hCG Levels Research Articles

Thyrotoxicosis in Partial Mola Hidatidosa

Thyrotoxicosis is a clinical condition associated with excessive thyroid hormone levels. Symptoms can range from asymptomatic to life-threatening due to thyroid storm. Thyrotoxicosis in hydatidiform moles is a rare condition but has a high mortality rate, so etiological studies are still needed for optimal management. Case Report: Patient Mrs. T, 25 years old Hindu, Balinese, 12 weeks pregnant (Gravida 1 Para 0 abortion 0), came to the obstetrics ER on September 24, 2023 with complaints of discharge from the birth canal since the morning, nausea (+), often shaking, easily tired and often sweaty. physical examination obtained blood pressure 100/60mmHg, pulse 78x/min, respiratory rate 20x/min, axillary temperature 36.80C oxygen saturation 99%. From obstetric examination, fundus uteri height ½ center, vaginal toucher vulva vagina within normal limits, portiono (-) fluxus (+), laboratory examination obtained HCG 387,392.8 mIU/m, FT4 31.05 pmol/L (N: 9-22), TSH <0.01 uIU/mL (N: 0.4-4.2) ultrasound results describe honey comb appearance and histopathology results describe partial mola. Evacuation by curettage was performed, resulting in reduced serum ?-hCG levels and reduced thyroid hormone levels. Discussion: The patient was diagnosed with partial hydatidiform mole and thyrotoxicosis. Hydatidiform moles can cause thyrotoxicosis. This condition is caused by the structure of ?- hCG which resembles TSH so that it can activate TSH receptors. After evacuation of hydatidiform moles, normal TSH and FT4 levels will be obtained. Conclusion: The female patient with thyrotoxicosis due to hydatidiform moles had the moles evacuated, resulting in normal thyroid hormone levels.

Is the Human Chorionic Gonadotropin Level on Day 10 After Cleaved Embryo Transfer a Predictor of Perinatal Outcome?: A Retrospective Cohort Study.

This study aimed to determine whether human chorionic gonadotropin (hCG) levels at day 10 after day 2 cleaved embryo transfer can predict pregnancy and perinatal outcomes. Patients who underwent oocyte retrieval with minimal stimulation or natural cycles and fresh or vitrified-warmed transfer of a single, day 2 cleaved embryo at our clinic between November 2018 and December 2020 were included in this study. Patients were classified into four age groups for oocyte retrieval and into ten groups based on the hCG level on day 10 after embryo transfer; pregnancy complications and delivery and neonatal outcomes were examined. Of the 5,840 cycles, 3,722 (63.7%) and 2,118 (36.3%) were fresh-cleaved and vitrified-warmed embryo transfers, respectively. The mean hCG level was 24.8 mIU/mL and the clinical pregnancy and live birth rates per transfer were 29.6% and 23.4%, respectively. Maternal age at the time of oocyte retrieval, husband's age, treatment cycle, embryo type and grade, cell number, and hCG levels were correlated with pregnancy and delivery outcomes in the univariate analysis. Conversely, only maternal age and hCG levels were correlated with the outcomes in the multivariate analysis. hCG levels on day 10 post-transfer are a useful predictor of pregnancy and delivery outcomes after cleaved embryo transfer. Live birth rates vary with maternal age, even when hCG levels are the same, but they do not vary according to the treatment cycle or type of embryo transferred. Low hCG levels may be associated with vasa previa but did not affect delivery outcomes.

