Viable Intrauterine Pregnancy Research Articles

Temporal and external validation of the algorithm predicting first trimester outcome of a viable pregnancy.

Symptoms like vaginal bleeding or abdominal pain in early pregnancy can create anxiety about potential miscarriage. Previous studies have demonstrated ultrasonographic variables at the first trimester transvaginal scan (TVS) which can assist in predicting outcomes by 12 weeks gestation. To validate the miscarriage risk prediction model (MRP) in women who present with a viable intrauterine pregnancy (IUP) at the primary ultrasound. A multi-centre diagnostic study of 1490 patients was performed between 2011 and 2019 for retrospective external and 2017-2019 for prospective temporal validation. The reference standard was a viable pregnancy at 12 + 6 weeks. The MRP model is a multinomial logistic regression model based on maternal age, embryonic heart rate, logarithm (gestational sac volume/crown-rump length (CRL)) ratio, CRL and presence or absence of clots. Temporal validation data from 290 viable IUPs were collected: 225 were viable at the end of the first trimester, 31 had miscarried and 34 were lost to follow-up. External validation data from 1203 viable IUPs were collected at two other ultrasound units: 1062 were viable, 69 had miscarried and 72 were lost to follow-up. Temporal validation with a cut-off of 0.1 demonstrated: area under the curve (AUC) of 0.8 (0.7-0.9), sensitivity 66.7%, specificity 83.9%, positive predictive value (PPV) 35.7%, negative predictive value (NPV) 94.9%, positive likelihood ration (LR+) 4.1 and negative LR (LR-) 0.4. External validation demonstrated: AUC 0.7 (0.7-0.8), sensitivity 44.9%, specificity 90.4%, PPV 23.3%, NPV 96.2%, LR+ 4.6 and LR- 0.6 (0.4-0.7). The MRP model is not able to be used in real time for counselling, and management should be individualised.

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

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). 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. 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). 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.

The impact of first-trimester subchorionic hematomas on pregnancy outcomes after euploid embryo transfer: a retrospective cohort study

BackgroundThe aim of the retrospective cohort study was to investigate the prognostic effect of subchorionic hematomas (SCH) in the first trimester on pregnancy outcomes after euploid embryo transfer.MethodsWe retrospectively analyzed women achieving singleton pregnancy by PGT-A or PGT-SR from January 2017 to January 2022. Patients were enrolled in the study if they had a viable intrauterine pregnancy at ultrasound between 6 0/7 and 8 0/7 weeks of gestation. Pregnancy outcomes as well as the incidence of maternal complications were compared between patients with and without SCH. Logistic regression was used for adjusting for potential confounding factors.ResultsA total of 1539 women were included, of which 298 with SCH and 1241 with non-SCH. The early miscarriage rate in SCH group was significantly higher than that in the non-SCH group (10.1% vs. 5.6%, adjusted odds ratio [aOR] 1.99, 95% confidence interval [CI] 1.25–3.16, P = 0.003). The live birth rate in SCH group was significantly lower than that in the non-SCH group. (85.6% vs. 91.2%, aOR 0.57, 95% CI 0.39–0.84, P = 0.005). In addition, SCH group had an increased risk of hypertensive disorder of pregnancy (HDP) (8.9% vs. 5.2%, P = 0.022), especially in hematoma with bleeding (19.3% vs. 6.0%, P = 0.002). The incidence of gestational diabetes mellitus (GDM), major congenital abnormalities rate, normal birth weight rate and low birth weight rate were similar between the two groups.ConclusionsThe presence of SCH in the first trimester was associated with worse pregnancy outcomes after euploid embryo transfer, including an increased risk of early miscarriage and hypertensive disorder of pregnancy, along with a reduced live birth rate.

Oral rehydration therapy versus intravenous rehydration therapy in the first 12 h following hospitalization for hyperemesis gravidarum: A randomized controlled trial.

