Management of fetal ovarian cyst using in utero aspiration

Introduction

A fetal ovarian cyst is the most common abdominal mass observed in female fetuses during pregnancy. It is seen in approximately 1 in 2500 pregnancies [1, 2]. Fetal ovarian cysts are usually formed during the third trimester. Most fetal ovarian cysts are functional, that is, they are stimulated by maternal and fetal hormones such as estrogen, follicle-stimulating hormone, luteinizing hormone and placental human chorionic gonadotropin during pregnancy [3, 4]. Torsion of an ovarian cyst is the most common complication, resulting in ovarian loss [5, 6].

There are two types of ovarian cysts, a simple cyst and a complex cyst [7]. A simple cyst is completely anechoic without complication, whereas a complex cyst is echogenic with complications most likely due to torsion. The antenatal course of ovarian cysts varies; some cysts resolve spontaneously or remain stable, whereas others become complex due to torsion and/or intracystic hemorrhage [8].

In utero aspiration of fetal ovarian cysts has been reported to be useful in preventing perinatal complications, especially in large ovarian cysts [5, 9–13]. However, the effectiveness and safety of cyst aspiration have not been fully elucidated due to the small number of studies and further limited by small sample sizes. Meanwhile, the clinical outcomes of expectant management without in utero aspiration have been reported to be favorable [14, 15]. Thus, management of fetal ovarian cysts using in utero aspiration to prevent complications remains controversial. To answer to this clinical question, accumulating experiences of in utero aspiration is no doubt crucial.

In our hospital, in utero aspiration of fetal ovarian cysts is performed in patients who meet the indicative criteria. For this study, we reviewed all cases of fetal ovarian cysts between 2002 and 2013 in our hospital and evaluated the clinical outcomes of this procedure.

Materials and methods

Between March 2002 and April 2013, 21 cases of fetal ovarian cysts were diagnosed at the National Center for Child Health and Development (NCCHD) in Tokyo, Japan. The patients’ medical records, which included gestational age at diagnosis, ultrasonographic data, maternal pre-pregnancy complications, perinatal management and postpartum outcomes, were reviewed. The study was approved by the in-house review board, which acted according to an external ethics code. The team that performed this study was the same one that managed fetal ovarian cases with in utero procedures at NCCHD.

When a patient with a suspected fetal ovarian cyst was referred to our institution, an abdominal ultrasound was performed as an initial evaluation. Accordingly, fetal ovarian cysts were diagnosed based on the following criteria: 1) female fetus; 2) non-midline regular cystic structure; 3) normal appearance of the urinary tract; and 4) normal appearance of the gastrointestinal tract [1, 2].

The indications for in utero aspiration of fetal ovarian cysts were: 1) simple cyst; 2) cyst diameter ≥4 cm; 3) fetus was in a suitable position for needle aspiration; 4) cyst did not decrease in size over one week of observation; and 5) gestational age at intervention was <37 weeks. In qualified cases, in utero aspiration was offered as one of the therapeutic options. Written informed consent was obtained from patients who agreed to undergo the procedure. For those cases, magnetic resonance imaging (MRI) of the fetus was performed before the therapy to exclude other anomalies. When simple cysts ≥4 cm became larger after diagnosis, in utero aspiration was performed within 1 week.

The fetal ovarian cyst was aspirated using a 21-gauge needle under ultrasound guidance with local maternal anesthesia of 1% lidocaine. Ritodrine for tocolysis was routinely used during aspiration. Fluid aspirated from the ovarian cyst was used for analysis of estradiol, progesterone and testosterone concentrations for further ascertainment of diagnosis. Patients who have complex cyst or a simple cyst <4 cm were managed expectantly.

For all 21 cases, weekly follow-up using ultrasonography was performed until delivery. The delivery mode was chosen according to obstetrical indications. Neonates were thoroughly examined by pediatricians and pediatric surgeons, and periodic follow-up was done with abdominal ultrasound. The primary outcome measure was any changes in a complex cyst.

