scholarly journals Reasons and Mechanisms of Recurrent Failed Implantation in IVF

2021 ◽  
Author(s):  
Violeta Fodina ◽  
Alesja Dudorova ◽  
Juris Erenpreiss
Keyword(s):  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Implantation Failure ◽  
Recurrent Implantation Failure ◽  
Reproductive Techniques ◽  
Immunological Factors

Recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF) are serious problems in IVF and ICSI cycles. Different factors are showed to be responsible for these clinical challenges – such as paternal, maternal, embryonic, immunological, infectious, hormonal, and others. In this chapter we have tried to review the available data on reasons for the RIF, and systematize them into: 1) uterine factors; 2) embryo factors; 3) immunological factors; 4) other factors. Interplay between all these factors play a role in RIF, and further investigations are needed to elucidate their significance and interactions – in order to elaborate more definite suggestions or guidelines for the clinicians dealing with artificial reproductive techniques and facing RPL and RIF.

scholarly journals Rapamycin Corrects T Regulatory Cell Depletion and Improves Embryo Implantation and Live Birth Rates in a Murine Model

2019 ◽  
Vol 26 (12) ◽  
pp. 1545-1556 ◽  
Author(s):  
Greene Donald Royster ◽  
Justine C. Harris ◽  
Amanda Nelson ◽  
Yessenia Castro ◽  
R. Patrick Weitzel ◽  
...  
Keyword(s):  
Murine Model ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Embryo Implantation ◽  
Mammalian Target Of Rapamycin ◽  
Unexplained Infertility ◽  
Implantation Failure ◽  
T Regulatory Cell ◽  
Recurrent Implantation Failure ◽  
Regulatory Cell

There are few treatments for patients with recurrent pregnancy loss (RPL) or recurrent implantation failure (RIF). Women with RPL and unexplained infertility have lower T regulatory cell (Treg) expression when compared to fertile controls. A murine model has been developed with depletion of regulatory T cells (DEREG) after administration of diphtheria toxin (DT), resulting in smaller litter sizes, secondary to embryo implantation failure. Numerous murine studies have shown that adoptive transfer of CD4+CD25+FoxP3+ Tregs from donors improves litter sizes in DEREG mice with depleted Tregs. Our hypothesis is that DEREG mice treated with a single dose of DT will deplete Tregs and subsequently decrease litter sizes and that treatment with rapamycin (sirolimus; Pfizer) during the time of embryo implantation will increase Tregs and restore litter sizes nearly back to normal levels. Syngeneic mating of DEREG mice after depletion of Tregs resulted in smaller litter sizes and this defect was reversed when these DEREG mice were treated with rapamycin at the time of embryo implantation. The importance of Tregs at the time of embryo implantation has been well established and immunotherapy treatments, such as rapamycin (mammalian target of rapamycin inhibitor), may prove to be an effective treatment for patients with RPL, RIF, or unexplained infertility with low Treg.

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