To evaluate oral rehydration therapy (ORT) compared with intravenous rehydration therapy (IVT) in the early inpatient management of hyperemesis gravidarum (HG). A total of 124 women hospitalized for HG from February 10, 2021 till January 6, 2023 were randomized to ORT (n = 61) or IVT (n = 63) for an initial 12 h. Inclusion criteria includes women older than 18 years, with a viable intrauterine pregnancy less than 14 weeks at their first hospitalization for HG with ketonuria of at least 2+. Primary outcomes were (1) satisfaction score with allocated intervention, (2) weight change, and (3) ketonuria change at 12 h. Secondary outcomes included vomiting frequency, nausea score, serial vital signs, hematocrit and electrolyte levels at 12 h, deviation from treatment protocol (cross-over therapy), participant recommendation of allocated treatment to a friend, and length of hospital stay. Primary outcomes of (1) participant satisfaction score (on a 0-10 visual numerical rating scale) was 7 (interquartile range [IQR] 5-8) versus 9 (IQR 8-10), P < 0.001; (2) weight gain was 293 ± 780 g versus 948 ± 758 g, P < 0.001; and (3) ketonuria improvement was 50/61 (82.0%) versus 49/63 (77.8%) (relative risk [RR] 1.05, 95% confidence interval [CI] 0.88-1.26, P = 0.561) for ORT versus IVT, respectively. For secondary outcomes, vomiting frequency was 2.6 ± 2.7 versus 1.1 ± 1.4 episodes (P < 0.001), participant cross-over rate to opposing treatment 20/61 (32.8%) versus 0/63 (0%) (P < 0.001) (in the 12-h study period) and participant recommendation of allocated treatment to a friend rate 24/61 (39.3%) versus 61/63 (96.8%) (RR 0.41, 95% CI 0.30-0.56, P < 0.001) for ORT versus IVT, respectively. By hospital discharge, 31/61 (50.8%) of women allocated to ORT had required IVT. Other secondary outcomes of serial assessments of nausea score and vital signs, hematocrit and electrolyte levels, and length of hospital stay were not different. ORT was inferior to IVT in two primary outcomes and three secondary outcomes. Cross-over rate to intravenous therapy from oral therapy was 50.8% by hospital discharge. Intravenous rehydration therapy should remain as first-line rehydration therapy in the early inpatient treatment of HG. The present study was registered in ISRCTN registry on December 6, 2020 with trial identification number: ISRCTN 40152556 (https://doi.org/10.1186/ISRCTN40152556). The first participant was recruited on February 10, 2021.

Endometrial compaction to predict pregnancy outcomes in patients undergoing assisted reproductive technologies: a systematic review and meta-analysis.

Does endometrial compaction (EC) help predict pregnancy outcomes in those undergoing ART? EC is associated with a significantly higher clinical pregnancy rate (CPR) and ongoing pregnancy rate (OPR), but this does not translate to live birth rate (LBR). EC describes the progesterone-induced decrease in endometrial thickness, which may be observed following the end of the proliferative phase, prior to embryo transfer. EC is proposed as a non-invasive tool to help predict pregnancy outcome in those undergoing ART, however, published data is conflicting. A literature search was carried out by two independent authors using PubMed, Cochrane Library, MEDLINE, Embase, Science Direct, Scopus, and Web of Science from inception of databases to May 2023. All peer-reviewed studies reporting EC and pregnancy outcomes in patients undergoing IVF/ICSI treatment were included. The primary outcome is LBR. Secondary outcomes included other pregnancy metrics (positive pregnancy test (PPT), CPR, OPR, miscarriage rate (MR)) and rate of EC. Comparative meta-analyses comparing EC and no EC were conducted for each outcome using a random-effects model if I 2 > 50%. The Mantel-Haenszel method was applied for pooling dichotomous data. Results are presented as odds ratios (OR) with 95% CI. Out of 4030 screened articles, 21 cohort studies were included in the final analysis (n = 27 857). No significant difference was found between LBR in the EC versus the no EC group (OR 0.95; 95% CI 0.87-1.04). OPR was significantly higher within the EC group (OR 1.61; 95% CI 1.09-2.38), particularly when EC ≥ 15% compared to no EC (OR 3.52; 95% CI 2.36-5.23). CPR was inconsistently defined across the studies, affecting the findings. When defined as a viable intrauterine pregnancy <12 weeks, the EC group had significantly higher CPR than no EC (OR 1.83; 95% CI 1.15-2.92). No significant differences were found between EC and no EC for PPT (OR 1.54; 95% CI 0.97-2.45) or MR (OR 1.06; 95% CI 0.92-1.56). The pooled weighted incidence of EC across all studies was 32% (95% CI 26-38%). Heterogeneity due to differences between reported pregnancy outcomes, definition of EC, method of ultrasound, and cycle protocol may account for the lack of translation between CPR/OPR and LBR findings; thus, all pooled data should be viewed with an element of caution. In this dataset, the significantly higher CPR/OPR with EC does not translate to LBR. Although stratification of women according to EC cannot currently be recommended in clinical practice, a large and well-designed clinical trial to rigorously assess EC as a non-invasive predictor of a successful pregnancy is warranted. We urge for consistent outcome reporting to be mandated for ART trials so that data can be pooled, compared, and concluded on. H.A. was supported by the Hewitt Fertility Centre. S.G.P. and J.W. were supported by the Liverpool University Hospital NHS Foundation Trust. D.K.H. was supported by a Wellbeing of Women project grant (RG2137) and MRC clinical research training fellowship (MR/V007238/1). N.T. was supported by the National Institute for Health and Care Research. D.K.H. had received honoraria for consultancy for Theramex and has received payment for presentations from Theramex and Gideon Richter. The remaining authors have no conflicts of interest to report. PROSPERO CRD42022378464.

The risk factors for miscarriage of viable intrauterine pregnancies in patients with heterotopic pregnancy after surgical intervention.

