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Subendometrial blood flow detected by Doppler ultrasound associates with pregnancy outcomes of frozen embryo transfer in patients with thin endometrium

  • Assisted Reproduction Technologies
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Abstract

Purpose

Multiple factors have been shown to influence the rate of clinical pregnancy after FET in IVF treatment, including embryo quality, synchronization of embryo and endometrium, and endometrial receptivity (ER). The subendometrial blood flow conditions could also contribute potentially major effects toward the establishment and maintenance of pregnancy. We conducted a retrospective cohort study to examine the correlation between subendometrial blood flow, as determined by Doppler ultrasound, and pregnancy outcomes in IVF patients with a thin endometrium (endometrium thickness [EMT] ≤ 0.7 cm).

Methods

This was a retrospective cohort study conducted at a university-affiliated reproductive hospital from January 2017 to April 2023. The EMT and subendometrial blood flows were assessed using transvaginal color Doppler ultrasound and evaluated by experienced clinical ultrasound physicians on the endometrial transformation day. The pregnancy outcomes were followed up and documented in clinical medical records through the IVF cohort study at our center.

Results

In the patients with 0.5 cm ≤ EMT ≤ 0.7 cm, the embryo implantation rate was statistically significant increased in the patients with the presence of subendometrial blood flow (OR 1.484; 95% CI, 1.001–2.200; P = 0.049; aOR 1.425; 95% CI, 1.030–2.123; P = 0.003). Patients with discernible subendometrial blood flow have superior live birth (P = 0.028), clinical pregnancy (P = 0.049), and embryo implantation (P = 0.027) compared to the patients without subendometrial blood flow when the EMT is ≤ 0.7 cm.

Conclusions

The presence of subendometrial blood flow detected by ultrasound was positively associated with successful embryo implantation and favorable pregnancy outcomes in patients with thin endometrium undergoing FET.

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Data availability

The datasets used and analyzed during the current study are available from the corresponding authors on reasonable request.

Code availability

Not applicable.

References

  1. Yan J, Qin Y, Zhao H, Sun Y, Gong F, Li R, et al. Live birth with or without preimplantation genetic testing for aneuploidy. N Engl J Med. 2021;385(22):2047–58. https://doi.org/10.1056/NEJMoa2103613.

    Article  PubMed  CAS  Google Scholar 

  2. Lessey BA, Young SL. What exactly is endometrial receptivity? Fertil Steril. 2019;111(4):611–7. https://doi.org/10.1016/j.fertnstert.2019.02.009.

    Article  PubMed  Google Scholar 

  3. Ke X, Liang X-F, Lin Y-H, Wang F. Pregnancy prediction via ultrasound-detected endometrial blood for hormone replacement therapy-frozen embryo transfer: a prospective observational study. Reprod Biol Endocrinol: RB&E. 2023;21(1):112. https://doi.org/10.1186/s12958-023-01164-9.

    Article  CAS  Google Scholar 

  4. Silva Martins R, Helio Oliani A, Vaz Oliani D, Martinez de Oliveira J. Subendometrial resistence and pulsatility index assessment of endometrial receptivity in assisted reproductive technology cycles. Reprod Biol Endocrinol: RB&E. 2019;17(1):62. https://doi.org/10.1186/s12958-019-0507-6.

    Article  CAS  Google Scholar 

  5. Bonilla-Musoles F, Raga F, Osborne NG, Castillo JC, Bonilla F. Endometrial receptivity: evaluation with ultrasound. Ultrasound Q. 2013;29(1):3–20. https://doi.org/10.1097/RUQ.0b013e318281b60a.

    Article  PubMed  Google Scholar 

  6. Zhao J, Zhang Q, Wang Y, Li Y. Endometrial pattern, thickness and growth in predicting pregnancy outcome following 3319 IVF cycle. Reprod Biomed Online. 2014;29(3):291–8. https://doi.org/10.1016/j.rbmo.2014.05.011.

    Article  PubMed  Google Scholar 

  7. Wu HM, Chiang CH, Huang HY, Chao AS, Wang HS, Soong YK. Detection of the subendometrial vascularization flow index by three-dimensional ultrasound may be useful for predicting the pregnancy rate for patients undergoing in vitro fertilization-embryo transfer. Fertil Steril. 2003;79(3):507–11. https://doi.org/10.1016/s0015-0282(02)04698-8.

