Insufficient Angiogenesis: Cause of Abnormally Thin Endometrium in Subfertile Patients?

Abstract

Introduction This study investigated subfertile patients with abnormally thin endometrium after infertility treatment. As they had adequate serum concentrations of hormones, an endometrial factor for subfertility was suspected. Methods To elucidate the cause of subfertility, endometrial biopsies were taken in each patient in the late proliferative and mid-secretory phases of one menstrual cycle. Endometrial biopsies from women with normal menstrual cycles and confirmed fertility who were undergoing hysterectomy for benign uterine disease were used as positive controls. The tissue samples were investigated for steroid hormone receptor expression and for the proliferation marker Ki-67. Immunohistochemistry was performed with antibodies against the marker molecules for endometrial receptivity – β3 integrin, VEGF, LIF, and CD56 (large granular lymphocytes, LGLs). Results The steroid hormone receptors for estrogen (E2) and progesterone (P) were expressed normally (at the first biopsy) and were down-regulated (at the second biopsy) within the cycle. Strikingly, all of the marker molecules investigated showed negative or weak and inadequate expression in the mid-secretory phase. Numbers of LGLs remained as low as in the proliferative phase. In contrast, fertile patients were found to express these marker molecules distinctly in the mid-secretory phase. Conclusions It may be hypothesized that a severe deficiency of these angiogenesis-related marker molecules leads to defective development of the endometrium, which remains thin. Deficient angiogenetic development may thus provide an explanation for the endometrial factor that causes infertility. Further investigations will need to focus on identifying the regulating factors that act between steroid receptor activation and the expression of these marker molecules.

Association between induced abortion history and later in vitro fertilization outcomes

“…It starts with the apposition of the blastocyst at the uterine endometrium and then attachment to the endometrial surface epithelium . Several studies have shown that a thin endometrium adversely affects the pregnancy rate in IVF …”

“…9 Several studies have shown that a thin endometrium adversely affects the pregnancy rate in IVF. [10][11][12] After surgical abortion, inflammation can occur in both the endometrium and the oviduct. Endometritis is chronic inflammation of the inner lining of the uterine cavity, and leads to abnormal uterine bleeding, recurrent spontaneous abortion, and infertility.…”

The ameliorating effects of Bushen Tiaoxue Granules and Kunling Wan on impaired angiogenesis and endometrial receptivity in rats following controlled ovarian hyperstimulation

“…The impaired angiogenesis in COH rats is expected to lead to defective development of the endometrium 44 and thus influence the morphologic feature of uterus. To verify this expectation, a morphometry analysis was performed for the HE-stained sections.…”

Remodeling of endometrial vascular system in woman of reproductive age in normal and pathological condition (a review)

“…Эстроген и прогестерон играют главную роль в формировании сосудистого русла, однако механизмы их воздействия до конца непонятны [3]. Эстрогены стимулируют рост эндометрия, активируя образование новых сосудов [6] и миграцию гладких миоцитов [7]. Повышение плотности сосудов в эндометрии обнаружено у женщин с гиперплазией эндометрия, связанной с гиперэстрогенемией [8].…”