To summarize the clinical characteristics and explore the risk factors for miscarriage of a viable intrauterine pregnancy following surgical intervention in patients with heterotopic pregnancy (HP). A total of 106 women diagnosed with HP that underwent surgical intervention in the Women's Hospital School of Medicine Zhejiang University between January 2014 and December 2021 were included in this retrospective study. They were divided into a miscarriage group (n = 13) and an ongoing pregnancy group (n = 93) according to the outcomes of the HP within 2 weeks after surgery. Data regarding clinical characteristics, surgical conditions, postoperative recovery, and complications were collected and compared between the groups. Logistic multivariate analysis was performed to explore the risk factors for miscarriage in patients with HP within 2 weeks of surgical intervention. Among the 106 women with HP, 80 had tubal HP, 8 had cornual HP, and 18 had interstitial HP. Eighty-seven (82.1%) patients developed clinical symptoms that manifested primarily as abnormal vaginal bleeding and/or abdominal pain, whereas 19 (17.9%) patients had no clinical symptoms. The mean gestational age on the day of surgery was 7.2 weeks (inter-quartile range, 6.4-8.3). The miscarriage rate within 2 weeks of surgical intervention was 12.3% in patients with HP. Compared to the ongoing pregnancy group, the miscarriage group had a higher body mass index, earlier gestational age at treatment, and higher volume of hemoperitoneum (P < .05 for all). Logistic multivariate analysis indicated that the women with a hemoperitoneum volume > 200 mL had significantly higher risk of miscarriage after adjusting covariates [OR (odds ratio) = 5.285, 95% CI (confidence interval) (1.152-24.238), P < .05]. Hemoperitoneum volume was independently associated with miscarriage of viable intrauterine pregnancies in patients with HP within 2 weeks of surgical intervention.

Evaluation of novel biomarkers for early pregnancy outcome prediction†.

To assess performance and discriminatory capacity of commercially available enzyme-linked immunosorbent assays of biomarkers for predicting first trimester pregnancy outcome in a multi-center cohort. In a case-control study at three academic centers of women with pain and bleeding in early pregnancy, enzyme-linked immunosorbent assays of biomarkers were screened for assay performance. Performance was assessed via functional sensitivity, assay reportable range, recovery/linearity, and intra-assay precision (%Coefficient of Variation). Top candidates were analyzed for discriminatory capacity for viability and location among 210 women with tubal ectopic pregnancy, viable intrauterine pregnancy, or miscarriage. Assay discrimination was assessed by visual plots, area under the curve with 95% confidence intervals, and measures of central tendency with two-sample t-tests. Of 25 biomarkers evaluated, 22 demonstrated good or acceptable assay performance. Transgelin-2, oviductal glycoprotein, and integrin-linked kinase were rejected due to poor performance. The best biomarkers for discrimination of pregnancy location were pregnancy-specific beta-1-glycoprotein 9, pregnancy-specific beta-1-glycoprotein 1, insulin-like growth factor binding protein 1, kisspeptin (KISS1), pregnancy-specific beta-1-glycoprotein 3, and beta parvin (PARVB). The best biomarkers for discrimination of pregnancy viability were pregnancy-specific beta-1-glycoprotein 9, pregnancy-specific beta-1-glycoprotein 3, EH domain-containing protein 3, KISS1, WAP four-disulfide core domain protein 2 (HE4), quiescin sulfhydryl oxidase 2, and pregnancy-specific beta-1-glycoprotein 1. Performance of commercially available enzyme-linked immunosorbent assays was acceptable for a panel of novel biomarkers to predict early pregnancy outcome. Of these, six and seven candidates demonstrated good discriminatory capacity of pregnancy location and viability, respectively, when validated in a distinct external population. Four markers demonstrated good discrimination for both location and viability.

Evaluation of a New Model for Human Chorionic Gonadotropin Rise in Pregnancies of Unknown Viability

Abstract For early pregnancy management, quantitative serum human chorionic gonadotropin (hCG) measurements and transvaginal ultrasonography are the standard clinical guides. Current guidelines use the change in hCG levels to determine likely location of the pregnancy but represent a minimal rate to predict viability. When incorrectly used, these are inaccurate. This study examined the performance of a new hCG threshold model and compared it with 3 established models. The study is a retrospective cohort study. All individuals with at least 2 consecutive quantitative hCG serum levels seen at the University of Missouri–Columbia from January 1, 2015, until March 1, 2020, were screened for study eligibility. Eligibility requirements were 3-fold: first, patients who presented with pregnancy of unknown viability; second, they had an initial hCG level between 2 and 5000 mIU/mL, maintaining the first interval of no greater than 7 days between testing; and third, the final pregnancy outcome was confirmed. Exclusion occurred for patients who had germ cell tumors, had molar pregnancies, had an intrauterine device in place, utilized hCG monitoring for a molar pregnancy or elective abortion, utilized assisted reproductive technology to achieve pregnancy, or were lost to follow-up. Results of the study came from a pool of 688 patients who met all the inclusion criteria. They contributed an average of 2.3 measurements per patient for a total of 1554 hCG measurements. There was an average of 10.1 days for follow-up. Of those patients included, 167 had viable intrauterine pregnancy (IUP) (24.3%), 463 experienced early pregnancy loss (67.3%), and 58 had ectopic pregnancies (8.4%). The rates of rise in values up to 4 days and again between 4 and 6 days were added for a total rate or rise. Because this was a retrospective study, a calculation was used when hCG levels were not available on day 4 or 6. The values were calculated to be conservative and to avoid incorrectly classifying any viable pregnancy as nonviable. Strengths of the study include its large sample size, its inclusion of all 3 pregnancy outcomes, verified pregnancy outcomes, and subsequent misclassification assessments based off of the aforementioned strength. This study confirmed 122 of 168 viable IUPs (72.6%) had live births, and the simple nature of the study allows for easy integration into clinical practice. Finally, the new model allows for greater variation in days on which a patient must present for care. Study limitations included imputed values from hCG samples not specifically collected on day 4 or 6. Despite this, application of the proposed model utilizing merely known values resulted in better performance. In addition, minimal rise for hCG rates in this data set may be a result of internal validation that may differ in larger, multi-institutional data sets. Furthermore, it must be remembered that current methods using hCG thresholds to determine pregnancy viability rely predominantly on mathematical data analysis and thereby do not reach 100% accuracy thresholds due to biologic variations. Based on this reason, hCG rises below cutoffs established should not mandate a reflexive nonviability diagnosis. The study concluded that although shared decision-making remains paramount in determining management steps, the proposed new model simultaneously reduced unnecessary interventions and optimized correct classification rates for all subgroups of pregnancy. Further prospective studies and investigations of cost-effectiveness are needed before widespread model implementation for pregnancy classification.

