Serum β-hCG Research Articles

8852 Incidence and Risk Factors of Tubal Ruptured Ectopic Pregnancy: An Analysis Based on 10-Year Experience in Our Tertiary Medical Center

<h3>Study Objective</h3> Determine predictors of tubal rupture in women with tubal ectopic pregnancy. <h3>Design</h3> Retrospective cohort study. <h3>Setting</h3> Tertiary university-affiliated hospital. <h3>Patients or Participants</h3> Patients admitted to our center with the diagnosis of tubal ectopic pregnancy between 2006 and 2016. <h3>Interventions</h3> Electronic medical records of all these patients were reviewed and analyzed. Data extraction included demographic, medical history, and laboratory results. The study aimed to assess risk factors and predictors for tubal rupture. Such as past obstetrical and surgical history, demographic characteristics, and serum β-hCG levels. <h3>Measurements and Main Results</h3> A total of 943 women were admitted in the above-mentioned period. Of those, 98 women had a clinical presentation of ruptured tubal pregnancy that was later confirmed by surgery. A comparison was made between the rupture group and 844 women with unruptured tubal pregnancy. Of 943 tubal pregnancies, 10.3% were ruptured. There was no difference in age, gravidity, admission gestational age, admission mean β-hCG levels, and history of previous ectopic pregnancies. There was a statistically significant difference between ruptured and unruptured groups in parity (1.1 vs. 0.81 respectively, P = 0.009) and live children rate (1.09 vs. 0.76, p=0.002). Tubal rupture occurred in any β-hCG level with the lowest level of 179 mIU/ml. although mean β-hCG levels did not differ between groups, we found that β-hCG level above 5000 mIU/ml was significantly higher in the rupture group. (21% vs. 10%, p=0.01) No significant difference was found when comparing tubal pregnancy risk factors such as a history of pelvic infection, IVF pregnancy, smoking, use of IUD or emergency contraceptive, past abdominopelvic surgeries, and endometriosis. <h3>Conclusion</h3> As seen in this large-scale study, women's parity, live children rate, and serum β-hCG levels >or=5,000 mIU/ml may help predict which tubal pregnancy will rupture. further investigation is needed to understand how this knowledge can be assimilated into the clinical decision-making process.

Predicting the Frequency of Pregnancy Induced Hypertension in Early Pregnancy by Maternal Serum Beta Human Chorionic Gonadotropin Levels

Background: During early pregnancy raised beta human chorionic gonadotropin (β-HCG) level occurs during placental development. It may be used for identifying the pregnancy induced hypertension. There are certain factors that causes pregnancy induced hypertension and preeclampsia. However, many of the associated factors and specific cause is not known. Some common risk factors for preeclampsia are nulliparity, preeclampsia in a previous pregnancy, family history, history of hypertension, renal disease and antiphospholipid antibody syndrome or thrombophilia. However no single lab investigation can be done cost-effectively to make the early diagnosis of pregnancy induced hypertension. The objective of this study was to determine the frequency of Pregnancy induced hypertension in patients with high maternal serum β-HCG at early pregnancy ( 13-20 weeks of gestation). Methodology: A descriptive cross sectional study was conducted on Out Patient Department and in patient wards of the Obstetrics and Gynecology Department of KRL General Hospital, Islamabad. The study was done from 28th December 2018 to 27th June 2019. A total of 75 pregnant women, primary gravida and multi gravida with age range from18-40years with raised β-HCG at 13-20 weeks of gestation were included. All patients were observed during their stay in the hospital for the development of any complications of pregnancy induced hypertension. Results: Mean age of pregnant females was 32.12 ± 5.29 years. Mean gestational period was 17.31 ± 2.05 weeks. Mean β-HCG levels was 7.63±3.71. Pregnancy induced hypertension (PIH) in patients with high maternal serum β-HCG at 13-20 weeks of gestation was found in 64 (85.33%) patients, however there was no Pregnancy induced hypertension in 11 (14.65%) ladies. Conclusion: The outcome of this study concluded that frequency of pregnancy induced hypertension in pregnant femal with high maternal serum β-HCG at 13-20 weeks of gestation was high. Early screening of raised β-HCG can be made for the prevention of complications due to pregnancy induced hypertension. Keywords: Beta Human chorionic gonadotropin, pre-eclampsia, pregnancy induced hypertension.

A 10-Year Review of Methotrexate Treatment for Ectopic Pregnancy in a Malaysian Tertiary Referral Hospital.

Background Ectopic pregnancy was recorded as the fourth principal cause of maternal death in Malaysia in 2019. Early diagnosis and use of methotrexate treatment proved to be safe and effective alternatives to surgical treatment. This study investigates the success rate of methotrexate treatment for ectopic pregnancy in a tertiary hospital in Malaysia. Methods This was a retrospective review of 73 patients with ectopic pregnancies treated with methotrexate according to a single-dose protocol from January 2009 until November 2019. The diagnosis of ectopic pregnancy was made using a combination of transvaginal scan and serial serum β-hCG levels. Their clinical and demographic data were reviewed. Serum β-hCG levels were measured at pre- and post-treatment to determine the rate of successful resolution. Results The overall success rate was 87.7% (64/73 patients) with methotrexate treatment. Fifty-six patients (76.7%) were successfully treated with a single dose of methotrexate, and eight patients (11.0%) required a second dose of methotrexate. There was no relation between socio-demographic, pre-treatment β-hCG levels, ectopic mass size, and treatment efficacy. Smaller size of ectopic pregnancy (adjusted OR=29.23; 95% CI: 2.69, 317.90; P=0.006) and absence of free fluid at the pouch of Douglas (POD) (adjusted OR=27.31; 95% CI: 2.84, 262.32; P=0.004) was found to increase the likelihood of overall treatment success. Absence of fetal cardiac activities was found to increase the likelihood of first-dose methotrexate treatment success (OR=10.20; 95% CI: 1.93, 53.79; P=0.006). Conclusions Early diagnosis of ectopic pregnancy may reduce morbidity and mortality. In carefully selected cases, methotrexate treatment has been proven to be cost-effective and avoided risks associated with surgery and anaesthesia.