Specific plasma microRNA profiles could be potential non-invasive biomarkers for biochemical pregnancy loss following embryo transfer

BackgroundPlasma microRNAs act as biomarkers for predicting and diagnosing diseases. Reliable non-invasive biomarkers for biochemical pregnancy loss have not been established. We aim to analyze the dynamic microRNA profiles during the peri-implantation period and investigate if plasma microRNAs could be non-invasive biomarkers predicting BPL.MethodsIn this study, we collected plasma samples from patients undergoing embryo transfer (ET) on ET day (ET0), 11 days after ET (ET11), and 14 days after ET (ET14). Patients were divided into the NP (negative pregnancy), BPL (biochemical pregnancy loss), and CP (clinical pregnancy) groups according to serum hCG levels at day11~14 and ultrasound at day28~35 following ET. MicroRNA profiles at different time-points were detected by miRNA-sequencing. We analyzed plasma microRNA signatures for BPL at the peri-implantation stage, we characterized the dynamic microRNA changes during the implantation period, constructed a microRNA co-expression network, and established predictive models for BPL. Finally, the sequencing results were confirmed by Taqman RT-qPCR.ResultsBPL patients have distinct plasma microRNA profiles compared to CP patients at multiple time-points during the peri-implantation period. Machine learning models revealed that plasma microRNAs could predict BPL. RT-qPCR confirmed that miR-181a-2-3p, miR-9-5p, miR-150-3p, miR-150-5p, and miR-98-5p, miR-363-3p were significantly differentially expressed between patients with different reproductive outcomes.ConclusionOur study highlights the non-invasive value of plasma microRNAs in predicting BPL.

Nongestational ovarian choriocarcinoma with bilateral teratoma: A rare case report and literature review.

Trophoblastic neoplasms are often associated with pregnancy, and nongestational trophoblastic neoplasms are extremely rare. Nongestational ovarian choriocarcinoma (NGCO) is a highly aggressive germ cell-derived tumor frequently presenting with early hematogenous metastasis. Herein, we report a case of a 28-year-old unmarried woman with regular menstruation who experienced vaginal bleeding 1 week after her last menstrual cycle. Doppler ultrasound revealed bilateral adnexal masses and elevated serum human chorionic gonadotropin (hCG) levels. The patient was initially misdiagnosed as presenting an ectopic pregnancy. The final pathology confirmed an International Federation of Gynecology and Obstetrics stage IA NGCO with bilateral mature teratoma of the ovary. This is an extraordinary instance of ovarian choriocarcinoma which emerged without any prior gestation, and the patient's lack of a history of pregnancy made the diagnosis ignored. After initial surgery and 1 cycle of bleomycin, etoposide, and cisplatin (BEP) chemotherapy, a laparoscopic fertility-preserving comprehensive staging surgery was performed. Two cycles of chemotherapy with BEP were administered as supplemental therapy postsurgery, and leuprorelin was administered to protect ovarian function. Menstruation resumed 4 months after chemotherapy completion, and tumor indicators were within the normal range. No signs of recurrence were observed at the 36-month follow-up. NGCO should be considered if a female patient exhibits irregular vaginal bleeding and masses in the adnexal area. The present case and our literature review also highlighted that fertility-sparing surgery and multidrug chemotherapy are effective methods for treating NGCO.

Characteristics Associated With Faster Human Chorionic Gonadotropin Resolution in C-Section Scar and Cervical Ectopic Pregnancies After Treatment With Double Balloon Catheter [ID 2683550

INTRODUCTION: C-section scar (CSP) and cervical (CXP) ectopic pregnancies are increasing in frequency and associated with significant maternal morbidity. Recently, double balloon catheter (DBC) has been shown as a successful treatment option, but data are limited regarding timing of human chorionic gonadotropin (hCG) resolution. We aimed to define characteristics associated with decreased time to hCG resolution. METHODS: This is a retrospective cohort study of CSPs and CXPs at a single tertiary center treated with DBC placement between 2018 and 2023. Institutional review board approval was obtained. The primary outcome was resolution of serum beta-hCG less than 5 within 30 days. Predictor variables included initial hCG levels, mean sac diameter, and DBC inflation volume. Multivariable logistic regression was used to adjust for gestational age and initial hCG. RESULTS: Thirty-three pregnancies were included; 13 (39%) had resolution of hCG in less than 30 days and 20 (61%) had resolution in greater than or equal to 30 days. Mean sac diameter less than 10 mm and initial hCG less than or equal to 25,000 were significantly associated with hCG resolution less than 30 days (77% versus 40%, aOR 7.18 [95% CI, 1.23–58.8] and 92% versus 60%, aOR 10.38 [95% CI, 1.39–239.98], respectively). There was no significant difference between lower balloon fill amount and hCG resolution. CONCLUSION: After treatment with DBC, most patients require greater than 30 days for hCG resolution. However, patients with mean sac diameter less than 10 mm and initial hCG less than or equal to 25,000 have higher odds of hCG resolution within 1 month, providing a framework for counseling of patients opting for this method.

