Preliminary findings on the experiences of care for women who suffered early pregnancy losses during the COVID-19 pandemic: a qualitative study.

BACKGROUND: Women who suffer an early pregnancy loss require specific clinical care, aftercare, and ongoing support. In the UK, the clinical management of early pregnancy complications, including loss is provided mainly through specialist Early Pregnancy Assessment Units. The COVID-19 pandemic fundamentally changed the way in which maternity and gynaecological care was delivered, as health systems moved to rapidly reconfigure and re-organise services, aiming to reduce the risk and spread of SARS-CoV-2 infection. PUDDLES is an international collaboration investigating the pandemic's impact on care for people who suffered a perinatal bereavement. Presented here are initial qualitative findings undertaken with UK-based women who suffered early pregnancy losses during the pandemic, about how they navigated the healthcare system and its restrictions, and how they were supported. METHODS: In-keeping with a qualitative research design, in-depth semi-structured interviews were undertaken with an opportunity sample of women (N = 32) who suffered any early pregnancy loss during the COVID-19 pandemic. Data were analysed using a template analysis to understand women's access to services, care, and networks of support, during the pandemic following their pregnancy loss. The thematic template was based on findings from parents who had suffered a late-miscarriage, stillbirth, or neonatal death in the UK, during the pandemic. RESULTS: All women had experienced reconfigured maternity and early pregnancy services. Data supported themes of: 1) COVID-19 Restrictions as Impractical & Impersonal; 2) Alone, with Only Staff to Support Them; 3) Reduction in Service Provision Leading to Perceived Devaluation in Care; and 4) Seeking Their Own Support. Results suggest access to early pregnancy loss services was reduced and pandemic-related restrictions were often impractical (i.e., restrictions added to burden of accessing or receiving care). Women often reported being isolated and, concerningly, aspects of early pregnancy loss services were reported as sub-optimal. CONCLUSIONS: These findings provide important insight for the recovery and rebuilding of health services in the post-pandemic period and help us prepare for providing a higher standard of care in the future and through any other health system shocks. Conclusions made can inform future policy and planning to ensure best possible support for women who experience early pregnancy loss.

Comparison of medication abortion outcomes at less than and greater than 6 weeks gestation.

OBJECTIVES: To compare outcomes and characteristics of two cohorts of patients: those receiving medication abortion (MAB) at ≤42 days gestation and those at 43 to 56 days gestation. STUDY DESIGN: We conducted a retrospective cohort study in 2022, comparing 142 patients accessing MAB at ≤42 days with 200 patients at 43 to 56 days. We sought to detect a 7% difference in MAB success with 80% power and alpha of 0.05. We assessed follow-up responses and unscheduled contacts with the health care system. RESULTS: Abortion success rates were similar between the ≤42-day and 43 to 56-day groups (94.3% vs 97%, p = 0.226). Those ≤42 days had more unscheduled office visits (13% vs 6%, p = 0.01) but no difference in phone calls or emergency room visits. More patients with successful MAB in the ≤42-day group answered that bleeding (11.7% vs 1.9%, p = 0.006) and cramping (10.5% vs 2.9%, p = 0.035) were not heavier or worse than a period and that they had no pregnancy symptoms prior to the abortion (15.8% vs 6.0%, p = 0.034). Patients ≤42 days gestation less often had a pretreatment ultrasound (48% vs 64%, p = 0.004). Patients without prior ultrasound more often needed uterine aspiration to complete the abortion (6.8% vs 2%, p = 0.027). CONCLUSIONS: Patients undergoing MAB at ≤42 days have similar success rates but more unscheduled office visits, and more ambiguous symptoms when using standardized questions for evaluating abortion success. Clinicians should adapt anticipatory guidance and counseling for this population. IMPLICATIONS: Access to very early abortion is increasingly relevant as legal restrictions on abortion increase. Earlier gestations may have different responses to standard follow-up questions despite a successful MAB and may have more interactions with the health care system.

Success of medication abortion with mifepristone followed by two doses of misoprostol in very early pregnancy.

