High Human Chorionic Gonadotropin Research Articles

A 20 year experience in the management of non-tubal ectopic pregnancies in a tertiary hospital – a retrospective review

BackgroundNon-tubal ectopic pregnancies account for < 10% of all ectopic pregnancies. Due to its rarity and wide variation in clinical practice, there is no guideline or consensus for its management. We reported our 20-year experience in the management of non-tubal ectopic pregnancies in a tertiary hospital.MethodsThis is a retrospective review of all women admitted for non-tubal ectopic pregnancies from January 2003 to December 2022 in a tertiary hospital. Women with non-tubal ectopic pregnancies diagnosed by ultrasound or operation were included for analysis.ResultsWithin the study period, 180 women were diagnosed to have non-tubal ectopic pregnancies at a mean gestation of 6.8 weeks. 16.7% (30/180) were conceived via assisted reproduction. Medical treatment was the first-line management option for 81 women, of which 75 (92.1%) women received intralesional methotrexate administered under transvaginal ultrasound guidance. The success rate of intralesional methotrexate ranges from 76.5% to 92.3%. Intralesional methotrexate was successful even in cases with a positive fetal pulsation or with high human chorionic gonadotrophin levels up to 252605U/L. Twenty seven women were managed expectantly and 40 underwent surgery. Nine (11.1%), two (6.1%), and one (2.3%) women required surgery due to massive or recurrent bleeding following medical, expectant, or surgical treatment. Hysterotomy and uterine artery embolization were necessary to control bleeding in one Caesarean scar and one cervical pregnancy.ConclusionsIntralesional methotrexate is more effective than systemic methotrexate and should be considered as first line medical treatment for non-tubal ectopic pregnancies. It has a high success rate in the management of unruptured non-tubal ectopic pregnancies even in the presence of fetal pulsations or high human chorionic gonadotrophin levels, but patients may require a prolonged period of monitoring. Close surveillance and readily available surgery were required due to the risk of heavy post-procedural intra-abdominal bleeding.

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.

Methotrexate as the first-line treatment of unruptured tubular ectopic pregnancies with high initial human chorionic gonadotropin levels: A retrospective cohort

ObjectivesTo evaluate the effectiveness of the first-line medical management with Methotrexate (MTX) in the treatment of patients with stable tubal Ectopic Pregnancies (EPs) and varying ranges of Beta-Human Chorionic Gonadotropin (β-HCG) levels. Materials and methodsIn this retrospective cohort study, we reviewed the medical records of a total of 184 patients with the diagnosis of tubal EP, who received MTX as their first-line treatment. Patients with a baseline β-HCG< 4800 mIU/mL received single-dose MTX (n = 136) and those with an initial β-HCG≥ 4800 mIU/mL underwent the double-dose MTX regimen (n = 48). The treatment success was determined by evaluating the reported weekly β-HCG levels of the patients. ResultsBaseline β-HCG and mass size in the single-dose group were 1895.1 ± 1463.4 mIU/mL and 2.2 ± 1.1 cm, respectively, compared to 17,867.6 ± 31,870.5 mIU/mL and 2.3 ± 1.1 cm in the double-dose group. Treatment duration was 30.6 ± 16.9 days for single dose and 41.0 ± 27.0 days for double dose, with additional MTX in 27.2% and 12.5% in respective groups. Single dose achieved a 92.6% success rate, and double dose, 81.3%, without serious adverse effects. No significant effects were seen for either baseline β-HCG and mass size on the treatment success rates of both groups (p-value>0.05). However, the presence of Fetal Heart Rate (FHR) was associated with poorer responses only in the single-dose group (p-value=0.034). ConclusionsMedical management with MTX shows promise as a first-line treatment for tubal EPs with β-HCG> 2000, suggesting a potential reassessment of existing guidelines in light of this emerging evidence. However, further research seems crucial in this field.

Multiple pregnancy with complete hydatidiform mole and coexisting normal fetus in a retrospective cohort of 141 patients