Pregnancy complications and placental histology in in vitro fertilization pregnancies with initial low serum β-hCG levels

To assess perinatal outcomes and placental findings after invitro fertilization (IVF) with an initial low serum β-human chorionic gonadotropin (hCG). A retrospective cohort study. University-affiliated tertiary hospital. Low serum β-hCG after transfer, defined as the low 10th percentile for the cohort on day 16 embryo age (low β-hCG group), compared with an initial serum β-hCG at or above the low 10th percentile (control group). Live singleton births after IVF between 2009 and2017. Primary outcomes were placental findings, including anatomic, inflammatory, vascular malperfusion, and villous maturation lesions, as categorized according to the Amsterdam Placental Workshop Group Consensus. Secondary outcomes included obstetric and perinatal outcomes. The low 10th percentile of β-hCG results corresponded to 149 mUI/mL. There were 103 cases in the low β-hCG group, and 928 in the control group. Maternal demographics were similar between the groups, whereas blastocyte transfer was more common in the control group. Deliveries in the low β-hCG group were associated with an increased rate of preterm births, 15.5% vs. 8.1%, which maintained significance after adjustment for confounders. Placentas in the low β-hCG group were notable for a high rate of velamentous cord insertion, 19.4% vs. 7.7%, single umbilical artery 3.8% vs. 0.6%, and histological maternal vasculopathy, 10.6% vs. 4.8%. Live births after IVF with an initial low β-hCG level are associated with a twofold increase in preterm births and placental gross and histological changes. It may thus be considered to observe such cases in a high-risk pregnancy setting.

Independent value of serum β-human chorionic gonadotropin in predicting early pregnancy loss risks in IVF/ICSI cycles.

BackgroundEarly pregnancy loss (EPL) is the most prevalent complication, particularly in couples undergoing assisted reproductive technology treatment. The present study aimed to determine whether the serum β-human chorionic gonadotropin (β-hCG) level after 14 days of embryo transfer, either alone or in conjunction with other parameters in IVF/ICSI cycles, could be used to predict subsequent EPL.MethodsThis was a retrospective cohort study of all couples who received clinical pregnancy and underwent fresh IVF/ICSI cycles at a single large reproductive medical center between January 2013 and June 2020. The research involved a total of 6600 cycles. For risk variables, we conducted the least absolute shrinkage and selection operator (LASSO) analysis, and for risk scoring, we used logistic regression coefficients. To analyze relevant risk factors for EPL, univariate and multivariate logistic regression analyses were employed. Areas under the curve (AUC) were determined and compared between β-hCG and other factors using receiver operating characteristic (ROC) curves.Results β-hCG level was considerably lower in women who had EPL than in those who were ongoing pregnancy (564.03 ± 838.16 vs 1139.04 ± 1048.72 IU/L, p< 0.001). Univariable and multivariable logistic regression revealed that β-hCG levels were significantly correlated with the probability of EPL, independent of other risk factors. More importantly, the β-hCG level could independently predict the occurrence of EPL and was comparable to the model that combined other risk factors. The optimal serum β-hCG cut-off value for predicting EPL was 542.45 IU/L.ConclusionsOur results suggest that the serum β-hCG level has a strong independent predictive value for EPL occurrence in fresh IVF/ICSI cycles.

Clinical analysis of high-intensity focused ultrasound (HIFU) combined with hysteroscopy-guided suction curettage (HGSC) in patients with cervical pregnancy

Objective To evaluate the effectiveness of high-intensity focused ultrasound (HIFU) combined with hysteroscopy-guided suction curettage (HGSC) in treating cervical pregnancy. Materials and methods This is a retrospective study. Seven patients with cervical pregnancy who visited the Third Xiangya Hospital of Central South University from January 2015 to December 2020 were enrolled in the current study. All seven patients were treated with HIFU under conscious sedation. All of them underwent HGSC at an average of 2 ± 1 days (range: 1–3 days) after HIFU. Before the therapy, the patient's clinical characteristics were collected, including duration of amenorrhea, gravidity and parity, the patient history of cesarean section and miscarriage, and the size of the gestational sac. The levels of β-hCG and hemoglobin in serum were also reviewed. To assess the clinical outcomes of this combined treatment, the suction time of HGSC, bleeding volume, the clearance time of β-hCG, and the time with returning of menstruation were evaluated. Results All seven patients (average age: 31 ± 6 years) have experienced amenorrhea (duration range, 48 ± 8 days) before the treatment of HIFU. The average number of pregnancies was four, and the number of deliveries was one. Previous medical history showed six patients had cesarean sections, and five patients have been miscarriages. After HIFU treatment, the fetal heartbeats were stopped in all seven patients based on the diagnosis by doppler ultrasound. The bleeding of gestational tissue decreased significantly. All patients had only mild lower abdominal pain, no fever, intestinal damage, or other complications were reported. The average operation time of operative suction curettage was 21 ± 9 min (range: 9–32 min), and the median bleeding volume was 10 ± 8 mL (range: 2–20 mL). Follow-up observations showed that the menstruations were returned in patients at an average of 38 ± 9 days (range: 30–50 days) after the treatment. The β-hCG decreased from 41773 ± 32242 mIU/mL to 13101 ± 8454 mIU/mL in 29 ± 10 days after surgery. Conclusion Based on these results with small subjects, we concluded that HIFU combined with HGSC might be an effective and safe treatment for patients with cervical pregnancy.

