Impaired Corpus Luteum Function in Ectopic Pregnancy Cannot be Explained by Altered Human Chorionic Gonadotropin

Abstract

We studied the cause of the low serum progesterone, 17 beta-estradiol, and 17-hydroxyprogesterone levels that occur in women with an ectopic pregnancy. Only women who had been amenorrheic for less than 8 weeks were studied in order to assess corpus luteum rather than placental biosynthesis of these steroids; each woman with an ectopic pregnancy was matched to a woman with a normal intrauterine pregnancy on the basis of serum intact hCG levels within 10% of one another to obviate the influence of different levels of this luteotropic hormone. Every woman with an ectopic pregnancy had lower serum progesterone, estradiol, and 17-hydroxyprogesterone levels than her matched normal pregnant pairmate (median values: progesterone, 27.9 vs. 83.5 mmol/L; estradiol, 0.36 vs. 1.79 nmol/L; 17-hydroxyprogesterone, 4.95 vs. 22.1 nmol/L, respectively; all P less than 0.002). The ratios of intact hCG, measured by immunoradiometric assay, to hCG, measured by a hCG beta-specific RIA, were similar in the two groups. Serum hCG bioactivity was assayed by measuring the ability of serum to stimulate testosterone secretion from mouse Leydig cells. The mean biological to intact immunological hCG ratios were 2.06 +/- 1.39 (+/- SD) for ectopic pregnancy and 1.91 +/- 0.81 for normal pregnancy (P greater than 0.05). The biological hCG to immunoreactive hCG beta ratios were 1.98 +/- 0.75 and 2.02 +/- 0.82, respectively. Serum hCG from both groups of women stimulated cAMP generation by testicular cells similarly. We conclude that the lower serum steroid levels in women with ectopic pregnancy cannot be explained by altered hCG bioactivity. The lower steroid levels may thus reflect a primary defect of the corpus luteum, absence of another stimulator of ovarian steroid biosynthesis, or more subtle alterations in hCG glycosylation which are important in vivo but not assessed by the in vitro bioassay.

Ciliated epithelial-specific and regional-specific expression and regulation of the estrogen receptor-β2 in the fallopian tubes of immature rats: a possible mechanism for estrogen-mediated transport process in vivo

“…Furthermore, fallopian tube malfunction may result in tubal ectopic pregnancy (when the embryo implants in the fallopian tube rather than in the uterus), which still remains a potentially life-threatening condition, without reliable diagnostics and prevention in women (38,70). Of particular interest is the association between low levels of estrogen and the increased incidence of tubal ectopic pregnancy (4,46), and there are indications that modulation of ovarian steroid levels may have clinical benefits in those patients (18). Therefore, elucidating the mechanisms of estrogens action involved in regulation of tubal functions in vivo is crucial to fully understanding this complex process.…”

The regulation of the human corpus luteum steroidogenesis: a hypothesis?

“…(Tulchinsky and Hobel, 1973;Norman et al, 1988;Johnson et al, 1993b). Simple dose± response curves do not exist for HCG and progesterone as shown by the relatively constant progesterone concentrations in early normal intrauterine pregnancies at the time that HCG concentrations are increasing markedly.…”

“…Norman and his colleagues were the ®rst group to draw attention to the differences in the progesterone concentrations between normal and ectopic pregnancies (Norman et al, 1988). They matched women with ectopic and normal intrauterine pregnancies of the same gestation by HCG concentration and found consistently lower concentrations of progesterone, 17-OH progesterone and oestradiol in the ectopic set.…”

“…They matched women with ectopic and normal intrauterine pregnancies of the same gestation by HCG concentration and found consistently lower concentrations of progesterone, 17-OH progesterone and oestradiol in the ectopic set. This group investigated whether differences in HCG bioactivity were responsible for the lower steroid concentrations, but found that the HCG bioactivity was similar in each set ( Figure 1, Norman et al, 1988). They concluded that the difference in the steroid concentrations may be a re¯ection of a primary defect in the CL function, the absence of another stimulator of ovarian steroid biosynthesis or that there were more subtle variations in the bioactivity of HCG than could be detected in their assays.…”

Serum Progesterone and 17-Hydroxyprogesterone in the Diagnosis of Ectopic Pregnancies and the Value of Progesterone Replacement in Intrauterine Pregnancies when Serum Progesterone Levels Are Low

“…Thus, this steroid may serve as a good marker in assessing CL function in early pregnancy. Previously low P and 17-OHP levels were found in EP which is likely to be caused by a primary luteal phase defect [4][5][6], This was, however, based on a single measurement.…”