Transvaginal ultrasonography has always been a classical method to predict pregnancy outcomes in cases where viability is suspected in patients with early pregnancy, but many publications have recently studied β-hCG and progesterone values, which are serum biochemistry markers. Using these parameters, 336 pregnant women were followed up in our study, in which we investigated whether they were related to the determination of early pregnancy outcome. The results of our study, which was completed with 100 pregnant women, were compared with the literature.
Advanced maternal age is known to be associated with the risk of fetal anomalies, early pregnancy loss and increased abortion rates (6, 7). Some studies show that maternal age is an important parameter for predicting fetal viability (2). Our findings regarding maternal age are not consistent with the literature. Although the mean maternal age was higher in the group diagnosed with early pregnancy loss compared to the group with fetal viability, this difference was not found to be statistically significant. The reason for this was that the mean age was close to each other and the mean age of the group with early pregnancy loss failed to meet the advanced maternal age criterion (> 35 years) mentioned in the literature.
As far as we know, this study is the first to include the evaluation of gravida and parity numbers in prediction of early pregnancy. The literature includes only a comparison of abortion rates and it is known that repeated abortions increase the risk of early pregnancy loss (6, 7). In the previous pregnancy anamnesis, no statistically significant results were obtained when the numbers of gravida, parity and optional curettages were evaluated according to the results of early pregnancy. Although the number of abortus had a 2 times more average in the group without heartbeat compared to the group with heartbeat, the difference between these two groups was not found to be statistically significant contrary to the literature. Although no significant results were obtained, we contributed to the literature by evaluating the previous pregnancy anamnesis in early pregnancy loss, except for the history of abortus.
In the literature, the probability of intrauterine cystic structure belonging to the gestational sac is 99.5% and the probability of false sac is 0.5% (8). In ectopic pregnancies, the rate of false sac was reported to be 10% (9, 10). In our study, 2 out of 100 patients were diagnosed with ectopic pregnancy. Considering that 81% of 100 patients had a gestational sac, the rate of false sac in patients with an observed gestational sac was 2.46%. This is highly above the 0.5% rate stated in the literature. Considering that only 10% of ectopic pregnancies have a false sac, it is interesting that such a high rate was found only in a study on intrauterine pregnancies. This led us to conclude that clinicians should be more careful in ultrasonography examination and understand the distinction between double decidual ring appearance and actual gestational sac.
This study includes a race question in a society against racism since it is thought that abort rates may be high due to the high number of Syrian asylum seekers in our country, poor living conditions and war stress. Although high rates of early pregnancy loss have been reported in African-Americans compared to other populations in the literature (6, 7), no literature data was found on races and or studies conducted in the Middle East. No statistically significant results were obtained in the comparison between nationalities. The limited number of foreign patients participating in the study was considered as the reason for this.
Oh et al. (11) found that mGSD measured in pregnancies < 37 days and below according to LMP had no predictive value for fetal outcome later in pregnancy. In another study, it was emphasized that there was no predictive value of gestational age before 37 days according to LMP, and a definitely unsuccessful pregnancy was given as any pregnancy with no observed gestational sac on the day 46 (12). Fritz et al. (13) found that gestational age and hCG doubling time were correlated and therefore, gestational age was prognostic for fetal outcome. Napolitano et al. (14) stated that 30% of women had an uncertain or unreliable menstrual date and therefore the gestational age could not be determined correctly. In our study, a statistically significant efficacy of gestational age was observed between the groups with and without fetal heartbeat according to the last menstrual period. This was found to be consistent with the general literature (11, 13). However, the information that the predictive value of gestational age was not significant before 37 days in the literature contradicted the occurrence of a heartbeat in all 7 women (100%) diagnosed with pregnancy before 35 days in our study. Again, the information that the pregnancies detected after the day 46 mentioned in the literature were unsuccessful contradicted with the incidence of fetal heartbeat in 18 (60%) of the 30 women diagnosed with pregnancy after the 46th day. However, the fact that 15% of the patients did not know their last menstrual periods and 11% were incorrect makes this result contradictory, and Napolitano et al. confirmed the argument that the last menstrual periods of 30% of the women was unreliable and concluded that the gestational age should be determined ultrasonographically or biochemically by experienced physicians.
Early pregnancy loss is known to be common in patients with symptoms (1, 6). Although our study includes patients with a higher rate of symptoms in the group without fetal heartbeat (in the FHR negative group: 31.8% - positive group: 17.4%), this information was not found to be statistically significant. This was found to be inconsistent with the literature. The reason for this was construed as the fact that the study was conducted in a small population.
