Clinical UM Guideline

This document addresses laboratory testing of human chorionic gonadotropin (hCG) in urine or blood.

Medically Necessary:

Urine hCG testing is considered medically necessary for confirming the presence or absence of pregnancy.

Blood hCG testing is considered medically necessary for any of the following indications:

1. Confirming presence or absence of pregnancy; or
2. Screening pregnant individuals for fetal abnormalities; or
3. Hypertensive disorders of pregnancy; or
4. Gestational trophoblastic neoplasia or molar pregnancy; or
5. Evaluation of germ cell tumors; or
6. Testicular cancer or suspicious testicular mass; or
7. Ovarian cancer; or
8. Pelvic mass; or
9. Mediastinal mass; or
10. Retroperitoneal mass; or
11. Thymomas or thymic cancer; or
12. Cancer of unknown primary

Not Medically Necessary:

Urine or blood hCG testing is considered not medically necessary when the above criteria are not met.

The following codes for treatments and procedures applicable to this guideline are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services are Medically Necessary:

When services are Not Medically Necessary:
For the procedure code listed above for all other diagnoses not listed.

Human chorionic gonadotropin (hCG) is a hormone made by the placenta during pregnancy. It signals the body to stop menstruation and promotes thickening of the uterine lining to support a growing embryo. During pregnancy, hCG can be found in the amniotic fluid and in the pregnant person’s blood and urine. Part of the hCG molecule, the beta subunit (β-hCG), is degraded in the kidney to make a core fragment that can be measured by urine hCG tests such as a typical at-home pregnancy test.

Measuring hCG levels in blood or urine is done to identify a pregnancy and can also be useful to confirm pregnancy loss. hCG is first found in urine or blood around 11 days after conception. hCG levels are the highest toward the end of the first trimester (10 weeks of pregnancy), then decline for the rest of the pregnancy. hCG disappears after birth and is not normally detectable in a healthy non-pregnant person.

hCG testing may also be performed during pregnancy to detect fetal abnormalities. A 2020 committee opinion by the American College of Obstetricians and Gynecologists recommended testing pregnant persons in the first trimester of pregnancy (10 to 14 weeks of gestation) for hCG along with pregnancy associated plasma protein A, and alpha-fetoprotein (AFP). A risk estimate for common fetal chromosomal abnormalities (generally trisomies 13, 18, and 21) can be calculated using these test results along with other information known about the pregnant person such as age, history of aneuploidy, weight, race, and number of fetuses. hCG measurements may also be performed during the second trimester as part of a combined screening for chromosome abnormalities and neural tube defects. This screening includes testing parental serum levels of hCG, AFP, unconjugated estriol and/or inhibin-A.

Hypertensive disorders of pregnancy can lead to adverse outcomes for both the pregnant individual and the fetus. hCG levels, especially during the second trimester, are valuable clinical predictors of preeclampsia (Zhang, 2021). High hCG levels are associated with a high incidence of pregnancy complications including preeclampsia, placental abruption and prenatal death (Huang, 2022).

In addition to pregnancy, hCG may be produced in some disease conditions. Gestational trophoblastic disease (GTD) is a condition in which a tumor develops from abnormal tissue that forms after conception. The most common type of GTD is hydatidiform mole (HM), also called a molar pregnancy. HM is a benign premalignant disease. Malignant forms of GTD, known as gestational trophoblastic neoplasia, include invasive mole, choriocarcinoma, placental site trophoblastic tumor, and epithelioid trophoblastic tumor. hCG is a sensitive marker to indicate the presence or absence of these diseases before, during, and after treatment.

Elevated levels of hCG when a person is not pregnant may indicate the presence of extra-uterine cancers such as germ cell tumors. Germ cells normally form sperm or eggs. A germ cell tumor (GCT) arises from these reproductive cells. These occur most commonly in the testes or ovaries. GCTs account for approximately 95% of testicular cancers but they occasionally originate in extragonadal sites such as the mediastinum or retroperitoneum. GCTs can be benign or malignant. When GCTs involve the testes, they can be further divided into seminomas and nonseminomatous tumors (also known as nonseninomas). Seminomas are typically located in the testes while nonseminomas are cancerous tumors commonly found in the pineal gland in the brain, the mediastinum, or the abdomen. Elevation of hCG is found in approximately 14% of individuals with stage I seminomas before orchiectomy and in about half of individuals with metastatic seminomas. Approximately 40% to 60% of those with nonseminomas have an elevated blood hCG.

