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In a trial involving girls and women with singleton pregnancies who had a cervical length of 25 mm or less at 20 to 24 weeks of gestation, placement of a cervical pessary did not result in a lower rate of spontaneous early preterm delivery than the rate with expectant management. Preterm birth is responsible for more than 70% of all neonatal and infant deaths. 1 In addition, the risk of cerebral palsy among children born preterm is 10 times as high as that among those born at term. 2 The risks of perinatal death and illness are inversely related to gestational age at delivery. 1 , 3 , 4 The risk of preterm birth is inversely related to cervical length as measured by ultrasonography at midgestation. 5 , 6 Randomized, controlled trials involving women who were pregnant with singletons (singleton pregnancies) and who had a short cervical length have shown that the prophylactic use of progesterone results . . .

Asymptomatic women who have a short cervix at midgestation are at increased risk for spontaneous early preterm delivery. In this randomized trial, women with a short cervix (15 mm or less in length) assigned to treatment with vaginal progesterone had a significantly lower rate of spontaneous delivery before 34 weeks of gestation than did women assigned to placebo. In contrast to another trial published in this issue of the Journal, which showed no reduction in the risk of preterm birth among women with twins treated with 17 alpha-hydroxyprogesterone caproate, this study indicates the efficacy of vaginal progesterone in reducing this risk among women with a short cervix. Women with a short cervix (15 mm or less in length) assigned to treatment with vaginal progesterone had a significantly lower rate of spontaneous delivery before 34 weeks of gestation than did women assigned to placebo. Prematurity is the leading cause of neonatal death and handicap. 1 Although all births before 37 weeks of gestation are defined as preterm, most damage and death occurs in infants delivered before 34 weeks. 2 , 3 Improvements in neonatal care have led to higher rates of survival among very premature infants, but a major effect on the associated mortality and morbidity will be achieved only by better identification of women at high risk for preterm delivery and by development of an effective intervention to prevent this complication. The prophylactic administration of progesterone beginning in midgestation to women who previously had a preterm . . .

Preterm-labour-associated preterm birth is a common cause of perinatal mortality and morbidity in twin pregnancy. We aimed to test the hypothesis that the Arabin pessary would reduce preterm-labour-associated preterm birth by 40% or greater in women with a twin pregnancy and a short cervix. We conducted an open-label randomised controlled trial in 57 hospital antenatal clinics in the UK and Europe. From 1 April 2015 to 14 February 2019, 2,228 women with a twin pregnancy underwent cervical length screening between 18 weeks 0 days and 20 weeks 6 days of gestation. In total, 503 women with cervical length ≤ 35 mm were randomly assigned to pessary in addition to standard care (n = 250, mean age 32.4 years, mean cervical length 29 mm, with pessary inserted in 230 women [92.0%]) or standard care alone (n = 253, mean age 32.7 years, mean cervical length 30 mm). The pessary was inserted before 21 completed weeks of gestation and removed at between 35 and 36 weeks or before birth if earlier. The primary obstetric outcome, spontaneous onset of labour and birth before 34 weeks 0 days of gestation, was present in 46/250 (18.4%) in the pessary group compared to 52/253 (20.6%) following standard care alone (adjusted odds ratio [aOR] 0.87 [95% CI 0.55-1.38], p = 0.54). The primary neonatal outcome-a composite of any of stillbirth, neonatal death, periventricular leukomalacia, early respiratory morbidity, intraventricular haemorrhage, necrotising enterocolitis, or proven sepsis, from birth to 28 days after the expected date of delivery-was present in 67/500 infants (13.4%) in the pessary group compared to 76/506 (15.0%) following standard care alone (aOR 0.86 [95% CI 0.54-1.36], p = 0.50). The positive and negative likelihood ratios of a short cervix (≤35 mm) to predict preterm birth before 34 weeks were 2.14 and 0.83, respectively. A meta-analysis of data from existing publications (4 studies, 313 women) and from STOPPIT-2 indicated that a cervical pessary does not reduce preterm birth before 34 weeks in women with a short cervix (risk ratio 0.74 [95% CI 0.50-1.11], p = 0.15). No women died in either arm of the study; 4.4% of babies in the Arabin pessary group and 5.5% of babies in the standard treatment group died in utero or in the neonatal period (p = 0.53). Study limitations include lack of power to exclude a smaller than 40% reduction in preterm labour associated preterm birth, and to be conclusive about subgroup analyses. These results led us to reject our hypothesis that the Arabin pessary would reduce the risk of the primary outcome by 40%. Smaller treatment effects cannot be ruled out. ISRCTN Registry ISRCTN 02235181. ClinicalTrials.gov NCT02235181.

