Use Of Vaginal Progesterone Research Articles

Routine Transvaginal Ultrasound at the Time of the Anatomy Scan: To Do or Not To Do?

There are no universal guidelines for transvaginal ultrasound (TVUS) at the time of the anatomy scan. TVUS can provide information on placental location and cervical length (CL) but may lead to more interventions. As a quality assurance initiative, a universal TVUS (UTVUS) protocol at the time of the anatomy scan was started at our institution. This study was conducted to assess whether there was a decrease in preterm birth (PTB), postpartum hemorrhage (PPH), and neonatal intensive care unit (NICU) admission once UTVUS was implemented. This was a retrospective cohort study performed on singleton gestations from February 2021 to January 2022. In the first 6 months of the study period, patients only had TVUS based on risk factors (pre group). In the second half of the study period, UTVUS was implemented at the time of the anatomy scan (post group). A total of 2,118 patients were included in the study. There were 1,037 patients in the pre group, of which 161 underwent TVUS based on high-risk factors (history of the cervical procedure, history of prior PTB, and placenta appearing low lying or cervix appearing short on abdominal ultrasound). The post group/UTVUS included 1,081 patients. Patients in the pre group had statistically significantly earlier gestational age at first TVUS (p < 0.0001), were less likely to have had a prior PTB <36 weeks (p = 0.03), and were more likely to have a history of cervical procedure (p = 0.0006) than patients in the post group. There was an increased use of vaginal progesterone in the UTVUS with 33 patients (as opposed to 10 patients in the pre group; p = 0.0007). The proportion of patients with PTB, PPH, or NICU admission did not significantly differ between the two groups even after adjusting for cofounders (p > 0.05). Our data show that UTVUS did not decrease the adverse pregnancy outcomes. In addition, the implementation of UTVUS adds more discomfort for a patient, more time to the patient's scan, and is an additional cost. Therefore, surveillance by abdominal ultrasound and adding TVUS based on risk factors may be a reasonable alternative. · UTVUS showed no difference between CLs.. · There is not sufficient evidence to conclude a difference between PTB or PPH in the two groups.. · There was significantly more placenta previa diagnosed in the post group, yet most resolved..

Introduction of universal transvaginal cervical length measurement does not decrease spontaneous preterm delivery rate compared to universal transabdominal screening with reflex cut‐off: A pre‐post study

AbstractObjectivesThe objective of our study is to examine cervical length measurements, identification of short cervix, vaginal progesterone use, and rate of spontaneous preterm delivery before and after departmental transition to a universal transvaginal ultrasound screening protocol from a universal transabdominal screening protocol.MethodsThis is a retrospective observational pre–post study examining the year prior to and year following a transition to a universal transvaginal ultrasound screening protocol to assess cervical length at the time of the anatomy survey. Prior to this transition, universal transabdominal cervical length screening was performed, with reflex transvaginal ultrasound measurement if transabdominal measurement was &lt;35 mm or was unable to be obtained.ResultsA total of 1760 charts were reviewed; 962 charts were from the pre‐transition/transabdominal year and 798 charts were from the post‐transition/transvaginal year. In the post‐transition/transvaginal year, cervical length less than 20 mm was identified in 1.5% of cases, compared to 0.7% of cases in the pre‐transition/transabdominal year (p = 0.114). There was no difference in the rate of spontaneous preterm delivery between the two groups (5.1% in the pre‐transition/transabdominal year vs. 6.9% in the post‐transition/transvaginal year; p = 0.111).ConclusionsIn this pre‐post study, introduction of a universal transvaginal cervical length screening did not decrease spontaneous preterm delivery rates or detection of short cervix &lt;20 mm, compared to a protocol of universal transabdominal cervical length screening with reflex to transvaginal for measurement &lt;35 mm.

Screening and prevention of preterm birth: how is it done in clinical practice?

