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

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.