OBJECTIVES: To compare medication abortion (MAB) success in very early pregnancy (VEP) with mifepristone followed by either one or two doses of misoprostol. STUDY DESIGN: We performed a retrospective cohort analysis of VEP MABs from July 1, 2021 to May 31, 2022 treated with mifepristone 200 mg oral followed by a single dose of misoprostol 800 mcg buccal 24 to 48 hours later and MABs from June 21, 2022 to October 31, 2022 treated with mifepristone 200 mg oral followed by two doses of misoprostol 800 mcg buccal spaced 4 hours apart, with first dose taken 24 to 48 hours after mifepristone. Serum BhCG was collected at the time of mifepristone treatment with additional BhCG collected 48 to 72 hours after misoprostol treatment in both groups. Success was defined as a BhCG decline of ≥50%. MAB failure was defined as ongoing, viable pregnancy determined by follow-up ultrasound or procedural intervention with aspiration. RESULTS: There were 423 patients in the single-dose misoprostol group and 262 patients in the two-dose misoprostol group. There were no significant differences between the two groups in baseline characteristics. In the single-dose group, 372 (87.9%) were treated successfully; in the two-dose group, 224 (85.5%) were treated successfully. There was no significant difference in MAB success between the groups (p = 0.73). CONCLUSIONS: The addition of a second dose of misoprostol does not improve the success of MAB in VEP. IMPLICATIONS: Additional research is needed to identify interventions to improve the success of MAB in VEP.

Systemic methotrexate (MTX) in early pregnancy: a retrospective study of a tertiary maternity hospital.

BACKGROUND: Methotrexate (MTX) is used in clinical practice as a medical treatment option in patients with early pregnancy complications like ectopic pregnancy. AIMS: To review systemic MTX therapy use in the first trimester of pregnancy in our hospital and to examine subsequent clinical outcomes. METHODS: Retrospective review of all women treated with systemic MTX in early pregnancy identified from electronic prescription records from 1 January 2018 to 31 December 2020 at Cork University Maternity Hospital, Ireland. Relevant data was transcribed from electronic health records. RESULTS: Indications for treatment were tubal ectopic pregnancy (70%, n = 51), persistent pregnancy of unknown location (22%, n = 16) and caesarean scar pregnancy (7%, n = 5). Treatment was successful in 88% (n = 44) of tubal ectopic pregnancies with 73% (n = 37) and 14% (n = 7) of women receiving a single dose and repeated doses, respectively. Only 8% (n = 4) of tubal ectopic pregnancies required emergency surgery for subsequent tubal rupture. In 93% (n = 15) of cases of persistent pregnancy of unknown location, treatment was successful with one patient requiring uterine evacuation. Women with caesarean scar pregnancy were treated with combined MTX and uterine evacuation without complication. CONCLUSIONS: The efficacy of medical treatment with systemic MTX for confirmed tubal ectopic pregnancy in our hospital is in line with national and international standards. Careful consideration should be given to treating caesarean scar pregnancy and persistent pregnancy of unknown location with systemic MTX. Systemic MTX use guided by clinicians specialised in early pregnancy complications and safe medication practices may improve treatment success and reduce adverse events.

Exploring Reasons for Loss to Follow-up in Pregnancy of Unknown Location: A Mixed-Methods Study.

Objective: To quantify proportions of loss to follow-up in patients presenting with a pregnancy of unknown location and explore patients' perspectives on follow-up for pregnancy of unknown location. A pregnancy of unknown location is a scenario in which a patient has a positive pregnancy test but the pregnancy is not visualized on transvaginal ultrasound. Study Design: We conducted a retrospective cohort study of patients with pregnancy of unknown location who presented to an urban academic emergency department or complex family planning outpatient office. We sought to calculate the proportion of patients lost to follow-up, defined as inability to contact the patient within 2 weeks. We then conducted focus groups of patients diagnosed with a pregnancy of unknown location. We used thematic analysis to identify themes related to follow-up. Results: We reviewed 464 charts of patients diagnosed with pregnancy of unknown location. The median age in this cohort was 27 with most patients identifying as Black (80%, n = 370) and using public insurance (67%, n = 315). When looking at loss to follow-up rates, Black patients experienced loss to follow-up (20%, n = 72) more often than White patients (4%, n = 2; p = 0.003). Focus group participants had a mean age of 31.8+/-4.8, and the majority were of Black race (n = 16, 72.7%). Participants identified barriers to follow-up including the long duration of management, general inconvenience, and poor communication with their health care team. Participants felt a burden of responsibility to learn about their condition and to self-advocate for their follow-up and communication of results. Conclusions: These data indicate that Black patients are more likely to experience loss to follow-up compared with White patients during monitoring for pregnancy of unknown location. Patients identified many barriers to follow-up and felt that successful follow-up required substantial self-efficacy.