To determine the relationship between high vaginal pro-inflammatory cytokines and cervical shortening in women at high risk of spontaneous preterm labor and to assess the influence of cervical cerclage and vaginal progesterone on this relationship. This prospective longitudinal observational study assessed 112 women with at least one previous preterm delivery between 16 and 34 weeks' gestation. Transvaginal cervical length was measured and cervico-vaginal fluid sampled every two weeks until 28 weeks. If the cervix shortened (<25 mm) before 24 weeks' gestation, women (cases) were randomly assigned to cerclage or progesterone and sampled weekly. Cytokine concentrations were measured in a subset of cervico-vaginal fluid samples (n = 477 from 78 women) by 11-plex fluid-phase immunoassay. All 11 inflammatory cytokines investigated were detected in cervico-vaginal fluid from women at high risk of preterm birth, irrespective of later cervical shortening. At less than 24 weeks' gestation and prior to intervention, women destined to develop a short cervix (n = 36) exhibited higher cervico-vaginal concentrations than controls (n = 42) of granulocyte-macrophage colony-stimulating factor [(GM-CSF) 16.2 fold increase, confidence interval (CI) 1.8-147; p = 0.01] and monocyte chemotactic protein-1 [(MCP-1) 4.8, CI 1.0-23.0; p = 0.05]. Other cytokines were similar between cases and controls. Progesterone treatment did not suppress cytokine concentrations. Interleukin (IL)-6, IL-8, granulocyte colony-stimulating factor (G-CSF), interferon (IFN)-γ and tumour necrosis factor (TNF)-α concentrations were higher following randomization to cerclage versus progesterone (p<0.05). Cerclage, but not progesterone treatment, was followed by a significant increase in cervical length [mean 11.4 mm, CI 5.0-17.7; p<0.001]. Although GM-CSF and MCP-1 cervico-vaginal fluid concentrations were raised, the majority of cervico-vaginal cytokines did not increase in association with cervical shortening. Progesterone treatment showed no significant anti-inflammation action on cytokine concentrations. Cerclage insertion was associated with an increase in the majority of inflammatory markers and cervical length.

Background Preterm birth is the leading cause of mortality and disability in newborn and infants. Having a short cervix increases the risk of preterm birth, which can be accessed by a transvaginal ultrasound scan during the second trimester. In women with a short cervix, vaginal progesterone and pessary can both reduce this risk, which progesterone more established than cervical pessary. The aim of this study is to compare the use of vaginal progesterone alone versus the association of progesterone plus pessary to prevent preterm birth in women with a short cervix. Methods This is a pragmatic open-label randomized controlled trial that will take place in 17 health facilities in Brazil. Pregnant women will be screened for a short cervix with a transvaginal ultrasound between 18 0/7 until 22 6/7 weeks of gestational age. Women with a cervical length below or equal to 30 mm will be randomized to the combination of progesterone (200 mg) and pessary or progesterone (200 mg) alone until 36 + 0 weeks. The primary outcome will be a composite of neonatal adverse events, to be collected at 10 weeks after birth. The analysis will be by intention to treat. The sample size is 936 women, and a prespecified subgroup analysis is planned for cervical length (= < or > 25 mm). Categorical variables will be expressed as a percentage and continuous variables as mean with standard deviation. Time to delivery will be assessed with Kaplan-Meier analysis and Cox proportional hazard analysis. Discussion I n clinical practice, the combination of progesterone and pessary is common however, few studies have studied this association. The combination of treatment might act in both the biochemical and mechanical routes related to the onset of preterm birth. Trial registration Brazilian Clinical Trial Registry (ReBec) RBR-3t8prz, UTN: U1111–1164-2636 , 2014/11/18.

