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Gestational trophoblastic disease is a group of pregnancy-related trophoblastic tumours. Gestational trophoblastic neoplasia refers to its invasive and malignant forms: invasive mole, choriocarcinoma, placental site trophoblastic tumour and epithelioid trophoblastic tumour. Patients exhibit elevated beta human chorionic gonadotropin (β hCG) levels, sometimes exceeding 100 000 mIU/mL. When the serum levels of hCG surpass 500 000 mIU/mL, there is a possibility of encountering a phenomenon called 'hook effect' which causes erroneously low or negative value when using the immunometric hCG assays that are presently available in the commercial market. We present a rare case involving a female in mid-30s with an invasive molar pregnancy presenting with bleeding, an abdominal mass, hypertension and hyperthyroidism. Despite a negative urine β hCG test, her serum hCG, after dilution, was recalculated to over 850 000 mIU/mL. MRI confirmed invasive mole. Post-hysterectomy, she received methotrexate chemotherapy. Her β hCG normalised after two cycles, and she remains disease-free for 14 months., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Epithelioid trophoblastic tumor (ETT) is an extremely rare chorionic-type neoplasm in the testis, with only seven cases reported in the literature. Here, we report five cases of testicular ETT from a single institution, constituting the largest series of this rare tumor to date. The patients had a mean age of 44 years (range, 20-68 years). Four patients had a previous history of testicular germ cell tumor (GCT) treated with chemotherapy, and they developed ETT in metastatic sites in a mean of 11 years (range, 3-15 years) after the initial diagnosis of testicular GCT. Only one patient had ETT in the testis. Three patients had a normal serum beta-human chorionic gonadotropin (β-hCG) level, and two patients had a level that was slightly elevated, but far below that typically seen in patients with choriocarcinoma. ETT was characterized by a proliferation of intermediate trophoblastic cells with abundant eosinophilic cytoplasm, and the tumors frequently had coagulative necrosis with eosinophilic debris, mimicking keratinizing squamous cell carcinoma. The trophoblastic phenotype of ETT was supported by its immunoreactivity for trophoblastic markers, including GATA-3 (3 of 3 cases tested), α-inhibin (3/4), p63 (3/5), and β-hCG (3/4). ETT was also positive for cytokeratin (4/4) and GCT marker SALL4 (3/3). Despite surgery and chemotherapy, two patients died of disease 17 months after ETT diagnosis, and three patients were alive with metastatic disease at a mean of 20 months (range, 15-28 months). Our results demonstrate that ETT may be an aggressive disease associated with distinct pathologic features and poor clinical outcome., Competing Interests: Declaration of competing interest All authors declare they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Pregnancy in-vitro fertilization (IVF) cases are associated with adverse first-trimester outcomes in comparison to spontaneously achieved pregnancies. Human chorionic gonadotrophin β subunit (β-HCG) is a well-known biomarker for the diagnosis and monitoring of pregnancy after IVF. Low levels of β-HCG during this period are related to miscarriage, ectopic pregnancy, and IVF procedure failures. Longitudinal profiles of β-HCG can be used to distinguish between normal and abnormal pregnancies and to assist and guide the clinician in better management and monitoring of post-IVF pregnancies. Therefore, assessing the association between longitudinally measured β-HCG serum concentration and time to early miscarriage is of crucial interest to clinicians. A common joint modeling approach is to use the longitudinal β-HCG trajectory to determine the risk of miscarriage. This work was motivated by a follow-up study with normal and abnormal pregnancies where β-HCG serum concentrations were measured in 173 young women during a gestational age of 9-86 days in Santiago, Chile. Some women experienced a miscarriage event, and their exact event times were unknown, so we have interval-censored data, with the event occurring between the last time of the observed measurement and ten days later. However, for those women belonging to the normal pregnancy group; that is, carrying a pregnancy to a full-term event, right censoring data are observed. Estimation procedures are based on the Stochastic Approximation of the Expectation-Maximization (SAEM) algorithm., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Research Question: What is the effect of embryo morphology score on 14-day β-HCG levels and 14-18-day β-HCG doubling values, and do they have differences in day-3 embryo or day-5 blastocyst transfers?, Design: Retrospective analysis of 4434 fresh cycles of single embryo transfers (SET) with β-HCG ≥15 mIU/ml on day 14 after transfer via IVF and ICSI. The correlation between embryo morphology score and 14-day β-HCG was examined. Doubling of 14-18 day β-HCG was analysed in 2628 cycles to determine correlations with embryo morphology score., Results: In day-3 SET, number of embryonic cells was positively correlated with 14-day post-transfer β-HCG values (R = 0.076; P = 0.013). No significant correlation was observed between the grade of the transferred embryos and the 14-18-day serum β-HCG doubling values. In day-5 single blastocyst transfers, the degree of blastocyst expansion, trophoblast cell and inner cell mass (ICM) grades demonstrated a significant positive correlation with 14-day post-transfer β-HCG (P < 0.001, P = 0.014, P = 0.003). Degree of blastocyst expansion was significantly correlated with 14-18-day β-HCG doubling values (R = -0.051, P = 0.027). Grades of the ICM and trophoblast cells showed no significant correlation with 14-18-day β-HCG doubling values., Conclusion: In fresh SET, embryo morphology score influences 14-day β-HCG values in day-3 embryos and day-5 blastocyst transfers. Embryo morphology score in day-3 SET does not affect 14-18-day β-HCG doubling values. Degree of blastocyst expansion significantly affects 14-18-day β-HCG doubling values in day-5 blastocyst transfers., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate the systemic immune-inflammation index (SII) and neutrophil-to-lymphocyte ratio (NLR) in predicting a successful methotrexate response in tubal ectopic pregnancy (TEP)., Methods: Women treated for TEP at a tertiary hospital between 2017 and 2021 were retrospectively reviewed. A total of 502 (100%) eligible patients who received methotrexate were included and divided into two groups based on whether or not they were successfully treated with methotrexate alone. Inflammatory parameters derived from the patients' hemograms at hospital admission were compared., Results: In total, 434 (86.4%) patients were successfully treated with methotrexate alone (Group 1), while 68 (13.6%) patients underwent surgery after methotrexate failure (Group 2). Median neutrophil count, NLR, platelet-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, SII, largest ectopic mass diameter, and β-human chorionic gonadotropin (β-hCG) were significantly lower, whereas median lymphocyte and platelet counts were significantly higher in Group 1. According to the receiver operating characteristic analysis performed for the discriminatory power of NLR, β-hCG, and SII for methotrexate response, the area under the curve values were 0.742, 0.730, and 0.699, respectively., Conclusion: Low NLR and SII are associated with methotrexate success and could be used to refine decision making regarding β-hCG for predicting successful response to methotrexate in patients with TEP., (© 2024 International Federation of Gynecology and Obstetrics.)

Aim: To assess the role of serum micro ribonucleic acids 323-3p, 517a and 519d in the diagnosis of ectopic pregnancy., Methods: The case-control study was conducted at the Gynaecology Department of Al-Yarmouk Teaching Hospital, Baghdad, Iraq, from June 1, 2020, to May 1, 2021, and comprised women with ectopic pregnancy in group A, and those with a viable intrauterine pregnancy in group B. Serum samples were taken for beta human chorionic gonadotropin measurement and for micro ribonucleic acids 323-3p, 517a and 519d testing using polymerase chain reaction. Data was analysed using SPSS 24., Results: Of the 100 women with mean age 26.8±5.29 years, 50(50%) were in each of the 2 groups. There was no significant difference between the groups in terms of age, gravida, parity, abortion, and gestational age (p>0.05). The mean beta human chorionic gonadotropin in group B was significantly greater than group A (p=0.001). In group A, micro ribonucleic acid 323-3p expression was significantly higher, mean micro ribonucleic acid 517a expression was significantly lower and mean micro ribonucleic acid 519d expression was significantly lower compared to group B (p<0.05). At micro ribonucleic acid 323-3p cut-off point 2.415, the test accurately distinguished between ectopic and viable pregnancy with 92% sensitivity, 100% specificity and total area under the curve 0.994 (p=0.001)., Conclusions: Serum micro ribonucleic acid 323-3p, 517a and 519d might be helpful biomarkers in the diagnosis and follow-up of patients with ectopic pregnancy.

Background: Prenatal serological screening is commonly used to screen for trisomy 21 syndrome (T21); however, it carries a risk of missed detection. In this study, we explored how to reduce missed diagnosis of T21 in serological screening., Methods: A total of 116 pregnant women with T21 fetuses confirmed by prenatal diagnosis were evaluated. Serological screening and non-invasive prenatal test (NIPT) findings were analyzed., Results: Twenty-nine T21 fetuses were missed in serological screening; the missed diagnosis rate was 25%, 67.65% of the missed cases were of moderate risk, and 79.31% of the missed pregnant women were under 35 years of age. Nuchal translucency (NT) and the free beta subunit of human chorionic gonadotropin (free-HCGβ) were higher in the detected T21 cases than in the missed T21 cases, while alpha-fetoprotein (AFP) levels were decreased. Forty-eight pregnant women who underwent NIPT in the second trimester were at high-risk for T21., Conclusions: Prenatal screening should not be ignored in young pregnant women. For serological screening, moderate risk and abnormal single serum markers should also receive greater attention. NIPT can be extended to first-tier screening.