Conventional and modern markers of pregnancy of unknown location: Update and narrative review.

Pregnancy of unknown location (PUL) is a temporary pathologic or physiologic phenomenon of early pregnancy that requires follow up to determine the final pregnancy outcome. Evidence indicated that PUL patients suffer a remarkably higher rate of adverse pregnancy outcomes, represented by ectopic gestation and early pregnancy loss, than the general population. In the past few decades, discussion about PUL has never stopped, and a variety of markers have been widely investigated for the early and accurate evaluation of PUL, including serum biomarkers, ultrasound imaging features, multivariate analysis, and the diagnosis of ectopic pregnancy based on risk stratification. So far, machine learning (ML) methods represented by M4 and M6 logistic regression have gained a level of recognition and are continually improving. Nevertheless, the heterogeneity of PUL markers, mainly caused by the limited sample size, the differences in population and technical maturity, etc., have hampered the management of PUL. With the advancement of multidisciplinary integration and cutting-edge technologies (e.g. artificial intelligence, prediction model development, and telemedicine), novel markers, and strategies for the management of PUL are expected to be developed. In this review, we summarize both conventional and novel markers (represented by artificial intelligence) for PUL assessment and management, investigate their advancements, limitations and challenges, and propose insights on future research direction and clinical application.

The predictors of successful methotrexate treatment of tubal ectopic pregnancy.

BACKGROUND: The pre-treatment characteristics of the patient and ectopic pregnancy to determine the patients who are likely to successfully respond to methotrexate (MTX) therapy remain controversial. This study investigated the outcomes of ectopic pregnancy after one and two MTX doses and their independent predictors. METHODS: Retrospective cross-sectional study of women who consented to MTX treatment in 2017-2018 at our institution (N = 317). Of these, patients with Caesarean scar pregnancies were excluded because they require different treatment protocols (n = 25). All patients were treated according to our institution's protocol based on international guidelines and standardised across the three hospitals included in the current study. We retrieved patients' demographics, laboratory, ultrasonography, and clinical characteristics from our hospital database. Serum ß-human chorionic gonadotropin (ß-hCG) was measured using electrochemiluminescence immunoassay; ectopic pregnancy was diagnosed using ultrasonography (transvaginal probe). RESULTS: Two ninety-two patients were included in the current analysis. Age, pre-treatment ß-hCG levels, sonographic presence of yolk sac, presence of foetal cardiac activity, and pelvic pain were significantly different between patients with successful and unsuccessful outcomes. Younger age (adjusted odds ratio [aOR] 2.33, 95% confidence interval (CI) 1.16-4.66, p = .017), no pelvic pain (aOR 2.65, 95%CI 1.03-6.83, p = .043), lower initial ß-hCG level (aOR 1.32, 95%CI 1.08-1.59, p = .005), and absence of foetal cardiac activity (aOR 12.63; 95% CI 1.04-153.6; p = .047) were independently associated with success. Treatment failure odds were >2 folds higher for each 10-year age increase (p = .017), 32% higher for each 1000 IU/L increase in initial ß-hCG level (p = .005), and >2 folds higher in presence of pelvic pain (p = .043). CONCLUSIONS: MTX is effective in most patients, averting invasive surgery, which might affect fertility. Pre-treatment ß-hCG levels, age, pelvic pain, and foetal cardiac activity was independently associated with outcomes. Research should assess the relationship between the ectopic pregnancy size and treatment outcomes and refine ß-hCG titres where treatment would be ineffective.

