Pregnancy Of Unknown Location Research Articles

24-hour vs 48-hour Beta-HCG Follow Up for Patients with Pregnancy of Unknown Location

24-hour vs 48-hour Beta-HCG Follow Up for Patients with Pregnancy of Unknown Location

Comparison of single- and double-dose methotrexate protocols for treatment of pregnancy of unknown location.

The use of various methotrexate (MTX) protocols for the treatment of ectopic pregnancy is well established. This study aimed to evaluate the efficacy of single- and double-dose MTX protocols for the treatment of pregnancy of unknown location (PUL). This retrospective study was conducted in the Department of Gynaecological Endocrinology, University Hospital, Krakow, Poland. Haemodynamically stable women with PUL were enrolled between January 2014 and September 2023. Demographics, gestational age and treatment outcomes were compared between women in the single-dose MTX group and women in the double-dose MTX group. The primary outcome was the success rate, measured as the number of women treated without surgical intervention. The secondary outcome was the number of days of MTX needed to achieve an appropriate decrease in beta-human chorionic gonadotrophin (β-hCG). Two hundred and eleven women (mean age 33±1.8years) with PUL were enrolled in the study, with an overall success rate of 89.1%. Single- and double-dose MTX protocols were found to have comparable treatment success rates (93% and 95%, respectively). Women with lower initial serum β-hCG (<2000mIU/ml) had higher treatment efficacy compared with women with higher initial serum β-hCG (96.5% vs 71.4%), regardless of protocol type. The length of hospital stay for the women treated with the single-dose MTX protocol was 1day shorter compared with that for the women treated with the double-dose MTX protocol. Single- and double-dose MTX protocols have comparable efficacy and safety, and should be equally considered in women with PUL with initial β-hCG<2000mIU/ml.

Diagnostic utility of clinicodemographic, biochemical and metabolite variables to identify viable pregnancies in a symptomatic cohort during early gestation

A significant number of pregnancies are lost in the first trimester and 1–2% are ectopic pregnancies (EPs). Early pregnancy loss in general can cause significant morbidity with bleeding or infection, while EPs are the leading cause of maternal mortality in the first trimester. Symptoms of pregnancy loss and EP are very similar (including pain and bleeding); however, these symptoms are also common in live normally sited pregnancies (LNSP). To date, no biomarkers have been identified to differentiate LNSP from pregnancies that will not progress beyond early gestation (non-viable or EPs), defined together as combined adverse outcomes (CAO). In this study, we present a novel machine learning pipeline to create prediction models that identify a composite biomarker to differentiate LNSP from CAO in symptomatic women. This prospective cohort study included 370 participants. A single blood sample was prospectively collected from participants on first emergency presentation prior to final clinical diagnosis of pregnancy outcome: LNSP, miscarriage, pregnancy of unknown location (PUL) or tubal EP (tEP). Miscarriage, PUL and tEP were grouped together into a CAO group. Human chorionic gonadotrophin β (β-hCG) and progesterone concentrations were measured in plasma. Serum samples were subjected to untargeted metabolomic profiling. The cohort was randomly split into train and validation data sets, with the train data set subjected to variable selection. Nine metabolite signals were identified as key discriminators of LNSP versus CAO. Random forest models were constructed using stable metabolite signals alone, or in combination with plasma hormone concentrations and demographic data. When comparing LNSP with CAO, a model with stable metabolite signals only demonstrated a modest predictive accuracy (0.68), which was comparable to a model of β-hCG and progesterone (0.71). The best model for LNSP prediction comprised stable metabolite signals and hormone concentrations (accuracy = 0.79). In conclusion, serum metabolite levels and biochemical markers from a single blood sample possess modest predictive utility in differentiating LNSP from CAO pregnancies upon first presentation, which is improved by variable selection and combination using machine learning. A diagnostic test to confirm LNSP and thus exclude pregnancies affecting maternal morbidity and potentially life-threatening outcomes would be invaluable in emergency situations.

