The prognostic value of antenatal ultrasound in cases complicated by fetal ovarian cysts

1. Introduction

Ovarian cysts represent a relatively common intra-abdominal finding in female fetuses which are usually diagnosed in the third trimester of pregnancy. Although their etiology is still not well understood, gonadal hyperstimulation by fetal gonadotropins, maternal estrogens, and human chorionic gonadotropin (HCG), seem responsible for the development of ovarian cysts [1, 2]. After birth, reduction in hormonal stimulation frequently leads to spontaneous regression within the first few months of life. The diagnosis is performed excluding other causes of intra-abdominal cystic masses. In particular, differential diagnosis should include mesenteric cyst, anorectal atresia, meconium pseudocyst, liver, biliar, splenic, renal or urachal cyst, hydronephrosis and hydrometrocolpos [3, 4]. Cyst size and echo-structure, longitudinally assessed by ultrasound scans, represent the main criteria for establishing prognosis. A complex cyst may suggest complications including intracystic hemorrhage, ovarian torsion or malignancy [5]. According to their appearance, fetal ovarian cysts are classified into simple or complex [5]. Simple cysts sonographic characteristics are: unilocular, anechogenic, round, small size, unilateral or seldom bilateral with a thin wall, while complex cysts characteristics are: echogenic with a fluid-debris level, retracting clot, septation and/or a thick wall. Although their management is still controversial, it should be aimed at preserving ovarian tissue [4, 6].

Cases complicated by ovarian torsion, persistent large size or clinical symptoms in the newborn (e.g. abdominal distension, bowel obstruction) undergo surgery [6]. Cyst prenatal aspiration has been proposed as an alternative to reduce the risk of ovarian complications leading to ovarian loss [7]. According to the Literature, cysts size and echo-structure antenatally assessed appears to be good predictor for postnatal surgery [8].

This study aims to evaluate the prognostic role of antenatal sonographic findings in predicting fetal ovarian cyst’s spontaneous regression or need for postnatal surgery. Moreover, we try to identify the best diameter cut off points for cysts, able to predict the probability of conservative or surgical management.

2. Methods

From January 2007 to December 2016, all cases with fetal ovarian cysts evaluated at the prenatal Diagnosis Center of the Department of Obstetrics and Gynecology of Brescia, Italy, were included in the study cohort. We excluded pregnancies complicated by chromosomal abnormalities, ascertained/suspected fetal malformations in the prenatal period and cases with fetal intra-abdominal masses not gonadal in origin.

All obstetric scans were performed by equally skilled sonographers. Cyst’s mean and maximum diameters were measured and their echo-structures were evaluated. According to Nussbaum et al. (5), a simple cyst was defined as a completely anechoic mass with a thin wall, while an echoic mass with a fluid-debris level, retracting clot or septation, was described as a complex cyst. After diagnosis, all women underwent a sonographic monitoring throughout gestation. Also, the newborn was followed up until spontaneous or surgical resolution. Only cases with a sonographic follow up longer than 12 months were included in the study cohort. Patients were divided into two groups according to their postnatal management: Group A included cases that required surgery while those that resolved spontaneously were collected in Group B. Data analysis was performed using IBM SPSS Statistics 20 for Windows (SPSS, Inc., Chicago, IL). Continuous variables were visually tested for normality using Q-Q plots and represented by median and range, while categorical variables as frequency (n) and percentage of the sample. Comparisons between values were performed using two-tailed paired samples Student t-test. Statistical significance was set to p < 0.05. Receiver-operating characteristic (ROC) curves were used to determine the predictive ability of mean and maximum cystic diameters for postnatal management; areas under ROC curves (AUROCs) and their CIs were also calculated. The optimal cut off points of cyst’s diameters have been chosen and their performance in predicting the need for postnatal surgery was calculated by the ability to correctly classify and positive/negative likelihood ratios.