Ectopic pregnancy is a pregnancy that occurs outside the uterus. It needs to be identified and treated quickly to prevent serious health complications. Ectopic pregnancies can be treated surgically or medically using a drug called methotrexate. Medical treatment of ectopic pregnancy is not always successful. Identifying the factors that predict the failure of medical treatment helps patients and doctors to choose more accurately between surgical and medical treatment options.A total of 292 women who received methotrexate for ectopic pregnancy and the factors that influence the outcomes of treatment were examined, 39 patients had treatment failure and required surgery. Older age, higher initial levels of ß-human chorionic gonadotropin (ß-hCG) hormone, the presence of pelvic pain, and foetal cardiac activity had increased risk of treatment failure. In the future, research could consider the relationship between the size of the ectopic pregnancy and the treatment outcomes and refine the ß-hCG level cut-off for better treatment effects.

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

OBJECTIVE: 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). STUDY DESIGN: 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 (ß-hCG). RESULTS: Two hundred and eleven women (mean age 33 ± 1.8 years) 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 ß-hCG (<2000 mIU/ml) had higher treatment efficacy compared with women with higher initial serum ß-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 1 day shorter compared with that for the women treated with the double-dose MTX protocol. CONCLUSION: Single- and double-dose MTX protocols have comparable efficacy and safety, and should be equally considered in women with PUL with initial ß-hCG < 2000 mIU/ml.

Medical management of early pregnancy loss with mifepristone and misoprostol in emergency departments compared to a Complex Family Planning office: Implementation of a COVID-19 institutional policy change.

OBJECTIVES: To evaluate the implementation of mifepristone and misoprostol for medical management of early pregnancy loss (EPL) in emergency departments (EDs) by comparing efficacy, complication, and follow-up rates for patients treated in EDs to the Complex Family Planning (CFP) outpatient office. STUDY DESIGN: In COVID-19's first wave, we expanded medical management of EPL to our EDs. This retrospective study evaluated 72 patients receiving mifepristone and misoprostol for EPL from April 1, 2020 to March 31, 2021, comparing treatment success, safety outcomes, and follow-up rates by location. RESULTS: Thirty-three (46%) patients received care in the ED and 39 (54%) at CFP. Treatment success was lower in EDs (23, 70%) compared to CFP (34, 87%), but after adjusting for insurance status and pregnancy type (miscarriage, uncertain viability, unknown location), this was not significant: adjusted odds ratio 0.48 (95% CI 0.13-1.81). More ED patients underwent emergent interventions (3 vs 0) including two emergent uterine aspirations, one uterine artery embolization, and two blood transfusions. Two cases were attributed to misdiagnosis (cesarean scar and cervical ectopic pregnancies interpreted as incomplete miscarriages) and one to guideline nonadherence. No complications occurred in the CFP group. Follow-up rates were over 80% in both groups. More ED patients engaged in telehealth follow-up (67% vs 18%, p ≤ 0.0001). CONCLUSIONS: In this small sample, we observed a trend toward less successful treatment in the ED compared to the CFP office. Both correctly making uncommon diagnoses and adhering to new guidelines presented implementation challenges. IMPLICATIONS: Implementing mifepristone and misoprostol for EPL in our EDs achieved lower rates of pregnancy resolution compared to outpatient management. Complex uncommon diagnoses and implementing new care pathways in EDs may have contributed to complications and highlighted opportunities for improvement. Additional studies are needed to further quantify safety outcomes for EPL management in EDs.

