Case report: Granulocytopenia induced by local injection of MTX for abdominal pregnancy

Abstract

Introduction

Abdominal ectopic pregnancies(APs) is a rare type of ectopic pregnancy, most commonly implanting in the rectouterine pouch. The treatment methods include surgical treatment and drug therapy. In the surgical treatment of ectopic pregnancy, local injection of methotrexate(MTX)at the site of pregnancy can reduce the occurrence of persistent ectopic pregnancy(PEP). However, there is no unified standard for the treatment dosage. We report a case of an AP patient who received local injection of MTX during surgery and developed neutropenia postoperatively.

Presentation of case

A 29-year-old woman with a 45-day history of missed menses and rectal pressure presented with suspected ruptured ectopic pregnancy. Intraoperative exploration revealed no abnormalities in the appearance of both ovaries and fallopian tubes. Upon careful examination, the pregnancy tissue was found to be located on the inner side of the right sacral ligament and the pregnancy tissue was removed. To prevent the occurrence of PEP, MTX was locally injected at a dose of 50 mg/m² during the surgery. Postoperatively, the patient developed leukopenia, with a white blood cell (WBC) count of 3.22 × 10⁹/L on day 4, which further decreased to 2.59 × 10⁹/L with a neutrophil (NEUT)count of 1.19 × 10⁹/L by day 10. The patient was treated with Di Yu Sheng Bai tablets, 3 tablets orally three times a day. On the 17th postoperative day, the WBC count was 3.1 × 10⁹/L and the absolute neutrophil(NEUT) count was 1.21 × 10⁹/L. The patient received recombinant human granulocyte colony-stimulating factor (G-CSF) at a dose of 200 μg for three days. Granulocytes returned to normal levels.

Discussion

APs is a rare form of ectopic pregnancy that can be treated with laparoscopy in the early stages of pregnancy. It is well known that local injection of MTX at the site of pregnancy during surgery can reduce the occurrence of PEP. There are documented cases of local MTX injection reducing the occurrence of PEP in special locations such as retroperitoneal pregnancy and cervical pregnancy. However, there is no unified standard for the therapeutic dosage. The minimum effective dose of locally injected MTX to prevent PEP needs further exploration. There have been no reports on the occurrence of granulocytopenia due to the local injection of MTX during surgery for ectopic pregnancy to prevent the PEP.

Conclusion

Ectopic pregnancy patients, such as those with abdominal pregnancy, if treated with a combination of local MTX injection during surgery, require close postoperative monitoring of blood routine. The minimum effective dose still needs further exploration.

Highlights

• •Abdominal ectopic pregnancies is a rare type of ectopic pregnancy
• •Ectopic pregnancy persists if trophoblast cells survive surgery.
• •Intraoperative MTX injection can prevent persistent ectopic pregnancy by killing trophoblast cells.
• •First report of neutropenia after local MTX injection during abdominal pregnancy surgery.

1. Introduction

Abdominal ectopic pregnancies (APs) are a rare form of ectopic pregnancy(EP) where the fertilized egg implants outside the uterine cavity and fallopian tubes, within the abdominal cavity. Implantation sites include the omentum, peritoneal surfaces of the pelvis and abdomen, and abdominal organs such as the liver [1]. The most common implantation site is the rectouterine pouch. The reported incidence of APs ranges from 1:10,000 to 1:30,000, accounting for about 1 % of ectopic pregnancies, with a maternal mortality rate approximately 7.7 times that of tubal pregnancies [2]. We report a case of early Abdominal ectopic pregnancy(AP) with the gestational sac implanted in the rectouterine pouch. To prevent trophoblastic cell infiltration, a local injection of methotrexate (MTX) at 50 mg/m² was administered intraoperatively, resulting in granulocytopenia. Whole blood cell reduction is one of the toxic effects of MTX, with few reports of granulocytopenia following local MTX injection.