Risk factors and predictors of persistent ectopic pregnancy after interstitial pregnancy surgery

Objective: To explore the related factors and early predictors of persistent ectopic pregnancy (PEP) in patients with interstitial pregnancy after operation. Methods: The clinical data of patients with interstitial pregnancy who underwent surgery in the Department of Obstetrics and Gynecology of Peking Union Medical College Hospital from January 2013 to August 2021 were collected. Patients were divided into two groups according to whether PEP occurred (8 patients in PEP group and 124 patients in non-PEP group). Using propensity score matching (PSM) analysis, the basic data, surgical methods, the ratio of postoperative to preoperative serum β-human chorionic gonadotropin (β-hCG), the duration of when the serum β-hCG had decreased to normal after the operation were compared and analyzed to find the related factors of PEP after interstitial pregnancy surgery. The sensitivity and specificity of the ratio of 24-48 hours postoperative β-hCG to preoperative β-hCG in predicting postoperative PEP were evaluated by drawing receiver operating characteristic (ROC) curve. Results: Before PSM, the ages of patients in PEP group and non-PEP group were (30.0±4.0) and (32.4±5.0) years old, respectively, P>0.05. After PSM, 8 PEP patients in the study group and 29 patients in the control group were matched successfully, and the ages of the two groups were (30.0±4.0) and (30.1±3.2) years old, respectively, P>0.05. After PSM, there was no significant difference in gravidity, parity, menopausal days, preoperative β-hCG level and maximum diameter of lesions, all P>0.05. After PSM, the proportion of patients with maximum diameter ≤ 2.6 cm in PEP group (6/8) was significantly higher than that in control group (31.0%, 9/29), P=0.025. The median (Q1, Q3) of the ratio of 24-48 hours postoperative β-hCG to preoperative β-hCG ratio was 52.9% (49.9%, 59.7%) in the PEP group, which was significantly higher than 31.5% (23.8%, 39.0%) in the control group (P=0.001); The median (Q1, Q3) of duration of when the serum β-hCG had decreased to normal after the operation in PEP group was 52.0 (34.8, 92.0) d, which was significantly higher than 24.0 (20.5, 31.0) d in control group (P<0.001). The ROC-Area Under Curve of the ratio of 24-48 hours postoperative β-hCG to preoperative β-hCG ratio for predicting postoperative PEP in the two groups was 0.892 (95%CI: 0.725-1.000, P=0.001). The cut-off value for predicting PEP was 48.5%, where the diagnostic sensitivity was 87.5%, the specificity was 93.1%. Conclusions: In the operation of interstitial pregnancy, the maximum diameter of lesion ≤ 2.6 cm is a related factor for postoperative PEP. There was no significant difference in the risk of PEP between cornuotomy and cornectomy. The ratio that 24-48 hours postoperative β-hCG/preoperative β-hCG ratio greater than 48.5% was a reference index for predicting postoperative PEP and guiding treatment.

CHARACTERISTIC CHEMOTHERAPY RESPONSE OF TESTICULAR CANCER PATIENTS IN TERTIARY HOSPITAL

Objective: The purpose of this study was to determine the correlation of testicular tumor markers on the success of chemotherapy in my institution. Material &amp; Methods: This research is a retrospective study single center using the medical record database at the span of the research period. The patient with testicular carcinoma who underwent complete chemotherapy between 2017 until 2022 was included. The data collected and analyzed by descriptive data and analytical correlation using SPSS Ver. 25. The comparation test using T-test and Anova. Results: A total of 31 testicular cancer patients were enrolled in the study. Fifteen patients were seminoma and 16 patients were non-seminoma. The mean age of patient at presentation of seminoma and non seminoma were 38.3 ± 17.03 and 30.74 ± 13.01. Most patients presented a karnofsky score about 79 ± 15. There was a negative correlation (r=-0.492) with a significant correlation between the types of testicular carcinoma cases and the response to chemotherapy (p=0.027). There was a significant difference in cases of seminoma and non-seminoma to the success of the chemotherapy response (p=0.024). There was a positive correlation between serum β-HCG, AFP, LDH with serial chemotherapy result with a no significant correlation (p=0.879; p=0.242; and p=0.277). Conclusion: Most types of the testicular carcinoma responses to chemotherapy. Patients with seminoma pathology have better response to chemotherapy compared to non-seminoma.

EP40.18: Medical versus surgical treatment of terminated first trimester pregnancies

The purpose of our study was to compare the efficacy and safety of vaginal misoprostol versus surgical evacuation in the management of first trimester aborted pregnancies. One G1 group received a drug procedure: misoprostol 800 ug vaginally repeated as needed 24 hours later. One G2 group underwent surgical evacuation. The main epidemiological characteristics of the patients were comparable between the two groups. Analysis of misoprostol efficacy by parity, gestational age, and serum BHCG level did not show significant differences. The success rate was comparable in G2. Immediate and short-term complications were less frequent with medical treatment with a cumulative rate of 8% versus 24% with surgical treatment. All these undesirable effects were well tolerated and transient and did not affect the acceptability of the medical treatment (88% of G1 patients were satisfied compared to 58% of G2). Vaginal misoprostol is a promising alternative to surgical evacuation of terminated first trimester pregnancies.