A 2010 guideline on Uses of Serum Tumor Markers in Adult Males with Germ Cell Tumors, by the American Society of Clinical Oncology (ASCO) provided recommendations on appropriate uses for serum markers of GCTs. The guideline recommends measuring 3 markers (hCG, AFP and lactate dehydrogenase [LDH]) before and after orchiectomy to stage patients with testicular nonseminomas, and before chemotherapy to stage those with extragonadal nonseminomas. They also recommended measuring hCG and AFP shortly before retroperitoneal lymph node dissection and at the start of each chemotherapy cycle for nonseminomas, and periodically to monitor for relapse. The guideline recommended measuring postorchiectomy hCG and LDH for individuals with seminoma who had elevated levels of these markers prior to orchiectomy. They also recommended measuring hCG and AFP to monitor for relapse in individuals treated for advanced seminoma.

In 2019 the American Urological Association (AUA) published guidelines for the Diagnosis and Treatment of Early Stage Testicular Cancer. These guidelines recommend testing for elevated hCG in individuals with a solid testicular mass that is suspicious for cancer. This testing should be done prior to any treatment, including orchiectomy (moderate recommendation, grade C).

According to NCCN’s 2023 guideline for Testicular Cancer, hCG is the most commonly elevated serum tumor marker in testicular cancer. Elevated serum concentrations of hCG may be present with both seminomas and nonseminomas. NCCN states that hCG levels are critical for determining prognosis and assessing treatment outcomes in individuals with testicular GCTs. hCG should be measured before and after treatment and throughout the follow-up period. However, further workup should be considered before initiating treatment for mildly elevated hCG since other factors, including hypogonadism and marijuana use, can cause false positive results.

The NCCN 2023 guideline for Ovarian Cancer states that hCG, along with other tumor markers such as AFP and LDH, may provide important information in the preoperative workup. Ovarian germ cell tumors can cause high levels of hCG while other types of ovarian tumors do not. hCG, AFP, and LDH are markers for malignant germ cell tumors that can be helpful in diagnosis, preoperative planning, and post-treatment monitoring for recurrence.

A mass in the mediastinum often stems from the thymus gland, but could be a GCT. The 2023 NCCN guideline for Thymomas and Thymic Carcinomas recommends hCG testing in the initial evaluation of mediastinal masses in order to rule out a GCT.

Cancers of unknown primary are metastatic tumors whose primary site of origin cannot be determined during standard pretreatment evaluation. The NCCN 2023 guideline for Occult Primary (Cancer of Unknown Primary [CUP]) recommends measurement of hCG when there is a mediastinal or retroperitoneal mass as it may be suggestive of a primary GCT. Identification of a GCT is important as GCTs are effectively treated with combination chemotherapy, and appropriate therapy may lead to cure.

Hydatidiform mole: A mass that forms in the uterus early in pregnancy made up of cells from an abnormally developed embryo and placenta.

Mediastinum: The central compartment of the thoracic cavity, especially that between the lungs.

Orchiectomy: Surgery to remove one or both of the testicles.

Peritoneum: The tissue that lines the abdominal wall and covers most of the organs in the abdomen.

Preeclampsia: A condition in pregnancy characterized by high blood pressure, fluid retention and proteinuria.

Retroperitoneum: The area in the back of the abdomen behind the peritoneum.

Trophoblastic: Pertaining to embryonic cells that facilitate attachment to the uterus and formation of the placenta.

Peer Reviewed Publications:

1. Alldred SK, Takwoingi Y, Guo B, et al. First and second trimester serum tests with and without first trimester ultrasound tests for Down's syndrome screening. Cochrane Database Syst Rev. 2017; 3(3):CD012599.
2. Huang J, Liu Y, Yang H, et al. The Effect of Serum β-Human Chorionic Gonadotropin on Pregnancy Complications and Adverse Pregnancy Outcomes: A Systematic Review and Meta-Analysis. Comput Math Methods Med. 2022; 2022:8315519.
3. Nicholson BD, Jones NR, Protheroe A, et al. The diagnostic performance of current tumour markers in surveillance for recurrent testicular cancer: a diagnostic test accuracy systematic review. Cancer Epidemiol. 2019; 59:15-21.
4. Zhang X, Huangfu Z, Shi F, Xiao Z. Predictive Performance of Serum β-hCG MoM Levels for Preeclampsia Screening: A Meta-Analysis. Front Endocrinol (Lausanne). 2021; 12:619530.