Objective: The objectives of the study were to correlate live birth rate with the initial level of β-hCG in all patients undergoing embryo transfer and develop a predictive model of live birth based on patients' and assisted reproductive technology (ART) characteristics., Study Design: Single-center retrospective cohort study, including a total of 7587 positive first serum β-hCG from women who performed fresh and frozen embryo transfer. Twenty-one variables related to patient characteristics and treatment modalities were analyzed by step-wise univariate analysis followed by multivariate analysis. The study included women between 18 and 45 years with a positive (>20 IU/L) serum β-hCG between January 2011 and December 2020 while it excluded cycles from donation of gametes, PGT and >3 embryos transferred simultaneously., Main Results and the Role of Chance: Among the positive serum β-hCG measurements 5085 (67.0 %) resulted in live births. β-hCG was higher in the live birth group (691 IU/L) compared to the failed pregnancies group (304 IU/L) (p500 IU/mL provided a positive predictive value for live birth of 85.3 % (95 %CI 84.0-86.4). Failed pregnancies were more common among older maternal and paternal age. Previous abortions were more common in the failed pregnancies group (25.0 %) compared to the live birth group (19.4 %). The most common indication to treatment was male infertility, accounting for a larger portion in the live birth group (41.7 %). At multivariate analysis, the factors independently associated with live birth were: first serum β-hCG (OR 1.35, 95 %CI 1.32-1.37), maternal age (OR 0.93, 95 %CI 0.91-0.95), previous abortions (OR 0.77, 95 % CI 0.68-0.88). The number of embryos transferred showed a positive correlation below a maternal age of 39 (<35 years old OR 1.60, CI 95 % 1.32-1.94; <39 years old OR 1.27 CI 95 % 1.09-1.47). The prediction model incorporating these four variables resulted in a sensitivity and specificity with an area under the ROC curve of 0.798., Conclusion: The study confirms the importance of the first value of β-hCG and proposes a predictive model that takes into account maternal age, number of embryos transferred, and obstetric history, thereby aiding in couples' counseling and ultimately improve patients' care., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Conservative management of placenta accreta spectrum (PAS) includes delivery of the fetus with retention of the placenta in situ. There are insufficient data evaluating the effect of leaving the placenta in situ with PAS on the ability to establish lactation. We performed a prospective cohort study of 126 patients diagnosed with PAS. Clinical data pertaining to breastfeeding were obtained, as well as laboratory values for β-hCG and progesterone. Our objective was to assess breast-milk production measured by time of onset of stage II lactogenesis and hormone values in individuals managed with placental retention compared with those undergoing hysterectomy. We found that the average time for onset of stage II lactogenesis was 5.6 days with conservative management and 3.8 days with cesarean hysterectomy ( P =.07). Although β-hCG levels did not differ between groups, postpartum progesterone levels were lower in the cesarean hysterectomy group compared with the retained placenta group (1.86 ng/mL vs 62.9 ng/mL, P <.001)., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2024 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Multiplex detection of low-abundance protein biomarkers in biofluids can contribute to diverse biomedical fields such as early diagnosis and precision medicine. However, conventional techniques such as digital ELISA, microarray, and hydrogel-based assay still face limitations in terms of efficient protein detection due to issues with multiplexing capability, sensitivity, or complicated assay procedures. In this study, we present the degassed micromold-based particle isolation technique for highly sensitive and multiplex immunoassay with enzymatic signal amplification. Using degassing treatment of nanoporous polydimethylsiloxane (PDMS) micromold, the encoded particles are isolated in the mold within 5 min absorbing trapped air bubbles into the mold by air suction capability. Through 10 min of signal amplification in the isolated spaces by fluorogenic substrate and horseradish peroxidase labeled in the particle, the assay signal is amplified with one order of magnitude compared to that of the standard hydrogel-based assay. Using the signal amplification assay, vascular endothelial growth factor (VEGF) and chorionic gonadotropin beta (CG beta), the preeclampsia-related protein biomarkers, are quantitatively detected with a limit of detection (LoD) of 249 fg/mL and 476 fg/mL in phosphate buffer saline. The multiplex immunoassay is conducted to validate negligible non-specific detection signals and robust recovery rates in the multiplex assay. Finally, the VEGF and CG beta in real urine samples are simultaneously and quantitatively detected by the developed assay. Given the high sensitivity, multiplexing capability, and process simplicity, the presented particle isolation-based signal amplification assay holds significant potential in biomedical and proteomic fields., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: This study's aim is to investigate whether the rise in β-hCG levels between days 0 and 4 in patients with tubal ectopic pregnancy who have received a single dose of methotrexate has prognostic value in treatment success, and to investigate whether administering a second dose on day 4 enhances treatment success., Material and Methods: Patients diagnosed with ectopic pregnancy and experiencing an increase in β- hCG levels on day 4 after initiation of methotrexate treatment were included in our study. Patients treated with a single dose Methotrexate (MTX) protocol until December 2019 were retrospectively screened from January 2018 to December 2019. Patients receiving a second dose on day 4 until September 2021 were prospectively enrolled from January 2020 to September 2021. A decrease of over 15 % in the β-hCG value after the 4th dose was considered as treatment success., Results: Treatment success rates were compared between these two groups. 115 patients with ectopic pregnancy were included in the study. A single dose methotrexate protocol was applied in 67 of the patients (Group 1), while an additional dose methotrexate was applied in 48 (Group 2). The treatment was successful in 40 patients (59.7 %) in Group 1 and in 39 patients (81.3 %) in Group 2. The success rate of the treatment was significantly higher in patients who received an additional dose methotrexate protocol (p = 0.014)., Discussion: This study shows that; it is possible to increase success rates by applying an additional MTX dose on the 4th day in cases with an increase in β-hCG on the 4th day., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: Maternal gestational diabetes (GDM), small (SGA) and large (LGA) for gestational age neonates are associated with increased morbidity in both mother and child. We studied how different levels of first trimester pregnancy associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (fβ-hCG) were associated with SGA and LGA in GDM pregnancies and controls., Methods: Altogether 23 482 women with singleton pregnancies participated in first trimester combined screening and delivered between 2014 and 2018 in Northern Finland and were included in this retrospective case-control study. Women with GDM (n = 4697) and controls without GDM (n = 18 492) were divided into groups below 5th and 10th or above 90th and 95th percentile (pc) PAPP-A and fβ-hCG MoM levels. SGA was defined as a birthweight more than two standard deviations (SD) below and LGA more than two SDs above the sex-specific and gestational age-specific reference mean. Odds ratios were adjusted (aOR) for maternal age, BMI, ethnicity, IVF/ICSI, parity and smoking., Results: In pregnancies with GDM the proportion of SGA was 2.6% and LGA 4.5%, compared to 3.3% (p = 0.011) and 1.8% (p < 0.001) in the control group, respectively. In ≤ 5th and ≤ 10th pc PAPP-A groups, aORs for SGA were 2.7 (95% CI 1.5-4.7) and 2.2 (95% CI 1.4-3.5) in the GDM group and 3.8 (95% CI 3.0-4.9) and 2.8 (95% CI 2.3-3.5) in the reference group, respectively. When considering LGA, there was no difference in aORs in any high PAPP-A groups. In the low ≤ 5 percentile fβ-hCG MoM group, aORs for SGA was 2.3 (95% CI 1.8-3.1) in the control group. In fβ-hCG groups with GDM there was no association with SGA and the only significant difference was ≥ 90 percentile group, aOR 1.6 (95% CI 1.1-2.5) for LGA., Conclusion: Association with low PAPP-A and SGA seems to be present despite GDM status. High PAPP-A levels are not associated with increased LGA risk in women with or without GDM. Low fβ-hCG levels are associated with SGA only in non-GDM pregnancies., (© 2024. The Author(s).)

