Effect of Methotrexate on Blood Loss During Laparoscopic Management of CS Scar Pregnancy

Cesarean scar pregnancy (CSP) is a rare form of ectopic pregnancy in which implantation occurs within the scar of a previous cesarean section. Early diagnosis and appropriate treatment are important because CSP may be associated with significant hemorrhage, uterine rupture, abnormal placentation, and impairment of future fertility. Transvaginal ultrasonography is used for diagnosis and assessment of pregnancy and cesarean scar characteristics.

Laparoscopic resection and repair is an established surgical approach for selected hemodynamically stable patients with cesarean scar pregnancy. The procedure allows removal of the gestational tissue and repair of the cesarean scar defect. Preoperative methotrexate may be used as an adjunct to surgical treatment with the aim of reducing trophoblastic activity and vascularity and potentially reducing intraoperative bleeding. However, the effect of preoperative methotrexate on blood loss and other surgical outcomes during laparoscopic management of cesarean scar pregnancy remains uncertain.

Study design: This is a prospective cohort study conducted at Women's Health Hospital, Assiut University, Egypt. Eligible women with ultrasound-confirmed cesarean scar pregnancy who are planned for laparoscopic resection and repair will be enrolled after providing written informed consent.

Participants will be followed according to the treatment plan determined by the attending consultant and institutional clinical practice. The study will not determine or randomize the treatment received. Patients who receive preoperative methotrexate will constitute the methotrexate group, while patients who undergo laparoscopic resection and repair without preoperative methotrexate will constitute the comparison group. The decision to administer methotrexate will be based on clinical assessment and standard patient care.

Eligibility: The study will include women aged 18 years or older with ultrasound-confirmed cesarean scar pregnancy and residual myometrial thickness less than 3 mm who are hemodynamically stable and planned for laparoscopic resection and repair. Participants must be willing and able to provide written informed consent.

Patients will be excluded if they have hemodynamic instability requiring emergency intervention, suspected or confirmed uterine rupture, contraindications to laparoscopic surgery or methotrexate administration, significant hepatic or renal impairment, or if they are managed primarily by hysteroscopy, suction evacuation, uterine artery embolization, or laparotomy. Patients unable to comply with follow-up assessments or unable to provide informed consent will also be excluded.

Preoperative assessment: A standardized clinical assessment will be performed before surgery. Demographic, medical, and obstetric information will be recorded, including age, body mass index, gravidity, parity, number of previous cesarean sections, previous uterine surgery, presenting symptoms, gestational age at diagnosis, and previous treatment attempts.

All participants will undergo transvaginal ultrasonography performed by experienced sonographers. Pregnancy-related parameters will include gestational sac diameter, crown-rump length when applicable, fetal cardiac activity, and gestational age. Cesarean scar characteristics will include residual myometrial thickness, the distance between the gestational sac and urinary bladder, presence of a scar niche, and the type of cesarean scar pregnancy according to the Vial classification. Color Doppler examination will be used to assess peritrophoblastic vascularity, with vascularity classified as mild, moderate, or marked according to institutional ultrasound criteria.

Preoperative laboratory investigations will include complete blood count, serum beta-human chorionic gonadotropin, liver function tests, kidney function tests, blood grouping, and cross-matching.

Methotrexate protocol: Patients receiving preoperative methotrexate will receive a single intramuscular dose of methotrexate at 50 mg/m², administered 48 hours before surgery. The administered dose, number of doses, interval between methotrexate administration and surgery, and any adverse effects will be documented.

Surgical management: All laparoscopic procedures will be performed under general anesthesia by surgeons experienced in advanced gynecologic laparoscopy. The operating surgeon will be recorded. The surgical procedure will include initial pelvic inspection, identification of the cesarean scar pregnancy, development of the vesicouterine space, bladder dissection, excision of the gestational tissue, excision of the scar defect, achievement of hemostasis, double-layer uterine repair, and final pelvic inspection. Any additional surgical procedure required during management will be recorded.

Intraoperative assessment: Operative time, estimated blood loss, need for blood transfusion, and the need for additional hemostatic procedures will be recorded. Additional hemostatic procedures may include additional hemostatic sutures, bilateral uterine artery ligation, or any other procedure required to control intraoperative bleeding. Intraoperative complications, including bladder injury, ureteric injury, bowel injury, major vascular injury, and conversion to laparotomy, will also be documented.

Estimated blood loss will be recorded in milliliters using the volume collected in the suction container after subtraction of irrigation fluids, together with assessment of blood absorbed by surgical gauzes.

