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1kits（10Vials）
▎HCG Research
What is the research background of HCG?
Human Chorionic Gonadotropin (HCG) is a molecule with multiple important functions and plays a crucial role in aspects such as pregnancy and human cancer. Firstly, HCG is an extreme molecule. It is the most acidic glycoprotein and contains the highest proportion of sugar. Secondly, HCG exists in various forms, including regular HCG, sulfated HCG, hyperglycosylated HCG, free β-HCG, and hyperglycosylated free β-HCG, etc. [1].
In terms of pregnancy, HCG is essential for the human menstrual cycle and human pregnancy. Regular HCG plays a role in promoting the production of corpus luteum progesterone and also has important functions in trophoblast cell differentiation and fetal nutrition. For example, it realizes the supply of fetal nutrition through angiogenesis in the spiral arteries of the myometrium [1]. Hyperglycosylated HCG also plays an important role in the early stages of pregnancy. It is the main HCG isoform in the early stages of pregnancy, which can inhibit apoptosis, promote cell invasion, growth, and malignant transformation, and control implantation and placental growth [1].
In terms of cancer, non-trophoblastic malignant tumors produce the hyperglycosylated free β subunit of HCG, which, as an autocrine factor, further promotes the growth and malignant transformation of cancer cells by antagonizing apoptosis[1].
In addition, the detection of HCG is also widely used in clinical applications, including pregnancy testing, monitoring pregnancy outcomes, determining the risk of fetuses with Down syndrome, predicting preeclampsia, detecting pituitary HCG, detecting and managing gestational trophoblastic diseases, diagnosing quiescent gestational trophoblastic diseases, diagnosing placental site trophoblastic tumors, managing testicular germ cell malignancies, and monitoring other human malignancies, etc. [1].
What is the mechanism of action of HCG?
1. Influence on the receptivity of the endometrium
Some studies have shown that HCG may affect the receptivity of the endometrium through the miR-126-3p/PIK3R2/PI3K/Akt/eNOS axis and play a key role in the process of embryo implantation (Wang W, 2023). The specific manifestations are as follows:
Improving the function of endometrial receptors: By establishing a mouse model of embryo implantation dysfunction (EID) and treating it with mifepristone, and simultaneously conducting experiments on human endometrial epithelial cells (EECs), it was found that after HCG treatment, the receptivity of the endometrium in EID mice was improved. For example, the expression level of CD105 in the mice and the protein levels of cadherins CD144 and CD146 were increased as determined by immunohistochemistry and Western blotting.
Regulating gene expression: HCG can promote the expression of miR-126-3p and inhibit the expression of PIK3R2, and miR-126-3p targets PIK3R2. Both in vivo and in vitro experiments have verified that HCG activates the PI3K/Akt/eNOS pathway through the miR-126-3p/PIK3R2 axis, thereby improving the receptivity of the endometrium.
2. Role in maintaining pregnancy
HCG is mainly produced by differentiated syncytiotrophoblast cells and is a crucial embryonic signal essential for maintaining pregnancy[2].
Activating multiple signal cascade reactions: HCG can bind to the luteinizing hormone/chorionic gonadotropin receptor (LHCGR) and potentially activate multiple signal cascade reactions, including the mothers against decapentaplegic homolog 2 (Smad2) for mothers with multiple capabilities, protein kinase C (PKC), and/or protein kinase A (PKA), through direct/indirect interactions with the transforming growth factor β receptor (TGFβR).
Promoting angiogenesis in the uterine endothelium: HCG plays a special role in promoting angiogenesis in the uterine endothelium, providing a good growth environment for the embryo.Maintaining the quiescence of the myometrium: It helps to maintain the stable state of the uterus and provides a suitable environment for the development of the embryo.Promoting immunomodulation at the maternal-fetal interface: It plays an important role in the immunomodulation at the maternal-fetal interface and balances the response of the maternal immune system to the embryo.
3. Role in frozen embryo transfer
Studies have found that transcutaneous electrical acupoint stimulation (TEAS) combined with HCG treatment can improve the pregnancy outcomes of patients undergoing frozen embryo transfer [3].
Increasing the thickness of the endometrium: TEAS treatment mainly helps to increase the thickness of the endometrium in patients undergoing frozen embryo transfer. The combined treatment of HCG and TEAS also helps to increase the thickness of the endometrium in these patients.