Objective: The aim of the present study was to compare accuracy, safety and cost-effectiveness of three β-hCG measurements protocols, applied in managing ectopic pregnancies (EP) with methotrexate (MTX): (1) day 1 to 7 β-hCG levels, (2) day 1 to 4 β-hCG levels and (3) day 4 to 7 β-hCG levels., Methods: Cost-minimization analysis (CMA) based on a retrospective study of patients treated with single-dose MTX for EP, was evaluated at a single institution between January 2001 to May 2021. Successful MTX treatment was defined as no surgical intervention. We evaluated safety by analyzing cases of day 4 interventions and cases of inconsistency between the different protocols. Predicting accuracy was assessed by the area under the receiver operating characteristic (AUC) curve., Results: A total of 229 patients with single dose MTX treatment were included. Overall, 184 (80.3%) patients were treated successfully with a single dose of MTX. For days 1 and 7 the optimal cutoff point was 7% reduction in β-hCG levels with sensitivity, specificity and PPV of 76.6% (69.9-82.5, 95% CI), 75.5% (60.5-87.1, 95% CI) and 92.8% (88.4-95.6, 95% CI), respectively. There was no significant difference between the protocols' AUC. None of the patients had any change of management during their day 4 visit in our 20 years of records. The cost for each visit day (day 4 and 7) was calculated with a total cost of 251 USD per patient., Conclusion: Patients treated with MTX for EP, measurement of day 1 and day 7 β-hCG serum levels has a cost minimization advantage and is not inferior to the traditional protocol for predictive accuracy and safety., (© 2024 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Objective: To systematically review the effect of contraceptive methods following gestational trophoblastic disease (GTD) on timing of beta-human chorionic gonadotropin (hCG) remission, risk of post-molar gestational trophoblastic neoplasia (GTN), risk of unintended incident pregnancy, and interactions between contraceptive methods and disease treatment., Study Design: We conducted a search of primary literature with search terms related to GTD and contraception through April 2023 in PubMed and extrapolated our search to other platforms. Randomized controlled trials, observational studies and case reports were eligible for inclusion if they reported on patients with known GTD who received a contraceptive method for pregnancy prevention. Data was abstracted on our main outcomes of interest: timing of beta-hCG remission, risk of post-molar GTN, risk of unintended incident pregnancy, and interactions between contraceptive methods and cancer-directed systemic disease treatment (e.g., chemotherapy). At least two authors reviewed manuscripts at each screening stage with consensus reached before data extraction. Quality assessment checklists were used to assess risk of bias for the different study types., Results: Five thousand one hundred and five studies were identified in the database search, of which 42 were included for analysis. Eight thousand two hundred and ninety four participants were evaluated. Over half of the studies were case reports and only two were randomized controlled trials. While there was sparse data on all outcomes, no differences were noted in beta-hCG monitoring, risk of post-molar GTN or incident pregnancies between different contraceptive types. Interactions between contraceptive methods and cancer-directed systemic disease treatment (e.g., chemotherapy) or specific adverse events of contraceptive methods were not identified., Conclusions: Data on contraceptive use following GTD is limited, but use of both hormonal and non-hormonal modern contraceptive methods appears safe. Counseling patients on the full range of contraceptive methods is important to help patients achieve their reproductive health goals and minimize the risk of disease progression through incomplete beta-hCG monitoring prior to future pregnancy., Implications: Hormonal and non-hormonal contraceptive options may be used by patients following gestational trophoblastic disease without apparent changes in beta-hCG regression or risk of post-molar gestational trophoblastic neoplasia., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the association, if any, between the grade of the trophectoderm (TE) and the rate at which β-human-chorionic gonadotropin (β-HCG) rises in early pregnancy., Methods: This is a retrospective cohort study including 1116 singleton clinical pregnancies resulting from in vitro fertilization with single day 5 blastocyst transfer at an academic fertility center. TE quality was assessed by trained embryologists employing standard criteria. Three groups were formed based on the TE grade: grade A (n = 358), grade B (n = 628), and grade C (n = 130). Main outcome measure was the rise (%) in serum levels of β-HCG (days 12 to 14 post embryo transfer), using the following formula [(β-HCG D14 - β-HCG D12) * 100/β-HCG D12]., Results: Fresh embryo transfers accounted for 64.1% of the population. Overall, in adjusted models there were no significant differences in the β-HCG% rise when comparing the TE grade C group to TE grade A [adjβ (95%CI): 10.09 (- 0.05, 20.22)] or when comparing TE grade Β group to TE grade A [4.46 (- 2.97, 11.88)]. When the analysis was restricted to fresh embryo transfers, significant differences were observed in the % rise of β-HCG when comparing the TE grade C group to TE grade A [adjβ (95%CI): 21.71 (5.67, 37.74)], but not when comparing the TE grade B group to TE grade A [2.68 (- 5.59, 10.95)]. In frozen transfers, there were no significant differences., Conclusion: TE grade appears to impact early pregnancy serum β-HCG levels in the setting of a fresh day 5 embryo transfer, even after adjusting for potential confounders., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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 β-human chorionic gonadotropin (β-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 β-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 β-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 β-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 β-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 β-hCG titres where treatment would be ineffective.

Background: Gestational diabetes mellitus (GDM) can result in adverse maternal and neonatal outcomes. Predicting those at high risk of GDM and early interventions can reduce the development of GDM. The aim of this study was to examine the associations between first-trimester prenatal screening biomarkers and maternal characteristics in relation to GDM in Chinese women., Methods: We conducted a retrospective cohort study of singleton pregnant women who received first-trimester aneuploidy and preeclampsia screening between January 2019 and May 2021. First-trimester prenatal screening biomarkers, including pregnancy-associated plasma protein A (PAPP-A), free beta-human chorionic gonadotropin, and placental growth factor (PLGF), along with maternal characteristics, were collected for analysis in relation to GDM. Receiver operating characteristic (ROC) curve and logistic regression analyses were used to evaluate variables associated with GDM., Results: Of the 1452 pregnant women enrolled, 96 developed GDM. PAPP-A (5.01 vs. 5.73 IU/L, P < 0.001) and PLGF (39.88 vs. 41.81 pg/mL, P = 0.044) were significantly lower in the GDM group than in the non-GDM group. The area under the ROC curve of combined maternal characteristics and biomarkers was 0.73 (95% confidence interval [CI] 0.68-0.79, P < 0.001). The formula for predicting GDM was as follows: P = 1/[1 + exp (-8.148 + 0.057 x age + 0.011 x pregestational body mass index + 1.752 x previous GDM history + 0.95 x previous preeclampsia history + 0.756 x family history of diabetes + 0.025 x chronic hypertension + 0.036 x mean arterial pressure - 0.09 x PAPP-A - 0.001 x PLGF)]. Logistic regression analysis revealed that higher pregestational body mass index (adjusted odds ratio [aOR] 1.03, 95% CI 1.01 - 1.06, P = 0.012), previous GDM history (aOR 9.97, 95% CI 3.92 - 25.37, P < 0.001), family history of diabetes (aOR 2.36, 95% CI 1.39 - 4.02, P = 0.001), higher mean arterial pressure (aOR 1.17, 95% CI 1.07 - 1.27, P < 0.001), and lower PAPP-A level (aOR 0.91, 95% CI 0.83 - 1.00, P  = 0.040) were independently associated with the development of GDM. The Hosmer-Lemeshow test demonstrated that the model exhibited an excellent discrimination ability (chi-square = 3.089, df = 8, P = 0.929)., Conclusion: Downregulation of first-trimester PAPP-A and PLGF was associated with the development of GDM. Combining first-trimester biomarkers with maternal characteristics could be valuable for predicting the risk of GDM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lu, Chen, Sun, Chen, Wang and Chen.)

Objective: To explore the association between the concentration of maternal serum biomarkers and the risk of fetal carrying chromosome copy number variants (CNVs)., Methods: Pregnant women identified as high risk in the second-trimester serological triple screening and underwent traditional amniotic fluid karyotype analysis, along with comparative genomic hybridization array (aCGH)/copy number variation sequencing (CNV-seq), were included in the study. We divided the concentration of serum biomarkers, free beta-human chorionic gonadotropin (fβ-hCG), alpha fetoprotein (AFP) and unconjugated estriol (uE3), into three levels: abnormally low, normal and abnormally high. The prevalence of abnormally low, normal and abnormally high serum fβ-hCG, AFP and uE3 levels in pregnant women with aberrant aCGH/CNV-seq results and normal controls was calculated., Results: Among the 2877 cases with high risk in the second-trimester serological triple screening, there were 98 chromosome abnormalities revealed by karyotype analysis, while 209 abnormalities were detected by aCGH/CNVseq (P＜0.001) . The carrying rate of aberrant CNVs increased significantly when the maternal serum uE3 level was less than 0.4 multiple of median (MoM) of corresponding gestational weeks compared to normal controls, while the carrying rate of aberrant CNVs decreased significantly when the maternal serum fβ-hCG level was greater than 2.5 MoM compared to normal controls. No significant difference was found in the AFP group., Conclusion: Low serum uE3 level (<0.4 MoM) was associated with an increased risk of aberrant CNVs., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: This work aimed to explore the relationship between epidermal growth factor (EGF) and β-human chorionic gonadotropin (β-HCG) and ectopic pregnancy types and impact on prognosis., Methods: Twenty women with normal pregnancies (NPs) were recruited as control group, and twenty women each with tubal pregnancy (TP) and cervical pregnancy (CP) were recruited. Blood samples were collected to detect EGF and β-HCG. Data on length of hospital stay and incidence of complications were collected. The differences in serum EGF and β-HCG levels were compared among groups and within various types of ectopic pregnancy using analysis of variance and Pearson correlation analysis., Results: Serum EGF and β-HCG were notably lower in TP and CP group vs. controls (P < 0.05). In subgroup analysis within the types of ectopic pregnancy, serum EGF levels were drastically higher in TP group vs. CP group (P < 0.05). Serum EGF levels were negatively correlated with pregnancy outcomes and incidence of complications (P < 0.05). In patients with TP and CP, serum EGF and β-HCG recovery time and hospital stay differed drastically (P < 0.05). Serum EGF and β-HCG levels showed optimal cutoff values identified at 2.65 μg/L and 11,745.35 IU/L, respectively. The corresponding area under the curve (AUC) values were 0.885 and 0.841., Conclusion: Elevated levels of EGF may be associated with the occurrence of ectopic pregnancy and may impact the type of ectopic pregnancy, pregnancy outcomes, and the incidence of complications. Further clinical research is warranted to investigate these findings., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: This study aimed to investigate the performance, cost-effectiveness and additional findings of combined detailed ultrasound and biochemical screening for risks of major fetal trisomies in the first-trimester., Methods: This is a retrospective analysis study, we estimated the risk of trisomies 21, 18 and 13 based on maternal age, fetal nuchal translucency thickness, nasal bone, ductus venosus pulsatility index velocity, tricuspid regurgitation, fetal heart rate, free beta-human chorionic gonadotropin, and pregnancy-associated plasma protein A in singleton pregnant women, and performed non-invasive prenatal testing for women with risks of trisomy 21 between 1:500 and 1:300. Invasive diagnostic testing was performed for women with positive or failed non-invasive prenatal testing result and in the high-risk group of this screening method. The direct costs were compared between this strategy and the non-invasive prenatal testing which alone used as first-line screening for all pregnant women., Results: Among 25,155 singleton pregnant women who underwent screening, 24,361 were available for analysis, of these, 194 cases underwent non-invasive prenatal testing. Among the 24,361 women, 39, 19, and 7 had trisomies 21, 18 and 13, respectively. The use of this strategy could potentially detect approximately 94.87% of trisomy 21 cases, 100% of trisomy 18 cases, and 100% of trisomy 13 cases, with false-positive rates of 2.49%, 0.41%, and 0.49%, respectively. The overall detection rate and overall false-positive rates were 96.92% and 2.52%, respectively. The detection rate was 100% in the advanced age group and 94.12% in the general age group. Additionally, structural abnormalities were detected in 137 fetuses, and 44 fetuses had other chromosomal abnormalities. The total cost of this strategy was $3,730,843.30, and the cost per person tested was $153.15. The total cost of using non-invasive prenatal testing as the first-line strategy would be $6,813,387.04 and the cost per person tested was $279.68., Conclusions: Our strategy is an efficient and cost-effective approach for detecting major trisomies and identifying more fetuses with a potential abnormality. Therefore, this strategy is a valuable screening method and highly feasible in the clinical setting., (© 2023. The Author(s).)

