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AIMS: Preterm labor is a severe problem after fetoscopic laser surgery (FLS), which often requires multiple tocolytic agents. We investigated the utility of indomethacin as a tocolytic agent after FLS. METHODS: This study included monochorionic diamniotic twin pregnancies who underwent FLS for twin-to-twin transfusion syndrome at our hospital from 2015 to 2023. Medical records of all cases were reviewed retrospectively. Since indomethacin has been used routinely since 2020, all cases were divided into the control group (without indomethacin) and IND group (with indomethacin). Indomethacin was administered until 48 h postoperatively. This study was approved by the ethics committee of our hospital, and written informed consent for indomethacin use was obtained from all patients. RESULTS: Fifty-seven patients were in the IND group and 97 were in the control group. No fetal adverse effects were observed in the IND group. Median gestational age at delivery did not differ between the groups (p = 0.670). pPROM within 14 days after FLS occurred more frequently in the control group (8.2%) than in the IND group (0%) (p = 0.022). The IND group had a shorter median duration of magnesium sulfate use (3 days [2-12]) than the control group (8 days [2-81]) (p < 0.001), and less frequent use of nifedipine (42% vs. 80%, p < 0.001). CONCLUSION: The short-term administration of indomethacin was not associated with fetal adverse events, and it may be useful in postoperative management by reducing immediate postoperative pPROM and the need for other tocolytic agents.

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OBJECTIVE: Membrane damage at or near the uterine entry site is a prevalent complication of fetal surgery and may result in chorioamniotic separation (CAS), preterm prelabor rupture of membranes (PPROM) and preterm birth. Transamniotic transuterine suturing approaches offer the potential to reduce the prevalence of CAS and PPROM accompanying fetoscopy, with the overarching aim of reducing preterm birth. This study aimed to explore the feasibility and potential efficacy of employing a novel vascular closure device for transamniotic transuterine suturing in a sheep model of fetoscopic surgery. METHODS: This study employed a pregnant sheep model to simulate fetal surgery and was conducted between December 2023 and February 2025. We used multiple methodologies to evaluate the Abbott Perclose™ vascular closure device for suturing membranes at the uterine entry site before or after the insertion of a 12-French outer diameter cannula. Feasibility was defined as successful suture placement by two independent surgical teams at two different gestational ages. Potential efficacy was demonstrated by the watertight closure of the entry site during in-vivo gross examination, along with organizing fibrosis and healing of membranes and myometrium, as assessed by postdelivery histopathological evaluation. The procedures were conducted in two phases during the sheep's gestation. Three approaches were used for abdominal entry to access the uterus: midline laparotomy and direct uterine entry; 2-cm mini laparotomy allowing access to the uterus; and a percutaneous approach. Histopathological examination of samples from the entry sites was conducted using routine microscopy, trichrome staining and immunohistochemistry for Connexin 43 (Cx43). This study was approved by the Institutional Animal Care and Use Committee (AN-2010). RESULTS: Ten pregnant sheep were included in this study, four of which had a twin pregnancy. The median gestational age at the occurrence of the first and second rounds of intervention was 85.5 and 104 days, respectively. Overall, 32 Perclose devices were used, and 75% (24/32) were placed successfully. Watertight closure of all sutures was observed during the first and second rounds of intervention, at Cesarean delivery and in situ. Histopathological examination confirmed organizing fibrosis surrounding the device entry site, in addition to overexpression of Cx43. CONCLUSIONS: Employing multiple orthogonal approaches, we have shown for the first time that the Perclose device is both feasible and potentially efficacious as a novel means of uterine port closure in our preclinical sheep model of fetoscopic surgery. Inspired by our success in this preclinical model, we anticipate that clinical validation studies will provide translational data and a direct means of measuring efficacy in the reduction of CAS, PPROM and preterm birth. © 2025 International Society of Ultrasound in Obstetrics and Gynecology.