To ascertain how screening for preterm birth is performed among obstetricians working in public and private practice in a middle-income country. Cross-sectional study of 265 obstetrician-gynecologists employed at public and private facilities. An online questionnaire was administered, with items designed to collect data on prematurity screening and prevention practices. The mean age of respondents was 44.5 years; 78.5% were female, and 97.7% had completed a medical residency program. Universal screening (i.e., by ultrasound measurement of cervical length) was carried out by only 11.3% of respondents in public practice; 43% request transvaginal ultrasound if the manual exam is abnormal, and 74.6% request it in pregnant women with risk factors for preterm birth. Conversely, 60.7% of respondents in private practice performed universal screening. This difference in screening practices between public and private practice was highly significant (p < 0.001). Nearly all respondents (90.6%) reported prescribing vaginal progesterone for short cervix. In the setting of this study, universal ultrasound screening to prevent preterm birth was used by just over half of doctors in private practice. In public facilities, screening was even less common. Use of vaginal progesterone in cervical shortening was highly prevalent. There is an unmet need for formal protocols for screening and prevention of preterm birth in middle-income settings.

Role Of Low Dose Aspirin In Preventing Preterm Birth In Patients With Previous History Of Preterm Delivery

Objective: Preterm birth (PTB) occurs between 24-37 weeks of gestation. The important risk factor for PTB is a previous PTB and currently progesterone is used for the management of recurrent spontaneous PTB. Some studies have shown good outcomes but recent studies revealed that the use of vaginal progesterone was not related to a decreased likelihood of PTB or neonatal adverse effects. Thus, the controversy in the literature suggests multiple underlying pathological mechanisms involved in the progression of PTB. This study aims to determine the role of low-dose aspirin in the prevention of preterm birth in patients with a previous history of preterm delivery. Methodology: In this randomized controlled trial, a total of 172 patients fulfilling the inclusion criteria were selected from the inpatient and outpatient departments. Patients were divided randomly into two groups (group A and group B), using random number tables. In Group A, low-dose aspirin (75mg) was given while group B was taken as a control group. Patients were called every 8 weeks in the outpatient department for the assessment of compliance and side effects of the drug. The data were entered and analyzed by using SPSS v25.0. Chi-square was used to compare the two groups for incidence of preterm birth. Relative risk (along with a 95% confidence interval) for the decrease in the incidence of preterm birth with the use of aspirin was calculated. Results: The age of participants included in the study was 18 to 40 years. The mean age of patients in group A was 33.85±5.210 years and in group B was 32.86±4.139 years. The mean fetal birth weight in group A was 2281.1962±363.125 grams and in group B was 2271.4344±374.797 grams. In the low-dose aspirin group, 10(11.6%) had preterm birth and 31(36.0%) in the control group with a p-value of 0.001, which is statistically significant. The risk of having preterm birth with low-dose aspirin was 1.801 times less than controls. Conclusion: aspirin in low dose given before 14 weeks of gestation decrease spontaneous preterm birth as compared to the control group in a woman with a history of previous preterm birth which was spontaneous

Cervical Pessary for Prevention of Preterm Birth in Individuals With a Short Cervix

A short cervix as assessed by transvaginal ultrasound is an established risk factor for preterm birth. Study findings for a cervical pessary to prevent preterm delivery in singleton pregnancies with transvaginal ultrasound evidence of a short cervix have been conflicting. To determine if cervical pessary placement decreases the risk of preterm birth or fetal death prior to 37 weeks among individuals with a short cervix. We performed a multicenter, randomized, unmasked trial comparing a cervical pessary vs usual care from February 2017 through November 5, 2021, at 12 centers in the US. Study participants were nonlaboring individuals with a singleton pregnancy and a transvaginal ultrasound cervical length of 20 mm or less at gestations of 16 weeks 0 days through 23 weeks 6 days. Individuals with a prior spontaneous preterm birth were excluded. Participants were randomized 1:1 to receive either a cervical pessary placed by a trained clinician (n = 280) or usual care (n = 264). Use of vaginal progesterone was at the discretion of treating clinicians. The primary outcome was delivery or fetal death prior to 37 weeks. A total of 544 participants (64%) of a planned sample size of 850 were enrolled in the study (mean age, 29.5 years [SD, 6 years]). Following the third interim analysis, study recruitment was stopped due to concern for fetal or neonatal/infant death as well as for futility. Baseline characteristics were balanced between participants randomized to pessary and those randomized to usual care; 98.9% received vaginal progesterone. In an as-randomized analysis, the primary outcome occurred in 127 participants (45.5%) randomized to pessary and 127 (45.6%) randomized to usual care (relative risk, 1.00; 95% CI, 0.83-1.20). Fetal or neonatal/infant death occurred in 13.3% of those randomized to receive a pessary and in 6.8% of those randomized to receive usual care (relative risk, 1.94; 95% CI, 1.13-3.32). Cervical pessary in nonlaboring individuals with a singleton gestation and with a cervical length of 20 mm or less did not decrease the risk of preterm birth and was associated with a higher rate of fetal or neonatal/infant mortality. ClinicalTrials.gov Identifier: NCT02901626.

