Advertisement

Endometrial thickness in the prediction of neonatal adverse outcomes in frozen cycles for singleton pregnancies

  • Author Footnotes
    # Contributed equally.
    Kai-Lun Hu
    Footnotes
    # Contributed equally.
    Affiliations
    Key Laboratory of Reproductive Genetics (Ministry of Education) and Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou Zhejiang 310006, PR China

    Key Laboratory of Women's Reproductive Health of Zhejiang Province
    Search for articles by this author
  • Author Footnotes
    # Contributed equally.
    Andrew Kawai
    Footnotes
    # Contributed equally.
    Affiliations
    Department of Obstetrics and Gynaecology, Monash University, Clayton Victoria, Australia
    Search for articles by this author
  • Sarah Hunt
    Affiliations
    Department of Obstetrics and Gynaecology, Monash University, Clayton Victoria, Australia
    Search for articles by this author
  • Wentao Li
    Affiliations
    Department of Obstetrics and Gynaecology, Monash University, Clayton Victoria, Australia
    Search for articles by this author
  • Xiaohong Li
    Affiliations
    Centre for Reproductive Medicine, Department of Obstetrics and Gynaecology, West China Second University Hospital of Sichuan University, Chengdu, China
    Search for articles by this author
  • Runjv Zhang
    Affiliations
    Key Laboratory of Reproductive Genetics (Ministry of Education) and Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou Zhejiang 310006, PR China
    Search for articles by this author
  • Yanjun Hu
    Affiliations
    Key Laboratory of Reproductive Genetics (Ministry of Education) and Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou Zhejiang 310006, PR China
    Search for articles by this author
  • Huijuan Gao
    Affiliations
    Key Laboratory of Reproductive Genetics (Ministry of Education) and Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou Zhejiang 310006, PR China
    Search for articles by this author
  • Yimin Zhu
    Affiliations
    Key Laboratory of Reproductive Genetics (Ministry of Education) and Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou Zhejiang 310006, PR China
    Search for articles by this author
  • Lanfeng Xing
    Affiliations
    Key Laboratory of Reproductive Genetics (Ministry of Education) and Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou Zhejiang 310006, PR China
    Search for articles by this author
  • Ben W. Mol
    Affiliations
    Department of Obstetrics and Gynaecology, Monash University, Clayton Victoria, Australia
    Search for articles by this author
  • Dan Zhang
    Correspondence
    Corresponding author.
    Affiliations
    Key Laboratory of Reproductive Genetics (Ministry of Education) and Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou Zhejiang 310006, PR China

    Key Laboratory of Women's Reproductive Health of Zhejiang Province
    Search for articles by this author
  • Daniel L. Rolnik
    Affiliations
    Department of Obstetrics and Gynaecology, Monash University, Clayton Victoria, Australia
    Search for articles by this author
  • Author Footnotes
    # Contributed equally.
Published:April 24, 2021DOI:https://doi.org/10.1016/j.rbmo.2021.04.014

      Abstract

      Research question

      Does endometrial thickness (EMT) predict adverse neonatal outcomes in singleton pregnancies after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) frozen embryo transfer (FET)?

      Design

      This retrospective study involved 13,383 women undergoing IVF/ICSI FET cycles between January 2010 and December 2018 in Women's Hospital of Zhejiang University. The primary outcome was preterm delivery (PTD). The secondary outcomes were small for gestational age (SGA), large for gestational age (LGA) and low birthweight (LBW).

      Results

      A total of 13,383 FET cycles resulting in 5220 singleton live births and 8163 failed cycles were included. Multiple spline regression visualization showed an increasing risk of PTD and LBW for a thin EMT. By comparing multiple cut-off points using area under the curve, a cut-off point of 8 mm was identified, which was used to categorize EMT. A reference point of EMT greater than 8 mm was used; after adjusting for covariates, individuals with EMT less than 8 mm had an adjusted odds ratio of 1.75 (95% CI 1.30 to 2.34) for PTD, 1.57 (95% CI 1.09 to 2.26) for LBW, 0.97 (95% CI 0.63 to 1.50) for SGA and 1.04 (95% CI 0.79 to 1.37) for LGA. Additional analyses showed similar increasing risk with a thin endometrium for both PTD with and without caesarean section, and PTD with low and normal birthweight percentiles.