Reducing the blood flow index of the uterine artery: The values of the endometrial blood flow PI and RI in the TEAS combined with HCG group and the TEAS group were significantly lower than those in the control group, indicating that the combined treatment of HCG and TEAS can reduce the blood flow index PI and RI of the uterine artery in patients.
Increasing the levels of factors related to pregnancy maintenance in the serum: HCG treatment mainly helps to increase the levels of serum P and leukemia inhibitory factor (LIF) in patients undergoing frozen embryo transfer. The serum LIF levels in the TEAS group, the HCG group, and the TEAS combined with HCG group were all significantly higher than those in the control group. The embryo implantation rate in the combined group was significantly higher than that in the control group, suggesting that the combined treatment of TEAS and HCG can improve the pregnancy outcomes of patients undergoing frozen embryo transfer.
4. Treatment of male hypogonadism
Hypogonadism caused by insufficient secretion of gonadotropin in men has a significant impact on the reproductive health and quality of life of patients. Human Chorionic Gonadotropin (HCG) plays an important role in the treatment of such diseases. HCG binds to the receptors on the surface of Leydig cells in the testis, activates the intracellular signaling pathway, and promotes the conversion of cholesterol into testosterone. The increase in testosterone can promote the growth and development of the testis and increase the volume of the testis. At the same time, testosterone can also stimulate the development of reproductive organs such as the epididymis and vas deferens. Testosterone plays a key role in the development of male secondary sexual characteristics. By increasing the level of testosterone, HCG treatment can promote the growth of beards and Adam's apples, enhance muscle strength, and increase sexual desire, etc
Cellular sources, targets, associated signaling cascades, and functions of various HCG isoforms in non-pregnant and pregnant women.
Source:PubMed[2]
What are the main applications of HCG?
1. Used for the diagnosis of early pregnancy
The value of measuring the contents of serum T-HCG and β-HCG in early pregnancy: Collect cases of early abnormal pregnancy, measure serum T-HCG using chemiluminescence, measure serum β-HCG using radioimmunoassay, and conduct dynamic observations. The results show that the contents of serum T-HCG and β-HCG in the ectopic pregnancy group are significantly lower than those in the abortion group and the intrauterine pregnancy group. This indicates that the measurement of the contents of serum T-HCG and β-HCG has good specificity and diagnostic rate for differentiating ectopic pregnancy and intrauterine pregnancy, and T-HCG has higher sensitivity and reliability [4].
Diagnosis of ectopic pregnancy by the combined detection of serum HCG, β-HCG, and progesterone: Detect serum HCG, β-HCG, and progesterone in normal pregnant women and pregnant women with ectopic pregnancy. The results show that the levels of serum HCG, β-HCG, and progesterone in normal pregnant women are better than those in pregnant women with ectopic pregnancy. When detected alone, the accuracy rate of serum HCG in the diagnosis of ectopic pregnancy is 70.83%; the accuracy rate of β-HCG is 66.7%; the accuracy rate of progesterone is 54.17%. The combined detection of serum HCG, β-HCG, and progesterone has an accuracy rate of up to 95.8% in the diagnosis of ectopic pregnancy[5].
2. Application in assisted reproductive technology
Optimizing follicular maturation: In ovarian stimulation, human menopausal gonadotropin (hMG) can optimize follicular maturation after pituitary desensitization induced by gonadotropin-releasing hormone analogues (Gn-RH-analogue). This is mainly because it avoids the irregular endogenous luteinizing hormone (LG) response that occurs during hMG treatment in approximately one-third of the treatment cycles. In several studies using buserelin or degarelix as Gn-RH analogues, 282 patients received in vitro fertilization, gamete intrafallopian transfer, or as part of an "in vivo" treatment. The combined treatment of GnRH analogue/hMG/HCG significantly increased the pregnancy rate in all groups. The pregnancy rate of patients treated with HMG/HCG was 17%, while the combined treatment made 25% of the patients pregnant [6].
Improving the receptivity of the endometrium: Human Chorionic Gonadotropin (HCG) is one of the important signals before embryo implantation. Research using endometrial tissue analysis found that after intrauterine administration of HCG, the number of cells expressing the endothelial cell adhesion molecules VE-cadherin (CD144) and S-Endo-1 (CD146) increased significantly, suggesting that endothelial cell adhesion molecules may be a potential mechanism by which HCG improves embryo implantation and the pregnancy rate[7].