Objective: This study aimed to investigate the effects of the presence of subchorionic hematoma (SH) in early pregnancies with threatened miscarriage (TM) on levels of first-trimester maternal serum markers, pregnancy-associated plasma protein-A (PAPP-A), and free β-human chorionic gonadotropin (β-hCG) levels., Methods: The data of TM cases with SH in the first trimester between 2015 and 2021 were evaluated retrospectively. The data of age and gestational age-matched TM cases without SH were also assessed to constitute a control group. Demographic characteristics, obstetric histories, ultrasonographic findings, and free β-hCG and PAPP-A levels of the groups were compared., Results: There were 119 cases in the study group and 153 cases in the control group. The median vertical and longitudinal lengths of the SH were 31 mm and 16 mm. The median age of both groups was similar (p=0.422). The MoM value of PAPP-A was 0.088 (.93) in the study group and 0.9 (0.63) in the control group (p=0.519). Similarly, the MoM value of free β-hCG was 1.04 (0.78) in the study group and 0.99 (0.86) in the control group (p=0.66). No significant relationship was found in the multivariate analysis between free β-hCG MoM, PAPP-A MoM, age, gravida, and vertical and longitudinal lengths of the hematoma (p>0.05)., Conclusion: The level of PAPP-A and free β-hCG were not affected by the SH. Therefore, these markers can be used reliably in TM cases with SH for the first-trimester fetal aneuploidy screening test., Competing Interests: Conflicts to interest: none to declare.

In this investigation, we explored the correlation between first-trimester biochemical markers and the incidence of preterm birth (PTB), irrespective of the cause, spontaneous preterm birth (sPTB), and preterm premature rupture of membranes (pPROM) within a cohort comprising 1164 patients. It was discovered that diminished levels of Pregnancy-Associated Plasma Protein-A (PAPP-A) between 11 and 13 + 6 weeks of gestation significantly contributed to the risk of preterm deliveries both before 35 and 37 weeks, as well as to pPROM instances. Furthermore, women experiencing sPTB before the 37th week of gestation also exhibited lower concentrations of PAPP-A. Moreover, reduced first-trimester concentrations of free beta-human chorionic gonadotropin (fb-HCG) were identified as a risk factor for deliveries preceding 37 weeks, pPROM, and sPTB before 35 weeks of gestation. Despite these correlations, the area under the curve for these biochemical markers did not surpass 0.7, indicating their limited diagnostic potential. The most significant discriminatory capability was noted for PAPP-A levels, with a threshold of < 0.71 multiples of the median (MoM) predicting PTB before 37 weeks, yielding an odds ratio of 3.11 (95% Confidence Interval [CI] 1.97-4.92). For sPTB, the greatest discriminatory potential was observed for PAPP-A < 0.688, providing an OR of 2.66 (95% CI 1.51-4.66). The cut-off points corresponded to accuracies of 76.05% and 79.1%, respectively. In regression analyses, the combined predictive models exhibited low explanatory power with R 2 values of 9.2% for PTB and 7.7% for sPTB below 35 weeks of gestation. In conclusion, while certain biochemical markers demonstrated associations with outcomes of preterm birth, their individual and collective predictive efficacies for foreseeing such events were found to be suboptimal., (© 2024. The Author(s).)

Abstract: An eight-year-old child presenting with increased thirst, raised intracranial tension and visual deterioration was diagnosed with synchronous suprasellar and pineal lesions, for which she underwent partial resection of the suprasellar lesion. Histopathological examination suggested pure germinoma. Tumor marker evaluation showed significantly raised levels of beta human chorionic gonadotropin (βHCG), favoring a non-germinoma germ cell tumor (NGGCT), leading to a diagnostic dilemma as the histology and βHCG levels were contradictory. Giving cognizance to the tumor marker levels, the treatment was designed on the lines of NGGCT. Planning of radiotherapy including craniospinal irradiation (CSI) and boost to both lesions was once again a challenge, given the proximity of the lesions to vital organs at risk (OAR). Given the child's age and location of lesions, the target volumes and doses of radiation were designed to optimize between the goals of achieving long-term local control and minimizing late-onset toxicities., (Copyright © 2023 Copyright: © 2023 Journal of Cancer Research and Therapeutics.)

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 (β-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 β-hCG (<2000 mIU/ml) had higher treatment efficacy compared with women with higher initial serum β-hCG (96.5 % vs 71.4 %), regardless of protocol type. The length of hospital stay for the women treated with the single-dose MTX protocol was 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 β-hCG < 2000 mIU/ml., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: The objective of the study was to increase the prediction of success of single-dose methotrexate therapy in ectopic pregnancy patients with modified parameters obtained from complete blood count and beta-human chorionic gonadotropin (β-hCG) parameters. In this way, it was aimed to predict patients whose methotrexate treatment may fail and rupture, to avoid unnecessary methotrexate treatment, to shorten the duration of hospital stay and to reduce patient mortality., Materials and Methods: 233 patients diagnosed with ectopic pregnancy between January 1, 2017, and March 01, 2022, in the obstetrics and gynecology service of a tertiary center were included in the study., Results: The mean of β-hCG was 1976 in the methotrexate group and 2358 in the surgery group (p < 0.05). The ROC curve determined the effect of BW (β-hCGxWBC/1000) and BP (β-hCGx1000/PLT) markers in diagnosing patients who will need surgery in ectopic pregnancy. The areas under the ROC curve for β-hCG, BW and BP were 0.86, 0.99 and 0.94, respectively (p < 0.05). β-hCG > 2139.03, BW > 30.96 and BP > 10.17 values were significantly associated with the need for surgery in ectopic pregnancy patients (p < 0.05). Logistic regression analysis revealed that a 1-unit increase in BP caused a statistically significant 1.77-fold increase in surgical need in patients with ectopic pregnancy. In contrast, a 1-unit increase in BW caused a 2.34-fold increase in surgical need (p < 0.05)., Conclusion: The study results showed that BW and BP values together with β-hCG are effective in predicting ectopic pregnancy patients who may undergo surgery., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: This study aimed to determine the association of first-trimester maternal serum biomarkers with preterm birth (PTB), fetal growth restriction (FGR) and hypertensive disorders of pregnancy (HDP) in twin pregnancies., Methods: This is a retrospective cohort study of twin pregnancies followed at Maternidade Dr. Alfredo da Costa, Lisbon, Portugal, between January 2010 and December 2022. We included women who completed first-trimester screening in our unit and had ongoing pregnancies with two live fetuses, and delivered after 24 weeks. Maternal characteristics, pregnancy-associated plasma protein-A (PAPP-A) and β-human chorionic gonadotropin (β-hCG) levels were analyzed for different outcomes: small for gestational age (SGA), gestational hypertension (GH), early and late-onset pre-eclampsia (PE), as well as the composite outcome of PTB associated with FGR and/or HDP. Univariable, multivariable logistic regression analyses and receiver-operating characteristic curve were used., Results: 466 twin pregnancies met the inclusion criteria. Overall, 185 (39.7%) pregnancies were affected by SGA < 5th percentile and/or HDP. PAPP-A demonstrated a linear association with gestational age at birth and mean birth weight. PAPP-A proved to be an independent risk factor for SGA and PTB (< 34 and < 36 weeks) related to FGR and/or HDP. None of the women with PAPP-A MoM > 90th percentile developed early-onset PE or PTB < 34 weeks., Conclusion: A high serum PAPP-A (> 90th percentile) ruled out early-onset PE and PTB < 34 weeks. Unless other major risk factors for hypertensive disorders are present, these women should not be considered candidates for aspirin prophylaxis. Nevertheless, close monitoring of all TwP for adverse obstetric outcomes is still recommended., (© 2024. The Author(s).)

Aim: This aim of this study was to detail maternal and fetal anomalies observed on a national scale in a large French cohort of patients presenting high hCG values (≥10 multiple of the median [MoM]) at Down syndrome screening in order to define clear and optimal guidelines., Methods: This is a retrospective multicenter study based on a French annual database of all trisomy 21 screenings. Our study targeted and studied cases with hCG or hCGβ values ≥10 MoM. Complementary exams and outcomes were analyzed., Results: The calculated frequency was 0.05% for hCGβ ≥10 MoM in unselected patients. For this series of 289 cases, a complication of the pregnancy or a poor outcome was observed in 145 cases (51%) as follows: 96 (66%) cases of fetal disease, 23 (16%) of maternal disease, 5 (3.5%) of placental anomalies and 21 (14.5%) of systemic disease concerning mother, fetus and placenta., Conclusion: This study establishes the frequency of hCG or hCGβ values ≥10 MoM, presents a flow chart that optimizes follow-up, and gives clear information for patients presenting with such abnormal values at trisomy 21 screening., (© 2024 The Author(s). Prenatal Diagnosis published by John Wiley & Sons Ltd.)

