Contractile properties of multiple pregnancy myometrium

Multiple pregnancies are associated with higher rates of perinatal mortality than singleton pregnancies. This is due to the higher rates of preterm delivery and its associated complications. However it is not understood why there is a difference in gestation and what mechanism is responsible for this. This thesis explores the possible different myometrial properties between multiple pregnancies and singletons, and the effect of progesterone on the uterine contractility by placing myometrial strips onto a force transducer, which recorded the trace reflecting the contractility of the strip. In a physiological saline solution there were no significant differences between the myometrial contractility properties of multiple pregnancies and singletons. The effect of progesterone showed a dose response relationship in singleton and twin myometrium as when incremental doses of progesterone were applied, greater amounts of reduction in force was exhibited. It was found that there were significant differences between twin and singleton myometrium at 10, 100μM progesterone with there being a significantly greater effect in singleton myometrium. This reduced effect in twins may explain why there was no effect found to prevent preterm birth in twins (Norman et al 2008), and suggests that a higher dose may have more beneficial in twins A possible explanation for this difference in non genomic action could be due to the greater quantities of stretch applied to twin myometrium earlier on in pregnancy, and this reducing the expression of the progesterone membrane receptor. This possible theory was explored by applied stretch on myometrial strips in 100μM progesterone. Although the paired stretched samples displayed a smaller response to progesterone, this was however not significant. Preterm delivery could also be affected by the maternal diet, as poor maternal nutrition leads to poor intrauterine growth, and is more likely to be preterm. A literature search was performed for studies that focused on maternal nutrition, and weight gain. It was found that early weight gain was associated with larger birthweights, and that total weight gain should be directed by maternal Body Mass Index (BMI), however much work is still required to explore how much weight gain is required, due to successful varying suggestions. It became apparent that when dietary supports (e.g. dieticians) were used, there were smaller rates of preterm delivery and preterm birth. Yet it was hard to clarify if this success was down to the dietary interventions or the content of the diet itself. This work has shown that twin and singleton myometrium respond differently to progesterone which plays a key role in uterine quiescence. This difference in response maybe the underlying trigger for preterm labor and that to improve the rates of preterm delivery we also need to think about the mother’s diet as well

A comparison of the contractile properties of myometrium from singleton and twin pregnancies.

OBJECTIVE: Over half of twin pregnancies in US and UK deliver prematurely but the reasons for this are unclear. The contractility of myometrium from twin pregnancies has not been directly investigated. The objective of this research was to determine if there are differences in the contractile activity and response to oxytocin, between myometrium from singleton and twin pregnancies, across a range of gestational ages. Furthermore, we wished to determine if contractile activity correlates with increasing level of stretch, using neonatal birth weights as a marker of uterine stretch. METHODS: This was an in vitro, laboratory based study of myometrial contractility in women pregnant with one or two babies, using biopsies obtained from non-labouring women undergoing Caesarean section. Spontaneous, oxytocin-stimulated and depolarization induced contractile activity was compared. RESULTS: Direct measurements of myometrial contractility under controlled conditions show that the frequency of contractions and responses to oxytocin are significantly increased in twins compared to singletons. The duration of contraction however was significantly reduced. We find that contractile activity correlates with increasing levels of stretch, using neonatal birth weights as a surrogate for uterine stretch, with response to oxytocin being significantly positively correlated with birth weight. CONCLUSIONS: We have found significant differences in contractile properties between myometrium from singleton and twin pregnancies and that increasing uterine stretch can alter the contractile properties of myometrium. We discuss the implication of these findings to preterm delivery and future studies

Contractile activity in human myometrium from singleton and twin pregnancy.

<p>Representative traces of spontaneous contractile activity of myometrium from singleton and twin pregnancies followed by (<b>A</b>) 2 min application of 40 mM KCl (K⁺) to depolarise the myometrium and (<b>B</b>) 20 min application of 10 nM oxytocin. In (A) contraction amplitude under high K was assigned 100%. The mean amplitude of control activity was then expressed as a percentage of high K and compared between groups. In (B), response to oxytocin was compared between singleton and twin samples by measuring the percentage increase in force amplitude of contraction under oxytocin where control activity equalled 100%.</p

Comparison of the contractile properties between myometrium from singleton and twin pregnancies.

<p>Data are represented by medians (IQR). * represents a significant difference (<i>P</i><0.05) found by Mann Whitney U test (ns  =  not significant). High K is 40 mM to depolarize the myometrium. Contraction frequency measured over at least 4 contractions. OT; oxytocin, 10 nM.</p

Maternal characteristics of women with singleton and twin pregnancy.

<p>Data is represented by means (± S.E.M.) or frequencies (counts, n and percentages).</p>*<p>denotes significant difference (<i>P</i><0.05) by unpaired t-test, or Chi Square (χ²) test (ns  =  not significant).</p

Comparison of the contractile properties of myometrium from singleton and twin myometrium according to gestational age group.

<p>Data are represented by medians (IQR) * represents a significant difference (<i>P</i><0.05) found by Mann Whitney U-test (ns  =  not significant). High K is 40 mM to depolarize the myometrium. Contraction frequency measured over at least 4 contractions. OT; oxytocin, 10 nM.</p

Evaluation and Outcomes of Women with a Breast Lump and a Normal Mammogram Result

BACKGROUND: Many women experience a breast lump. Clinical guidelines suggest that a normal mammogram result alone is not adequate to exclude a diagnosis of cancer. OBJECTIVE: To examine the characteristics of women with a breast lump and a normal mammogram that were associated with receiving further evaluation, and to examine cancer outcomes. DESIGN: Observational cohort. PARTICIPANTS: Women aged 35 to 70 years who participated in a population-based mammography registry and who did not have a history of breast cancer noted at the time of their mammogram that they had a breast lump, and had a “normal” (Breast Imaging Reporting and Data System 1 or 2) mammogram result (n=771). MEASUREMENTS: Telephone survey performed 6 months after the mammogram to ascertain information about evaluation. Cancer outcomes within 12 months of the index mammogram were confirmed through linkage with a cancer registry. RESULTS: Only 56.9% of women reported receiving an adequate evaluation for their breast lump, including a subsequent clinical breast exam, a visit to a breast specialist, an ultrasound, a biopsy, or aspiration. Latinas were less likely than white women to have received adequate evaluation, as were obese women compared with normal-weight women, and uninsured women compared with women with insurance. Among women with at least 12 months of follow-up, 1.4% were diagnosed with cancer. CONCLUSIONS: Many women do not receive adequate evaluation for a recent breast lump. Interventions should be designed to improve the follow-up of women with this common clinical problem