Application of a Multiplex Platform to Identify Novel Biomarkers for Pregnancy Location and Viability.

Determining early pregnancy location and viability can be cumbersome, often requiring serial evaluations. This study aimed to identify novel biomarker candidates for pregnancy location and viability using a pseudodiscovery high-throughput technique. This was a case-control study among patients presenting for early pregnancy assessment, including ectopic pregnancies, early pregnancy losses, and viable intrauterine pregnancies. For pregnancy location, ectopic pregnancy was considered "case" and non-ectopic considered "control." For pregnancy viability, viable intrauterine pregnancy was considered "case" and early pregnancy loss + ectopic pregnancy were considered "control." Using Proximity Extension Assay technology from Olink Proteomics, serum levels of 1012 proteins were compared separately for pregnancy location and viability. Receiver operator characteristic curves were generated to determine a biomarker's discriminative abilities. Analysis included 13 ectopic pregnancies, 76 early pregnancy losses, and 27 viable intrauterine pregnancies. For pregnancy location, 18 markers had an area under the curve (AUC) ≥0.80, with three being expressed more in ectopic compared to non-ectopic pregnancies: thyrotropin subunit beta, carbonic anhydrase 3, and DEAD (Asp-Glu-Ala-Asp) box polypeptide 58. For pregnancy viability, two markers had an AUC ≥0.80: lutropin subunit beta and serpin B8. While some of the markers had previously beenimplicated in early pregnancy physiology, others were from pathways not previously explored. Using a high-throughput platform, a large number of proteins were screened as potential biomarkers for pregnancy location and viability, and twenty candidate biomarkers were identified. Further exploration of these proteins may facilitate validation as diagnostic tools for establishing early pregnancy diagnoses.

Intracytoplasmic sperm injection versus conventional in vitro fertilisation in couples with males presenting with normal total sperm count and motility.

Starting over 40 years ago, in vitro fertilisation (IVF) has become the cornerstone for fertility treatment. Since then, in 1992, Palermo and colleagues successfully applied the technique intracytoplasmic sperm injection (ICSI) to benefit couples where conventional in vitro fertilisation (c-IVF) and sub-zonal insemination (SUZI) proved unsuccessful. After this case report, ICSI has become the treatment of choice for couples with severe male factor subfertility. Over time, ICSI has been used in the treatment of couples with mild male and even unexplained infertility. This review is an update of the review, first published in 1999, comparing ICSI with c-IVF for couples with males presenting with normal total sperm count and motility. To evaluate the effectiveness and safety of ICSI relative to c-IVF in couples with males presenting with normal total sperm count and motility. We searched the following databases and trial registers: Cochrane Central Register of Controlled Trials (CENTRAL), Embase (excerpta Medica Database), MEDLINE (Medical Literature Analysis and Retrieval System Online) and PsycINFO (Psychological literature database) for articles between January 2010 and 22 February 2023. We included randomised controlled trials (RCTs) that compared ICSI with c-IVF in couples with males presenting with normal total sperm count and motility. We used standard methodical procedures recommended by Cochrane. The primary review outcomes were live birth and adverse events. Secondary outcomes included clinical pregnancy, viable intrauterine pregnancy and miscarriage. The original review published in 2003 included one RCT. In this 2023 update, we identified an additional two RCTs totalling a cohort of 1539 couples, comparing ICSI with c-IVF techniques. Two studies reported on live birth. Using the GRADE method, we assessed the certainty of evidence and reported evidence as low-certainty for live birth. We are uncertain of the effect of ICSI versus c-IVF for live birth rates (risk ratio (RR) 1.11, 95% confidence interval (CI 0.94 to 1.30, I2 = 0%, 2 studies, n = 1124, low-certainty evidence). The evidence suggests that if the chance of live birth following c-IVF is assumed to be 32%, the chance of live birth with ICSI would be between 30% and 41%. For adverse events; multiple pregnancy, ectopic pregnancy, pre-eclampsia and prematurity, there was probably little or no difference between the two techniques. No study reported the primary outcome stillbirth. For secondary outcomes, we are uncertain of the effect of ICSI versus c-IVF for clinical pregnancy rates (RR 1.00, 95% CI 0.88 to 1.13, I2 = 45%, 3 studies, n = 1539, low-certainty evidence). Comparison of viable intrauterine pregnancy rates showed probably little or no difference between ICSI and c-IVF (RR 1.00, 95% CI 0.86 to 1.16, I2=75%, 2 studies, n = 1479 couples, moderate-certainty evidence). The high heterogeneity may have been caused by one older study conducted when protocols were less rigorous. The evidence suggests that if the chance of viable intrauterine pregnancy following c-IVF is assumed to be 33%, the chance of viable intrauterine pregnancy with ICSI would be between 28% and 38%. Miscarriage rates also showed probably little or no difference between the two techniques. The current available studies that compare ICSI and c-IVF in couples with males presenting with normal total sperm count and motility, show neither method was superior to the other, in achieving live birth, adverse events (multiple pregnancy, ectopic pregnancy, pre-eclampsia and prematurity), also alongside secondary outcomes, clinical pregnancy, viable intrauterine pregnancy or miscarriage.