    Article  PubMed  Google Scholar 

  8. Liu KE, Hartman M, Hartman A. Management of thin endometrium in assisted reproduction: a clinical practice guideline from the Canadian Fertility and Andrology Society. Reprod Biomed Online. 2019;39(1):49–62. https://doi.org/10.1016/j.rbmo.2019.02.013.

    Article  PubMed  Google Scholar 

  9. Mathyk B, Schwartz A, DeCherney A, Ata B. A critical appraisal of studies on endometrial thickness and embryo transfer outcome. Reprod Biomed Online. 2023;47(4):103259. https://doi.org/10.1016/j.rbmo.2023.103259.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Liu KE, Hartman M, Hartman A, Luo ZC, Mahutte N. The impact of a thin endometrial lining on fresh and frozen-thaw IVF outcomes: an analysis of over 40 000 embryo transfers. Hum Reprod. 2018;33(10):1883–8. https://doi.org/10.1093/humrep/dey281.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Mishra VV, Agarwal R, Sharma U, Aggarwal R, Choudhary S, Bandwal P. Endometrial and subendometrial vascularity by three-dimensional (3D) power Doppler and its correlation with pregnancy outcome in frozen embryo transfer (FET) cycles. J Obstet Gynaecol India. 2016;66(Suppl 1):521–7. https://doi.org/10.1007/s13224-016-0871-5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Sardana D, Upadhyay AJ, Deepika K, Pranesh GT, Rao KA. Correlation of subendometrial-endometrial blood flow assessment by two-dimensional power Doppler with pregnancy outcome in frozen-thawed embryo transfer cycles. J Hum Reprod Sci. 2014;7(2):130–5. https://doi.org/10.4103/0974-1208.138872.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Chen ZJ, Shi Y, Sun Y, Zhang B, Liang X, Cao Y, et al. Fresh versus frozen embryos for infertility in the polycystic ovary syndrome. N Engl J Med. 2016;375(6):523–33. https://doi.org/10.1056/NEJMoa1513873.

    Article  PubMed  Google Scholar 

  14. Gardner DK, Lane M, Stevens J, Schlenker T, Schoolcraft WB. Blastocyst score affects implantation and pregnancy outcome: towards a single blastocyst transfer. Fertil Steril. 2000;73(6):1155–8. https://doi.org/10.1016/s0015-0282(00)00518-5.

    Article  PubMed  CAS  Google Scholar 

  15. Shi Y, Sun Y, Hao C, Zhang H, Wei D, Zhang Y, et al. Transfer of fresh versus frozen embryos in ovulatory women. N Engl J Med. 2018;378(2):126–36. https://doi.org/10.1056/NEJMoa1705334.

    Article  PubMed  Google Scholar 

  16. Hwuang E, Wu PH, Rodriguez-Soto A, Langham M, Wehrli FW, Vidorreta M, et al. Cross-modality and in-vivo validation of 4D flow MRI evaluation of uterine artery blood flow in human pregnancy. Ultrasound Obstet Gynecol. 2021;58(5):722–31. https://doi.org/10.1002/uog.23112.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Yeo L, Romero R. Color and power Doppler combined with fetal intelligent navigation echocardiography (FINE) to evaluate the fetal heart. Ultrasound Obstet Gynecol. 2017;50(4):476–91. https://doi.org/10.1002/uog.17522.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Applebaum M. The uterine biophysical profile. Ultrasound Obstet Gynecol. 1995;5(1):67–8.

    Article  PubMed  CAS  Google Scholar 

  19. Duc-Goiran P, Mignot TM, Bourgeois C, Ferré F. Embryo-maternal interactions at the implantation site: a delicate equilibrium. Eur J Obstet Gynecol Reprod Biol. 1999;83(1):85–100.

    Article  PubMed  CAS  Google Scholar 

  20. Lawrenz B, Fatemi HM. Effect of progesterone elevation in follicular phase of IVF-cycles on the endometrial receptivity. Reprod Biomed Online. 2017;34(4):422–8. https://doi.org/10.1016/j.rbmo.2017.01.011.

