W. L. Herrmann

Effect of lumbar epidural analgesia on lower urinary tract function in the immediate postpartum period

Summary. Urodynamic investigations including cystometry and electronic simultaneous urethro‐cystometry were made in 27 primiparae between 2 and 5 days after delivery to assess possible effects of lumbar epidural analgesia on the function of the lower urinary tract. Three groups of patients were studied: 11 patients had vaginal delivery without epidural analgesia, 11 patients with similar obstetrical characteristics were delivered vaginally with epidural analgesia, and five others were delivered by caesarean section under epidural analgesia. The group of patients who were delivered vaginally under epidural analgesia had a significantly higher incidence (n= 4) of hypotonic bladders as determined by cystometry than the group without epidural analgesia (n= 0), (P < 0 05). The maximum cystometric capacity was significantly greater (P < 0.05) in the group who delivered vaginally with epidural analgesia than in the group without epidural analgesia, as well as the caesarean section group (with epidural analgesia), (P < 0.01). Possible side effects of epidural analgesia implied by these results are discussed and a method for surveillance of urethro‐vesical function both during labour and after parturition is proposed.

Amniotic fluid and plasma concentrations of pregnancy-associated plasma protein-A (PAPP-A) throughout pregnancy: comparison with other fetoplacental products

Summary. The development of a sensitive radioimmunoassay has enabled measurements of pregnancy‐associated plasma protein‐A (PAPP‐A) to be performed from early pregnancy. The present paper compares the plasma concentrations of PAPP‐A with the levels of two trophoblastic proteins, human placental lactogen (hPL) and the β‐subunit of human chorionic gonadotrophin (β‐hCG), with a steroid of fetoplacental origin, total oestriol (total E3), and with a fetal protein, α‐fetoprotein (AFP). PAPP‐A was also measured in amniotic fluid and in maternal urine. In contrast with the secretion of the other substances studied, which either reach a plateau or even decrease during the last 4 weeks of pregnancy, PAPP‐A steadily increased in the maternal circulation from 7 to 40 weeks gestation. It is proposed that PAPP‐A production is either not related to placental mass or that PAPP‐A is not of trophoblastic origin. The increase of PAPP‐A in amniotic fluids parallels the increase in maternal blood; virtually no PAPP‐A is excreted in urine.

PREGNANCY‐ASSOCIATED PLASMA PROTEIN‐A (PAPP‐A) AND hCG IN EARLY PREGNANCY

Pregnancy‐associated plasma protein‐A (PAPP‐A) is a recently described glycoprotein of unknown biological function. The development of a radioimmunoassay enabled us to measure plasma levels of PAPP‐A and human chorionic gonadotrophin (hCG) in 12 non‐pregnant volunteers and in 159 women in early pregnancy attending the outpatient clinic for legal abortion. PAPP‐A but not hCG was measurable in all non‐pregnant women. In pregnant patients (with 36 to 86 days of amenorrhea) hCG reached a peak value (163.1–197.6 ng/ml) between the 9th and the 13th week whereas PAPP‐A steadily increased throughout this period of pregnancy. Between the 6th and the 13th week after the last menstrual period, levels of PAPP‐A increased proportionally more than hCG. This work provides the first evidence of a PAPP‐A production in non‐pregnant subjects and the very early marked increase of PAPP‐A secretion during pregnancy.

In vitro production of pregnancy-associated plasma protein A by human decidua and trophoblast

Immunohistochemical techniques and direct measurements of pregnancy-associated plasma protein A (PAPP-A) have demonstrated the presence of PAPP-A in trophoblast and decidua. The purpose of the present study was to investigate the possibility that these tissues are capable of producing PAPP-A in vitro. Trophoblast and decidua were obtained from term deliveries and from legal surgical terminations of pregnancy (7 to 12 weeks). In addition to trophoblast and decidua, myometrium was also obtained during two hysterectomies in the first trimester of pregnancy. Tissues were incubated in medium 199 at 37 degrees C under an oxygen/carbon dioxide atmosphere. Media containing either pregnancy-associated serum or non-pregnancy-associated serum were changed after 8 hours of incubation in medium 199 alone. In addition to PAPP-A, human placental lactogen (hPL) and prolactin (Prl) were measured in homogenates and media by radioimmunoassays in order to confirm the viability of the cultured tissues. Addition of pregnancy-associated serum to the media induced a significant release of PAPP-A from trophoblast and decidua when compared to that in control cultures. Non-pregnancy-associated serum had no effect. Myometrium did not release any measurable PAPP-A into the medium even in the presence of pregnancy-associated serum. Cycloheximide added to pregnancy-associated serum significantly inhibited the release of PAPP-A from trophoblast and decidua. These last tissues, irrespective of the culture condition, released significantly more PAPP-A as well as hPL and Prl than was initially present in the tissue. These data demonstrate that PAPP-A is released in vitro by trophoblast and decidua (but not by myometrium) and that this release can be magnified by a factor present only in pregnancy-associated serum. The release of PAPP-A, hPL, and Prl is considered as a de novo production since concentration of these proteins are higher in media and tissues after incubation compared to concentrations initially present in the tissue before culture and since cycloheximide significantly inhibits the release of PAPP-A, Prl, and hPL from the cultured tissues.