Effectiveness of laparoscopic niche resection versus expectant management in patients with unexplained infertility and a large uterine caesarean scar defect (uterine niche): protocol for a randomised controlled trial (the LAPRES study)

IntroductionA uterine niche is a defect at the site of the uterine caesarean scar that is associated with gynaecological symptoms and infertility. Promising results are reported in cohort studies after...

Pregnancy outcomes with a copper 380 mm2 intrauterine device in place: A retrospective cohort study in Turkey, 2011-2021

ObjectivesTo investigate pregnancy outcomes in patients with pregnancies with a copper 380 mm2 intrauterine device (IUD) in situ at conception. Study designIn this retrospective study, we identified patients with pregnancies with a copper 380 mm2 IUD between 2011 and 2021 from the electronic health record system. According to their initial diagnosis, we classified the patients as having nonviable intrauterine pregnancies (IUPs), viable IUPs, or ectopic pregnancies. Among the viable IUPs, we divided the ongoing pregnancies into two subgroups as IUD-removed and IUD-retained. We compared the pregnancy loss (miscarriage before 22 weeks) rates and adverse pregnancy outcomes (at least one of preterm birth, preterm premature rupture of membranes, chorioamnionitis, placental abruption, or postpartum hemorrhage) of IUD-removed and IUD-retained pregnancies. ResultsWe identified a total of 246 patients with pregnancies with an IUD. We excluded six (2.4%) patients without follow-up data and seven (2.8%) patients with levonorgestrel-IUD and included the remaining 233 (44 [18.9%] ectopic pregnancy, 31 [13.3%] nonviable IUP, and 158 [67.5%] viable IUP) patients. Among the 158 women with viable IUP, 21 (13.3%) underwent abortion, leaving 137 (86.7%) who elected to continue the pregnancy. A total of 54 (39.4%) patients with ongoing pregnancy had the IUD removed. We found a lower rate of pregnancy loss among those who underwent removal (18/54 [33.3%]) compared to those with a retained IUD (51/83 [61.4%], p < 0.001). After accounting for pregnancy loss, adverse pregnancy outcomes remained increased in the IUD-retained group (17/32 [53.1%]) compared to the IUD-removed group (10/36 [27.8%], p = 0.03). ConclusionsPregnancy in the setting of a copper 380 mm2 IUD is high risk. Our results demonstrate that pregnancy outcomes improve by removal of the copper 380 mm2 IUD. ImplicationsPrior studies have suggested that the removal of the IUD improves outcomes, but all have limitations. Our results from a very large series with care in a single institution provide contemporary evidence to support copper 380 mm2 IUD removal to reduce the risk of both early pregnancy loss and later adverse outcomes

Evaluation of a New Model for Human Chorionic Gonadotropin Rise in Pregnancies of Unknown Viability.