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OBJECTIVE: Aim: Based on retrospective analysis recognize the key factors of development of premature childbirth and elaborate highly specific criteria for individual prognosis to improve perinatal outcomes. PATIENTS AND METHODS: Materials and Methods: A retrospective analysis of the birth histories of 250 women and their newborns with spontaneous preterm births at 22-36 weeks was conducted using archival data from the department for pregnant women with obstetric pathology of the State Institution "Institute of Pediatrics, Obstetrics and Gynecology named by academician OM Lukianova of the National Academy of Medical Sciences of Ukraine". RESULTS: Results: Important risk factors for premature rupture of membranes (PROM) in preterm pregnancy include the presence of sexually transmitted diseases (χ2=31.188, p=0.001), bacterial vaginosis (χ2=30.913, p=0.0001), a history of abortion and/or preterm birth (χ2=16.62, p=0.0002), SARS during pregnancy (χ2=16.444, p=0.0002), chronic adnexitis in anamnesis (χ2=11.522, p=0.0031), inflammatory cervical disease (χ2=11.437, p=0.0032), anaemia (χ2=10.815, p=0.0044), isthmic-cervical insufficiency (ІСІ) (χ2=10.345, p=0.0057), chronic pyelonephritis with exacerbation (χ2=9.16, p=0.01), smoking during pregnancy (χ2=10.815, p=0.0044). CONCLUSION: Conclusions: The results of a retrospective analysis of 250 cases of preterm birth at 22 to 36 weeks allowed us to identify ways to effectively use existing diagnostic measures to determine readiness for pregnancy and the possibility of prolonging pregnancy to the viability of the newborn. Ways to improve the prevention of preterm birth and the design of further research were identified.

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OBJECTIVES: Fetoscopic laser coagulation of placental anastomoses is usually performed for a treatment of twin-to-twin transfusion syndrome (TTTS). A common complication of fetoscopic laser coagulation for TTTS is preterm preliminary rupture of fetal membranes (PPROM) aggravating the neonatal outcome significantly. However, use of an flexible 1 mm fetoscope with an curved sheath could reduce iatrogenic damage of the amniotic membrane and improve neonatal outcomes after laser treatment. The aim of this study was to compare neonatal outcomes using this flexible fetoscope with curved sheath vs. use of a standard lens technique. METHODS: Outcomes were retrospective analyzed after use of a standard lens fetoscope of 2 mm (sheath 6.63 mm2 or 11.27 mm2 for anterior placenta) and a flexible fetoscope of 1 mm or 1.2 mm (sheath 2.65 mm2 or 3.34 mm2) in two German centers of fetal surgery, performed during 2006-2019. RESULTS: Neonatal outcome of 247 TTTS patients were analyzed including the rates of double and single fetal survival. The survival of at least one fetus was 97.2 % in the group with the ultrathin technique (n=154) compared to 88.3 % (n=93) in the group with the standard lens fetoscope (p=0.008). Survival of both fetuses was not different between groups (81.0 vs. 75.3 %). The procedure to delivery interval was significantly increased using the ultrathin fetoscope (89.1±35.0 d vs. 71.4±35.4 d, p=0.001) resulting in an increased gestational age at delivery by 11 days on average (231.9±28.1 d vs. 221.1±32.7 d, p=0.012). CONCLUSIONS: Fetal survival can be significantly increased following TTTS using flexible fetoscope of 1 mm or 1.2 mm (sheath 2.65 mm2 or 3.34 mm2).

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OBJECTIVE: To assess the feasibility of using a novel device designed for minimally invasive suturing to anchor fetal membranes to the uterine wall and to close surgical defects after fetoscopy. METHODS: We tested the WestStitch™ suturing device both ex vivo and in vivo. In the ex-vivo studies, 12-Fr trocar defects were created with a fetoscope in five specimens of human uterine tissue with fetal membranes attached. Specimens were examined for integrity of the anchoring stitch. For the in-vivo studies, trocar defects were created in the two uterine horns of three pregnant ewes, each carrying twins at approximately 79-90 days' gestation. One trocar defect in each ewe was repaired using the suture device, and the other was left unrepaired as a control. The repair sites were examined for membrane-anchoring integrity when the defect was created and at delivery. RESULTS: Fetal membranes were anchored successfully to the uterine myometrium using the suture-delivery device in all five experiments performed ex vivo. The in-vivo experiments also revealed successful membrane anchoring compared with controls, both at the time of device deployment and 1-9 weeks after the procedure. CONCLUSIONS: We successfully anchored amniotic membranes to the underlying myometrium using a suturing device, both ex vivo and in vivo. Further studies are needed to evaluate the efficacy of the device and to determine whether it can successfully anchor fetal membranes percutaneously in human patients. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