Objective: Chronic ectopic pregnancy is a variant of ectopic pregnancy featured with a low or normal serum beta-human chorionic gonadotropin (β-hCG) test. Obscure clinical presentations and non-specific images make chronic ectopic pregnancy a diagnostic dilemma until now., Case Report: A 40-year-old female was misdiagnosed as tubo-ovarian abscess initially due to chronic lower abdominal pain, negative pregnancy test, and a complicated pelvic mass on abdominal CT scan and serial follow-up ultrasonography. Diagnostic laparoscopy was performed because of persistent pelvic mass with abdominal pain and irregular vaginal bleeding. Left tubal salpingectomy was performed and pathology reported a hematocele with inactive trophoblast tissue. Chronic ectopic pregnancy was proved. The symptoms resolved completely after our surgery., Conclusion: An abnormal adnexal mass with a history of recent pregnancy could still be possible for chronic ectopic pregnancy even with a negative pregnancy test. Diagnostic laparoscopy and pathology confirmation could be helpful when the clinical manifestation is confusing., (Copyright © 2024. Published by Elsevier B.V.)

Background: Choriocarcinoma is a highly malignant pregnancy-related trophoblastic neoplasm, characterized by early metastasis to the lungs. Therefore, patients may manifest nongynecological symptoms owing to distant metastases. The incidence of choriocarcinoma after a term pregnancy is really rare (1/160,000 pregnancies)., Case Presentation: We report a case of a 20-year-old Iranian woman, gravida 2 para 1 live 1 abortion 1, who was referred to our gynecology department with sudden onset dyspnea and pain in the left hemithorax the day after her labor. The index pregnancy was without any complications. After the initial workup, the elevation of β-human chorionic gonadotropin (HCG) levels (> 1,000,000) along with the identification of clinical (vaginal lesions) and radiological evidence of distant metastases (bilateral pulmonary nodes) directed us toward pulmonary metastatic choriocarcinoma diagnosis. After the oncology consult, the etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine chemotherapy regimen was started for the patient. She responded well to the treatment and is currently continuing her chemotherapy process., Conclusion: The prognosis of choriocarcinoma is very good if the treatment is started on time. We suggest that clinicians should consider gestational trophoblastic neoplasia in their differential diagnosis of the post-natal period complications, especially after a term and nonmolar pregnancy., (© 2024. The Author(s).)

Background: The accurate prediction of pregnancy outcomes in in vitro fertilization (IVF) cycles is crucial. While several studies have been conducted on the predictive power of serum estradiol (E 2 ) and β-hCG concentrations post-embryo transfer (ET) for pregnancy outcomes, there is debate on the predictive value of E 2 . The objective of this study was to investigate the predictive efficacy of combining serum E 2 and β-hCG levels on early reproductive outcomes 12 days after embryo transfer., Methods: A total of 1521 patients with β-hCG positive values on day 12 following frozen-thawed embryo transfer (FET) with natural endometrial preparation cycles (NCs) were gathered in affiliated Women's Hospital of Jiangnan University. Using logistic regression, the relationship between pregnancy outcome and early serum E 2 and β-hCG concentrations was examined. The receiver-operating characteristic (ROC) analysis was used to assess the predictive accuracy of the serum E 2 and β-hCG concentrations., Results: Notable distinctions were observed in the serum E 2 and β-hCG levels on the twelfth day following FET with NCs between the groups classified as clinical pregnancy group (CP Group) and biochemical pregnancy group (BP Group). In addition, the cutoff values for E 2 and β-hCG on day 12 following FET with NCs in cleavage embryo group (CE Group) were 129.25 pg/mL and 156.60 mIU/mL, respectively. The threshold values for E 2 and β-hCG for the blastocyst group (B Group) were 174.45 pg/mL and 217.70 mIU/mL. Serum E 2 day12 and β-hCG day12 were found to be substantially linked with clinical pregnancy by logistic regression analysis., Conclusions: Serum E 2 and β-hCG concentrations were found to be significantly different between the CP Group and BP Group in infertility women underwent FET with NCs. Our retrospective cohort study's findings suggest that the combination of early E 2 and β-hCG levels on day 12 post-FET could be used as a predictive tool to evaluate the likelihood of both positive and negative pregnancy outcomes in FET with NCs., (© 2024. The Author(s).)

Purpose: We aimed to evaluate the diagnostic sensitivity and specificity of the miRNA-371a-3p for the primary diagnosis of germ cell tumors (GCT) and to investigate its relationship with pathological factors and clinical stage in the Turkish population., Materials and Methods: In this prospective study, a total of 60 patients with GCTs, and 40 healthy male controls were examined for serum levels of miRNA-371a-3p before orchiectomy and again two weeks after surgery. The miRNA-371a-3p, alpha-fetoprotein (AFP), and beta-human chorionic gonadotropin (bHCG) levels in the preoperative and postoperative periods were compared at different clinical stages. Receiver operating characteristics curve analyses were performed to determine the sensitivity and specificity of miRNA-371a-3p. Clinical and pathological factors such as clinical stage (CS), tumor size, histology, rete testis invasion, and lymphovascular invasion, potentially impacting miRNA-371a-3p expression levels (relative quantity, RQ), were evaluated statistically., Results: The sensitivity of miR-371a-3p in GCT patients was 98.3%, and the specificity was 95% (AUC = 0.997 [95%Cl:0.99-1], p < .001). miR-371a-3p expression was not detected in two patients with teratoma. The median miR-371a-3p RQ was 489 times in GCT and 2.2 times in the Control group (p < .001). In the postoperative period, there was a significant decrease in AFP and bHCG levels in all CS-1 (p = .01) and 30% of the other CS (p = .3). Throughout this time there was a decrease of 19 times at the miR-371a-3p RQ in CS-1(p < .001) and 1.6 times in the other CS (p < .001). The miR-371a-3p RQs were correlated with tumor size and CS., Conclusion: The miR-371a-3p seems to have higher diagnostic accuracy than classical serum tumor markers in GCT.

Background: A retrospective cohort study was conducted to collect the data of pregnant women who received hospital delivery in Hangzhou Women's Hospital from January 2018 to December 2020, and who participated in the second trimester (15-20 +6  weeks) of free beta human chorionic gonadotropin (free β-hCG). And the study was conducted to explore the relationship between maternal serum free β-hCG and adverse pregnancy outcomes (APO)., Methods: We retrospectively analyzed the clinical data of 1,978 women in the elevated maternal serum free β-hCG group (free β-hCG ≥ 2.50 multiples of the median, MoM) and 20,767 women in the normal group (0.25 MoM ≤ free β-hCG < 2.50 MoM) from a total of 22,745 singleton pregnancies, and modified Poisson regression analysis was used to calculate risk ratios (RRs) and 95% confidence intervals (CI) of the two groups., Results: The gravidity and parity in the elevated free β-hCG group were lower, and the differences between the groups were statistically significant (all, P < 0.05). The risks of polyhydramnios, preeclampsia, and hyperlipidemia, were increased in women with elevated free β-hCG levels (RRs: 1.996, 95% CI: 1.322-3.014; 1.469, 95% CI: 1.130-1.911 and 1.257, 95% CI: 1.029-1.535, respectively, all P < 0.05), intrauterine growth restriction (IUGR) and female infants were also likely to happen (RRs = 1.641, 95% CI: 1.103-2.443 and 1.101, 95% CI: 1.011-1.198, both P < 0.05). Additionally, there was an association between elevated AFP and free β-hCG levels in second-trimester (RR = 1.211, 95% CI: 1.121-1.307, P < 0.001)., Conclusions: APOs, such as polyhydramnios, preeclampsia, and hyperlipidemia, were increased risks of elevated free β-hCG levels, IUGR and female infants were also likely to happen. Furthermore, there was an association between elevated AFP levels and elevated free β-hCG levels in second-trimester. We recommend prenatal monitoring according to the elevated maternal serum free β-hCG level and the occurrence of APO., (© 2024. The Author(s).)

Objectives: To compute a set of atypicality indices based on combined first-trimester screening (cFTS) markers and second-trimester estimated fetal weight (EFW), and to demonstrate their potential in identifying pregnancies at reduced or increased risk of chromosomal aberrations following a low-risk cFTS result., Methods: The atypicality index quantifies the unusualness of an individual set of measurements relative to a reference distribution and can be computed from any variables or measurements available. A score of 0% on the atypicality index represents the most typical profiles, while a score of 100% indicates the highest level of atypicality. From the Danish Fetal Medicine Database, we retrieved data on all pregnant women seen for cFTS in the Central Denmark Region between January 2008 and December 2018. All pregnancies with a cytogenetic or molecular analysis obtained prenatally, postnatally or following pregnancy loss or termination were identified. A first-trimester atypicality index (A cFTS ) was computed based on nuchal translucency (NT) thickness, maternal serum free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A). Furthermore, a second-trimester index (A cFTS + EFW ) was computed from cFTS markers and EFW from a routine second-trimester anomaly scan. All pregnancies were stratified into subgroups based on their atypicality levels and their cFTS risk estimates. The risk of chromosomal aberrations in each subgroup was then compared with the overall prevalence, and a graphical presentation of the multivariate measurement profiles was developed., Results: We retrieved data on 145 955 singleton pregnancies, of which 9824 (6.7%) were genetically examined. Overall, 1 in 122 (0.82% (95% CI, 0.77-0.87%)) of all pregnancies seen for cFTS were affected by a fetal chromosomal aberration, and in screen-negative pregnancies (cFTS trisomy 21 risk < 1 in 100 and/or trisomy 18/13 risk < 1 in 50), 0.41% (95% CI, 0.38-0.44%) were affected. In screen-negative pregnancies with a typical first-trimester profile (A cFTS < 80% ), the risk of chromosomal aberrations was significantly reduced (0.28%) compared with the overall risk. The risk of chromosomal aberrations increased with higher atypicality index to 0.49% (A cFTS [80-90%) ), 1.52% (A cFTS [90-99%) ) and 4.44% (A cFTS ≥ 99% ) and was significantly increased in the two most atypical subgroups. The same applied for the second-trimester atypicality index, with risks of chromosomal aberrations of 0.76% and 4.16% in the two most atypical subgroups (A cFTS + EFW [90-99%) and A cFTS + EFW ≥ 99% , respectively)., Conclusions: As an add-on to cFTS, the atypicality index identifies women with typical measurement profiles, which may provide reassurance, whereas atypical profiles may warrant specialist referral and further investigation. In pregnancies identified as low risk on cFTS but with a highly atypical distribution of NT, PAPP-A and β-hCG, the risk of a chromosomal aberration is substantially increased. The atypicality index optimizes the interpretation of pre-existing prenatal screening profiles and is not limited to cFTS markers or EFW. © 2023 International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 International Society of Ultrasound in Obstetrics and Gynecology.)