To evaluate the performance of a new human chorionic gonadotropin (hCG) threshold model to classify pregnancies as viable or nonviable using a longitudinal cohort of individuals with pregnancy of unknown viability. The secondary objective was to compare the new model with three established models. This is a single-center, retrospective cohort study of individuals seen at the University of Missouri from January 1, 2015, until March 1, 2020, who had at least two consecutive quantitative hCG serum levels with an initial level greater than 2 milli-international units/mL and 5,000 milli-international units/mL or less, with the first interval between laboratory draws no greater than 7 days. Prevalence of correct classification of viable intrauterine pregnancies, ectopic pregnancies, and early pregnancy losses was evaluated with a new proposed hCG threshold model and compared with three established models describing minimum expected rates of hCG rise for a viable intrauterine pregnancy. Of an initial cohort of 1,295 individuals, 688 patients met inclusion criteria. One hundred sixty-seven individuals (24.3%) had a viable intrauterine pregnancy; 463 (67.3%) had an early pregnancy loss; and 58 (8.4%) had an ectopic pregnancy. A new model based on the total additive percent rise of hCG at 4 and 6 days after initial hCG (70% or greater and 200% or greater rise, respectively) was created. The new model was able to correctly identify 100% of viable intrauterine pregnancies while minimizing incorrect classification of early pregnancy losses and ectopic pregnancies as normal pregnancies. At 4 days after initial hCG, 14 ectopic pregnancies (24.1%) and 44 early pregnancy losses (9.5%) were incorrectly classified as potentially normal pregnancies. At 6 days after initial hCG, only seven ectopic pregnancies (12.1%) and 25 early pregnancy losses (5.6%) were incorrectly classified as potentially normal pregnancies. In established models, up to nine intrauterine pregnancies (5.4%) were misclassified as abnormal pregnancies and up to 26 ectopic pregnancies (44.8%) and 58 early pregnancy losses (12.5%) were incorrectly classified as potentially normal pregnancies. The proposed new hCG threshold model optimizes a balance between identifying potentially viable intrauterine pregnancies and minimizing misdiagnosis of ectopic pregnancies and early pregnancy losses. External validation in other cohorts is needed before widespread clinical use.

Management of heterotopic pregnancy: clinical analysis of sixty-five cases from a single institution.

This retrospective study aims to analyze the influence of different treatment modalities on viable intrauterine pregnancy and to summarize the clinical features of heterotopic pregnancy (HP) patients. All patients diagnosed with HP between January 2012 and December 2022 in Tianjin Central Obstetrics and Gynecology Hospital were reviewed retrospectively. This study diagnosed 65 patients using transvaginal ultrasound (TVS), including two cases of natural pregnancy, seven cases of ovulation induction pregnancy, and 56 cases after in vitro fertilization and embryo transfer (IVF-ET). The gestational age was 50.2 ± 13.0 days at the time of diagnosis. The most frequent manifestations were abdominal pain (61.5%) and vaginal bleeding (55.4%), while 11 patients (16.9%) had no symptoms before the diagnosis. The primary treatment was expectant and surgical management, including laparotomy and laparoscopic surgery. In the expectant management group, four patients were transferred to surgery due to rupture of ectopic pregnancy or ectopic pregnancy mass gradually enlarged. In the surgical management group, 53 patients underwent laparoscopic surgery, and six underwent laparotomy. The laparoscopic group's mean operation time was 51.3 ± 14.2 min (range: 15-140 min), and the median intraoperative blood loss was 20 mL (range 5-200 mL). In contrast, the laparotomy group's mean operation time was 80.0 ± 25.3 min (range 50-120 min), and the median intraoperative blood loss was 22.5 mL (range 20-50 mL). Four patients had postoperative abortions. Sixty-one newborns had no birth abnormalities, and no developmental malformations were discovered after a median follow-up of 32 months. Expectant treatment has a high failure rate in HP, and laparoscopic surgery is a safe and effective treatment for removing ectopic pregnancy without increasing the risk of abortion or newborn birth defects.

A short versus a long time interval between semen collection and intrauterine insemination: a randomized controlled clinical trial.

Does a short interval (i.e. ≤90 min), compared to a long interval (i.e. ≥180 min), between semen collection and intrauterine insemination (IUI) increase the cumulative chance of an ongoing pregnancy after six IUI cycles? A long interval between semen collection and IUI resulted in a borderline significant improvement in cumulative ongoing pregnancies and a statistically significant shorter time to pregnancy. Retrospective studies assessing the effect of the time interval between semen collection and IUI on pregnancy outcomes have shown inconclusive results. Some studies have indicated a beneficial effect of a short interval between semen collection and IUI on IUI outcomes, while others have not found any differences. To date, no prospective trials have been published on this subject. The study was performed as a non-blinded, single-center RCT with 297 couples undergoing IUI treatment in a natural or stimulated cycle. The study was conducted between February 2012 and December 2018. Couples with unexplained or mild male subfertility and an indication for IUI were randomly assigned for up to six IUI cycles into either the control group (long interval, i.e. 180 min or more between semen collection and insemination) or the study group (short interval, i.e. insemination as soon as possible after semen processing and within 90 min of semen collection). The study was carried out in an academic hospital-based IVF center in the Netherlands. The primary endpoint of the study was ongoing pregnancy rate per couple, defined as a viable intrauterine pregnancy at 10 weeks after insemination. In the short interval group, 142 couples were analyzed versus 138 couples in the long interval group. In the intention-to-treat (ITT) analysis, the cumulative ongoing pregnancy rate was significantly higher in the long interval group (71/138; 51.4%) compared to that in the short interval group (56/142; 39.4%; relative risks 0.77; 95% CI 0.59-0.99; P = 0.044). The time to pregnancy was significantly shorter in the long interval group (log-rank test, P = 0.012). A Cox regression analysis showed similar results (adjusted hazard ratio 1.528, 95% CI 1.074-2.174, P = 0.019). Limitations of our study are the non-blinded design, the long inclusion and follow-up period of nearly seven years and the large number of protocol violations, especially because they predominantly occurred in the short interval group. The non-significant results in the per-protocol (PP) analyses and the weaknesses of the study should be taken into account in the assessment of the borderline significance of the results in the ITT analyses. Because it is not necessary to perform the IUI immediately after semen processing, there can be more time available to choose the optimum work-flow and clinic occupancy. Clinics and laboratories should find their optimal timing of insemination, considering the time between human chorionic gonadotropin injection and insemination in relation to the sperm preparation techniques used as well as the storage time and conditions until insemination. There were no external funding and no competing interests to declare. Dutch trial registry, trial registration number NTR3144. 14 November 2011. 5 February 2012.

