Unusual course of hyperreactio luteinalis in twin pregnancy complicated by twin-twin transfusion syndrome.

Abstract

We report the case of a 35-year-old primigravida with a spontaneously conceived twin pregnancy who presented at our fetal center with suspected twin–twin transfusion syndrome (TTTS). On evaluation at 16 + 6 weeks, a diagnosis of selective fetal growth restriction Type III (intermittent absent/reversed end-diastolic flow in the umbilical arteries) was made. Following counseling, the parents opted for expectant management. During ultrasound assessment, significant bilateral multicystic ovarian enlargement (right ovary, 8.2 × 8.7 × 7.8 cm; left ovary, 9.4 × 7.2 × 5.9 cm) was noted (Figure 1). Differential diagnosis included spontaneous ovarian hyperstimulation syndrome and hyperreactio luteinalis. A hormone panel was used to further explore the differential diagnosis. The patient did not present any manifestations of virilization or any other symptoms at that time. Five days later, the condition progressed to Stage-III TTTS and laser photocoagulation was offered. The patient underwent the procedure at 17 + 4 weeks, which was challenging due to anterior location of the placenta and significant bilateral ovarian enlargement. The hormone panel showed extremely elevated serum human chorionic gonadotropin (hCG) level (414 000 mIU/mL), very low thyroid-stimulating hormone (TSH) level (< 0.020 μIU/mL), high free thyroxine (T4) level (1.7 ng/mL) and very high testosterone level (256 ng/dL). The patient was advised to report any persistent abdominal pain suggestive of ovarian torsion. Based on these laboratory findings, the diagnosis of hyperreactio luteinalis was considered. One month later, both fetuses showed adequate recovery from TTTS, and a significant decrease in the size of both ovaries was noted on a follow-up scan. The patient remained asymptomatic, and no virilization or symptoms of hyperthyroidism were reported. Normal-size ovaries were also observed on follow-up scans. A repeat hormonal panel at the time of follow-up revealed marked reductions in hCG (118 000 mIU/mL) and testosterone (172 ng/dL) levels, as well as normal TSH and T4 levels. Follow-up ultrasound examination revealed an iatrogenic monoamniotic twin pregnancy without evidence of cord entanglement. Interestingly, 2 months later, bilateral ovarian enlargement was noted again. A repeat hormone panel revealed markedly elevated hCG (290 000 mIU/mL) and testosterone (466 ng/dL) levels and decreased TSH level. The condition persisted until the time of delivery by Cesarean section at 33 weeks' gestation due to preterm labor. At the time of delivery, the ovaries showed bilateral multicystic enlargement (Figure 2) and absence of cord entanglement was confirmed. Clinical evaluation at 6 weeks postpartum confirmed resolution of hyperreactio luteinalis. Hyperreactio luteinalis is a rare condition that can be discovered accidentally during routine ultrasound evaluation, and is characterized by significant bilateral cystic ovarian enlargement during pregnancy1. The condition occurs more commonly in multiple gestations and can sometimes be misdiagnosed as malignancy, leading to unnecessary surgical intervention with serious consequences2. In the majority of cases, hyperreactio luteinalis is a self-limiting condition that resolves spontaneously after delivery. It can be associated with adverse pregnancy outcomes that have been correlated with hCG level, including pre-eclampsia, hyperthyroidism, gestational diabetes, preterm birth, acute abdominal pain requiring surgery and fetal growth restriction. Virilization has been reported in some cases of hyperreactio luteinalis, which is mainly maternal (30%) and rarely fetal (3.5%)3. An interesting finding in the current case is the resolution and recurrence of hyperreactio luteinalis during pregnancy, which, to the best of our knowledge, has not been reported before. One explanation for this unusual presentation could be improved fetal and placental hemodynamics after successful laser surgery, as well as improvement in maternal venous return following the correction of polyhydramnios. These factors may have played a role in decreasing hCG production secondary to improvement in fetal circulation and placental perfusion. However, as pregnancy advances, progressive placental dysfunction is not unusual in complicated monochorionic pregnancies with significant growth discordance and unequal placental sharing. It is possible that worsening placental function in the third trimester contributed to increased placental production of hCG as a compensatory mechanism. In turn, elevated hCG level might have led to a relapse of hyperreactio luteinalis. Any fetal intervention should be performed carefully in patients with hyperreactio luteinalis to reduce the risk of injuring the enlarged ovaries. In addition, it is advisable to manage properly the associated medical complications, including hyperthyroidism, before planning surgery, to reduce the risk of life-threatening complications such as thyroid storm.