Human chorionic gonadotropin (hCG), a glycoprotein produced in the placenta, is crucial for a healthy pregnancy. We investigated the relationship between hCG levels and adverse pregnancy outcomes. We conducted a systematic review including studies measuring hCG blood levels in the first or second trimester, reporting on any of the 12 predefined adverse pregnancy outcomes with logistic regression-adjusted association estimates. The primary outcomes were placenta-associated complications, such as miscarriage, preeclampsia, intrauterine growth restriction, and preterm delivery. We searched PubMed, Embase and CINAHL Complete. The hCG levels were analysed as multiple of the median (MoM). Odds ratio (OR) and 95% confidence interval (CI) were used. Risk of bias and the certainty of evidence were assessed using ROBINS-I and GRADE, respectively. Meta-analysis also showed that hCG levels, reported as MoM ≥2/2.31/2.5, might be associated with an increased risk of preeclampsia (OR 2.08, 95% CI 1.26 to 3.44) and preterm delivery (OR 1.29, 95% CI 1.12 to 1.47), but the evidence is very uncertain. High second trimester hCG levels may be associated with preeclampsia and preterm delivery but confidence in evidence is low.

Background and Objectives: Gestational trophoblastic disease (GTD) is a group of pregnancy-related malignant and premalignant diseases. The aim of this study was to assess the prognostic value of clinical characteristics to predict treatment outcomes in women with GTD. Materials and Methods: In this retrospective study, 34 patients treated for GTD at the Division of Gynaecology and Perinatology, University Medical Centre Maribor, between 2008 and 2022 were identified. Clinical and pathological characteristics were obtained by analysing patient data records. Results: Within the cohort of 34 patients with GTD, 29 patients (85.3%) had a partial hydatidiform mole (HM) and five patients545 (14.7%) had a complete HM. Two patients with a complete HM developed a postmolar gestational trophoblastic neoplasia (GTN), which represents 5.8% of all cases. Conclusions: GTD is a rare disease that is frequently asymptomatic. The subsequent consequences of GTD, which can lead to malignant transformation, as well life-threatening disease complications, warrant training for early recognition of HMs and timely treatment and surveillance.

OBJECTIVE: To conduct a systematic review andmeta-analysis of all randomized controlled trials (RCTs) that investigated whether dual triggering [a combination of gonadotropin-releasing hormone (GnRH) agonist and human chorionic gonadotropin (hCG)] of final oocyte maturation can improve the number of oocytes retrieved and clinical pregnancy rate in low or normal responders undergoing in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles using a GnRH-antagonist protocol.
METHODS: Studies up to October 2022 were identified from PubMed, Scopus, Cochrane Library and Web of Science. The risk of bias of included studies was assessed. Dichotomous outcomes were reported as relative risks (RR), and continuous outcomes were reported as weighted mean differences (WMD) with 95% confidence intervals (CI). The primary outcomes were number of oocytes retrieved, number of mature [metaphase II (MII)] oocytes, clinical pregnancy rate and ongoing pregnancy rate; other IVF outcomes were considered as secondary outcomes.
RESULTS: Seven studies were identified, and 898 patients were eligible for inclusion in this meta-analysis. The results showed that the number of oocytes retrieved [WMD = 1.38 (95% CI 0.47-2.28), I2 = 66%, p = 0.003, low evidence], number of MII oocytes [WMD = 0.7 (95% CI 0.35-1.05), I2 = 42%, p < 0.0001, moderate evidence], number of embryos [WMD = 0.68 (95% CI 0.07-1.3), I2 = 67%, p = 0.03, low evidence] and number of good-quality embryos [WMD = 1.14 (95% CI 0.35-1.93), I2 = 0%, p = 0.005, moderate evidence] in the dual trigger group were significantly higher than in the hCG trigger group. The results of the ovarian response subgroup analysis showed significant differences in all of these outcomes in normal responders, and no differences in any of the outcomes in low responders, except for the number of MII oocytes. In low responders, clinical pregnancy rates may be improved in the dual trigger group [RR = 2.2 (95% CI 1.05-4.61), I2 = 28%, p = 0.04, low evidence].
CONCLUSIONS: Dual triggering by GnRH agonist and hCG improved oocyte maturity and embryo grading for normal responders in GnRH-antagonist cycles. Dual triggering for final oocyte maturation may improve clinical pregnancy rates in low responders.

