Advertisement

In vitro fertilization as an independent risk factor for placenta accreta spectrum

Published:August 11, 2021DOI:https://doi.org/10.1016/j.ajog.2021.08.008
      To the Editors:
      Salmanian et al
      • Salmanian B.
      • Fox K.A.
      • Arian S.E.
      • et al.
      In vitro fertilization as an independent risk factor for placenta accreta spectrum.
      discussed the possible effects of less physiological levels of estradiol on the risk of placenta accrete spectrum (PAS) development in in vitro fertilization (IVF) cycles, especially in frozen embryo transfer (FET) cycles, through manipulating the process of normal implantation and placentation. To date, the exact effect of altered levels of estradiol on endometrial microenvironment around the time of implantation remains uncertain. In this letter, we will explain one mechanism by which altered levels of estradiol could modulate the process of normal placentation.
      The mechanism by which altered levels of estradiol affect the decidua formation and placentation could include immune response modulation. PAS pathophysiology involves thin decidua formation and excessive trophoblast invasion, both of which could be mediated by altered levels of cytokines that are otherwise required in controlled and balanced concentrations for normal decidua formation and trophoblast invasion (eg, interleukin 6 [IL-6], IL-8, and IL-1β).
      • Dimitriadis E.
      • White C.A.
      • Jones R.L.
      • Salamonsen L.A.
      Cytokines, chemokines and growth factors in endometrium related to implantation.
      Previously, we have explained the possible role of less physiological levels of estradiol in preeclampsia development in artificial FET cycles through, at least in part, the modulation of various cytokines required for normal trophoblast invasion, including IL-6, IL-8, and IL-1β.
      • Al-Lami R.A.
      • Sibai B.M.
      • Salih S.M.
      Risk of preeclampsia in artificial cycles of frozen embryo transfer in vitro fertilization pregnancies.
      Thus, it is reasonable to think that less physiological levels of estradiol, such as that associated with IVF pregnancies, could lead to either augmented or less than required concentrations of these cytokines that might ultimately contribute to shallow (with subsequent ischemia and preeclampsia development), excessive trophoblast invasion or thin decidua formation (with future development of PAS).
      However, the exact dosage of estradiol that could impair normal placentation remains inconclusive. In the literature, Kaser et al
      • Kaser D.J.
      • Melamed A.
      • Bormann C.L.
      • et al.
      Cryopreserved embryo transfer is an independent risk factor for plaenta accreta.
      and Imudia et al
      • Imudia A.N.
      • Awonuga A.O.
      • Doyle J.O.
      • et al.
      Peak serum estradiol level during controlled ovarian hyperstimulation is associated with increased risk of small for gestational age and preeclampsia in singleton pregnancies after in vitro fertilization.
      have identified the potential cutoff of estradiol that could affect placentation, 732 pg/mL to predict PAS in cryopreserved embryo transfer cycles and 3450 pg/mL to predict preeclampsia in fresh cycles, respectively. More research studies are needed to understand the exact mechanism by which less physiological levels of estradiol affect the microenvironment in the endometrium around the time of implantation and the subsequent abnormal placentation in IVF pregnancies.

      References

        • Salmanian B.
        • Fox K.A.
        • Arian S.E.
        • et al.
        In vitro fertilization as an independent risk factor for placenta accreta spectrum.
        Am J Obstet Gynecol. 2020; 223: 568.e1-568.e5
        • Dimitriadis E.
        • White C.A.
        • Jones R.L.
        • Salamonsen L.A.
        Cytokines, chemokines and growth factors in endometrium related to implantation.
        Hum Reprod Update. 2005; 11: 613-630
        • Al-Lami R.A.
        • Sibai B.M.
        • Salih S.M.
        Risk of preeclampsia in artificial cycles of frozen embryo transfer in vitro fertilization pregnancies.
        Am J Obstet Gynecol. 2021; 225: 466-467
        • Kaser D.J.
        • Melamed A.
        • Bormann C.L.
        • et al.
        Cryopreserved embryo transfer is an independent risk factor for plaenta accreta.
        Fertil Steril. 2015; 103: 1176-1184.e2
        • Imudia A.N.
        • Awonuga A.O.
        • Doyle J.O.
        • et al.
        Peak serum estradiol level during controlled ovarian hyperstimulation is associated with increased risk of small for gestational age and preeclampsia in singleton pregnancies after in vitro fertilization.
        Fertil Steril. 2012; 97: 1374-1379

      Linked Article