Laparoscopic cornuostomy combined with methotrexate intralesional injection for conservative management to interstitial pregnancy: a case report

A 24-year-old primiparous woman, 8 weeks of gestation came to the outpatient clinic in our hospital with experience of vaginal bleeding and abdominal pain. There was no complaint of other vaginal tissue expulsion. Patient did not have any chronic diseases, history of infection, history of surgical interventions, or history of abdominal trauma. There was no history of any drug intake or contraceptive use, allergies, smoking, and alcohol consumption. First-degree family members had not had similar complaints. Physical examinations including vital signs were stable. Abdominal examination revealed soft abdomen with minimal tenderness at left lower quadrant. Speculum examination showed normal cervix and vaginal examination revealed an enlarged uterus of 8–10 weeks size, mobile, with no adnexal masses or tenderness. Transvaginal ultrasound examination showed gestational sac within the left unruptured cornual uterus, with positive fetal heart rate, and crown rump length (CRL) measured of 1.19 cm in accordance to 7–8 weeks gestational age (Fig. 1 ). Bilateral adnexa were normal and no free fluid were detected in the abdomen. Serum beta-human chorionic gonadotropin (β-hCG) levels was 59 588.4 mIU/ml. Based on the examinations performed, the patient was diagnosed with unruptured interstitial pregnancy. Figure 1. Pre-operative ultrasound. Pre-operative ultrasound. Patients and families are given detailed counseling about their current condition, possible treatment options, and possible complication. Laparoscopic surgery was planned and explained. From the laparoscopy, it was found that the left cornual was enlarged (approximately 3 × 2 × 2 cm). The left tube was normal. Right adnexa was also normal (Fig. 2 a). Laparoscopic cornuostomy combined with intralesional injection of MTX 1 mg/kg body weight done by transvaginal ultrasound guiding was performed (Fig. 2 b and c). A linear incision was made on the superior cornual surface of the uterus using Unipolar cautery, and products of conception were evacuated. Followed by interrupted suturing of the cornual uterus with an absorbable suture (Fig. 2 d). The estimated blood loss during the procedure was 50 ml. There were no complications encountered during the surgical procedure. Figure 2. Intraoperative images, (a) uterus with left interstitial pregnancy; (b) incision of the cornual; (c) MTX injection; (d) post-cornuostomy suturing and closure. Intraoperative images, (a) uterus with left interstitial pregnancy; (b) incision of the cornual; (c) MTX injection; (d) post-cornuostomy suturing and closure. Postoperative period was uneventful. The patient was discharged on second postoperative day. Patient was kept on a routine follow‑up of post-operative β-hCG level which in 1 day after the surgery, it has declined into 12 982.9 mIU/ml with further decrease each week up to 1 month after surgery (639, 80, and 23 mIU/ml until negative). The patient was followed up 5 months post-operatively at the outpatient clinic with pelvic ultrasonography evaluation that revealed a normal uterus and hysterosalpingogram also confirms tubal patency, which showed bilateral-free peritoneal spill.

Interstitial pregnancy is a rare subtype of ectopic pregnancy where the implantation occurs at the interstitial part of the fallopian tube, at the most proximal section within the myometrium. This subtype represents 2–4% of all ectopic pregnancies and contributes to 2–2.5% of the mortality rate due to the anatomy that allows large fetus size before uterine rupture or hemorrhage. Up to 3/4 of interstitial pregnancy cases end up in miscarriage at 12 weeks of gestation. However, when progression continues, a life-threatening condition arises. This subtype is commonly misdiagnosed due to the deep implantation that allows significant growth before detection. Risk factors include endometriosis, uterine leiomyoma, or pelvic inflammatory disease that may cause tubal anatomic changes and alter the physiological implantation process [ 1 – 4 ] . HIGHLIGHTS Interstitial pregnancy is a rare and life-threatening form of ectopic pregnancy. Early diagnosis enabled successful conservative laparoscopic management. Laparoscopic cornuostomy was combined with intralesional methotrexate injection in this case. Postoperative β-hCG monitoring showed rapid decline and fertility preservation. This combination technique provided effective treatment with minimal invasiveness. Interstitial pregnancy is a rare and life-threatening form of ectopic pregnancy. Early diagnosis enabled successful conservative laparoscopic management. Laparoscopic cornuostomy was combined with intralesional methotrexate injection in this case. Postoperative β-hCG monitoring showed rapid decline and fertility preservation. This combination technique provided effective treatment with minimal invasiveness. Early diagnosis is possible in interstitial pregnancies with 2D and 3D ultrasound to increase accuracy. Diagnostic criteria include empty uterine cavity, a chorionic sac located eccentrically and at <1 cm from the lateral edge of the uterine cavity, thin myometrial layer surrounding gestational sac (<5 mm), interstitial line sign, and absence of the double decidual layer sign. The interstitial line sign is an echogenic line between the eccentrically located gestational sac and endometrial cavity. Through the possibility of early diagnosis, conservative management has been used more often. Management options include laparoscopic surgery, local injection of methotrexate (MTX) or systemic, and expectant management. Surgical approach includes laparoscopic cornuostomy or wedge resection, uterine horn resection, and hysterectomy. The most commonly used non-surgical management method is MTX, with the success rate of 66.7% in interstitial pregnancy, while surgical method commonly involves wedge resection. In hemodynamically unstable patients with acute abdomen, hemoperitoneum, and/or gestational sac diameter greater than 3.5 cm, surgical management is indicated [ 1 , 3 , 5 , 6 ] . The combination of surgery and intralesional MTX injection in cases of interstitial pregnancies has not been used and discussed widely. Here we present a case of interstitial pregnancy managed with conservative surgical approach with laparoscopic cornuostomy that was combined with MTX intralesional injection in order to preserve fertility. This case report has been reported in line with the SCARE checklist[ 7 ].