Assessment of Pregnancy Desires for Patients With Pregnancy of Unknown Location Seen in the Emergency Department [ID 2683447

INTRODUCTION: Desire for pregnancy should be centered in all discussions surrounding pregnancy management, including management of pregnancy of unknown location (PUL). Little is known about the evaluation of pregnancy desires for patients presenting to the emergency department (ED) found to have PUL. METHODS: We performed a retrospective cohort study of patients presenting to a tertiary-care ED with a positive pregnancy test and previously unconfirmed intrauterine pregnancy in the first trimester between January 2020 and December 2022. We excluded patients with chief complaints regarding known intrauterine pregnancy. The primary outcome was documentation of pregnancy desire by the ED provider. The secondary outcome was assessment of pregnancy desiredness by consulting gynecologic providers. Chi-squared and Fisher exact tests assessed for demographic variables. Institutional review board approval was obtained. RESULTS: Four hundred ninety-seven patients were included. Overall, only 105 (21.1%) of all patients and 12 (13.5%) patients with PUL were asked about pregnancy desiredness by the ED provider. While not statistically significant, patients with PUL had the lowest rate of being asked their pregnancy desires, compared to patients with confirmed intrauterine pregnancy (22.7%), ongoing miscarriage (28.1%), or ectopic/adnexal pathology (20.0%) (P=.15). Of those asked, 11 patients (10.5%) reported the pregnancy was undesired and 7 (6.7%) were unsure. There were no significant associations between asking pregnancy desires and age, race, ethnicity, parity, insurance, and language. For patients added to the beta book and followed by gynecology, 59.3% of patients were asked about their pregnancy desires. CONCLUSION: This study highlights gaps in early pregnancy evaluation and counseling, with only one in five patients asked their pregnancy desires. Patients with adnexal pathology and PUL had among the lowest rates of counseling, compared to those with ongoing miscarriage. This research suggests a missed opportunity for comprehensive pregnancy options counseling and management in the ED and the potential for improvement of care for patients with undesired PUL.

24-Hour Compared With 48-Hour β-hCG Follow-up for Patients With Pregnancy of Unknown Location [ID 2683407

INTRODUCTION: Patients who are followed with a pregnancy of unknown location (PUL) are generally advised to return for repeat β-hCG level after 48 hours. This study compares the time to final diagnosis for patients who had repeat β-hCG levels 24 versus 48 hours after diagnosis of PUL. METHODS: This was a retrospective cohort study of patients diagnosed with PUL who were recommended to return at 24 versus 48 hours at a single site from 2021 to 2022. We reviewed charts for time to final diagnosis, demographic characteristics, pregnancy history, β-hCG levels, interventions, and whether the patient was lost to follow-up. We compared the time to final diagnosis using Kaplan–Meier curves and log-rank tests between the two cohorts. RESULTS: Over the two-year time period, 61 patients were eligible for inclusion, 18 of whom followed up at 24 hours and 43 of whom followed up at 48 hours. Most patients completed the recommended follow-up (94.4% 24-hour versus 83.7% 48-hour). The median time to final diagnosis was 2 days (interquartile range [IQR] 1–5 days) for the 24-hour cohort compared to 6 days (IQR 3–13) for the 48-hour cohort (P=.03). None of the 24-hour group was lost to follow-up compared to 11.6% (n=5) in the 48-hour group. CONCLUSION: We found the time to final diagnosis was shorter in the 24-hour group compared to the 48-hour group. Clinicians may consider 24-hour follow-up for patients at higher risk for ectopic pregnancy or to expedite the time to a final diagnosis.

Risk Factors Associated With Being Lost to Follow-up Among Patients With Pregnancy of Unknown Location [ID 2683399

INTRODUCTION: Managing pregnancy of unknown location (PUL) is a logistical challenge for obstetrician–gynecologists. Close follow-up is a key component of management to reduce the risk of a ruptured ectopic pregnancy. We examined factors that may put patients at increased risk of being lost to follow-up. METHODS: We performed a case–control study of patients presenting to our emergency room with a positive pregnancy test and without previously confirmed intrauterine pregnancy in the first trimester between January 2020 and December 2022. Patients with newly diagnosed PUL were added to a secure list for follow-up (“beta book”). We compared patients who were lost to follow-up, which was defined as after three failed attempts at contact made multiple days apart, with those who were not. Chi-square and Fisher exact assessed demographic exposures putting patients at risk of being lost to follow-up. RESULTS: One hundred nineteen patients had PUL and were added to the beta book. Overall, 15 (12.6%) of patients were lost to follow-up (cases) compared to 104 (87.4%) of patients who were not (controls). No associations were found between sociodemographic variables and risk of being lost to follow-up, including age (P=.15), parity (P=.59), insurance type (P=.81), primary language (P=.77), race (P=.26), and ethnicity (P=.80). Finally, lost to follow-up rates were similar among women enrolled and not enrolled in the institution’s app-based medical communication system (P=.75). CONCLUSION: In a state in which pregnancy-related care is available regardless of immigration status, we found no demographic associations with risk of being lost to follow-up. As 12% of people in this study were still lost to follow-up, qualitative interviews may be useful to better understand factors not captured in a retrospective chart review to improve safe and equitable care.

