Myometrial contractile strain at uteroplacental separation during parturition

OBJECTIVE: A simplified geometric model of the uterine wall during the second and third stages of labor was created to estimate the magnitude of myometrial strain associated with the initiation of placental separation. STUDY DESIGN: The uterine wall was modeled as an isovolumetric, incompressible spherical shell whose overall radius decreased and mural thickness increased on uterine muscle contraction after delivery of the fetus. Either a 3.5-MHz or a 5-MHz ultrasonography probe was used to measure the change in uterine mural thickness of 14 healthy patients from just before delivery to the time of initial separation of the placenta. The measured change in uterine wall thickness was then used to calculate its average radial and circumferential strain with a simple mathematic model. RESULTS: Placental separation occurred at radial and circumferential strains (mean +/- SD) of 450% +/- 182% and -75% +/- 11%, respectively. These strains are consistent with the known maximal contractile strains achievable by smooth muscle. CONCLUSION: Placental separation is likely associated with maximal myometrial contractile strain. Before birth the presence of the fetal and amniotic fluid volumes usually renders such contractile strains unachievable, thereby helping to guard against premature placental separation.     

Phospholipases in the control of human parturition

Prostaglandins play a key role in human labor in that prostaglandins can cause abortion or labor and prostaglandin antagonists can inhibit preterm labor. However, the factors determining prostaglandin synthesis and release in human pregnancy are uncertain. An increase in the synthesis of prostaglandins at the start of labor could result from either increased release of free arachidonic acid or removal of constraint on prostaglandin H synthase activity, or both. The points in the biosynthetic pathway of prostaglandins at which control could be exerted physiologically are examined, with emphasis on the phospholipases.     

A possible role for progesterone metabolites in human parturition

There has been a recent resurgence of interest in the role of progesterone in the maintenance of human pregnancy and the onset of labour, following recent reports of its use to prevent preterm labour in high-risk patients. One possible mechanism by which progesterone might contribute to uterine quiescence is through the actions of its metabolites. This article provides a brief overview of progesterone in human pregnancy and an outline of progesterone metabolism in the various reproductive tract tissues as well as the evidence for actions of progesterone metabolites in pregnancy.     

Myometrial response to prostaglandins enhanced by progesterone

The effect of estrogen and progesterone on prostaglandin-induced uterine contractions was studied in ovariectomized rats fitted with intrauterine recording balloons. The effects of the three prostaglandins, PGE₁, PGE₂, and PGF_2α, injected intravenously were very similar. Pretreatment with estradiol benzoate (1 μg per rat per day) resulted in a considerable reduction of the contractile response to the prostaglandins and was frequently associated with tachyphylactic reactions. Progesterone pretreatment (5 mg. per rat per day), on the other hand, markedly increased the uterine response to prostaglandins and no tachyphylaxis was observed. Intact pregnant rats were studied at mid-gestation; the uterine response in these rats was similar to the response in progesterone-treated rats.     

Differential regulation of the progesterone receptor A and B in the human uterine cervix at parturition.

The concept of a blockade of progesterone during human pregnancy and withdrawal of this blockade at parturition remains controversial There is no sharp fall in serum progesterone before parturition, but treatment with an antiprogestin is successful for labor induction at term pregnancy. The human progesterone receptor (PR) exists in two isoforms (PR-A and PR-B), mediating different biological responses. Here, the hypothesis of a progesterone withdrawal at parturition in terms of a change in PR isoforms was tested. Cervical biopsies were obtained at term before the onset of labor, immediately after parturition and from non-pregnant women. Solution hybridization showed a tendency for the PR mRNA level to be decreased at parturition. Immunohistochemistry displayed decreased PR(A + B) and PR-B levels (p < 0.05) immediately after parturition. The relative importance of PR-A seemed higher immediately after parturition as compared to its importance in non-pregnant and term pregnant women. Our results are consistent with the concept of a functional progesterone blockade at the receptor level at term pregnancy, and withdrawal of this blockade at parturition. These observations may have important clinical and therapeutic implications.     

