Initial hCG Level Research Articles

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.

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.

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

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

DO EARLY HCG DYNAMICS AFTER EMBRYO TRANSFER DIFFER BASED ON DAY OF EMBRYO BIOPSY?

Serum HCG threshold levels and rate of rise are established predictors of successful pregnancy in IVF embryo transfer cycles. While prior studies on HCG dynamics in early IVF pregnancies have accounted for factors such as stage of embryo development, these studies have not accounted for the speed of embryo development. Day 7 embryos have been shown to have reduced implantation potential.1 However, no study has yet to review the relationship between day 7 embryo transfer and the level of HCG secretion when early pregnancy is achieved. The objective of this study is to compare initial HCG levels and the rate of HCG increase between day 5, 6, and 7 single, euploid frozen embryo transfers (FET). The study included patients who underwent a single, euploid FET, from January 2012 to March 2021. Initial serum HCG levels were reviewed on day 9 post FET, and if positive, the rate of HCG rise, by day 11, was noted. FET cycles were stratified by day of embryo biopsy and cryopreservation (Group A: Day 5; Group B: Day 6; Group C: Day 7). Baseline demographics were compared and analyzed by ANOVA and Kruskal-Wallis. A logistic regression was then performed to evaluate the differences in HCG levels when controlling for Patient Age, Oocyte age, BMI, AMH, BAFC, day 3 FSH, and endometrial thickness at progesterone initiation. A total of 1,707 single euploid FETs were included and separated into three groups: Group A (n = 1,104), Group B (n = 577), and Group C (n = 26). The mean serum HCG value on day 9 after ET was 168.7 in Group A, 143.0 in Group B, and 94.8 in Group C. Initial HCG level and the percent of HCG rise was significantly different between the three groups (p < 0.0001). Day 5 embryos had a significantly higher absolute difference in HCG levels, from day 9 to day 11, compared with day 6 embryos (OR 1.41 [95% CI 1.23-1.75]) and day 7 embryos (OR 4.74 [95% CI 2.16-10.40]). The percent rise of HCG between days 9 and 11 in day 5 embryos was significantly lower than day 7 embryos (OR 2.36 [95% CI 1.079-5.16]), but was similar compared with day 6 embryos (OR 1.19 [95% CI 0.955-1.48]). The HCG dynamics of early pregnancies from a single, euploid FET, are significantly impacted by the day of embryo development. Our findings show that reproductively competent day 7 embryos have lower initial HCG levels, but then a higher rate of HCG rise compared with faster growing day 5/6 embryos. The increased rate of HCG rise in day 7 embryos may reflect a mechanism such as compensation for a delayed activation of the embryonic transcriptome which these slower growing embryos are able to overcome to be able to successfully implant.