Association of Early Beta Human Chorionic Gonadotropin With Ischemic Placental Disease in Singleton Pregnancies After In Vitro Fertilization.

Objectives: To evaluate whether an initial or two-day percent increase in serum beta-human chorionic gonadotropin (βhCG) is associated with ischemic placental disease (IPD) in singleton pregnancies after autologous or donor IVF.Study design: This was a secondary analysis of a retrospective cohort study of deliveries linked to IVF cycles at a single academic tertiary hospital and infertility treatment center. We included all patients (≥18 years old) who had a singleton live birth or intrauterine fetal demise (IUFD) resulting from either autologous fresh (n=1,347), autologous frozen (n=454), or donor (n=253) IVF cycles.Main outcome reassures: The primary outcome was a composite outcome of IPD or IUFD due to placental insufficiency. IPDs included preeclampsia, placental abruption, and small for gestational age (SGA).Results: Neither initial βhCG nor two-day percent increases in βhCG were associated with an increased risk of IPD for any type of IVF cycle. Initial and two-day percent increases in βhCG were significantly higher when comparing frozen with fresh IVF and donor with autologous IVF (all P≤0.01).Conclusions: Among singleton autologous and donor IVF cycles, the initial and two-day percent increase in serum βhCG were not associated with IPD or its components. However, significant βhCG differences existed by cycle type and oocyte source.

TSH Receptor Antibody Testing in Early Pregnancy.

Graves disease (GD) is the leading cause of hyperthyroidism in women of childbearing age, and thus, low serum thyrotropin (TSH) during pregnancy might be expected to be largely secondary to GD. This is not the case for 2 reasons. First, autoimmunity frequently abates during pregnancy, including thyroid-specific autoimmunity (1), so that even those with previously diagnosed GD may go into remission during pregnancy. Second, the physiology of thyroid hormone regulation is altered as a result of the agonist activity of β-human chorionic gonadotropin (βhCG) at the TSH receptor (2). Under normal conditions this leads to a slight increase in thyroid hormone production, which is independent of pituitary TSH secretion. Serum TSH levels fall, resulting in a left shift of the TSH reference range in pregnancy, and a lower limit of 0.1 mU/L in most assays (3). In early pregnancy especially, elevations of serum βhCG above those typically seen can cause a further rise in serum free thyroxine and more dramatic suppression of the serum TSH, resulting in “gestational transient thyrotoxicosis” (GTT) (3). This is typically mild and resolves after the first trimester, and is not associated with adverse pregnancy outcomes (4). The very high levels of βhCG found in hyperemesis gravidarum are associated with more severe biochemical thyrotoxicosis, and extremely high levels seen with molar pregnancy and choriocarcinoma can require antithyroid drug therapy and other measures to mitigate thyrotoxicosis. Indeed, persistent thyrotoxicosis during pregnancy from any cause, especially GD, has been associated with poor outcomes including fetal loss, maternal heart failure, and preeclampsia (5).

Misdiagnosis and Chemotherapy Delaying Reduces the Chemosensitivity of Choriocarcinoma Patient: Analysis of 36 Cases

Background: Choriocarcinoma is a curable malignant neoplasm when chemotherapy is properly implemented. However, when chemotherapy resistance occurs, disease can be fatal. Misdiagnosis is common, which may lead to delaying of the first cycle of chemotherapy and increase the possibility of chemoresistance. Methods: We analyzed 36 choriocarcinoma cases who were treated in our department about their clinical characteristics, and their diagnosis and treatment processes together with the serum β-hCG variation. Results: Analysis showed that the disease onset age, FIGO (International Federation of Gynecology and Obstetrics) stage distribution were similar to the other cohort. The primary origins were uterine canals, and the serum β-hCG elevated with or without vaginal bleeding were common, which all easily lead to misdiagnosis of benign pregnancy related diseases. Our data demonstrated that the misdiagnosis of choriocarcinoma resulted in delaying of the first cycle of chemotherapy, followed by decreased control of serum β-hCG after one chemotherapy cycle and more cycles for serum β-hCG normalization, which meant the possibility of generating chemoresistance. Conclusions: In summary, standardized surveillance and treatment process to decrease misdiagnosis rate of choriocarcinoma can be an effective measure to improve the prognosis of patients.

IL-6 of follicular fluid and outcome of in vitro fertilization.

The quality of an oocyte is influenced by its microenvironment, which includes cumulus cells and follicular fluid, as well as cells of the immune system and their products. The ovarian interleukins, which are secreted by the granulosa cells and other immune cells within the ovaries and follicles, regulate various functions between the cells. IL-6 is a cytokine that is present in the follicular fluid and may affect the quality of oocytes. There are some inconsistencies in the literature regarding the concentration of interleukin 6 in the follicular fluid.The main objective of this study was to examine whether the concentration of interleukin 6 in the follicular fluid affects the outcome of IVF.This study involved 83 patients who underwent IVF. Follicular fluid was used as the biological material for the analysis. Examination of the obtained follicular fluid and collection of oocytes under a stereomicroscope was performed in the embryological laboratory. The concentration of IL-6 in the follicular fluid was analyzed. IVF and ICSI methods were used as the fertilization methods. Pregnancy was confirmed by the positive serum β-hCG level. The software package SPSS 20 was used for statistical data processing.Analysis of the follicular fluid samples showed a correlation between the concentration of IL-6 in the follicular fluid and the outcome of IVF. The concentration of IL-6 in the follicular fluid was higher in patients with confirmed pregnancy (9.55 ± 7.47 ng/ml).Based on our results, we conclude that the concentration of IL-6 affects the outcome of IVF. If the range of IL-6 concentration is between 3,67 ng/ml and 10 ng/ml, we can expect good IVF outcome with vital pregnancy.

