A Successful Methotrexate Management Of Pregnancy Of Unknown Location (Pul) With Associated Pre-Existing Leukopenia: A Case Study

1 Introduction#

Pregnancy of unknown location (PUL) is diagnosed when no intrauterine or ectopic gestation is seen on transvaginal ultrasound despite a positive pregnancy test and elevated β-hCG^[1].

This entity requires careful follow-up to prevent rupture from undetected ectopic pregnancy or unnecessary intervention in early intrauterine pregnancy^[2].

Methotrexate (MTX) is a folate antagonist used as first-line treatment for selected cases of ectopic pregnancy and some PULs, provided the patient is stable, β-hCG levels are relatively low, and there are no contraindications^[3]. MTX may cause myelosuppression,hepatotoxicity, and mucositis, making baseline laboratory evaluation essential^[4].

Leukopenia and neutropenia are relative contraindications; most guidelines advise withholding MTX if ANC <1.0×10³/µL^[3,5]. However, evidence is limited on MTX use in patients with mild pre-existing leukopenia. This report presents such a case, highlighting the role of multidisciplinary decision-making and close hematologic monitoring.

2 Case Presentation#

A 45-year-old woman, gravida 8 para 5 (two prior first-trimester spontaneous abortions), presented to the early pregnancy assessment unit with amenorrhea of approximately 7 weeks by last menstrual period (25 January 2025). She reported no abdominal pain, vaginal bleeding, fever, or systemic symptoms. Her obstetric history included five uncomplicated spontaneous vaginal deliveries; she had no significant gynecologic or medical history and was on no regular medications.

On examination, she was afebrile, blood pressure 118/72 mmHg, pulse 84 bpm, and oxygen saturation 98% on room air. Abdominal and pelvic examination were unremarkable; there was no adnexal tenderness or palpable mass.

Initial laboratory investigations revealed β-hCG of 328 mIU/ mL (16 March 2025), which dropped slightly to 295 mIU/mL (18 March) but then increased to 325 mIU/mL (20 March), demonstrating a plateau pattern. Complete blood count (CBC) showed leukopenia with WBC 3.15×10³/µL and absolute neutrophil count (ANC) 1.24×10³/µL. Hemoglobin was 13.2 g/ dL,and platelets were 265×10³/µL. Renal and liver function tests were normal.

Transvaginal ultrasound performed twice, by different operators, demonstrated an empty uterus with thin endometrium, no adnexal mass, and no free fluid in the pelvis.

Given the plateauing β-hCG and absent intrauterine pregnancy, ectopic pregnancy was suspected. However, the patient’s baseline leukopenia raised concerns regarding MTX administration. Hematology consultation was sought, and the assessment concluded that the leukopenia was mild, likely transient, and not associated with infection. Vitamin B12 and folate levels were within normal limits. The hematologist advised that MTX could be given with strict weekly CBC monitoring and readiness to initiate granulocyte colony-stimulating factor (G-CSF) if ANC fell below 0.5×10³/µL or if febrile neutropenia developed.

On 20 March 2025, the patient received a single intramuscular dose of MTX 79.5 mg (50mg/m²). She was counseled to avoid folic acid, NSAIDs, and pregnancy for at least 3 months.

Barrier contraception was advised. She was also instructed to report immediately if she developed fever, sore throat, mucositis, or abdominal pain.

Follow-up on day 4 post-MTX showed β-hCG 279 mIU/mL, WBC 3.35×10³/µL, ANC 1.01 ×10³/µL. The patient remained asymptomatic. Day 7 post-MTX revealed β-hCG 183 mIU/mL, ANC 0.77×10³/µL, but she remained afebrile with no signs of infection. No G-CSF was given.

By day 14, β-hCG had dropped to 54 mIU/mL, and ANC had started to recover. On 16 April 2025, β-hCG was <2.3 mIU/ mL, WBC 3.87×10³/µL, ANC 1.74×10³/µL. The patient was discharged from both gynecology and hematology follow-up without complications.

3 Discussion#

MTX is an established treatment for selected ectopic pregnancies and PUL^[1,3]. Baseline hematologic abnormalities, particularly neutropenia, may increase the risk of infectious complications^[4,5]. Our patient had mild neutropenia at baseline, with ANC above 1.0×10³/µL, which is a threshold often considered safe for MTX in non-oncology settings when close monitoring is available^[6,7].

The observed ANC nadir on day 7 (0.77×10³/µL) is consistent with the expected timing of MTX-induced myelosuppression^[4]. The absence of clinical infection and spontaneous recovery without intervention aligns with previous reports of transient MTX-related neutropenia^[5,8].

This case demonstrates that in a stable patient with mild pre-existing leukopenia, MTX may be used safely if there is hematology input, strict follow-up, and access to rescue therapies.

Avoiding unnecessary surgery in a hemodynamically stable patient also aligns with current recommendations favoring medical management in selected cases^[3].

4 Conclusion#

MTX may be considered in PUL with mild pre-existing leukopenia in tertiary care settings with specialist oversight and vigilant hematologic monitoring. Individualized assessment remains essential.