Aim: The single-dose methotrexate (MTX) regimen is effective and minimizes side effects but an additional second dose is needed in case of failure in an ectopic pregnancy (EP). We aimed to predict the additional MTX dose by evaluating the change in β-hCG values between day 0 and day 4 in EPs with administered single-dose MTX regimen., Method: A total of 454 tubal EPs between 2013 and 2019 were evaluated retrospectively. Cases cured with a single dose of MTX without an additional dose were accepted as the control group, and cases under a single-dose regimen were cured by applying a second dose of MTX on the 7th day were accepted as the study group. Obstetric and demographic characteristics and the change in β-hCG values compared in both groups., Results: Age, body mass index (BMI), gravida, smoking, abdominal surgery, presence of IUDs, initial β-hCG levels (0th day), and EP size were similar in both groups, but the presence of previous EP history was significantly higher in the study group. The change of β-hCG from days 0 and 4 determined that a 20% increase predicts the need for a second dose of MTX with 72.4% sensitivity, and 87.8% negative predictive value (NPV)., Conclusion: The single-dose MTX protocol is successful in 83.3% of convenient cases (as the control group), but an increase of 20% in β-hCG between days 0 and 4 predicts the patients who need to be administered second-dose MTX, and thus, a double-dose MTX protocol will be achieved early., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: We aimed to assess the impact of the coronavirus disease 2019 pandemic on the clinical presentation of tubal ectopic pregnancies., Methods: This retrospective cohort study was conducted at a tertiary center and included 76 cases of tubal ectopic pregnancies. The study period was divided into two groups: the pre-coronavirus disease group (January 2018 to February 2020, Group 1; n=47, 61.8%) and the coronavirus disease group (March 2020 to February 2022, Group 2; n=29, 38.2%). Subgroup analysis was also performed for tubal ruptured ectopic pregnancies as Group 1 (n=15, 62.5%) and Group 2 (n=9, 37.5%)., Results: No statistically significant differences were observed between the pre-coronavirus disease and coronavirus disease groups in terms of demographic characteristics. Although the serum beta-human chorionic gonadotropin level was found to be higher in Group 2, the difference was not statistically significant (p=0.7). The groups appeared to be similar in treatment management, duration of hospitalization, and blood transfusion needs (p=0.3, p=0.6, and p=0.5, respectively). Additionally, no significant difference was observed between the groups in the evaluation of ruptured ectopic pregnancies (p=0.5). In the subgroup analysis of tubal ruptured ectopic pregnancies, no significant difference was observed., Conclusion: To the best of our knowledge, there are few studies evaluating the effect of the pandemic on tubal ectopic pregnancies in the literature. Although we did not report statistically significant differences between groups in our study, given the potential prolonged duration of the pandemic, healthcare professionals should actively prompt their patients to seek necessary medical assistance.

A significant number of pregnancies are lost in the first trimester and 1-2% are ectopic pregnancies (EPs). Early pregnancy loss in general can cause significant morbidity with bleeding or infection, while EPs are the leading cause of maternal mortality in the first trimester. Symptoms of pregnancy loss and EP are very similar (including pain and bleeding); however, these symptoms are also common in live normally sited pregnancies (LNSP). To date, no biomarkers have been identified to differentiate LNSP from pregnancies that will not progress beyond early gestation (non-viable or EPs), defined together as combined adverse outcomes (CAO). In this study, we present a novel machine learning pipeline to create prediction models that identify a composite biomarker to differentiate LNSP from CAO in symptomatic women. This prospective cohort study included 370 participants. A single blood sample was prospectively collected from participants on first emergency presentation prior to final clinical diagnosis of pregnancy outcome: LNSP, miscarriage, pregnancy of unknown location (PUL) or tubal EP (tEP). Miscarriage, PUL and tEP were grouped together into a CAO group. Human chorionic gonadotrophin β (β-hCG) and progesterone concentrations were measured in plasma. Serum samples were subjected to untargeted metabolomic profiling. The cohort was randomly split into train and validation data sets, with the train data set subjected to variable selection. Nine metabolite signals were identified as key discriminators of LNSP versus CAO. Random forest models were constructed using stable metabolite signals alone, or in combination with plasma hormone concentrations and demographic data. When comparing LNSP with CAO, a model with stable metabolite signals only demonstrated a modest predictive accuracy (0.68), which was comparable to a model of β-hCG and progesterone (0.71). The best model for LNSP prediction comprised stable metabolite signals and hormone concentrations (accuracy = 0.79). In conclusion, serum metabolite levels and biochemical markers from a single blood sample possess modest predictive utility in differentiating LNSP from CAO pregnancies upon first presentation, which is improved by variable selection and combination using machine learning. A diagnostic test to confirm LNSP and thus exclude pregnancies affecting maternal morbidity and potentially life-threatening outcomes would be invaluable in emergency situations., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Aim: Methotrexate has demonstrated efficacy in treating ectopic pregnancies. This study explores factors influencing treatment success, focusing on laboratory and ultrasonographic findings, particularly the day 4 to day 1 β-hCG level ratio., Methods: Retrospective cohort study was conducted within patients diagnosed with tubal ectopic pregnancy. Patients' characteristics, ultrasound findings, laboratory data, and β-hCG levels (days 1, 4, 7), and operation findings were reviewed. Women's characteristics were investigated who were treated with single dose of MTX (50 mg/m 2 ). Patients who were performed surgery after MTX treatment were identified as MTX treatment failure., Results: Among 439 women, 259 underwent surgery due to acute symptoms. Of those treated with MTX, 143 experienced treatment success, while 37 underwent surgery after MTX (MTX failure). Comparative analysis revealed significant differences in β-hCG levels on admission (1128 and 4125 mIU/mL) and the day 4 to day 1 β-hCG ratio (0.91 and 1.25). The overall MTX success rate was 79%, reaching 93% and 89% for β-hCG levels <1000 mIU/mL and <2000 mIU/mL, respectively. Success dropped to 50% with levels exceeding 5000 mIU/mL. ROC analysis identified a crucial 2255 mIU/mL cut-off for β-hCG (sensitivity 70.3% and specificity 68.5%) and a day 4 to day 1 β-hCG ratio of 95.5% (sensitivity 84.7%, specificity 72.5%, positive predictive value 75.4%) for predicting MTX success., Conclusion: Establishing a β-hCG cutoff can reduce hospital stay. The day 4 to day 1 β-hCG ratio holds promise as a widely applicable predictor for MTX success or for determining MTX administration on day 4., (© 2024 Japan Society of Obstetrics and Gynecology.)

Background: Medical treatment, expectant approaches, and surgical treatment options are available in the treatment of ectopic pregnancy. Regardless of the treatment, in addition to its effectiveness, the main concern is to limit the risk of relapse and preserve fertility., Objectives: Determine the impact of medical or surgical treatment for ectopic pregnancy on future fertility., Design: Retrospective., Setting: Department of obstrtrics and gynecolgy at Ankara Etlik Zübeyde Hanım Women's Health Training and Research Hospital, Ankara, Turkey., Patients and Methods: Patients who were treated for ectopic pregnancy between June 2016 and November 2019 were allocated into two groups. Expectant approach or medical treatment by methotrexate constituted the conservative treatment group while salpingectomy by laparoscopy indicated the surgical treatment group., Main Outcome Measures: Fertility rates within two years following treatment were evaluated according to treatment options., Sample Size: 202 patients., Results: Of the 202 patients, 128 had medical treatment and 74 patients had surgical treatment for ectopic pregnancy. Of 272 diagnosed with ectopic pregnancy, 70 were excluded for various reasons. Parity and unemployment rate was significantly higher in the surgical treatment ( P =.006 and P =.12, respectively). Moreover, ectopic mass size and serum β-hCG levels were significantly higher in the surgical treatment group ( P <.001 and P <.001, respectively). There were no significant differences between the conservative and surgical treatment groups in time to pregnancy (17.0 months vs 19.0 months, P =.255). Similarly, there was no significant difference between the conservative and surgical treatment groups with respect to history of infertility ( P =.12). There were no significant differences between the conservative and surgical treatment groups in terms of live birth (51.6% vs 44.6%) and ectopic pregnancy (2.3% vs 1.4%) ( P =.72 for both). There was no significant difference between the conservative and surgical treatment groups with respect to infertility rate (35.9% vs 41.9%, P =.72) and admittance to the IVF program (3.9% vs 6.8%, P =.39) following ectopic pregnancy treatment., Conclusions: Reproductive outcomes did not differ significantly in women undergoing expectant management, medical treatment, and surgery for ectopic pregnancy. This finding suggests that clinicians should not hesitate to act in favor of surgical treatment for ectopic pregnancy even if there were concerns for future fertility., Limitations: Retrospective study., Competing Interests: CONFLICT OF INTEREST: None.