Multiple pregnancy with a complete hydatidiform mole and a normal fetus is prone to severe obstetrical complications and malignant transformation after birth. Prognostic information is limited for this rare form of gestational trophoblastic disease. This study aimed to determine obstetrical outcomes and the risk of gestational trophoblastic neoplasia in women with multiple pregnancy with complete hydatidiform mole and coexisting normal fetus, and to identify risk factors for poor obstetrical and oncological outcomes to improve patient information and management. This was a retrospective national cohort study of 11,411 records from the French National Center for Trophoblastic Disease registered between January 2001 and January2022. Among 11,411 molar pregnancies, 141 involved histologically confirmed multiple pregnancy with complete hydatidiform mole and coexisting normal fetus. Roughly a quarter of women (23%; 33/141) decided to terminate pregnancy because of presumed poor prognosis or by choice. Among the 77% of women (108/141) who continued their pregnancy, 16% of pregnancies (17/108) were terminated because of maternal complications, and 37% (40/108) ended in spontaneous miscarriage before 24 weeks' gestation. The median gestational age at delivery in the remaining 47% of pregnancies (51/108) was 32 weeks. The overall neonatal survival rate at day 8 was 36% (39/108; 95% confidence interval, 27-46) after excluding elective pregnancy terminations. Patients with free beta human chorionic gonadotropin levels <10 multiples of the median were significantly more likely to reach 24 weeks' gestation compared with those with free beta human chorionic gonadotropin levels >10 multiples of the median (odds ratio, 7.0; 95% confidence interval, 1.3-36.5; P=.022). A lower free beta human chorionic gonadotropin level was also associated with better early neonatal survival (the median free beta human chorionic gonadotropin level was 9.4 multiples of the median in patients whose child was alive at day 8 vs 20.0 multiples of the median in those whose child was deceased; P=.02). The overall rate of gestational trophoblastic neoplasia after a multiple pregnancy with complete hydatidiform mole and a normal fetus was 26% (35/136; 95% confidence interval, 19-34). All 35 patients had low-risk International Federation of Gynecology and Obstetrics scores, and the cure rate was 100%. Termination of pregnancy on patient request was not associated with lower risk of gestational trophoblastic neoplasia. Maternal complications such as preeclampsia and postpartum hemorrhage were not associated with higher risk of gestational trophoblastic neoplasia, and neither were high human chorionic gonadotropin levels or newborn survival at day8. Multiple pregnancy with complete hydatidiform mole and coexisting fetus carries a high risk of obstetrical complications. In patients who continued their pregnancy, approximately one-third of neonates were alive at day 8, and roughly 1 in 4 patients developed gestational trophoblastic neoplasia. Therefore, the risk of malignant transformation appears to be higher compared with singleton complete moles. Low levels of free beta human chorionic gonadotropin may be indicative of better early neonatal survival, and this relationship warrants further study.

Ovarian Hyperstimulation Syndrome Post-dilation and Evacuation of a Hydatidiform Mole: A Case Report

The present study reports a complete hydatidiform mole presenting with ovarian hyperstimulation syndrome after dilatation and evacuation. A 30-year-old female came to the emergency room with abdominal pain and genital bleeding at 14 weeks of pregnancy. Ultrasonography revealed vesicular cystic swelling of chorionic villi with high human chorionic gonadotrophin (625,000 IU/L). Dilatation and evacuation was performed. Symptoms of ovarian hyperstimulation syndrome appeared on the 8th day after dilatation and evacuation, and bilateral enlarged multicystic ovaries were found, measuring 13.07x8.45x9.77 cm on the left and 9.02x8.45x5.5 cm on the right. The cysts gradually reduced in size and finally disappeared at Day 42, and human chorionic gonadotrophin reached below cut-off value at Day 72.

Abstract #1409027: Paraneoplastic Hyperthyroidism

Non-seminomatous germ cell tumors producing human chorionic gonadotropin (HCG) were first described in 1964. HCG is capable of inducing hyperthyroidism by stimulating the TSH receptor, due to its identical alpha subunit. We report a case of HCG-mediated hyperthyroidism in the setting of a choriocarcinoma. A 28-year-old man presented with a 3-week history of unintentional weight loss, cough, hemoptysis, palpitations, shortness of breath, nausea and vomiting. Chest x-ray showed a large pleural effusion and multifocal nodular opacities on lungs measuring up to 4 cm. CT abdomen/pelvis showed a 1.4 cm left renal mass concerning for metastasis, and hepatomegaly. CT chest demonstrated a 16 cm heterogeneous enhancing mass in the mediastinum, a large pericardial effusion, moderate left pleural effusion and metastatic pulmonary nodules. Laboratory results showed elevated HCG of 947,825 mIU/mL, AFP 25 ng/ml, LDH 1,394 U/L, TSH 0.011 mcIU/mL, FT4 2.0 ng/dL, Ferritin 2680 ng/mL, CRP 118 mg/L. Testicular ultrasound was unremarkable. Biopsy of mediastinal mass was consistent with choriocarcinoma. Endocrinology was consulted for evaluation of abnormal thyroid function. He was tachycardic, without other overt symptoms of hyperthyroidism and no clinical findings of Graves’ Disease. TRAB, TSI, TPO antibodies were negative. Propylthiouracil (PTU) 100mg every 8 hours and low dose propranolol were started. Chemotherapy with Etoposide, Ifosfamide, and Cisplatin was initiated. Thyroid function improved 5 days after initiation of therapy. After 3 cycles of chemotherapy, his TSH and Free T4 levels normalized and the HCG level decreased to 1,521 mIU/mL. His most recent thyroid function tests were TSH 5.8 mcIU/ml and Free T4 level 1.1 ng/dL and the decision was made to stop PTU. HCG is a heterodimer with an alpha subunit identical to that of TSH, LH and FSH. High HCG levels can stimulate the TSH receptor and cause hyperthyroidism. Hyperthyroidism has been reported in trophoblastic tumors when HCG levels are >200,000 mIU/mL. Initiation of chemotherapy produces rapid decline in HCG levels and improvement of Free T4 levels. Diagnosis of paraneoplastic hyperthyroidism is challenging, as symptoms of hyperthyroidism may overlap with those of metastatic disease. Symptomatic patients should be started on thianomide and beta blocker which improve well-being and tolerance to chemotherapy. We illustrated the challenge of diagnosing hyperthyroidism in HCG-secreting choriocarcinoma and the importance of initiating chemotherapy and anti-thyroidal medication in symptomatic patients to improve outcomes.