Diagnostic accuracy validation study of the M6 model without initial serum progesterone (M6NP) in triage of pregnancy of unknown location

ObjectivesThe M6 prediction model stratifies the risk of development of ectopic pregnancy (EP) for women with pregnancy of unknown location (PUL) into low risk or high risk, using human chorionic gonadotrophin (hCG) and progesterone levels at the initial visit to a gynaecological emergency room and hCG level at 48 h. This study evaluated a second model, the M6NP model, which does not include the progesterone level at the initial visit. The main aim of this study was to validate the diagnostic accuracy of the M6NP model in a population of French women. Study designBetween January and December 2021, all women with an hCG measurement from the gynaecological emergency department of a teaching hospital were screened for inclusion in this study. Women with a pregnancy location determined before or at the second visit were excluded. The diagnostic test was based on logistic regression of the M6NP model, with classification into two groups: high risk of EP (≥5%) and low risk of EP (<5%). The reference test was the final outcome based on clinical, biological and sonographic results: failed PUL (FPUL), intrauterine pregnancy (IUP) or EP. Diagnostic performance for risk prediction of EP, and also IUP and FPUL, was calculated. ResultsIn total, 759 women with possible PUL were identified. After screening, 341 women with PUL were included in the main analysis. Of these, 186 (54.5%) were classified as low risk, including three (1.6%) with a final outcome of EP. The remaining 155 women with PUL were classified as high risk, of whom 60 (38.7%), 66 (42.8%) and 29 (18.7%) had a final outcome of FPUL, IUP and EP, respectively. Of the 32 women with PUL with a final outcome of EP, 29 (90.6%) were classified as high risk and three (9.4%) were classified as low risk. Therefore, the performance of the M6NP model to predict EP had a negative predictive value of 98.4%, a positive predictive value of 18.7%, sensitivity of 90.6% and specificity of 59.2%. If the prediction model had been used, it is estimated that 4.5 visits per patient could have been prevented. ConclusionThe M6NP model could be used safely in the French population for risk stratification of PUL. Its use in clinical practice should result in a substantial reduction in the number of visits to a gynaecological emergency room.

Updating M6 pregnancy of unknown location risk-prediction model including evaluation of clinical factors.

Ectopic pregnancy (EP) is a major high-risk outcome following a pregnancy of unknown location (PUL) classification. Biochemical markers are used to triage PUL as high vs low risk to guide appropriate follow-up. The M6 model is currently the best risk-prediction model. We aimed to update the M6 model and evaluate whether performance can be improved by including clinical factors. This prospective cohort study recruited consecutive PUL between January 2015 and January 2017 at eight units (Phase 1), with two centers continuing recruitment between January 2017 and March 2021 (Phase 2). Serum samples were collected routinely and sent for β-human chorionic gonadotropin (β-hCG) and progesterone measurement. Clinical factors recorded were maternal age, pain score, bleeding score and history of EP. Based on transvaginal ultrasonography and/or biochemical confirmation during follow-up, PUL were classified subsequently as failed PUL (FPUL), intrauterine pregnancy (IUP) or EP (including persistent PUL (PPUL)). The M6 models with (M6P ) and without (M6NP ) progesterone were refitted and extended with clinical factors. Model validation was performed using internal-external cross-validation (IECV) (Phase 1) and temporal external validation (EV) (Phase 2). Missing values were handled using multiple imputation. Overall, 5473 PUL were recruited over both phases. A total of 709 PUL were excluded because maternal age was < 16 years or initial β-hCG was ≤ 25 IU/L, leaving 4764 (87%) PUL for analysis (2894 in Phase 1 and 1870 in Phase 2). For the refitted M6P model, the area under the receiver-operating-characteristics curve (AUC) for EP/PPUL vs IUP/FPUL was 0.89 for IECV and 0.84-0.88 for EV, with respective sensitivities of 94% and 92-93%. For the refitted M6NP model, the AUCs were 0.85 for IECV and 0.82-0.86 for EV, with respective sensitivities of 92% and 93-94%. Calibration performance was good overall, but with heterogeneity between centers. Net Benefit confirmed clinical utility. The change in AUC when M6P was extended to include maternal age, bleeding score and history of EP was between -0.02 and 0.01, depending on center and phase. The corresponding change in AUC when M6NP was extended was between -0.01 and 0.03. At the 5% threshold to define high risk of EP/PPUL, extending M6P altered sensitivity by -0.02 to -0.01, specificity by0.03 to 0.04 and Net Benefit by -0.005 to 0.006. Extending M6NP altered sensitivity by -0.03 to -0.01, specificity by 0.05 to 0.07 and Net Benefit by -0.005 to 0.006. The updated M6 model offers accurate diagnostic performance, with excellent sensitivity for EP. Adding clinical factors to the model improved performance in some centers, especially when progesterone levels were not suitable or unavailable. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Cost-effectiveness analysis of expectant vs active management for treatment of persistent pregnancies of unknown location

