Human chorionic gonadotrophin in early pregnancy
As perinatal mortality has fallen in most countries, the problem of early pregnancy loss has attracted greater attention. The two particular problems relating to early pregnancy loss which have been examined in this thesis are the incidence of 'biochemical pregnancy' and the early diagnosis of ectopic pregnancy. These problems were chosen because the new generation of pregnancy tests using sensitive assays for human chorionic gonadotrophin (hCG) carried the potential of giving new, and potentially valuable, clinical insights into these conditions. In the first study in this thesis, daily urinary measurements of luteinising hormone, oestrone glucuronide and pregnanediol glucuronide were used in a group of normally fertile women, to define ovulation and its precise timing in 25 conception and 50 non-conception ovulatory cycles. Daily analysis of urinary hCG, using two separate antisera, indicated that previous reports had substantially overestimated the incidence of 'biochemical pregnancy' occurring before next anticipated menstruation. Using similar methods, cycles from women wearing intra-uterine contraceptive devices and from women undergoing in vitro fertilisation also revealed low incidences of biochemical pregnancy in these clinical situations. In a comparison of conception and non-conception cycles, urinary endocrine assays showed no significant differences in the early luteal phases. The earliest quantitative differences between conception and non-conception cycles were detected in pregnanediol glucuronide on day 9 after the luteinising hormone (LH) surge, in oestrone glucuronide on day 11 and in hCG on day 13, failing to confirm earlier reports of quantitative endocrine differences between conception and non-conception cycles detectable early in the luteal phase. In an assessment of the value of a side room qualitative enzyme linked immunosorbent assay (ELISA) for hCG, it was found that pregnancy was reliably diagnosed by day 16 after the LH surge. The ELISA test was invariably positive in association with a clinically proven ectopic pregnancy and the introduction into clinical practice of this test significantly reduced the incidence of negative laparoscopies for abdominal pain. The work in this thesis failed to find confirmatory evidence to support the concept of biochemical pregnancy but suggests that the appropriate use of sensitive tests for hCG may have an important role in the clinical management of ectopic pregnancy.