Introduction: Ectopic pregnancies are a significant cause of morbidity and mortality in the first trimester of pregnancy. Hospital protocols requiring a specific beta-human chorionic gonadotropin (β-hCG) level to qualify for diagnostic testing (pelvic ultrasound) can delay diagnosis and treatment. In this study we sought to determine the relationship between β-hCG level and the size of ectopic pregnancy with associated outcomes., Methods: We performed a retrospective case review of patients diagnosed with ectopic pregnancy in an urban, academic emergency department specializing in obstetrical care, from January 1, 2015-December 31, 2017. Variables extracted included presentation, treatment, adverse outcomes, and rates of rupture., Results: We identified 519 unique ectopic pregnancies. Of those ectopic pregnancies, 22.9% presented with evidence of rupture on ultrasound, and 14.4% showed evidence of hemodynamic instability (pulse >100 beats per minute; systolic blood pressure <90 millimeters of mercury; or evidence of significant blood loss) on presentation. Medical management outcomes were as follows: of 177 patients who received single-dose methotrexate, 14.7% failed medical management and required surgical intervention; of 46 who received multi-dose methotrexate, 36.9% failed medical management and required surgical intervention. Ultimately, 55.7% of patients required operative management of their ectopic pregnancy. Mean β-hCG level at initial presentation was 7,096 milli-international units per milliliter (mIU/mL) (SD 88,872 mIU/mL) with a median of 1,289 mIU/mL; 50.4% of ectopic pregnancies presented with β-hCG levels less than the standard discriminatory zone of 1,500 mIU/mL. Additionally, 44% of the patients who presented with evidence of rupture had β-hCG levels less than 1,500 mIU/mL. Comparison of size of ectopic pregnancy (based on maximum dimension in millimeters) to β-hCG levels revealed a very weak correlation (r = 0.144, P  < .001 ), and detection of ectopic pregnancies by ultrasound was independent of β-hCG levels., Conclusion: Levels of β-hCG do not correlate with the presence or size of an ectopic pregnancy, indicating need for diagnostic imaging regardless of β-hCG level in patients with clinical suspicion for ectopic pregnancy. Almost one-sixth of patients presented with evidence of hemodynamic instability, and approximately one quarter of patients presented with evidence of rupture requiring emergent operative management. Ultimately, more than half of patients required an operative procedure to definitively manage their ectopic pregnancy., Competing Interests: Conflicts of Interest: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. No author has professional or financial relationships with any companies that are relevant to this study. There are no conflicts of interest or sources of funding to declare.

Aim: This study aims to determine whether second-trimester uterine artery (UtA) Doppler combined with first-trimester abnormal pregnancy-associated plasma protein-A (PAPP-A) and β-human chorionic gonadotropin (β-Hcg) levels predicts adverse obstetric and neonatal outcomes., Materials and Methods: This study of 289 pregnant women included 196 with normal PAPP-A and free β-HCG values (control group) and 93 with abnormal values (study group) in the first-trimester screening test. Second-trimester UtA Doppler sonography was done in these pregnancies. The perinatal prediction and screening potential of UtA Doppler pulsatility index (PI) parameters were examined in the study group., Results: UtA PI >95 percentile increased birth before the 37th week by 4.46 times, birth before the 34th week by 7.44 times, preeclampsia risk by 3.25 times, fetal growth restriction (FGR) risk by 4.89 times, and neonatal intensive care unit (NICU) admission rates by 3.66 times in the study group (p < 0.05 for all). UtA PI >95 percentile had 49.2% sensitivity and 82.1% specificity for birth before 37 weeks. For birth before 34 weeks, sensitivity was 80.0% and specificity 65.0%. FGR has 70.5% sensitivity and 67.1% specificity. Screening for preeclampsia has 66.6% sensitivity and 61.9% specificity., Conclusion: Adding UtA Doppler in the second trimester to pregnancies with abnormal PAPP-A and/or free β-Hcg values in the first trimester may be a useful screening method for adverse outcomes., (© 2024 Wiley Periodicals LLC.)

Objective: We investigated the efficacy of a combination of laparoscopy and bilateral uterine artery occlusion (BUAO) for the treatment of type II cesarean scar pregnancy (CSP)., Methods: Patients with type II CSP underwent laparoscopy + bilateral uterine artery embolization (control group) or laparoscopy + BUAO (study group). Data regarding the duration of surgery, intraoperative hemorrhage, postoperative complications, the duration of the hospital stay, and the costs of hospitalization were retrospectively collected. One year later, the time to the return of the β-human chorionic gonadotropin (β-hCG) concentration to normal and to the return of menstruation were compared., Results: The duration of surgery, time to the return of menstruation, and incidence of postoperative complications in the study group were significantly less than in the control group, but there was no significant difference in the time for β-hCG to return to normal or the volume of intraoperative hemorrhage. The duration of hospitalization and costs for the control group were higher than those for the study group., Conclusion: Laparoscopy in combination with BUAO is associated with minimal trauma, rapid recovery, a short duration of surgery, low cost of hospitalization, and a low postoperative complication rate. Thus, it represents a useful new surgical treatment for type II CSP., Competing Interests: Declaration of conflicting interestThe authors declare that there is no conflict of interest.

Aim of the study - the assessment of the diagnostic value of Progesterone-Induced Blocking Factor (PIBF) in Early Pregnancy Loss (EPL), in naturally conceived women and in women who underwent In Vitro Fertilization (IVF). In the prospective and retrospective study 50 naturally conceived women were divided into three groups: Group I - patients with progressive pregnancy; Group II- patients with EPL; Group III - patients with biochemical pregnancy (BP). 36 pregnant women after IVF were divided into three groups: Group IV - patients with progressive pregnancy, Group V - patients with EPL, and Group VI - patients with BP. β human Chorionic Gonadotropin (βhCG), PIBF and Progesterone (PG) were assessed in the women conceived naturally and after IVF on the 12th to 14th day after ovulation and embryo transfer (ET), respectively. PG and PIBF levels were significantly higher in the progressive and significantly lower in the biochemical pregnancy groups as in the naturally conceived women, so after IVF. PIBF was not significantly different in EPL and BP groups of naturally conceived and IVF pregnant, opposite to the PG, which was significantly lower in the BP group. Thus, PIBF is more informative in the prognosis of EPL and PG - in the diagnosis of clinical pregnancy. PIBF emerges as a prognostic indicator for early pregnancy loss, encompassing even its preclinical stage.

Abstract: Primary epithelioid trophoblastic tumor (ETT) of the lung is exceedingly rare. Only about three cases have been reported in Pubmed and worldwide literature. We presented a case of multiple primary ETT of the lung occurring in a 33-year-old Chinese female patient. Comprehensive physical examinations revealed no evidence of a primary lesion on the uterus or cervix uteri. Microscopic examination of the tumor demonstrated ETT of the lung, which was confirmed by immunohistochemical staining and declining level of beta-human choriogonadotropin ( β -HCG) after the operation. Our case revealed that the ETT can occur in the lung and should be considered when a female had a tumor of lung with increasing β -HCG., (Copyright © 2023 Copyright: © 2023 Indian Journal of Pathology and Microbiology.)

Introduction: Paraneoplastic hyperthyroidism (PH) has been reported in patients with testicular germ cell tumors (GCTs), sporadically. This disorder is caused by extremely elevated serum levels of beta-human chorionic gonadotropin (bHCG). To date, little is known about the prevalence of PH, and its clinical features are poorly understood. The aim of the present study was to analyze the relative frequency and clinical features of PH in GCTs and evaluate their effects on therapeutic outcomes., Methods: A cohort of 438 patients treated for testicular GCT from 2017 to 2023 was retrospectively analyzed for histology, age, clinical stage, and presence of PH. The clinical features of the patients with PH were evaluated descriptively. The relative frequency of PH was compared among the subgroups using descriptive statistical methods., Results: Three patients with PH were identified; all had clinical symptoms of hyperthyroidism, suppressed serum levels of thyroid-stimulating hormone (TSH), and increased levels of tri-iodothyronin (fT3). All the patients had advanced, metastasized, and non-seminomatous GCTs. Serum bHCG levels ranged from 225,00 U/L to 1,520,000 U/L. The prevalence of PH was 0.7% in the entire GCT population and 60% in those with very high bHCG serum levels. All the patients received standard cisplatin-based chemotherapy along with thyrostatic treatment. The clinical symptoms of the hyperthyroidism rapidly disappeared. TSH levels normalized with decreasing bHCG levels. The PH treatment did not affect the therapeutic outcomes of the patients., Conclusion: PH may occur in 0.7% of all patients with GCT but may be present in up to 60% of patients with very high levels of bHCG. Measuring serum levels of TSH and fT3 should be performed in addition to routine diagnostic measures in all patients with poor prognosis GCTs. Thyrostatic medication is recommended for patients with the clinical symptoms of hyperthyroidism. Early recognition of hyperthyroidism and prompt intervention will reduce comorbidity and help optimize therapeutic outcomes., (© 2024 S. Karger AG, Basel.)

