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Risk of preeclampsia in artificial cycles of frozen embryo transfer in vitro fertilization pregnancies: a response

      We would like to thank Drs Al-Lami, Sibai, and Salih for their interest and comments on our recent publication “Letrozole-induced frozen embryo transfer cycles are associated with a lower risk of hypertensive disorders of pregnancy among women with polycystic ovary syndrome.”
      • Zhang J.
      • Wei M.
      • Bian X.
      • et al.
      Letrozole-induced frozen embryo transfer cycles are associated with a lower risk of hypertensive disorders of pregnancy among women with polycystic ovary syndrome.
      Because research on this topic is relatively limited, all contributions are very welcome to understand the mechanism behind the observed increased risk of hypertensive disorder of pregnancy in artificial frozen embryo transfer cycles.
      First, we fully agree with Dr Al-Lami and colleagues that immune mediators play an important role in trophoblast invasion and placentation. We do benefit a lot from their opinions. Second, the pathogenesis for the increased risk of preeclampsia associated with in vitro fertilization might be multifactorial. The cryopreservation technique,
      • Sites C.K.
      • Wilson D.
      • Barsky M.
      • et al.
      Embryo cryopreservation and preeclampsia risk.
      immune response,
      • Savasi V.M.
      • Mandia L.
      • Laoreti A.
      • Cetin I.
      Maternal and fetal outcomes in oocyte donation pregnancies.
      controlled ovarian stimulation,
      • 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.
      and the type of endometrial preparation
      • Hu K.L.
      • Zhang D.
      • Li R.
      Endometrium preparation and perinatal outcomes in women undergoing single-blastocyst transfer in frozen cycles.
      may predispose women to develop preeclampsia. Finally, our study found that a physiological frozen embryo transfer cycle regimen was associated with a lower risk of hypertensive disorders of pregnancy among women with polycystic ovary syndrome. The underlying molecular mechanism behind these findings warrants further investigation.

      References

        • Zhang J.
        • Wei M.
        • Bian X.
        • et al.
        Letrozole-induced frozen embryo transfer cycles are associated with a lower risk of hypertensive disorders of pregnancy among women with polycystic ovary syndrome.
        Am J Obstet Gynecol. 2021; 225: 59.e1-59.e9
        • Sites C.K.
        • Wilson D.
        • Barsky M.
        • et al.
        Embryo cryopreservation and preeclampsia risk.
        Fertil Steril. 2017; 108: 784-790
        • Savasi V.M.
        • Mandia L.
        • Laoreti A.
        • Cetin I.
        Maternal and fetal outcomes in oocyte donation pregnancies.
        Hum Reprod Update. 2016; 22: 620-633
        • 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
        • Hu K.L.
        • Zhang D.
        • Li R.
        Endometrium preparation and perinatal outcomes in women undergoing single-blastocyst transfer in frozen cycles.
        Fertil Steril. 2021; 115: 1487-1494

      Linked Article

      • Risk of preeclampsia in artificial cycles of frozen embryo transfer in vitro fertilization pregnancies
        American Journal of Obstetrics & GynecologyVol. 225Issue 4
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          Zhang et al1 investigated the importance of corpus luteum and relaxin in preventing hypertensive disorders of pregnancy (HDP), including preeclampsia, in women with polycystic ovarian syndrome who were undergoing artificial frozen embryo transfer (FET) cycles when compared to letrozole ovulation induction cycles. They also discussed perturbed vascular remodeling caused by prematurely elevated estrogen levels and impaired angiogenesis as potential culprits to the increased risk of HDP in women undergoing FET cycles.
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