The Role of Beta hCG Value Measured on the 12th and 14th Days After Embryo Transfer in Determining Early Complications of Pregnancy

Aim: This study aimed to investigate the role of beta human chorionic gonadotropin (beta hCG) levels on post embryo transfer (ET) 12th- and 14th-day, and its folding after 48 hours in predicting live birth, abortion, and biochemical pregnancy. Material and Methods: The study included 124 patients who had a positive pregnancy test after a fresh single day 3 ET at the in vitro fertilization (IVF) center between 2017 and 2021. The first beta hCG value was measured 12th day and the second 14th day after ET. The beta hCG fold was calculated by dividing the second beta hCG value by the first beta hCG value. Results: The patients' IVF indications included unexplained (n=40, 41.1%), poor ovarian reserve (n=23, 25.0%), male factor (n=31, 29.8%), and tubal factor (n=3, 4.1%). Of the 124 patients, 97 (78.2%) had a fetal sac, 81 (63.5%) had a fetal heartbeat (FHB), and 70 (56.5%) had a live birth. The results indicated that the post-ET 14th-day beta hCG level was the best predictor of biochemical pregnancy. It has a high sensitivity (92.5%) and specificity (86.6%), with an optimal cut-off value of 175 U/L. The post-ET 14th-day beta hCG level was the best predictor of a live birth. The post-ET 14th-day beta hCG value of 214.5 U/L had an 82.7% sensitivity and 74.4% specificity to predict the FHB. Conclusion: The beta hCG value, measured between the 12th and 14th days after ET, as well as the folding rate on these two days, can provide information about the pregnancy progression.

The Effect of Prenatal Yoga on Emesis Gravidarum in the First Trimester Pregnant Women

Background: Increased levels of progesterone, estrogen, and HCG (chorionic gonadotropin hormone) during the first trimester of pregnancy can produce morning sickness, also known as emesis gravidarum (nausea and vomiting). To lessen the release of hormones that induce anxiety, severe nausea, and vomiting, prenatal yoga practitioners can block the stimulation of sympathetic nerves by practicing muscle relaxation. This study aims to ascertain how prenatal yoga affects first-trimester emesis gravidarum. Method: This study used a pre-experimental design with a pretest-posttest design in one group, involving 16 mothers who had emesis gravidarum at PMB Fatimah Bandung Rejosari, Sukun, Malang. Data collection was done using the questionnaire. Results: The result was that two prenatal yoga sessions over two weeks demonstrated significant benefits. Prenatal yoga affects emesis gravidarum in the first trimester of pregnancy, as indicated by the independent t-test technique (2-tailed) of 0.000 <0.005. Discussion: Steroid hormones can slow down stomach emptying, which causes emesis gravidarum. Excessive or low cortisol levels can be brought back to normal with yoga. Yoga offers numerous mental and physical health advantages. Conclusion We can conclude that the course of treatment impacts the severity of emesis gravidarum, or nausea and vomiting, during the first trimester of pregnancy.