Background: This study aimed to evaluate the predictive power of a model combining maternal risk factors and the Quadruple screen test for late-onset preeclampsia (PE)., Methods: All pregnant women that received the Quadruple test for Down syndrome at 15 + 0 -20 + 6 weeks' gestation were recruited. Maternal serum α-fetoprotein, β-human chorionic gonadotropin, unconjugated estriol, and inhibin A were measured as multiples of the median. A logistic regression model was used to identify predictors associated with late-onset PE with severe features. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to assess the model's predictive ability., Results: Fifty-five of the 2,000 pregnant women had PE, and 31 of 55 women had late-onset PE. Multivariate analysis identified maternal age ≥ 35 years, inhibin A, history of previous PE, history of infertile, cardiac disease, chronic hypertension, and thyroid disease as significant risk factors. The area under the curve of the receiver operating characteristic curve was 0.78. The likelihood ratio to predict late-onset PE was 49.4 (total score > 60)., Conclusions: Our model combining serum inhibin A with maternal risk factors was useful in predicting late-onset PE. Close monitoring of these patients is recommended., (© 2023. The Author(s).)

To probe the diagnostic value of transvaginal color Doppler ultrasonography plus serum β-human chorionic gonadotropin (β-HCG) dynamic monitoring in intrauterine residue after medical abortion.In total, 200 pregnant women undergoing medical abortion in our institution from January 2017 to December 2019 were picked, and assigned to either group A (n = 75, with residue) or group B (n = 125, without residue). We detected serum β-HCG, progesterone (P), follicle stimulating estrogen (FSH) levels and ultrasonic indicators endometrial thickness (ET), peak systolic velocity (PSV), resistance index (RI) values, dissected correlation of indicators using logistic linear regression analysis, and prospected the diagnostic value of relevant indicators in intrauterine residue after medical abortion utilizingreceiver operating characteristic curve.At 7 days after abortion (T3), total vaginal bleeding and visual analogue scalescore in group A were saliently higher in contrast to group B ( P < .05). At 72 hours after abortion (T2) and T3, serum β-HCG, P and FSH levels declined strikingly in both groups, but group B held plainly higher decrease rate than group A ( P HC.05). At T3, ET and PSV levels in both groups considerably waned, whereas RI levels notedly waxed, and group B owned markedly higher decrease/increase than group A ( P wa.05). At T3, serum β-HCG in group A possessed positive association with serum P, FSH, intrauterine ET, PSV levels separately ( P HC.05), whereas negative link with RI levels ( P , .05). The specificity and sensitivity of β-HCG, P, FSH, β-HCG/ET, β-HCG/PSV and β-HCG/RI in the diagnosis of intrauterine residue after medical abortion were high ( P < .05).Serum β-HCG dynamic monitoring plus transvaginal color Doppler ultrasonography is of great value in diagnosing intrauterine residue after medical abortion. Serum β-HCG, P, FSH levels can be combined with the results of intrauterine ET, PSV, RI values, so as to boost the diagnostic accuracy of the intrauterine residue after medical abortion., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aim: This study aimed to study serum beta-human chorionic gonadotropin level trends after medical abortion using mifepristone and misoprostol in the early first trimester., Methods: We enrolled women at ≤63 days of gestation who were indicated for pregnancy termination. We excluded women with incomplete abortions, nonviable pregnancies, extrauterine pregnancies, and contraindications for mifepristone/misoprostol use. Women received oral mifepristone (200 mg), followed by vaginal misoprostol (800 mcg) after 48 h. Serum beta-human chorionic gonadotropin levels were monitored pre-mifepristone administration (day 1); 48 h post-mifepristone, pre-misoprostol administration (day 3); day 10; and weekly after day 10, until negative beta-human chorionic gonadotropin levels (<25 mIU/mL) were achieved., Results: Among 39 enrolled women, 36 (92.3%) who underwent complete abortion without further interventions were included. The median gestational age was 51 (32-61) days. Three phases of beta-human chorionic gonadotropin levels were observed: an increase of up to 5.1% within 48 h of taking mifepristone, before misoprostol administration; a rapid decline on day 10 (by 98.5% compared with initial levels); and a slow decline after day 10 until negative results were attained within 7 weeks., Conclusion: Serum beta-human chorionic gonadotropin levels minimally increased 48 h after taking mifepristone, rapidly declined within 1 week of misoprostol administration, and slowly declined until negative within 7 weeks post-abortion., (© 2022 Japan Society of Obstetrics and Gynecology.)

Background: Ectopic pregnancy (EP) affects 1-2% of all pregnant females'(Barnhart et al., Expert Opin Pharmacother 2(3):409-417, 2001) that can require emergent surgical intervention. Noninvasive diagnostic tests like transvaginal ultrasound (TVUS), and serial β-hCG levels have enabled early diagnosis and allowed medical therapy to be tried. Methotrexate (MTX) versus expectant management, both have been considered safe but superiority of one over the other is lacking., Methods: We searched for RCT that have shown efficacy of MTX versus expectant management in hemodynamically stable patients. Our primary outcome was whether one modality is superior to the other., Results: Four RCT were included in the meta-analysis after review. Our pooled analysis when comparing MTX and expectant management showed us that the difference between the uneventful decline in β-hCG levels (treatment success) was statistically insignificant (RR = 1.06, 95% CI 0.93-1.21) with no significant heterogeneity between trials (I 2  = 0.0%, P = 0.578). The difference between need for surgical intervention between methotrexate and expectant management was also statistically insignificant (RR = 0.77, 95% CI 0.43-1.40) with no significant heterogeneity between trials (I 2  = 0.0%, P = 0.552)., Conclusion: We conclude that expectant management is not inferior to MTX in hemodynamically stable patients with ectopic pregnancy that have declining or low β-hCG levels., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To assess the levels of pregnancy-associated plasma protein-A (PAPP-A) and β-human chorionic gonadotropin (fb-hCG) in cases of diabetic pregnancy, to determine whether these biomarkers can be considered significant predictors for macrosomia, preeclampsia (PE), intrauterine growth restriction (IUGR), and preterm birth in mothers with different types of pregestational diabetes mellitus (DM)., Methods: It was a retrospective cohort study. Study groups were presented: type 1 DM ( n  = 100), type 2 DM ( n  = 50), and controls ( n  = 25). At 11 + 0 to 13 + 6 week's gestation, we recorded maternal characteristics and medical history, and performed a combined test for the detection of risk of chromosomal abnormalities. To assess the performance of the markers in the prediction of the main obstetrical complications (PE, IUGR, preterm birth, and macrosomia), receiver-operating characteristic (ROC) curves were produced and area under the curves was calculated., Results: The study has shown that DM is associated with a high rate of perinatal complications: PE, IUGR, macrosomia, and preterm birth. The median level of PAPP-A was significantly lower in case of type 1 DM- 0.89 (inter quartile range (IQR), 0.51-1.1), and type 2 DM-0.88 (IQR, 0.42-1.15) compared to the unaffected group 1.03 (IQR, 0.96-1.12; p  = .025). There were no significant differences in the fb-hCG multiples of the normal median (MoM; p  = .14) between the diabetic and unaffected groups. More significant results were obtained when calculated by percentile: in diabetic pregnancies, PAPP-A and fb-hCG MoMs values were lower in the 5-10% ranges and higher in the 95% range, compared to the control group. ROC-analysis did not show any significant data that first-trimester PAPP-A and fb-hCG serum levels are predictors for PE, IUGR, macrosomia, and preterm birth., Conclusion: The routine first-trimester serum screening of fetal Down syndrome cannot be used as a tool of risk identification for PE, IUGR, macrosomia, and preterm birth in case of diabetic pregnancy.

Purpose: To predict miscarriage outcome within 12 weeks of gestational age by evaluating values of serum estradiol, progesterone and β-human chorionic gonadotropin (β-HCG) within 9 weeks of gestation., Methods: One hundred sixty-five women with singleton pregnancies were retrospectively studied. Estradiol, progesterone and β-HCG levels were measured at 5-6 weeks of gestation and the measurements were repeated at 7-9 weeks. According to pregnancy outcome at 12 weeks of gestation, 71 cases were categorized into miscarriage group, and 94 cases into group of normal pregnancy. Each group was further divided into 5-6 and 7-9 weeks of gestation sub-group. Predictive values of estradiol, progesterone and β- HCG levels at 5-6 weeks and 7-9 weeks of gestation were analyzed with receiver operating characteristic (ROC) curves and logistic regression., Results: Serum levels of estradiol at 7-9 weeks identified miscarriage with an area under the ROC curve (AUC) of 0.866 (95% CI 0. 793 ~ 0.938, P = 0.000), diagnostic cutoff value of 576 pg/ml, sensitivity of 0.804, and specificity of 0.829 respectively at the optimal threshold, according to Youden index. Progesterone levels at 7-9 weeks were with AUC of 0.766 (95% CI 0. 672 ~ 0.861, P = 0.000), cutoff value of 15.27 ng/ml, sensitivity of 0.921, and specificity of 0.558, respectively; Estradiol at 5-6 weeks were with AUC of 0.709 (95% CI 0. 616 ~ 0.801, P < 0.001), the diagnostic cutoff value of 320 pg/ml, sensitivity of 0.800, and specificity of 0.574, respectively. The performance of the dual markers of estradiol and progesterone analysis (AUC 0.871, CI 0.793-0.950), three-markers analysis (AUC 0.869, CI 0.759-0.980)were slightly better than the single marker at 7-9 weeks. β-HCG or progesterone provide additional utility of estradiol prediction at 5-6 weeks with AUC 0.770 (0.672-0.869) for β-HCG and estradiol, AUC0.768(CI 0.670-0.866) for β-HCG, estradiol and progesterone and AUC 0.739 (CI 0.651-0.827) for progesterone and estradiol., Conclusions: Low serum levels such as dual of estradiol and progesterone or estradiol alone at 7-9 weeks, β-HCG or progesterone combing estradiol at 5-6 weeks of gestation can be used better to predict miscarriage in first trimester., (© 2022. The Author(s).)