High concentration of first-measured HCG after embryo transfer is associated with subsequent development of pre-eclampsia

Research questionAre outlier high values of first-measured human chorionic gonadotrophin (HCG) following embryo transfer related to pregnancy complications, specifically pre-eclampsia? DesignThis retrospective cohort study screened 3448 women aged 18–45 years who underwent IVF between 2014 and 2019 and evaluated 614 women who had an intrauterine pregnancy following single embryo transfer (SET), 423 of whom had a live birth. Pregnancy and birth outcome information was available for final analysis in 280 cases. The setting was a university-based IVF centre. HCG was measured at a standardized time after the embryo transfer and the values correlated with adverse pregnancy outcomes associated with poor placentation. ResultsWomen with first-measured HCG in the highest quintile had a higher incidence of pre-eclampsia than those with lower HCG concentrations (odds ratio [OR] 4.08, 95% confidence interval [CI] 1.41–11.82) even after controlling for age, body mass index, parity and type of embryo transfer. Additionally controlling for embryo stage at embryo transfer did not change the results (OR 3.97, 95% CI 1.37–11.46). No differences were found in the incidence of fetal growth restriction. ConclusionsThis is the first known report that links high first-measured HCG after SET to an adverse pregnancy outcome. If confirmed by future studies, initiation of preventive interventions at a very early stage of pregnancy merits further evaluation in this cohort of patients.

Paclitaxel, ifosfamide, cisplatin (TIP) for the treatment of intermediateand poor-risk nonseminomatous germ cell tumors with an inadequate decrease in tumor markers: a phase II study

Purpose: To evaluate efficacy of TIP (paclitaxel, ifosfamid, cisplatin) in the 1st line treatment of germ cell tumors patients with unfavorable decline of serum tumor markers after 1 cycle of the standard regimen of chemotherapy. Patients and methods: In this phase II multicenter, nonrandomized trial, patients were enrolled from 4 centers of the Russian Federation. Patients were included if they were older than 18 years, had evidence of testicular, retroperitoneal, or mediastinal nonseminoma based on histologic findings or clinical evidence (high serum human chorionic gonadotropin or alpha-fetoprotein levels) that matched International Germ Cell Cancer Consensus Group (IGCCCG) intermediate and poor prognosis criteria. All patients got one cycle of BEP regimen (bleomycin 30 mg on days 1, 3, 5, etoposide 100 mg / m 2 on days 1–5, cisplatin 20 mg / m 2 on days 1–5). Patients with unfavorable serum tumor markers decline after the first cycle of chemotherapy at day 18–21 received four cycles of TIP regimen (paclitaxel 120 mg / m 2 on days 1–2, ifosfamide 1500 mg / m 2 on days 2–5, and cisplatin 25 mg / m 2 om days 2–5, granulocyte-colony stimulating factor 5 mg / kg on days 6–15). In the presence of a residual tumor larger than 1 cm and the technical possibility of its removal, surgical treatment was performed. The primary endpoint was 1-year progression-free survival. Results: Between 2017 and 2021, 28 patients were included in our study: seven patients with an intermediate prognosis according to IGCCCG classification and twenty-one with poor risk. Median follow-up was 15,5 months (range, 4,4–38,3 months). The 1-year progression-free survival and overall survival in intention-to-treat population were 76,6 % and 81,0 %, respectively. One-year progression-free survival and overall survival according IGCCCG classification were 100 % and 100 % for an intermediate risk patients and 68 % and 73,8 % for a poor risk, respectively. The favorable response rate (complete response + partial response with normalization STM) was observed in 19 (68 %) patients. During the follow-up period, disease progression was noted in 9 (32 %) patients, 7 (25 %) patients died, including one from an aggressive growing mature teratoma syndrome. Eleven (39 %) patients underwent surgical treatment: retroperitoneal lymph node dissection (55 %), mediastinal lymph node dissection (36 %), pulmonary resection (9 %). Pathological complete response was achieved in 6 (55 %) patients, mature teratoma — 2 (18 %), viable tumour — 3 (27 %). TIP showed acceptable safety profile and only in one case tumor lysis syndrome was observed. Conclusions: The TIP regimen may improve the results of treatment in the first line with unfavorable decrease of serum tumor markers after the first cycle of chemotherapy, which requires further study in a randomized trial.