The efficiency of using maternal markers in early detection and management of congenital anomalies in Majmaah city, KSA

Nowadays the serum analytic investigations have become the first step, noninvasive, detecting method of choice of foetal abnormalities specially for at-risk patients.This study volenteers were Saudi pregnant women in King Khalid General Hospital (KKGH) at Majmaah city, Riyadh, Saudi Arabia.The study intended to judge and evaluate using the concentrations of Beta Human Chorionic Gonadotropin (βHCG) in serum as efficient maternal markers for early detection as well as management of foetal abnormalities and pregnancy complications.A total of 201 serum samples were studied. 101 sera of pregnant women were taken in the first trimester, while the other 100 non-pregnant females were acted as control volenteers. The sensitive Enzyme immunoassay (ELISA) method was applied for quantitative scoring of beta HCG levels. Pregnant women were followed up by a consultant obstetrician till delivery. Trisomy 21 and blighted ovum disorders were selected as cases of interest.Serum βHCG concentrations multiple of median (MoM) for the mothers of affected babies compared with the healthy ones. Defrences were significant as p: value showed 0.001 for each appraisal.Non-pregnant serum beta HCG (2.1 IU/ml) compared with only three weeks of gestation (576 IU/ml) for early detection of pregnancy. Upon comparison a significant high level of β HCG was recorded for the three weeks gestation with (p,value:0.001) which clearly indicates the existence of pregnancy.The use of β HCG could be the method of choice for early detection of pregnancy. This will save the embryo life during the first trimester of gestation especially in the radiology departments.

O-148 Does trophectoderm biopsy affect the initial level and rate of increase in serum ß-HCG levels? A comparison of preimplantation genetic testing (PGT) and non-PGT cycles

Abstract Study question Does trophectoderm biopsy affect the initial level and rate of increase in ß-HCG levels after single frozen-thawed blastocyst transfer?A comparison of PGT and non-PGT cycles. Summary answer Initial serum β-hCG concentrations from cycles resulting in a live birth was significantly lower than that for the non-PGT group. What is known already β-hCG may serve as early predictor of pregnancy outcome and potentially assist in reducing stress related to the uncertainty of outcome in assisted reproductive technologies (ART) treatments and counselling. hCG is produced primarily by differentiated syncytiotrophoblasts. Due to removal of trophectoderm cells, the secretion of β-hCG may be affected. Little, however, is known about the influence of trophectoderm biopsy on serum β-hCG levels in early pregnancy. Therefore, it is important to investigate if the levels and pregnancy outcomes predictive values of β-hCG vary in PGT and non-PGT cycles. Study design, size, duration This was a single center retrospective cohort study conducted at Assisted Reproductive Technologies and Reproductive Genetics Center, Istanbul Memorial Hospital, Istanbul, Turkey between January 2012-January 2021. A cohort of women with frozen-thawed single blastocysts transfers and having positive serum ß-HCG results on day 9 following ET (≥20 IU/L) were allocated into two groups; PGT group (1777 cycles) and non-PGT group (1874 cycles). Participants/materials, setting, methods The serum ß-hCG levels on day 9 and 11 after embryo transfer (ET) and the rate of ß-hCG increase were compared between the PGT and non-PGT cycles with respect to biochemical pregnancy loss (BPL), clinical pregnancy loss (CPL), and live birth. The cutoff values of initial β-hCG levels and the rate of ß-hCG increase from day- 9 to day-11 were evaluated for live birth and compared between the two groups. Main results and the role of chance Initial β-hCG levels were significantly higher in pregnancies resulting in live birth (184.68±99.54 IU/L, p = &amp;lt;0.001) compared to BPL (66.65±55.29 IU/L) and CLP (140.51±88.98 IU/L) in the PGT group. Moreover, initial β-hCG levels were significantly higher in pregnancies resulting in live birth (192.53±97.93 IU/L, p = &amp;lt;0.001) compared to BPL (73.67±58.07 IU/L) and CLP (156.28±98.29 IU/L) in the non-PGT group. In addition, initial serum β-hCG concentrations from cycles resulting in a live birth was 184.68±99.54 IU/L for the PGT group, which was significantly lower than that for the non-PGT group (192.53±97.93 IU/L, p = 0.004). The diagnostic threshold of initial β-hCG levels predicting a live birth was 122.5 IU/L (sensitivity 70.1 %, specificity 60.1 %, PPV 84.7 %, and NPV 38.9 %) and 130.5 IU/L (sensitivity 71.7 %, specificity 61.6 %, PPV 82.2 %, and NPV 46.9 %) in the PGT and non-PGT groups, respectively. The rate of increase of serum β-hCG threshold predicting a live birth for the PGT group was 2.33 (sensitivity 73.8 %, specificity 59.9 %, PPV 85.3 %, and NPV 42 %) and 2.42 (sensitivity 64.6 %, specificity 60.1 %, PPV 80 % and NPV 40.7 %) for the non-PGT group. Limitations, reasons for caution This is a retrospective analysis. Wider implications of the findings Initial serum β-hCG values and the rate of β-hCG increase may be useful for predicting pregnancy outcomes in PGT cases undergoing trophectoderm biopsy. Trial registration number Not applicable

P-400 Methotrexate versus expectant management for treatment of tubal ectopic pregnancy: an individual participant data meta-analysis (IPD-MA)

