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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, playing a key 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 crucial 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 enables fetal nutrition supply through the angiogenesis of spiral arteries in the myometrium (Cole L A, 2012). 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. As an autocrine factor, it 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. Effects on Endometrial Receptivity
Some studies have shown that HCG may affect endometrial receptivity through the miR-126-3p/PIK3R2/PI3K/Akt/eNOS axis and play a key role in the process of embryo implantation[2]. 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 conducting experiments on human endometrial epithelial cells (EECs), it was found that after HCG treatment, the endometrial receptivity of EID mice was improved. For example, the expression level of CD105 in 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 endometrial receptivity.
2. Role in Maintaining Pregnancy
HCG is mainly produced by differentiated syncytiotrophoblast cells and is a key embryonic signal essential for maintaining pregnancy [3].
Activating Multiple Signal Cascade Reactions: HCG can bind to the luteinizing hormone/chorionic gonadotropin receptor (LHCGR), potentially activating multiple signal cascade reactions, including the mothers' decapentaplegic homolog 2 (Smad2), protein kinase C (PKC), and/or protein kinase A (PKA) for mothers with multiple capabilities, through direct/indirect interactions with the transforming growth factor β receptor (TGFβR).
Promoting Uterine Endothelial Angiogenesis: HCG plays a special role in promoting uterine endothelial angiogenesis, providing a good growth environment for the embryo.
Maintaining Myometrial Quiescence: It helps 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, balancing the maternal immune system's response 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[4].
Increasing Endometrial Thickness: TEAS treatment mainly helps increase the endometrial thickness of patients undergoing frozen embryo transfer. The combined treatment of HCG and TEAS also helps increase the endometrial thickness of these patients.
Reducing the Uterine Artery Blood Flow Index: 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 uterine artery blood flow index PI and RI of patients.
Increasing the Levels of Factors Related to Pregnancy Maintenance in Serum: HCG treatment mainly helps increase the serum levels of P and 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 gonadotropin secretion in men has a significant impact on the patient's reproductive health and quality of life. 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, activating the intracellular signaling pathway and promoting 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[3]
What are the main applications of HCG?
1. Used for Early Pregnancy Diagnosis
The Value of Measuring Serum T-HCG and β-HCG Levels in Early Pregnancy: By collecting cases of early abnormal pregnancy, measuring serum T-HCG using chemiluminescence and measuring serum β-HCG using radioimmunoassay and conducting dynamic observations, the results showed that the serum T-HCG and β-HCG levels in the ectopic pregnancy group were significantly lower than those in the abortion group and the intrauterine pregnancy group. This indicates that the measurement of serum T-HCG and β-HCG levels has good specificity and diagnostic accuracy for differentiating ectopic pregnancy from intrauterine pregnancy, and T-HCG has higher sensitivity and reliability [5].
Combined Detection of Serum HCG, β-HCG, and Progesterone for the Diagnosis of Ectopic Pregnancy: By detecting serum HCG, β-HCG, and progesterone in normal pregnant women and pregnant women with ectopic pregnancy, the results showed that the levels of serum HCG, β-HCG, and progesterone in normal pregnant women were better than those in pregnant women with ectopic pregnancy. When detected alone, the accuracy rate of serum HCG in the diagnosis of ectopic pregnancy was 70.83%; the accuracy rate of β-HCG was 66.7%; and the accuracy rate of progesterone was 54.17%. However, the combined detection of serum HCG, β-HCG, and progesterone had an accuracy rate of up to 95.8% in the diagnosis of ectopic pregnancy[6].
2. Applications in Assisted Reproductive Technology
Optimizing Follicular Maturity: In ovarian stimulation, human menopausal gonadotropin (hMG) can optimize follicular maturity 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 about 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 "in vivo" treatment. The combined GnRH analogue/hMG/HCG treatment 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[7].
Improving Endometrial Receptivity: Human Chorionic Gonadotropin (HCG) is one of the important signals before embryo implantation. Through the analysis of endometrial tissues in research, it was found that after the intrauterine administration of HCG, the number of cells expressing the endothelial cell adhesion molecules VE-cadherin (CD144) and S-Endo-1 (CD146) increased significantly. This suggests that endothelial cell adhesion molecules may be a potential mechanism by which HCG improves the embryo implantation and pregnancy rates[8].
2. Treatment of Luteal Insufficiency
For the past two decades, exogenous progesterone administration has been used as luteal phase support (LPS), combined with the use of human chorionic gonadotropin (HCG) to trigger the final maturation of follicles in controlled ovarian stimulation. The introduction of GnRHa to trigger ovulation indicates that without HCG supplementation, exogenous progesterone administration is insufficient to achieve a satisfactory pregnancy rate. 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, combined with several different HCG administration methods as luteal phase support, a mathematical model of the HCG concentration distribution during the luteal phase was evaluated. 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. And the preliminary clinical results of the micro-dose HCG method were given[9].
3. Treatment of Unilateral Intra-abdominal Undescended Testis
A study was conducted on patients who underwent orchiopexy 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 protocol. The patients received a subcutaneous injection of 500 UI (Gonasi-HP) every week. Follow-ups were conducted at the end of the treatment and 6 months later. The testis volume was measured by ultrasound and elastography each time and compared with that of patients who did not receive treatment. The results showed that 45 patients received the treatment, with an average age of 18.0±9.7 months. 32 patients received postoperative hormone treatment, and there were no adverse reactions or dropouts. All patients completed the follow-up. There were no cases of testicular atrophy in either group. In the treatment group, 81% of the patients reached the normal testis size at 6 months, while the testis volume of the 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 increase the testis volume and function by stimulating the growth and development of the testis [10].
4. Applications in the Research of β-HCG Vaccine: An HCG stimulation test was conducted on women who were immunized with the NII beta-HCG vaccine but had no anti-HCG antibody titers, with 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 significantly higher progesterone secretion levels after HCG stimulation than the baseline level, while the peak progesterone levels in women in the immunized group did not exceed the baseline level after vaccination, indicating that the antibodies produced by the vaccine can intercept the effect of exogenous HCG[11].
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 maturity. 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 gonadotropin secretion, HCG can stimulate the Leydig cells in the testis to synthesize and secrete testosterone, promoting the development of the testis, improving secondary sexual characteristics, and enhancing the patient's reproductive function and quality of life. 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 HCG level 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 [3].