THE EARLIER THE BETTER: INITIAL SERUM HCG LEVELS PREDICT LIVE BIRTH AFTER SINGLE EMBRYO TRANSFER

To examine how early serum human chorionic gonadotropin (hCG) levels predict live birth (LB) after single embryo transfer (SET). All fresh and frozen embryo transfers between 2002 and 2019 where a single embryo was transferred and a detectable hCG level was confirmed were reviewed. In our practice, serum hCG levels are routinely examined with serum testing done eight days after blastocyst SET (B-SET) and ten days after cleavage stage SET (C-SET). In order to compare hCG levels across IVF cycles where embryos were transferred at different stages, hCG levels were determined in reference to days “after oocyte retrieval (AOR),” which was calculated as the number of days after fertilization. Two hCG parameters were examined to evaluate their relationship with live birth: “reached 100” which was defined as an hCG level of >100 mIU/mL 15 days AOR and “doubled” which was defined as an hCG level that at least doubled over a 48 hour period between the first and second measurements. Analysis of the descriptive statistics was performed. A total of 1397 IVF cycles (1065 patients) where an SET was performed and the initial hCG level was detectable were included in the analysis (82% B-SET and 18 % C-SET). 35% were fresh and 65% were frozen. The mean age at the time of SET was 35.5 years. 62% of cycles where hCG was detectable on first examination ended in LB. In the cycles that ended in LB the median hCG level was 268.4 mIU/mL (interquartile range [IQR] 181.6, 375.0) 15 days AOR. In the cycles that did not end in LB the median hCG level was 56.7 mIU/mL (IQR 18.8, 142.6) 15 days AOR. In cycles where hCG levels only “doubled” the LB rate was 33%, while in cycles where hCG levels only “reached 100” by 15 days AOR the LB rate was 54%. In cycles where hCG levels both “doubled” and “reached 100” by 15 days AOR the LB rate was 84%. In cycles where hCG levels did not “double” or “reach 100” by 15 days AOR the LB rate was 9%. Among cycles that ended in LB there was no relationship between patient age at time of SET and early hCG levels. In those <35, the median hCG level was 121.7 mIU/mL (IQR 86.0, 115.5), in those 35 - 40 the median hCG level was 110.2 mIU/mL (IQR 75.8, 155.8), and in those > 40 the median hCG level was 119.8 mIU/mL (IQR 78.2, 173.8) at mean of 13.4 days AOR. Specific rises in early hCG levels after SET were associated with LB when hCG levels were checked 15 days AOR. In cycles where hCG levels both doubled and reached 100 mIU/mL by 15 days AOR, the LB rate was 84% and this was a stronger predictor of LB than either parameter alone. LB was only achieved in 9% of cycles where hCG levels neither “doubled” nor “reached 100”. Age was not associated with early hCG levels in cycles that ended in LB.

Early Serum hCG in IVF: Are We Trending in the Right Direction?

Human chorionic gonadotropin (hCG) measurements may be the earliest indicator of fertility cycle success, available several weeks before an ultrasound would be diagnostic for pregnancy. Outcomes of these cycles are high stakes for a couple, and the earliest reassurance of a normal pregnancy would be beneficial for their well-being. Additionally, earlier diagnosis can allow for more rapid management by providers in the case of abnormal pregnancies. Therefore, establishing normal values for initial hCG level and early hCG kinetics is of great interest. There are many factors involved in assisted reproductive techniques that may lead to alterations in hCG kinetics when compared with spontaneous pregnancies. We aim to characterize normal hCG values for in vitro fertilization (IVF) pregnancies and review how different aspects of the IVF process may alter these trends in order to establish how best to counsel patients during the waiting period.

SUN-523 Thyroid Storm: A Rare Presentation of HCG Producing Metastatic Choriocarcinoma

Background: The beta subunit of human Chorionic Gonadotropin (hCG) and TSH are very similar and hCG is known to weakly bind the TSH receptor. hCG induced hyperthyroidism has been previously reported as a rare paraneoplastic syndrome in non-seminomatous germ-cell tumors and usually presents with subclinical thyrotoxicosis. We present a noteworthy case of thyroid storm in a patient with hCG producing testicular Choriocarcinoma. Clinical case: A 19-year-old Hispanic man presented to an outside emergency department (ED) with one day of abdominal pain, nausea, recurrent emesis and subjective fever. He had presented to the same ED 9 days prior with similar symptoms which prompted contrasted CT Abdomen/Pelvis demonstrating hepatic masses and a large right testicular mass, suspicious for primary testicular malignancy. On return evaluation, he was noted to have tachycardia with HR 165, mild scleral icterus, tenderness to palpation of right upper quadrant, abdominal pain and a right scrotal mass (5x5 cm). CBC revealed; WBC 12.0 k/uL (n: 4-10.8), AST: 428 u/L (n: 3-34); ALT: 176 u/L (n: 15-41); total bilirubin: 6.3 mg/dL (n: 0.2-1.3), TSH <0.005 uIU/mL (n: 0.4-4.0) and FT4 5.02 ng/dL (n: 0.7-1.4). Clinical scenario was consistent with thyrotoxicosis concerning for thyroid storm (Burch-Wartofsky Point Scale: 50) requiring intensive care for which he was transferred to our institution. Thyroid US revealed increased thyroid vascularity without nodularity. Laboratory workup revealed negative TG Ab, Anti-TPO Ab, TRAb, and TSIG. Conversely, TBG was elevated at 31.2 mcg/ml (n: 13-30). Initial hCG level was obtained as 6,074. After re-testing with dilution was specifically requested, initial hCG was corrected to 6,760,713. Oncologic workup confirmed diagnosis of hCG producing testicular choriocarcinoma with liver and lung metastases. On admission, he was started on oral methimazole and propranolol as well as intravenous steroids which led to marked symptomatic improvement and normalization of FT4 to 1.37 allowing for discontinuation of antithyroid medication on 7th day of hospitalization. He completed 1 cycle of cisplatin/etoposide and experienced marked reduction of his hCG level to 951,460 which correlated with improvement of his TFTs and resolution of his hyperthyroid symptoms.Conclusion:A low threshold of suspicion should be maintained for the possibility of hyperthyroidism in patients with suspected testicular choriocarcinoma, particularly in the context of recent iodinated contrast imaging. If the clinical picture does not support a primary etiology of hyperthyroidism and hCG is not concordantly elevated, re-assessment of hCG by dilution should be considered as hCG assay is also subject to prozone (hook) effect. Hyperthyroidism should be actively managed and closely monitored as response to treatment can be rapid.