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

BACKGROUND: Persistent pregnancies of unknown location are defined by abnormally trending serum human chorionic gonadotropin with nondiagnostic ultrasound. There is no consensus on optimal management. OBJECTIVE: This study aimed to assess the cost-effectiveness of 3 primary management strategies for persistent pregnancies of unknown location: (1) expectant management, (2) empirical 2-dose methotrexate, and (3) uterine evacuation followed by methotrexate, if indicated. STUDY DESIGN: This was a prospective economic evaluation performed concurrently with the Expectant versus Active Management for Treatment of Persistent Pregnancies of Unknown Location multicenter randomized trial that was conducted from July 2014 to June 2019. Participants were randomized 1:1:1 to expectant management, 2-dose methotrexate, or uterine evacuation. The analysis was from the healthcare sector perspective with a 6-week time horizon after randomization. Costs were expressed in 2018 US dollars. Effectiveness was measured in quality-adjusted life years and the rate of salpingectomy. Incremental cost-effectiveness ratios and cost-effectiveness acceptability curves were generated. Sensitivity analyses were performed to assess the robustness of the analysis. RESULTS: Methotrexate had the lowest mean cost ($875), followed by expectant management ($1085) and uterine evacuation ($1902) (P=.001). Expectant management had the highest mean quality-adjusted life years (0.1043), followed by methotrexate (0.1031) and uterine evacuation (0.0992) (P=.0001). The salpingectomy rate was higher for expectant management than for methotrexate (9.4% vs 1.2%, respectively; P=.02) and for expectant management than for uterine evacuation (9.4% vs 8.1%, respectively; P=.04). Uterine evacuation, with the highest costs and the lowest quality-adjusted life years, was dominated by both expectant management and methotrexate. In the base case analysis, expectant management was not cost-effective compared with methotrexate at a willingness to pay of $150,000 per quality-adjusted life year given an incremental cost-effectiveness ratio of $175,083 per quality-adjusted life year gained (95% confidence interval, -$1,666,825 to $2,676,375). Threshold analysis demonstrated that methotrexate administration would have to cost $214 (an increase of $16 or 8%) to favor expectant management. Moreover, expectant management would 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 of expectant management being cost-effective compared with methotrexate at a willingness to pay of $150,000 per quality-adjusted life year gained was 50%. The results were dependent on the cost of surgical intervention and the expected rate of methotrexate failure. CONCLUSION: The management of pregnancies of unknown location with a 2-dose methotrexate protocol may be cost-effective compared with expectant management and uterine evacuation. Although uterine evacuation was dominated, expectant management vs methotrexate results were sensitive to modest changes in treatment costs of both methotrexate and surgical management.

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

OBJECTIVES: The 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 DESIGN: Between 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. RESULTS: In 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. CONCLUSION: The 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.

Safety of methotrexate administration in women with pregnancy of unknown location at high risk of ectopic pregnancy.

OBJECTIVES: To evaluate the safety of current guidelines on methotrexate (MTX) administration in women with pregnancy of unknown location (PUL) who are considered to have a high risk of underlying ectopic pregnancy (EP), and to investigate whether implementation of these guidelines would result in inadvertent exposure to MTX of viable intrauterine pregnancies (IUPs). METHODS: This was a retrospective observational study of consecutive clinically stable women who were classified with PUL at the early pregnancy unit of Nepean Hospital, Sydney, Australia, between 2007 and 2021. PUL was defined as a positive pregnancy test in the absence of signs of IUP or EP on transvaginal ultrasound. Patients with a PUL that behaved biochemically like an EP, but for which the location of pregnancy was not confirmed on ultrasound, were eligible for MTX to minimize the risk of subsequent tubal rupture. Criteria discussed in the guidelines of the American College of Obstetricians and Gynecologists (ACOG), American Society for Reproductive Medicine (ASRM), Royal College of Obstetricians and Gynaecologists (RCOG) and National Institute for Health and Care Excellence (NICE) were applied to the PUL database. The number of patients eligible to receive MTX and the number with an underlying viable IUP who would be inadvertently prescribed MTX were calculated. RESULTS: A total of 816 women with PUL were reviewed, of whom 724 had complete data and were included in the final analysis. Six patients had persistent PUL and the remaining 718 had a diagnosis of viable IUP, non-viable IUP, EP or failed PUL. According to the ACOG, ASRM, RCOG and NICE guidelines, the rate of MTX administration among patients with PUL would have been 2.76%, 4.56%, 0.41% and 35.36%, respectively. However, no persistent PUL would have received MTX according to the ACOG, ASRM and RCOG protocols (the NICE protocol identified patients with persistent PUL with a sensitivity of 100%), and the majority of MTX treatments were unnecessary because those patients were later classified as having non-viable IUP or failed PUL. Application of ACOG and ASRM guidance could result theoretically in inadvertent MTX administration to women with an underlying viable IUP at a rate of 4.1/1000 (3/724). CONCLUSIONS: Current guidelines used to predict high risk of EP in the PUL population lead to inadvertent MTX administration to women with an underlying viable IUP. These guidelines should be used wisely to ensure that no wanted pregnancy is exposed to MTX. Women with PUL should be monitored carefully, and MTX should be used judiciously when the location of pregnancy is yet to be confirmed. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

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

RESEARCH QUESTION: Does 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? DESIGN: Women 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. RESULTS: A 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). CONCLUSIONS: POCT 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.