P-752 Cervical cerclage versus vaginal progesterone in the prevention of preterm birth in singleton pregnancies among women with a short cervical length: A retrospective cohort study

Abstract Study question To compare the maternal and neonatal effects of cervical cerclage and vaginal progesterone in preventing singleton preterm births in women with a short cervical length. Summary answer Cervical cerclage showed no benefit in preventing preterm birth; however, it prolonged gestation by 39 days compared to vaginal progesterone treatment. What is known already Clinically, there may be a bias toward the choice of cervical cerclage if the cervix is short (&amp;lt;10 mm) and, similarly, toward vaginal progesterone use if the cervix is long (&amp;gt;30 mm). However, there are no clear treatment guidelines for the best options for singleton pregnant women with a CL between 10 and 30 mm. Furthermore, there is insufficient evidence to determine whether one treatment is superior to the other in preventing PTB and decreasing adverse neonatal outcomes in singleton pregnancies in such cases. Study design, size, duration Asymptomatic pregnant women having singleton pregnancies, with a CL between 10 and 30 mm, measured using transvaginal ultrasound at 12–26 weeks of gestation, who delivered at our hospital between January 2009 and August 2020, were included in our study. Based on the inclusion and exclusion criteria, 267 singleton pregnant women, of whom 116 were treated with cervical cerclage and 151 with vaginal progesterone, were finally included. Participants/materials, setting, methods Independent sample t-tests and differential analysis were used to analyze the data based on their distribution. The Cox semi-parametric regression model was used to analyze the gestation weeks at delivery and neonatal outcomes. The decision regarding cesarean delivery was based on a binary logistic regression model. Main results and the role of chance In the initial analysis, the number of preterm births was significantly higher in the cerclage group than in the vaginal progesterone group; however, after multivariate adjustment for confounding factors, the latency period from diagnosis to delivery was found to be significantly prolonged in the cerclage group. Limitations, reasons for caution There are currently no uniform criteria for determining whether study subjects are eligible for cervical cerclage or vaginal progesterone treatment, which may present some cases of noncompliance. Wider implications of the findings In our study, we found that cervical cerclage did not have significant advantages over vaginal progesterone treatment in preventing PTB. However, upon adjustment for confounding factors, it was shown to prolong the gestational age by 39 days compared to vaginal progesterone treatment. Trial registration number non-clinical trials

Changes in use of 17-OHPC after the PROLONG trial: a physician survey.

To determine if 17α-hydroxyprogesterone caproate (17OHPC) or vaginal progesterone use for patients at risk for preterm birth has changed since the publication of the 17-OHPC to Prevent Recurrent Preterm Birth in Singleton Gestations (PROLONG) trial, and to assess which organizations' (Food and Drug Administration's [FDA], American College of Obstetrics and Gynecology's [ACOG] or Society of Maternal Fetal Medicine's [SMFM]) statements most influenced change. Through a vignette-based physician survey, we sought to measure (by Likert scale) how counseling tendencies regarding 17OHPC and vaginal progesterone have changed since the PROLONG trial publication. Participants were also asked which organizations' statements most influenced change. With response rate of 97 % (141/145), a pre-to-post PROLONG trial comparison revealed significant changes in counseling for progesterone. Respondents were less likely to recommend 17OHPC (p<0.001) and more likely to recommend vaginal (p<0.001). The FDA statement most influenced the decision not to recommend 17OHPC for the prevention of preterm birth (r=-0.23, p=0.005). Providers have made significant changes in their counseling regarding progesterone use for patients at risk for preterm birth after the publication of the PRLONG trial.