METHODS: The purpose of this study was to assess whether the implementation of a \"dual trigger\" approach, utilizing gonadotropin-releasing hormone agonist (GnRHa) and human chorionic gonadotropin (hCG) in the GnRH antagonist protocol for in vitro fertilization (IVF), leads to improved pregnancy outcomes compared to the conventional hCG trigger alone. Previous meta-analyses have not provided sufficient evidence to support the superiority of the dual trigger over the hCG trigger in fresh or frozen embryo transfer cycles. Thus, a systematic review and meta-analysis of randomized trials were conducted to provide a comprehensive evaluation of the impact of the dual trigger on pregnancy outcomes in fresh or frozen embryo transfer cycles.
METHODS: A systematic review and meta-analysis of randomised controlled trials (RCTs) were conducted. We searched the Medline and Embase databases for articles up to 2023 by using search terms: \"dual trigger,\" \"GnRHa,\" \"hCG,\" \"IVF.\" Eligible RCTs comparing the dual trigger with the hCG trigger were included. The primary outcome was the live birth rate (LBR) per cycle. The secondary outcomes were the number of oocytes retrieved, number of mature oocytes retrieved, implantation rate, biochemical pregnancy rate, CPR, miscarriage rate and ovarian hyperstimulation syndrome (OHSS) rate per started cycle We compared the oocyte maturation and pregnancy outcomes in the dual trigger and hCG trigger groups. In patients undergoing fresh embryo transfer (ET) and frozen-thawed ET, we also conducted a subgroup analysis to evaluate whether dual trigger improves the clinical pregnancy rate (CPR).
RESULTS: We included 10 randomised studies, with 825 participants in the dual trigger group and 813 in the hCG trigger group. Compared with the hCG trigger, dual trigger was associated with a significant increase in the LBR per cycle (odds ratio (OR) = 1.61[1.16, 2.25]), number of oocytes retrieved (mean difference [MD] = 1.05 [0.43, 1.68]), number of mature oocytes retrieved (MD = 0.82 [0. 84, 1.16]), and CPR (OR = 1.48 [1.08, 2.01]). Subgroup analyses revealed that dual trigger was associated with a significantly increased CPR in patients who received fresh ET (OR = 1.68 [1.14, 2.48]). By contrast, the dual trigger was not associated with an increased CPR in the patient group with frozen-thawed ET (OR = 1.15 [0.64, 2.08]).
CONCLUSIONS: The dual trigger was associated with a significantly higher number of retrieved oocytes, number of mature oocytes, CPR, and LBR in IVF than the hCG trigger. The beneficial effect for fresh ET cycles compared with frozen-thawed ET might be associated with increased endometrial receptivity.
CONCLUSIONS: After dual trigger, delaying ET due to the concern of endometrial receptivity might not be needed.

BACKGROUND: Nausea and vomiting in pregnancy (NVP) affects 50-80% of pregnant women and is correlated to the level of human chorionic gonadotropin (hCG). Hyperemesis gravidarum (HG) is a severe condition, with an incidence of 0.2-1.5%, characterized by consistent nausea, vomiting, weight loss and dehydration continuing after the second trimester.
OBJECTIVE: The aim of this systematic review was to investigate a potential correlation between NVP or HG with adverse pregnancy outcomes and hCG levels.
METHODS: A systematic search in PubMed, Embase and CINAHL Complete was conducted. Studies on pregnant women with nausea in the first or second trimester, reporting either pregnancy outcomes or levels of hCG were included. The primary outcomes were preterm delivery (PTD), preeclampsia, miscarriage, and fetal growth restriction. Risk of bias was assessed using ROBINS-I. The overall certainty of evidence was assessed using GRADE.
RESULTS: The search resulted in 2023 potentially relevant studies; 23 were included. The evidence was uncertain for all outcomes, however women with HG had a tendency to have an increased risk for preeclampsia [odds ratio (OR) 1.18, 95% confidence of interval (CI) 1.03 to 1.35], PTD [OR 1.35, 95% CI 1.13 to 1.61], small for gestational age (SGA) [OR 1.24, 95% CI 1.13 to 1.35], and low birth weight (LBW) [OR 1.35, 95% CI 1.26 to 1.44]. Further, a higher fetal female/male ratio was observed [OR 1.36, 95% CI 1.15 to 1.60]. Meta-analyses were not performed for women with NVP; however, most of these studies indicated that women with NVP have a lower risk for PTD and LBW and a higher risk for SGA, and a higher fetal female/male ratio.
CONCLUSIONS: There may be an increased risk in women with HG and a decreased risk in women with NVP for adverse placenta-associated pregnancy outcomes, however the evidence is very uncertain.
BACKGROUND: PROSPERO: CRD42021281218.

