12.     Beta-HCG in early pregnancy.  

Whole HCG has both alpha and beta sub chains. 

The alpha chain is shared by LH.

Old tests for HCG, which detected both chains, could give a false positive by detecting the high levels of LH at the time of ovulation. 

They could even detect the elevated levels in postmenopausal women!  

The beta chain is unique to HCG, so spares us this problem. 

Output of HCG doubles every 1.5 days in the early weeks and every three days at about eight weeks. 

Ectopic pregnancy tends to produce less and the rate of increase is diminished. 

By the time normal pregnancy is producing > 6,000 iu./l., an intrauterine pregnancy can be seen on abdominal scan in almost all cases. 

Transvaginal scanning is much more sensitive in detecting intrauterine pregnancy, and will almost always show a pregnancy with HCG levels > 1,000 iu./l. 

Hence levels above these with no scan sighting of an intrauterine pregnancy suggest it is elsewhere. 

The so-called "pregnancy of unknown location".

A low rate of increase in HCG levels is usually due to a doomed pregnancy or an ectopic. 

Similarly, a very low level of HCG after the early weeks is most probably due to a failed pregnancy or ectopic pregnancy. 

HCG production peaks at about 12 - 14 weeks. 

In the past, pregnancy tests were less sensitive and relied on high levels of HCG.

So, pregnancy tests could be negative after 12 - 14 weeks.

Professional embarrassment could ensue.

E. g. the eighteen-week sized lump diagnosed as an ovarian cyst because of a negative pregnancy test that proved to be a pregnancy. 

Twin pregnancy and hydatidiform moles produce high levels, which may be the explanation for their association with hyperemesis.

The DRCOG database has a question about pregnancy tests, much along the lines of the questions I have put to you.

The most sensitive test I could find (November 06) for home urine-testing, claimed to be able to detect HCG at levels as low as 10 iu/l.

Most are in the 25 – 50 range.

One comes in at 100.

Obviously, the more sensitive the test, the earlier that diagnosis is feasible.

The problem is that a lot of these early pregnancies will come to grief.

Some woman might prefer to think that their late or abnormal period was not a miscarriage.

HCG will not be produced until implantation has occurred – it comes from the placenta, not the developing embryo.

This is believed to occur in most women 6-8 days after ovulation (or egg retrieval in cases of IVF).

This means that the earliest a pregnancy test could become positive is day 6.

Wilcox et al published a paper on the accuracy of pregnancy tests done on the day the next period is due. JAMA; 2001;286:1759-1761.

They found that 10% showed no HCG.

They concluded that implantation had not occurred in this group by the first day one of the due period.

You could be asked the maximum sensitivity of a pregnancy test done on the first day of the missed period.

It is obviously 90%.

To avoid false negatives, women should give it a week from the first day of the missed period, but few will be able to wait that long.

You could be asked about the earliest day a test could become positive.

You could be asked about tests becoming negative after 20 weeks. 

The modern tests are so sensitive that it is possible, but unlikely.