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.

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