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INTRODUCTION: -
Human Chronic Gonadotropin (HCG) has proved to be an amazing
molecule. It was introduced as a hormone with endocrinal
bearings. However, recent reports have completely changed the
understanding of this molecule and opened new areas of
application. No wonder, obstetricians require to take a new look
at it.
THE ACADEMICS: -
HCG is detected both in urine and in serum. With modern methods
of detection being very sensitive, the correlation between serum
& urinary levels is very consistent. As a result, it matters
little which one is assayed for clinical application. However,
serum HCG is most popularly assayed now.
HCG has an endocrinal half-life of maximum 72 hours. However,
HCG half-life as a hormone has much farther bearing that will be
understood in the paragraphs to follow.
HCG levels are at its peak on 70th day of pregnancy and plateau
by 100th day of pregnancy. This is exactly congruent with the
behavior of emesis gravidarum. Vomiting of pregnancy is also at
its peak at around 70th day and plateaus by 100th day.
WHO INFORMS THE MOTHER THAT SHE IS PREGNANT?
It may seen strange but is indeed true that it is HCG which
informs the mother that she has conceived. Thus HCG is secreted
by the blastocyst itself and by the time the chorionic tissue
takes over, HCG is already old in the mother. This HCG secretion
is required by the mother to tolerate the pregnancy
immunologicaly. Mother at her decidual-placental interface
mounts a complex but intricate protective response so as to
protect the conceptus. The conceptus is immunologicaly similar
to the mother but is distinct due to paternal contribution. This
can endanger every conceptus. On sensing that a conceptus is
within her, thanks to HCG, the mother starts protecting it.
HCG AND SEX DIFFERATIATION: -
A conceptus is indeed a male or a female due to its basic
chromosomal structure - XX or XY. However, this chromosomal
structure has to affect a series of changes in the conceptus so
that the fetus is either a male or a female. Interestingly an
essential agent that helps the genetic expression of this sex
structure of the conceptus is HCG. It acts on the adrenal and
ovarian tissues to bring about a differentiation into a male or
a female.
HCG: THE GROWTH FACTOR: -
Various articles and work done by many groups showed a
distinct role of HCG supplement in preventing recurrent
pregnancy loss. In some of these studies it was found that HCG
if given weekly, also showed its results. This created an
enigma. On one side we have a short half life of HCG tittering
around 72 hours. On the other had one was getting good results
with HCG being supplemented at a weekly interval. If was soon
obvious that there was much more to HCG than merely a hormone.
Soon studies got published showing a contamination of HCG with,
growth factors. It was thence explained that it was this
contamination which resulted in protecting the pregnancy much
beyond the endocrinal half-life. Soon further interesting
results emerged. One of these showed that HCG has a very similar
structure to growth factors. Studies in late 1997 and 1998 in
fact showed that HCG itself was the growth factor. Once HCG is
proved to be the growth factor, it is very clear that when in a
given clinical situation, HCG is administered, one is not giving
an endocrinal substance but an immunological substance.
To what extent is this similar to the LH is being currently
investigated. LH is now proved to have both endocrinal LH
component and an immunoreactive LH component. Whether, this is
true for HCG as well, is a matter being investigated. All in
all, the clinical discovery of such an investigation gives the
explanation to the affectivity of HCG even when administered at
a seven days interval.
HCG IN ECTOPIC PREGNANCY: -
Nowhere has the face of an obstetric condition changed as
has been in ectopic pregnancy. This has been largely due to HCG
and Trans Vaginal Sonography (TVS). Doubling time was a singular
parameter used clinically wherein an early diagnosis of ectopic
pregnancy became possible. It was found that in an intra uterine
pregnancy, HCG levels double every 48 hours. However, if by 48
hours HCG levels increase by less than 66% one should strongly
suspect an ectopic pregnancy.
However, when HCG is combined with ultra
sonography very early diagnosis of an ectopic pregnancy became
easy. It is now well established that in a given case if HCG
levels are greater than 1500 miu/ml and one fails to visualize
an intrauterine gestation, ectopic pregnancy is one the cards.
On other hand if a Trans Abdominal Sonography (TAS) does not
show an intrauterine pregnancy at or above 6500 miu/ml of HCG –
an ectopic pregnancy is on the cards.
Modern management of ectopic pregnancy
includes medical and expectant. In a given case if the G.S. is
less than 2.5 cms in size, fetal pole does not show cardiac
activity and free blood is less than 50 ml., medical treatment
can be given. 75 mgms. of methotrexate is preferred by us and
monitoring with 12 hourly USG and 48 hrs. HCG be done. Soon HCG
start falling indicating the response is said to have achieved.
Even in expectant management, when methotrexate is not given and
spontaneous resolution is expected HCG and TVS are the mainstays
in their treatment.
HCG IN NON INVASIVE DIAGNOSIS OF CHROMOSOMAL DISORDERS: -
HCG as a part of triple test in combination with urinary
estriol (UE3) and serum alpha feto protein can reasonably
accurately diagnose a trisomy 21 (T21). It has been found that
maternal age greater than 35, low UE3 High serum HCG and low
serum <AFP can give a diagnosis of T21 with a near 96% accuracy.
Similar combinations have been worked out for T18, anencephaly
etc.
HCG IN PREDICTING PIH: -
With the immunological role of HCG now well defined it is
understandable that HCG may be employed to pick up PIH. HCG
estimated at 15 weeks can predict a PIH with reasonable
accuracy. Studies are currently on to understand this aspect of
HCG before it is established.
MISCELLANY: -
Use of HCG in cases of trophoblastic diseases and ovulation
induction is well known. This can span the span of entire
articles and are therefore just mentioned to complete the list.
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