Are vaginal fluid concentrations of prolactin, α‐fetoprotein and human placental lactogen useful for diagnosing ruptured membranes?

Summary. Vaginal fluid levels of prolactin (Prl), α‐fetoprotein (AFP) and human placental lactogen (hPL) were assayed to investigate their usefulness in the diagnosis of ruptured membranes. Fifty‐two patients at term were divided into those with intact membranes, and those with ruptured membranes. In patients with intact membranes the concentration of all three substances was low with few exceptions. The mean vaginal concentrations of the three proteins were significantly higher in patients with ruptured membranes, but low values were also found in this group. It is concluded, that because of the overlap between the values, Prl, AFP and hPL measurements in vaginal fluid do not represent a useful advance in the assessment of rupture of the membranes.

Effects of the antiprogesterone RU 486 in early pregnancy and during the menstrual cycle

The antiprogesterone RU 486 produces an abortifacient effect during the early stages of most, but not all, pregnancies. The rate of complication appears similar to that occurring in spontaneous abortions. At this time there is no definitive explanation for failures.

Tissue and plasma concentrations of pregnancy-associated plasma protein-A (PAPP-A): comparison with other fetoplacental products.

Summary. Human placental lactogen (hPL), α‐fetoprotein (AFP), prolactin (PRL) and pregnancy‐associated plasma protein‐A (PAPP‐A) were measured by radioimmunoassay in plasma, in homogenates of trophoblast, decidua, chorion, amnion and in amniotic fluid from 10 patients after non‐complicated term delivery. Plasma samples and homogenates of trophoblast and decidua were also collected from 10 patients undergoing surgical termination of pregnancy between 7 and 12 weeks gestation. In addition, plasma and endometrial samples from 10 patients undergoing hysterectomy for other indications than malignancy were analysed for comparison. The highest tissue concentrations of hPL, AFP and PRL corresponded in each case to the known site of synthesis. For PAPP‐A the highest concentration was found in maternal plasma at term [238·8±75·6 (SEM)μg/ml]. The highest tissue concentration was found at term in the decidua (57·0±2·0 μg/g), more than three times higher than that in the trophoblast (16·9±5·4 μg/g). The concentrations of PAPP‐A in endometrial samples from non‐pregnant women (1·9±0·6 μg/g) was 40 times higher than that in the corresponding plasma samples (0·05±0·02 μg/ml). These observations point to the decidua as a possible source of PAPP‐A.

Endometrial and plasma concentrations of pregnancy‐associated plasma protein‐A (PAPP‐A)

Summary. Pregnancy‐associated plasma protein‐A (PAPP‐A), oestradiol and progesterone levels have been measured by radioimmunoassay in plasma and in endometrial homogenates of 30 women undergoing hysterectomy. Results were grouped according to the histological stages of the endometrium. In plasma, oestradiol and progesterone concentrations changed from proliferative to secretory stages in the well‐established pattern of the menstrual cycle, but PAPP‐A levels did not change. In endometrium, oestradiol levels were high during the proliferative stage and low in inactive and secretory endometrium. Endometrial PAPP‐A and progesterone concentrations increased from inactive to secretory stages, but only the increase in PAPP‐A was statistically significant. A positive correlation observed between endometrial PAPP‐A concentrations and plasma oestradiol/progesterone ratio suggests a possible hormonal control for the presence of PAPP‐A in the uterus.

Pregnancy‐associated plasma protein‐A (PAPP‐A): concentration in uterine fluid and immunohistochemical localization in the endometrium

Summary. Pregnancy‐associated plasma protein‐A (PAPP‐A) was localized immunohistochemically in the endometrium and measured in uterine fluid of non‐pregnant women. The variations of PAPP‐A concentrations in uterine fluid during the menstrual cycle paralleled those found in the endometrium. In patients receiving hormone therapy there was a significant correlation between the uterine fluid PAPP‐A concentration and the progestogen to oestrogen potency ratio of the hormonal treatment. The presence of PAPP‐A in the uterine fluid cannot simply be explained by blood contamination or cell damage. These results are interpreted as indirect evidence for an exocrine as well as an endocrine secretion of PAPP‐A by the endometrium which might be influenced by hormones.

Circulating levels of pregnancy-associated plasma protein-A (PAPP-A) and human chorionic gonadotrophin (hCG) in intrauterine and extrauterine pregnancies.

Summary. Pregnancy‐associated plasma protein‐A (PAPP‐A) and human chorionic gonadotrophin (hCG) have been measured in the plasma of pregnant and non‐pregnant women attending the outpatient clinic for suspicion of pregnancy. The plasma concentrations obtained were grouped into intrauterine or extrauterine pregnancies and compared with values obtained in non‐pregnant patients with similar periods of amenorrhoea. Patients with ectopic pregnancies had slightly lower PAPP‐A levels and significantly lower hCG concentrations than those in women with normal intrauterine pregnancies. Non‐pregnant women had very low hCG and PAPP‐A levels compared with those in pregnant patients. These data suggest that in patients with extrauterine pregnancies the poorly sustained ectopic trophoblast is unable to produce normal concentrations of hCG and probably PAPP‐A and that the slightly diminished levels of PAPP‐A in ectopic pregnancies might be derived from a decidual production.