3. Results

In total, 45 cases of antenatally-detected fetal ovarian cysts were recruited. Out of these, 3 cases were excluded because of other causes of intra-abdominal masses were diagnosed in postnatal period (n = 1 intestinal duplication, n = 1 congenital cloaca, n = 1 anorectal malformation); 4 cases were lost in postnatal follow up and were also excluded. No cases of chromosomal abnormalities were reported. Data from 38 study participants was used for the statistical analysis. Two cases were diagnosed in the second trimester of gestation while the others were detected in the third trimester. 36/38 (94.7%) cases were unilateral: the right side was involved in 17/38 (44.7%) cases. Concerning their echo-structure, 20/38 (52.6%) cases appeared simple while 18/38 (47.3%) were complex. All fetuses were born at term: 33/38 (86.8%) women underwent vaginal delivery while 5/38 (13.1%) were delivered by elective cesarean section because of obstetric indications. No cases of adverse neonatal outcome (e.g. Apgar score at five minutes <7, umbilical artery pH less than 7.20 or neonatal care unit admission) were reported. As provided in Table 1, 12/38 (31.5%) cases underwent surgery (Group A). Among these, 2/12 (16.6%) presented a simple cyst while 10/12 (83.4%) fetuses had a complex cyst (p = 0.01). No cases of postnatal change of ultrasound pattern were reported. Prenatal ultrasound characteristics of cases that underwent surgery (group A) are shown in Table 2. 26/38 (68.4%) cases resolved spontaneously (Group B). Out of these, 12/26 (46.1%) cases disappeared during fetal life, 10/26 (38,4%) cysts regressed spontaneously within one month after birth while 4/26 (15.4%) masses diminished in size one year after delivery. Interestingly, despite their complex echo-structure 6/26 (23%) cysts included in Group B disappeared on follow-up imaging within 12 months after birth as confirmed by follow-up ultrasonography.

Maternal characteristics did not differ among groups. In Group A, all patients underwent surgery within 4 months after birth because of suspected ovarian torsion, which was confirmed at surgery, except for one case who required an oophorectomy 2 years later. In this case there wasn’t evidence of ovarian torsion at surgery. The antenatal mean and maximum diameters of the ovarian cysts that were subsequently excised surgically, were significantly different compared to ovarian cysts that resolved spontaneously (p = 0.03). ROC curve pointed to 45 mm (sensibility 0.33, specificity 0.85, positive likelihood ratio 2.22, negative likelihood ratio 0.78) and 47 mm (sensibility 0.67, specificity 0.70, positive likelihood ratio 2.22, negative likelihood ratio 0.48) as optimal cut off points for cyst’s mean and maximum diameters, respectively. The ability to correctly classify was 68, 97% for both cysts mean and maximum diameter. We also performed the analysis for simple and complex cyst groups as reported in Fig. 1.

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Fig.1

The figure shows the mean diameter predictive value for surgery for the simple cysts group (A): AUC 0,80 (95% CI 0,55–1,00) and the maximum diameter predictive value for surgery (B): AUC 0,77 (95% CI 0,47–1,00). For the complex cyst group the mean diameter predictive value for surgery (C): AUC 0,63 (95% CI 0,25–1,00) and the maximum diameter predictive value for surgery (D): AUC 0,74 (95% CI 0,42–1,00). AUC = area under ROC curve; CI = confidence interval.

The incidence of fetal ovarian cysts has increased since the widespread use of routine antenatal sonography, which raises questions about their management. After the diagnosis, serial ultrasound scans have been recommended in order to detect any complication (10). Various complications of ovarian cysts have been described including compression of intra-abdominal organs, rupture of the cyst, hemorrhage and ovarian torsion, which is considered the most frequent. This study is aimed at evaluating the prognostic value of sonographic findings in pregnancies complicated by fetal ovarian cysts. Our report suggests that cases who need surgery after birth have much larger and more echoic cysts compared to the others. According to Bascietto et al., [8], our data highlighted the prognostic role of cyst size and appearance in pregnancies complicated by fetal ovarian cysts. In addition, we identified the optimal cut off points of cyst diameters in predicting the need for postnatal surgery. Although a great part of these cysts resolve spontaneously or diminish in size within one year after birth [2–8], their management is still debated and there is no standard treatment of fetal ovarian cysts. In our study cohort, more than a half of ovarian cysts regress spontaneously, usually during the end of the third trimester of gestation or within one month of life. This trend seems to reflect the pattern of hormonal stimulation by both maternal and placental hormones which decreased immediately after birth. Prenatal needle aspiration has been proposed as an alternative technique able to reduce the risk of ovarian loss due to surgical oophorectomy or autoamputation [7] but it remains controversial. Being an intra-amniotic procedure, prenatal needle aspiration carries a risk of needle injuries to fetal organs, infection, bleeding, premature rupture of membranes and/or labor. Postnatal surgery is required in cases complicated by ovarian torsion, persistent large cysts at sonographic follow-up, clinical symptoms in the newborn or suspicious for malignant ovarian neoplasm [10, 11]. In our study cohort, all patients who required surgical management confirmed the suspicion of ovarian torsion at surgery, except for one case that underwent surgery at the age of two years old because of cyst persistency at the sonographic follow up. The main limitation of the present study is the relatively small number of patients included. Our major strength consists in the identification of two statistically-derived cut off points of cystic diameters in order to predict the need for postnatal surgery. To conclude, the present study highlighted the prognostic value of antenatal sonographic findings, including cyst size and appearance. This suggests that 45 mm and 47 mm are the optimal dimensional cut off points for the need of surgery after birth. This evidence may improve prenatal counseling and help in identifying cases eligible for prenatal aspiration of the cysts.