      Conclusion

      A clinical cut-off point of 8 mm has been identified, below which risk of PTD and LBW increases in women undergoing IVF/ICSI.

      KEYWORDS

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Reproductive BioMedicine Online
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Altman D.G.
        • Lausen B.
        • Sauerbrei W.
        • Schumacher M.
        Dangers of Using “Optimal” Cutpoints in the Evaluation of Prognostic Factors.
        JNCI: Journal of the National Cancer Institute. 1994; 86: 829-835
      1. Chieve, A. A. S., S. Usan, F. M. Eikle, C. Ynthia, F. Erre, E. B. P. Eterson, G. Ary, J. Eng, L. Ynne, and S. W. Ilcox. 2002. Low and Very Low Birth Weight in Infants Conceived With Use of Assisted Reproductive Technology, 731-737.

        • Chung K.
        • Coutifaris C.
        • Chalian R.
        • Lin K.
        • Ratcliffe S.J.
        • Castelbaum A.J.
        • Freedman M.F.
        • Barnhart K.T.
        Factors influencing adverse perinatal outcomes in pregnancies achieved through use of in vitro fertilization.
        Fertil. Steril. 2006; 86: 1634-1641
        • Dai L.
        • Deng C.
        • Li Y.
        • Zhu J.
        • Mu Y.
        • Deng Y.
        • Mao M.
        • Wang Y.
        • Li Q.
        • Ma S.
        • Ma X.
        • Zhang Y.
        Birth weight reference percentiles for Chinese.
        PLoS One. 2014; 9
        • Donald G.
        • Iv R.
        • Krishnamoorthy K.
        • Csokmay J.M.
        • Yauger B.J.
        • Chason R.J.
        • Decherney A.H.
        • Wolff E.F.
        • Hill M.J.
        • Author F.S.
        Are ICSI and high serum estradiol compounding risk factors for adverse obstetric outcomes in ART? HHS Public Access Author manuscript.
        Fertil. Steril. 2016; 106: 363-370
        • Guo Z.
        • Xu X.
        • Zhang L.
        • Zhang L.
        • Yan L.
        • Ma J.
        Endometrial thickness is associated with incidence of small-for-gestational-age infants in fresh in vitro fertilization–intracytoplasmic sperm injection and embryo transfer cycles.
        Fertil. Steril. 2020; 113: 745-752
      2. Helmerhorst, F. M., D. A. M. Perquin, D. Donker, and M. J. N. C. Keirse. 2004. Perinatal outcome of singletons and twins after assisted conception: A systematic review of controlled studies, 261-264.

      3. Jackson, R. A., K. A. Gibson, Y. W. Wu, and M. S. Croughan. 2004. Perinatal outcomes in singletons following in vitro fertilization: A meta-analysis, 551-563.

        • Jing S.
        • Li X.
        • Zhang S.
        • Gong F.
        • Lu G.
        • Lin G.
        The risk of placenta previa and cesarean section associated with a thin endometrial thickness: a retrospective study of 5251 singleton births during frozen embryo transfer in China.
        Arch. Gynecol. Obstet. 2019; 300: 1227-1237
        • Kasius A.
        • Smit J.G.
        • Torrance H.L.
        • Eijkemans M.J.C.
        • Mol B.Willem
        • Opmeer B.C.
        • Broekmans F.J.M.
        Endometrial thickness and pregnancy rates after IVF: a systematic review and meta-analysis.
        Hum. Reprod. Update. 2014; 20: 530-541
        • Kovalevsky G.
        • Rinaudo P.
        • Coutifaris C.
        Do assisted reproductive technologies cause adverse fetal outcomes?.
        Fertil. Steril. 2003; 79: 1270-1272
        • Marrie R.A.
        • Dawson N.V.
        • Garland A.
        Quantile regression and restricted cubic splines are useful for exploring relationships between continuous variables.
        J. Clin. Epidemiol. 2009; 62 (511-517.e511)
        • McGovern P.G.
        • Llorens A.J.
        • Skurnick J.H.
        • Weiss G.
        • Goldsmith L.T.
        Increased risk of preterm birth in singleton pregnancies resulting from in vitro fertilization-embryo transfer or gamete intrafallopian transfer: A meta-analysis.
        Fertil. Steril. 2004; 82: 1514-1520
        • Miwa I.
        • Tamura H.
        • Takasaki A.
        • Yamagata Y.
        • Shimamura K.
        • Sugino N.
        Pathophysiologic features of "thin" endometrium.
        Fertil. Steril. 2009; 91: 998-1004
        • Moffat R.
        • Beutler S.
        • Schötzau A.
        • De Geyter M.
        • De Geyter C.
        Endometrial thickness influences neonatal birth weight in pregnancies with obstetric complications achieved after fresh IVF-ICSI cycles.
        Arch. Gynecol. Obstet. 2017; 296: 115-122
      4. Oron, G., L. Hiersch, S. Rona, R. Prag-Rosenberg, O. Sapir, M. Tuttnauer-Hamburger, Y. Shufaro, B. Fisch, and A. Ben-Haroush. 2018. Endometrial thickness of less than 7.5 mm is associated with obstetric complications in fresh IVF cycles: a retrospective cohort study. 37:2018-2018.

