Evaluating cut-off levels for progesterone, ß human chorionic gonadotropin and ß human chorionic gonadotropin ratio to exclude pregnancy viability in women with a pregnancy of unknown location: A prospective multicenter cohort study.

INTRODUCTION: There is no global agreement on how to best determine pregnancy of unknown location viability and location using biomarkers. Measurements of progesterone and ß human chorionic gonadotropin (ßhCG) are still used in clinical practice to exclude the possibility of a viable intrauterine pregnancy (VIUP). We evaluate the predictive value of progesterone, ßhCG, and ßhCG ratio cut-off levels to exclude a VIUP in women with a pregnancy of unknown location. MATERIAL AND METHODS: This was a secondary analysis of prospective multicenter study data of consecutive women with a pregnancy of unknown location between January 2015 and 2017 collected from dedicated early pregnancy assessment units of eight hospitals. Single progesterone and serial ßhCG measurements were taken. Women were followed up until final pregnancy outcome between 11 and 14 weeks of gestation was confirmed using transvaginal ultrasonography: (1) VIUP, (2) non-viable intrauterine pregnancy or failed pregnancy of unknown location, and (3) ectopic pregnancy or persisting pregnancy of unknown location. The predictive value of cut-off levels for ruling out VIUP were evaluated across a range of values likely to be encountered clinically for progesterone, ßhCG, and ßhCG ratio. RESULTS: Data from 2507 of 3272 (76.6%) women were suitable for analysis. All had data for ßhCG levels, 2248 (89.7%) had progesterone levels, and 1809 (72.2%) had ßhCG ratio. The likelihood of viability falls with the progesterone level. Although the median progesterone level associated with viability was 59 nmol/L, VIUP were identified with levels as low as 5 nmol/L. No single ßhCG cut-off reliably ruled out the presence of viability with certainty, even when the level was more than 3000 IU/L, there were 39/358 (11%) women who had a VIUP. The probability of viability decreases with the ßhCG ratio. Although the median ßhCG ratio associated with viability was 2.26, VIUP were identified with ratios as low as 1.02. A progesterone level below 2 nmol/L and ßhCG ratio below 0.87 were unlikely to be associated with viability but were not definitive when considering multiple imputation. CONCLUSIONS: Cut-off levels for ßhCG, ßhCG ratio, and progesterone are not safe to be used clinically to exclude viability in early pregnancy. Although ßhCG ratio and progesterone have slightly better performance in comparison, single ßhCG used in this manner is highly unreliable.

The Impact of Oral Intake of Dydrogesterone on Fetal Heart Development During Early Pregnancy.

Congenital heart disease is the most frequent form of congenital anomaly in newborn infants and accounts for more than a quarter of all serious congenital afflictions worldwide. A genetic etiology is identified in <20 % of cases of congenital heart defects, and in most cases the etiology remains a mystery. In the context of the health burden caused by congenital heart disease, the contribution of non-inherited risk factors is important especially if it turns out to be caused by a drug which can be avoided during pregnancy. We sought to determine whether maternal dydrogesterone treatment in early pregnancy is associated with congenital heart disease in the infant. We conducted a retrospective case-control study of birth defects and associated risk factors. Data were obtained and compared between 202 children born with congenital heart disease and a control group consisting of 200 children. All children were born in the period of 2010-2013. Dydrogesterone exposure was defined as any reported use during the first trimester of pregnancy. Exclusion criteria included stillbirths, children with chromosomal abnormalities and infants of mothers with chronic medical illnesses, e.g., diabetes. Binary logistic regression analyses were used to analyze the data and attempt to identify a causal relationship between drug exposure and congenital heart disease. Mothers of children born with congenital heart disease received more dydrogesterone during first trimester of pregnancy than mothers of children in the control group [adjusted odds ratio 2.71; (95 % CI 1.54-4.24); P = 0.001]. We identified a positive association between dydrogesterone usage during early pregnancy and congenital heart disease in the offspring. Nevertheless, further studies are needed to confirm these results.