Universal Transvaginal Ultrasounds: Does It Really Make a Difference? [ID: 1369458

INTRODUCTION: There are no universal guidelines for transvaginal ultrasound (TVUS) at time of anatomy scan. TVUS can provide valuable information on placental location and cervical length (CL). As a quality assurance initiative, universal TVUS (UTVUS) protocol was started. The aim of this study was to evaluate differences in diagnoses and interventions in the 6 months prior to UTVUS protocol to 6 months after implementation. METHODS: This was an institutional review board-approved retrospective cohort study performed on singleton gestations from February 2021 to January 2022. The pre-group underwent TVUS for history of preterm birth, if the cervix appeared short or if the placenta appeared low lying on transabdominal scan. In the post-group, all patients underwent TVUS. RESULTS: Of the 1,197 patients, 148 underwent TVUS in the pre-group and 1,049 received UTVUS in the post-group. A greater proportion of patients had short CL identified in the post-group compared to the pre-group (2.2% versus 0.9%, P&lt;.01). Additionally, CL was shorter in the post-group compared to the pre-group (median 1.6 versus 2.2 cm, P=.03). A greater proportion of patients in the post-group received vaginal progesterone (3.1% versus 0.7%, P&lt;.01) and cerclage (2.3% versus 0.7%, P&lt;.01) compared to those in the pre-group, and had a later gestational age at cerclage placement (median 17 weeks 2 days versus 13 weeks 6 days, P=.04). Patients in the pre-group had a higher rate of prior preterm birth (P&lt;.01), delivered at an earlier gestational age (P&lt;.01), and were more likely to have neonatal intensive care unit admission compared to patients in the post-group (P=.02). The overall preterm birth rate in both time periods was not significantly different (11.4% versus 11.2%, P=.82). CONCLUSION: UTVUS identifies shorter CL, which leads to increased use of vaginal progesterone and cerclage as compared to abdominal ultrasound with targeted TVUS. UTVUS may lead to increased intervention. However, the cost-effectiveness and clinical significance need to be further evaluated.

Society for Maternal-Fetal Medicine Statement: Response to the Food and Drug Administration’s withdrawal of 17-alpha hydroxyprogesterone caproate

On April 5, 2023, the US Food and Drug Administration withdrew the approval of 17-alpha hydroxyprogesterone caproate, effective immediately, because of the lack of evidence that it reduces the risk of recurrent spontaneous preterm birth. This decision withdraws approval for all formulations of 17-alpha hydroxyprogesterone caproate (both intramuscular and subcutaneous) and applies to both brand name (Makena) and generic versions of the medication. We agree with the Food and Drug Administration determination and discourage continued prescribing of 17-alpha hydroxyprogesterone caproate, including through compounding pharmacies. We do not recommend changing indications for cerclage, indications for vaginal progesterone in patients with a short cervix, or recommendations against activity restriction based on the Food and Drug Administration withdrawal of 17-alpha hydroxyprogesterone caproate from the market. We recommend that discussion of the use of vaginal progesterone for primary prevention of recurrent preterm birth without input of cervical length or in those with a cervical length of ≥25 mm includes a shared decision-making process, especially if a progesterone formulation for preterm birth prevention was received in a previous pregnancy. The Food and Drug Administration determined that it would be inappropriate to delay the effective date of the withdrawal to allow patients currently receiving 17-alpha hydroxyprogesterone caproate to finish treatment. We agree with the Food and Drug Administration that there is no evidence of benefit with continued treatment. Patients currently receiving 17-alpha hydroxyprogesterone caproate can be counseled that the Food and Drug Administration's Center for Drug Evaluation and Research has not identified evidence of harm from discontinuation before 37 weeks of gestation.

Association of Vaginal Progesterone Treatment With Prevention of Recurrent Preterm Birth

Association of Vaginal Progesterone Treatment With Prevention of Recurrent Preterm Birth

The role of isthmic-cervical insufficiency in miscarriage

Cervical insufficiency (CI) is one of the main pathological conditions that leads to pregnancy loss, in particular, recurrence miscarriages and premature births, which account for up to 5 % of all obstetric cases. Recurrence pregnancy losses caused by CI lead to serious psychological trauma for both the woman and her family members, as well as significant economic losses for the society. However, many women in some regions of the world still do not know about this pathology, and clinicians do not always diagnose this condition in time.At the same time, etiology of CI remains uncertain, and there are still ambiguous points regarding the diagnosis of this pathology and its treatment. The diagnosis of CI should be established by analyzing the medical history, clinical manifestations and results of ultrasound examination. Treatment of CI mainly includes surgical and conservative methods. Surgical treatment is performed with cervical cerclage, while conservative techniques mainly include the use of vaginal progesterone and insertion of various types cervical pessaries. This article summarizes the potential risk factors associated with cervical insufficiency that are of great attention and may be useful for future researches. Also, the review of the literature considers modern methods of diagnosis and treatment of CI to understand this pathology of the cervix better. From a modern standpoint, a consensus and problematic issues are presented in accordance with the recently updated recommendations, which are of practical importance, and are also important for further deeper research on this topical issue of modern obstetrics.

