We have attempted to review from a study of various literature articles in twenty five different
subjects written by 143 separate investigations and our own work an assessment of factors
involved in the cause of nausea and vomiting in pregnancy (NVP) including the most severe
symptoms of the condition hyperemesis gravidarum (HG).
We and other researchers found that maternal serum human chronic gonadotrophin, beta human
chorionic gonadotrophin and progesterone levels can each be associated with the symptoms of
nausea and vomiting of pregnancy, the first two showing a positive association and the latter a
negative association. A study of the early development of the trophoblast demonstrates that the
primary, secondary and tertiary chorionic villi are present at the end of the 5th week of pregnancy at
which time the symptoms of nausea and vomiting will typically start. These chorionic villi increase
to surround the whole gestational sac by 6 weeks from the first day of the last menstrual period
(LMP), that is called weeks of gestation, tripling in size from 6-8 weeks of gestation. During the
weeks 6-10 of gestation the symptoms of nausea and vomiting are typically at their worst. After 10
weeks of gestation two thirds of the ring of chorionic villi ceases to grow while the rest which
becomes the definitive placenta continues to develop. At this stage of gestation the nausea and
vomiting typically begin to reduce in severity. Therefore we need to look at these chorionic villi for
the source of the symptoms.
Villous cytotrophoblast cells of the chorionic villi produce little hormone but they unite to form
syncytiotrophoblast cells which synthesize and secrete large quantities of regular hormones
including chorionic gonadotrophin. At the weeks 6-10 of gestation the time of increasing severe
symptoms of NVP to reach their peak typically at 9-10 weeks there is an enormous increase in the
total synthesis of human chorionic gonadotrophin (hCG) again demonstrating an association
between hCG and NVP. There are at least 5 isoforms of regular hCG from which the more acidic
long acting isoform is produced in week 6-10 of gestation. This isoform of hCG changes to the
more basic less active isoform of hCG at weeks 11-15 of gestation, the most significant change
occurring at 13 weeks. Weeks 12-14 of gestation are the weeks in which symptoms of NVP most
often cease. The relationship between maternal serum hCG and NVP are again associated at this
stage of gestation but is hCG a significantly emetic hormone? One that can cause severe nausea
and vomiting in about 1.5% of all pregnant women, even in some of these pregnant women
throughout their pregnancy?

In order to dig a little further into the cause of nausea and vomiting of pregnancy we need to
consider hormones cytokines and eicosanoids produced by trophoblast cells which will stimulate
increased synthesis of human chorionic/gonadotrophin or which human chorionic gonadotrophin
will stimulate from these cells. One of the eicosanoids is very emetic namely prostaglandin E2
(PGE2). PGE2 is synthesised and released when a cell wall receptor is stimulated by its activator for
example “the ability of IL-1 to initiate prostaglandin synthesis is perhaps one of its most important
biological properties”. Prostaglandin E2 has been shown to be a very emetic eicosanoid when given
to obtain a legal abortion in early pregnancy. Prostaglandin E2 has been shown to be secreted from
syncytiotrophoblast villous cells which bathe in maternal blood in the inter villous space and from
decidual stroma cells and macrophages as well as in the decidual extracellular matrix. Professor
Sincha Yagel has told us in 1998 that there is plenty of prostaglandin E2 in the trophoblast cells
during the early weeks of pregnancy. However the first stage of the breakdown of prostaglandin E2
to its inactive metabolite involves oxidation of the 15-hydroxyl group to 15 ketoprostandin E2 by a
NAD-linked 15 hydroxyprostaglandin dehydrogenese (PGDH). PGDH is present in
syncytiotrophoblast cells of the chorionic villi, in the decidua and in the extracellular matrix in early human pregnancy. In normal pregnancy PGDH, which is under progesterone control, falls in
mean placental values in gestational weeks 5-9 then gradually rises to weeks 15-16. There is a ten
fold increase in placental values between gestational weeks 7-15. There is also a large variation in
PGDH activity between individual placentae for each early gestational age.

We have presented an investigation demonstrating a statistically significant association between
maternal PGE2 levels and nausea and vomiting of pregnancy symptoms between weeks 7-9 of
pregnancy (P <0.001). The result for each woman (number 18) showed a raised maternal PGE2
serum level in the symptomatic sample versus the control maternal serum PGE2 level on the same
day. The results could not have been due to any diurnal variation of serum PGE2 because eight
experimental samples were taken in the mornings and ten taken after mid-day. These results
showing an association between prostaglandin E2 maternal serum levels and nausea and vomiting
of pregnancy need confirmation in larger studies. However prostaglandin E2 plays such a vital role
in early pregnancy that suppressing that eicosanoid at this stage of pregnancy might have adverse
effects for the welfare of the pregnancy.
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human chorionic gonadotrophin maternal serum levels can be associated with the cause of nausea
and vomiting of pregnancy but are these hormones significantly emetic in nature to cause the
variation of degree in pregnancy nausea and vomiting which occur possibly throughout all three
trimesters of pregnancy? However prostaglandin E2 is an eicosanoid which is known to be a strong
emetic substance when given to obtain legal abortion in early pregnancy. Could the finding that
gonadotrophin stimulates the secretion of prostaglandin E2 from syncytiotrophoblast villous cells
and from decidual cells and the metabolism of prostaglandin E2 by prostaglandin dehydrogenase,
be a link to the cause of the various degrees of severity of episodic nausea and vomiting of
pregnancy and the ceasation of these symptoms in pregnancy. Certainly these symptoms are awful
for nearly 30% of pregnancy women who develop nausea and vomiting and for about 1.5% of all
pregnant women who suffer from the extreme form of this nausea and vomiting called hyperemesis
gravidarum. We know from our experience working with the charity Pregnancy Sickness Support
that those pregnant women would be most grateful if more sympathetic heed and investigation
were given to the cause and treatment of this severe nausea and vomiting of pregnancy. In fact
these symptoms are for them a frightening problem which may abolish their natural joy of being
pregnant and even cause some women to have no further pregnancies, or worst of all a termination
of their pregnancy.


"It was so comforting to speak to someone that listened to me, understood my symptoms and most importantly made me feel like I wasn't overreacting."

Did you know?

Early access to treatments is likely to be more effective and may prevent symptoms developing into HG


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If you think you are suffering from HG please call us for support on: 024 7638 2020
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