Emerging evidence suggests an association of hyperemesis gravidarum (HG) with transient hyperthyroidism and high HCG levels. For synthesizing the current evidence to determine the association between HG with hormones related to thyroid function, a comprehensive systematic search was performed in the electronic databases comprised Medline, Web of Science, Scopus, Embase, ProQuest, and Cochrane Library up to December 2021. All published observational studies that evaluated the association of hyperemesis gravidarum with transient hyperthyroidism were investigated considering the PICO method. The standardized Joanna Briggs Institute Meta-Analysis of Statistics, Assessment, and Review Instrument were applied to appraise the included studies. Twenty-nine studies consisted of 6525 women included in the systematic review. Among them, 28 studies with 2446 participants were included in the meta-analysis. There were significant associations of HG with fT3 (MD: 1.31 pg/mL, 95% CI: 0.61 to 2.01), fT4 (MD: 1.95 ng/dL, 95% CI: 1.17 to 2.73), TSH (MD: -1.22μIU/mL, 95% CI: -1.75 to -0.68), TT4 (MD: 0.56 nmol/L, 95% CI:-0.43 to 1.24), and HCG (MD: 1.90IU/L, 95% CI: 0.497 to 3.301). In conclusion, the serum levels of fT3, fT4, and TT4 increased but TSH decreased significantly in women with compared without HG, indicating the significant association of HG with GTT.

Various interventions have been proposed to improve embryo implantation in IVF. Among these, intrauterine injections of human chorionic gonadotropin seem to have promising results. Consequently, we conducted a review and meta-analysis to assess IVF outcomes by comparing couples who underwent intrauterine hCG injection transfer versus those who underwent embryo transfer with intrauterine injection of placebo, or without any additional intervention. The primary outcome was the clinical pregnancy rate. Secondary outcomes were the implantation rate, miscarriage rate, and live birth rate. A meta-analysis was conducted using the random effects model, while bias within studies was detected using the Cochrane risk of bias tool. Ectopic pregnancies and stillbirths were also assessed. The clinical pregnancy (RR 1.38, 95% CI 1.17−1.62, p < 0.0001) and implantation rate (RR 1.40, 95% CI 1.12−1.75, p = 0.003) were significantly higher in women who underwent hCG injection than in the control group. These significant effects persisted only in women who underwent cleavage-stage embryo transfer. No significant differences between groups were observed in the other secondary outcomes. In conclusion, our systematic review and meta-analysis demonstrate that intrauterine injection of hCG could be a valuable approach in women who undergo cleavage-stage embryo transfer. Given the lack of data about the live birth rate, caution should be exercised in interpreting these data.

Circulating progesterone concentrations during the growth of the ovulatory follicle and early embryo development have been positively associated with embryo quality and survival and pregnancy success. As a potent luteotropic agent with LH-like activity, human chorionic gonadotropin (hCG) has been tested in different studies to improve pregnancy outcomes by increasing circulating progesterone concentrations during the growth of the ovulatory follicle or early embryonic development. Nevertheless, hCG has produced inconsistent, contradictory, and intriguing results. Furthermore, recent research indicates that hCG, when used before artificial insemination, may affect physiological events necessary for the ovulation of a viable oocyte. In addition, the use of hCG-inducing accessory corpus luteum during the estrous cycle seems to disturb luteolysis and follicle and luteal dynamics during the estrous cycle. This literature review discusses past and current research exploring the effects of hCG on the estrous cycle characteristics and pregnancy per artificial insemination and embryo transfer.

The objective of this study is to investigate whether kisspeptin levels in early pregnancy have a better diagnostic value on early pregnancy outcome as compared with human chorionic gonadotropin (hCG). This study was a systematic review and meta-analysis aiming to investigate the diagnostic value of kisspeptin levels on early pregnancy outcome. The primary outcome was miscarriage or viable intrauterine pregnancy. Five studies were included for systematic review, and three studies were included for meta-analysis. Meta-analysis showed kisspeptin levels had a good diagnostic value with the area under the curve (AUC) 0.902 (0.866, 0.937) when kisspeptin was measured after 6 weeks of gestation. Sensitivity analysis demonstrated kisspeptin levels had a diagnostic value with AUC = 0.881 (0.855, 0.906). hCG levels had a diagnostic value with AUC = 0.834 (0.785, 0.883), which was inferior to the diagnostic value of kisspeptin (mean difference = 0.09 (0.02, 0.16)). Kisspeptin measurement has a potential for comparable or even higher accuracy than hCG in differentiating between miscarriage and viable intrauterine pregnancy after 6 weeks of gestation.

Human chorionic gonadotropin (hCG) has four major isoforms: classical hCG, hyperglycosylated hCG, free β subunit, and sulphated hCG. Classical hCG is the first molecule synthesized by the embryo. Its RNA is transcribed as early as the eight-cell stage and the blastocyst produces the protein before its implantation. This review synthetizes everything currently known on this multi-effect hormone: hCG levels, angiogenetic activity, immunological actions, and effects on miscarriages and thyroid function.