Skip to main content
SpringerLink
Log in

Frozen-thawed embryo transfer is an independent risk factor for third stage of labor complications

  • Gynecologic Endocrinology and Reproductive Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

Third stage of labor complications are more prevalent following singleton vaginal deliveries of gestations conceived through in vitro fertilization (IVF) and fresh embryo transfer. This study aimed to evaluate these complications in pregnancies conceived through frozen-thawed embryo transfer (FET), in which endometrial preparation differs from fresh cycles.

Methods

A cohort study of all singleton pregnancies conceived through IVF-FET who delivered vaginally at a tertiary medical center during 2007–2017. The study group consisted of 88 IVF-FET gestations (cases) that were matched to 176 spontaneous pregnancies based on age, gravidity, parity and gestational week at delivery (controls). The association between mode of conception and third stage of labor complication rate was examined.

Results

Baseline characteristics were similar between groups, except for a lower prevalence of induction of labor in the control group (23.3% vs. 36.3%, p = 0.03). The rate of post-partum hemorrhage (PPH), manual lysis and revision of the uterine cavity were all higher in pregnancies conceived through IVF-FET versus spontaneously (13.6% vs. 5.7%, p = 0.018; 17% vs. 2.3%, p < 0.001; and 21.6% vs. 6.8%, p < 0.001, respectively). Multivariate analysis adjusting for age, previous cesarean section, induction of labor, neonatal weight and use of analgesia demonstrated that deliveries following IVF-FET were independently associated with an increased risk for third stage of labor complications (estimated OR = 3.45, p = 0.0002).

Conclusion

IVF-FET is an independent risk factor for PPH, need for manual lysis and revision of the uterine cavity. Precautionary measures should be undertaken in the third stage in deliveries following IVF-FET, even if no other risk factors are present.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Availability of data and materials

The data underlying this article are available in the text and attached tables.

References

  1. De Geyter C, Calhaz-Jorge C, Kupka MS, Wyns C, Mocanu E, Motrenko T, Scaravelli G, Smeenk J, Vidakovic S, Goossens V (2020) The European IVF-monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE) ART in Europe, 2015: results generated from European registries by ESHRE. Hum Reprod Open. https://doi.org/10.1093/hropen/hoz038

    Article  PubMed  PubMed Central  Google Scholar 

  2. Assisted reproductive technology, national summery report (2015). https://www.cdc.gov/art/pdf/2015-report/ART-2015-National-Summary-Report.pdf. Accessed 10 May 2020

  3. Singh B, Reschke L, Segars J, Baker VL (2020) Frozen-thawed embryo transfer: the potential importance of the corpus luteum in preventing obstetrical complications. Fertil Steril 113(2):252–257. https://doi.org/10.1016/j.fertnstert.2019.12.007

    Article  PubMed  PubMed Central  Google Scholar 

  4. Roque M, Valle M, Sampaio M, Geber S (2018) Obstetric outcomes after fresh versus frozen-thawed embryo transfers: a systematic review and meta-analysis. JBRA Assist Reprod. 22(3):253–260. https://doi.org/10.5935/1518-0557.20180049

    Article  PubMed  PubMed Central  Google Scholar 

  5. Wei D, Liu JY, Sun Y, Shi Y, Zhang B, Liu JQ et al (2019) Frozen versus fresh single blastocyst transfer in ovulatory women: a multicentre, randomised controlled trial. Lancet 393(10178):1310–1318. https://doi.org/10.1016/S0140-6736(18)32843-5

    Article  PubMed  Google Scholar 

  6. Sha T, Yin X, Cheng W, Massey IY (2018) Pregnancy-related complications and perinatal outcomes resulting from transfer of cryopreserved versus fresh embryos in vitro fertilization: a meta-analysis. Fertil Steril 109:330–342.e9

    Article  Google Scholar 

  7. Ginstrom EE, Wennerholm UB, Khatibi A, Petzold M, Bergh C (2019) Neonatal and maternal outcome after frozen embryo transfer: Increased risks in programmed cycles. Am J Obstet Gynecol 221:126.e1–126.e18

    Article  Google Scholar 

  8. Steer P, Flint C (1999) ABC of labour care: physiology and management of normal labour. Br Med J 318:793–796

    Article  CAS  Google Scholar 

  9. Wise A, Clark V (2008) Strategies to manage major obstetric haemorrhage. Curr Opin Anaesthesiol 21:281–287

    Article  Google Scholar 

  10. American College of Obstetricians and Gynecologists (2006) ACOG Practice Bulletin: Clinical Management Guidelines for Obstetrician-Gynecologists Number 76, October 2006: postpartum hemorrhage. Obstet Gynecol 108:1039–1047

    Article  Google Scholar 

  11. WHO Guidelines Approved by the Guidelines Review Committee (2007) Pregnancy, childbirth, postpartum and newborn care: a guide for essential practice, 2nd edn. World Health Organization, Geneva

    Google Scholar 

  12. Wertheimer A, Melamed S, Ashwal E, Sapir O, Oron G, Ben-Haroush A, Shochat T, Wiznitzer A, Shufaro Y (2020) Complications of the third stage of labor are more prevalent in IVF pregnancies [published online ahead of print, 2020 Feb 23]. J Matern Fetal Neonatal Med 5:1–5. https://doi.org/10.1080/14767058.2020.1730797

    Article  Google Scholar 

  13. Esh-Broder E, Ariel I, Abas-Bashir N, Bdolah Y, Hochner Celnikier D (2011) Placenta accreta is associated with IVF pregnancies: a retrospective chart review. BJOG 118:1084–1089

