Predictive Value of Sequential βHCG in IVF Pregnancy

Single-centre Retrospective Study on the Predictive Value of Sequential Early βHCG Measurements in IVF Pregnancies.

Early diagnosis of pregnancy with its localization and evolution has always been one of the major objectives of gynecology and obstetrics, even more so in Artificial Reproductive Technology (ART) centers.

The pivotal test is the βHCG assay. Various protocols have been proposed over the years, including single assessment and serial assays.

Several studies in the past years have tried to define a cut-off predictive of a successful pregnancy.

Abnormal levels of βHCG are associated with biochemical pregnancies, non-viable pregnancies and ectopic pregnancies (EP). The efficacy of a single serum βHCG test to predict EP is low and a significant amount of time and resources are spent diagnosing it.

In recent studies, better sensitivity was obtained from the ratio of two successive time points of βHCG concentration, with better specificity instead from regression models. These proposed models however lack validation and require further improvement.

Study Overview

• Status: Completed
• Conditions: Pregnancy Early
• Intervention / Treatment: Behavioral: Prompt diagnois pregnancy outcome

Detailed Description

Fertility clinics follow different protocols for the measurement of βHCG. Typically the initial serum measurement is performed 10-12 days after blastocyst transfer or 12-14 days after transfer at cleavage stage. Often a second serum measurement of hCG is performed at 48h since an increase of at least 50% is known to be a good predictor of ongoing pregnancy.

The doubling time was first described in natural pregnancies where the rate of βHCG rise was reported to be at least 53% in two days, with a median of 50% increase at day 1 and 124% at day 2. Following the first detection and rise of serum βHCG, it is possible to predict earlier than with transvaginal ultrasound non-viable pregnancies, ectopic pregnancies, biochemical pregnancies and spontaneous abortion or reassure the couple when these values are representative of an ongoing pregnancy (OP). Conversely, however, many studies have found different thresholds of βHCG to be representative of OP, with many women under the cut-off value ending up having a normal pregnancy.

The variability within the threshold expresses the need for a better biological marker or cut-off value. Implementing patient characteristics in a model to redefine and personalize the cut-off is necessary to improve pregnancy detection and management.

• Study Type: Observational
• Enrollment (Actual): 4000

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

The study will include retrospectively all patients that underwent IVF cycles (including fresh and thawed embryo transfers) between January 2011 and December 2020 at a Third level University-affiliated center, Humanitas Fertility Center in (Rozzano, MI).

The internal database (Art-it) will be used to retrieve data on age, body mass index (BMI), baseline sex hormone levels, main causes of infertility, endometrial thickness, details of stimulation protocols, date of insemination, date of embryo transfer, number of embryos transferred, date of βHCG examination, serum concentrations of βHCG, fertilization results, pregnancy types (EP, biochemical pregnancy, intrauterine)

Description

All women that underwent IVF cycles (including fresh and thawed embryo transfers) between January 2011 and December 2020.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
IVF patients: first serum βHCG; IVF patients who undergo βHCG after fresh or frozen embryo transfer	Behavioral: Prompt diagnois pregnancy outcome

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Live birth incidence per serum βHCG value	Compare the incidence of Live Birth according to serum βHCG (IU/L) measurement in all patients undergoing ART procedures.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of live birth incidence with serum βHCG confounders	Comparison of live birth incidence according to possible risk factors for serum βHCG (IU/L) measurements, among patients undergoing ART procedures.	1 year

Collaborators and Investigators

• Sponsor: Istituto Clinico Humanitas
• Investigators: Study Director: Paolo Emanuele Levi Setti, MD, Istituto Clinico Humanitas

Publications and helpful links

General Publications

• Seeber BE, Sammel MD, Guo W, Zhou L, Hummel A, Barnhart KT. Application of redefined human chorionic gonadotropin curves for the diagnosis of women at risk for ectopic pregnancy. Fertil Steril. 2006 Aug;86(2):454-9. doi: 10.1016/j.fertnstert.2005.12.056. Epub 2006 Jun 6.
• Wang Z, Gao Y, Zhang D, Li Y, Luo L, Xu Y. Predictive value of serum beta-human chorionic gonadotropin for early pregnancy outcomes. Arch Gynecol Obstet. 2020 Jan;301(1):295-302. doi: 10.1007/s00404-019-05388-2. Epub 2019 Nov 22.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2011
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: February 3, 2022
• First Submitted That Met QC Criteria: March 22, 2022
• First Posted (Actual): March 31, 2022

Study Record Updates

• Last Update Posted (Actual): March 31, 2022
• Last Update Submitted That Met QC Criteria: March 22, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: 21012021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No