2. Case report

A 29-year-old woman, gravida 2, para 0, with a history of one miscarriage, presented with a 45-day history of missed menses and a sensation of rectal pressure. The patient has no history of diseases. Ultrasound scan at an external hospital indicated an unclear pregnancy location. Upon admission, she reported significant tenesmus without abdominal pain or vaginal bleeding. Repeat ultrasound at our hospital showed a heterogenous echo area of approximately 6.4 × 5.6 × 3.1 cm in the right pelvic cavity, unclear boundaries, suggesting possible ruptured EP and intrauterine fluid. Serum human chorionic gonadotrophin(HCG)was 5560mIU/mL. Given the possibility of rupture, an emergency single-port laparoscopic exploration was performed. During surgery, approximately 100 mL of pelvic blood was noted, with no abnormalities in both ovaries and fallopian tubes. Careful exploration revealed a 2×2×1.5 cm hematoma on the medial side of the right sacral ligament, with typical villi observed. A 2×1×0.5 cm peritoneal depression with rough surface at the site of attachment was found (Fig. 1). Local MTX injection at 50 mg/m² was administered. The patient's BMI is 21.1 kg/m². The patient did not develop any infections postoperatively. No antibiotics were used postoperatively. Postoperative pathology showed villi and trophoblasts. The patient's postoperative recovery was uneventful initially, with HCG levels dropping to 824.2 mIU/mL on day 2 and becoming negative by day 16 (Fig. 2). However, on the 4th postoperative day, there was a decrease in white blood cells(WBC), leukopenia was observed, with a WBC count of 3.22 × 10⁹/L. On day 10, the WBC count further decreased to 2.59 × 10⁹/L, and neutrophil count fell to 1.19 × 10⁹/L. The patient was treated with Di Yu Sheng Bai tablets(Chengdu Di'ao Group Tianfu Pharmaceutical Co., Ltd., Approval Number: Z20026497, Specification: 0.1 g per tablet), which are a traditional Chinese medicine, mainly used to increase white blood cells and are applicable to various types of leukopenia., 3 tablets orally three times a day. On the 17th postoperative day, the WBC count was 3.1 × 10⁹/L and the absolute neutrophil(NEUT) count was 1.21 × 10 [9]/L. The patient received recombinant human granulocyte colony-stimulating factor (G-CSF) at a dose of 200 μg for three days. Granulocytes returned to normal levels (Fig. 3). The patient has already visited the reproductive medicine department and plans to undergo assisted reproductive therapies (ART). The work has been reported in line with the SCARE criteria [3].

Fig. 1.

(a) a 2 × 2 × 1.5 cm hematoma on the medial side of the right sacral ligament and approximately 100 mL of pelvic blood was noted

(b) a 2 × 1 × 0.5 cm peritoneal depression with rough surface at the site of attachment.

Fig. 2.

The dynamic change in the patient's serum hCG level during treatment.

Fig. 3.

WBC and NEUT levels in blood change during treatment.

3. Discussion

APs are extremely rare, often lacking typical clinical features, with abdominal pain being the most common symptom. Early diagnosis is challenging, with a preoperative diagnostic rate of about 45 % [4]. Transvaginal ultrasound is the preferred diagnostic method, while pelvic Magnetic Resonance Imaging (MRI) and Computed Tomography(CT) improve preoperative diagnostic accuracy, clarify placental location, assess adhesion and implantation with surrounding organs, and monitor retained placental tissue.

APs are classified as primary or secondary. The diagnostic criteria for primary APs, proposed by Studdiford in 1942 [5], include: (1) normal bilateral fallopian tubes and ovaries, (2) absence of uteroperitoneal fistula, (3) pregnancy solely within the peritoneal cavity and (4) exclusion of tubal pregnancy. In this case, the patient had no surgical history and intact fallopian tubes, suggesting APs. Secondary APs often follow the rupture or abortion of a tubal pregnancy or conservative treatment of a tubal pregnancy. Studies have also reported cases secondary to the rupture of cornual pregnancies [6] and trophoblastic cell implantation into the abdominal cavity post-tubal resection [7].

Risk factors associated with APs include tubal damage, pelvic inflammatory disease, endometriosis, assisted reproductive technologies, multiple pregnancies and conservative treatment of tubal pregnancies [8]. In this case, the patient conceived naturally and had no history of tubal surgery, leaving the cause of the abdominal pregnancy unclear.

