Uterine contractile activity in healthy women throughout the menstrual cycle measured using a novel quantitative two-dimensional transvaginal ultrasound speckle tracking method.

RESEARCH QUESTION: To explore normal uterine contractile function across the menstrual cycle using a novel quantitative ultrasound method. DESIGN: This multicentre prospective observational study took place in three European centres from 2014 to 2022. Uterine contraction frequency (contractions/minute), amplitude, direction (cervix-to-fundus, C2F; fundus-to-cervix; F2C), velocity and coordination were investigated. Features were extracted from transvaginal ultrasound recordings (TVUS) using speckle tracking. Premenopausal women ≥18 years of age, with normal, natural menstrual cycles were included. A normal cycle was defined as: regular (duration 28 ± 2 days), no dysmenorrhoea, no menometrorrhagia. Four-minute TVUS were performed during the menstrual phase, mid-follicular, late follicular phase, early luteal phase and/or late luteal phase. Of the 96 recordings available from 64 women, 70 were suitable for inclusion in the analysis. RESULTS: Contraction frequency (for the posterior wall) and velocity (for the anterior uterine wall in the F2C direction) were highest in the late follicular phase and lowest in the menstrual and late luteal phases (1.61 versus 1.31 and 1.35 contractions/min, P < 0.001 and 0.81 versus 0.67 and 0.62 mm/s, P < 0.001, respectively). No significant difference was found for contraction amplitude. Contraction coordination (simultaneous contraction of the anterior and posterior walls in the same direction) was least coordinated in the mid-follicular phase (P = 0.002). CONCLUSIONS: This is the first study to objectively measure uterine contraction features in healthy women during the natural menstrual cycle on TVUS. Likewise, it introduces contraction coordination as a specific feature of uterine peristalsis. Differences in uterine contractility across the menstrual cycle are confirmed, with highest activity seen in the late follicular phase, and lowest in the late luteal phase.

Assessment of uterine activity during IVF by quantitative ultrasound imaging: a pilot study.

RESEARCH QUESTION: Does uterine activity differ in patients who have undergone successful IVF treatment compared with patients who have undergone unsuccessful IVF treatment? DESIGN: Prospective study of 16 women who underwent fresh single embryo transfer. All patients underwent transvaginal ultrasound in three phases of the IVF treatment: ovarian stimulation 1 h before embryo transfer (ET1) and 5-7 days after embryo transfer (ET5-7). Uterine motion analysis was implemented by a dedicated speckle tracking algorithm; frequency- and amplitude-related features were extracted from the derived signals to characterize the uterine activity in relation to ongoing implantation (positive HCG after 6 weeks) and ongoing pregnancy at 11 weeks. RESULTS: Uterine activity in terms of frequency (ovarian stimulation ET1, P = 0.04; ovarian stimulation ET5-7, P = 0.002) and amplitude (ovarian stimulation ET1, P = 0.0003; ovarian stimulation ET5-7, P = 0.000008) is significantly higher in the ovarian stimulation phase compared with ET1 and ET5-7. Women with ongoing pregnancies showed significantly higher uterine contraction frequency compared with those with no ongoing pregnancies in all phases (ovarian stimulation, P = 0.006; ET1, P = 0.015; ET5-7, P = 0.007). Uterine contraction amplitude was significantly lower (P = 0.037) in women at ET5-7 in women with ongoing pregnancies. CONCLUSIONS: This study is a first step towards assessing uterine activity during IVF objectively and non-invasively. It is an essential step to understanding the previously suggested effect of contractions on IVF failure. Uterine activity after embryo transfer characterized by high frequency and low amplitude may favour embryo implantation. Research with larger patient cohorts is needed to build on current evidence and knowledge of uterine contractions during IVF.

Propagation of spontaneous electrical activity in the ex vivo human uterus.

Contractions of the non-pregnant uterus play a key role in fertility. Yet, the electrophysiology underlying these contractions is poorly understood. In this paper, we investigate the presence of uterine electrical activity and characterize its propagation in unstimulated ex vivo human uteri. Multichannel electrohysterographic measurements were performed in five freshly resected human uteri starting immediately after hysterectomy. Using an electrode grid externally and an electrode array internally, measurements were performed up to 24 h after hysterectomy and compared with control. Up to 2 h after hysterectomy, we measured biopotentials in all included uteri. The median root mean squared (RMS) values of the external measurements ranged between 3.95 µV (interquartile range (IQR) 2.41-14.18 µV) and 39.4 µV (interquartile range (IQR) 10.84-105.64 µV) and were all significantly higher than control (median RMS of 1.69 µV, IQR 1.13-3.11 µV), consisting of chicken breast meat. The RMS values decreased significantly over time. After 24 h, the median RMS (1.27 µV, IQR 0.86-3.04 µV) was comparable with the control (1.69 µV, IQR 1.13-3.11 µV, p = 0.125). The internal measurements showed a comparable pattern over time, but overall lower amplitude. The measured biopotentials propagated over the uterine surface, following both a plane-wave as well as an erratic pattern. No clear pacemaker location nor a preferred propagation direction could be identified. These results show that ex vivo uteri can spontaneously generate propagating biopotentials and provide novel insight contributing to improving our understanding of the electrophysiology of the human non-pregnant uterus.

Dedicated Ultrasound Speckle Tracking for Quantitative Analysis of Uterine Motion Outside Pregnancy.