Tapered Side-Polished Microfibre Sensor for High Sensitivity hCG Detection

A high sensitivity human chorionic gonado-tropin (hCG) detection was conducted by a tapered side-polished (TSP) optical fiber sensor. Experimentally, the TSP fiber sensor was made by side polishing a short section of single mode fiber to a D shape structure and tapering the D shape section to a small diameter (<inline-formula> <tex-math notation="LaTeX">$ &lt; 10~\mu \text{m}$ </tex-math></inline-formula> in the experiments). By functionalizing the primary antibody of hCG onto the TSP fiber surface, the sensor was used for detecting hCG concentration. Experimental results show that when the hCG concentration is 0.1 mIU/mL, the sensor has an average wavelength shift of 0.82 nm. The limit of detection (LoD) of the hCG is estimated 0.058 mIU/mL, assuming three times of maximum wavelength variation (<inline-formula> <tex-math notation="LaTeX">${3}\times {0}.{15}=0.45$ </tex-math></inline-formula> nm) in Phosphate buffer saline (PBS) to the measurement limit. The specificity has also been tested by immersing the sensor into a mixed biomaterial solution (hCG - 1 mIU/mL, pig-IgG - 1 <inline-formula> <tex-math notation="LaTeX">$\mu \text{g}$ </tex-math></inline-formula>/mL, Staphylococcus aureus <inline-formula> <tex-math notation="LaTeX">$-{6}\times {10}^{{5}}$ </tex-math></inline-formula> CFU/mL and Escherichia coli - <inline-formula> <tex-math notation="LaTeX">${2.5}\times {10}^{{5}}$ </tex-math></inline-formula> CFU/mL). The result showed that the TSP optical fiber sensor has excellent specificity. The biosensor has potential application in clinical/medical diagnostics, human health, environmental quality and food safety monitoring.

IS A SINGLE-DOSE OR TWO-DOSE METHOTREXATE PROTOCOL MORE EFFECTIVE IN TREATING AN ECTOPIC PREGNANCY AFTER IVF?

The medical management of ectopic pregnancy with methotrexate is geared towards resolution without the need for surgical intervention. Prior studies comparing single-dose and two-dose methotrexate (MTX) protocols found that a two-dose protocol is effective, particularly among patients with a high initial human chorionic gonadotropin (hCG) level [1-3]. However, there have been no studies comparing the outcome of single vs. two-dose MTX protocol for the treatment of an ectopic pregnancy in patients that conceive from IVF.

A study of Thyroid Function test and Lipid Profile in Pregnancy

Pregnancy is known to create profound changes in the body. It causes hormonal changes in the bodywhich may lead to changes in lipid profile. TSH levels are usually suppressed due to very high levelsof Human chorionic gonadotropin (hCG) during the first half of the pregnancy. Thyroid dysfunction mayresult in various changes in triglycerides, phospholipids, cholesterol and other lipoproteins. Dyslipidemia, aconsequence of thyroid dysfunction, generally increases the risk for cardiovascular disease.The study was conducted in the Department of Biochemistry, MMC&amp;RI, Mysore. 100 women with asingleton pregnancy irrespective of parity and gravida were enrolled and cases like chronic hypertension,Diabetes mellitus, Renal Disorders and Thyroid Disorders, Obstetric and Foetal Complications (Hydropsfoetalis, congenital foetal anomalies) were excluded from the study. Blood was analysed for thyroid andlipid profile.Conclusion: T3, T4 and TSH levels are within normal range during pregnancy. There is a positive correlationbetween TSH levels and cholesterol. This suggest that regular TSH and cholesterol estimation is veryimportant during pregnancy to reduce the maternal and fetal complications.