        • Pereira N.
        • Elias R.T.
        • Christos P.J.
        • Petrini A.C.
        • Hancock K.
        • Lekovich J.P.
        • Rosenwaks Z.
        • The R.O.
        • Perelman C.
        Supraphysiologic estradiol is an independent predictor of low birth weight in full-term singletons born after fresh embryo transfer † Is supraphysiologic estradiol (E 2) an independent predictor of low birth weight (LBW) in singletons born after fresh IVF-embryo transfer (ET) cycles?.
        Human Reproduction. 2017; 32: 1410-1417
        • Romero R.
        • Dey S.K.
        • Fisher S.J.
        Preterm labor: one syndrome, many causes.
        Science. 2014; 345: 760-765
        • Shi Y.
        • Sun Y.
        • Hao C.
        • Zhang H.
        • Wei D.
        • Zhang Y.
        • Zhu Y.
        • Deng X.
        • Qi X.
        • Li H.
        • Ma X.
        • Ren H.
        • Wang Y.
        • Zhang D.
        • Wang B.
        • Liu F.
        • Wu Q.
        • Wang Z.
        • Bai H.
        • Li Y.
        • Zhou Y.
        • Sun M.
        • Liu H.
        • Li J.
        • Zhang L.
        • Chen X.
        • Zhang S.
        • Sun X.
        • Legro R.S.
        • Chen Z.J.
        Transfer of Fresh versus Frozen Embryos in Ovulatory Women.
        N. Engl. J. Med. 2018; 378: 126-136
        • Sunderam S.
        • Kissin D.M.
        • Crawford S.B.
        • Folger S.G.
        • Boulet S.L.
        • Warner L.
        • Barfield W.D.
        Assisted reproductive technology surveillance - United States, 2015.
        MMWR Surveillance Summaries. 2018; 67: 1-28
      5. Team., R. D. C. 2018 s. R: A language and environment for statistical computing.

        • White I.R.
        • Royston P.
        • Wood A.M.
        Multiple imputation using chained equations: Issues and guidance for practice.
        Statistics in Medicine. 2011; 30: 377-399
        • Yao F.
        • Miao H.
        • Li B.
        • Wu Y.
        • Zhao Q.
        New birthweight percentiles by sex and gestational age in Southern China and its comparison with the INTERGROWTH-21st Standard.
        Sci. Rep. 2018; 8: 7567
        • Zhang J.
        • Du M.
        • Li Z.
        • Wang L.
        • Hu J.
        • Zhao B.
        • Feng Y.
        • Chen X.
        • Sun L.
        Fresh versus frozen embryo transfer for full-term singleton birth: a retrospective cohort study.
        J. Ovarian Res. 2018; 11: 59
        • Zhang J.
        • Liu H.
        • Mao X.
        • Chen Q.
        • Si J.
        • Fan Y.
        • Xiao Y.
        • Wang Y.
        • Kuang Y.
        Effect of endometrial thickness on birthweight in frozen embryo transfer cycles: An analysis including 6181 singleton newborns.
        Human Reproduction. 2019; 34: 1707-1715

      Biography

      Andrew Kawai is a medical student at Monash University and has an interest in applying machine learning and statistical methodology to obstetrics and gynaecology. He is a strong believer in evidence-based practice.
      Key message
      A clinical cut-off point of 8 mm of endometrial thickness has been identified, below which the risk of preterm delivery and low birthweight increases in women undergoing IVF and intracytoplasmic sperm injection.