Absence of teratogenicity of sirolimus used during early pregnancy in a liver transplant recipient

Everolimus, an mTOR pathway inhibitor, is highly successful on ovarian hyperstimulation syndrome by reducing ovarian weight and progesterone levels: a preclinical experimental randomized controlled study

“…Indeed, Metformin caused a slight reduction in the vascular permeability but it was proven ineffective in reducing ovarian weight. Taking into account these findings as well as previous studies [13], we could assume that AMPK pathway activation does not play any role in VEGF induction. Finally, regarding Vitamin C, although it has been shown to downregulate VEGF production [19], in our animal model failed to show any positive effect against OHSS.…”

“…Therefore, the inhibition of mTOR pathway by Everolimus can explain the lower PRG levels observed in the current study. Taking into account that mTOR inhibition had no effect on the subsequent embryo development to the blastocyst stage [6] and that successful pregnancies have been reported in patients receiving other mTOR inhibitors [10][11][12][13], we could support the use of everolimus for the control of OHSS in human trials. Moreover, given the pharmacokinetics of Everolimus as well as the increase of mTOR mRNA levels between the third and the fifth day in pregnant mouse endometrium [14], we could administer Everolimus either before b-hCG administration (the administration days depend on the desired follicle reduction) or only for one day after hCG administration.…”

Pregnancy Outcomes in Solid Organ Transplant Recipients With Exposure to Mycophenolate Mofetil or Sirolimus

“…Another means to address the concerns of MMF exposures during pregnancy would be to evaluate pregnancy exposures to MMF in the non-transplant population, many of whom would not likely be taking the multiplicity of agents similar to transplant recipients. Regarding sirolimus, in addition to the results from our series, Jankowska et al published a recent case report of a female liver recipient maintained on tacrolimus, sirolimus and prednisone before conception and during the first trimester (16). The recipient delivered a healthy term infant at 39 weeks with no structural malformations (16).…”

“…Regarding sirolimus, in addition to the results from our series, Jankowska et al published a recent case report of a female liver recipient maintained on tacrolimus, sirolimus and prednisone before conception and during the first trimester (16). The recipient delivered a healthy term infant at 39 weeks with no structural malformations (16). More recently, in a letter to the editor, Guardia et al reported on a successful pregnancy under sirolimus based immunosuppression (17).…”

Transplantation hépatique et grossesse

“…De plus, il n'existe pas de données suffisamment pertinentes concernant l'utilisation d'inhibiteurs de mTOR chez la femme enceinte (3 cas publiés à ce jour) [35,40].…”