Journal of Assisted Reproduction and Genetics

, Volume 34, Issue 4, pp 465–470 | Cite as

Increased incidence of post-term delivery and Cesarean section after frozen-thawed embryo transfer during a hormone replacement cycle

  • Kazuki Saito
  • Kenji Miyado
  • Kenji Yamatoya
  • Akira Kuwahara
  • Eisuke Inoue
  • Mami Miyado
  • Maki Fukami
  • Tomonori Ishikawa
  • Takakazu Saito
  • Toshiro Kubota
  • Hidekazu SaitoEmail author
Assisted Reproduction Technologies



This study aimed to clarify the risks of adverse pregnancy outcomes in patients who conceive singletons after frozen embryo transfer (FET) during a hormone replacement cycle and their offspring.


A retrospective cohort study was conducted in patients who conceived after FET, based on the Japanese-assisted reproductive technology registry for 2013. The perinatal outcomes in cases with live-born singletons achieved through natural ovulatory cycle FET (NC-FET) (n = 6287) or hormone replacement cycle FET (HRC-FET) (n = 10,235) were compared. Multiple logistic regression analyses were performed to determine the potential confounding factors.


The frequencies of macrosomia (1.1% in NC-FET and 1.4% in HRC-FET; P = 0.058) were comparable between patients after NC-FET and HRC-FET. The proportions of post-term delivery (0.2% in NC-FET and 1.3% in HRC-FET; P < 0.001) and Cesarean section (33.6% in NC-FET and 43.0% in HRC-FET; P < 0.001) were higher in patients after HRC-FET than in patients after NC-FET. The risks of post-term delivery (adjusted odds ratio (AOR) 5.68, 95% confidence interval (CI) 3.30–9.80) and Cesarean section (AOR 1.64, 95% CI 1.52–1.76) were also higher in patients after HRC-FET than in patients after NC-FET.


Patients who conceived singletons after HRC-FET were at increased risk of post-term delivery and Cesarean section compared with those who conceived after NC-FET.


Assisted reproductive technology Hormone replacement cycle Post-term delivery Cesarean section 



We would like to thank all of the Japanese fertility clinics for reporting the data and the JSOG for kindly providing the data.

Authors’ roles

K.S. and H.S. initiated and planned the study. K.S., K.M., K.Y., A.K., E.I., and M.M. analyzed the data. K.S., K.M., A.K., M.F., T.I., T.S., T.K., and H.S. interpreted the results. K.S. and K.M. drafted the manuscript. All of the authors critically reviewed and approved the manuscript.

Compliance with ethical standards

This study was approved by the Institutional Review Board and the registration and research subcommittee of the Japan Society of Obstetrics and Gynecology (JSOG) Ethics Committee.