Abstract Study question Is medical management with methotrexate superior over expectant management in the resolution of tubal ectopic pregnancy in clinically stable women and low serum hCG? Summary answer In women with tubal ectopic pregnancy and low serum hCG, methotrexate was not better than expectant management. There were no subgroups benefiting from methotrexate. What is known already Women with tubal pregnancy who are clinically stable and have low hCG concentrations can be treated medically with methotrexate, an anti-folate drug that has a range of adverse effects and requires women to avoid conceiving three months after administration due to teratogenic effects. Expectant management with close monitoring is as effective compared to methotrexate in this subgroup of women. There are three randomised controlled trials (RCTs) not showing a statistically significant difference in uneventful resolution of ectopic pregnancy between methotrexate and expectant management. These studies were too small to define if certain subgroups could benefit from either treatment. Study design, size, duration We performed an individual participant data meta-analysis (IPD-MA) of RCTs based on a search of international scientific databases. We selected RCTs comparing methotrexate and expectant management in women with suspected tubal ectopic pregnancy. The primary outcome was treatment success, defined as resolution of clinical symptoms and decline in level of serum hCG to &amp;lt; 20 IU/L or a negative urine pregnancy test by the initial intervention strategy, without any additional treatment. Participants/materials, setting, methods Analyses were performed on an intention-to-treat basis. A one-stage IPDMA was performed to assess overall treatment effects of methotrexate and expectant management to generate a pooled intervention effect. This included a random intercept (for baseline differences between studies) and random slope (for differences in treatment effect between studies). A log-binomial model for dichotomous outcomes yielded a risk ratio (RR) with 95% confidence interval (CI). Subgroup analyses were undertaken according to baseline serum β-hCG levels. Main results and the role of chance We obtained data from two relevant trials reporting on 153 women with suspected tubal ectopic pregnancy who were randomised to expectant management or methotrexate. The third RCT was excluded as their inclusion criteria required declining titres of hCG 48 hours prior to treatment. The success rate was 65/82 (79.3%) after methotrexate and 48/70 (68.6%) after expectant management (IPD RR 1.16, 95%CI 0.71-2.38). 9/82 (11%) in the methotrexate group and 9/70 (12.8%) after expectant required additional methotrexate. 8/82 (9.8%) in the methotrexate group and 13/70 (18.6%) in the expectant group required surgical intervention (RR 0.65, 95%CI 0.66-3.54). The mean time to success was 21.2 days (95%CI 17.4 to 25.6) after expectant management and 19.7 days (95%CI 17.1-22.2) after methotrexate (p = 0.25). There was no interaction with treatment of maternal age, parity, previous ectopic pregnancy, and serum β-hCG on success rate. Serum hCG &amp;lt;1000 IU/l was associated with a higher success rate in both groups. Only one woman in the expectant group required a blood transfusion. Methotrexate users had side effects (N = 7/49) including vomiting, diarrhoea, mucositis, conjunctivitis and photosensitivity that were not seen in the expectant group (N = 0/49). Limitations, reasons for caution One of the trials had a higher proportion of pregnancy of unknown location (PUL) which were presumed to be tubal ectopic pregnancies due to plateauing serum hCG levels and caution is therefore advised on the application of these findings to ectopic pregnancies visualised on ultrasound. Wider implications of the findings Initial expectant management might be the preferred strategy for women with suspected tubal ectopic pregnancy in clinically stable women with lower hCG levels in view of less adverse effects, less cost and enabling women who wish to conceive soon after resolution of ectopic pregnancy to do so. Trial registration number Prospero ID: CRD42021214093

P-681 Balance of Estrogen:Androgen ratio (Estradiol E2: Dehydroepiandrosterone-sulphate DHEAS) and its symbiotic correlationship with Vascular-Endothelial Growth-Factor (VEGF) critically foments implantation and pregnancy outcomes in IVF cycles

