Screening vs no screening for preterm delivery in low risk singleton pregnancies

Introduction: To compare the effect of a policy of screening for spontaneous preterm delivery (SPD) by transvaginal cervical length (CL) measurement versus a no screening policy in the prevention of severe prematurity. Methods: Retrospective study on low risk singleton pregnancies examined at 20-24 weeks. Two cohorts one with SPD screening and the other without screening were matched using propensity analysis to create the study groups. Women with short CL were treated with vaginal progesterone and/or cervical cerclage/pessary. The outcomes examined were SPD<32 weeks (SPD 32) and SPD between 20 and 32 weeks (SPD 20-32). Results: Screening for SPD was associated with a significant reduction in the rate of SPD at less than 32 weeks (0.3% vs 0.8%, p=0.001 in the screened and no screened pregnancies respectively) and in the rate of SPD 20-32 (0.3% vs 0.9%, p=0.005 in the screened and no screened pregnancies respectively). After adjusting for maternal age, parity, body mass index, smoking and mode of conception, the screening group had significantly lower hazard for SPD 20-32 (HR=0.36, 95% CI: 0.18-0.75, p=0.006) and SPD32 (HR=0.39, 95% CI: 0.19-0.82, p=0.013). Conclusion: Screening for SPD by transvaginal CL measurement in mid pregnancy may reduce the incidence of severe prematurity in low risk singleton pregnancies.

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

Objective To examine whether vaginal progesterone is noninferior to 17-α hydroxyprogesterone caproate (17OHP-C) in the prevention of recurrent preterm birth (PTB). Study Design 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. Results 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. Conclusion 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. Key Points

Implantation Failures and Miscarriages in Frozen Embryo Transfers Timed in Hormone Replacement Cycles (HRT): A Narrative Review

The recent advent of embryo vitrification and its remarkable efficacy has focused interest on the quality of hormone administration for priming frozen embryo transfers (FETs). Products available for progesterone administration have only been tested in fresh assisted reproduction technologies (ARTs) and not in FET. Recently, there have been numerous concordant reports pointing at the inefficacy of vaginal preparations at delivering sufficient progesterone levels in a sizable fraction of FET patients. The options available for coping with these shortcomings of vaginal progesterone include (i) rescue options with the addition of injectable subcutaneous (SC) progesterone at the dose of 25 mg/day administered either solely to women whose circulating progesterone is <10 ng/mL or to all in a combo option and (ii) the exclusive administration of SC progesterone at the dose of 25 mg BID. The wider use of segmented ART accompanied with FET forces hormone replacement regimens used for priming endometrial receptivity to be adjusted in order to optimize ART outcomes.

“PREGNANCY OUTCOME IN CERVICAL INCOMPETENCE: COMPARISON OF COMBINED USE OF CERCLAGE AND ORAL PROGESTERONE VERSES HIGH DOSE OF VAGINAL PROGESTERONE”

INTRODUCTION- Cervical insufciency, earlier known as cervical incompetence, is the inability of the cervix to maintain pregnancy till term due to structural or functional defects. Approximately 16.25% of second-trimester pregnancy losses and 2% of premature deliveries are due to cervical incompetence. OBJECTIVE- The purpose of this study was to compare the outcome of pregnancy in patients who underwent early (12-16 weeks) cervical cerclage along with oral progesterone supplementation versus those having remedied with high dose intravaginal progesterone supplementation. MATERIAL AND METHODst This retrospective study was conducted in a maternity hospital in Gwalior from 1 January 2018 to th 30 June 2021. Comprehensive history, thorough clinical examination, laboratory investigations, ultrasonography measurement of cervical length, mode of delivery, gestational age at the time of delivery, neonatal outcome, NICU admission, and other parameters were collected from the medical les. patients were divided into two groups. Ÿ Group 1(N-49) – Those who were remedied with high-dose vaginal progesterone supplementation continued uptil 34 wks of gestation. Group 2 (N-49) – Those who underwent Mc Donald type of cervical encerclage at 12-16 weeks along with oral progesterone (10 mg Duphaston twice daily dose) supplementation continued up till 34 weeks of gestation. RESULT- In our study, in the cervical cerclage group, only (4.1%) patients were delivered before 34 weeks while in the vaginal progesterone group (18.4%) patients were delivered before 34 weeks. In the cervical cerclage group (53.1%) patients were delivered between 34-37 weeks while in the vaginal progesterone group, (44.9%) of the patient delivered between 34-37 weeks. In the cervical cerclage group, the cesarean section rate was lower than only the vaginal progesterone group and admission to NICU of babies was also less (22.4%) in this group in comparison to the vaginal progesterone only group (36.7%). CONCLUSION- Our study showed that cervical cerclage plus oral progesterone supplementation in women with extremely shortened cervix signicantly decreased overall spontaneous preterm birth rates, prolonged pregnancy latency, and decreased the overall neonatal morbidity and mortality and is more effective than the vaginal progesterone group.