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BACKGROUND: Miscarriage and preterm birth are leading causes of loss and disability in monochorionic twins after laser treatment of twin-twin transfusion syndrome. OBJECTIVE: This study aimed to investigate the use of cervical pessary to reduce preterm birth before 32 weeks of gestation in monochorionic diamniotic twin pregnancies after fetal surgery for twin-twin transfusion syndrome. STUDY DESIGN: In this open-label multicenter randomized trial, pregnant women carrying monochorionic diamniotic twins requiring fetoscopic laser coagulation for twin-twin transfusion syndrome were randomly assigned in a 1:1 ratio to pessary placement or conservative management. The primary outcome was birth before 32 weeks of gestation. The secondary outcomes were birth before 28, 30, 34, or 37 weeks of gestation; preterm premature rupture of membranes; fetal and neonatal survival; and a composite of maternal and neonatal complications. The estimated sample size was 364 patients, with 182 cases in each arm of the study. The analysis was performed according to the intention-to-treat principle. Moreover, 2 interim analyses were planned. RESULTS: The trial was stopped prematurely after the first planned interim analysis for futility. Overall, 137 women were included in the analysis, 67 in the pessary group and 70 in the conservative management group. Preterm birth before 32 weeks of gestation occurred in 27 of 67 women (40.3%) in the pessary group and in 25 of 70 women (35.7%) in the conservative management group (adjusted odds ratio, 1.19; 95% confidence interval, 0.58-2.47; P=.63). No differences between groups were observed in the rate of deliveries before 28, 30, 34, and 37 weeks of gestation. Overall survival to delivery was 91.2% (125/137) for at least 1 twin, and 70.8% (97/137) for both twins, with no difference between groups. Neonatal survival at 30 days was 76.5% (208/272). There was no difference between the groups in maternal or neonatal morbidity. CONCLUSION: In monochorionic diamniotic twin pregnancies requiring fetal therapy for twin-twin transfusion syndrome, routine use of cervical pessary did not reduce the rate of preterm birth before 32 weeks of gestation.

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Introducción: La ruptura prematura de membranas (RPM) es un problema obstétrico muy frecuente. Los índices plaqueta/linfocitos (IPL) y neutrófilo/linfocitos (INL) se estudian como posibles predictores de infección en pacientes con RPM, lo que puede contribuir a la prevención de complicaciones asociadas a la RPM. Objetivo: Evaluar la utilidad del IPL e INL como predictores de infección en gestaciones pretérminos con RPM en el Hospital Alfredo Paulson, de Ecuador, entre los años 2018 y 2020. Métodos: Se realizó un estudio observacional, retrospectivo y transversal, enmarcado en un diseño epidemiológico, que se apoyó en la prueba de ChiCuadrado. La población de estudio fueron 70 pacientes con RPM. Resultados: Diez pacientes tuvieron mayor su riesgo al estar más de 4 días con RPM. En 11 se presentaron complicaciones y una estadía hospitalaria larga (más de 8 días). Predominaron las pacientes con compromiso del bienestar fetal y las cesáreas. El 80 % reportó algún grado de infección como la amnionitis, corionitis y la corioamnionitis. Al ingreso, el INL y el IPL estuvieron altos en el 82,86 % y en el 44,29 %, respectivamente. Se encontraron diferencias significativas entre las pacientes con valores altos a estas pruebas y aquellas que tuvieron diagnóstico histopatológico positivo para infección. Conclusiones: El INL guarda correlación con el resultado histopatológico como marcador temprano de infección, mientras que el IPL es un marcador de compromiso o presencia de sepsis, que pone en riesgo la vida de la madre y el feto.