Expectant management versus systemic methotrexate in the management of persistent pregnancy of unknown location, a seven-year retrospective analysis.

PURPOSE: To compare Expectant management to systemic methotrexate in the management of persistent pregnancy of unknown location with beta-hCG levels below the discrimination zone. METHODS: A retrospective cohort study was conducted on 71 women with persistent pregnancy of unknown location. They were divided into two groups according to the applied management; Group 1, (n = 40) who were managed expectantly and Group 2 (n = 31) who were given a single dose of methotrexate. Data variables were collected and analyzed to evaluate whether expectant management was as effective as methotrexate. RESULTS: There was no significant difference between the two groups regarding age, parity, gestational age, body mass index and day seven beta-hCG. Success rates were (32 patients (80%) and 28 patients (90.3%) in expectant management and methotrexate groups, respectively (P > 0.05). The mean values for day zero and day four beta-hCG were significantly higher and the mean duration for complete recovery was statistically shorter in the methotrexate group (P < 0.05). There were no significant differences between the two groups regarding prior ectopic, percentage of beta-hCG level drop on day four and day seven, success rate, occurrence of sequelae and patient satisfaction that area under the curve (AUC) for group 1 (expectant management) is 0.566 at 95% Confidence Interval of (0.388: 0.745). CONCLUSION: Expectant management is an effective and safe alternative to single-dose methotrexate for persistent PUL with beta-hCG levels below the discrimination zone.

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

OBJECTIVES: 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. METHODS: 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 ß-human chorionic gonadotropin (ß-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. RESULTS: Overall, 5473 PUL were recruited over both phases. A total of 709 PUL were excluded because maternal age was < 16 years or initial ß-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 by 0.03 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. CONCLUSIONS: 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.

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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

hCG trends after mifepristone and misoprostol for undesired pregnancy of unknown location.

OBJECTIVES: To 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 DESIGN: This 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. RESULTS: Of 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). CONCLUSIONS: Serum hCG trends can help differentiate ectopic pregnancy from successful medication abortion, but cannot distinguish between ectopic and retained intrauterine pregnancy. IMPLICATIONS: Serial 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.

Telephone-Based Intervention to Improve Family Planning Care in Pregnancies of Unknown Location: Retrospective Pre-Post Study.

BACKGROUND: Patients followed for a pregnancy of unknown location are generally followed by a team of clinicians through telephone calls, and their contraceptive needs at the time of pregnancy resolution may not be addressed. OBJECTIVE: This study aimed to assess contraceptive counseling and contraceptive uptake before and after a telephone-based intervention. METHODS: This was a retrospective pre-post study assessing pregnancy intendedness in patients with a pregnancy of unknown location and the proportion of patients who received contraceptive counseling and a contraceptive prescription before and after the initiation of a telephone-based intervention. We reviewed medical records 1 year before and 1 year after implementation of our intervention for demographic characteristics, pregnancy intendedness, pregnancy outcome, contraceptive counseling documentation, receipt of contraception, and repeat pregnancy within 6 months. We assessed the effects of an implementation strategy to address family planning needs once pregnancy was resolved by comparing the proportions of patients who were counseled and received contraception before and after our intervention was implemented. We performed logistic regression to identify associations between covariates and the outcomes of contraceptive counseling documentation and receipt of contraception. RESULTS: Of the 220 patients in the combined cohort, the majority were Black (161/220, 73%) and ultimately had a resolved pregnancy of unknown location (162/220, 74%), and the proportion of pregnancies documented as unintended was 60% (132/220). Before our intervention, 27 of 100 (27%) patients received contraceptive counseling, compared with 94 of 120 (78%) patients after the intervention (odds ratio [OR] 9.77, 95% CI 5.26-18.16). Before the intervention, 17 of 90 (19%) patients who did not desire repeat pregnancy received contraception, compared with 32 of 86 (37%) patients after the intervention (OR 2.54, 95% CI 1.28-5.05). Our postintervention cohort had an increased odds of receiving contraceptive counseling (OR 9.77, 95% CI 5.26-18.16) and of receiving a contraceptive prescription (OR 2.54, 95% CI 1.28-5.05) compared with our preintervention cohort. CONCLUSIONS: We found that over half of patients with a pregnancy of unknown location have an unintended pregnancy, and standardization of care through a telephone-based intervention improves contraceptive counseling and prescribing in patients with a resolved pregnancy of unknown location. This intervention could be used at any institution that follows patients with a pregnancy of unknown location remotely to improve care.