Pregnancy outcomes of fresh IVF conceived pregnancies after embryo transfer at different stages of early embryonic development

Objective To compare pregnancy outcomes between pregnancies following day 2, day 3, and days 5/6 fresh embryo transfer (ET). Methods A retrospective cohort study including all pregnancies following fresh IVF/intracytoplasmic sperm injection (ICSI) ET cycles performed between January 2014 and December 2015 at Fertility and In Vitro Fertilization (IVF) Unit of the tertiary Soroka University Medical Center. The study groups consisted of 48, 72, 120, and 144 hours embryos. Pregnancies were confirmed by a serum beta-human chorionic gonadotropin measurement. Data regarding patients’ medical history, infertility workup, fertility treatment characteristics, and outcome, as well as obstetrical outcome, were collected from patients’ medical records and IVF Laboratory database. Multiple regression models were constructed to control for confounders. Patients who underwent fertility preservation treatment, cycles of oocyte donation or in vitro maturation oocytes, and cases of preimplantation genetic testing were excluded. Results A total of 534 pregnancies following fresh IVF/ICSI ET on day 2 (n = 189, 35.4%), day 3 (n = 200, 37.5%), and days 5 or 6 (n = 145, 27.2%) were included. Live birth rate demonstrated a linear association to the developmental stage at ET with the highest rates in blastocysts and gradually lower in day 3 and day 2 ET (79.2, 65.8, and 60.6%, respectively, p = .001). A positive linear association was also observed between ET age and clinical pregnancy rate (77.3, 87.5, and 90.3% for days 2, 3, and 5/6, respectively, p = .002), as well as with combined pregnancy complication rate (29, 37.3, and 43.3%, p = .026). However, using multivariate logistic regression model controlling for ET age, maternal age, smoking, obesity, initial HCG level and peak E2 level, live birth rate was comparable between the study groups regardless of ET age. Pregnancy complications were comparable between the groups; however, a composite pregnancy complications variable was higher in the blastocyst pregnancies compared to cleavage embryos pregnancies. Conclusions The common approach of blastocyst transfer, as high quality of the embryo, has not proven beneficial in terms of live birth rate. Moreover, cleavage stage embryos were not associated with adverse perinatal outcomes. The current data suggest maternal age has an independent effect on live birth.

Human chorionic gonadotropin value and its change prior to methotrexate treatment can predict the prognosis in ectopic tubal pregnancies.