Trends in Screening for Diabetes in Early Pregnancy in the United States.

Objective: The aim of this study was to characterize current diabetes screening practices in the first trimester of pregnancy in the United States, evaluate patient characteristics and risk factors associated with early diabetes screening, and compare perinatal outcomes by early diabetes screening. Methods: This was a retrospective cohort study of US medical claims data of persons diagnosed with a viable intrauterine pregnancy and who presented for care with private insurance before 14 weeks of gestation, without pre-existing pregestational diabetes, from the IBM MarketScan® database for the period January 1, 2016, to December 31, 2018. Univariate and multivariate analyses were used to evaluate perinatal outcomes. Results: A total of 400,588 pregnancies were identified as eligible for inclusion, with 18.0% of persons receiving early screening for diabetes. Of those with laboratory order claims, 53.1% underwent hemoglobin A1c testing, 30.0% underwent fasting glucose testing, and 16.9% underwent oral glucose tolerance testing. Compared with those who did not undergo early diabetes screening, those who did were more likely to be older; obese; having a history of gestational diabetes, chronic hypertension, polycystic ovarian syndrome, or hyperlipidemia; and having a family history of diabetes. In adjusted logistic regression, history of gestational diabetes (adjusted odds ratio 3.99; 95% confidence interval 3.73-4.26) had the strongest association with early diabetes screening. Adverse perinatal outcomes, including a higher rate of cesarean delivery, preterm delivery, preeclampsia, and gestational diabetes, occurred more frequently among women who underwent early diabetes screening. Conclusions: First-trimester early diabetes screening was mostly commonly performed by hemoglobin A1c evaluation, and persons who underwent early diabetes screening were more likely to experience adverse perinatal outcomes.

Validation of a multiple marker test for early pregnancy outcome prediction.

To validate the use of a multiple biomarker test panel for predicting first trimester pregnancy outcome in a multi-center cohort. A case-control study of women presenting with pain and bleeding in early pregnancy at 5-10 weeks gestational age was performed at three academic centers. Sera from women with ectopic pregnancy (EP), viable intrauterine pregnancy (IUP), and miscarriage (SAB) were analyzed via immunoassay for Activin A (AA), Progesterone (P4), A Disintegrin And Metalloprotease-12 (ADAM12), pregnancy-associated plasma protein A (PAPP-A), glycodelin (Glyc), and human chorionic gonadotropin (hCG). Biomarkers were assessed for reproducibility using medians, ranges, standard deviations, and area under receiver-operating characteristic curve (AUC) and accuracy in early pregnancy outcome classification compared to a previous derivation population. In 192 pregnancies, the biomarkers demonstrated good reproducibility with similar medians, ranges, and AUCs when compared to the derivation population except glycodelin. Pregnancy location was conclusively classified in 53% (n = 94) of the whole study sample with 78% accuracy. Pregnancy viability was conclusively classified in 58% (n = 112) of the new sample with 89% accuracy. Results were similar with subsequent model revisions where glycodelin was excluded and in the subgroups of subjects with a hCG below 2000 mIU/mL and a gestational age less than 6 weeks. The use of a panel of biomarkers to maximize test accuracy of a prediction of pregnancy location and prediction of pregnancy viability was reproducible and validated in an external population from which it was derived, but clinical utility is limited based on the test characteristics obtained.

Development of a Machine Learning Model for Sonographic Assessment of Gestational Age