High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Salvage Therapy of Relapsed/Refractory Germ Cell Tumors: A Single-Center Experience

Introduction: The optimal management of relapsed/refractory germ cell tumors remains unsettled. In this study, we aimed to evaluate the efficacy of high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) as salvage therapy in patients who progressed after at least one line of cisplatin-based chemotherapy. Methods: We retrospectively reported the results of 133 patients who underwent HDCT and ASCT as salvage therapy from 2016 to 2021. Patients received 3 cycles of paclitaxel, ifosfomide and cisplatin (TIP) regimen as induction and 1 cycle of carboplatin 700 mg/m2 on days 1–3 plus etoposide 750 mg/m2 on days 1–3, followed by ASCT. Demographic and clinicopathological features of patients, the International Germ Cell Cancer Collaborative Group (IGCCCG) risk group at diagnosis, serum alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (HCG) levels before HDCT, treatment-related complications and survival outcomes were recorded. Results: The median age of the patients was 31 (range 18–62). The median follow-up was 31.1 months (95% CI, 28.9–33.3 months). During the median follow-up period, 74 of the 133 patients were still alive, and 63 of these were in complete remission. The median progression-free survival (PFS) was 25.8 months (95% CI, 8.1–43.4 months). The 2-year PFS rate was 50.3% and the 2-year overall survival (OS) rate was 60.8%. Variables that remained statistically significant in multivariable analysis and were associated with poor prognosis were mediastinal primary tumor location, presence of brain metastases, and higher AFP and HCG levels at baseline. Conclusion: One course of HDCT and ASCT after induction with TIP is an effective and feasible treatment option for salvage treatment of relapsed/refractory germ cell tumors, with cure rates of up to 60%.

Surgical Outcomes and Trends in Incidence of Ectopic Pregnancy.

We aimed to evaluate the surgical results for ectopic pregnancy (EP) treated at Fukushima Red Cross Hospital for over a 20-year period from 2002 to 2021. We evaluated the incidence, surgical procedures, site of implantation, amount of hemoperitoneum, and the proportion of cases with risk factors of EP. Two hundred and fifty-nine cases of EP were treated surgically. The incidence of EP seemed to be gradually decreasing in recent years. By pregnancy site, 235 (90.7%) of EPs were tubal pregnancies (TPs), 13 in interstitial pregnancies (IPs), 7 in ovarian pregnancies, and 4 in peritoneal pregnancies. For IPs, human chorionic gonadotropin (hCG) levels were statistically higher than with TP and intraperitoneal bleeding was less than with other EP sites. Thirty-nine patients (15.0%) were with massive hemoperitoneum (>500 mL), and laparoscopic surgery was performed in all patients with massive hemoperitoneum except in two patients. The proportion of cases with risk factors for EP such as Chlamydia trachomatis infection or history of smoking was 5.4% and 40.6%, respectively. Epidemiological research shows that the number of patients with chlamydia infection, rates of smokers, or the occurrence of EP with assisted reproductive technology has been decreasing in recent years in Japan. Appropriate surgical intervention should be selected while considering such as facility capabilities, context, and surgeon skill, especially in critical cases, such as cases involving massive hemoperitoneum and hemorrhagic shock. The recent presumed decrease in the occurrence of EP may partly be associated with the decrease in the occurrence of risk factors.

Readmission following methotrexate treatment for tubal pregnancy.

To identify risk factors for readmission following methotrexate treatment for tubal pregnancy. A retrospective study undertaken in two tertiary medical centers, including all individuals with medically treated tubal pregnancy (N = 511), between December 2009 and June 2021. Individuals with and without readmission following methotrexate treatment were compared. The primary outcome was the readmission rate. Secondary outcomes included the rate of post-discharge gynecological emergency department visits, tubal rupture rate, and the eventual need for surgical treatment. Readmission following methotrexate treatment occurred in 224/511 patients (43.8%). Most readmissions were due to abdominal pain or suspicion of treatment failure. Readmitted individuals were more likely to have a history of pelvic inflammatory disease and pretreatment serum human chorionic gonadotropin (hCG) >2000 mIU/mL. Both factors remained significantly associated with higher readmission rates in a logistic regression analysis (adjusted odds ratio [OR] 6.28, 95% confidence interval [CI] 1.30-30.45, and adjusted OR 2.73, 95% CI 1.83-4.07, respectively) after adjustment for age, endometriosis, tubal pathology, abdominal pain, and presence of yolk sac or embryo at diagnosis. A dose-dependent association was observed between pretreatment serum hCG levels and readmission rate (P < 0.001). Pretreatment hCG levels were also associated with tubal rupture and the eventual need for surgical treatment (P < 0.001 for both). A prediction model using hCG was not sufficiently accurate to predict readmission risk. Readmission following methotrexate treatment for tubal pregnancy was independently associated with previous pelvic inflammatory disease and pretreatment serum hCG levels. The latter was also associated with surgical intervention rate.

