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Lower risk of adverse perinatal outcomes in natural versus artificial frozen–thawed embryo transfer cycles: a systematic review and meta-analysis

  • José Moreno-Sepulveda
    Correspondence
    Corresponding author.
    Affiliations
    Obstetrics and Gynecology Department, Universitat Autònoma de Barcelona, Campus Universitario UAB, Bellaterra Cerdanyola del Vallès 08193, Spain

    Clínica de la Mujer Medicina Reproductiva, Alejandro Navarrete 2606, Viña del Mar, Chile
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  • Juan Jose Espinós
    Affiliations
    Obstetrics and Gynecology Department, Universitat Autònoma de Barcelona, Campus Universitario UAB, Bellaterra Cerdanyola del Vallès 08193, Spain

    Fertty International, Carrer d'Ausiàs Marc, 25, Barcelona 08010, Spain

    Department of Obstetrics and Gynaecology, Hospital de la Santa Creu i Sant Pau, Carrer de Sant Quintí, 89 Barcelona 08041, Spain
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  • Miguel Angel Checa
    Affiliations
    Obstetrics and Gynecology Department, Universitat Autònoma de Barcelona, Campus Universitario UAB, Bellaterra Cerdanyola del Vallès 08193, Spain

    Fertty International, Carrer d'Ausiàs Marc, 25, Barcelona 08010, Spain

    GRI-BCN, Barcelona Infertility Research Group, IMIM, Institut Hospital del Mar d'Investigacions Mèdiques, Carrer del Dr. Aiguader, 88, Barcelona 08003, Spain
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Published:March 10, 2021DOI:https://doi.org/10.1016/j.rbmo.2021.03.002

      Highlights

      • NC-FET is associated with a lower risk of hypertensive disorders of pregnancy
      • The risk of LGA and macrosomia may be reduced in newborns after NC-FET
      • Postpartum hemorrhage and placenta accreta are other outcomes improved after NC-FET
      • Cesarean section rates are high in FET, both in natural and artificial cycles

      Abstract

      This systematic review of literature and meta-analysis of observational studies reports on perinatal outcomes after frozen embryo transfer (FET). The aim was to determine whether natural cycle frozen embryo transfer (NC-FET) in singleton pregnancies conceived after IVF decreased the risk of adverse perinatal outcomes compared with artificial cycle frozen embryo transfer (AC-FET). Thirteen cohort studies, including 93,201 cycles, met the inclusion criteria. NC-FET was associated with a lower risk of hypertensive disorders in pregnancy (HDP) (RR 0.61, 95% CI 0.50 to 0.73), preeclampsia (RR 0.47, 95% CI 0.42 to 0.53), large for gestational age (LGA) (RR 0.93, 95% CI 0.90 to 0.96) and macrosomia (RR 0.82, 95% CI 0.69 to 0.97) compared with AC-FET. No significant difference was found in the risk of gestational hypertension and small for gestational age. Secondary outcomes assessed were the risk of preterm birth (RR 0.83, 95% CI 0.79 to 0.88); post-term birth (RR 0.48, 95% CI 0.29 to 0.80); low birth weight (RR 0.84, 95% CI 0.80 to 0.89); caesarean section (RR 0.84, 95% CI 0.77 to 0.91); postpartum haemorrhage (RR 0.39, 95% CI 0.35 to 0.45); placental abruption (RR 0.61, 95% CI 0.38 to 0.98); and placenta accreta (RR 0.18, 95% CI 0.10 to 0.33). All were significantly lower with NC-FET compared with AC-FET. In assessing safety, NC-FET significantly decreased the risk of HDP, preeclampsia, LGA, macrosomia, preterm birth, post-term birth, low birth weight, caesarean section, postpartum haemorrhage, placental abruption and placenta accreta. Further randomized controlled trials addressing the effect of NC-FET and AC-FET on maternal and perinatal outcomes are warranted. Clinicians should carefully monitor pregnancies achieved by FET in artificial cycles prenatally, during labour and postnatally.

      KEYWORDS

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        • Zhou L.
        • Wei D.
        • Ding L.
        • Qin Y.
        Increased risk of maternal and neonatal complications in hormone replacement therapy cycles in frozen embryo transfer.
        Reprod. Biol. Endocrinol. 2020; 18: 36

      Biography

      José Moreno-Sepúlveda obtained his medical degree from Valparaiso School of Medicine, 2009, and his PhD from the Department of Obstetrics and Gynecology, Universitat Autonoma de Barcelona, 2019. Currently, his main research project is on safety in assisted reproductive techniques, focusing on maternal and perinatal outcomes after IVF.
      Key message
      The risk of adverse perinatal outcomes, including hypertensive disorders of pregnancy, preeclampsia, large-for-gestational-age infants and macrosomia is significantly lower for frozen–thawed embryo transfers (FET) carried out in natural cycles compared with artificial cycles. Clinicians should carefully monitor pregnancies achieved by FET in artificial cycles prenatally, during labour and postnatally.