PurposeTo investigate the role of beta‐human chorionic gonadotropin (HCG) level and its change prior to methotrexate (MTX) treatment as predictors of treatment success and to access the posttreatment observation period for ectopic tubal pregnancy.MethodsClinical data of 41 females treated with MTX for tubal pregnancies were reviewed and analyzed retrospectively.ResultsAmong 41 patients, 34 achieved complete resolution without surgery. No statistically significant difference was observed in the presence of hemorrhagic ascites, serum progesterone levels, or diameters of adnexal mass between the MTX success and failure groups. Serum HCG levels on the day of MTX administration (day 1) were significantly lower in the MTX success group. Moreover, % HCG change per day, which represents the increment ratio of HCG prior to MTX treatment, was significantly lower in the MTX success group. Receiver operating characteristic (ROC) curves demonstrated that the treatment success was predicted by % HCG change per day less than +12.6% per day with a sensitivity of 87% and a specificity of 71%. The duration from treatment to complete recovery was strongly correlated with day 1 HCG levels.ConclusionsPretreatment HCG change is a significant predictor of therapeutic success of MTX treatment, and the treatment period may be predicted from initial HCG levels.

Initial serum human chorionic gonadotropin levels predict live birth outcomes following frozen embryo transfer with and without preimplantation genetic testing for aneuploidy (PGT-A)

Initial serum human chorionic gonadotropin (hCG) levels have an established association with IVF pregnancy outcomes1-3. However, many studies that have examined this association involved fresh transfers, transfer of multiple embryos, and embryos at varying stages of development. As contemporary practice patterns have shifted towards frozen transfer of a single blastocyst, evaluating the predictive value of initial hCG levels in this population is of interest. Additionally, it is not known if the predictive value of the initial hCG level is different for embryos that have undergone PGT-A. The objective of this study is to evaluate early serum human chorionic gonadotropin levels as a predictor of live birth following frozen embryo transfer (FET) of a single blastocyst with and without PGT-A. Retrospective cohort study. All FETs of a single blastocyst at a large IVF center between 2010 and 2016 were reviewed for inclusion. Only those FET cycles resulting in a positive hCG nine days post-transfer were included in this analysis. Initial hCG levels were stratified and live birth rates were analyzed. Chi square analysis was used to compare live birth rates for each hCG category following transfer of embryos with and without PGT-A. A total of 5280 FET cycles were included and 3417 (64.7%) of those cycles resulted in live birth. The mean hCG for a pregnancy resulting in live birth was 185 (+101.4) versus 60.7 (+76.1) mIU/mL for a non-viable gestation (P<0.01). Table 1 displays the live birth rate following FET of embryos with and without PGT-A, stratified by hCG level 9 days post-transfer. Initial serum hCG levels < 50 mIU/mL were associated with reduced live birth rates. For initial hCG levels between 50 and 150 mIU/mL, the live birth rate was approximately 10% higher following transfer of a genetically screened embryo.Tabled 1Live Birth RatesInitial hCG (mIU/mL)Live birth rate with PGT-A (n=3,592)Live bith rate with no PGT-A (n=1,688)P-value0.1-5094/779 (12.1%)48/510 (9.4%)0.1450.1-100377/534 (70.6%)163/269 (60.6%)<0.01100.1-150549/688 (79.8%)199/283 (70.3%)<0.01150.1-200487/567 (85.9%)207/244 (84.8%)0.70>200947/1024 (92.5%)346/382 (90.6%)0.24 Open table in a new tab Even when initial serum hCG levels nine days after FET are low, there is still a chance of live birth. When the initial hCG level is between 50 and 150 mIU/mL, live birth rates are significantly higher with genetically screened embryos.

Predictive value of initial serum human chorionic gonadotropin levels for pregnancies after single fresh and frozen blastocyst transfer.

