIO, НОШІ) studies were conducted. The serum progesterone threshold />4.77 nml/l (1.5 ng/ml; conversion rate 3.18)] on the day of administration of an ovulation trigger was used to verify premature luteinization. According to the preovulatory progesterone concentration, the patients were divided into 2 groups: 1) P >4.77 nmol/l (n = 16) and 2) P <4.77 nmol/l (n = 20). Results. On premature luteinization development there was a more considerable advance in its development than that in the normal progesterone level group (3.9±0.6 and 2.3±0.3 days; p = 0.048). Mature pinopodia on the day of oocyte aspiration were detected at equal frequency in the patients with normal and elevated preovulatoiy progesterone levels (95 and 93.7%;p = 0.918); in this case their amount was significantly higher in those with premature luteinization (Me 25 and 15%; p = 0.026). Estimation of the endometrial expression of PR and ER-a (Fig. 2) in relation to progesterone levels showed a statistically significant difference in the expression of the former in the glands and stroma on day of hCG administration. The expression of ERa in the glands and stroma was comparable between the groups. That of LIF in the endometrial stroma was much higher in the patients with increased progesterone levels (3.2+0.5and 1.6+0.4scores;p = 0.05). The expression of TNF-amRNA was 1.4 times less (p = 0.042). It was found that when the endometrial development advanced more than 3 days, there was a substantial decrease in the mRNA expression of the key genes of implantation markers: H0XA11 by 1.8 times (p = 0.022), IGFBP1 by 5 times (p = ft 028), and CD68 by 1.7 times (p = ft 043). The expression of other receptivity markers was comparable between the groups. Conclusion. Endometrial estimation on the day of oocyte aspiration showed that the patients with premature luteinization showed an endometrial maturation advance by an average of 3.9±0.6 days, early LIF expression mainly in the endometrial stroma, moderate PR expression in the glands and stroma, the emergence of mature pinopodia on more than 20% of the epithelial surface, and a change in the mRNA expression profile of the genes of implantation markers, which is a verification of impaired endometrial receptivity, as well as prognostic factors for implantation failures in the IVF programs.

in vitro fertilization, premature luteinization, endometrial receptivity