Cemal ÜNLÜ, Hüseyin AKSOY, Harika GÖÇER, Merve GENCO, Emrah GÖÇER, Gonca TÜRKER ERGÜN
Anatolian Journal of Obstetrics and Gynecology Research - 2026;3(2):131-138
Purpose: Medical treatment with methotrexate (MTX) is an established option for some patients with ectopic pregnancies or persistent pregnancy of unknown location (PUL). This study evaluated whether serial progesterone kinetics provide clinically useful information beyond beta-human chorionic gonadotropin (beta-hCG) kinetics during early follow-up after MTX treatment for persistent PUL or presumed ectopic pregnancy. Methods: In this retrospective cohort study, hemodynamically stable patients treated with systemic MTX between 1 January 2025 and 1 September 2025 were screened. Serum beta-hCG and progesterone were measured on day 1, day 4, and day 7, with day 1 defined as the day of MTX administration. The primary outcome was insufficient early biochemical response, defined as a beta-hCG decrease of less than 15% from day 4 to day 7. The main secondary outcome was actual second-dose MTX administration. Results: Among 73 assessed patients, 50 (68.5%) met the inclusion criteria. Seven (14%) patients had sonographic findings compatible with tubal ectopic pregnancy, and 43 (86%) were managed as persistent PUL or presumed ectopic pregnancy. Twelve patients (24.0%) had an insufficient day 4-day 7 beta-hCG response, and 9 (18.0%) received a second MTX dose. Day 7 beta-hCG was higher in patients with insufficient early response, whereas day 1, day 4, and day 7 progesterone concentrations did not differ significantly between response groups. In exploratory receiver operating characteristic analysis for actual second-dose MTX administration, day 7 beta-hCG and lower day 4-day 7 beta-hCG decline showed greater discrimination than progesterone-derived variables. Five clinically stable patients with subthreshold beta-hCG decline refused additional MTX and achieved biochemical cure with close follow-up. Conclusion: In this predominantly PUL/presumed ectopic pregnancy cohort, early beta-hCG kinetics appeared more informative than serial progesterone kinetics for identifying insufficient response and second-dose MTX administration. Serial progesterone measurement was feasible but showed limited additional discriminatory value. These preliminary findings require validation in larger prospective cohorts.