Abstract Study question Is the estrogen/androgen balance vital for implantation and does this E2:DHEAS ratio coordinate with neoangiogenesis/neovascularisation (VEGF) to facilitate establishment of viable pregnancy in IVF cycles? Summary answer The Estradiol E2:DHEAS ratio independently as well as in symbiotic correlationship with VEGF is strongly predictive of invasive implantation and pregnancy outcomes in IVF cycles What is known already Decidualization of endometrial stroma and vascularization at feto-maternal interface is necessary for implantation. Estrogen Estradiol E2 is among the factors widely known to regulate these processes. Androgen Dehydroepiandrosterone (DHEA) is the designated primary precursor for natural estrogens. DHEA-induced PCOS mice have demonstrated adverse impacts on Embryo implantation and decidualization. However, role of DHEA/S in human implantation has not yet been explored. Vascular-Endothelial growth-factor (VEGF) is known to influence vascularization, angiogenesis, endometrial receptivity. Higher VEGF expression in endometrium is associated with pregnancy. However endometrial-biopsy for VEGF estimation is an invasive method for implantation studies and cannot be applied to ongoing cycles. Study design, size, duration Prospective study of n = 235 (Power of study&amp;gt;85%) non-PCOS, normal-responder infertile females (mean age 31.77±2.42 years, BMI 24.4±4.1, W/H ratio 0.82±0.07) undergoing fresh IVF treatment cycles using standard antagonist stimulation protocol at our fertility clinic during January 2019-December 2020. Elderly women (age&amp;gt;35 years), women with polycystic-ovaries, endometriosis and frozen-thawed cycles were excluded.7 cycles were cancelled owing to no embryo transfer (ET). Day3-cleavage stage or day5-blastocyst stage embryos were transferred (n = 228). Luteal-phase was supported with Micronized progesterone. Participants/materials, setting, methods Serum levels of Estradiol E2 and DHEAS were measured by Radio-Immunoassay and VEGF estimation by ELISA on day ET, day7, day14 post ET. Cycles were divided into Pregnant (P:n=73) and Non-Pregnant (NP=n=155) groups. Main outcome measures: Clinical Pregnancy (CPR:n=70=30.70%), Live-Birth (LBR:28.94%) rates. Secondary outcome measures: Biochemical-pregnancy (BCP:n=3=1.31%), Early-Miscarriage (EM:n=4=1.75%) rates. Pregnant=Serum βhCG&amp;gt;50 on d14ET. BCP=No exponential rise/tapering βhCG levels post d14ET, CP=positive cardiac activity at 6-8 weeks gestation, EM=non-viable intra-uterine pregnancy upto 12 weeks gestation. Main results and the role of chance dET: E2 did not differ significantly (780±50 vs. 750±30 pg/ml;p=0.61) whereas DHEAS = (212±11 vs. 170±6 ng/dL;p=0.0005), E2:DHEAS = (3.72±0.13 vs. 4.65±0.17;p=0.0011), VEGF = (658±20 vs. 495±16;p&amp;lt;0.0001) differed significantly between P vs. NP groups; indicating importance of E2/DHEAS ratio. D7ET: E2 = (790±57 vs. 222±19;p&amp;lt;0.0001), DHEAS = (381±28 vs. 1262±70;p&amp;lt;0.0001), E2:DHEAS = (2.37±0.25 vs. 0.30±0.029;p&amp;lt;0.0001), VEGF = (636±23.61 vs. 480±10.13;p&amp;lt;0.0001) displayed statistically robust differences between P vs. NP groups. d14ET: E2 = (855±73.45 vs. 193.2±13.31;p&amp;lt;0.0001), VEGF = (544.2±15.80 vs. 452.3±16.77;p=0.0011) displayed statistically robust differences between P vs. NP groups. Interestingly, although DHEAS = (685±41.05 vs. 806±55.37;p=0.18) did not differ significantly, E2:DHEAS = (1.643±0.26 vs. 0.45±0.048;p&amp;lt;0.0001) showed highly significant difference; again highlighting importance of E2/DHEAS balance. Ratio E2:DHEAS on d7ET correlated strongly with d7VEGF (Pearson r = 0.31,p&amp;lt;0.0001). ROC curve for d7 E2:DHEAS had AUC 78%, p &amp;lt; 0.0001 Hormone values and their rising trends (d/ET to d7/ET to d14/ET) varied with pregnancy outcome status E2= LB:(d/ET:780±50 to d7/ET:790±57 to d14/ET:855±73.45) vs. BCP:(d/ET:723.3±157.6 to d7/ET:743.3±159 to d14/ET:770±153) vs. EM:(d/ET:906.3±104 to d7/ET:1150±113 to d14/ET:1758±127) DHEAS= LB:(d/ET:212±11 to d7/ET:381±28 to d14/ET:685±41.05) vs. BCP:(d/ET:248.3±55 to d7/ET:266.7±71.2 to d14/ET:400±120.3) vs. EM:(d/ET:243.8±27 to d7/ET:303.8±11.43 to d14/ET:391.3±49) E2:DHEAS= LB:(d/ET:3.72±0.13 to d7/ET:2.37±0.25 to d14/ET:1.643±0.26) vs. BCP:(d/ET:2.93±0.15 to d7/ET:2.97±0.4 to d14/ET:2.12±0.32) vs. EM:(d/ET:3.78±0.40 to d7/ET:3.77±0.26 to d14/ET:4.68±0.59) Decreasing E2:DHEAS ratio (d/ET-d7/ET-d14/ET) is vital for successful implantation/Live-birth VEGF= LB:(d/ET:658±20 to d7/ET:636±23.61 to d14/ET:544.2±15.80) vs. BCP:(d/ET:513.3±37.56 to d7/ET:628.3±40.45 to d14/ET:468.3±35.63) vs. EM:(d/ET:647.5±78.8 to d7/ET:887.5±60 to d14/ET:1138±94.4) Limitations, reasons for caution This study is limited by small sample size and is not a randomized controlled trial. We have taken only representative molecules into consideration. There is a plethora of factors involved during the implantation process. Multi-centric systematic studies are needed to corroborate these findings and account for the probable confounding factors. Wider implications of the findings This novel study explores and highlights significance of maintenance of a critical estrogen/androgen ratio (E2:DHEAS), rather than individual estrogen or androgen markers, in the implantation process. We have also underscored how this ratio coordinates symbiotically with VEGF as a critical non-invasive determinant of implantation and pregnancy-outcomes in ongoing IVF cycles. Trial registration number Not Applicable

