Cornual pregnancy accounts for 2-4% of all ectopic pregnancy and approximately 1 in 2500-5000 live births [1]. Its mortality rate of 2.5% is 7 times greater than other ectopic pregnancies and accounts for 20% of all deaths amongst ectopic pregnancies [2,3]. The incidence of recurrent cornual pregnancy is not known but it poses significant diagnostic and therapeutic challenges. Various medical and surgical methods can be used. The treatment of choice often depends on the time of diagnosis, the haemodynamic status of the patient, the level of the initial bHCG level and the size of the ectopic pregnancy. We report a case of recurrent ipsilateral cornual pregnancy which was successful treated with single dose of systemic methotrexate injection with bHCG level > 7000 IU/L.

A 33 year old lady Gravida 2 Parity 0 lady presented to our unit with vaginal bleeding and abdominal pain at 6 weeks of amenorrhea.

Her first pregnancy in 2010 resulted in a left ectopic pregnancy where a laparoscopic left salpingectomy was performed. During her second pregnancy in 2011, she encountered a ruptured left cornual ectopic pregnancy. A laparoscopic left cornual resection was performed and histopathology confirmed the diagnosis.

In her latest pregnancy, she presented at 6 weeks gestation with vaginal bleeding and abdominal pain. Physical examination revealed minimal tenderness in the lower abdomen with no rebound or guarding. Vaginal examination showed mild blood stained and minimal adnexal tenderness. There was no adnexal mass or cervical excitation tenderness. Her vital signs were stable and the first bHCG level was 2954 IU/L.

Ultrasound scan of her pelvic organs showed no intrauterine sac. Right ovary showed a normal 2.4 cm corpus luteal cyst while the left ovary was normal. Free fluid of 2.47 cm was identified in the Pouch of Douglas. After detailed review of the uterus, the left cornual area was slightly swollen with a possible small sac was seen within it (Figure 1). In view of her history of ectopic pregnancies, significant bHCG levels, abdominal pain and ultrasound findings, a diagnostic laparoscopy was performed for suspected early rupture of recurrent cornual pregnancy.

Figure 1: Transabdominal ultrasound showing transverse uterus and small possible left cornual sac

During the diagnostic laparoscopy, both cornua appeared normal and no obvious ectopic pregnancy was seen. The left tube was absent in compatible with previous left salpingectomy and there were small amount of clear free fluid in the Pouch of Douglas. No further actions were taken as no obvious ectopic pregnancy was found and patient returned to the ward for monitoring of symptoms of abdominal pain and bHCG level.

BHCG level at 48 hours showed a rise from 2954 to 4596 IU/L. A repeat ultrasound scan showed a mixed echogenic shadow 1.52x1.31x1.03 cm³ with a sac like structure within (0.39x1.03 cm) (Figures 2 and 3).

Figure 2: Transabdominal scan-transverse view-a mixed echogenic shadow 1.52x1.31x1.03 cm³ with a sac like structure within (0.39x1.03 cm)

Figure 3: Transabdominal scan-longitudinal view-a mixed echogenic shadow 1.52x1.31x1.03 cm³ with a sac like structure within (0.39x1.03 cm)

Myometrium thickness of 0.89 cm measured next to this mass suggested of a left cornual pregnancy (Figure 4). There was also 1.48 cm depth of free fluid in the Pouch of Douglas.

Figure 4: Myometrium thickness of 0.89 cm was measured next to this mass suggested of a left cornual pregnancy

Patient persisted with mild abdominal pain only and was clinically and haemodynamically stable. Options of medical, surgical or combined management of her condition had been discussed thoroughly with patient and her relatives. She preferred systemic medical management in the form of methotrexate only and was made aware that if the initial medical treatment fails, she may require repeated dose of systemic or local methotrexate and or radical resection of her uterus via the laparoscopic or laparotomy route. Patient opted and consented for medical management at the first instance with a view of repeated medical or combined surgical treatment if the proposed plan fails. Methotrexate 67 mg was given intramuscularly according to the patient’s body surface area (50 mg/m²) after bloods checking for liver and renal abnormalities. bHCG level was 7299 IU/L before administration of methotrexate.

Repeat bHCG level and ultrasound follow ups were carried out after methotrexate injection. BHCG levels dropped significantly to 2944 IU/L on Day 4 and 1628 IU/L on Day 7 while the echogenic area seen previously in ultrasound scan was reduced to 0.28x0.22 cm. Patient remained pain free throughout. Due to the rarity of the case, bHCG level was monitored weekly. The level dropped to 508 IU/L on day 14, 87 IU/L on day 21 and was continued to fall to a level of 5 IU/L on day 34. The previous echogenic area had disappeared on the last ultrasound scan. Patient was advised for contraception and detailed discussion will be required if patient wants to conceive in the future.