SAT-LB89 Choriocarcinoma Induced Hyperthyroidism: Molecular Mimicry Between HCG and TSH

Introduction: Human chorionic gonadotropin(HCG) induced hyperthyroidism is a rare cause of hyperthyroidism. It is usually seen in conditions with extremely high beta HCG levels like hyperemesis gravidarum, hydatiform moles and germ cell tumors. We present a young male patient who had primary mediastinal choriocarcinoma with widespread lung metastasis and hyperthyroidism. Case: 18-year-old male presented to the emergency department for a fever of 105 F, cough, shortness of breath and night sweats for 9 days. He also reported unintentional weight loss for the past few weeks. Upon presentation, he was tachycardic at 104 beats/min, tachypneic and febrile. Physical examination revealed bibasilar crackles. Thyroid and scrotal examination were unremarkable. Laboratory work was significant for leukocytosis of 18.7 k/cmm, AST: 69 Unit/L, ALT: 60 Unit/L, ALP: 123 unit/L and LDH: 438Unit/L. Chest radiology showed bilateral multiple cannonball lesions with mediastinal and periaortic lymphadenopathy. CT chest, abdomen, and pelvis revealed innumerable diffuse bilateral lung masses, large anterior mediastinal mass, enlarged periaortic and paratracheal lymph nodes. Infectious workup was unremarkable. MRI brain revealed leptomeningeal involvement and vasogenic edema. Ultrasound of testicles revealed bilateral severe microlithiasis. CT guided biopsy of lung mass showed poorly differentiated choriocarcinoma. Treatment was initiated with systemic steroids, bleomycin, and cisplatin. Additional blood work revealed, B-HCG:736,598 mIU/mL, TSH:0.009UIU/ml, free T4:2.95ng/dL and total T3: 292.3ng/Dl. Thyroid radioiodine uptake scan was normal and planar imaging was also normal. Treatment with methimazole was deferred due to the up-trending transaminases and the resolution of tachycardia. Repeat labs after chemotherapy were TSH: 0.005UIU/mL, free T4: 2.04ng/dL, free T3:1.70pg/mL and BHCG: 202,471UIU/mL. Unfortunately, the patient had chemotherapy-resistant choriocarcinoma and succumbed to death after 4 cycles. Discussion: Beta HCG has an intrinsic thyroid-stimulating activity. The HCG -alpha subunit is common to all glycoprotein hormones like follicle-stimulating hormone, luteinizing hormone or thyroid-stimulating hormone. Frankly elevated levels should be treated symptomatically with beta-blockers and/or anti-thyroid drugs. Subclinical hyperthyroidism should be monitored closely. Some patients do not develop hyperthyroidism or a toxic goiter, as it is dependent on the timing of onset of cancer or due to the secondary modifications of HCG that can affect the bioactivity of HCG on the TSH receptor. This case draws our attention to the importance of focusing on the molecular mimicry of the HCG and TSH and management of HCG mediated hyperthyroidism.

Exclusive use of intrasac potassium chloride and methotrexate for treating cesarean scar pregnancy: effectiveness and subsequent fecundity

STUDY QUESTIONIs exclusive use of intragestational sac potassium chloride (KCl) and methotrexate (MTX) effective in the management of viable cesarean scar pregnancy (CSP)?SUMMARY ANSWERExclusive use of intragestational sac KCl and MTX was effective in the management of viable CSP.WHAT IS KNOWN ALREADYOwing to a paucity of randomized studies on management of CSP, evidence-based management remains unclear. Intragestational sac KCl or MTX along with either systemic MTX or surgical intervention, such as uterine artery embolization or dilation and curettage, has proved to be effective in the management of CSP. Furthermore, there are limited data in the literature on the use of exclusive intragestational sac KCl and MTX for management of CSP and subsequent fecundity.STUDY DESIGN, SIZE, DURATIONA prospective cohort study was conducted from June 2017 to September 2019. We recruited nine CSP patients referred to our unit. There was no lost to follow-up noted.PARTICIPANTS/MATERIALS, SETTING, METHODSPatients with an ultrasound diagnosis of CSP who fulfilled the inclusion criteria were recruited. The study was conducted in a tertiary care center. Clinical symptoms, pregnancy viability, gestational age and human chorionic gonadotrophin (HCG) values determined the management in each individual case. Accordingly, patients were grouped into the expectant management (Group I, n = 3) and intragestational sac KCl with MTX (Group II, n = 6) groups. Demographic details, clinical characteristics, ultrasound details at diagnosis, post-treatment HCG normalization time, menses resumption, mass resolution and subsequent fecundity were noted. Descriptive statistics were used for analyses.MAIN RESULTS AND THE ROLE OF CHANCEOf the nine patients with CSP, six patients had viable CSP and required intervention. Out of these, four patients expressed a desire for future fertility. Mean gestational age at treatment among patients in Group II was 54.33 ± 7.51 days (range 46–65). Mean HCG value at the time of diagnosis was 84 110 ± 38 679.39 IU/l in Group II patients as compared with 2512 ± 709.36 in Group I. HCG had decreased by 92.7 ± 3.78% 2 weeks after intervention and normalized (<5 IU/l) by 53.5 ± 14.97 days. No major complications occurred and additional treatment was not required in these patients. Menstruation had resumed by 26 ± 6.6 days after treatment in Group II. On follow up, a small unresolved mass was present in two patients and the cesarean scar niche was visible in the remaining four patients. Out of the four patients desirous of future conception, three conceived naturally and one delivered a term baby via repeat lower segment cesarean section.LIMITATIONS, REASONS FOR CAUTIONThe main limitation of our study was small sample size. All the patients were asymptomatic at presentation and hence we cannot comment on use of this method in those presenting with active vaginal bleeding.WIDER IMPLICATIONS OF THE FINDINGSIntragestational sac KCl plus MTX may be a highly effective approach for the management of viable CSP despite high initial HCG values. There seems to be no need for any further intervention. It can be considered as the first line minimally invasive treatment option in patients desirous of future fertility. Nevertheless, accumulation of further cases is required to validate this treatment modality.STUDY FUNDING/COMPETING INTERESTSNo specific funding was received to undertake this study. The authors report no conflict of interest.TRIAL REGISTRATION NUMBERN/A