Introduction: Premature rupture of membranes (PRM) is a very common obstetric problem. Platelet/lymphocyte (PLI) and neutrophil/lymphocyte (INL) indices are being studied as possible predictors of infection in patients with PRM, which may contribute to the prevention of complications associated with PRM. Objective: To evaluate the usefulness of the IPL and INL as predictors of infection in preterm pregnancies with PRM at the Alfredo Paulson Hospital, in Ecuador, between 2018 and 2020. Methods: An observational, retrospective and cross-sectional study was carried out, framed in an epidemiological design, which was supported by the Chi-Square test. The study population was 70 patients with PRM. Results: Ten patients had a higher risk by spending more than 4 days with PRM. In 11 there were complications and a long hospital stay (more than 8 days). Patients with compromised fetal well-being and cesarean sections predominated. 80% reported some degree of infection such as amnionitis, chorionitis and chorioamnionitis. On admission, the INL and IPL were high in 82.86% and 44.29%, respectively. Significant differences were found between patients with high values for these tests and those who had a positive histopathological diagnosis for infection. Conclusions: The INL is correlated with the histopathological result as an early marker of infection, while the IPL is a marker of commitment or presence of sepsis, which puts the life of the mother and the fetus at risk.

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El parto pretérmino en la región centroamericana tiene variaciones en cada país, así como la mortalidad perinatal neonatal y materna que se deriva de la condición. La atención adecuada sigue siendo una barrera en las zonas con más limitaciones en los servicios y el personal sanitario disponible. El parto pretérmino es considerado un problema con implicaciones sociales y económicas que produce impacto a corto, mediano y largo plazo (Goldenberg, 2012). El 75% de las complicaciones que genera conllevan a un aumento en la mortalidad infantil. La mayoría de sus factores de riesgo son considerados como prevenibles con la implementación de medidas sencillas y económicas (WHO, 2015). La investigación clínica de esta condición, en una gran mayoría, se ha generado en países de alto ingreso (Opiyo, 2017) 1 . Algunas veces se desconocen los resultados de algunas intervenciones en condiciones de recursos limitados. Esta guía presenta y pretende abordar algunas de estas limitaciones. También alerta sobre algunas intervenciones que pueden producir más problemas y dificultades si se implementan, al considerar los recursos disponibles en los lugares donde se desarrollaron las investigaciones que generaron la evidencia y hacer la comparación con la realidad de los países de Centroamérica en donde se usará la evidencia. Por otra parte, para cada recomendación que en este instrumento se facilita, los resúmenes de evidencia consideran las efectividades clínicas y los efectos adversos cuando han estado disponibles.

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The role and mechanisms of progesterone in preterm premature rupture of membranes (PPROM) remains unclear. This study aims to investigate the molecular mechanisms of action of progesterone in pre-labor full-term fetal amniotic membrane cells with and without stimulation by microbial, pro-inflammatory, or thrombogenic agents. Fetal amniotic membranes were collected from 30 women with a normal singleton pregnancy undergoing elective cesarean section at term prior to the onset of labor. The human amniotic epithelial cells isolated were pretreated with and without medroxyprogesterone acetate for 24 h. Then, cells were treated with and without TLR/NLR agonists, pro-inflammatory cytokines, or thrombin for 48 h. Semi-quantitative RT-PCR, Western blot, and caspase-3 activity measurement were performed. Progesterone stimulation decreased the expression of TLR2, TLR5, and Nod2 genes (alone and/or in combination with TLR/NLR agonists) and decreased the expression of IL-1ß and IL-8 genes increased by stimulation with specific agonists for TLR2, TLR4, TLR5, Nod1, and Nod2. Moreover, progesterone decreased thrombin-induced IL-8 gene expression. Progesterone also decreased expression of Bax and Bid proteins (pro-apoptotic factors) increased by stimulation with pro-inflammatory cytokines (TNF-α, NGAL, IL-18, and IL-1ß) and thrombin. Progesterone stimulation alone as well as co-stimulation with TNF-α, NGAL, IL-18, IL-1ß, or thrombin with progesterone either increased, decreased, or did not change the expression of Bcl-2, Bcl-XL, or XIAP genes (anti-apoptotic factors). These data suggest progesterone plays protective roles against PPROM through anti-microbial, anti-inflammatory, and anti-thrombogenic actions on human-term fetal amniotic membrane cells. Progesterone alters pro-inflammatory cytokine- and thrombin-induced apoptosis by controlling the expression of pro-apoptotic and anti-apoptotic factors.