Tiny Hydatidiform Mole Presenting As Pregnancy of Unknown Location.

Pregnancy of unknown location (PUL) is a condition in which a pregnancy test, such as elevation of serum or urine ß-human chorionic gonadotrophin (hCG) level, is rendered positive; however, intrauterine or extrauterine pregnancy cannot be confirmed by transvaginal sonography (TVS). Diagnostic dilation and curettage (D&C) or laparoscopy may be performed to search for the pregnancy location. We experienced a case of PUL in which D&C was performed and histological examination revealed a tiny complete hydatidiform mole within the uterine contents. A retrospective review of the clinical course of this case, such as the evaluation of serum ß-hCG levels and TVS findings, suggested that this medical entity could be explained by a tiny hydatidiform mole. In PUL, during D&C, when abnormal villi are detected, even if the lesion is tiny, a suspicion of a hydatidiform mole should be considered by the pathologists, and immunostaining and/or chromosome testing/molecular genotyping should be subsequently performed. Whether a tiny hydatidiform mole poses a risk of persistent gestational trophoblastic disease requires further study based on the accumulation of cases. D&C for PUL patients may be a useful procedure to determine such diagnoses and pick up cases.

Diagnostic value of a urine test in pregnancy of unknown location.

BACKGRO: Pregnancy of unknown location (PUL) is a term used when there is a positive pregnancy test but no sonographic evidence for an intrauterine pregnancy (IUP) or ectopic pregnancy (EP). This term is a classification and not a final diagnosis. OBJECTIVE: This study aimed to evaluate the diagnostic value of the Inexscreen test on the outcome of patients with pregnancies of unknown location. STUDY DESIGN: In this prospective study, a total of 251 patients with a diagnosis of pregnancy of unknown location at the gynecologic emergency department of the La Conception Hospital, Marseille, France, between June 2015 and February 2019 were included. The Inexscreen (semiquantitative determination of intact human urinary chorionic gonadotropin) test was performed on patients with a diagnosis of pregnancy of unknown location. They participated in the study after information and consent collection. The main outcome measures (sensitivity, specificity, predictive values, and the Youden index) of Inexscreen were calculated for the diagnosis of abnormal pregnancy (nonprogressive pregnancy) and ectopic pregnancy. RESULTS: The sensitivity and specificity of Inexscreen for the diagnosis of abnormal pregnancy in patients with pregnancy of unknown location were 56.3% (95% confidence interval, 47.0%-65.1%) and 62.8% (95% confidence interval, 53.1%-71.5%), respectively. The sensitivity and specificity of Inexscreen for the diagnosis of ectopic pregnancy in patients with pregnancy of unknown location were 81.3% (95% confidence interval, 57.0%-93.4%) and 55.6% (95% confidence interval, 48.6%-62.3%), respectively. The positive predictive value and negative predictive value of Inexscreen for ectopic pregnancy were 12.9% (95% confidence interval, 7.7%-20.8%) and 97.4% (95% confidence interval, 92.5%-99.1%), respectively. CONCLUSION: Inexscreen is a rapid, non-operator-dependent, noninvasive, and inexpensive test that allows the selection of patients at high risk of ectopic pregnancy in case of pregnancy of unknown location. This test allows an adapted follow-up according to the technical platform available in a gynecologic emergency service.