Management of an incompetent mid-second (mid-2nd) trimester absent ecto-cervix: a case series. Cervical amplification pre-cerclage insertion.

Cervical cerclage is a treatment for an incompetent cervix, the latter being a contributor to spontaneous preterm birth. There is significant difficulty with a transvaginal cerclage insertion for the absent vaginal or ecto-cervix in the mid-2nd trimester period resulting in a higher risk of late miscarriages, extremely preterm labour with increased neonatal morbidity and mortality. A retrospective review of 5 consecutive cases managed by a surgical technique-modified high vaginal cerclage insertion at 18-20 weeks-and adjunct protocols which included vaginal progesterone use, serial infection screening and lifestyle advice, over a 12-month period ending in August 2021, is presented. Inclusion criteria included minimal or absent ecto-cervix, singleton pregnancies with an incompetent cervix attending for a vaginal cerclage whilst exclusion criteria were the usual contraindications to a cerclage insertion. Primary outcome was delivery after 34 weeks whilst seconday outcomes included maternal hemorrhage, bowel/bladder injury, chorioamnionitis and neonatal admission. A increased gestational latency of 13 gestational weeks (range 12-18). Mean gestational age at delivery was 36 weeks +1 (253 days) with a range of 241-264 days. Delivery after 34 weeks gestational age was 100% with no maternal surgical complications and corresponding neonatal outcomes. There is a potential therapeutic benefit of this technique and adjunct management, in managing an incompetent mid-2nd trimester absent ecto-cervix.

Early Initiation and Long-Term Use of Vaginal Progesterone may Cause Gestational Diabetes Mellitus.

Preterm birth (PTB) is an important cause of neonatal mortality and morbidity. Spontaneous PTB (sPTB) is the most common cause of PTB. In patients with a singleton pregnancy, progesterone treatment appears to reduce the rate of spontaneous preterm birth in those with a previous history of spontaneous preterm labor and/or cervical shortening in the current pregnancy. Progesterone therapies used for the prevention of sPTB may increase the risk of gestational diabetes mellitus (GDM) towards the end of pregnancy owing to their effects on carbohydrate metabolism. We aimed to show the effects of vaginal progesterone use, starting time, and duration of treatment on GDM. A retrospective cohort study was carried out in pregnant women 18 to 39 years old who came to our hospital between January 1, 2021, and August 31, 2021, and who had a 2-hour 75-g oral glucose tolerance test (OGTT) at 24 to 28 weeks of gestation. In a total of 540 patients, 68 were diagnosed with GDM based on at least one abnormal plasma glucose value at screening. The remaining 472 patients with normal plasma glucose levels were considered as the control group. The groups were compared in terms of age, parity, pre-pregnancy body mass index (BMI), smoking, gestational age, and vaginal progesterone use. Patients using vaginal progesterone with and without GDM were then compared again in terms of indications for vaginal progesterone use, initiation time of progesterone therapy, duration of progesterone use, and cervical length. The incidence of GDM in our study group was 12.5%. Despite the use of vaginal progesterone at a higher rate in the GDM group than in the control group (23.5 vs. 13.9%; p=0.07), it was not statistically significant. When we examined patients using progesterone as a subgroup analysis, the mean time to start vaginal progesterone treatment was 19.8±2.6 (14-24), and it was significantly earlier in the GDM group (18.1±2.0 vs. 20.2±2.6; p=0.007). Initiation of vaginal progesterone before 20 weeks of gestation was statistically significantly more frequent in the GDM group than the control group (68.8 vs. 39.4%; p=0.050 OR :3.3, 95%CI: 1.0-10.8). The mean duration of vaginal progesterone use was 50.0±15.6 days (28-90) and it was longer in the GDM group (57.8±13.4 vs. 48.1±15.6; p=0.027). Since the duration of vaginal progesterone use will be prolonged, there may be a risk of GDM, especially in patients who started vaginal progesterone before the 20th week of pregnancy. Even if the OGTT test performed between 24-28 weeks is normal, it should be kept in mind that these patients may have GDM in the later weeks of pregnancy, and repeating the OGTT test should be considered if necessary.

