Predictive Value of Sequential βHCG in IVF Pregnancy
Condition: Pregnancy Early
Study type: Observational

Summary: 
      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.
    

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.
    

Intervention name(s): Prompt diagnois pregnancy outcome
Intervention type(s): Behavioral
Observational model: Cohort
Time perspective: Retrospective
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)