The Predictive Value of Serum ß-HCG Levels in The Detection of Ectopic Pregnancy Sixteen Days after Embryo Transfer: A Cross-Sectional Study

Document Type : Original Article

Authors

1 Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

2 Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

Abstract

Background: To detect the predictive value of beta human chorionic gonadotropin (β-hCG) levels 16 days post
embryo transfer (ET) regarding detection of an ectopic pregnancy (EP) in assisted reproductive technology
(ART) cycles.
Materials and Methods: In this cross-sectional study, we reviewed the database of Royan Institute from January
2011 to December 2014 and from January 2017 to December 2019 retrospectively. All cases with positive β-hCG
levels sixteen days after ET were screened (n=4149). The pregnancies with oocyte or embryo donation and the multiple
pregnancies based on the first ultrasound were excluded. All eligible singleton pregnancies with documented
serum β-hCG levels at Royan institute laboratory (n=765) were included and then classified according to the type
of pregnancy: EP (n=189) or non-EP (n=576). The data of the treatment cycle was extracted from the patients’ files.
A receiver operating characteristic (ROC) curve was used to detect the predictive power of the first measurement
of β-hCG level in distinguishing EP from ongoing pregnancy in the ART and intrauterine insemination (IUI) cycles
separately. Sensitivity, specificity, area under the ROC curve and 95% confidence intervals (CI) were calculated for
each of the estimates.
Results: The mean levels of β-hCG 16 days after ET were remarkably higher in the ongoing pregnancy group than
the EP group (1592.35 ± 87 IU/L vs. 369.69 ± 50.61 IU/L, P<0.001). The β-hCG thresholds predictive of ongoing
pregnancy were 278 IU/L as the most suitable cut-off to predict viable pregnancy with a sensitivity of 72.8%, a
specificity of 67.5%, a positive predictive value of 77.8%, standard error of 0.02, and a confidence interval of 73.8-
81.7%. However, this relationship was not found in IUI cycles.
Conclusion: Based on these findings, if β-hCG levels 16 days after ET are below 278 IU/l, close follow-up is recommended,
until either the diagnosis of EP or miscarriage is established.

Keywords

Main Subjects

References

  1. Refaat B, Dalton E, Ledger WL. Ectopic pregnancy secondary to in vitro fertilisation-embryo transfer: pathogenic mechanisms and management strategies. Reprod Biol Endocrinol. 2015; 13: 30.
  2. Ishihara O, Kuwahara A, Saitoh H. Frozen-thawed blastocyst transfer reduces ectopic pregnancy risk: an analysis of single embryo transfer cycles in Japan. Fertil Steril. 2011; 95(6): 1966- 1969.
  3. Perkins KM, Boulet SL, Kissin DM, Jamieson DJ; National ART Surveillance (NASS) Group. Risk of ectopic pregnancy associated with assisted reproductive technology in the United States, 2001- 2011. Obstet Gynecol. 2015; 125(1): 70-78.
  4. Wang LL, Chen X, Ye DS, Liu YD, He YX, Guo W, et al. Misdiagnosis and delayed diagnosis for ectopic and heterotopic pregnancies after in vitro fertilization and embryo transfer. J Huazhong Univ Sci Technolog Med Sci. 2014; 34(1): 103-107.
  5. Porat S, Savchev S, Bdolah Y, Hurwitz A, Haimov-Kochman R. Early serum beta-human chorionic gonadotropin in pregnancies after in vitro fertilization: contribution of treatment variables and prediction of long-term pregnancy outcome. Fertil Steril. 2007; 88(1): 82-89.
  6. Zhao WE, Li YJ, Ou JP, Sun P, Chen WQ, Liang XY. Predictive value of initial serum human chorionic gonadotropin levels for pregnancies after single fresh and frozen blastocyst transfer. J Huazhong Univ Sci Technolog Med Sci. 2017; 37(3): 395-400.
  7. Zhang Q, Yan J, Tang R, Gao X, Zhang B, Chen Z-J. Serum human chorionic gonadotropin level measured 17 days after oocyte retrieval can predict final clinical pregnancy outcomes in IVF/ICSI treatment cycles. J Reprod Med. 2014; 59(5-6): 285-292.
  8. Khadra MM, Freij MA, Al-Ramahi MQ, Al-Jamal AY, Thekrallah FM, Tahtamouni LH. Human chorionic gonadotropin cutoff value determined by receiver operating characteristic curve analysis is useful but not absolute for determining pregnancy outcomes. Middle East Fertil Soc J. 2016; 21(2): 120-124.
  9. Mashayekhi M, Barabi F, Arabipoor A, Zolfaghari Z. Live birth rates in different subgroups of poor ovarian responders according to Bologna and POSEIDON group classification criteria. J Gynecol Obstet Hum Reprod. 2021; 50(9): 102169.
  10. Valojerdi MR, Eftekhari-Yazdi P, Karimian L, Hassani F, Movaghar B. Vitrification versus slow freezing gives excellent survival, post warming embryo morphology and pregnancy outcomes for human cleaved embryos. J Assist Reprod Genet. 2009; 26(6): 347-354.
  11. Kim JH, Shin MS, Yi G, Jee BC, Lee JR, Suh CS, et al. Serum biomarkers for predicting pregnancy outcome in women undergoing IVF: human chorionic gonadotropin, progesterone, and inhibin A level at 11 days post-ET. Clin Exp Reprod Med. 2012; 39(1): 28-32.
  12. Lesny P, Killick SR, Robinson J, Maguiness SD. Transcervical embryo transfer as a risk factor for ectopic pregnancy. Fertil Steril. 1999; 72(2): 305-309.
  13. Naredi N, Singh S, Sharma R. Does first serum beta-human chorionic gonadotropin value prognosticate the early pregnancy outcome in an In-vitro fertilisation cycle? J Hum Reprod Sci. 2017; 10(2): 108-113.
  14. Ribic-Pucelj M, Tomazevic T, Vogler A, Meden-Vrtovec H. Risk factors for ectopic pregnancy after in vitro fertilization and embryo transfer. J Assist Reprod Genet. 1995; 12(9): 594-598.
  15. Bu Z, Xiong Y, Wang K, Sun Y. Risk factors for ectopic pregnancy in assisted reproductive technology: a 6-year, single-center study. Fertil Steril. 2016; 106(1): 90-94.
  16. Reljič M, Knez J, Vlaisavljević V. Human chorionic gonadotropin levels are equally predictive for pregnancy outcome after fresh and vitrified-warmed blastocyst transfer. J Assist Reprod Genet. 2013; 30(11): 1459-1463.
  17. Poikkeus P, Hiilesmaa V, Tiitinen A. Serum HCG 12 days after embryo transfer in predicting pregnancy outcome. Hum Reprod. 2002; 17(7): 1901-1905.
  18. Bjercke S, Tanbo T, Dale PO, Morkrid L, Åbyholm T. Human chorionic gonadotrophin concentrations in early pregnancy after in-vitro fertilization. Hum Reprod. 1999; 14(6): 1642-1646.
International Journal of Fertility and Sterility
Volume 17, Issue 3
July 2023
Pages 181-186

Files

Cited by

Share

How to cite

Statistics