In the initial and 48-hour follow-up serum β-hCG controls, a statistically significant difference was found between the fetal heart rate positive group and the negative group. Claire et al. (1) found that serum β-hCG predicts viability with 100% sensitivity and 31% specificity when the doubling rate is 75% or more. Barnhart et al. (5) found the rate of determination of viability as 124% increase in 2 days. Bignardi et al. (12) found that the rate of determining viability with β-hCG doubled was 78% sensitive and 67% specific. As the main purpose of our study, the fact that hCG doubling rate provides prediction of viability is also consistent with many recent studies although the rates are different. What makes our study different is that the prediction of viability is mentioned by giving only certain ratios in the literature (1, 15), while in our study, a percentage is assigned to each patient in terms of viability at each increase rate of β-hCG (Figure-1). With this information, we believe that a clear rate will be provided to the patients during early pregnancy and that both the anxiety of the patients due to uncertainty will be reduced and their own anxiety will be reduced by physicians providing clear information and ratio to the patients. In addition to creating an early pregnancy prediction modality, our study examined the increase rates of β-hCG in the ROC curve and determined high sensitivity cut-off values and confirmed that the β-hCG increase rate in recent literature could be used to predict early pregnancy outcomes. In our study, live pregnancy was achieved even with a low rate of β-hCG increase of 31%. Therefore, physicians should not diagnose pregnancy loss early, and early interventions should be avoided. The cut-off value determined in the 95% confidence interval was achieved with a minimum 97% increase in hCG at the hour 48. A 100% heart rate positivity was achieved with an increase of 181%.
Claire et al. (1) found 100% pregnancy failure where the progesterone value was 6.2 ng/ml or less. In a recent French guideline, an abnormal IUP or ectopic pregnancy was found to be associated with an initial serum progesterone value of 3.2 ng/ml or less (3). In our study, a significant statistical result was obtained when the initial progesterone values of the fetal heartbeat and non-fetal heartbeat groups were compared. This was found to be consistent with the general literature (1, 3). What makes our study different is that while the prediction of viability is mentioned in the literature only by giving certain ratios (12, 16), in our study, a percentage can be assigned to patients in terms of viability at each value of the initial serum progesterone (Figure-4). Thiis information makes it possible to give a clear rate to the patients during early pregnancy, and reducing the anxiety of families caused by waiting for weeks. Furthermore, our study examined initial serum progesterone on the ROC curve and determined high sensitivity cut-off values and confirmed that serum progesterone in the literature could be used to predict early pregnancy outcomes. A successful pregnancy was achieved even at an initial progesterone value of 3.71 ng/ml. Therefore, the physicians are recommended to avoid early interventions. Besides, the cut-off value determined in the 95% confidence interval was provided at 21.7 ng/ml and above. A 100% heart rate positivity was achieved with values of 37.5 ng/ml and above. The reason why we found slightly higher cut-off values compared to the general literature is the low number of patients, which is also the limitation of our study .
The 22% early pregnancy loss rate obtained as a result of our study is higher than the EEC rate of 10–15% in the literature, but also lower than the EEC rate of 31% after implantation (1, 6, 7). Although our population was a heterogeneous group of healthy and symptomatic patients, the presence of symptomatic patients at a higher rate than the rate in the community was considered as the likely reason for the higher rate of our EEC rates than the literature statistics. The reason why our EEC rate was lower than the EEC rate observed after implantation was considered as the fact that patients with EEC were not evaluated without creating an intrauterine finding due to the inclusion of IUPs only with TV-USG in our population. Although the incidence of embryos was higher in the FHR positive group compared to the negative group, the incidence of gestational sacs or embryos between the FHR +/- groups was not statistically significant. This result is inconsistent with the literature because the literature states that the presence of embryos is more valuable than other ultrasound findings (yolk sac, GS) and it is among the good prognostic factors (2, 3). Pexster et al. (17) found variations up to 20% between the operators in CRL and mGSD measurement accuracy. It is possible to see many variations and cut-off values in the literature for diagnosis and definitions (18). Although our population is not as heterogeneous as the community and we do not study inter-operator variations, we think that ultrasound is a subjective diagnostic tool. This is perhaps another reason why our ultrasound findings were not statistically significant in predicting early pregnancy outcomes.