Hysteroscopy for the Diagnosis and Treatment of Pregnancy of Unknown Location

Infertility patients have a higher baseline risk of ectopic pregnancy compared to the general population. If an early pregnancy is not visible by ultrasound, patients with a pregnancy of unknown location (PUL) will undergo uterine aspiration (D&C) in order to diagnose an ectopic pregnancy and/or treat an abnormal intrauterine pregnancy destined for miscarriage. If the pathologic specimen obtained after D&C does not contain chorionic villi, the presumptive diagnosis of ectopic pregnancy is made and methotrexate therapy is typically recommended. In many institutions, a D&C must be scheduled in the operating room so that it may be performed under anesthesia, potentially delaying the urgent treatment of ectopic pregnancy.

Office hysteroscopy is a safe and well-tolerated means of evaluating the uterine cavity, though little literature exists supporting its use in the evaluation of PUL. The objective of this study is to compare hysteroscopic biopsy to the gold standard D&C for the diagnosis and treatment of PUL. The investigators propose a prospective study including patients undergoing care at the University of Pennsylvania. Patients will be included if they have at least three bHCG values demonstrating a <50% increase in over 48 hours. A hysteroscopy with possible biopsy followed by uterine aspiration will be performed, and the final pathology results will be compared. Although pathology results from the procedure are considered the gold standard of diagnosis, physicians typically do not wait for results to return before proceeding with necessary treatment. Instead, all patients will have a serum bHCG drawn on post-operative day 1, and those with a <50% decrease compared to pre-procedural values will undergo treatment with methotrexate therapy per institutional protocol.

The findings from this pilot study will inform future research comparing hysteroscopic vs. D&C for management of PUL. If hysteroscopic targeted biopsy is more accurate than D&C in detecting an abnormal IUP, this technique could reduce unnecessary methotrexate exposure in patients with abnormal IUPs. If adapted to the office setting, hysteroscopic biopsy could also shorten time to diagnosis and definitive treatment. In addition, targeted treatment in the office setting could lower the rate of intrauterine adhesions, and may improve overall the patient experience.

Study Overview

• Status: Recruiting
• Conditions: Pregnancy of Unknown Location
• Intervention / Treatment: Diagnostic test: Hysteroscopy for diagnosis and treatment of pregnancy of unknown location

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Margaret A Rush, MD; Phone Number: 267-624-4249; Email: margaret.rush@pennmedicine.upenn.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19103
      • Recruiting
      • Penn Fertility Care
      • Contact: Margaret Rush Physician, MD; Phone Number: 215-662-2971; Email: margaret.rush15@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients 18 years of age and older
• Patients undergoing care with (1) positive serum hcg and (2) abnormal hcg trend, as defined by <50% rise in bHCG over 48h period, repeated across three lab values.
• Patients with pregnancy via unassisted conception, conception after ovulation induction and/or intrauterine insemination, and/or embryo transfer
• Well established pregnancy dating, either with known LMP, or dating by IUI or embryo transfer

Exclusion Criteria:

• Patients with known abnormal cavity (history of fibroids, septum, or uterine anomaly)
• Patients who are hemodynamically unstable or with an acute abdomen

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hysteroscopy prior to Dilation and Curettage; All patients in this study will have a diagnostic hysteroscopy with possible biopsy of abnormal pregnancy tissue prior to dilation and curettage	Diagnostic test: Hysteroscopy for diagnosis and treatment of pregnancy of unknown location; All patients in this trial will have a diagnostic hysteroscopy performed prior to a dilation and curettage in the treatment of their pregnancy of unknown location

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence or absence of abnormal tissue within the endometrial cavity	Intra-operative photographs will be taken of the participants uterine cavities at five standardized locations (left cornua, right cornua, anterior uterine wall, posterior uterine wall, and entire uterine cavity at level of internal os). The presence or absence of abnormal tissue will be documented, and findings qualitatively compared between the cavities of participants with the final diagnosis of non-viable intrauterine pregnancy and an ectopic pregnancy.	From enrollment to 1 week post-operatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity of hysteroscopy compared to gold-standard dilation and curettage	Sensitivity, specificity, and positive and negative predictive values of hysteroscopic biopsy as a diagnostic test will be compared to that of D&C. Statistical significance will be determined with the use of Fisher exact test analysis with Stata software, with a probability value of <0.05 considered statistically significant	From enrollment to 1 week post-operatively
Specificity of hysteroscopy compared to gold-standard dilation and curettage	Specificity of hysteroscopic biopsy as a diagnostic test will be compared to that of D&C. Statistical significance will be determined with the use of Fisher exact test analysis with Stata software, with a probability value of <0.05 considered statistically significant	From enrollment to 1 week post-operatively
Positive predictive value of hysteroscopy compared to gold-standard dilation and curettage	Positive predictive value of hysteroscopic biopsy as a diagnostic test will be compared to that of D&C. Statistical significance will be determined with the use of Fisher exact test analysis with Stata software, with a probability value of <0.05 considered statistically significant	From enrollment to 1 week post-operatively
Negative predictive value of hysteroscopy compared to gold-standard dilation and curettage	Negative predictive value of hysteroscopic biopsy as a diagnostic test will be compared to that of D&C. Statistical significance will be determined with the use of Fisher exact test analysis with Stata software, with a probability value of <0.05 considered statistically significant	From enrollment to 1 week post-operatively

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: American Society for Reproductive Medicine

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: November 18, 2025
• First Submitted That Met QC Criteria: March 10, 2026
• First Posted (Actual): March 13, 2026

Study Record Updates

• Last Update Posted (Actual): March 13, 2026
• Last Update Submitted That Met QC Criteria: March 10, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Miscarriage; Ectopic Pregnancy; Pregnancy of Unknown Location
• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Pregnancy Complications; Abortion, Spontaneous; Pregnancy, Ectopic; Diagnostic Techniques and Procedures; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures; Diagnostic Techniques, Surgical; Endoscopy; Urogenital Surgical Procedures; Gynecologic Surgical Procedures; Obstetric Surgical Procedures; Diagnostic Techniques, Obstetrical and Gynecological; Diagnosis; Hysteroscopy
• Other Study ID Numbers: 859064

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No