Co-administration of GnRH agonists with vaginal progesterone compared to vaginal progesterone in luteal phase support of the frozen-thawed embryo transfer cycle: An RCT

Background: Since progesterone alone does not seem to be enough for luteal phase support (LPS), especially in frozen embryo transfer (FET) cycles, so gonadotropin-releasing hormone agonist (GnRH-a) is suggested as an adjuvant therapy in combination with progesterone for LPS. Objective: To evaluate the effects of the administration of GnRH agonists with vaginal progesterone compared to vaginal progesterone alone in luteal phase support of the frozen-thawed embryo transfer cycles. Materials and Methods: In this randomized controlled clinical trial, 240 infertile women who were candidates for FET were evaluated into two groups (n = 120/each). Group I received 400 mg vaginal progesterone twice a day from the time of transfer. The second group received vaginal progesterone and also 0.1 mg diphereline on days 0, 3, and 6 of FET for LPS. Finally, the clinical and ongoing pregnancy rates, and the implantation, and spontaneous abortion rates were compared in two groups. Results: Results showed that there was no significant difference between the mean age of women and the duration of infertility (p = 0.78, p = 0.58, respectively). There were no significant differences between groups in the terms of implantation and spontaneous abortion rates (p = 0.19, p = 0.31, respectively). However, in terms of clinical and ongoing pregnancy rates, the significant differences were seen between groups (p = 0.008 and p = 0.005, respectively). Conclusion: Co-administration of GnRH-a and vaginal progesterone in LPS may be superior to vaginal progesterone alone in women who underwent a frozen-selected embryo transfer cycle. Key words: Luteal phase, Fertilization in vitro, Embryo transfer.

Reviewing short cervix in singleton pregnancies: a multicentric prospective cohort study in the Brazilian population

Objective: To identify the association between cervical length (CL) and gestational age at birth. Design: Prospective cohort study. Setting: Seventeen Brazilian reference hospitals. Population: A cohort of 3139 asymptomatic singleton pregnant women who participated in the screening phase of a Brazilian multicenter randomized controlled trial (P5 trial). Methods: Transvaginal ultrasound (TVU) to measure CL was performed from 18 to 22+6 weeks. Women with CL ≤ 30 mm received vaginal progesterone (200 mg/day) until 36 weeks’ gestation. Main Outcome Measures: Area under receive operating characteristic curve (AUC), sensitivity, specificity, Kaplan-Meier curves for preterm birth (PTB), number needed to screen (NNS). Results: CL ≤25mm was associated with extremely severe, severe, moderate and late PTB, whereas a CL 25–30mm was directly associated with late sPTB. The AUC to predict sPTB<28 weeks was 0.82 and for sPTB<34 weeks was 0.67. Almost half of the sPTB occurred in nulliparous women and CL ≤30mm was associated with sPTB <37 weeks (OR = 7.84; 95%CI = 5.5–11.1). The NNS to detect one sPTB <34 weeks in women with CL ≤25mm is 121 and 248 screening tests are necessary to prevent one sPTB <34 weeks using vaginal progesterone prophylaxis. Conclusions: CL measured by TVU is associated with sPTB <34 weeks. Women with CL ≤30mm are at increased risk for late sPTB. Funding: Bill & Melinda Gates Foundation [OPP1107597], the Brazilian Ministry of Health, and the Brazilian National Council for Scientific and Technological Development (CNPq) [401615/20138]. Keywords: cervical length; number needed to screen; preterm birth; short cervix.