IntroductionWomen with twin pregnancies and a short cervix are at increased risk for preterm birth (PTB). Given the burden of prematurity and its attendant risks, the quest for effective interventions in twins has been an area of considerable research. Studies investigating the effectiveness of cervical cerclage, cervical pessary and vaginal progesterone in preventing PTB have yielded conflicting results. The aim of this study is to compare the effectiveness of cervical pessary and cervical cerclage with or without vaginal progesterone to prevent PTB in women with twin pregnancies and a cervical length (CL) ≤ 28 mm.Methods and analysisThis multicentre, randomised clinical trial will be conducted at My Duc Hospital and My Duc Phu Nhuan Hospital, Vietnam. Asymptomatic women with twin pregnancies and a CL ≤28 mm, measured at 16–22 weeks’ gestation, will be randomised in a 1:1:1:1 ratio to receive a cerclage, pessary, cerclage plus progesterone or pessary plus progesterone. Primary outcome will be PTB <34 weeks. Secondary outcomes will be maternal and neonatal complications. We preplanned a subgroup analysis according to CL from all women after randomisation and divided into four quartiles. Analysis will be conducted on an intention-to-treat basis. The rate of PTB <34 weeks’ gestation in women with twin pregnancies and a cervix ≤28 mm and treated with pessary in our previous study at My Duc Hospital was 24.2%. A sample size of 340 women will be required to show or refute that cervical cerclage decreases the rate of PTB <34 weeks by 50% compared with pessary (from 24.2% to 12.1%, α level 0.05, power 80%, 5% lost to follow-up and protocol deviation). This study is not to be powered to assess interactions between interventions.Ethics and disseminationEthical approval was obtained from the Institutional Ethics Committee of My Duc Hospital and informed patient consent was obtained before study enrolment. Results of the study will be submitted for publication in a peer-reviewed journal.Trial registration numberNCT03863613 (date of registration: 4 March 2019).

Background Preterm birth is a major cause of neonatal mortality and morbidity. As preventive strategies are largely ineffective, threatened preterm labor is a frequent problem that affects approximately 10 % of pregnancies. In recent years, risk assessment in these women has incorporated cervical length measurement and fetal fibronectin testing, and this has improved the capacity to identify women at increased risk for delivery within 14 days. Despite these improvements, risk for preterm birth continues to be increased in women who did not deliver after an episode of threatened preterm labor, as indicated by a preterm birth rate between 30 to 60 % in this group of women. Currently no effective treatment is available. Studies on maintenance tocolysis and progesterone have shown ambiguous results. The pessary has not been evaluated in women with threatened preterm labor, however studies in asymptomatic women with a short cervix show reduced rates of preterm birth rates as well as perinatal complications. The APOSTEL VI trial aims to assess the effectiveness of a cervical pessary in women who did not deliver within 48 h after an episode of threatened preterm labor. Methods/Design This is a nationwide multicenter open-label randomized clinical trial. Women with a singleton or twin gestation with intact membranes, who were admitted for threatened preterm labor, at a gestational age between 24 and 34 weeks, a cervical length between 15 and 30 mm and a positive fibronectin test or a cervical length below 15 mm, who did not deliver after 48 h will be eligible for inclusion. Women will be allocated to a pessary or no intervention (usual care). Primary outcome is preterm delivery < 37 weeks. Secondary outcomes are amongst others a composite of perinatal morbidity and mortality. Sample size is based on an expected 50 % reduction of preterm birth before 37 weeks (two-sided test, α 0.05 and β 0.2). Two hundred women with a singleton pregnancy need to be randomized. Analysis will be done by intention to treat. Discussion The APOSTEL VI trial will provide evidence whether a pessary is effective in preventing preterm birth in women who did not deliver 48 h after admission for threatened preterm labor and who remain at high risk for preterm birth. Trial registration Trial is registered at the Dutch Trial Register: http://www.trialregister.nl , NTR4210, date of registration: October 16th 2013.