Exceptional Case of Spontaneous Ovarian Hyperstimulation Syndrome in Complete Molar Pregnancy: A Case Study

Spontaneous ovarian hyperstimulation syndrome (OHS) is an uncommon condition. We report the case of a 38-year-old woman admitted to the emergency department with vaginal bleeding, pelvic pain, and an extraordinarily high human chorionic gonadotropin (hCG) level of 1,000,000 mIU/mL. Uterine aspiration confirmed a complete hydatidiform mole. Ten days post-discharge, she returned, exhibiting severe abdominal pain, vomiting, an hCG level of 46,769 mIU/mL, and ultrasound evidence of theca lutein cysts (right ovary: 1329 cm³; left ovary: 500 cm³) along with ascites. Suspected of having OHS, she was hospitalized for clinical management. Treatment included intravenous hydration, analgesia, thromboprophylaxis, and daily laboratory tests, leading to symptomatic improvement despite rising hCG levels. After a 35-day hospital stay, she commenced chemotherapy at a specialized cancer hospital. This case emphasizes the importance of healthcare professionals being alert and aware of the possibility of this diagnostic suspicion in such cases, particularly highlighting the need for hospitalization in moderate to severe instances.

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

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

Mid-Trimester (13-20 Weeks) Maternal Serum β HCG As a Predictor of Hypertensive Disorders of Pregnancy

Background: Hypertensive disorders of pregnancy are a significant contributor to maternal mortality, with early identification of risk factors being crucial for proactive management. This study explores the potential of mid-trimester maternal serum β HCG levels as a predictive marker for hypertensive disorders during pregnancy. Objective: The primary objective of this prospective study was to evaluate the clinical utility of second-trimester serum β HCG levels in predicting the development of hypertensive disorders during pregnancy. Methods: The study, conducted from June 2020 to July 2021, recruited pregnant women aged 13-20 weeks who were normotensive and non-proteinuric. Data from 100 respondents were collected, with 50 in each group (Group A with β HCG &gt; 35000 m IU/ml and Group B with β HCG &lt; 35000 m IU/ml). Statistical analysis was performed using SPSS 24.0, and the significance level was set at p &lt; 0.05. Results: Group A had a significantly higher proportion of hypertensive disorders compared to Group B (38% vs. 10%, p &lt; 0.001), with Group A being more than five times as likely to develop hypertensive disorders (cOR = 5.5, 95% CI: 1.862, 16.344). Serum β HCG levels in respondents with hypertensive disorders (Mean = 60626.88 m IU/ml) were significantly higher than those who were normotensive (Mean = 32812.18 m IU/ml, p &lt; 0.001). Sensitivity was 79.17%, specificity was 59.21%, and positive and negative predictive values were 38% and 90%, respectively. Conclusions: Mid-trimester serum β HCG levels are an efficient non-invasive predictor of hypertensive disorders during pregnancy. With its high sensitivity and negative predictive value, this cost-effective test can aid in the early identification and proactive management of at-risk pregnancies.