BackgroundPersistent pregnancies of unknown location (PUL) are defined by abnormally trending serum human chorionic gonadotropin with nondiagnostic ultrasound. There is no consensus on optimal management. ObjectiveThis study was designed to assess the cost-effectiveness between three primary management strategies for persistent pregnancies of unknown location: (1) expectant management, (2) empirical two-dose methotrexate, (3) uterine evacuation followed by methotrexate, if indicated. Study DesignWe conducted a prospective economic evaluation performed concurrently with the Expectant versus Active Management for Treatment of Persistent Pregnancies of Unknown Location (ACT or NOT) multicenter randomized trial conducted from July 2014 to June 2019. Participants were randomized 1:1:1 to expectant management, two-dose methotrexate, or uterine evacuation. The analysis was from the healthcare sector perspective with a 6-week time horizon following randomization. Costs were expressed in 2018 U.S. dollars. Effectiveness was measured in quality-adjusted life-years (QALYs) and the rate of salpingectomy. Incremental cost-effectiveness ratios (ICERs) and cost-effectiveness acceptability curves were generated. Sensitivity analyses were performed to assess the robustness of the analysis. ResultsMethotrexate had the lowest mean cost, $875, followed by expectant management $1085, and uterine evacuation $1902 (p=0.001). Expectant management had the highest mean QALY (0.1043) followed by methotrexate (0.1031) and uterine evacuation (0.0992) (p=0.0001). Salpingectomy rate was higher for expectant management compared to methotrexate (9.4% vs 1.2%; p=0.02) and expectant management compared to uterine evacuation (9.4% vs 8.1%; p=0.04). Uterine evacuation, with highest costs and lowest QALYs, was dominated by both expectant management and methotrexate. In the base case analysis, expectant management was not cost-effective compared to methotrexate at a willingness-to-pay of $150,000/QALY given an ICER of $175,083/QALY gained (95% CI, -$1,666,825-2,676,375). Threshold analysis demonstrated methotrexate administration would have to cost $214 (an increase of $16 or 8%) to favor expectant management. Expectant management would also be favorable in lower risk patient populations with rates of laparoscopic surgical management for ectopic pregnancy not exceeding 4% of pregnancies of unknown location. Based on the cost-effectiveness acceptability curves, the probability expectant management was cost-effective compared to methotrexate at a willingness-to-pay of $150,000/QALY gained was 50%. Results were dependent on the cost of surgical intervention, and the expected rate of methotrexate failure. ConclusionManagement of pregnancies of unknown location with a two-dose methotrexate protocol may be cost-effective compared to expectant management and uterine evacuation. While uterine evacuation was dominated, expectant management versus methotrexate results were sensitive to modest changes in treatment costs of both methotrexate and surgical management.

Safety of methotrexate administration in women with pregnancy of unknown location deemed to have high risk of ectopic pregnancy.

This study evaluates the safety of current guidelines on methotrexate (MTX) administration in women with pregnancy of unknown location (PUL) who are considered to have high risk of underlying ectopic pregnancy (EP) and to investigate whether this would result in inadvertent exposure of MTX to viable intra-uterine pregnancy (IUP). A retrospective observational study was conducted on clinically stable women who were classified PUL at Early Pregnancy Unit, Nepean Hospital, between 2007 and 2021. PUL is defined as when a woman presents with a positive pregnancy test but has no signs of IUP or EP on the transvaginal ultrasound (TVS). If patients with a PUL behave biochemically like an EP but the location is not confirmed on ultrasound, these women are eligible for MTX to minimize the risk of subsequent tubal rupture.Criteria discussed in the guidelines of American College of Obstetricians and Gynaecologists (ACOG),American Society for Reproductive Medicine (ASRM),Royal College of Obstetricians & Gynaecologists(RCOG)and National Institute for Health Care Excellence (NICE)were applied to the collected PUL database. The number of patients eligible to receive MTX and the number of women with underlying viable IUP who would be inadvertently given MTX were calculated. A total of 816 consecutive women with PUL were reviewed, and 724 had complete data and were included in the final analysis. 6 patients were persistent PULs,and 718 fell among outcomes of 4 subgroups: viable IUP, non-viable IUP, EP, failed PUL. According to the ACOG, ASRM, RCOG and NICE, the rate of possible MTX administration among patients with a PUL is 2.76%, 4.56%, 0.41% and 35.36%, respectively. However, no single persistent-PUL would have received MTX according to the above protocols, and majority of the MTX treatment were unnecessary because those patients were classified as NVIUP or FPUL later. More importantly, ACOG and ASRM could theoretically result in inadvertent MTX administration to women with an underlying IVUP at rates of 4.1/1000 (3/724). Current guidelines used to predict high risk of EP among PUL population are not safe enough to avoid inadvertent MTX administration to women with an underlying viable IUP.These guidelines need to be wisely used to ensure that no wanted pregnancy is exposed to MTX. Women with PULs should be carefully monitored and MTX should be used with judicious care when the location of pregnancy is yet to be confirmed. This article is protected by copyright. All rights reserved.