Results

Characteristics of patients and cysts are shown in Table 1 and Figure 1. Among the 21 cases, four (19%) had complex cysts and 17 (81%) had simple cysts at the time of referral. All patients had singleton pregnancies, and the mean gestational age at diagnosis was 33.9±2.3 weeks (mean±SD; range, 29.9–36.9 weeks). The mean cyst diameter at diagnosis was 3.7±1.0 cm (range, 1.5–5.2 cm). There were no maternal risk factors for fetal ovarian cysts, such as rhesus isoimmunization, pre-eclampsia, gestational diabetes mellitus or hypothyroidism. Eight patients (38%) had ovarian cysts on the right side, and 13 (62%) had ovarian cysts on the left side. No patients had bilateral ovarian cysts. Gestational age at delivery was 38.8±1.2 weeks (range, 36.3–41.3 weeks). Five fetuses were delivered by cesarean section. The mean neonatal birth weight was 3233±397 g (range, 2450–3682 g). Median Apgar scores were 9 (range, 7–9) and 9 (range, 8–10) after 1 and 5 min, respectively.

Figure 1:

Flow diagram of 21 cases of fetal ovarian cysts.

Among the 17 patients with simple cysts, nine met the indications (cases 1–9 in Table 1) for in utero aspiration, of which seven received therapy and one declined (case 8 in Table 1). The other patient did not undergo the therapy as the fetus was near-term at diagnosis (case 9 in Table 1). The gestational age at in utero aspiration was 34.4±1.5 weeks (range, 31.7–36.0 weeks) (Table 2).

Analysis of cyst fluid following in utero aspiration is shown in Table 2. Cyst aspiration yielded 35.4±15.4 mL (range, 12–58 mL) of clear, yellow fluid in all patients. Estradiol, progesterone and testosterone levels in cyst fluid were 116,316±235,989 pg/mL (range, 1320–645,000 pg/mL), 186±83.3 ng/mL (range, 79–303 ng/mL) and 64.0±132 ng/mL (range, 4.6–363 ng/mL), respectively.

There were no complications arising in any of the patients who underwent the procedure, and none required multiple aspirations. Further, none of the patients developed complex cysts after in utero aspiration. One patient, however, needed additional aspiration after birth due to the large size of the cyst, with a diameter of 4.7 cm (case 4 in Table 2). Cysts in the other six patients resolved spontaneously within 1–3 months after birth. For the two patients who did not receive therapy, one underwent ovarian cystectomy after birth, and the other developed complex cysts and received cystectomy 4 months after birth.

Among the eight patients with simple cysts who did not meet the indications for in utero aspiration, seven had cysts that regressed spontaneously within 3 months. In the other patient (cyst size 2.8 cm at diagnosis), the cyst became complex at the ultrasound examination a week later. She eventually received a laparotomy after birth (case 10 in Table 1).

In the patients with complex cysts, two received postnatal surgical intervention (cases 18 and 19 in Table 1). A cystectomy or ovarian cyst aspiration was performed in the patients in which torsion was confirmed.

Discussion

We have demonstrated the clinical outcome of fetal ovarian cyst managed by in utero aspiration according to indicative criteria. At the time of referral, 19% (4 of 21) of ovarian cysts were complex, and 57% (9 of 17) of simple cysts qualified for indication of in utero aspiration. In the seven cases that received in utero aspiration, none of the cysts developed into a complex cyst. One in eight cases (diameter <4 cm) and one in two cases (diameter >4 cm) did not receive aspiration, and the cysts became complex. Thus, 20% (2 of 10) of simple ovarian cysts became complex with expectant management. Torsion of fetal ovarian cysts was common with expectant management, whereas torsion of ovarian cysts was rare with in utero aspiration.

