Anti-phospholipid antibody may reduce endometrial receptivity during the window of embryo implantation

J Gynecol Obstet Hum Reprod. 2021 Jun;50(6):101912. doi: 10.1016/j.jogoh.2020.101912. Epub 2020 Sep 17.

Abstract

Background: Anti-phospholipid antibodies (aPL) have been reported to be associated with repeated implantation failure (RIF), but the mechanism remains controversial. Endometrial receptivity is well known to be crucial for embryo implantation. This study aims to investigate the effect of aPL on endometrial receptivity in RIF women with positive aPL.

Methods: Sixty-four infertile women with normal menstrual cycles were enrolled. The control group comprised 32 pregnant women with negative aPL who conceived successfully after their first in vitro fertilization-embryo transfer (IVF-ET) cycle, and the RIF group comprised 32 women with positive aPL. Endometrial biopsy samples were collected seven days after the luteinizing hormone surge (LH + 7). The expression of LIF and HOXA10 was evaluated by immunohistochemistry, qRT-PCR and Western blot. Endometrial pinopode development was examined by scanning electron microscopy.

Results: The mRNA expression of LIF and HOXA10 in the RIF group was significantly decreased compared with that in the control group during the implantation window. The immunohistochemistry and Western blot results confirmed these findings. Then, ultrastructural analyses of endometrial cells showed fewer pinopode processes, a more atypical morphology and increased atrophy in the RIF group compared with the control group, and these results were statistically significant.

Conclusion: aPL positivity may inhibit the expression of LIF and HOXA10 in the endometrium and influence pinopode development. Our findings suggest that positivity for aPL is associated with impaired endometrial receptivity, which results in the development of RIF.

Keywords: Antiphospholipid antibody; Endometrial receptivity; HOXA10; Leukemia inhibitory factor; Pinopode; Repeated implantation failure.

MeSH terms

  • Adult
  • Antibodies, Antiphospholipid / blood*
  • Biomarkers / blood
  • Case-Control Studies
  • Embryo Implantation*
  • Embryo Transfer
  • Endometrium / metabolism*
  • Endometrium / ultrastructure
  • Female
  • Fertilization in Vitro
  • Homeobox A10 Proteins / genetics
  • Homeobox A10 Proteins / metabolism*
  • Humans
  • Infertility, Female / therapy
  • Leukemia Inhibitory Factor / genetics
  • Leukemia Inhibitory Factor / metabolism*
  • RNA, Messenger / metabolism

Substances

  • Antibodies, Antiphospholipid
  • Biomarkers
  • Homeobox A10 Proteins
  • LIF protein, human
  • Leukemia Inhibitory Factor
  • RNA, Messenger
  • HOXA10 protein, human