As one of the earliest markers for predicting pregnancy outcomes, human chorionic gonadotropin (hCG) values have been inconclusive on reliability of the prediction after frozen and fresh embryo transfer (ET). In this retrospective study, patients with positive hCG (day 12 after transfer) were included to examine the hCG levels and their predictive value for pregnancy outcomes following 214 fresh and 1513 vitrified-warmed single-blastocyst transfer cycles. For patients who got clinical pregnancy, the mean initial hCG value was significantly higher after frozen cycles than fresh cycles, and the similar result was demonstrated for patients with live births (LB). The difference in hCG value existed even after adjusting for the potential covariates. The area under curves (AUC) and threshold values calculated by receiver operator characteristic curves were 0.944 and 213.05 mIU/mL for clinical pregnancy after fresh ET, 0.894 and 399.50 mIU/mL for clinical pregnancy after frozen ET, 0.812 and 222.86 mIU/mL for LB after fresh ET, and 0.808 and 410.80 mIU/mL for LB after frozen ET with acceptable sensitivity and specificity, respectively. In conclusion, single frozen blastocyst transfer leads to higher initial hCG values than single fresh blastocyst transfer, and the initial hCG level is a reliable predictive factor for predicting IVF outcomes.

Predictive factors for the methotrexate treatment outcome in ectopic pregnancy: A comparative study of 400 cases

ObjectiveWe sought to evaluate the global success rate of intramuscular methotrexate for the treatment of ectopic pregnancy, identify factors predictive of treatment success or failure, and study methotrexate tolerability in a large patient cohort. Study designFor this single-center retrospective observational study, we retrieved the records of all women who had a clinically or echographically confirmed ectopic pregnancy with a Fernandez score <13 and who were treated according to a 1mg/kg intramuscular single-dose methotrexate protocol. Medical treatment failure was defined by an obligation to proceed to laparoscopy. Needing a second injection was not considered to be medical treatment failure. ResultsBetween February 2008 and November 2013 (69 months), 400 women received methotrexate for ectopic pregnancy. The medical treatment protocol was effective for 314 patients, i.e., an overall success rate of 78.5%. A single methotrexate dose was sufficient for 63.5% of the women and a second dose was successful for 73.2% of the remaining women. The medical treatment success rate fell as initial hCG levels climbed. The main factors associated with methotrexate failure included day (D) 0, D4 and D7 hCG levels, pretherapeutic blood progesterone, hematosalpinx at D0 and pain at D7. Early favorable kinetics of hCG levels was predictive of success. Methotrexate treatment was successful in 90% of women who had D0 hCG <1000IU/l. Methotrexate tolerability was good, with only 9% of the women reporting non-severe adverse effects. The fertility rate with delivery after medical treatment for ectopic pregnancy was 80.7%. ConclusionIn this study, we showed that an initial hCG value <1000IU/l and favorable early HCG kinetics were predictive factors for the successful medical treatment of ectopic pregnancy by methotrexate, and hematosalpinx and pretherapeutic blood progesterone >5ng/ml at diagnosis were predictive of its failure. We also confirmed good tolerability for single-dose methotrexate protocols.

Thyroid Hormone Levels and Its Relationship with Human Chorionic Gonadotropin in Patients with Hydatidiform Mole

Objective: Hydatidiform pregnancy occurs in 1:1000 pregnancies worldwide; incidence is higher in Asian countries. In approximately 5% of cases of hydatidiform mole, clinical hyperthyroidism is present. The aim of this study was to examine the relation between HCG level and thyroid function test. Methods: During 5 years (2009-2013) we included 146 cases of molar pregnancies into the study at Imam Reza teaching hospital. The demographic and clinical data as well as serum initial HCG level and thyroid function test (TSH T3 T4) were retrieved and entered into prepared proformas. p In this study significantly inverse relation was observed between B-HCG and TSH (p = 0.05). We also found a significantly direct correlation between B-HCG and T3 (p = 0.01) and T4 (p = 0.01). Conclusion: We concluded significantly meaningful relationship between BHCG and T3, T4, TSH.

The relationship between initial HCG levels and development of preeclampsia in pregnancies following in vitro fertilization

The relationship between initial HCG levels and development of preeclampsia in pregnancies following in vitro fertilization

Do you need to follow hCG (human chorionic gonadotropin) levels to zero for everyone who has had a spontaneous abortion?

Evidence-Based Answer Probably not. Rapidly declining hCG levels noted in the first 2–7 days after a patient presents with symptoms of miscarriage have a 95% probability of indicating a completed spontaneous abortion. For clinical application, the higher the initial hCG level, the greater the percentage decrease in hCG is needed. A very small percentage (0.7%) of patients with declining hCG levels will have an ectopic pregnancy (SOR: B, limited prospective, retrospective cohort, and cross-sectional studies).