Postoperative assessment and follow-up: Postoperative management will follow institutional protocols. Postoperative hemoglobin, need for blood transfusion, pain assessment, and early postoperative complications will be recorded. Length of hospital stay will be calculated from the time of surgery until discharge.

Participants will undergo clinical follow-up at one week after surgery for assessment of recovery and postoperative complications. A further assessment will be performed at three months after surgery, including clinical evaluation and transvaginal ultrasonography.

At the three-month ultrasound assessment, cesarean scar healing will be evaluated by assessment of residual myometrial thickness, scar integrity, and the presence of a niche defect.

Study outcomes: The primary outcome of the study is intraoperative blood loss during laparoscopic resection and repair of cesarean scar pregnancy. Secondary outcomes include operative time, need for blood transfusion, need for additional hemostatic procedures, conversion to laparotomy, intraoperative complications, perioperative hemoglobin change, length of hospital stay, postoperative complications, and cesarean scar healing at three months.

Exploratory analyses will assess the relationship between intraoperative blood loss and potentially relevant clinical and ultrasound characteristics, including residual myometrial thickness, gestational age, gestational sac size, fetal cardiac activity, Doppler vascularity, type of cesarean scar pregnancy, and number of previous cesarean sections.

Data will be collected using standardized case report forms. Continuous variables will be assessed for distribution and analyzed using appropriate parametric or non-parametric statistical methods. Categorical variables will be analyzed using appropriate categorical data tests. Multivariable regression analysis will be used, where appropriate, to evaluate independent predictors of intraoperative blood loss and other relevant continuous outcomes while accounting for clinically relevant potential confounding factors.

The study is observational in nature. No treatment will be assigned solely for research purposes, and participants will receive management according to the clinical judgment of their treating physicians and institutional practice. Written informed consent will be obtained from all participants, and confidentiality of participant information will be maintained throughout the study.

Primary outcomes

• Intraoperative blood loss [During laparoscopic surgery, from the beginning of the procedure until completion of surgical hemostasis.]: Estimated blood loss during laparoscopic resection and repair of cesarean scar pregnancy, measured in milliliters using the volume collected in the suction container after subtraction of irrigation fluids, together with assessment of blood absorbed by surgical gauzes.

Secondary outcomes

• Operative time [From insertion of the first trocar to removal of the last trocar.]: Duration of the laparoscopic surgical procedure, measured in minutes.
• Perioperative hemoglobin change [Preoperative and 6 hours post operative.]: Change in hemoglobin concentration between the preoperative and postoperative measurements.
• Blood transfusion requirement [From start of surgery till hospital discharge.]: Need for blood transfusion
• Additional hemostatic procedures [From insertion of the first trocar to removal of the last trocar.]: Requirement for additional procedures to control intraoperative bleeding, including additional hemostatic sutures, bilateral uterine artery ligation, or other hemostatic procedures.
• Intraoperative complications [From insertion of the first trocar to removal of the last trocar.]: Occurrence of intraoperative complications including bladder injury, ureteric injury, bowel injury, major vascular injury, or conversion to laparotomy.
• Length of post operative hospital stay [From completion of surgery until hospital discharge.]: Duration of hospitalization measured from surgery until discharge.
• Postoperative complications [From hospital discharge to 1 week after discharge.]: Occurrence of postoperative complications during follow-up after laparoscopic surgery.
• Cesarean scar healing [3 months after surgery]: Cesarean scar healing assessed by transvaginal ultrasonography, including residual myometrial thickness, scar integrity, and presence of a niche defect.

Sex: Female, ages: 18 Years to any

Inclusion Criteria:

1. Women aged ≥18 years.
2. Ultrasound-confirmed cesarean scar pregnancy with residual myometrial thickness (RMT) <3 mm.
3. Planned laparoscopic resection and repair of cesarean scar pregnancy.
4. Hemodynamically stable patients.
5. Ability and willingness to provide written informed consent.

Exclusion Criteria:

\- 1. Hemodynamic instability requiring emergency intervention. 2. Suspected or confirmed uterine rupture. 3. Contraindications to laparoscopic surgery. 4. Contraindications to methotrexate administration. 5. Significant hepatic or renal impairment. 6. Patients managed primarily by hysteroscopy, suction evacuation, uterine artery embolization, or laparotomy.

7\. Inability to comply with follow-up assessments. 8. Refusal or inability to provide informed consent.