Fetal ultrasonography is essential for confirmation of gestational age (GA), and accurate GA assessment is important for providing appropriate care throughout pregnancy and for identifying complications, including fetal growth disorders. Derivation of GA from manual fetal biometry measurements (ie, head, abdomen, and femur) is operator dependent and time-consuming. To develop artificial intelligence (AI) models to estimate GA with higher accuracy and reliability, leveraging standard biometry images and fly-to ultrasonography videos. To improve GA estimates, this diagnostic study used AI to interpret standard plane ultrasonography images and fly-to ultrasonography videos, which are 5- to 10-second videos that can be automatically recorded as part of the standard of care before the still image is captured. Three AI models were developed and validated: (1) an image model using standard plane images, (2) a video model using fly-to videos, and (3) an ensemble model (combining both image and video models). The models were trained and evaluated on data from the Fetal Age Machine Learning Initiative (FAMLI) cohort, which included participants from 2 study sites at Chapel Hill, North Carolina (US), and Lusaka, Zambia. Participants were eligible to be part of this study if they received routine antenatal care at 1 of these sites, were aged 18 years or older, had a viable intrauterine singleton pregnancy, and could provide written consent. They were not eligible if they had known uterine or fetal abnormality, or had any other conditions that would make participation unsafe or complicate interpretation. Data analysis was performed from January to July 2022. The primary analysis outcome for GA was the mean difference in absolute error between the GA model estimate and the clinical standard estimate, with the ground truth GA extrapolated from the initial GA estimated at an initial examination. Of the total cohort of 3842 participants, data were calculated for a test set of 404 participants with a mean (SD) age of 28.8 (5.6) years at enrollment. All models were statistically superior to standard fetal biometry-based GA estimates derived from images captured by expert sonographers. The ensemble model had the lowest mean absolute error compared with the clinical standard fetal biometry (mean [SD] difference, -1.51 [3.96] days; 95% CI, -1.90 to -1.10 days). All 3 models outperformed standard biometry by a more substantial margin on fetuses that were predicted to be small for their GA. These findings suggest that AI models have the potential to empower trained operators to estimate GA with higher accuracy.

Pseudotumor cerebri in pregnant obese patient: A case report

Introduction: Pseudotumor cerebri (PTC), idiopathic intracranial hypertension, is a serious condition that is most associated with pregnancy. It is believed that symptoms are due to increased stroke volume and fluid retention ultimately increasing intracranial pressure. This increased pressure can lead to cerebral edema and dysfunction of the optic nerve fibers. The initial workup for PTC is conducting a computed tomography (CT) or magnetic resonance imaging (MRI) brain scan to rule out structural abnormalities that may induce a headache. A lumbar puncture can be performed to acutely relieve the symptoms and definitively diagnose PTC; however, the definitive treatment is acetazolamide through the inhibition of carbonic anhydrase alleviating intracranial pressure. Case Report: This case report discusses how a pseudotumor cerebri affected the pregnancy of a 29-year-old female who presented with headache, blurry vision with eye pain, and abdominal pain. Her pregnancy was complicated by several comorbidities. Ultrasound showed a viable intrauterine pregnancy, while an MRI without contrast of the head revealed bilateral papilledema. She was treated with acetazolamide and underwent a primary low transverse cesarean section due to fetal malpresentation and pseudotumor cerebri diagnosis. Conclusion: It is imperative that symptoms of PTC are recognized as a larger diagnosis and that imaging confirms the increased intracranial pressure. The initial workup for PTC is conducting a CT or MRI brain scan to rule out structural abnormalities that may induce a headache. A lumbar puncture can relieve the symptoms and definitively diagnose PTC. The definitive treatment is acetazolamide through the inhibition of carbonic anhydrase alleviating intracranial pressure.

Study on diagnosis and management strategies on heterotopic pregnancy: a retrospective study

Heterotopic pregnancy (HP) is a rare but potentially life-threatening event with a high risk of maternal death, which also jeopardise the coexisting intrauterine pregnancy (IUP), thus an early accurate diagnosis and prompt treatment can decrease adverse complications. We aimed to explore the early predictors for pregnancy outcomes of HP. We reviewed patients with HP following assisted reproductive technology in our institution between January 2013 and December 2020. The relationships between pregnancy outcomes and clinical features were analysed by logistic regression. We found that 29 patients (72.5%) of HP were accurately diagnosed by transvaginal ultrasonography (TVS). Eighteen patients in the surgery group had live births, three of whom delivered preterm. Additionally, the miscarriage rate was lower for patients with IUP cardiac activity than those without (16.7% vs. 90.0%, p < .001). Further by logistic regression analysis, an IUP with cardiac activity at HP diagnosis was identified as favourable independent predictor of live birth (p < .001). Therefore, early diagnosis and prompt surgical intervention are recommended to prevent the development of HP. Impact of statement What is already known on this subject? Heterotopic pregnancy (HP) has long been thought to be a rare but potentially life-threatening event with a high risk of complications. The early diagnosis of HP is challenging due to the co-existence of a viable intrauterine pregnancy (IUP) and the absence of typical clinical symptoms. What do the results of this study add? This stduy showed that symptoms combined with routine transvaginal ultrasonography (TVS) scans reduce the rates of misdiagnosis of HP and prompt surgical intervention after diagnosis may minimise the incidence of miscarriage of the IUP. What are the implications of these findings for clinical practice and/or further research? An IUP with cardiac activity at HP diagnosis is a predictor of a favourable prognosis of HP, and laparoscopy under general anaesthesia is effective and safe during the first trimester of pregnancy. Awareness, assessment and early interventions in view of symptoms combined with routine TVS is recommended to reduce the risk of miscarriage and ensure a favourable live birth rate.