Daily urine samples were obtained from 38 women of proven fertility, who were attempting to conceive, to assess the frequency of clinically unsuspected 'biochemical pregnancies' on the basis of late luteal phase rises of hCG. In 25 clinically confirmed conception cycles, the earliest pregnancy-induced hCG rises from baseline occurred 8 days after the endocrinologically defined date of ovulation (mean 11.1 days, SD 1.3). Urine samples obtained throughout 50 non-conception ovulatory cycles provided no evidence of any 'biochemical pregnancies' on the basis of late luteal phase rises of hCG occurring 8 or more days after the endocrinologically defined date of ovulation. If, as in previous studies, the date of ovulation had been estimated on the basis of menstrual cycle length and only the relatively non-specific NIH antiserum had been used in RIAs, 7 of the SO (14%) cycles would have been classified as resulting in biochemical pregnancies on the basis of hCG >50 m-i.u./ml on one occasion or >20 m-i.u./ml on two or more occasions after day 20 of the cycle. These levels of 'hCG' occurred at or soon after ovulation and could be explained by LH cross-reacting in the RIA. The rises of -hCG' were not confirmed when the urine samples were retested with an antiserum (Wellcome 895) of very high specificity f o r hCG. These results raise the possibility that the frequency of clinically unsuspected 'biochemical pregnancy' may have been substantially overestimated.Several studies have been published suggesting that many women miscarry pregnancies at such an early stage that neither they nor their attendants recognize that a pregnancy has occurred. In most studies the subjccts have been women attending infertility clinics, and samples have been obtained following stimulation of ovarian function with or without in-vitro fertilization
Assays of first morning urine samples for oestrone-3-glucuronide, LH and pregnanediol-3-glucuronide, were used to study endocrine function and return to ovulation in 18 subjects following spontaneous miscarriage. On the basis of the endocrine data, ovulation occurred in all 18 women in the cycle prior to first menses at a mean of 29 days post-partum (range 13-103 days) with one subject conceiving in that cycle. Compared with the second cycle, the first cycle after spontaneous abortion had similar levels of follicular phase peak ovulatory oestrone excretion but lower levels during the late luteal phase (P less than 0.02), lower levels of peak LH (50.5 IU/g creatinine (C) cf. 68.8 IU/g C; P less than 0.04) and lower late secretory peak pregnanediol (4.6 mg/g C cf. 6.1 mg/g C; P less than 0.02). The mean luteal phase length of 12.9 days in the first cycle was shorter than the mean of 14.4 days in the second cycle (P less than 0.02). These data show that, although there is some disturbance of endocrine function in the first cycle after spontaneous abortion, the majority of women have a rapid return to ovulation, making the early use of contraception necessary for those wishing to avoid conception.
1 Prolactin levels in response to sulpiride were studied in healthy volunteers. 2 Oral doses of 1 mg-50 mg sulpiride or placebo were given. 3 A 3 mg sulpiride dose produced similar levels to those achieved with both 10 mg and 50mg. 4 Circadian effects were studied showing no significant differences in the prolactin response to sulpiride. 5Acute or chronic responses showed an attenuation with chronic sulpiride treatment to 50% of the peak levels attained with acute treatment. 6 These results indicate that sulpiride retains its potent ability to produce prolactin release even at the low doses studied here.
A progestogen (norethisterone) and a dopamine antagonist (sulpiride) were given alone and in combination to volunteers to examine their effects on excretion of ovarian steroids. Compared with non-treatment cycles (n= 15), contraception with a progestogen alone (n= 10) was associated with increased excretion of oestrone and partial suppression of excretion of pregnanediol, suggesting partial luteinisation of unruptured follicles. By contrast, the combination of norethisterone and sulpiride (n=9) suppressed both ovarian steroids to basal values, the suppression being even greater than with sulpiride alone (n=5).These results suggest that a combination ofa progestogen with a dopamine antagonist might have a role in contraception.
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