Role of Granulocyte Colony Stimulating Factor Effects on Unresponsive Thin Endometrium in Women Undergoing Controlled Ovarian Stimulated Intrauterine Insemination Cycles

Back Ground: It is a prospective observational study that included unexplained infertility cycles with COS –IUI protocols. Thin endometrium of less than 7mm has a negative effect on pregnancy rate. Endometrial function and receptivity factors are important in the success of implantation.&#x0D; Aim: To monitor the effects of G-CSF on thin endometrium in improving endometrium thickness and pregnancy rates in G-CSF administered COS-IUI cycles.&#x0D; Methods: This study was conducted in the Laxmi Narasimha hospital IVF center under the guidence Dr. Adaboina Anitha,Hanamkonda, warangal. Thin endometrium was defined less than 7mm on Trans vaginal ultrasound. Letrozole 5mg (2.5mg, BD) is used for ovulation induction on day 2 or day 3 of their cycle, G CSF 300units was added with significantly improved pregnancy rates in ART cycles. Trigger used was injection 10,000IU urinary hCG &amp; 300 units G-CSF was instilled into the uterus. After 48hours ET was measured &amp; IUI was performed under aseptic precautions. After 16 days β -hCG levels were monitored to determine whether there is a pregnancy.&#x0D; Results: In present study, we concluded that, 250 COS-IUI cycles were analysed and 50 cycles showed a thin endometrium and in them G-CSF was used. The pregnancy rate (28%) was evaluated, 14 members are positive for pregnancy.&#x0D; Conclusion: In our study we concluded that G-CSF and letrozole will improve increases endometrium thickness and conceiving rates in COS-IUI cycles.

MORTALITY FACTORS IN HIGH AND ULTRA-HIGH-RISK GESTATIONAL TROPHOBLASTIC NEOPLASIA AT MOI TEACHING &amp; REFERRAL HOSPITAL: A DECADE-LONG OBSERVATION IN KENYA

Keywords: Gestational trophoblastic neoplasia, mortality, ultra-high risk, chemotherapy &#x0D; ABSTRACT&#x0D; Background: &#x0D; Prior to the advent of effective chemotherapy, Gestational Trophoblastic Neoplasia (GTN) typically resulted in fatality. The prognosis hinges on early detection and the provision of suitable, timely, and sufficient treatment. In low-middle-income countries (LMIC), delayed patient presentation and suboptimal treatment are common due to challenges such as insufficient staffing, limited resources, and inadequate infrastructure.&#x0D; Objectives: The objective of this study was to examine incidents of mortality associated with Gestational Trophoblastic Neoplasia (GTN) at a tertiary care facility in Western Kenya over a 10-year period.&#x0D; Methods: This was a cross-sectional retrospective study involving review of GTN database with supplemental information from medical charts of GTN patients managed at the Moi Teaching and Referral Hospital (MTRH), Eldoret Kenya from January 2013 to December 2022. Bivariate and multivariate logistic regression analysis was done to determine factors that were independently associated with mortality. Survival curves were generated using Kaplan Meier method.&#x0D; Results: Of the 98 cases analyzed, 71.4% were referrals from a different center. Majority of the women who died had heavy burden disease with 16/31 being ultra-high-risk while 26/31 had FIGO stages 3 and 4 disease. The lungs were the commonest site of metastasis in 39.8% of the cases while 11.2% of the patients had brain metastasis. An ECOG status of &gt;1 (AOR 5.11 (95% CI: 1.543-19.218)), complications arising from either the disease or its treatment (AOR 5.112 95% CI: 1.087-24.045) and HCG levels ≥100000, (AOR 4.733 95% CI: 1.278-17.526) were identified as significantly correlated with mortality.&#x0D; Conclusion: Mortality associated with GTN is significantly high in LMICs and women with WHO score of ≥ 13 have an increased risk of death. Late presentations at advanced stages of disease, delay in treatment, and poor supportive care as well as healthcare constraints are thought to be predictors of mortality.&#x0D;

Hypothyroxinaemia during gestation is associated with low ferritin and increased levels of inflammatory markers.