Development of a single-visit protocol for the management of pregnancy of unknown location following in vitro fertilization: a retrospective study.

Can women with pregnancy of unknown location (PUL) following in vitro fertilization (IVF) be risk-stratified regarding the subsequent need for medical intervention, based on their demographic characteristics and the results of serum biochemistry at the initial visit? The ratio of serum hCG to number of days from conception (hCG/C) or the initial serum hCG level at ≥5 weeks' gestation could be used to estimate the risk of women presenting with PUL following IVF and needing medical intervention during their follow-up. In women with uncertain conception dates presenting with PUL, a single serum hCG measurement cannot be used to predict the final pregnancy outcomes, thus, serial levels are mandatory to establish a correct diagnosis. Serum progesterone levels can help to risk-stratify women at their initial visit but are not accurate in those taking progesterone supplementation, such as women pregnant following IVF. This was a retrospective study carried out at two specialist early pregnancy assessment units between May 2008 and January 2021. A total of 224 women met the criteria for inclusion, but 14 women did not complete the follow-up and were excluded from the study. We selected women who had an IVF pregnancy and presented with PUL at ≥5 weeks' gestation. A total of 30/210 (14.0%, 95% CI 9.9-19.8) women initially diagnosed with PUL required surgical intervention. The hCG/C was significantly higher in the group of women requiring an intervention compared to those who did not (P = 0.003), with an odds ratio of 3.65 (95% CI 1.49-8.89, P = 0.004). A hCG/C <4.0 was associated with a 1.9% risk of intervention, which accounted for 25.7% of the study population. A similar result was obtained by substituting hCG/C <4.0 with an initial hCG level <100 IU/l, which was associated with 2.0% risk of intervention, and accounted for 23.8% of the study population (P > 0.05). A limitation of our study is that it is retrospective in nature, and as such, we were reliant on existing data. A previous study in women with PUL after spontaneous conception found that a 2% intervention rate was considered low enough to eliminate the need for close follow-up and serial blood tests. Using the same 2% cut-off, a quarter of women with PUL after IVF could also avoid attending for further visits and investigations. No external funding was required for this study. No conflicts of interest are required to be declared. N/A.