Interstitial Pregnancy after Ipsilateral Salpingectomy: Analysis of 46 Cases and a Literature Review

To investigate the relationship between previous ipsilateral salpingectomy and interstitial pregnancy and report on our experience of laparoscopic cornuostomy for interstitial pregnancy. Single-center, retrospective review. University-based hospital. All patients who had undergone ipsilateral salpingectomy previously, diagnosed with interstitial pregnancy and treated between July 2010 and September 2018. Laparoscopy or laparotomy as a treatment for interstitial pregnancy after ipsilateral salpingectomy. A total of 414 cases of interstitial pregnancy were identified, of which 46 (11.1%) were after ipsilateral salpingectomy. Of the 46 patients, 20 (43.5%) became pregnant by in vitro fertilization and embryo transfer. Ipsilateral salpingectomy was the result of an ectopic pregnancy in 40 patients, hydrosalpinx in 5 patients, and torsion of an ovarian tumor in 1 patient. The laparoscopic approach was used to treat 78.3% of patients with history of previous salpingectomy. Patients who underwent ipsilateral salpingectomy by laparoscopy previously had a shorter interval from salpingectomy to interstitial pregnancy (24 months vs 60 months; p = .038) compared with patients who underwent ipsilateral salpingectomy by laparotomy. Laparoscopic cornuostomy was performed in 38 patients (82.6%); 12 had fetal cardiac activity, 15 had ruptured masses, and 16 used prophylactic methotrexate (MTX) intraoperatively. The median size of the ectopic mass was 2.5 cm (1.0-5.0 cm). At the time of laparoscopic cornuostomy, more patients with interstitial pregnancies with intact ectopic masses were administered prophylactic MTX (81.3% vs 45.5%; p = .043). Only 1 patient with a ruptured ectopic mass, high preoperative human chorionic gonadotropin levels, and without prophylactic MTX administration experienced a persistent ectopic pregnancy. Patients with a history of ipsilateral salpingectomy should be cautioned regarding the possibility of interstitial pregnancy. Laparoscopic cornuostomy appears to be an appropriate treatment for interstitial pregnancy in patients wishing to preserve fertility, and the use of concomitant prophylactic MTX may reduce the risk of persistent ectopic pregnancy, especially in patients with ruptured masses and high human chorionic gonadotropin levels.

Thyroid function among women with gestational trophoblastic diseases. A cross-sectional study.

Gestational trophoblastic diseases (GTDs) are treatable rare tumors with wide distribution. The estimated incidence of GTDs varies dramatically between different regions globally. In early pregnancy, there may be high human chorionic gonadotropin (HCG) concentrations, normal or slightly increased free T4 (fT4) and subnormal thyroid-stimulating hormone (TSH), causing hyperthyroidism ranging from subclinical to severe. Beta-HCG causes thyrotoxicosis through thyroid stimulation in patients with trophoblastic tumors. To assess thyroid function among patients diagnosed with complete or partial hydatidiform mole, within the GTD spectrum. Cross-sectional study based on patients' medical records at Van University Hospital, Van, Turkey. 50 patients monitored due to diagnoses of hydatidiform mole were included and were examined regarding thyroid function. Thyroid gland size and volume were measured using thyroid ultrasonography. Beta-HCG, TSH, fT4, free T3 (fT3), total T4 (TT4), total T3 (TT3), anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-TG) and thyroglobulin levels were measured. Among these patients, 15 (30%) were diagnosed with complete hydatidiform mole and 35 (70%) with partial hydatidiform mole, according to pathology results. Those with complete hydatidiform mole were older (P = 0.003), with higher number of pregnancies (P = 0.032), lower TSH level (P = 0.011) and higher fT4 and TT4 levels (P = 0.04; P = 0.028), compared with partial hydatidiform mole patients. In hydatidiform mole patients, thyroid disease severity increases with age, parity, beta-HCG level and mole size. However, prospective multicenter studies on this topic are needed, with larger numbers of patients and closer monitoring.