This was a case of an interstitial pregnancy managed with laparoscopy surgery and intralesional MTX injection with post-operative decline of β-hCG levels. Compared to the other types of tubal ectopic pregnancies, mortality rate in interstitial pregnancy is reported to be seven times higher up to 1 per 50 women. Risk of spontaneous abortion and uterine rupture is respectively around 18 and 28%, with the consequence of severe hemorrhage. Early diagnosis is essential in order to decide on the optimal management along with reduction of morbidity and mortality risk. In the first trimester of a normal pregnancy, β-hCG level doubles in about every 2 days. The diagnosis of interstitial pregnancy may be made through ultrasonography examination by discovering a gestational sac separate from the uterine cavity, an empty uterine cavity, and a thin zone of endometrium (<5 mm) around the gestational sac. An echogenic line is commonly found in the central of the endometrial cavity, extending to the gestational sac, or may be called as an interstitial line sign [ 1 , 6 , 8 ] . The general management plan of ectopic pregnancies is divided into medical and surgical management. Treatment plans should consider all aspects such as the patient’s obstetrical history, gestational age, time of diagnosis, and the desire of fertility preservation. The ideal indications of medical management include stable hemodynamic condition, no fetal cardiac activity, gestational sac <3.5 cm in diameter, unruptured mass, β-hCG <5000 mIU/ml, no significant contraindications to MTX, and willingness of follow-up [ 1 , 9 , 10 ] . Although patient in this case of interstitial pregnancy was in a stable condition, but there is fetal cardiac activity, unruptured large sized mass, and β-hCG level >5000 mIU/ml. So that surgical management is indicated in our case. Surgical choices have evolved onto minimally invasive laparoscopic surgery as an option of conservative management. While in cases with hemodynamic instability, available options would be laparotomy and cornuectomy or hysterectomy. The option of management in this case was between wedge resection and cornuostomy become dilemma. Previous studies showed that cornuostomy had better future pregnancy outcome, which aligns with the purpose in our study, and shorter surgical time that is not affected by the surgeon’s experience[ 11 ]. In patients that underwent wedge resection, the incidence of uterine rupture and dehiscence was 30% in women that achieved pregnancy afterwards. Although so, there were no cases of persistent ectopic pregnancy and recurrent interstitial pregnancy found. Fertility preservation was achieved in 71.4% of the subjects[ 12 ]. Cornuostomy has also been found with less tubal damage. Risk of recurrent ectopic pregnancy is higher in patients with the size <2 cm and rapidly rising pre-operative β-hCG[ 13 ]. Risk of uterine rupture at the site of prior cornuostomy within vaginal delivery was reported, but delivery with caesarean section resulted in great outcomes[ 14 ]. While fertility preservation was intended in this case and diagnosis was made early, conservative laparoscopic was an available option. Medical management method with injection of MTX, whether intralesional or systemic, in interstitial pregnancy has a high success rate up to 83%. MTX injection can be done via single, double, or multiple injections depending on the BMI and β-hCG levels. MTX is a chemotherapeutic agent that arrests the growth of the trophoblast by inhibiting DNA synthesis. This therapy works by affecting rapidly growing tissues as an antifolate antimetabolite agent. Contraindications include active pulmonary disease, active peptic ulcer disease, breastfeeding, intrauterine gestational sac, thrombocytopenia, immunodeficiency, hepatic disease, renal disease, leukopenia, etc. Success rate of MTX therapy decreases as β-hCG level increases. In patients with β-hCG level 10 000 mIU/ml, it decreases to 81% for cases with systemic injection [ 6 , 9 , 15 , 16 ] . A previous study successfully managed a persistently elevated β-hCG level case after laparoscopic cornual excision with MTX injection[ 17 ]. Combination of therapy may prevent the chance of treatment failure. Compared to systemic MTX injection, intralesional injection in early-diagnosed cases have proven to be more effective as the bolus may reach the affected area in large amounts. Local injection is more effective due to the achieved therapeutic levels of the drug at the site of injection with decreased systemic toxicity and a quicker evaluation time for the cessation of heartbeat. Doses of local MTX injection varies (12.5, 25, and 100 mg), but higher doses are needed for higher β-hCG levels. Intralesional injection with ultrasound guidance resulted in great outcomes and lower incidence of side effects, as it is minimally invasive, while preserving fertility [ 6 ] . In non-tubal ectopic pregnancies, intralesional MTX injection is considered more effective and may be applied as a first line therapy. The combination therapy of surgery and intralesional MTX injection has not been reported before. Decreased β-hCG levels after intralesional MTX injection was proven in this case and might be researched further as a choice of management in cases of interstitial pregnancy. A larger research group may uncover possible complications under this combination therapy.

This case report reveals that the management of interstitial pregnancy by combining conservative surgery and intralesional MTX injection resulted in good outcomes. The management plan was affected by the early establishment of diagnosis through ultrasound examination. Conservative management in interstitial pregnancy allows preservation of fertility.