Changes in the T-helper 1 and 2 cell populations during pregnancy in tacrolimus-treated women with repeated implantation failure and recurrent pregnancy loss

Abstract

Tacrolimus has received considerable attention as a treatment approach for infertility associated with maternal-foetal immune abnormalities, such as repeated implantation failure (RIF) and recurrent pregnancy loss (RPL). This study examined the changes in T-helper (Th) 1 and 2 cell populations during pregnancy in peripheral blood of tacrolimus-treated RIF patients who delivered a liveborn infant from August 2012 to February 2020 at the National Centre for Child Health and Development. A total of 58 eligible study subjects were divided into two groups according to the presence of a history of RPL: (i) RIF-alone group (n = 31); and (ii) RIF-plus-RPL group (n = 27). In a flow cytometric analysis, the Th1/Th2 cell ratios were significantly higher before pregnancy than after pregnancy, and during the first trimester than the second trimester in the RIF-alone group (p = 0.0071 and p = 0.0087, respectively). However, no significant differences were present in the RIF-plus-RPL group. Although the Th1 immunity was suppressed under tacrolimus treatment in both groups, a delayed reduction in the Th1 cell percentage after initiation of treatment was observed in the RIF-plus-RPL group. In conclusion, the cellular immune alterations in tacrolimus-treated patients with RIF were different depending on the presence or absence of a history of RPL.

Keywords:

• Infertility
• abortion
• immunology of pregnancy
• tacrolimus
• repeated implantation failure
• recurrent pregnancy loss
• maternal-foetal immune abnormality
• T-helper 1 and 2 cell populations

Acknowledgments

The authors would like to thank H. Nakamura, K. Kikuchi, and N. Nakayama for assistance with the data analysis.

Disclosure statement

The authors declare no conflicts of interest.