Effectiveness of Vaginal Progesterone for Short Cervix Diagnosed Between 24 and 28 Weeks of Gestation

Vaginal progesterone is widely accepted as a treatment option to prevent preterm delivery (PTD) in patients diagnosed with short cervix before 24 weeks. While many advocate for cervical length measurement up to 28 weeks in patients at risk for PTD, there is no evidence regarding the use of vaginal progesterone in this setting. The goal of this study is to determine the effectiveness of vaginal progesterone for the prevention of PTD in patients diagnosed with short cervix between 24 & 28 weeks.

A Comparison of Vaginal and Intramuscular Progesterone for the Prevention of Recurrent Preterm Birth.

This study aimed to examine whether vaginal progesterone is noninferior to 17-α hydroxyprogesterone caproate (17OHP-C) in the prevention of recurrent preterm birth (PTB). This retrospective cohort study included singleton pregnancies among women with a history of spontaneous PTB who received prenatal care at a single tertiary center from 2011 to 2016. Pregnancies were excluded if progesterone was not initiated prior to 24 weeks or the fetus had a major congenital anomaly. The primary outcome was PTB <37 weeks. A priori, noninferiority was to be established if the upper bound of the adjusted two-sided 90% confidence interval (CI) for the difference in PTB fell below 9%. Inverse probability of treatment weighting (IPTW) was used to carefully control for confounding associated with choice of treatment and PTB. Adjusted differences in PTB proportions were estimated via IPTW regression, with standard errors adjustment for multiple pregnancies per woman. Secondary outcomes included PTB <34 and <28 weeks, spontaneous PTB, neonatal intensive care unit admission, and gestational age at delivery. Among 858 pregnancies, 41% (n = 353) received vaginal progesterone and 59% (n = 505) were given 17OHP-C. Vaginal progesterone use was more common later in the study period, and among women who established prenatal care later, had prior PTBs at later gestational ages, and whose race/ethnicity was neither non-Hispanic white nor non-Hispanic Black. Vaginal progesterone did not meet noninferiority criteria compared with 17-OHPC in examining PTB <37 weeks, with an IPTW adjusted difference of 3.4% (90% CI: -3.5, 10.3). For secondary outcomes, IPTW adjusted differences between treatment groups were generally small and CIs were wide. We could not conclude noninferiority of vaginal progesterone to 17OHP-C; however, women and providers may be willing to accept a larger difference (>9%) when considering the cost and availability of vaginal progesterone versus 17OHP-C. A well-designed randomized trial is needed. · Vaginal progesterone is not noninferior to 17OHP-C.. · PTB risk may be 10% higher with vaginal progesterone.. · Associations did not differ based on obesity status..

Vaginal progesterone for preterm birth prevention in women with arrested preterm labor

Objective We tested the hypothesis that administration of vaginal progesterone in women with arrested preterm labor would result in lower rates of preterm birth <37 weeks compared to placebo. Study design We performed a randomized, placebo-controlled trial comparing vaginal progesterone to placebo in women with arrested preterm labor. Our trial included women with a singleton or twin gestation at 240 /7–336/7 weeks’ gestation who presented with preterm labor with cervical dilation ≥1 centimeter but remained undelivered. Participants were randomized to receive vaginal progesterone 200 mg daily or an identical placebo. The primary outcome was preterm birth <37 weeks. We performed an updated systematic review and meta-analysis of clinical trials, including our results. We searched MEDLINE, EMBASE, CINHAL, Scopus, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov using the key terms to identify relevant trials. The risk of bias was appraised using the Cochrane risk-of-bias tool. Data were synthesized using random-effects models. Heterogeneity was assessed using Higgins I 2. Results The randomized trial was prematurely terminated due to slow recruitment. There were 18 women randomized to receive vaginal progesterone who had complete follow-up data and 18 women in the placebo group. The risk of preterm birth <37 weeks was not significantly different in the groups (RR 1.10, 95% CI 0.63–1.19). Secondary outcomes were also similar. Thirteen trials with 1658 women (835 in the vaginal progesterone and 823 in the control groups) were included in the meta-analysis. Risk of preterm birth <37 weeks was similar in women who received progesterone and those in the control group (pooled RR 1.06, 95% CI 0.83–1.35). Latency was significantly longer among women with arrested preterm labor who received vaginal progesterone (weighted mean difference: 9.2 d, 95% CI 3.2–15.1), but further analysis showed that prolonged latency was only observed in the subgroup of studies that were not placebo-controlled. Conclusions This randomized controlled trial and meta-analysis do not support the use of vaginal progesterone for the prevention of preterm birth in women who present in preterm labor.