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INTRODUCTION: The main aim of the fetal surgery of myelomeningocele (MMC) is the improvement in prognosis for children with this defect and at the same time high safety of the procedure for mother and fetus. OBJECTIVE: The aim of the study was to determine the effectiveness of alternative hysterotomy technique for fetal surgery of MMC in prevention of essential perinatal complications. METHODS: Forty-nine pregnant women diagnosed with fetal MMC (fMMC) who underwent classic hysterotomy without the use of stapler formed the study cohort. Two cases of intrauterine fetal death or neonatal death in the immediate perioperative period in the study group (SG) were excluded from further analyses. In the historical control group (46 patients) from our center hysterotomy was performed according to Management of Myelomeningocele Study (MOMS) protocol. The study cohort's outcomes were compared with the historical controls and with post-MOMS results in Children's Hospital of Philadelphia (CHOP) and Vanderbilt University Medical Center (VUMC). RESULTS: In the SG we did not observe delivery before 30 weeks of gestation (0/47; 0%) and the incidence of chorionamniotic membrane separation (CMS, 3/47; 6%) and preterm premature rupture of membranes (PPROM, 7/47; 15%) was lower compared to the other groups. Preterm delivery as a result of uterine contractions occurred significantly less frequently in the SG (8/47; 17%). Fetal surgery with classic hysterotomy resulted in rare use of magnesium sulfate (3/47; 6%). CONCLUSIONS: The alternative hysterotomy technique for fetal surgery of MMC results in low occurrences of CMS, PPROM, preterm delivery, and the rare use of tocolytics.

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Using a novel in vitro model system combining biochemical/histologic with bioengineering approaches has provided significant insights into the physiology of fetal membrane weakening and rupture along with potential mechanistic reasons for lack of efficacy of currently clinically used agents to prevent preterm premature rupture of the membranes (pPROM) and preterm births. Likewise, the model has also facilitated screening of agents with potential for preventing pPROM and preterm birth.

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INTRODUCTION: The benefits of endoscopic fetal surgery are deteriorated by the high risk of iatrogenic preterm prelabor rupture of fetal membranes (iPPROM). While previous studies have reported good sealing candidates to prevent membrane rupture, the delivery of these materials to the location of membrane puncture remains unsolved. MATERIALS AND METHODS: We describe an approach to apply sealing materials onto the amnion through the fetoscopy port. We developed a device composed of an umbrella-shaped polyester coated nitinol mesh and an applicator. The spontaneously unfolding umbrella is pushed through the port, pulled against the amnion, and glued onto the amnion defect site. We tested the adhesion strength of multiple glues and tested the feasibility and reproducibility of this fetal membrane sealing approach in an ex vivo model. RESULTS: The umbrella unfolded and was well positioned in all tests (n = 18). When applied via the fetoscopy port, umbrellas were successfully glued onto the fetal membrane, and all of them completely covered the defect (n = 5). The mean time needed for the whole procedure was 3 min. DISCUSSION: This study is a proof of concept presenting a potential future solution for the precise local application of bioadhesives for the prevention of iPPROM.