Government Agency, Medical Society, and Other Authoritative Publications:

1. American College of Obstetricians and Gynecologists’ Committee on Obstetric Practice, Society for Maternal-Fetal Medicine. Indications for outpatient antenatal fetal surveillance: ACOG Committee Opinion, Number 828. Obstetrics and gynecology. 2021; 137(6):e177-e197.
2. American College of Obstetricians and Gynecologists, Society for Maternal-Fetal Medicine. Screening for fetal chromosomal abnormalities: ACOG Practice Bulletin, Number 226. Obstetrics and gynecology. 2020; 136(4):e48-e69.
3. Centers for Disease Control and Prevention. Diagnosis of Birth Defects. Available at: https://www.cdc.gov/ncbddd/birthdefects/diagnosis.html. Accessed on December 7, 2023.
4. Centers for Disease Control and Prevention. How To Be Reasonably Certain that a Woman Is Not Pregnant. Available at: https://www.cdc.gov/reproductivehealth/contraception/mmwr/spr/notpregnant.html. Accessed on December 7, 2023.
5. Gilligan TD, Seidenfeld J, Basch EM, et al. American Society of Clinical Oncology clinical practice guideline on uses of serum tumor markers in adult males with germ cell tumors. J Clin Oncol. 2010; 28(20):3388-3404.
6. National Cancer Institute. Gestational Trophoblastic Disease Treatment. Available at: https://www.cancer.gov/types/gestational-trophoblastic/hp/gtd-treatment-pdq. Accessed on December 7, 2023.
7. National Cancer Institute. Infantile Choriocarcinoma of the Liver. Available at: https://www.cancer.gov/types/liver/childhood-liver-cancer/infantile-choriocarcinoma. Accessed on December 7, 2023.
8. National Cancer Institute. Ovarian Germ Cell Tumors Treatment. Available at: https://www.cancer.gov/types/ovarian/hp/ovarian-germ-cell-treatment-pdq. Accessed on December 7, 2023.
9. National Cancer Institute. Testicular Cancer Treatment. Available at: https://www.cancer.gov/types/testicular/patient/testicular-treatment-pdq. Accessed on December 7, 2023.
10. NCCN Clinical Practice Guidelines in Oncology^®. © 2023 National Comprehensive Cancer Network, Inc. For additional information visit the NCCN website: http://www.nccn.org/index.asp. Accessed on December 7, 2023.
    • Gestational Trophoblastic Neoplasia (V1.2024). Revised October 27, 2023.
    • Occult Primary (Cancer of Unknown Primary [CUP]) (V1.2024). Revised September 6, 2023.
    • Ovarian Cancer including Fallopian Tube Cancer and Primary Peritoneal Cancer (V2. 2023). Revised June 2, 2023.
    • Testicular Cancer (V1.2023). Revised January 26, 2023.
    • Thymomas and Thymic Carcinomas (V1.2024). Revised November 21, 2023.
11. Stephenson A, Eggener SE, Bass EB, et al. Diagnosis and treatment of early stage testicular cancer: AUA guideline. J Urol 2019; 202:272-281.
12. Sturgeon CM, Duffy MJ, Stenman UH, et al. National Academy of Clinical Biochemistry laboratory medicine practice guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers. Clin Chem. 2008; 54(12):e11-79.

1. American Cancer Society. Tests for Testicular Cancer. Available at: https://www.cancer.org/cancer/testicular-cancer/detection-diagnosis-staging/how-diagnosed.html. Accessed on December 7, 2023.
2. American Cancer Society. Treatment for Germ Cell Tumors of the Ovary. Available at: https://www.cancer.org/cancer/ovarian-cancer/treating/germ-cell-tumors.html. Accessed on December 7, 2023.
3. American Cancer Society. What is Testicular Cancer? Available at: https://www.cancer.org/cancer/testicular-cancer/about/what-is-testicular-cancer.html. Accessed on December 7, 2023.
4. United States Food and Drug Administration. Home Use Tests / Pregnancy. Available at: https://www.fda.gov/medical-devices/home-use-tests/pregnancy. Accessed on December 7, 2023.

β-hCG
hCG
human chorionic gonadotropin

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