Risk Factors And Aetiology For Pregnancy Failure

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Risk factors include advancing maternal age, previous failed pregnancy, smoking, moderate to heavy alcohol use, cocaine, NSAIDs/aspirin (by interference with prostaglandins), fever, caffeine (dose related, questionably secondary to cytochrome P450 enzyme activation) and low folate.

The aetiology of pregnancy failure is complicated and could be the subject of an entire chapter. Suffice it to say that it can be associated with chromosomal abnormalities. Pregnancies associated with trisomy 21, 18 and 13 are the most likely to survive. All other trisomies end in early pregnancy failure. Congenital anomalies are also a source of pregnancy failure. Maternal endocrinopathies, especially diabetes, and haemoglobin A1C levels at conception correlate with risk of pregnancy failure. Other related conditions include uterine abnormalities (adhesions, septae and submucous fibroids). Acute or chronic maternal illness and/or infection can result in early pregnancy failure. Thrombophilia as well as auto-immune disorders are controversial as to their role, if any, in early pregnancy failure and recurrent miscarriage in particular.

Our modern understanding of early pregnancy and its failure results from firstly the ability to detect minute levels of serum hCG, secondly lessons learned from the assisted reproductive technologies and finally from the improved resolution available using TVS.

Serum hCG is produced by trophoblastic tissue. It is detectable 8 days post conception.

Erroneously it is still referred to by some as a 'beta subunit' or simply 'beta' to distinguish it from the alpha subunit shared with TSH and other molecules. Most current tests however measure the intact hCG molecule. Over-the-counter home pregnancy tests will turn positive at or around the time of the missed menses at a level of 25 IU/L. Serum hCG normally rises by a minimum of 66% every 48 hours although it often doubles in that period of time. A total of 15-20% of ectopic pregnancies will follow a normal doubling time of hCG. These are the ones that will usually end up with an embryo and/or heart beat in an extrauterine location. Most normal early pregnancies are seen on TVS once the serum hCG level is >1000 IU/L. Thus there may be a variable but lengthy period of time from when a woman can diagnose a pregnancy event with a home pregnancy test and when one will first be able to visualize it.

TVS provides a degree of image magnification that is as if we were performing ultra-sonography through a low power microscope ('sonomicroscopy'). Prior to the vaginal probe, ultrasonography was a tool mainly of the obstetrician. Early equipment had barely enough resolution for limited functions such as placen-tal localization, establishing fetal lie, and to perform measurements of gestational age based on parameters such as the biparietal diameter and crown-rump length.

Several decades of conventional wisdom taught us that '25% of all pregnancies will experience bleeding in the first trimester and of those half will miscarry'. Such women were often told to go home, put their feet up and that they had a 50/50 chance of the pregnancy continuing. Although these statistics are very close to accurate, modern practice allows us to tell such women much more. The outcome, however, will usually remain the same.

A biochemical pregnancy has been defined as a pregnancy detected by assays of serum hCG but one that has failed before it can be clinically recognized (as bleeding then occurs at or around the time of the expected menses). Wilcox et al.1 studied 221 women attempting to conceive by measuring daily hCG levels by radioimmunoassay. Twenty-two per cent of pregnancies detected by assay were lost prior to clinical recognition. However, of these, 35% became clinically pregnant the next cycle, 65% clinically pregnant by the third cycle and 83% by the sixth cycle. Such a chemical pregnancy is an excellent prognostic sign indicating that the woman is ovulatory, has tubal patency (at least on one side), has a fertile partner and is herself capable of capacitating her partner's semen.

Now that women have the ability to clinically recognize their own pregnancies by the time of their missed menses, a more appropriate definition of chemical pregnancy would be one in which loss occurs prior to the onset of the embryonic period.

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