The morphofunctional status of the endometrium in stimulated in vitro fertilization cycles


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Abstract

Objective. To evaluate the impact of ovarian stimulation and to estimate the level of serum progesterone (P) in the late follicular phase of the cycle in GnRH agonist protocols on endometrial receptivity. Subjects and methods. Morphological and immunohistochemical (IHC) examinations were made of 50 endometrial biopsy specimens, including 28 ones obtained on the day of oocyte aspiration in the therapeutic cycle of IVF without further embryo transfer (a study group) and 22 ones taken in the natural cycle (the day of luteinizing hormone + 7) (a comparison group). Ovarian function was stimulated according to the standard long protocol using recombinant follicle-stimulating hormone and human menopausal gonadotropin. Serum P concentrations were determined on the day of ovulation triggering. The serum P threshold value was used to identify premature lutein-ization, which was equivalent to 4.77 nmol/l. The patients were divided into groups according to the level of P on the day of human chorionic gonadotropin administration: 1) Р ≥ 4.77nmol/l (n = 13); 2) P< 4.77nmol/l (n = 15). Results. On the day of oocyte aspiration, most (75%) of the patients were observed to have secretory transformation of the endometrium, as well as mature or regressing pinopodia on more than 20% of the endometrial surface in 100% of cases, which was similar to the implantation window in the natural cycle. IHC examination of the endometrium indicated that on the day of oocyte aspiration the expression of progesterone receptors (PR) in the endometrial glands (142.1±8.1%) was similar to the natural cycle during the implantation window (112.5±15.1; р = 0.470); that in the stroma was substantially lower (144.2±7.8 and 176.8±7.7, respectively;р = 0.001). In the stimulated cycle, the amount of estrogen receptors (ER) in the glands and stroma averaged 128.9±4.1 and 27.8±4.1%, respectively. In the implantation window of a natural cycle, the expression of ER in the glands was considerably lower (mean 92.9±12.0%;р = 0.018); it was much higher in the stroma (mean 66.1±9.3%;р = 0.001). In the stimulated cycle, the expressions of leukemia inhibitory factor in the surface epithelium and endometrial stroma (2.2±0.5 and 2.3±0.3) corresponded to those in the implantation window in the natural cycle (3.75±0.5 and 3.2±0.4;р = 0.07 and р = 0.180) and significantly lower in the glands and pinopodia. The results of endometrial dating using the Noyes criteria demonstrated that in the patients with a serum P level of < 4.77 nmol/l on the day of ovulation triggering, the endometrium on the day of oocyte aspiration was equal to 15.2±0.5 days of the cycle, by advancing the development by an average of 2.6±0.4 days; the endometrium at Р ≥ 4.77 nmol/l, was equal to 17.4±0.6 days of the cycle, by advancing the development by an average of 4.09±0.6 days (р = 0.023 and р = 0.048). The expressions of PR in the glands (126.6±13.1%) and stroma (130.6±12.8%) with normal P levels on the day of ovulation triggering were much lower than those in the elevated P group (160.0±5.9% (in the gland); р = 0.042; 163.3±5.4% (in the stroma); р = 0.041. The expression of ER in both the glands and stroma was similar in the groups. That of LIF in the endometrial stroma was significantly higher in the patients with elevated P levels (3.2±0.5 and 1.6±0.4 scores; р = 0.05). Mature pinopidia on the day of transvaginal oocyte retrieval were detected with an equal frequency in patients with normal or higher P levels (93.3% and 92.3%; р = 0.918). Conclusion. Ovarian stimulation in the IVF programs and as a result an anticipatory increase in P levels give rise to advanced endometrial maturation, as demonstrated by the detection of secretory transformation of the endometrium on the day of oocyte aspiration, mature pinopidia, decreased ER expression in the stroma, and early LIF expression in the epithelium and stroma.

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About the authors

Elena Viktorovna Mityurina

Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: mity-elena@yandex.ru
graduate student

Svetlana Grigorievna Perminova

Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: perisvet@list.ru
MD, Leading Researcher 1st gynecological department

Tatyana Alexandrovna Demura

Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: demura-t@yandex.ru
Candidate of medical sciences, senior researcher at the 1st Pathology Department

Elena Maratovna Gallyamova

Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: nikson2003@inbox.ru
graduate student

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