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OBJECTIVE: To investigate whether the classification of a previous spontaneous preterm birth (sPTB) as preterm labor (PTL) with intact membranes (IM) or as preterm prelabor rupture of membranes (PPROM) impacts the efficacy of cervical pessary or vaginal progesterone for prevention of sPTB in pregnant women with short cervix on transvaginal ultrasound. METHODS: This was a retrospective cohort study of asymptomatic high-risk singleton pregnancies with a short cervix and history of sPTB, treated using Arabin pessary or vaginal progesterone for primary PTB prevention, conducted at four European hospitals. A log-rank test on Kaplan-Meier curves was used to assess the difference in performance of pessary and progesterone, according to history of PTL-IM or PPROM. Linear regression analysis was used to evaluate significant predictors of gestational age at delivery. RESULTS: Between 2008 and 2015, 170 women were treated with a pessary and 88 with vaginal progesterone. In women treated with a pessary, rate of sPTB < 34 weeks was 16% in those with a history of PTL-IM and 55% in those with a history of PPROM. In women treated with progesterone, rate of sPTB < 34 weeks was 13% in those with a history of PTL-IM and 21% in those with a history of PPROM. Treatment with a pessary resulted in earlier delivery in women with previous PPROM than in any other subgroup (P < 0.0001). Linear regression analysis showed a clear effect of PPROM history (P < 0.0001), combination of PPROM history and treatment (P = 0.0003) and cervical length (P = 0.0004) on gestational age at birth. CONCLUSIONS: Cervical pessary may be a less efficacious treatment option for women with previous PPROM; however, these results require prospective validation before change in practice is recommended. Phenotype of previous preterm birth may be an important risk predictor and treatment effect modifier; this information should be reported in future clinical trials. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

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OBJECTIVE: To evaluate the impact of cervical length and cervical pessary application in congenital diaphragmatic hernia (CDH) treated by the fetoscopic endotracheal occlusion (FETO) procedure. METHODS: The study group consisted of 80 patients with severe CDH treated by FETO. Cervical length measurement was performed by transvaginal ultrasound in all patients within the 24 h prior to the FETO procedure. The study group (n = 44) had cervical pessaries applied routinely within the 24 h following the FETO procedure, whereas the control group (n = 36) were not offered pessaries and only had cervical length measurement performed. RESULTS: The median cervical length was 31 (range 22-45) mm. The median gestational age at delivery was 34.7 (range 27.8-39.2) weeks. Gestational age at delivery correlated significantly with gestational age at balloon removal (r = 0.768; p < 0.0001) and premature rupture of membranes (r = 0.501; p = 0.003). There was no significant correlation between gestational age at delivery and cervical length before the procedure (r = 0.141; p = 0.26) or pessary application (r = 0.081; p = 0.51). In the multivariate linear regression model, the only factor independently associated with gestational age at delivery was gestational age at fetoscopic balloon removal (ß = 0.713; p < 0.0001). CONCLUSION: In cases of severe CDH treated by the FETO procedure, neither cervical length before the procedure nor cervical pessary application was associated with gestational age at delivery.

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OBJECTIVE: To evaluate novel sealing techniques for their biocompatibility and sealing capacity of iatrogenic fetal membrane defects in a pregnant rabbit model. METHOD: At day 23 of gestation (term = d31), a standardized fetoscopy was performed through a 14G cannula. The resulting fetal membrane defect was closed with condensed collagen, collagen with fibrinogen, Tissuepatch, Duraseal, or a conventional collagen plug (Lyostypt) as reference. At d30, the fetuses were harvested and full thickness fetal membrane samples were analyzed. The study consisted of 2 consecutive parts: (1) biocompatibility testing by fetal survival, apoptosis, and infiltration of polymorphonuclear cells in the membranes and (2) the efficacy to seal fetal membrane defects. RESULTS: Three sealants (collagen with fibrinogen, Duraseal, or Lyostypt) were associated with a higher fetal mortality compared to control unmanipulated littermates and hence were excluded from further analysis. Tissuepatch was biocompatible, and amniotic fluid levels were comparable to those of control untouched littermates. Compared to the condensed collagen, Tissuepatch was also easier in surgical handling and induced limited cell proliferation. CONCLUSION: Tissuepatch had the best biocompatibility and efficacy in sealing an iatrogenic fetal membrane defect in the pregnant rabbit compared to other readily available sealants.