    Article  CAS  Google Scholar 

  14. Iacovelli A, Liberati M, Khalil A, Timor-Trisch I, Leombroni M, Buca D et al (2018) Risk factors for abnormally invasive placenta: a systematic review and meta-analysis. J Matern Fetal Neonatal Med 22:1–11

    Google Scholar 

  15. Healy DL, Breheny S, Halliday J, Jaques A, Rushford D, Garrett C, Talbot JM, Baker HWG (2010) Prevalence and risk factors for obstetric haemorrhage in 6730 singleton births after assisted reproductive technology in Victoria Australia. Hum Reprod 25:265–274

    Article  CAS  Google Scholar 

  16. Hayashi M, Nakai A, Satoh S, Matsuda Y (2012) Adverse obstetric and perinatal outcomes of singleton pregnancies may be related to maternal factors associated with infertility rather than the type of assisted reproductive technology procedure used. Fertil Steril 98:922–928

    Article  Google Scholar 

  17. Nyfløt LT, Sandven I, Oldereid NB, Stray-Pedersen B, Vangen S (2017) Assisted reproductive technology and severe postpartum haemorrhage: a case-control study. BJOG 124:1198–1205

    Article  Google Scholar 

  18. Wikland M, Hardarson T, Hillensjö T, Westin C, Westlander G, Wood M, Wennerholm UB (2010) Obstetric outcomes after transfer of vitrified blastocysts. Hum Reprod 25(7):1699–1707. https://doi.org/10.1093/humrep/deq117

    Article  CAS  PubMed  Google Scholar 

  19. Aziz MM, Guirguis G, Maratto S, Benito C, Forman EJ (2016) Is there an association between assisted reproductive technologies and time and complications of the third stage of labor? Arch Gynecol Obstet 293:1193–1196

    Article  Google Scholar 

  20. Saito K, Kuwahara A, Ishikawa T, Morisaki N, Miyado M, Miyado K et al (2019) Endometrial preparation methods for frozen-thawed embryo transfer are associated with altered risks of hypertensive disorders of pregnancy, placenta accreta, and gestational diabetes mellitus. Hum Reprod 34(8):1567–1575. https://doi.org/10.1093/humrep/dez079

    Article  PubMed  Google Scholar 

  21. Wang Z, Liu H, Song H, Li X, Jiang J, Sheng Y, Shi Y (2020) Increased risk of pre-eclampsia after frozen-thawed embryo transfer in programming cycles. Front Med (Lausanne) 7:104. https://doi.org/10.3389/fmed.2020.00104

    Article  Google Scholar 

  22. Pereira N, Elias RT, Christos PJ, Petrini AC, Hancock K, Lekovich JP, Rosenwaks Z (2017) Supraphysiologic estradiol is an independent predictor of low birth weight in full-term singletons born after fresh embryo transfer. Hum Reprod 32(7):1410–1417. https://doi.org/10.1093/humrep/dex095

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Jing S, Li X, Zhang S, Gong F, Lu G, Lin G (2019) 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 300(5):1227–1237. https://doi.org/10.1007/s00404-019-05295-6

    Article  CAS  PubMed  Google Scholar 

  24. Nakamura Y, Yaguchi C, Itoh H, Sakamoto R, Kimura T, Furuta N, et al (2015) Morphologic characteristics of the placental basal plate in in vitro fertilization pregnancies: a possible association with the amount of bleeding in delivery. Hum Pathol 46(8):1171–1179. https://doi.org/10.1016/j.humpath.2015.04.007

    Article  PubMed  Google Scholar 

  25. Lee B, Koeppel AF, Wang ET, Gonzalez TL, Sun T, Kroener L et al (2019) Differential gene expression during placentation in pregnancies conceived with different fertility treatments compared with spontaneous pregnancies. Fertil Steril 111(3):535–546. https://doi.org/10.1016/j.fertnstert.2018.11.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Blanks AM, Zhao ZH, Shmygol A, Bru-Mercier G, Astle S, Thornton S (2007) Characterization of the molecular and electrophysiological properties of the T-type calcium channel in human myometrium. J Physiol 581(Pt 3):915–926. https://doi.org/10.1113/jphysiol.2007.132126

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

None.

Author information

Authors and Affiliations

  1. Helen Schneider Hospital for Women, Rabin Medical Center, 4941492, Petah Tiqva, Israel

    Avital Wertheimer, Alyssa Hochberg, Eyal Krispin, Onit Sapir, Avi Ben-Haroush, Eran Altman, Tzippy Schohat & Yoel Shufaro

  2. The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Avital Wertheimer, Alyssa Hochberg, Eyal Krispin, Onit Sapir, Avi Ben-Haroush, Eran Altman, Tzippy Schohat & Yoel Shufaro

Authors
  1. Avital Wertheimer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alyssa Hochberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eyal Krispin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Onit Sapir
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Avi Ben-Haroush
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Eran Altman
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tzippy Schohat
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yoel Shufaro
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

AW: study design, data collection, analysis and manuscript preparation, AH: revision and preparation of manuscript, EK and OS: study design and data collection, ABH and EA: data interpretation, review of the manuscript, TS: statistical analysis. YS: study idea, design and manuscript revision.

Corresponding author

Correspondence to Avital Wertheimer.

Ethics declarations

Conflict of interest

The authors have no conflict of interest to declare.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by our local Institutional Review Board (RMC-19-0697).

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wertheimer, A., Hochberg, A., Krispin, E. et al. Frozen-thawed embryo transfer is an independent risk factor for third stage of labor complications. Arch Gynecol Obstet 304, 531–537 (2021). https://doi.org/10.1007/s00404-020-05935-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-020-05935-2

Keywords

Search

Navigation