The status of fetal autonomic nervous regulation in women with «short cervix» syndrome

The objective: was to investigate the coefficients of acceleration capacity (AC) and deceleration capacity (DC) in women with «short cervix» syndrome.Materials and methods. A total of 292 pregnant women were examined. They were divided into several groups according to the results of the study of cervical length and methods of prevention of premature birth. Group I included women with normal cervicometry data. In other groups there were women with a «short cevix». In group II, there were women who underwent cerclage. In group III – used a pessary; Group IV – prescribed intravaginal progesterone; V – used cerclage and pessary; and in VI – cerclage and progesterone vaginally.Results. The level of preterm births was 2.1%, 10.9%, 8.9%, 9.3%, 6.9% and 7.5% in women of groups I, II, III, IV, V and VI, respectively (p&lt;0.05 by criterion χ2 compared with women with normal cervical length).The values of AC/DC at 26 weeks were low and did not differ by groups. Subsequently, the values of AC/DC in women with cervical shortening were equal to the control only in groups III and VI. The fact that women who received vaginal progesterone as monotherapy or additionally to cervical cerclage significantly reduced the relative risk of fetal distress is of great interest. Thus, the normalization of AC/DC in pregnant women with «short cervix» syndrome under the influence of progesterone reflected the development of nervous regulation, which contributed the reduction the level of fetal distress.Conclusions. In patients with «short cervix» syndrome, there was a decrease in the level of AC/DC, which reflected the deterioration of the processes of autonomic nervous regulation of fetal hemodynamics. This captured the increased level of fetal distress. The use of vaginal progesterone contributed to normalize AC/DC and reduce the relative risk of fetal distress.

Use of cervical elastography at 18 to 22 weeks’ gestation in the prediction of spontaneous preterm birth

Accurate identification of the women who will have spontaneous preterm birth continues to be a great challenge. The use of cervical elastography for prediction of preterm birth is promising, but several limitations exist. Newer cervical elastography technology has been developed that may prove useful in evaluation of risk of preterm birth. This study aimed to develop standard cervical elastography nomograms for singleton pregnancies at 18 to 22 weeks' gestation using the E-Cervix ultrasound application, assess intraobserver reliability of the E-Cervix elastography parameters, and determine whether these cervical elastography measurements can be used in the prediction of spontaneous preterm birth. This was a prospective cohort study of pregnant women undergoing cervical length screening assessment via transvaginal ultrasound examination at 18 to 22 weeks' gestation. A semiautomatic, cervical elastography application (E-Cervix) was used during the transvaginal examination to calculate 5 quantitative parameters (internal os stiffness, external os stiffness, internal -to -external os stiffness ratio, hardness ratio, and elasticity contrast index) and create a standard nomogram for each one of them. The intraobserver reliability was calculated using Shrout-Fleiss reliability. Cervical elastography parameters were compared between those who delivered preterm (<37 weeks) spontaneously and those who delivered full term. A multivariable logistic regression model was performed to determine the ability of the cervical elastography parameters to predict spontaneous preterm birth. A total of 742 women were included, of which 49 (6.6%) had a spontaneous preterm delivery. A standard nomogram was created for each of the cervical elastography parameters from those who had a full-term birth in the index pregnancy (n=693). Intraobserver reliability was good or excellent (intraclass correlation, 0.757-0.887) for each of the cervical elastography parameters except external os stiffness which was poor (intraclass correlation, 0.441). In univariate analysis, none of the cervical elastography parameters were associated with a statistically significant increased risk of spontaneous preterm birth. In a multivariable model adjusting for history of preterm birth, gravidity, ethnicity, cervical cerclage, and vaginal progesterone use, increasing elasticity contrast index was significantly associated with an increased risk of spontaneous preterm birth (odds ratio, 1.15; 95% confidence interval, 1.02-1.30; P=.02). Cervical elastography parameters are reliably measured and are stable across 18 to 22 weeks' gestation. Based on our findings, the elasticity contrast index was associated with an increased risk of spontaneous preterm birth and may be a useful parameter for future research.