P-704 Post trigger progesterone levels as a predictor of oocyte recovery rate

Abstract Study question Do progesterone (P) levels the day after trigger for oocyte maturation impact the oocyte recovery rate? Summary answer A progesterone cutoff value of ≤ 5.0 ng/ml the day after trigger for oocyte maturation is associated with a lower oocyte recovery rate. What is known already Oocyte maturation and embryo development are controlled by intra-ovarian factors such as steroid hormones. P exists in the follicular fluid, and it is known to mediate some luteinizing hormone (LH)- initiated periovulatory events through autocrine/paracrine mechanisms that help mediate granulasa cell luteinization and oocyte maturation. More importantly, a rise in P levels is associated with an adequate follicular rupture. To date, no study has evaluated if lower P levels after oocyte maturation induction are a reflection of impaired physiological periovulatory mechanisms required for the oocyte release from the follicular wall. Study design, size, duration This monocentric retrospective analysis from January 2017 to December 2021 included 435 controlled ovarian hyperstimulation cycles for in vitro fertilization (IVF)/ egg freezing. Serum P, estradiol (E2), bHCG, and LH levels were measured the day after trigger for oocyte maturation to assure adequate luteinization. Participants/materials, setting, methods Women &amp;lt;4O years, that underwent controlled ovarian hyperstimulation with a GnRH antagonist protocol and final oocyte maturation (when ≥2 follicles reached ≥18 mm in diameter) induction with dual trigger (Leuprolide acetate and hCG) were segregated into two groups: Group 1: progesterone cutoff value of ≤ 5.0 ng/ml the day after trigger; Group 2: progesterone cutoff value of ≥ 5.1 ng/ml the day after trigger. Main results and the role of chance 147 cycles in Group 1 were compared with 288 cycles on Group 2. No significant differences were noted in mean patient’s age, BMI, baseline FSH, AMH, baseline antral follicle count, serum P and E2 levels the day of trigger, total dose of gonadotropins, day of trigger as well as serum E2, LH, and bHCG levels the day after trigger among cohorts. A total of 5765 oocytes were retrieved: 1703 corresponding to group 1 and 4692 to group B. Women with progesterone levels higher than ≥5.1 ng/ml the day after trigger had a greater number of oocytes retrieved compared to women with a progesterone cutoff value of ≤ 5.0 ng/ml (16.3 ± 9.1 versus 11.5 ± 7.4, p = &amp;lt; 0.0001). The oocyte/follicle rate was also significantly higher in women in Group 2 vs Group 1 (80.3% vs 63.7%, p = 0.003) However, the mature oocyte (MII) rate was comparable among cohorts (Group 1: 78.0 ± 20.2% vs Group 2: 78.8 ± 17.7%, p = 0.38). Limitations, reasons for caution The retrospective nature of the study, small sample size, selected progesterone cutoff value, and progesterone assay techniques compared to other ART centers may limit the external validity of our findings. Wider implications of the findings Our findings suggest for the first time that lower progesterone levels after final oocyte maturation induction may be a result of compromised mechanisms associated with the release of the oocyte from the follicular wall as demonstrated by a lower oocyte recovery rate. Trial registration number NA

Biological relevance of trophectoderm morphology: initial β-hCG measurements correlate with trophectoderm grading on euploid frozen embryo transfers.

To analyze the correlation between TE grading and initial β-hCG serum level after single euploid embryo transfer. Secondarily, to explore the association between TE grading with subsequent IVF outcomes. Retrospective cohort analysis. Single, academic, private infertility and assisted reproductive care institute. Infertility patients who underwent a single euploid embryo transfer that resulted in a positive pregnancy test. β-hCG measurements. Correlation between TE grade with first β-hCG measurement. Second outcome measurements included ongoing pregnancy, biochemical pregnancy loss, and clinical pregnancy loss rates. 2,798 cases were analyzed. A significant difference in initial β-hCG measurement among groups (TE A: median 143.4 mIU/mL IQR 79.2-211.2; TE B: 119 mIU/mL IQR 57.1-177.8; TE C: 82.4 mIU/mL IQR 36.3-136.4, p ≤ 0.0001) was observed. There was a significant correlation found between the TE grade and β-hCG measurements (p ≤ 0.0001, r2 = 0.10). TE grade was not associated with higher odds of biochemical pregnancy loss (TE A vs. TE B: aOR 1.01 CI95% 0.97-1.05; TE A vs. TE C: aOR 1.03 CI95% 0.98-1.08), or higher odds of clinical pregnancy loss (TE A vs. TE B: aOR 1.02 CI95% 0.98-1.05; TE A vs. TE C: aOR 1.03 CI95% 0.98-1.07). In patients with euploid embryos, TE grade correlates with the first pregnancy test measurement of β-hCG. We propose this finding helps to appoint a relevant link between morphology assessment and early embryo development in vivo.

Diagnostic value of a single β-hCG test in predicting reproductive outcomes in women undergoing cleavage embryo transfer: a retrospective analysis from a single center

PurposeThe present study investigated the role of β-hCG in predicting reproductive outcomes and established optimal β-hCG cutoff values in women undergoing cleavage embryo transfer.MethodsThe patients were transferred with fresh or frozen-thawed embryos and had serum β-hCG levels tested on the 14th day post-embryo transfer. Serum β-hCG levels were compared between different groups. Different cutoff values of β-hCG were established and used to divide the patients into different groups. Reproductive outcomes between groups based on β-hCG levels were compared.ResultsSignificant discrepancies in general characteristics were observed in the subgroups. The cutoff values of β-hCG for predicting the presence/absence of pregnancy, biochemical pregnancy/clinical pregnancy, presence/absence of adverse pregnancy outcomes, and singleton/twin live birth in the cleavage groups were 89.6, 241.1, 585.9, and 981.1 mIU/L, respectively. Biochemical pregnancy rates and adverse pregnancy outcome rates significantly decreased from the low β-hCG group to the higher β-hCG group in sequence. Significantly higher full-term live birth rates were observed in the highest β-hCG group (P < 0.001).ConclusionSerum β-hCG levels were strongly associated with reproductive outcomes. However, the interpretation of β-hCG levels must consider the number and quality of embryos and transfer protocols. When β-hCG was tested on a fixed day post-ET, different cutoff values were required for the prediction of early clinical outcomes. The association between β-hCG and obstetric outcomes must be investigated.