Immunohistochemical and morphometric analysis of thin endometrium

The problem of infertility due to endometrial hypoplasia is very relevant, due to the difficulty of diagnosis, since there are no uniform morphometric and immunohistochemical criteria for this condition. 

The aim of this study is to assess the endometrial condition of patients with endometrial hypoplasia and infertility, using morphometry and microscopy, taking into account the severity of expression of receptors for estrogen, progesterone, VEGF, CD34, LIF and LIFR. 

Materials and methods. Morphometric, immunohistochemical and statistical analysis of endometrial samples of 34 women with infertility due to thin endometrium and 29 healthy fertile women was carried out. 

Results. Fibroplastic transformation of the stroma in women with infertility was recorded 1.9 times more often. A significant decrease in the relative number of abundant pinopodia in the group of women with infertility was found. Immature pinopodia in the group of women with thin endometrium were recorded almost 10 times more often, and mature ones - 4 times less than in fertile women. An immunohistochemical study found a decrease by 43% in the level of progesterone receptors expression by stromal cells in women with thin endometrium, as well as in VEGFR3 expression by 48% and 84%, both by gland cells and stromal cells. The number of capillaries in the field of view in women with thin endometrium was reduced by 2 times. 

Conclusion. In women with thin endometrium and infertility, a decrease in the area of the integumentary epithelium with pinopodia was established, with the predominance of their immature forms; a moderately reduced expression of progesterone receptors by stromal cells, a decrease in LIF expression and an increase in LIFR expression by glands and stroma, as well as a decrease in the level of VEGF and CD34 expression, which indicates the impaired endometrial receptivity and neoangiogenesis processes, which subsequently lead to a decrease in endometrial height and inferior cytotrophoblast invasion.

1. Афян А.И, Долгушина Н.В. Тонкий эндометрий в клинике вспомогательных репродуктивных технологий (обзор литературы). Гинекология. 2014;16(5):78-83

2. Здановский В.М., Буравченко Н.Б. Результаты применения вспомогательных репродуктивных технологий у бесплодных пациенток с патологией эндометрия. Российский вестник акушера-гинеколога. 2010;10(2):39-42

3. Кузнецова И.В., Землина Н.С., Рашидов Т.Н., Коваленко М.А. Проблема тонкого эндометрия и возможные пути ее решения. Эффективная фармакотерапия. 2015;5:42-49

4. Серова О.Ф., Седая Л.В., Шутикова Н.В., Соваев Н.И., Елисеев Э.Н. Морфофункциональное состояние тонкого эндометрия и возможности его коррекции. Лечение и профилактика. 2015;2(14):10-14

5. Achache H. Endometrium receptivity markers, the journey to successful embryo implantation. Hum Reprod Update. 2006;12(6):731-746. DOI: 10.1093/humupd/dml004

6. Alfer J., Happel L., Dittrich R., Beckmann M.W., Hartmann A., Gaumann A., Buck V.U., Classen-Linke I. Insufficient Angiogenesis: Cause of Abnormally Thin Endometrium in Subfertile Patients? Geburtshilfe Frauenheilkd. 2017;77(7):756-764. DOI: 10.1055/s-0043-111899

7. El-Toukhy T., Coomarasamy A., Khairy N., Sunkara K., Seed P., Khalaf Y., Braude P. The relationship between endometrial thickness and outcome of medicated frozen embryo replacement cycles. Fertil Steril. 2008;89(4):832-839. DOI: 10.1016/j.fertnstert.2007.04.031

8. Miwa I., Tamura H., Takasaki A., Yamagata Y., Shimamura K., Sugino N. Pathophysiologic features of “thin” endometrium. Fertil Steril. 2009;91(4):998-1004. DOI: 10.1016/j.fertnstert.2008.01.029

9. Mouhayar Y., Sharara F.I. G-CSF and stem cell therapy for the treatment of refractory thin lining in assisted reproductive technology. J Assist Reprod Genet. 2017;34(7):831-837. DOI: 10.1007/s10815-017-0922-6

10. Rosario G.X., Hondo E., Jeong J.W., Mutalif R., Ye X., Yee L.X., Stewart C.L. The LIF-mediated molecular signature regulating murine embryo implantation. Biol Reprod. 2014;91(3):66. DOI: 10.1095/biolreprod.114.118513