Pregnancy is a state of physiological inflammation facilitating implantation. Early isolated hypothyroxinaemia (IH) and increased inflammation (including obesity) have been associated with severe obstetric complications. The current study evaluated the association between IH, low ferritin and inflammation parameters (interleukin 6 (IL-6), C-reactive protein (CRP), human chorionic gonadotrophin (hCG) and obesity. Moreover, the course of these parameters throughout pregnancy was evaluated in relation to IH. In the cross-sectional study (A) at 12 weeks, 2759 women participated and 2433 participated in the longitudinal study (B) with assessments at 12, 20 and 28 weeks gestation. At the first trimester, 122 (4.4%) IH women (free thyroxine (FT4) <5th percentile, normal TSH levels) were compared with 2114 (76.6%) reference women (FT4 between tenth and 90th percentiles, normal thyrotrophin (TSH) levels), in study B these figures were 99 (4.1%) and 1847 (75.9%), respectively. Cross-sectionally, compared to reference women, IH was independently associated with low ferritin (<5th percentile, OR: 2.6, 95% CI: 1.4-4.9), high CRP (>95th percentile: OR: 1.9, 95% CI: 1.04-3.7), low hCG (<median, OR: 2.1, 95% CI: 1.40-3.16), obesity (BMI > 30, OR: 1.7, 95% CI: 1.12.9) and higher age (OR: 1.1, 95% CI: 1.04-1.15). Longitudinally, compared to reference women, women with IH at 12 weeks gestation showed persistently and significantly lower ferritin and hCG levels, and persistently higher CRP and IL-6 levels throughout gestation. Gestational IH could be viewed as a condition of increased inflammation, as reported in non-thyroidal illness syndrome. Less favourable inflammation parameters and low iron status during early gestation in IH women seem to persist throughout gestation.

Treatment efficacy implications of incorrect utilization of tumor marker levels and risk group assignment according to the International Germ Cell Consensus Classification (IGCCCG).

505 Background: Patients withmetastatic germ cell tumors of the testis (GCTs) are risk-stratified according to the International Germ Cell Cancer Collaborative Group (IGCCCG) classification system for further therapy decision. This risk classification is based on metastatic load as well as tumor marker levels of AFP, HCG and LDH assessed pre-chemotherapy after orchiectomy treatment. An incorrect classification is possible when pre-orchiectomy marker levels are used, possibly resulting in over- or undertreatment of patients. Therefore, the aim was to investigate the potential frequency and clinical relevance of incorrect risk stratification using pre-orchiectomy tumor marker levels. Methods: Patients with metastasized nonseminomatous GCT (NSGCT)were included in a multicenter registry analysis which was conducted by investigators of the German Testicular Cancer Study Group (GTCSG). Based on the marker levels at different timepoints, IGCCCG risk groups were calculated. The agreement was tested using Cohen’s kappa. Results: A total of698 of 1983 (35%) patients were diagnosed with metastatic NSGCTs, and 546 (78%) had sufficient data for 232 follow-up data points. By using pre-orchiectomy tumor marker levels, 111 patients (20%) would have been incorrectly classified. Seventy-five patients (14%) were classified into a higher risk category, and 36 patients (6%) were classified into a lower risk category. Cohen’s kappa was 0.69 (p &lt; 0.001), showing a strong agreement between the use of both marker timepoints. The treatment of misclassified patients would have resulted in an overtreatment of 75 patients or undertreatment of 36 patients. Conclusions: The use of pre-orchiectomy tumor marker levels may lead to an incorrect risk classification and might subsequently lead to under- or overtreatment of patients. Part of these data were published in: Majewski et al. Cancer Med. 2023.

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

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

Diagnostic Role of Cell-Free miRNAs in Identifying Placenta Accreta Spectrum during First-Trimester Screening.