    Article  PubMed  CAS  Google Scholar 

  21. Gao J, Gu F, Miao B-Y, Chen M-H, Zhou C-Q, Xu Y-W. Effect of the initiation of progesterone supplementation in in vitro fertilization-embryo transfer outcomes: a prospective randomized controlled trial. Fertil Steril. 2018;109(1):97–103. https://doi.org/10.1016/j.fertnstert.2017.09.033.

    Article  PubMed  CAS  Google Scholar 

  22. Wang J, Xia F, Zhou Y, Wei X, Zhuang Y, Huang Y. Association between endometrial/subendometrial vasculature and embryo transfer outcome: a meta-analysis and subgroup analysis. J Ultrasound Med. 2018;37(1):149–63. https://doi.org/10.1002/jum.14319.

    Article  PubMed  Google Scholar 

  23. Adibi A, Khadem M, Mardanian F, Hovsepian S. Uterine and arcuate arteries blood flow for predicting of ongoing pregnancy in in vitro fertilization. J Res Med Sci. 2015;20(9):879–84. https://doi.org/10.4103/1735-1995.170622.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Chien L-W, Au H-K, Chen P-L, Xiao J, Tzeng C-R. Assessment of uterine receptivity by the endometrial-subendometrial blood flow distribution pattern in women undergoing in vitro fertilization-embryo transfer. Fertil Steril. 2002;78(2):245–51.

    Article  PubMed  Google Scholar 

  25. Zhang T, He Y, Wang Y, Zhu Q, Yang J, Zhao X, et al. The role of three-dimensional power Doppler ultrasound parameters measured on hCG day in the prediction of pregnancy during in vitro fertilization treatment. Eur J Obstet Gynecol Reprod Biol. 2016;203:66–71. https://doi.org/10.1016/j.ejogrb.2016.05.016.

    Article  PubMed  CAS  Google Scholar 

  26. Casper RF. It’s time to pay attention to the endometrium. Fertil Steril. 2011;96(3):519–21. https://doi.org/10.1016/j.fertnstert.2011.07.1096.

    Article  PubMed  Google Scholar 

  27. Miwa I, Tamura H, Takasaki A, Yamagata Y, Shimamura K, Sugino N. Pathophysiologic features of “thin” endometrium. Fertil Steril. 2009;91(4):998–1004. https://doi.org/10.1016/j.fertnstert.2008.01.029.

    Article  PubMed  CAS  Google Scholar 

  28. Takasaki A, Tamura H, Miwa I, Taketani T, Shimamura K, Sugino N. Endometrial growth and uterine blood flow: a pilot study for improving endometrial thickness in the patients with a thin endometrium. Fertil Steril. 2010;93(6):1851–8. https://doi.org/10.1016/j.fertnstert.2008.12.062.

    Article  PubMed  CAS  Google Scholar 

  29. Gharibeh N, Aghebati-Maleki L, Madani J, Pourakbari R, Yousefi M, Ahmadian HJ. Cell-based therapy in thin endometrium and Asherman syndrome. Stem Cell Res Ther. 2022;13(1):33. https://doi.org/10.1186/s13287-021-02698-8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Sapozhak IM, Gubar OS, Rodnichenko AE, Zlatska AV. Application of autologous endometrial mesenchymal stromal/stem cells increases thin endometrium receptivity: a case report. J Med Case Rep. 2020;14(1):190. https://doi.org/10.1186/s13256-020-02515-5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Mouanness M, Ali-Bynom S, Jackman J, Seckin S, Merhi Z. Use of intra-uterine injection of platelet-rich plasma (PRP) for Endometrial receptivity and thickness: a literature review of the mechanisms of action. Reprod Sci. 2021;28(6):1659–70. https://doi.org/10.1007/s43032-021-00579-2.

    Article  PubMed  Google Scholar 

  32. Altmäe S, Aghajanova L. Growth hormone and endometrial receptivity. Front Endocrinol (Lausanne). 2019;10:653. https://doi.org/10.3389/fendo.2019.00653.

