The Relationship Of Peak Symptoms And Cessation Of NVP To The Isoforms Of hCG In Maternal Blood.

The Relationship Of Peak Symptoms And Cessation Of NVP To The Isoforms Of hCG In  Maternal Blood.


There are two main types of hCG secreted from the trophoblast into maternal blood
hyperglycosylated hCG or regular hCG (1). In fact each type is produced from different cells of the
early trophoblast hyperglycosulated is derived from cytotrophoblasts cells whereas the less
glycosulated regular hCG is derived from syncytiotrophoblasts cells (1). In the first 3-6 weeks from
LMP the ratio between the two hCGs moves away from being highly in favour of
.<7*68=<(:0<=4-*+$F/!DEG$'&(6*40'&8$-:946+$a higher quantity of regular hCG (1). This change of
ratio continues to become a marked increase of regular hCG between 6-10 weeks from LMP. At
the same time the total synthesis of regular hCG is greatly increased (2). The regular hCG has been
separated into 5 different isorforms moving from acidic to a more basic form of hCG (3). Regular
hCG of early pregnancy has a greater ratio of the acidic form of the compound, as it has a higher
carbohydrate content which has been shown to be essential for the bioactivity of hCG (4). The
acidic form is also the more biologically active as it has a longer half life in maternal blood (5). It
is more prominent in maternal blood in weeks 6-10 from LMP whereas from week 11-15 the more
basic lower carbohydrate content less active type of regular hCG becomes more prominent in
maternal blood. The major change occurs at week 13 from LMP (5). There is a decrease in the
amount of regular hCG in maternal blood synthesised by week 11 until week 14 from LMP after
which the level of hCG remains fairly constant throughout the pregnancy (5). Nausea and vomiting
rapidly increases in incidence and severity from week 6 from LMP becoming markedly worse from
weeks 6-9, then generally decreases at first in week 10 then gradually declines in weeks 11-12 and
typically ceases between weeks 12-14 from LMP (6). There appears to be an association between
the changes in the regular hCG to the acidic isoform secreted from syncytiotrophoblast cells of the
early trophoblast causing the severity of nausea and vomiting symptoms at their peak weeks 6-10
from LMP, followed by a change to the basic form of hCG weeks 11-15 from LMP associated with
the reduction and cessation of these symptoms of NVP.  

In Jordan’s investigation of 20 women with hyperemesis gravidarum the hCG profile differed
significantly from those without HG (p<0.001). The ten European and ten Samoan women with
hyperemesis gravidarum had higher concentrations in the acidic third of hCG when compared to
controls. Peak 6 (ph 3.3) was observed only in hCG profiles of women suffering from HG. Peak 5
(ph 3.6) occurs significantly more frequently in hCG profiles of HG women than with control
subjects (p <0.05). Therefore the acidic forms of hCG might be responsible for pregnancy related
nausea and vomiting either by direct action on the brain stem centres or in intestinal mobility or by
indirect effects through secretion of hormones normally related to other glycoproteins such as
thyroid hormones (7).

As there are LH/hCG receptors in at least three areas of human brains such as hippocampus,
hypothalamus and brain stem (1) these receptors may explain the cause of hyperemesis gravidarum
or the grades of severity of nausea and vomiting which occur during normal pregnancy.
It will also be necessary in considering the aetiology of various grades of pregnancy sickness which
women may experience to remember that pregnancy sickness is an episodic condition, about 85%
of women who have the condition have at least two episodes of nausea daily (6). There does appear
to be a similar episodic daily pattern for maternal serum hCG (8).  


Goodwin writes in his significant article, despite the evidence that hCG is very closely related to the symptoms of hyperemesis gravidarum there still lacks a good explanation of how hCG causes hyperemesis gravidarum. We ask could the association of maternal prostaglandin E2 and the symptoms of NVP and HG be a further link in the detection of the mystery, what causes this condition in otherwise normal pregnancies?

REFERENCES

1. COLE L.A. Review article.
Biological functions of hCG and hCG-related molecules.
Reproductive Biology and Endocrinology 2010; 8:102.
http://www.rbej.com/content/8/1/102

2. KOVALEVSKAYA G., BENBACEV O, FISHER S.J., CACARES E., O’CONNOR J.F.
Trophoblast origin of hCG isoforms : cytotrophoblasts are the primary source of choriocarcinoma like hCG.
Molecular Cellular Endocrinology 2002; 194:147-155.

3. YAZAKI K., YAZAKI C., WAKABAYASHI K., IGARASHI M.
Isoelectric heterogeneity of Human Chorionic Gonadotrophin.
Presence of Choriocarcinoma specific components
Am J Obstet. Gynecol. 1980; 138:189-194.

4. MOCK P., KOVALEVSKAYA G., O’CONNOR J.F., CAMPANA A.
Choriocarcinoma-like human chronic gonadotrophin (hCG) and hCG bioactivity during the first trimester of pregnancy.
Human Reproduction 2000; 15,10, 2209-2214.

5. WIDE L., LEE JIA-YING., RASMUSSEN C.
A change in the isoforms of Human Chorionic Gonadotrophin occurs around the 13th week of gestation.
J. Clin. Endocrinol. Metab. 1994; 78:1419-1423.

6. GADSBY R., BARNIE-ADSHEAD A.M., JAGGER C.
A prospective study of nausea and vomiting during pregnancy.
Brit. J. Gen. Pract. 1993; 43:245-248.

7. JORDAN V., GREBE S.K.G., COOKE R.R., FORD H.C., LARSEN P.D., STONE P.R., SALMOND C.E.
Acidic Isoforms of Chronic Gonadotrophin in European and Samoan Women and Associated with Hyperemesis Gravidarum and may be Thyrotrophic.
J. Clin. Endocrinol. 1999; 50:619-627.

8. O’DELL M., OWENS K., RYAN J.
Episodic secretion of Human Chorionic Gonadotrophin in Early Pregnancy.
J. Clin. Endocrinol. Metab. 1981;53:6, 1307-1309.

9. GOODWIN T.M.
Human Chrorionic Gonadotrophin and Hypermemesis Gravidarum in Nausea and Vomiting of Pregnancy State of the Art 2000.
Eds. Korn G., Bishai R. The Motherisk Program at hospital for sick children, University of Toronto, Canada.

Did you know?

Hyperemesis Gravidarum rarely ends at 12 weeks of pregnancy. It typically improves in the middle of pregnancy, but symptoms often last until birth.

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