2. Treatment of luteal insufficiency
For the past two decades, exogenous progesterone administration has been used as luteal phase support (LPS) in combination with controlled ovarian stimulation using human Chorionic Gonadotropin (HCG) to trigger the final maturation of follicles. The introduction of GnRHa to trigger ovulation indicates that exogenous progesterone administration is insufficient to achieve a satisfactory pregnancy rate without HCG supplementation.
This has prompted the development of alternative strategies for luteal phase support. Increasing the local endogenous progesterone production of multiple corpora lutea is a key point, on the one hand, to avoid the development of ovarian hyperstimulation syndrome, and on the other hand, to provide an adequate level of progesterone to maintain implantation.
Current research has evaluated the role of micro-dose HCG for luteal phase support and studied its potential advantages and disadvantages. Based on the pharmacokinetic characteristics of HCG, a mathematical model of the concentration distribution of HCG during the luteal phase was evaluated by combining several different HCG administration methods as luteal phase support. It is suggested that the current luteal phase support provided together with GnRHa triggering (i.e., 1500IU) is too strong, and daily micro-dose HCG administration may provide optimized luteal phase support for currently available drugs. The preliminary clinical results of the micro-dose HCG method are also given[8].
3. Treatment of unilateral intra-abdominal undescended testis
A study was conducted on patients who underwent orchidopexy for unilateral intra-abdominal undescended testis from September 2010 to September 2016. Two weeks after the operation, the parents of the patients who received hormone treatment needed to follow a 6-week regimen. The patients received a subcutaneous injection of 500 UI (Gonasi-HP) per week. Follow-up was conducted at the end of the treatment and 6 months later.
The volume of the testis was measured by ultrasound and ultrasonic elastography at each follow-up and compared with that of patients who did not receive treatment. The results showed that 45 patients received treatment, with an average age of 18.0±9.7 months. 32 patients received postoperative hormone treatment, and there were no adverse reactions or cases of withdrawal.
All patients completed the follow-up. There were no cases of testicular atrophy in both groups. In the treatment group, 81% of the patients reached the normal testis size at 6 months, while the testis volume of other patients was still small. In the untreated group, 46% of the patients reached the normal testis size. The postoperative use of human Chorionic Gonadotropin (u-HCG) may improve the volume and function of the testis by stimulating the growth and development of the testis[9].
4. Application in the research of β-HCG vaccine
Conduct an HCG stimulation test on women who were immunized with the NII beta-HCG vaccine but had no anti-HCG antibody titers, and use the stimulation of serum progesterone secretion as an indicator of the corpus luteum's response to intravenous HCG. The results showed that in the control group, most women had a significantly higher progesterone secretion level after HCG stimulation than the basal level, while the peak progesterone level in women in the immunized group did not exceed the basal level after vaccination, indicating that the antibodies produced by the vaccine can intercept the effect of exogenous HCG [10].
In conclusion, HCG plays an irreplaceable role in the medical field, especially in aspects related to reproduction. In reproductive treatment, it can effectively induce ovulation, bringing hope to patients with infertility caused by ovulation disorders. By binding to the LH receptors in the body, it can make up for the insufficient LH level in the antagonist protocol and help with follicular maturation. For luteal insufficiency, HCG can stimulate the corpus luteum to secrete progesterone and maintain an appropriate hormonal environment to support pregnancy.
For male hypogonadism caused by insufficient secretion of gonadotropin, HCG can stimulate Leydig cells in the testis to synthesize and secrete testosterone, promote testicular development, improve secondary sexual characteristics, and enhance the reproductive function and quality of life of patients. At the same time, HCG plays a key role in maintaining early pregnancy, stimulating the corpus luteum to continuously secrete progesterone to ensure embryo implantation and development. In clinical diagnosis, detecting the level of HCG is an important basis for determining early pregnancy and identifying abnormal pregnancies such as ectopic pregnancy, providing strong support for timely intervention and treatment.
About The Author
The above-mentioned materials are all researched, edited and compiled by Cocer Peptides.
Scientific Journal Author
Chinedu Nwabuobi is a researcher with expertise in the fields of Obstetrics & Gynecology, Reproductive Biology, Biochemistry & Molecular Biology, Chemistry, and Oncology. He has been affiliated with several prestigious institutions, including the University of South Florida, the University of Rochester, and Memorial Sloan Kettering Cancer Center. His research focuses on topics such as the biological functions and clinical applications of human chorionic gonadotropin (HCG), with contributions to understanding its role in reproductive health and related pathologies. Chinedu Nwabuobi is listed in the reference of citation [2].