Vaginal progesterone for prevention of preterm birth in asymptomatic high-risk women with a normal cervical length: a systematic review and meta-analysis protocol

BackgroundPreterm birth (PTB) is estimated to affect 14.9 million babies globally every year. Global rates of PTB continue to increase from 9.8 to 10.6% over a 15-year period from 2000 to 2014. Vaginal progesterone is commonly used by clinicians as a prevention strategy, with recent evidence affirming the benefit of vaginal (micronised) progesterone to prevent PTB in women with a shortened cervix (< 25 mm). Given the low incidence of a short cervix at mid-gestation in high-risk populations further evidence is required. The objective of this review is to determine if vaginal progesterone reduces spontaneous preterm birth (sPTB) before 37 weeks in asymptomatic high-risk women with a singleton pregnancy with a normal mid-gestation cervical length.MethodsStudies will be sourced from MEDLINE, Embase and Cochrane Register of Trials (CENTRAL) from their inception onwards with the search terms ‘progesterone’ and ‘preterm birth’. Studies will be screened and included if they assess vaginal progesterone compared to placebo in women with a normal cervical length. The primary outcome will be sPTB < 37 weeks, with secondary outcomes of sPTB < 34 weeks.Two independent reviewers will conduct study screening at abstract and full text level, data extraction and risk of bias assessment with disagreements resolved by an experienced researcher. The Mantel-Haenszel statistical method and random effects analysis model will be used to produce treatment effect odds ratios and corresponding 95% confidence intervals.DiscussionThis review will assess the current body of evidence and provide clarity regarding the potential benefits and best practice of use of vaginal progesterone in asymptomatic women with high-risk singleton pregnancies and normal cervical length.Trial registrationPROSPERO CRD42020152051

Utilization of hydroxyprogesterone caproate among pregnancies with live birth deliveries in the sentinel distributed database

Background The U.S. Food and Drug Administration (FDA) approved Makena® (hydroxyprogesterone caproate [HPC] injection) in February 2011 for reducing the risk of preterm birth (PTB) in women with a singleton pregnancy who had a history of singleton spontaneous PTB (sPTB). Makena was approved under accelerated approval and required a postmarketing study to verify its clinical benefits. However, the postmarketing trial (PROLONG) failed to verify Makena’s clinical benefit to neonates and substantiate its effect on reducing the risk of recurrent PTB. This study examined the utilization of HPC, along with another progestogen (vaginal progesterone) used to reduce the risk of sPTB during pregnancy, to inform the landscape of HPC use in the United States. Methods We included pregnant women aged 10–54 years with a live birth delivery from 1 January, 2008 to 31 December, 2018 in the Sentinel Distributed Database (SDD). We examined the prevalence of injectable HPC (Makena and its generics), compounded HPC, and vaginal progesterone use during the second and third trimesters during the study period. We also assessed the proportion of these HPC-exposed pregnancies with obstetrical conditions of interest as potential reasons for use: (1) history of preterm delivery; (2) cervical shortening in the current pregnancy; and (3) preterm labor in the current pregnancy. Results We identified a total of 3,445,739 live-birth pregnancies (among 2.9 million women) between 2008 and 2018 in the SDD. Of these pregnancies, 6.5 per 1,000 pregnancies used injectable HPC, 2.3 per 1,000 pregnancies used compounded HPC, and 1.5 per 1,000 pregnancies used vaginal progesterone during the second and/or third trimesters. The yearly uptakeof pregnancies with injectable HPC use increased during the study period from 2.1 per 1,000 pregnancies in 2012 to 12.6 per 1,000 pregnancies in 2018; use of compounded HPC decreased from 3.3 per 1,000 pregnancies to 0.25 per 1,000 pregnancies over the same period. Of 16,524 pregnancies with injectable HPC use, 12,054 (73%) had at least one related obstetrical condition, including 6,439 (39%) with a recorded history of preterm delivery. In addition, 4,665 (28%) had a PTB recorded as the outcome for the current pregnancy. Conclusions We found modest use of HPC during the second and/or third trimesters among all live-birth pregnancies in SDD. The majority of pregnancies with injectable HPC use had at least one of three obstetrical indications of interest recorded before or during the pregnancy.