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BACKGROUND: The progestogen 17-α hydroxyprogesterone caproate (17-OHPC) is 1 of only 2 agents recommended for clinical use in the prevention of spontaneous preterm delivery, and studies of its efficacy have been conflicting. We have developed an in-vitro model to study the fetal membrane weakening process that leads to rupture in preterm premature rupture of the fetal membranes (pPROM). Inflammation/infection associated with tumor necrosis factor-α (TNF-α) induction and decidual bleeding/abruption associated thrombin release are leading causes of preterm premature rupture of the fetal membranes. Both agents (TNF-α and thrombin) cause fetal membrane weakening in the model system. Furthermore, granulocyte-macrophage colony-stimulating factor (GM-CSF) is a critical intermediate for both TNF-α and thrombin-induced fetal membrane weakening. In a previous report, we demonstrated that 3 progestogens, progesterone, 17-alpha hydroxyprogesterone (17-OHP), and medroxyprogesterone acetate (MPA), each inhibit both TNF-α- and thrombin-induced fetal membrane weakening at 2 distinct points of the fetal membrane weakening pathway. Each block both the production of and the downstream action of the critical intermediate granulocyte-macrophage colony-stimulating factor. OBJECTIVE: The objective of the study was to characterize the inhibitory effects of 17-OHPC on TNF-α- and thrombin-induced fetal membrane weakening in vitro. STUDY DESIGN: Full-thickness human fetal membrane fragments from uncomplicated term repeat cesarean deliveries were mounted in 2.5 cm Transwell inserts and cultured with/without 17-alpha hydroxyprogesterone caproate (10-9 to 10-7 M). After 24 hours, medium (supernatant) was removed and replaced with/without the addition of tumor necrosis factor-alpha (20 ng/mL) or thrombin (10 U/mL) or granulocyte-macrophage colony-stimulating factor (200 ng/mL). After 48 hours of culture, medium from the maternal side compartment of the model was assayed for granulocyte-macrophage colony-stimulating factor and the fetal membrane fragments were rupture strength tested. RESULTS: Tumor necrosis factor-alpha and thrombin both weakened fetal membranes (43% and 62%, respectively) and increased granulocyte-macrophage colony-stimulating factor levels (3.7- and 5.9-fold, respectively). Pretreatment with 17-alpha hydroxyprogesterone caproate inhibited both tumor necrosis factor-alpha- and thrombin-induced fetal membrane weakening and concomitantly inhibited the induced increase in granulocyte-macrophage colony-stimulating factor in a concentration-dependent manner. However, contrary to our prior reports regarding progesterone and other progestogens, 17-alpha hydroxyprogesterone caproate did not also inhibit granulocyte-macrophage colony-stimulating factor-induced fetal membrane weakening. CONCLUSION: 17-Alpha hydroxyprogesterone caproate blocks tumor necrosis factor-alpha- and thrombin-induced fetal membrane weakening by inhibiting the production of granulocyte-macrophage colony-stimulating factor. However, 17-alpha hydroxyprogesterone caproate did not also inhibit granulocyte-macrophage colony-stimulating factor-induced weakening. We speculate that progestogens other than 17-alpha hydroxyprogesterone caproate may be more efficacious in preventing preterm premature rupture of the fetal membranes-related spontaneous preterm birth.

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OBJECTIVE: To present the feasibility of fetal myelomeningocele (MMC) repair through a mini-hysterotomy and to describe the perinatal results from our initial experience. METHODS: A descriptive study of cases of fetal MMC correction via mini-hysterotomy performed between 2014 and 2016. RESULTS: Forty-five women underwent fetal surgery and 87% (39/45) delivered. A complete multilayer correction of the MMC was possible in all cases. There were no maternal, fetal or neonatal deaths. No maternal or fetal complications occurred from fetal MMC correction until maternal hospital discharge. The average gestational age (GA) at surgery was 24.5 weeks (standard deviation, SD: 1.7; range: 20.7-26.9). The median hysterotomy length was 3.05 cm (SD: 0.39; range: 2.50-3.50). One patient (1/39; 2.6%) experienced chorioamniotic separation. Nine patients (9/39; 23.1%) had premature preterm rupture of membranes at a median GA of 34.1 weeks (range: 31.1-36.0). The average GA at delivery was 35.3 weeks (SD: 2.2; range: 27.9-39.1). Ninety-five percent (37/39) of our patients had an intact hysterotomy site at delivery. Ventriculoperitoneal shunt placement was necessary for 7.7% (3/39) of the neonates. CONCLUSION: Fetal MMC repair is feasible through a mini-hysterotomy. This approach appears to be associated with reduced risks of very preterm delivery and maternal, fetal and neonatal complications.