The control of parturition

A chart showing the principal maternal and fetal mechanisms which may control the onset of parturition is presented. Many factors influence the contractive activity of the uterus. These factors are discussed and include autonomic motor innervation, estrogens, external environment, fetal stress, ACTH and corticosteroids, mechanical stimulation, oxytocin, progesterone, and prostaglandins. Authorities are without agreement as to the relative importance of these factors to the determination of the time of onset of labor. The crucial triggering mechanism could differ between species, between individuals of a species and on successive occasions in the same individual. Some feel 1 particular mechanism is crucial, others support a balance between factors. Parturition is described as a "cascade phenomenon" in which a number of positive feedback mechanisms act together to maintain and carry the process through to completion. The stages of parturition are listed. Molecular structure of crucial steroids are presented. Graphs display the duration of pregnancy according to maternal weight for a variety of species and in a primiparous group of women. Circulating estrogen and progesterone levels in maternal plasma and placental weights during pregnancy in women and sheep are depicted.     

Evidence for a local change in the progesterone/estrogen ratio in human parturition at term

The purpose of this study was to determine if a local change in the concentrations of estrogen and progesterone occurs in the amniotic fluid during human parturition at term. Amniotic fluid was retrieved from 20 women in active labor and from 20 women not in labor. Patients were matched for maternal age and gestational age. Estradiol, estriol, progesterone, and dehydroepiandrosterone sulfate were measured in amniotic fluid by radioimmunoassay. For women in active labor, the median concentrations (range) of these steroid hormones were 2.4 ng/ml (1 to 9.2 ng/ml), 1661.2 ng/ml (556.6 to 3928.1 ng/ml), 12.3 ng/ml (4.7 to 41.4 ng/ml), and 187.5 ng/ml (61.2 to 470 ng/ml), respectively. The median concentrations (range) for women not in labor were 1.6 ng/ml (0.3 to 5.7 ng/ml), 684.2 ng/ml (70.6 to 2103.1 ng/ml), 13.2 ng/ml (7.5 to 63 ng/ml), and 65.6 ng/ml (20 to 334 ng/ml), respectively. Thus spontaneous human parturition at term was associated with significantly increased amniotic fluid concentrations of estradiol, estriol, and dehydroepiandrosterone sulfate (p = 0.02, p = 0.002, p = 0.003, respectively). The progesterone/estrogen ratios (progesterone/estradiol and progesterone/estriol) were significantly lower for women in active labor compared with those not in labor (p = 0.002 and p = 0.0006, respectively). We conclude that a local change in the progesterone/estrogen ratio occurs during human parturition at term.     