    Article  PubMed  Google Scholar 

  33. Wu Y, Tian Y, Zhang L, Zeng L, Wang Y, Shao R, et al. Effectiveness of growth hormone in promoting endometrial growth in patients with endometrial dysplasia in frozen embryo transfer. Afr J Reprod Health. 2023;27(3):32–9. https://doi.org/10.29063/ajrh2023/v27i3.4.

    Article  PubMed  Google Scholar 

  34. Sher G, Fisch JD. Vaginal sildenafil (Viagra): a preliminary report of a novel method to improve uterine artery blood flow and endometrial development in patients undergoing IVF. Hum Reprod. 2000;15(4):806–9.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

The authors would like to thank all patients who participated in this study and give special thanks to colleagues of the IVF laboratory, PGT laboratory, and nurses and doctors at the Reproductive Hospital Affiliated to Shandong University.

Funding

This study was supported by grants from the National Key Research and Development Program of China (2021YFC2700604, 2022YFC2702400), the National Natural Science Foundation of China (82101784, 82171648), the Key Research and Development Program of Shandong Province (2021LCZX02), the Natural Science Foundation of Shandong Province (ZR2020QH051), the Taishan Scholars Program for Young Experts of Shandong Province (tsqn201812154), the Shandong Provincial University Young Innovators Team Initiative Plan, and the Young Scholars Program of Shandong University.

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Author notes

  1. Zhaowen Zang and Jianan Lyu contributed equally to this work.

Authors and Affiliations

  1. Institute of Women, Children and Reproductive Health, Shandong University, Jinan, 250012, Shandong, China

    Zhaowen Zang, Jianan Lyu, Yuchen Yan, Qian Zhang, Yan Li & Junhao Yan

  2. State Key Laboratory of Reproductive Medicine and Offspring Health, Shandong University, Jinan, 250012, Shandong, China

    Zhaowen Zang, Jianan Lyu, Yuchen Yan, Qian Zhang, Yan Li & Junhao Yan

  3. National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, 250012, Shandong, China

    Zhaowen Zang, Jianan Lyu, Yuchen Yan, Qian Zhang, Yan Li & Junhao Yan

  4. Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, 250012, Shandong, China

    Zhaowen Zang, Jianan Lyu, Yuchen Yan, Qian Zhang, Yan Li & Junhao Yan

  5. Shandong Technology Innovation Center for Reproductive Health, Jinan, 250012, Shandong, China

    Zhaowen Zang, Jianan Lyu, Yuchen Yan, Qian Zhang, Yan Li & Junhao Yan

  6. Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, 250012, Shandong, China

    Zhaowen Zang, Jianan Lyu, Yuchen Yan, Qian Zhang, Yan Li & Junhao Yan

  7. Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250012, Shandong, China

    Zhaowen Zang, Jianan Lyu, Yuchen Yan, Qian Zhang, Yan Li & Junhao Yan

  8. Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No.2021RU001), Jinan, 250012, Shandong, China

    Zhaowen Zang, Jianan Lyu, Yuchen Yan, Qian Zhang, Yan Li & Junhao Yan

  9. Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, 250014, Shandong, China

    Mingwei Zhong & Guangyong Zhang

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  1. Zhaowen Zang
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Contributions

JH.Y., Y.L., and GY.Z. conceived and designed the project; ZW.Z., JN.L., YC. Y., and MW. Z. analyzed the data and wrote the manuscript; JH.Y., Y.L., GY.Z., and Q.Z. critically revised the manuscript. All authors were involved in interpreting the data and had final approval of the submitted and published versions.

Corresponding authors

Correspondence to Guangyong Zhang, Yan Li or Junhao Yan.

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Ethics approval

This study was conducted according to the ethical guidelines of the World Medical Association (Declaration of Helsinki) and was approved on 24 December 2021 by the Ethics Committee of Reproductive Hospital Affiliated to Shandong University (IRB no. 140).

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Written informed consent was obtained from all patients before treatment, and the patients consented to the use of their retrospective data in scientific publications.

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Not applicable.

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The authors declare no competing interests.

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Zang, Z., Lyu, J., Yan, Y. et al. Subendometrial blood flow detected by Doppler ultrasound associates with pregnancy outcomes of frozen embryo transfer in patients with thin endometrium. J Assist Reprod Genet 41, 2625–2633 (2024). https://doi.org/10.1007/s10815-024-03245-z

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