Surgical and medical treatments are available for APs. Early APs with stable vital signs can be treated laparoscopically, while late APs or unstable cases may require laparotomy. The single-port laparoscopic technique we employed is less invasive. The largest reported late AP was 41 weeks [9]. Placental management in mid-to-late APs is controversial due to the risk of severe bleeding, with some studies reporting blood loss up to 5500 mL [10]. Placental adhesions and implantation to adjacent organs can lead to organ damage [2] and death. Retained placenta poses risks of slow absorption, secondary bleeding, infection and bowel obstruction [8]. Some scholars propose that if the placenta is attached to organs with rich blood vessels and low mobility, such as the pelvic ligaments, iliac vessels, liver, and spleen, the placenta should be left in place and not be detached, allowing it to be absorbed on its own [11].

MTX is the first-line drug for the treatment of EP. It can disrupt the villi of the trophoblast and inhibit the regeneration of the muscular layer of the fallopian tube wall trophoblast. It can also be used to treat rare ectopic pregnancies, such as rectal ectopic pregnancy [12]. MTX is widely used in the treatment of EP and intraoperative local injection of methotrexate helps to kill trophoblast cells, effectively preventing the occurrence of persistent ectopic pregnancy(PEP). The incidence of PEP after salpingostomy for embryo extraction is approximately 9 %. Over 30 years ago, local injection of methotrexate during conservative salpingectomy to prevent the occurrence of PEP had already been initiated. For patients with an ectopic pregnancy lesion size of 2 cm and preoperative hCG levels ≥2500 IU/mL, the risk of PEP is relatively high [13]. Local prophylactic administration of MTX can be considered to reduce the occurrence of PEP. The patient in this case was preoperatively considered to have a ruptured EP. During surgery, an intra-abdominal pregnancy was discovered and the gestational tissue was removed via laparoscopy. Considering the invasive nature of the trophoblast cells, to prevent the occurrence of PEP, MTX was locally injected at a dose of 50 mg/m². The patient subsequently experienced a decrease in granulocyte count, as shown in Fig. 2. There have been numerous reports on the use of local MTX injections during surgery for ectopic pregnancy. However, there is no unified treatment dosage. Wen et al. [14]in the treatment of para-aortic EP, after the removal of the gestational tissue, to prevent the occurrence of PEP, locally injected MTX at a dose of 50 mg/m². Giannopoulos et al. [15]administered local MTX injections at a dosage of 50 mg/m² for the treatment of ectopic pregnancies in the rectal fossa. Wang et al. [16]utilized local MTX injections of 10 mg for the treatment of psoas major muscle ectopic pregnancies. Bettaiah et al. [17]applied local MTX injections of 50 mg in the treatment of cervical pregnancies. Kooi et al. [18] administered local MTX injections of 100 mg for the treatment of fallopian tube ectopic pregnancies. Currently, there is no standardized protocol for the dosage of local MTX injections. This case report suggests that close monitoring of blood routine is necessary when administering local MTX and the minimum effective dosage requires further investigation.

4. Conclusion

APs is a rare form of ectopic pregnancy. Early APs can be treated laparoscopically and careful exploration for abdominal implantation is necessary in tubal pregnancies. Postoperative HCG monitoring until negative is crucial. Patients receiving local MTX injection should have regular blood count monitoring and the optimal injection dose requires further study.

CRediT authorship contribution statement

Huang Xiaoyan was responsible for drafting the manuscript, as well as the study's concept and design.

Li Juan handled the data collection process.

Wu Yurui was in charge of data analysis and interpretation.

Wang Jidong contributed to the study's concept and design.

Consent statement

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request. This work has been reported in line with the SCARE criteria [3].

Guarantor

Wang Jidong

Ethical approval statement

The ethical approval for this study was approved by the Ethical Committee. The reference number of ethical approval is NO.2024-085.

Sources of funding statement

This article did not receive any funding.

Declaration of competing interest

The authors declare no conflict of interest for this article.

Data availability

The data supporting the findings of this study are presented in Fig. 1, Fig. 2, Fig. 3, which are incorporated within this manuscript.