HUMAN CHORIONIC GONADOTROPIN (hCG)

Human chorionic gonadotropin (hCG) is a glycoprotein hormone heterodimer comprised of an a and a subunit. Multiple forms of hCG are typically found in blood and urine. The early placental trophoblasts produce a and -hCG molecules. Alpha and -hCG is detectable within approximately one week of implantation and then rises exponentially (initial doubling time of about 1.5-2.5 days). The cytotrophblastic cells secrete dimer hCG and the syncytial trophoblast cells secrete free alpha-hCG. There is no free beta-hCG in the placenta, but it is in blood.

         After ovulation, if ovum is fertilized, the blastocyst implants in the endometrium on day 21. As soon as the blastocyst implants, hCG is present in the outer syncytial layer.

         Beta hCG levels should double approximately every 2 days for the first four weeks of pregnancy [2].

         As pregnancy progresses the doubling time increases.

         By 6 to 7 weeks gestation beta hCG levels may take as long as 3 1/2 days to double [3,4].

         Then rate of secretion rises rapidly between 3 and 9 weeks after ovulation and reaches a peak about 10 to 12 weeks after ovulation and decreases to a much lower value by 16 to 20 weeks after ovulation. It continues at this level between 20 to 40 weeks pregnant period and disappears in blood 2 weeks after delivery.

         Rising hCG reflects rapidly proliferating and invasive placenta.

         Falling hCG is associated with a relative reduction in trophoblasts.



Normal levels

Week from the Last Menstrual Period (LMP)

Amount of hCG in mIU/ml (1)

 

Mean Level

Amount of hCG in mIU/ml (1)

 

 

Range of values

3

 

5 - 50

4

37

4 - 426

5

373

19 - 7,340

6

7800

1,080 - 56,500

7 - 8

31,800 – 72,600

7,650 - 229,000

9 - 12

9 wks -116,000

10 wks - 108,000

11 wks – 87,700

12 wks – 76,100

25,700 - 288,000

13 - 16

13 wks - 80,000

14 wks – 56,600

15 wks – 50,600

16 wks – 37,500

13,300 - 254,000

17 - 24

17 wks – 21,500

18 wks – 24,200

19 wks – 17,400

20 wks – 15,700

21 wks – 15,100

22 wks – 14,500

23 wks – 14,800

24 wks – 10,600

4,060 - 165,400

25 - 40

25 wks – 10,800

26 wks –11,500

27 wks – 13,600

28 wks – 14,400

29 wks – 13,700

30 wks – 16,000

31 wks – 12,100

32 wks – 19,600

33 wks – 15,200

34 wks – 23,900

35 wks – 24,500

36 wks – 16,500

37 – 40 wks – 29,000

 

3,640 - 117,000

 

 

 

 

 

 

  • Normal Gestational Sac – Each laboratory should determine their own discriminatory level, as there is an interassay variability of 10-15%.
    • Visualized transabdominally when bhCG =
      1800 mIU/ml (Second IRP).
    • Visualized endovaginally when bhCG =
      500-1000 mIU/ml.
  • Doubling time of bhCG = 1.4 to 2.1 days, or an increase of 66% over 48 hours.
    • 85% of viable intrauterine pregnancies – rise of titer is 66% every 48 hours during first 40 days of gestation.
    • 15% of viable intrauterine pregnancies – rise in titer is <66% in a 48 hour period during the first 40 days of gestation.
    • An increase of 50% or less in 48 hours is usually associated with a non viable pregnancy (which may be either intrauterine or extrauterine).
    • An appropriate rise in bhCG titer does not eliminate the possibility of an ectopic pregnancy.
  • Levels measured depend on which preparation is used:
    • 1st International Standard (2X 2nd IS).
    • 2nd International Standard.
    • 3rd International Reference Preparation (IRP).

There are several physiological functions of hCG during pregnancy.

  1. The most important function is to prevent the normal corpus from involution to maintain pregnancy. Before 12 weeks, placenta could not produce enough estrogens and progesterone to maintain pregnancy. During that period, hCG converts menstrual corpus luteum to pregnant corpus luteum and promotes it to secrete larger quantities of estrogen and progesterone which prevent menstruation and cause the endometrium to continue growing. After 12 weeks, the placenta itself secretes sufficient quantities of estrogen and progesterone to maintain pregnancy for remainder of the gestation period. The corpus luteum involutes slowly after 13th to 17th week of gestation.
  2. hCG inhibits the secretion of FSH, which causes follicles development stops, then ovulation stops, finally, menstrual cycle stops.
  3. hCG stimulates the fetal testes to secrete testosterone and the development of male sex organs.
  4. hCG stimulates adrenal and placental steroidogenesis.

 

REFERENCES

1. Chartier M et al. Measurement of plasma chorionic gonadotropin (hCG) and CG activities in the late luteal phase: Evidence of the occurence of spontaneous menstrual abortions in infertile

women, Fertil Steril 1979;31:134.
2. Ashitaka Y et al. Production and secretion of hCG andhCG subunits by trophoblastic tissue. In Segal S (ed):Chorionic Gonadotropins. New York, Plenum, 1980 p 151.
3. Pittawy DE et al. Doubling times of human chorionic gonadotropin increase in early viable intrauterine pregnancies. Am J Obstet Gynecol 1985; 299-302.
4. American College of Obstetricians and Gynecologists. Medical Management of Tubal Pregnancy. Practice Bulletin Number 3, December 1998. Washington, D.C. ACOG, 1998

5. Lipscomb GH, Stovall TG, Ling FW. Non surgical treatment of ectopic pregnancy. NEJM 200;343(18):1325-1329.