Frozen Embryo Transfers Following Trophectoderm Biopsy Result in Lower Initial hCG Levels, But Result in High Pregnancy Rates and Normal Pregnancy Outcomes

Initial human chorionic gonadotropin (iHCG) levels are routinely used to counsel patients regarding likelihood of pregnancy.1 Low iHCG levels indicate high risk of early pregnancy loss. Trophectoderm (TE) biopsy for aneuploidy screening is being increasingly utilized to improve pregnancy rates. Given that TE biopsies necessarily reduce the trophoblast volume, this procedure might decrease iHCG levels and ultimately placental function. This study examined whether TE biopsy altered iHCG levels, their predictive values, and birth outcomes in frozen transfer cycles.

Overexpression of Karyopherin 2 in Human Ovarian Malignant Germ Cell Tumor Correlates with Poor Prognosis

BackgroundThe aim of this study was to identify a biomarker useful in the diagnosis and therapy of ovarian malignant germ cell tumor (OMGCT).MethodsThe karyopherin 2 (KPNA2) expression in OMGCT and normal ovarian tissue was determined by standard gene microarray assays, and further validated by a quantitative RT-PCR and immunohistochemistry. The correlation between KPNA2 expression in OMGCT and certain clinicopathological features were analyzed. Expression of SALL4, a stem cell marker, was also examined in comparison with KPNA2.ResultsKPNA2 was found to be over-expressed by approximately eight-fold in yolk sac tumors and immature teratomas compared to normal ovarian tissue by microarray assays. Overexpression was detected in yolk sac tumors, immature teratomas, dysgerminomas, embryonal carcinomas, mature teratomas with malignant transformation and mixed ovarian germ cell tumors at both the transcription and translation levels. A positive correlation between KPNA2 and SALL4 expression at both the transcription level (R = 0.5120, P = 0.0125), and the translation level (R = 0.6636, P<0.0001), was presented. Extensive expression of KPNA2 was positively associated with pathologic type, recurrence and uncontrolled, ascitic fluid presence, suboptimal cytoreductive surgery necessity, resistance/refraction to initial chemotherapy, HCG level and SALL4 level in OMGCT patients. KPNA2 was found to be an independent factor for 5-year disease-free survival (DFS) of OMGCT (P = 0.02). The 5-year overall survival (OS) and DFS rate for KPNA2-low expression patients (88% and 79%, n = 48) were significantly higher than the OS and DFS rate for KPNA2-high expression patients (69% and 57.1%, n = 42)(P = 0.0151, P = 0.0109, respectively). The 5-year OS and DFS rate for SALL4-low expression patients (84% and 74%, n = 62) was marginally significantly higher than the high expression patients (78.6% and 71.4%, n = 28)(P = 0.0519, P = 0.0647, respectively).ConclusionsKPNA2 is a potential candidate molecular marker and important prognostic marker in OMGCT patients.

Trophectoderm (TE) biopsy for aneuploidy screening results in lower initial hCG levels with altered predictive values: low initial levels still have high delivery rates and normal pregnancy outcomes

Lower initial HCG (iHCG) levels 2 weeks after oocyte retrieval predict higher early pregnancy loss risk and may be used for counseling and to direct treatment. TE biopsy is becoming routine and given that it necessarily reduces initial trophoblast volume, it might alter iHCG levels and eventually placental sufficiency. This study seeks to determine whether TE biopsy impacts iHCG levels, their predictive value for delivery, and eventual newborn outcomes.

Validation of the predictive value of modeled HCG residual production “P” in low-risk gestational trophoblastic neoplasia (GTN) patients treated in GOG-174 phase III trial.