Placenta accreta spectrum (PAS) is a severe complication of pregnancy associated with excessive invasion of cytotrophoblast cells at the sites of the endometrial-myometrial interface and the myometrium itself in cases of adherent (creta) and invasive (increta and percreta) forms, respectively. This leads to a high risk of massive blood loss, maternal hysterectomy, and preterm birth. Despite advancements in ultrasound protocols and found associations of alpha-fetoprotein, PAPP-A, hCG, PLGF, sFlt-1, IL-8, and IL-33 peripheral blood levels with PAS, there is a high need for an additional non-invasive test to improve the diagnostic accuracy and to select the real PAS from the suspected ones in the first-trimester screening. miRNA signatures of placental tissue, myometrium, and blood plasma from women with PAS in the third trimester of pregnancy, as well as miRNA profiles in exosomes from the blood serum of women in the first trimester with physiologically progressing pregnancy, complicated by PAS or pre-eclampsia, were obtained using deep sequencing. Two logistic regression models were constructed, both featuring statistically significant parameters related to the levels of miR-26a-5p, miR-17-5p, and miR-101-3p, quantified by real-time PCR in native blood serum. These models demonstrated 100% sensitivity in detecting PAS during the first pregnancy screening. These miRNAs were identified as specific markers for PAS, showing significant differences in their blood serum levels during the first trimester in the PAS group compared to those in physiological pregnancies, early- or late-onset pre-eclampsia groups. Furthermore, these miRNAs exhibited differential expression in the PAS placenta and/or myometrium in the third trimester and, according to data from the literature, control angiogenesis. Significant correlations were found between extracellular hsa-miR-101-3p and nuchal translucency thickness, hsa-miR-17-5p and uterine artery pulsatility index, and hsa-miR-26a-5p and hsa-miR-17-5p with PLGF. The developed test system for early non-invasive PAS diagnosis based on the blood serum level of extracellular miR-26a-5p, miR-17-5p, and miR-101-3p can serve as an auxiliary method for first-trimester screening of pregnant women, subject to validation with independent test samples.

Fetal sexual dimorphism of maternal thyroid function parameters during pregnancy, a single center retrospective real-world study.

Thyroid function during pregnancy fluctuates with gestational weeks, seasons and other factors. However, it is currently unknown whether there is a fetal sex-specific thyroid function in pregnant women. The purpose of this study was to investigate the fetal sex differences of maternal thyroid-stimulating hormone (TSH) and free thyroxine (FT4) in pregnant women. This single-center retrospective real-world study was performed by reviewing the medical records of pregnant women who received regular antenatal health care and delivered liveborn infants in Shanghai First Maternity and Infant Hospital (Pudong branch), from Aug. 18, 2013 to Jul. 18, 2020. Quantile regression was used to evaluate the relationship between various variables and TSH and FT4 concentrations. The quantile regression also evaluated the sex impact of different gestational weeks on the median of TSH and FT4. A total of 69,243 pregnant women with a mean age of 30.36 years were included. 36197 (52.28%) deliveries were boys. In the three different trimesters, the median levels (interquartile range) of TSH were 1.18 (0.66, 1.82) mIU/L and 1.39 (0.85, 2.05) mIU/L, 1.70 (1.19, 2.40) mIU/L; and the median levels (interquartile range) of FT4 were 16.63 (15.16, 18.31) pmol/L, 14.09 (12.30, 16.20) pmol/L and 13.40 (11.52, 14.71) pmol/L, respectively. The maternal TSH upper limit of reference ranges was decreased more in mothers with female fetuses during gestational weeks 7 to 12, while their FT4 upper limit of the reference ranges was increased more than those with male fetuses. After model adjustment, the median TSH level was 0.11 mIU/L lower (P <0.001), and FT4 level was 0.14 pmol/L higher (P <0.001) for mothers with female fetuses than those with male fetuses during gestational weeks 9 to 12. We identified sexual dimorphism in maternal thyroid function parameters, especially during 9-12 weeks of pregnancy. Based on previous research, we speculated that it may be related to the higher HCG levels of mothers who were pregnant with girls during this period. However, longitudinal studies are needed to determine if fetal sex differences impact the maternal thyroid function across pregnancy.