Primary Hepatic Ectopic Pregnancy: Diagnosis and Laparoscopic Management

To demonstrate and discuss a case of primary hepatic ectopic pregnancy and laparoscopic management. Case presentation with demonstration of surgical hepatic wedge resection. Tertiary referral center in Manchester, United Kingdom. A 33-year-old women gravida 13 para 2 with a body mass index of 55 kg/m2 and previous 2 cesarean sections and a laparoscopic cholecystectomy presented to the emergency services after a private ultrasound scan showing a pregnancy of unknown location and a serum human chorionic gonadotropin (hCG) of 18 336 IU/mL. A diagnostic laparoscopy was performed but fallopian tubes were normal with no signs of ectopic pregnancy seen. An abdominal ultrasound scan was performed but did not identify the ectopic pregnancy. Owing to worsening symptoms of pain and rising hCG levels, she underwent a further laparoscopy converted to laparotomy and a left salpingo-oophorectomy for suspected left ovarian pregnancy. However, serum hCG levels continued to rise after the surgery, reaching 36 960 IU/mL. An magnetic resonance imaging scan of her abdomen and pelvis was arranged that showed a 4 cm cystic lesion in the segment V of the liver. Further ultrasound correlation showed a hyperechoic lesion with echogenic components suspicious of an ectopic pregnancy with a fetal pole. Fetal heart action was not visualized. A multidisciplinary team approach was adopted with involvement of the hepatobiliary surgical team, and the option of medical management with methotrexate and surgical excision was considered. A decision was made for surgical excision based on the accessible location of the ectopic pregnancy on segment V and the more controlled and predictable outcome with surgical excision. A preoperative computed tomography scan confirmed the lesion in segment V of liver in keeping with liver capsular implantation of ectopic pregnancy (Video still 1). At laparoscopy the ectopic pregnancy was visualized on the inferior surface of liver close to the inferior margin with a band of overlying omental adhesion (Video still 2). The overlying omental adhesions were sealed and cut with advanced bipolar diathermy, keeping a safe margin from the ectopic pregnancy to minimize any bleeding. The liver capsule was then opened with monopolar diathermy, and the small segment of liver with the ectopic pregnancy was excised using a combination of Bowa-Lotus liver blade (Bowa Medical Ltd). Hemostasis was controlled using Floseal hemostatic matrix and applied pressure laparoscopically. Total operating time was 80 minutes with an estimated blood loss of 500 mL. The patient was discharged on day 3 postoperatively, and follow-up serum hCG excluded residual trophoblastic disease. On review of the clinical case, earlier imaging of the upper abdomen when confronted by a persistent pregnancy of unknown location with high levels of serum hCG would have prevented the second laparoscopy, laparotomy, and salpingo-oophorectomy. In similar cases, it would also help exclude poorly differentiated malignancies as a source of serum hCG. Only 27 cases of ectopic pregnancy on the liver have been identified in English literature since 1952, based on a MEDLINE and Embase enquiry and further review of all case reports by the authors to avoid duplicates. Estimated incidence of hepatic implantation is 1 in 15 000 pregnancies; 4 case reports of laparoscopic liver resection have been identified and another case managed by suction from the liver surface [1,2]. The key principle demonstrated is to resect the ectopic pregnancy with a safe margin of liver tissue and any adhesions to avoid catastrophic bleeding from direct handling of the ectopic pregnancy.

HCG trends after mifepristone and misoprostol for undesired pregnancy of unknown location

ObjectivesTo describe human chorionic gonadotropin (hCG) trends for patients with a pregnancy of unknown location (PUL) presenting for medication abortion by management strategy and outcome. Study designThis retrospective cohort study included patients presenting for medication abortion with a PUL at ≤42 days gestation managed with either (1) immediate mifepristone with serial hCG follow-up (same-day-start) or (2) hCG testing every 48 to 72 hours ± ultrasonography to confirm pregnancy location followed by treatment (delay-for-diagnosis). The primary outcome was percent hCG change over time between presentation and diagnosis, summarized using a multivariate regression model. ResultsOf the 55 same-day-start patients, none were treated for ectopic. The eight who eventually required suction curettage had median hCG percent changes (interquartile range) on days 3, 4, and 5 of +57% (−14 to 127; n = 2), +292% (226–353; n = 4), and +392% (n = 1), while the 41 successful medication abortions had declines of −64% (n = 1), −65% (−75 to −27; n = 17), and −77% (−85 to −68; n = 13). Of the 380 delay-for-diagnosis patients, the 30 ectopic pregnancies had day 3, 4, and 5 changes of +38% (−17 to 56; n = 14), +50% (17–71; n = 7), and +115% (87–177; n = 4). None of the ectopic pregnancies declined ≥50% by days 3 to 5. The hCG trend for ectopic pregnancies differed from successful medication abortions (p < 0.01), but not medication abortions with retained intrauterine pregnancies (p = 0.41). ConclusionsSerum hCG trends can help differentiate ectopic pregnancy from successful medication abortion, but cannot distinguish between ectopic and retained intrauterine pregnancy. ImplicationsSerial serum hCG testing is effective for confirming successful medication abortion and identifying patients requiring further follow-up among patients undergoing medication abortion for an undesired PUL.

Ethics, Abortion Access, and Emergency Care Post-Dobbs: The Gray Areas.

Clinical management of emergency pregnancy care, such as ectopic pregnancy or heavy bleeding with pregnancy of unknown location, includes upholding legal and ethical standards. For health care providers unwilling to provide evidence-based life-saving abortion care due to personal beliefs, clear guidance dictates disclosure of these limitations to the patient and colleagues, followed by immediate referral for appropriate care. However, this decision-making pathway may not be engaged due to a variety of factors: providers' beliefs preclude adherence to referral responsibilities, political discourse confuses patients as to their options and rights, and a constantly changing state and national legal landscape leads providers to question their ability to practice to their full scope of clinical care. Although this disruption of evidence-based standard of care existed pre-Dobbs, the moral disorder is now heightened. This Clinical Rounds highlights a patient vignette describing the risks of abortion restrictions for patients and providers alike, particularly when an individual provider's concerns for violating institutional guidelines sets a precedent for nursing response and forecloses on collaborative input or ethics consultation. The history of physician-only abortion exceptionalism and exclusion of nurses and midwives despite a significant history of nurses and midwives in abortion care grounds an argument for focusing on the impact of unethical and substandard care on the interprofessional care team leading to moral distress and negative patient outcomes. Patient-centered models of care, such as frameworks common in nursing and midwifery, offer opportunities to consider how all providers practicing to their full scope in interprofessional and collaborative ways, such as in emergency rooms and labor departments, might mitigate obstructions to abortion care that risk pregnant people's lives.