Myometrial thickness during human labor and immediately post partum

OBJECTIVE: Morphologic studies suggest dramatic, asymmetric uterine growth during pregnancy that is caused by muscle cell hypertrophy. This growth is most marked at the fundus. Our objective was to evaluate sonographically the in vivo changes in myometrial thickness during active labor, second-stage labor, and after delivery. STUDY DESIGN: Abdominal ultrasound scans were performed on 52 term pregnant women to investigate the dynamic changes in myometrial thickness during the active and second stages of labor and immediately after delivery. Twenty-six women (mean +/- SEM gestational age, 39.09 +/- 0.3 weeks) were in active labor (cervical dilatation >4 cm with regular uterine contractions). An additional 26 nonlaboring women (gestational age, 39.8 +/- 0.2 weeks) provided control measurements. The myometrium was defined sonographically as the echo homogeneous layer between the serosa and the decidua. Myometrial thickness was measured at the low segment and mid anterior, fundal, and posterior uterine walls by the same observer. Myometrial thickness was also measured during uterine contractions and after artificial rupture of the amniotic membranes. All laboring women had uncomplicated labor patterns when studied and were delivered spontaneously. RESULTS: The myometrium was significantly thinner during active labor compared with nonlabor at each site studied: midanterior (mean [+/-SEM] myometrial thickness, 5.8 +/- 0.27 vs 8.83 +/- 0.51 mm; t test, P <.001), fundus (mean myometrial thickness, 6.78 +/- 0.32 vs 8.49 +/- 0.35 mm; P =.0015), and posterior (mean myometrial thickness, 6.22 +/- 0.34 vs 8.12 +/- 0.30 mm; P <.001). However, myometrial thickness did not differ among sites within the two groups. The thickness of the low segment was not affected by labor status (nonlabor, 4.68 +/- 0.48 vs labor, 4.66 +/- 0.37 mm; P =.97). Similarly, the myometrial thickness of the anterior uterine wall was unaffected by contractions (no contractions, 5.56 +/- 0.2 vs contractions, 5.68 +/- 0.22 mm; t test, P =.654). There was no change in myometrial thickness measured immediately before and after rupture of the amniotic membranes, despite a significant decrease of the amniotic fluid index. There was significant thickening of the anterior and fundal myometrium during the second stage of labor after the fetal head descended to +3 station by digital examination (anterior, 12.99 +/- 0.60 vs 5.8 +/- 0.27 mm; t test, P <.001; fundus, 10.61 +/- 1.63 vs 6.78 +/- 0.32 mm; t test, P =.04). Valsalva maneuver (pushing) during contractions did not affect myometrial thickness at the fundus (between contractions, 10.61 +/- 1.63 vs pushing, 10.76 +/- 1.95 mm; t test, P =.99). Immediately after delivery, the myometrial thickness at the placental insertion site was the thinnest. After completion of the third stage of labor, the uterine fundus remained significantly thinner than the anterior and posterior walls (fundus, 27.37 +/- 3.5 mm vs anterior, 40.94 +/- 3.5 vs posterior, 42.34 +/- 2.44; one-way analysis of variance, P =.02). CONCLUSION: There is significant and widespread thinning of the myometrium during active labor. Descent of the fetal head during the second stage of labor is associated with a significant relative thickening of the anterior and fundal myometrium. After delivery, the relationship reverses. These findings suggest the directionality of the expulsive force vectors (fundal dominance) is not determined by asymmetric myometrial growth but, rather, may be a function of increased "myometrial mass" that results from increased surface area at the fundus.     

The onset of human parturition

Background  

Despite impressive progress in the science and technology of reproduction, the mechanism by which labour is initiated in humans remains obscure.     

Plasma oxytocin in human pregnancy and parturition

Oxytocin concentrations were determined in serial peripheral plasma samples collected from clinically normal women during pregnancy and labor. Measurable concentrations of this hormone were detected in all maternal plasma samples during pregnancy, but there were wide differences in values between patients. Serial samples from individual patients revealed a pattern of gradual rise of oxytocin levels with advancing gestation and the increase in concentration was statistically significant. There were no significant differences in oxytocin levels at any stage of labor, with or without epidural analgesia. Oxytocin levels at the onset of the second stage did not differ statistically from those at crowning. Comparison of cross-sectional data showed no significant difference between the mean oxytocin concentration in early labor and in late pregnancy. Oxytocin surges occurred, but not in a regular pattern. Plasma oxytocin concentration did not increase after pelvic examination, sweeping of the membranes, low amniotomy or after cervical vibration. After spontaneous vaginal delivery, umbilical arterial plasma levels of oxytocin were consistently higher than plasma concentrations from the umbilical vein. The fetal arterio-venous difference was less pronounced at elective cesarean section. At spontaneous vaginal delivery, with and without epidural anesthesia, plasma levels from the umbilical artery were significantly higher than the maternal levels. After vaginal delivery, oxytocin levels in cord plasma were significantly higher than at elective abdominal delivery. Some methodological aspects with regard to blood sampling and to plasma oxytocin radioimmunoassay procedures are discussed. From the results presented it is concluded that the human fetus can be an important source of oxytocin and that neurohumoral birth reflexes described in animals do not occur systematically in man.