Variable clinical and gynecologic characteristics associated with anatomical site of ectopic pregnancy

Abstract

An ectopic pregnancy refers to the implantation of a gestational sac outside the uterine cavity.¹ Most ectopic pregnancies occur in the fallopian tube, but extra-tubal ectopic pregnancy can happen in the abdomino-pelvic cavity.² Clinical characteristics of extra-tubal ectopic pregnancy has been not well studied due to its rarity. The objective of this study was to describe patient and gynecologic characteristics associated with anatomical site of ectopic pregnancy implantation.

This cross-sectional study examined the Healthcare Cost and Utilization Project's two nationwide databases: the National Inpatient Sample and the Nationwide Ambulatory Surgical Sample.^{3, 4} Patient encounters with a diagnosis of ectopic pregnancy from 2016 to 2020 were evaluated.

Identification of ectopic pregnancy followed the World Health Organization's International Classification of Disease, 10th revision, Clinical Modification codes per prior investigation (Table S1):¹ fallopian tube (O00.1), ovary (O00.2), abdomen (O00.0), cervico-corpus including uterine cervix, uterine cornua, broad ligament, and uterine myometrium (O00.8). Ectopic pregnancies occurring in two or more of these four sites were categorized as the study-defined multi-classifier (e.g., fallopian tube and abdomen).

The outcome measures were 13 patient characteristics and 14 gynecologic diagnoses, selected in a view of relevance to clinical practice (Table S1). Patient characteristics included demographics, comorbidity, substance use factor, mental health condition, and hospital parameters. Gynecologic diagnoses included past surgical history, uterine factors, adnexal factors, endometriosis, infectious conditions, and other pregnancy conditions.

Descriptive statistics were performed to outline the measured outcomes by generating frequency table in each program separately, weighting for the national estimates. The University of Southern California Institutional Review Board (registration number, HS-16-00481) deemed this study exempt due to the use of publicly available, deidentified data (informed consent, not required).

A total of 142 769 ectopic pregnancies were examined (Table 1). The fallopian tube (n = 128 532, 90.0%) was the most common anatomical site, followed by cervico-corpus (n = 9338, 6.5%), ovary (n = 3300, 2.3%), and abdomen (n = 840, 0.6%). Multi-classifier ectopic pregnancy was reported in less than 1% (n = 859, 0.6%). During the study period, ovarian ectopic pregnancy increased from 1.9% to 2.7% while cervico-corpal ectopic pregnancy decreased from 7.5% to 6.0% (both, P-trend <0.001; Figure S1).

Patients with abdominal ectopic pregnancy were more likely to be obese (10.4% vs 6.8%–8.1%), comorbid (Charlson Comorbidity Index ≥2, 6.4% vs 1.3%–2.3%), and have adnexal endometriosis (2.0% vs 0.7%–1.5%) and heterotopic pregnancy (20.2% vs 1.6%–6.3%) (all, P < 0.001). Patients with cervico-corpal ectopic pregnancy were more likely to be older (≥40 years, 5.9% vs 3.7%–5.1%), and have a uterine scar due to prior surgery (7.2% vs 1.1%–5.1%) (both, P < 0.001). Patients with abdominal or cervico-corpal ectopic pregnancy were more likely to receive inpatient care (61.9%–63.3% vs 25.8%–39.6%, P < 0.001). Patients with ovarian ectopic pregnancy were more likely to have a diagnosis of ovarian cyst (11.3% vs 4.6%–7.4%, P < 0.001).

In conclusion, this comprehensive national-level assessment suggests that clinical and gynecologic characteristics differ in relation to the anatomical site of ectopic pregnancy. Specifically, the three key findings of the current investigation are: (1) increasing trend of ovarian ectopic pregnancy; (2) cervico-corpal ectopic pregnancy in relation to prior uterine scar; and (3) heterotopic pregnancy in abdominal pregnancy.

The implantation of the gestational sac at extra-tubal ectopic sites may predispose these patients due to unknown gynecological factors. The association of abdominal and heterotopic pregnancy observed in this study warrants external validation.⁵ The increasing trend for ovarian ectopic pregnancy may be due in part to the increased use of the assisted reproductive technique.⁶

Key limitations included the inability to assess granularity in specific anatomical sites of abdominal and cervico-corpal ectopic implants due to coding schema. Accuracy of data was not assessed without actual medical record review. Despite these limitations, the results of this analysis call for further studies to determine whether there is a direct physiologic effect of the endometrial gestation on the implanting extra-endometrial gestation. Developing coding schemas for cervical, cesarean scar, and interstitial ectopic pregnancy is recommended due to clinical relevance.

CRediT author contributions: Conceptualization: K.M.; Data curation: R.S.M.; Formal analysis: K.M.; Funding acquisition: K.M.; Investigation: all authors; Methodology: K.M.; Project administration: K.M.; Resources: J.G.O.; Software: K.M., R.S.M.; Supervision: J.G.O.; Validation: K.M.; Visualization: K.M.; Writing - original draft: A.M.G., K.M.; Writing - review & editing: all authors.

Ensign Endowment for Gynecologic Cancer Research (K.M.). The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

The authors have no conflicts of interest.

The manuscript's corresponding author (K.M.) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained. The Nationwide Ambulatory Surgery Sample was a part of the Healthcare Cost and Utilization Project by the Agency for Healthcare Research and Quality is the source of the deidentified data used; and the program has not verified and is not responsible for the statistical validity of the data analysis or the conclusions derived by the study team.