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BACKGROUND: Preterm premature rupture of membranes remains a major complication after fetoscopic laser surgery (FLS) for twin-twin transfusion syndrome (TTTS). We studied the histologic changes of fetal membranes post-FLS and investigated a possible impact of amniotic fluid (AF) dilution. METHODS: Fetal membranes of 31 pregnancies that underwent FLS for TTTS were investigated histologically at delivery at different sites: trocar site of recipient sac and at distance, donor sac, and inter-twin membrane. RESULTS: The trocar insertion site on the recipient sac showed no signs of histologic hallmarks of healing. Wide-spread alteration in collagen organization and higher apoptotic index in the amnion of the recipient sac which were absent in donor's and reference membranes. To explain the mechanisms, we analyzed the AF composition of recipient sacs from TTTS pregnancies vs. GA-matched healthy singleton controls and found glucose, protein and lactate dehydrogenase activity were all significantly lower in TTTS sacs consistent with over-dilution of recipient's AF (~2-fold). In-vitro exposure of healthy amniochorion to analogous dilutional stress conditions recapitulated the histologic changes and induced apoptosis and autophagy. CONCLUSION: Alteration in structural integrity of the recipient's amniochorion, possibly in response to dilution stress, along with ineffective repair mechanisms may explain the increased incidence of preterm birth post-FLS.

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Genital mycoplasmas are frequently found in the vaginal flora across socioeconomic and ethnic groups and have been demonstrated to be involved in adverse perinatal outcomes. Both Mycoplasma and Ureaplasma spp cause inflammation potentially leading to spontaneous preterm birth and PPROM as well as postdelivery infectious complications and neonatal infections. Herein we have provided an overview of the existing literature and supportive evidence for genital mycoplasma's role in perinatal complications. Future research will need to focus on clearly delineating the species, allowing for discrimination of their effects.

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UNLABELLED: OBJECT.: As more pediatric neurosurgeons become involved with fetal myelomeningocele closure efforts, examining refined techniques in the overall surgical approach that could maximize beneficial outcomes becomes critical. The authors compared outcomes for patients who had undergone a modified technique with those for patients who had undergone fetal repair as part of the earlier Management of Myelomeningocele Study (MOMS). METHODS: Demographic and outcomes data were collected for a series of 43 delivered patients who had undergone in utero myelomeningocele closure at the Fetal Center at Vanderbilt from March 2011 through January 2013 (the study cohort) and were compared with data for 78 patients who had undergone fetal repair as part of MOMS (the MOMS cohort). For the study cohort, no uterine trocar was used, and uterine entry, manipulation, and closure were modified to minimize separation of the amniotic membrane. Weekly ultrasound reports were obtained from primary maternal-fetal medicine providers and reviewed. A test for normality revealed that distribution for the study cohort was normal; therefore, parametric statistics were used for comparisons. RESULTS: The incidence of premature rupture of membranes (22% vs 46%, p = 0.011) and chorioamnion separation (0% vs 26%, p < 0.001) were lower for the study cohort than for the MOMS cohort. Incidence of oligohydramnios did not differ between the cohorts. The mean (± SD) gestational age of 34.4 (± 6.6) weeks for the study cohort was similar to that for the MOMS cohort (34.1 ± 3.1 weeks). However, the proportion of infants born at term (37 weeks or greater) was significantly higher for the study cohort (16 of 41; 39%) than for the MOMS cohort (16 of 78; 21%) (p = 0.030). Compared with 10 (13%) of 78 patients in the MOMS cohort, only 2 (4%) of 41 infants in the study cohort were delivered earlier than 30 weeks of gestation (p = 0.084, approaching significance). For the study cohort, 2 fetal deaths were attributed to the intervention, and both were believed to be associated with placental disruption; one of these mothers had previously unidentified thrombophilia. Mortality rates did not statistically differ between the cohorts. CONCLUSIONS: These early results suggest that careful attention to uterine entry, manipulation, and closure by the surgical team can result in a decreased rate of premature rupture of membranes and chorioamnion separation and can reduce early preterm delivery. Although these results are promising, their confirmation will require further study of a larger series of patients.