Fertility problems are nowadays being paralleled by important advances in assisted reproductive technologies. Yet the success rate of these technologies remains low. There is evidence that fertilization outcome is affected by uterine motion, but solutions for quantitative analysis of uterine motion are lacking. This work proposes a dedicated method for uterine-motion quantification by B-mode transvaginal ultrasound. Motion analysis is implemented by speckle tracking based on block matching after speckle-size regularization. Sum of absolute differences is the adopted matching metrics. Prior to the analysis, dedicated singular value decomposition (SVD) filtering is implemented to enhance the uterine motion over noise, clutter, and uncorrelated motion induced by neighboring organs and probe movements. SVD and block matching are first optimized by a dedicated ex vivo setup. Robustness to noise and speckle decorrelation is improved by median filtering of the tracking coordinates from surrounding blocks. Speckle tracking is further accelerated by a diamond search. The method feasibility was tested in vivo with a longitudinal study on nine women, aimed at discriminating between four selected phases of the menstrual cycle known to show different uterine behavior. Each woman was scanned in each phase for 4 min; four sites on the uterine fundus were tracked over time to extract strain and distance signals along the longitudinal and transversal directions of the uterus. Several features were extracted from these signals. Among these features, median frequency and contraction frequency showed significant differences between active and quiet phases. These promising results motivate toward an extended validation in the context of fertilization procedures.

Machine learning for classification of uterine activity outside pregnancy.

The objective of this study was to investigate the use of classification methods by a machine-learning approach for discriminating the uterine activity during the four phases of the menstrual cycle. Four different classifiers, including support vector machine (SVM), K-nearest neighbors (KNN), Gaussian mixture model (GMM) and naïve Bayes are here proposed. A set of amplitude- and frequency-features were extracted from signals measured by two different quantitative and noninvasive methods, such as electrohysterography and ultrasound speckle tracking. The proposed classifiers were trained using all possible feature combinations. The method was applied on a database (24 measurements) collected in different phases of the menstrual cycle, comprising uterine active and quiescent phases. The SVM classifier showed the best performance for discrimination between the different menstrual phases. The classification accuracy, sensitivity, and specificity were 90%, 79%, 93%, respectively. Similar methods can in the future contribute to the diagnosis of infertility or other common uterine diseases such as endometriosis.

Feasibility of Transabdominal Electrohysterography for Analysis of Uterine Activity in Nonpregnant Women.

PURPOSE: Uterine activity plays a key role in reproduction, and altered patterns of uterine contractility have been associated with important physiopathological conditions, such as subfertility, dysmenorrhea, and endometriosis. However, there is currently no method to objectively quantify uterine contractility outside pregnancy without interfering with the spontaneous contraction pattern. Transabdominal electrohysterography has great potential as a clinical tool to characterize noninvasively uterine activity, but results of this technique in nonpregnant women are poorly documented. The purpose of this study is to investigate the feasibility of transabdominal electrohysterography in nonpregnant women. METHODS: Longitudinal measurements were performed on 22 healthy women in 4 representative phases of the menstrual cycle. Twelve electrohysterogram-based indicators previously validated in pregnancy have been estimated and compared in the 4 phases of the cycle. Using the Tukey honest significance test, significant differences were defined for P values below .05. RESULTS: Half of the selected electrohysterogram-based indicators showed significant differences between menses and at least 1 of the other 3 phases, that is the luteal phase. CONCLUSION: Our results suggest transabdominal electrohysterography to be feasible for analysis of uterine activity in nonpregnant women. Due to the lack of a golden standard, this feasibility study is indirectly validated based on physiological observations. However, these promising results motivate further research aiming at evaluating electrohysterography as a method to improve understanding and management of dysfunctions (possibly) related to altered uterine contractility, such as infertility, endometriosis, and dysmenorrhea.

Uterine peristalsis and fertility: current knowledge and future perspectives: a review and meta-analysis.

Although uterine contractions in the non-pregnant uterus have been studied extensively, the knowledge gained has not been used in general fertility treatment work-up. In this review paper, we provide an overview of the current knowledge on uterine peristalsis (UP), based on the available literature. This literature shows that UP influences pregnancy chances in both natural and artificial cycles. Although the physiological background of these contractions is not completely clear, we know that several factors can be of influence, like uterine pathologies and hormones. Several options to alter pregnancy outcome by interfering with uterine contractions have been studied. Our meta-analysis on therapeutic options shows positive results of progesterone at time of embryo transfer in IVF cycles or prostaglandins at time of intrauterine insemination, although the quality of evidence is low. These therapies are probably most beneficial in selected groups of patients with abnormal contraction patterns. The introduction of an objective and user-friendly UP measuring tool suitable for use in daily practice would make it possible to identify and monitor these patients. We suggest that future research should focus on the physiology of initiation of UP and on the development of an effective standard measuring tool.

Analysis of uterine activity in nonpregnant women by electrohysterography: A feasibility study.

With an overall effectiveness below 30%, in vitro fertilization (IVF) is in urgent need for improvements, especially in view of the increasing trend in postponing childbirth in developed societies. Abnormal contraction of the uterus may underlie impaired fertility and unsuccessful IVF. However, currently, there is no method for quantitative assessment of uterine activity and guidance of dedicated intervention. Analysis of the electrohysterogram (EHG) has been extensively used in pregnancy for quantifying uterine contractions. In this paper, we evaluate, for the first time, the use of EHG analysis for characterizing contractions in women in two different phases of the menstrual cycle, when the uterus is expected to be active and quiescent. In this preliminary study, by estimating the time evolution of the EHG signal energy, we derive the contraction frequency, fC, as a possible marker for quantifying the activity of the uterus and discriminate between active and quiescent status. Ultrasound (US) image sequences are simultaneously recorded and visually analyzed for a qualitative validation of the results. The high correlation (0.91) between fC obtained by EHG and US analysis and the measured different values of fC in the two phases motivate further research to confirm the value of EHG analysis for contraction quantification in nonpregnant women.