Ambulatory human chorionic gonadotrophin (hCG) testing: a verification of two hCG point of care devices.

Quantitative human chorionic gonadotropin (hCG) measurements are used to manage women classified with a pregnancy of unknown location (PUL). Two point of care testing (POCT) devices that quantify hCG are commercially available. We verified the i-STAT 1 (Abbott) and the AQT 90 FLEX (Radiometer) prior to use in PUL triage. Tests for precision, external quality assurance (EQA), correlation, hook effect and recovery were undertaken alongside a POCT usability assessment during this prospective multi-center verification. Coefficients of variation ranged between 4.0 and 5.1 % for the three i-STAT 1 internal quality control (IQC) solutions and between 6.8 and 7.3 % for the two AQT IQC solutions. Symmetric differences in POCT EQA results when compared with laboratory and EQA stock values ranged between 3.2 and 24.5 % for the i-STAT 1 and between 3.3 and 36.9 % for the AQT. Correlation coefficients (i-STAT 1: 0.96, AQT: 0.99) and goodness of fit curves (i-STAT 1: 0.92, AQT: 0.99) were excellent when using suitable whole blood samples. An hCG hook effect was noted with the i-STAT 1 between 572,194 and 799,089 IU/L, lower than the hook effect noted with the AQT, which was between 799,089 and 1,619,309 IU/L. When hematocrit concentration was considered in sample types validated for use with each device, hCG recovery was 108 % with the i-STAT 1 and 98 % with the AQT. The i-STAT 1 scored lower on usability overall (90/130) than the AQT (121/130, p<0.001, Mann-Whitney). Both hCG POCT devices were verified for use in clinical practice. Practical factors must also be considered when choosing which device to use in each unit.

Beta-human chorionic gonadotrophin point of care testing for the management of pregnancy of unknown location

Research questionDoes a commercially available quantitative beta-human chorionic gonadotrophin (BHCG) point of care testing (POCT) device improve workflow management in early pregnancy by performing comparably to gold standard laboratory methods, and is the performance of a validated pregnancy of unknown location (PUL) triage strategy maintained using POCT BHCG results? DesignWomen classified with a PUL between 2018 and 2021 at three early pregnancy units were included. The linear relationship of untreated whole-blood POCT and serum laboratory BHCG values was defined using coefficients and regression. Paired serial BHCG values were then incorporated into the validated M6 multinomial logistic regression model to stratify the PUL as at high risk or at low risk of clinical complications. The sensitivity and negative predictive value were assessed. The timings required for equivocal POCT and laboratory care pathways were compared. ResultsA total of 462 PUL were included. The discrepancy between 571 laboratory and POCT BHCG values was –5.2% (–6.2 IU/l), with a correlation coefficient of 0.96. The 133 PUL with paired 0 and 48 h BHCG values were compared using the M6 model. The sensitivity for high-risk outcomes (96.2%) and negative predictive values (98.5%) was excellent for both. Sample receipt and laboratory processing took 135 min (421 timings), compared with 12 min (91 timings) when using POCT (P < 0.0001). ConclusionsPOCT BHCG values correlated well with laboratory testing measurements. The M6 model retained its performance when using POCT BHCG values. Using the model with POCT may improve workflow and patient care without compromising on effective PUL triage.

OC04.03: Does a negative urine pregnancy test exclude ectopic pregnancy in women classified with a pregnancy of unknown location?

OC04.03: Does a negative urine pregnancy test exclude ectopic pregnancy in women classified with a pregnancy of unknown location?