Bagolan et al. reported 14 patients that received in utero aspiration for ovarian cysts larger than 5 cm. The patients demonstrated a significantly reduced risk of subsequent torsion compared with their historical controls [5]. Noia et al. recently reported 13 cases of fetal ovarian cysts treated with in utero aspiration regardless of the characteristics and size of the cyst [12]. Among them, no maternal or fetal complications related to the procedure were observed. Other case series of in utero aspiration have also been reported [9–13]. In terms of clinical outcome, our findings are consistent with previous studies, that is, in utero aspiration of fetal ovarian cysts has very low risk for mother and fetus with a reduction of the chance of torsion.

Torsion is more frequent during pregnancy than in the postnatal period [3, 9]. Unilateral loss of ovary resulting from torsion can cause enormous damage to future fertility [16]. Severe life-threatening complications associated with complex cysts, such as intestinal perforation, urinary tract obstruction and death, have also been reported [5, 6, 17]. However, a recent observational study conducted by Nakamura et al. demonstrated favorable clinical outcomes of expectant management [14]. The authors reported that 28 out of 33 neonates (85%) were able to preserve their two ovaries with expectant management, but 5 of the 18 simple cyst cases with diameters of more than 4 cm (28%) became complex. Further, among 14 cases treated surgically, torsion was confirmed in four (29%) with cysts of more than 4 cm in diameter. Accordingly, they concluded that expectant management might be suitable for cysts of <4 cm in diameter.

Interestingly, the indication for in utero aspiration remains controversial. Some studies have reported intervention for cysts larger than 4 cm [9, 13], whereas others applied a cut-off level of 5 cm [5] or 3.5 cm [12]. Slodki et al. suggested intervention for ovarian cysts >5 cm with functional impairment in echocardiography [18]. The likelihood of torsion increases with the size of the cyst, even though small ovarian cysts can still pose a risk for torsion [6, 8]. In view of that, we chose a cut-off value of 4 cm for aspiration. From our experience, if a cyst is larger than 4 cm, the cyst tends to be located just under the abdominal wall. In such cases, there is a lower possibility that other organs such as the bowel might be involved due to aspiration needle-related accidents. A cut-off level of 4 cm has also been recommended previously [3, 5, 12]. More than half of simple cysts qualified for indication of in utero aspiration. Our study showed that in utero aspiration with this cut-off value is feasible and can lead to acceptable maternal/fetal outcomes, as the studies that applied the same cut-off level included only small sample sizes of seven [9] and three [13] patients, respectively.

Hormonal testing of cyst fluid may help to determine the origin of the cyst [9, 11–13]. Misdiagnosis of fetal ovarian cysts in cases that had undergone in utero aspiration has also been recorded [12]. Noia et al. reported a case of in utero aspiration performed in a male fetus with a pancreatic cyst in a polymalformative condition (ventriculomegaly and corpus callosum agenesis). The cyst fluid in our study showed high levels of estradiol, progesterone and testosterone, suggesting an ovarian origin in all cases with in utero aspiration. Based on our study protocol, fetal ovarian cases for in utero aspiration were correctly included.

Although we set our indication for in utero aspiration as before 37 weeks’ gestation, we encountered a patient who did not receive the procedure due to near-term gestation and developed a complex cyst just after birth. For term gestation cases, in utero aspiration can be considered as a management option instead of termination of pregnancy and be followed by subsequent surgical intervention after birth or expectant management.

Our study has several limitations. First, it was a retrospective investigation. Second, not unlike previous studies, we did not have enough controls to evaluate the effectiveness of in utero aspiration. Furthermore, the small number of patients did not allow sufficient evaluation of the effectiveness of the therapy. Although our sample size was small, it is noteworthy there are no previous large-scale case studies or randomized controlled trials investigating the effectiveness of this therapy. Also, the other studies on in utero aspiration consisted of small sample sizes. [5, 9–13]. Nonetheless, those studies can contribute to future meta-analysis. Our study is no exception.

We conclude that torsion of fetal ovarian cysts is common with expectant management, whereas the management of fetal ovarian cysts larger than 4 cm using in utero aspiration may avoid torsion, which could otherwise lead to ovarian loss. Although our sample size was small, the results encourage further studies to investigate the effectiveness and feasibility of this procedure and its associated indications.