This study was supported by a Grant from the Japan Agency for Medical Research and Development (No. 15gk0110001h0103). The sponsor had no role in the study design; in the collection, analysis, or interpretation of data; in the writing of the report; or in the decision to submit the article for publication.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Gera PS, Tatpati LL, Allemand MC, Wentworth MA, Coddington CC. Ovarian hyperstimulation syndrome: steps to maximize success and minimize effect for assisted reproductive outcome. Fertil Steril. 2010;94:173–8.CrossRefPubMedGoogle Scholar
  2. 2.
    Takeshima K, Jwa SC, Saito H, Nakaza A, Kuwahara A, Ishihara O, et al. Impact of single embryo transfer policy on perinatal outcomes in fresh and frozen cycles-analysis of the Japanese Assisted Reproduction Technology registry between 2007 and 2012. Fertil Steril. 2016;105:337–46.CrossRefPubMedGoogle Scholar
  3. 3.
    Groenewoud ER, Cantineau AE, Kollen BJ, Macklon NS, Cohlen BJ. What is the optimal means of preparing the endometrium in frozen-thawed embryo transfer cycles? A systematic review and meta-analysis. Hum Reprod Update. 2013;19:458–70.CrossRefPubMedGoogle Scholar
  4. 4.
    Kaser DJ, Melamed A, Bormann CL, Myers DE, Missmer SA, Walsh BW, et al. Cryopreserved embryo transfer is an independent risk factor for placenta accrete. Fertil Steril. 2015;103:1176–84.CrossRefPubMedGoogle Scholar
  5. 5.
    Ishihara O, Araki R, Kuwahara A, Itakura A, Saito H, Adamson GD. Impact of frozen-thawed single-blastocyst transfer on maternal and neonatal outcome: an analysis of 277,042 single-embryo transfer cycles from 2008 to 2010 in Japan. Fertil Steril. 2014;101:128–33.CrossRefPubMedGoogle Scholar
  6. 6.
    Opdahl S, Henningsen AA, Tiitinen A, Bergh C, Pinborg A, Romundstad PR, et al. Risk of hypertensive disorders in pregnancies following assisted reproductive technology: a cohort study from the CoNARTaS group. Hum Reprod. 2015;30:1724–31.CrossRefPubMedGoogle Scholar
  7. 7.
    Wennerholm UB, Henningsen AK, Romundstad LB, Bergh C, Pinborg A, Skjaerven R, et al. Perinatal outcomes of children born after frozen-thawed embryo transfer: a Nordic cohort study from the CoNARTaS group. Hum Reprod. 2013;28:2545–53.CrossRefPubMedGoogle Scholar
  8. 8.
    Nastri CO, Lensen SF, Gibreel A, Raine-Fenning N, Ferriani RA, Bhattacharya S, et al. Endometrial injury in women undergoing assisted reproductive techniques. Cochrane Database Syst Rev. 2015;3:CD009517.Google Scholar
  9. 9.
    Jauniaux E, Jurkovic D. Placenta accreta: pathogenesis of a 20th century iatrogenic uterine disease. Placenta. 2012;33:244–51.CrossRefPubMedGoogle Scholar
  10. 10.
    Imudia AN, Awonuga AO, Doyle JO, Kaimal AJ, Wright DL, Toth TL, 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;97:1374–9.CrossRefPubMedGoogle Scholar
  11. 11.
    Roos N, Kieler H, Sahlin L, Ekman-Ordeberg G, Falconer H, Stephansson O. Risk of adverse pregnancy outcomes in women with polycystic ovary syndrome: population based cohort study. BMJ. 2011;343:d6309.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Givens CR, Markun LC, Ryan IP, Chenette PE, Herbert CM, Schriock ED. Outcomes of natural cycles versus programmed cycles for 1677 frozen-thawed embryo transfers. Reprod Biomed Online. 2009;19:380–4.CrossRefPubMedGoogle Scholar
  13. 13.
    Zheng Y, Li Z, Xiong M, Luo T, Dong X, Huang B, et al. Hormonal replacement treatment improves clinical pregnancy in frozen-thawed embryos transfer cycles: a retrospective cohort study. Am J Transl Res. 2014;6:85–90.Google Scholar
  14. 14.
    Nakashima A, Araki R, Tani H, Ishihara O, Kuwahara A, Irahara M, et al. Implications of assisted reproductive technologies on term singleton birth weight: an analysis of 25,777 children in the national assisted reproduction registry of Japan. Fertil Steril. 2013;99:450–5.CrossRefPubMedGoogle Scholar
  15. 15.
    Itabashi K, Fujimura M, Kusuda S, Tamura M, Hayashi T, Takahashi T, et al. New standard of average size and weight of newborn in Japan. Jap J Pediat. 2010;114:1271–93 (in Japanese).Google Scholar
  16. 16.
    Practice ACOG. Bulletin. Clinical management guidelines for obstetricians-gynecologists. Number 55, September 2004 (replaces practice pattern number 6, October 1997). Management of postterm pregnancy. Obstet Gynecol. 2004;104:639–46.CrossRefGoogle Scholar
  17. 17.
    American College of Obstetricians and Gynecologists. Practice bulletin no. 146: management of late-term and postterm pregnancies. Obstet Gynecol. 2014;124:390–6.CrossRefGoogle Scholar
  18. 18.
    Tummon I, Gavrilova-Jordan L, Allemand MC, Session D. Polycystic ovaries and ovarian hyperstimulation syndrome: a systematic review*. Acta Obstet Gynecol Scand. 2005;84:611–6.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Kazuki Saito
    • 1
    • 2
    • 3
  • Kenji Miyado
    • 4
  • Kenji Yamatoya
    • 1
    • 4
  • Akira Kuwahara
    • 5
  • Eisuke Inoue
    • 6
  • Mami Miyado
    • 3
  • Maki Fukami
    • 3
  • Tomonori Ishikawa
    • 2
  • Takakazu Saito
    • 1
  • Toshiro Kubota
    • 2
  • Hidekazu Saito
    • 1
    Email author
  1. 1.Department of Perinatal Medicine and Maternal CareNational Center for Child Health and DevelopmentTokyoJapan
  2. 2.Department of Comprehensive Reproductive Medicine, Graduate SchoolTokyo Medical and Dental UniversityTokyoJapan
  3. 3.Department of Molecular EndocrinologyNational Research Institute for Child Health and DevelopmentTokyoJapan
  4. 4.Department of Reproductive BiologyNational Research Institute for Child Health and DevelopmentTokyoJapan
  5. 5.Department of Obstetrics and Gynecology, Institute of Health BiosciencesThe University of Tokushima Graduate SchoolTokushimaJapan
  6. 6.Division of Statistical Analysis, Center for Clinical Research and DevelopmentNational Center for Child Health and DevelopmentTokyoJapan

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