Low dose human chorionic gonadotropin administration at the time of gonadotropin releasing-hormone agonist trigger versus 35\u2009h later in women at high risk of developing ovarian hyperstimulation syndrome \u2013 a prospective randomized double-blind clinical trial

BackgroundOvarian hyperstimulation syndrome remains a serious complication during in vitro fertilization cycles if high dose human chorionic gonadotropin (hCG) is used to trigger ovulation in high responder patients. Though much of this risk is mitigated with trigger using gonadotropin releasing-hormone (GnRH) agonist alone, it may result in lower birth rates. GnRH-agonist trigger and adjuvant low dose hCG has been proposed to improve birth rates, but timing of this hCG support to corpus luteum function has never been fully described. In this randomized, prospective trial, we explore differences in live birth rates and incidence of ovarian hyperstimulation syndrome (OHSS) in high-responder patients undergoing in vitro fertilization (IVF) receiving low dose hCG at the time of GnRH-agonist (dual trigger) or hCG adjuvant at the time of oocyte retrieval. Does the timing of hCG support make a difference?ResultsThirty-four subjects high-responder patients were randomized to receive low-dose hCG at the time of GnRH-agonist trigger (Group 1) and 37 received low-dose hCG at the time of oocyte retrieval (Group 2). There were no differences in the baseline characteristics and outcome of ovarian stimulation between the two groups. There were no differences in the live birth rates between Group 1 and Group 2 by intention-to-treat (14/34, 41.2% versus 21/37, 56.8%, p = 0.19) or per-protocol (14/26, 53.8% versus 19/31, 61.3%, p = 0.57) analyses. There was a slightly higher incidence of OHSS in Group 2 compared to Group 1 although the difference was not statistically significant (3/31, 9.7% versus 1/26, 3.8%). All the cases of OHSS in Group 2 were moderate while the one case of OHSS in Group 1 was mild.ConclusionsFor high responder patients receiving GnRH-agonist trigger, low dose hCG supplementation allowed high pregnancy rates after fresh embryo transfer, regardless of whether it was given at the time of trigger or at oocyte retrieval. Dual trigger may be preferable to reduce the risk of OHSS.

Obstetric and perinatal outcomes of pregnancies according to initial maternal serum HCG concentrations after vitrified-warmed single blastocyst transfer.

Do pregnancy, obstetric and perinatal outcomes differ according to initial maternal serum human chorionic gonadotrophin (HCG) level measured on day 11 after single blastocyst transfer? Vitrified-warmed single blastocyst transfer cycles (n = 640) were collected between 1 January 2013 and 30 April 2017 with positive HCG values and retrospectively analysed by receiver operating characteristic curves to predict clinical pregnancy, ongoing pregnancy and delivery. Cycles were divided into a low HCG group (n = 155) and high HCG group (n = 485) based on cut-off value of live birth prediction. Cycles in the HCG group were subdivided into a low-high subgroup (n = 162), medium-high subgroup (n = 162) and high-high subgroup (n = 161) based on tertile points. Pregnancy rates and obstetric and perinatal outcomes were compared. The area under curves for clinical pregnancy, ongoing pregnancy and live birth prediction were 0.95, 0.81 and 0.79, respectively; corresponding cut-off values were 152.2 IU/l, 211.9 IU/l and 211.9 IU/l; HCG less than 211.9 IU/l indicated an extremely low clinical pregnancy rate (34.84%), a high early miscarriage rate (61.11%) and a low live birth rate (12.26%). Rates of gestational diabetes mellitus (GDM) (P = 0.007) and female neonates (P = 0.001) were significantly higher in the LHG group compared with the HHG group; no significant differences were observed in the low versus high HCG group overall. Lower initial maternal serum HCG levels indicated poorer clinical outcomes. Within the high HCG group, a lower initial maternal HCG level was found to be associated with GDM occurrence and proportion of female neonates.

Effect of different-sized gold nanoflowers on the detection performance of immunochromatographic assay for human chorionic gonadotropin detection