OC04.07: The significance of intracavity fluid (or pseudo‐sac) in women classified with a pregnancy of unknown location

OC04.07: The significance of intracavity fluid (or pseudo‐sac) in women classified with a pregnancy of unknown location

Four-dimensional ultrasound guided embryo transfers improve live birth rates when compared to the clinical touch technique: a randomised controlled trial

Most aspects of in-vitro fertilisation (IVF) have changed dramatically since introduction, but embryo transfer (ET) technique remains largely unaltered. We aimed to determine whether four-dimensional ultrasound guided embryo transfers (4D UGET) could improve pregnancy rates when compared with clinical touch technique (CTT). This was a single centre open labelled randomised controlled trial in a tertiary fertility centre in the UK. 320 women were randomised on the day of single ET. The primary outcome was clinical pregnancy rate (CPR), secondary outcomes included live birth rate (LBR), biochemical pregnancy rate (BPR), miscarriage, pregnancy of unknown location (PUL) and ectopic pregnancy. 4D-UGET resulted in significantly higher CPR [50% vs 36% p = 0.02, OR 1.78 (1.12–2.84)] and LBR [41% vs 28%, p = 0.02, OR 1.77 (1.09–2.87)] when compared to CTT technique. Miscarriage (p = 0.49), PUL (p = 0.14) and ectopic pregnancy (p = 0.96) were similar between the two groups. LBR, from this trial, are significantly higher than the current UK average (41% vs 24%). 4D UGET allows for superior imaging of the uterine cavity, whilst tailoring the embryo deposition point specifically to the patient. Further RCTs are required to determine if these results can be replicated in other units and whether 4D UGET is superior to 2D UGET.

Medication Abortion and Uterine Aspiration for Undesired Pregnancy of Unknown Location: A Retrospective Cohort Study

ABSTRACT Uncertain diagnosis can complicate the evaluation and treatment of patients presenting for undesired pregnancy termination at early gestational ages. Pregnant patients with no ultrasonography-identifiable pregnancy location receive classification of pregnancy of unknown location (PUL). Until receiving a definitive intrauterine pregnancy (IUP), ectopic pregnancy, or early pregnancy loss diagnosis, these patients are often managed expectantly with serial serum human chorionic gonadotropin (hCG) measurements and ultrasonography. Immediate treatment of undesired PUL with low-risk for ectopic pregnancy can be performed in ways that minimize the risk. This retrospective cohort study reviewed outcomes of pregnancies for PUL-diagnosed patients presenting at Planned Parenthood in Minnesota, North Dakota, and South Dakota to receive induced abortions between July 1, 2016, and December 31, 2019. Care of patients with PUL included assessment of health history, counseling, and ectopic pregnancy precaution reviews. Clinicians then proceeded to triage patients into low- and high-risk groups based on transvaginal ultrasonography findings and patient symptoms. For PUL patients deemed low risk for ectopic pregnancy, the choices of expectant management or induced abortion were given. Patients proceeding with induced abortions then proceeded with uterine aspiration or medication abortion. The primary objective compared the diagnosis of pregnancy location to time for 3 groups, which included the groups of patients choosing immediate treatment (via uterine aspiration or medical management), and the group of patients who initially chose expectant management (delay for diagnosis). Time to diagnosis, as measured in days, was recorded from initial PUL diagnosis until final pregnancy location diagnosis. A spontaneous decline of serum hCG after 48–72 hours in the delay-for-diagnosis group was recorded as a spontaneously resolved PUL consistent with spontaneous abortion. Incidence of ectopic pregnancies, complications such as transfusion-requiring hemorrhages, and failure to adhere with follow-up guidelines (greater than 60 days from PUL diagnosis without clinical contact and/or a pregnancy diagnosis) were also recorded. From a total of 19,151 abortion counters across the study period, 2.9% of patients (553) were diagnosed with PUL. High-risk diagnoses were given to 9.4% of patients (52), based on concerns from symptoms and ultrasounds (27 of these had ectopic pregnancies [51.9%]). Low-risk diagnoses were given to 90.6% of the remaining patients (501), who were given a choice of management. When compared with expectant management, results indicated that low-risk patients with undesired PUL experienced fewer days to diagnosis with immediate treatment by uterine aspiration (and a similar time frame to diagnosis with abortion via medication). For uterine aspiration, abortion treatment using simultaneous serial hCG trending was effective. Although this study lacked statistical power to detect differences between groups, there was an overall low complication rate (0.2%). Strengths of the study include the exclusive focus on true-PUL patients, as well as the large sample size. Generalizability was potentially increased by the fact that various physicians triaged PUL patients in the study setting without increases in complications. A weakness of the study was that even with a 60-day follow-up window, the 27% follow-up nonadherence rate was higher than the 16% of Goldberg et al. In addition, the retrospective nature of the study was also a weakness. Finally, given the inability to observe direct comparison for efficacy of delayed medication versus immediate abortion due to higher rates of spontaneous abortion in the delay-for-diagnosis group, the outcomes of the study are limited by small numbers. This study shows that proceeding with an induced abortion in patients with PUL and undesired pregnancy are effective and safe as long as a plan for close follow-up with hCG is in place.