5110 Background: In low-risk GTN, chemotherapy is changed according to serum hCG levels. We previously showed mathematical modeling of hCG kinetics provides a parameter production “P”, a useful early predictor of methotrexate (MTX) resistance (You et al; Ann Oncol 2010; ASCO and ISSTD 2011). We applied this approach to patient cohort of GOG-174 trial, in which weekly MTX (Arm 1) was compared to dactinomycin (Arm 2). Methods: Database (210 patients, including 78 with resistance) was split into 2 sets. A 126 patient Model Set was initially used to adjust model parameters. Patient hCG kinetics from day7 to day50 were fit with NONMEM™ program to: “[hCG(time)] = hCG0i * exp(–k*time) + P”; where P is residual hCG tumor production, hCG0i is the initial hCG level, and k is the rate constant. Three putative P-based classifiers of resistance were assessed using ROC analyses. Then an 84 patient Test Set with blinded-resistance status was used to assess the validity of predictions. The primary endpoint was treatment resistance defined as relapse and/or lack of hCG normalization. Results: Due to initial surge in 14% patients, hCG kinetic modeling was started on day7. Individual hCG decline profiles of Model Set patients were modeled. There was no impact of treatment arm on variability of kinetic parameter estimates. The best P cut-offs to discriminate resistant vs. sensitive patients were 7.7 in Arm 1 and 74.0 in Arm 2. They were combined to define 2 predictive groups with low vs. high risks of resistance (ROC AUC = 0.82; Se = 93.8%; Sp = 70.5%). The model was then applied to Test Set patient cohort. The predictive value of P-based predictive groups regarding resistance was reproducible (ROC AUC = 0.81; Se = 88.9% (95% CI: 70.8%-97.7%); Sp = 73.1% (95% CI: 60.0%-84.4%)). Both P and treatment arm were associated with resistance using multivariate logistic regression tests. Predictive value of P was less accurate in dactinomycin arm. Conclusions: The early predictive value of the modeled kinetic parameter P regarding resistance appears promising in GOG-174 study, especially in MTX arm. This is the second positive evaluation of this procedure study. Prospective validation is warranted.

Validation of the predictive value of modeled hCG decline profiles in low-risk gestational trophoblastic neoplasia (GTN) treated with methotrexate (MTX).

5099 Background: In low-risk GTN, MTX treatment is changed according to serum hCG levels. We previously showed that population modeling of hCG levels using kinetic equations provided parameters that could be used as independent predictors of MTX resistance (You et al; Ann Oncol 2010). In the present study we applied this approach to a large independent patient cohort in which hCG measurements were made using the same immunoassay. Methods: The hCG kinetic profiles of 563 patients with low-risk GTN (281 MTX Resistant: 282 MTX Sensitive) treated at Charing Cross Hospital were retrospectively analyzed in a 3-step validation study. Initially a 189 patient “Model Set” was used to derive kinetic parameters of the model using the NONMEM program. Patient hCG kinetics were described from day0 to day50 using: “[hCG(time)] = hCG0i * exp(–k*time)+ P”, where P is residual hCG tumor production, hCG0i is the initial hCG level, and k is the rate constant. The predictive values of different kinetic parameters (clearance, area under the curve, AUC and P) were assessed using ROC curves and logistic regression. Subsequently, 2 independent datasets comprising 149 and 225 patients with blinded-resistance status (Validation1 and Validation2 sets) were used to assess the validity of the modeling and predictions. Results: Despite large inter-individual variability, individual hCG decline profiles of the Model Set patients were well fitted by the model. The best discriminator of MTX resistant vs. sensitive patients was median P (cut-off = 23: ROC AUC = 77.3). P was the only significant predictor of resistance against WHO score items. The model was then applied to the Validation1 and 2 patient cohorts. Again, the decreasing hCG values were well fitted by the kinetic model. The predictive value of P for MTX resistance was confirmed: Validation1 ROC AUC = 82.1% (Sensitivity = 75%; Specificity = 89%) and Validation2 ROC AUC = 92.0% (Sensitivity = 94%; Specificity = 89%). Conclusions: We have validated population kinetic modeling of hCG decline profiles in a large cohort of low-risk GTN patients treated with MTX and confirmed its clinical utility for early prediction of MTX resistance.