Traditional colloidal gold based immunochromatographic assays (ICAs) that use 20–40 nm gold nanospheres (AuNSs) as signal reporters have low sensitivity given the insufficient brightness of AuNSs. Gold nanoflowers (AuNFs) possess high optical brightness and strong target binding affinity because of their multibranched structures and large specific surface areas. Thus, ICAs with AuNF reporters have better sensitivity than ICAs with conventional AuNSs reporters. In addition, large AuNFs exhibit higher optical absorbance than small AuNFs. To elucidate the effect of AuNF size on the sensitivity of sandwich ICA, AuNFs with five different sizes of 33, 47, 79, 152, and 195 nm were synthesized and used as reporters in ICA strips for pregnancy diagnosis based on the detection of human chorionic gonadotropin (HCG). Medium-sized AuNFs with diameters of 47–79 nm showed the highest sensitivity of 9 mIU/mL. When used to test actual HCG-spiked urine samples, the 47 nm AuNF-based ICA showed two independent linear correlations in low (9 mIU/mL ~ 288 mIU/mL) and high (288 mIU/mL ~ 2304 mIU/mL) HCG concentrations for HCG quantitative detection. The intra- and interassay recovery rates for HCG spiked urine samples ranged from 81.19% to 114.44% with the coefficient of variation (CV) from 3.29% to 8.08%. These results collectively indicate that the AuNF-based ICA has high accuracy. In addition, the proposed AuNF-based ICA method exhibited excellent selectivity for HCG determination. In summary, medium-sized AuNFs can serve as optimal ICA labels in the high-sensitivity detection of disease-related protein biomarkers.

Maternal concentrations of human chorionic gonadotrophin in very early IVF pregnancies and duration of pregnancy: a follow-up study.

Are maternal concentrations of human chorionic gonadotropin (HCG) on a fixed day after embryo transfer associated with duration of pregnancy? A follow-up study of 1917 singleton pregnancies after IVF was performed. Embryos were cultured for 2 days and maternal HCG concentration quantified on day 12 after embryo transfer. Duration of pregnancy was obtained from the Medical Birth Registry of Norway. Association of HCG concentration (log2-transformed) with duration of pregnancy was estimated as hazard ratios (HR) with 95% confidence intervals (CI) by applying Cox regression proportional hazard models, where time to delivery for pregnancies shortened because of planned Caesarean delivery or induction of labour was treated as censored. The estimated median duration of pregnancy from embryo transfer was 266 days (95% CI 266-267 days). Maternal concentration of HCG on day 12 after embryo transfer varied from 1 to 588 IU/l (median 117 IU/l). Duration of pregnancy decreased by increasing HCG concentration, significantly in pregnancies delivered at full term ((257-270 days after embryo transfer; HR 1.127, 95% CI 1.026-1.238, P = 0.012). For each doubling of HCG concentration on day 12 after embryo transfer, duration of pregnancy was shortened by 0.51 days. Adjustment for maternal age, prepregnancy body mass index, being a first-time mother and number of embryos transferred did not change the association. High maternal HCG concentration on a fixed day after embryo transfer is likely to indicate early embryo implantation. After embryo transfer, pregnancies with early implantation are shorter than pregnancies with late implantation.

195: Are women with abnormal 1st and 2nd trimester serum screening markers at risk for recurrence for the same or other abnormal markers in a subsequent pregnancy?

Abnormal 1st and 2nd trimester (1T, 2T) serum markers used for aneuploidy screening are associated with other adverse pregnancy outcomes. Limited data exist on recurrence risks for elevated 2T alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG), but no such data exist for low 1T pregnancy associated plasma protein A (PAPP-A) and HCG or high 2T inhibin and low estriol. Whether women with one abnormal biomarker are at risk for a different abnormal biomarker in a subsequent pregnancy is unknown. We sought to determine the relative risks (RR) of recurrence in the next pregnancy of low PAPP-A (<0.5 MoM) and HCG (<0.5 MoM) in the 1T, and high AFP (>2.5 MoM), HCG (>3.0 MoM), inhibin (>2.0 MoM) and low estriol (<0.5 MoM) in the 2T. Using a database of 14,349 serum markers, we identified 1969 patients with 2 consecutive pregnancies screened during the 1T and 2T for AFP, PAPP-A, HCG, inhibin, and estriol, between 1/2007-12/2016. We compared women with a normal vs abnormal serum marker in the initial pregnancy to determine the rates and RR of an abnormal value for that same marker or a different abnormal marker in the subsequent pregnancy. Chi squared or Fisher's exact tests were used as appropriate. For each serum marker analyzed, we found a statistically significant increased risk for having an abnormal level in the 2nd pregnancy after having an abnormal level in the 1st. Incidence of an abnormal marker in the 1st pregnancy and RR of recurrence are shown in Table 1. There was no association between abnormal PAPP-A in the 1st pregnancy and elevated AFP or HCG in the 2nd pregnancy. Similarly, there was no association between high AFP and abnormal PAPP-A or HCG in the 2nd pregnancy. Abnormal PAPP-A, HCG, AFP, inhibin, and estriol are associated with increased risk of adverse outcomes such as preeclampsia and IUGR. Our results show that patients with an abnormal marker in their 1st pregnancy are at an increased risk for the same abnormal marker in the next pregnancy. Our findings suggest that biomarkers may be indicative of underlying maternal pathophysiology potentially driven by genetic or environmental factors. Additional studies are needed to further investigate the maternal pathophysiologic mechanisms leading to these adverse outcomes which may identify opportunities for therapeutic intervention.