Recurrent ipsilateral corneal ectopic is a rare phenomenon and its incidence remains unknown. In general, the interstitial portion of a damaged tube is not removed by routine salpingectomy and even cornual resection does not protect against cornual pregnancy. Our patient had recurrent cornual pregnancy after both ipsilateral salpingectomy and cornual resection. The most likely explanations include the possibility of incomplete resection or implantation onto the defective area from the previous resection site.

Currently, various options are available in managing cornual pregnancy. Treatment option depends on various factors including thehaemodynamic status of the patient, size and gestation of the ectopic pregnancy, bHCG level as well as patient’s wish.

Traditionally, hysterectomy or laparotomy and cornual resection have been the gold standard management [2]. In recent times, moreconservative approaches have been used. Surgically, laparoscopic techniques such as cornual resection, cornuostomy are most commonly used [4] but some reported the use of xylocaine-adrenalline injection or vasopressin prior resection can reduce bleeding. Laparoscopically assisted, hysteroscopic removal and selective uterine artery embolisation after systemic methotrexate or failure of this treatment can also be used [5,6].

Medical treatments using systemic methotrexate have proved to be successful. Lau S et al. [2] reported 83% successful rate of local, systemic or in combination of methotrexate injection for cornual pregnancy. However, early recognition of such pregnancy and patient being haemodynamically stable without signs of rupture are essential factors for using methotrexate [7]. Injection of methotrexate and mifepristone, potassium chloride or prostaglandins have been reported to be successful while methotrexate and folinic acid had shown a 91% success rate with minimal side effects [8]. A combination of surgical and medical techniques has also been carried out successfully [7].

Our patient was diagnosed to have recurrent ipsilateral cornual pregnancy at 6+ weeks of gestation, with ultrasound scan showed an unruptured small cornual pregnancy and bHCG level >7000 IU/L in a haemodynamically stable status.

Surgical management may have been a more ideal management compared with methotrexate in view of her clinical history, history of recurrent ipsilateral cornual pregnancy and high initial bHCG level. However, given the first negative laparoscopy, failing to identify the cornual ectopic and subsequent fail to resect remains a possibility if a repeat laparoscopy was performed. Laparotomy otherwise would have resulted in a large cornual resection leading to high morbidity and may affect future fertility.

Local injection of methotrexate or other cytotoxic drugs under ultrasound guidance or laparoscopy into the cornual pregnancy could have been alternative treatment options for our patient. However, despite having the expertise to perform such procedure, the systemic route of administration was chosen due to the minimal symptoms expressed by the patient and it offered the advantages of being less invasive.

The Royal College of Obstetricians and Gynecologists recommends that the women with tubal pregnancy who are most suitable for methotrexate treatment are those with a bHCG level of < 3000 IU/L and with minimal symptoms [9]. However, in one prospective study for conservative management of cornual pregnancy, 17 out of 20 women with cornual pregnancy were treated with singledose intramuscular methotrexate, which was administered on day 0. The median initial bHCG level was 6452 IU/L. Sixteen were treated successfully (94%). All women with initial bHCG level < 5000 IU/L were treatment successfully with single-dose methotrexate. A second dose of methotrexate was needed in six patients, in which all of them had serum bHCG level > 5000 IU. Only two cases with high serum bHCG level (>9000 IU/L) managed to be treated successful with single-dose intramuscular methotrexate injection [10]. Borgatta et al. also reported a successful resolution of cornual pregnancy using a single dose of systemic intramuscular methotrexate despite bHCG level of 7400 mIU/ml [11].

This case illustrated that if an ectopic pregnancy presented with a small gestation sac with the absence of a fetal heart at the first trimester and the patient is haemodynamically stable, a single dose of systemic methotrexate can be sufficient to manage such an ectopic pregnancy with bHCG level over 7200 IU/L, especially when surgical and local infiltration of cytotoxic drugs may deem to be risky or difficult in such a small recurrent cornual ectopic pregnancy.

In conclusion, cornual pregnancy is a dangerous condition given its high mortality rate. Despite its rarity, recurrent cornual pregnancy remains a possibility. Systemic methotrexate injection can be recommended in such cases of unruptured small cornual pregnancy at first trimester despite high bHCG level. Early recognition of cornual pregnancy however remains essential.