Fetal MRI provides superior tissue contrast and true 3D spatial information however there is only a limited number of MRI studies investigating cervix during pregnancy 1 , 2 – 3 . Furthermore, there are no clearly formalised protocols or automated methods for MRI cervical measurements. This work introduces the first deep learning pipeline for automated multi-layer segmentation and biometry for 3D T2w reconstructed images of the pregnant cervix. Evaluation on 20 datasets from 0.55T and 3T acquisitions showed good performance in comparison to manual measurements. This solution could potentially minimise the need for manual editing, significantly reduce analysis time and address inter- and intra-observer bias. Next, we used the pipeline to process 270 normal term cases from 16 to 40 weeks gestational age (GA) range. The inlet diameter and length showed the strongest correlation with GA which is in agreement with the gradual remodeling and softening of the cervix prior to birth. We also generated 3D population-averaged MRI atlases of the cervix that are publicly available online.

Significance Mammalian females must selectively allow sperm with normal morphology and motility to ascend the reproductive tract while rejecting invasion of pathogens. By using microfluidic modeling, we revealed that microgrooves and gentle fluid flows, two major biophysical characteristics of the female tract, synergistically provide preferential pathways for sperm. In contrast, the sexually transmitted pathogen, Tritrichomonas foetus , is swept away from these pathways. These findings are not only valuable to dairy and beef industries for maximizing fertility and suppressing disease, but also to human medicine, because the morphology and movement of bull sperm closely resemble those of human sperm, and T. foetus closely resembles Trichomonas vaginalis , which infects 170 million people annually worldwide. Successful mammalian reproduction requires that sperm migrate through a long and convoluted female reproductive tract before reaching oocytes. For many years, fertility studies have focused on biochemical and physiological requirements of sperm. Here we show that the biophysical environment of the female reproductive tract critically guides sperm migration, while at the same time preventing the invasion of sexually transmitted pathogens. Using a microfluidic model, we demonstrate that a gentle fluid flow and microgrooves, typically found in the female reproductive tract, synergistically facilitate bull sperm migration toward the site of fertilization. In contrast, a flagellated sexually transmitted bovine pathogen, Tritrichomonas foetus , is swept downstream under the same conditions. We attribute the differential ability of sperm and T. foetus to swim against flow to the distinct motility types of sperm and T. foetus ; specifically, sperm swim using a posterior flagellum and are near-surface swimmers, whereas T. foetus swims primarily via three anterior flagella and demonstrates much lower attraction to surfaces. This work highlights the importance of biophysical cues within the female reproductive tract in the reproductive process and provides insight into coevolution of males and females to promote fertilization while suppressing infection. Furthermore, the results provide previously unidentified directions for the development of in vitro fertilization devices and contraceptives.

Since the first publications about surgery for cervical cancer, many radical procedures that accord with different degrees of radicality have been described and done. Here, we propose a basis for a new and simple classification for cervical-cancer surgery, taking into account the curative effect of surgery and adverse effects, such as bladder dysfunction. The international anatomical nomenclature is used where it applies. For simplification, the classification is based only on lateral extent of resection. We describe four types of radical hysterectomy (A–D), adding when necessary a few subtypes that consider nerve preservation and paracervical lymphadenectomy. Lymph-node dissection is considered separately: four levels (1–4) are defined according to corresponding arterial anatomy and radicality of the procedure. The classification applies to fertility-sparing surgery, and can be adapted to open, vaginal, laparoscopic, or robotic surgery. In the future, internationally standardised description of techniques for communication, comparison, clinical research, and quality control will be a basic part of every surgical procedure.