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Background Previously manual human embryology in many in vitro fertilization (IVF) centers is rapidly being replaced by closed embryo incubation systems with time-lapse imaging. Whether such systems perform comparably to manual embryology in different IVF patient populations has, however, never before been investigated. We, therefore, prospectively compared embryo quality following closed system culture with time-lapse photography (EmbryoScope™) and standard embryology. We performed a two-part prospectively randomized study in IVF (clinical trial # NCT92256309). Part A involved 31 infertile poor prognosis patients prospectively randomized to EmbryoScope™ and standard embryology. Part B involved embryos from 17 egg donor-recipient cycles resulting in large egg/embryo numbers, thus permitting prospectively alternative embryo assignments to EmbryoScope™ and standard embryology. We then compared pregnancy rates and embryo quality on day-3 after fertilization and embryologist time utilized per processed embryo. Results Part A revealed in poor prognosis patients no differences in day-3 embryo scores, implantation and clinical pregnancy rates between EmbryoScope™ and standard embryology. The EmbryoScope™, however, more than doubled embryology staff time ( P  < 0.0001). In Part B, embryos grown in the EmbyoScope™ demonstrated significantly poorer day-3 quality (depending on embryo parameter between P  = 0.005 and P  = 0.01). Suspicion that conical culture dishes of the EmbryoScope™ (EmbryoSlide™) may be the cause was disproven when standard culture dishes demonstrated no outcome difference in standard incubation. Conclusions Though due to small patient numbers preliminary, this study raises concerns about the mostly uncontrolled introduction of closed incubation systems with time lapse imaging into routine clinical embryology. Appropriately designed and powered prospectively randomized studies appear urgently needed in well-defined patient populations before the uncontrolled utilization of these instruments further expands. Trial registration NCT02246309 Registered September 18, 2014.

One of the drawbacks of fetoscopic endoluminal tracheal occlusion (FETO) for congenital diaphragmatic hernia is the need for a second invasive intervention to reestablish airway patency. The \"Smart-TO\" (Strasbourg University-BSMTI, France) is a new balloon for FETO, which spontaneously deflates when positioned near a strong magnetic field, e.g., generated by a magnetic resonance image (MRI) scanner. Translational experiments have demonstrated its efficacy and safety. We will now use the Smart-TO balloon for the first time in humans. Our main objective is to evaluate the effectiveness of prenatal deflation of the balloon by the magnetic field generated by an MRI scanner. These studies were first in human (patients) trials conducted in the fetal medicine units of Antoine-Béclère Hospital, France, and UZ Leuven, Belgium. Conceived in parallel, protocols were amended by the local Ethics Committees, resulting in some minor differences. These trials were single-arm interventional feasibility studies. Twenty (France) and 25 (Belgium) participants will have FETO with the Smart-TO balloon. Balloon deflation will be scheduled at 34 weeks or earlier if clinically required. The primary endpoint is the successful deflation of the Smart-TO balloon after exposure to the magnetic field of an MRI. The secondary objective is to report on the safety of the balloon. The percentage of fetuses in whom the balloon is deflated after exposure will be calculated with its 95% confidence interval. Safety will be evaluated by reporting the nature, number, and percentage of serious unexpected or adverse reactions. These first in human (patients) trials may provide the first evidence of the potential to reverse the occlusion by Smart-TO and free the airways non-invasively, as well a safety data.

OBJECTIVES: We aimed to show how increased experience of a surgery team in fMMC repair influences maternal andfetal/neonatal outcomes. MATERIAL AND METHODS: We compare perinatal results of fMMC repair in our Fetal Surgery Center (FSC) in cohort groups forthe early period (2005–2011 year; previous — PFSC, n = 46) and current period (2012–2015 year; current — CFSC, n = 74)to results of the randomized Management of Myelomeningocele Study (MOMS, 78 patients). RESULTS: The maternal morbidity due to fMMC repair was low and there was no difference comparing CFSC to PFSC andMOMS. The frequency of iatrogenic preterm labor (iPTL) ≤ 30 weeks of gestation decreased from 34.1% in PFSC to 23.9%in CFSC. Iatrogenic preterm premature rupture of membranes (iPPROM) was a common complication after fMMC repair inall cohorts. The total reduction rate of hindbrain hernation (HH) was similar in CFSC — 90.3% and PFSC — 82.1%. CONCLUSIONS: The increasing experience of our surgery team in fMMC repair majorly decreased the risk of iPTL.

In this trial involving fetuses with severe left congenital diaphragmatic hernia, fetoscopic endoluminal tracheal occlusion at 27 to 29 weeks of gestation significantly increased survival to discharge, but it resulted in an increased incidence of preterm, prelabor rupture of membranes and preterm birth.

Introduction Our objective was to investigate outcomes in twin‐to‐twin transfusion syndrome (TTTS) treated with fetoscopic laser surgery (FLS) at <18 weeks vs ≥18 weeks, and to conduct subgroup analysis of TTTS with FLS at <16 weeks vs 16–18 weeks. Material and methods PubMed, Scopus and Web of Science were searched systematically from inception until May 2023. Primary outcome was survival, and secondary outcomes included preterm premature rupture of membranes (PPROM), preterm birth and gestational age (GA) at delivery. Results Nine studies encompassing 1691 TTTS pregnancies were included. TTTS stage III was significantly more common in TTTS pregnancies treated with FLS at <18 weeks (odds ratio [OR] 2.84, 95% confidence interval [CI] 1.24–6.54), and procedure duration was shorter at <18 weeks (MD −5.27 minutes, 95% CI −9.19 to −1.34). GA at delivery was significantly earlier in TTTS pregnancies treated with FLS at <18 weeks (MD −3.12 weeks, 95% CI −6.11 to −0.13). There were no significant differences in outcomes, including PPROM, PPROM at <7 days post‐FLS, preterm birth at <28 and <32 weeks, delivery at <7 days post‐FLS, and survival outcomes, including fetal demise, live birth and neonatal survival. Similarly, TTTS stage III was more common in TTTS with FLS at <16 weeks than at 16–18 weeks (OR 2.95, 95% CI 1.62–5.35), with no significant differences in the aforementioned outcomes. Conclusions In early TTTS treated with FLS, outcomes were comparable between those treated at <18 weeks compared with ≥18 weeks except for GA at delivery, which was 3 weeks earlier. In the subset treated at <16 weeks vs 16–18 weeks, the procedure was feasible without an increased risk of very early preterm birth or perinatal mortality. Although gestational age at delivery was 3 weeks earlier in twin‐to‐twin transfusion syndrome with FLS at <18 weeks, there was no difference in outcomes, including very early preterm birth, premature rupture of membranes and survival with similar findings in the subset that underwent laser surgery at <16 weeks.

BackgroundFetoscopic endoluminal tracheal occlusion (FETO) has been shown to improve survival of infants with congenital diaphragmatic hernia (CDH). However, there are concerns that FETO may lead to tracheomegaly, tracheomalacia and related complications.MethodsA systematic review was conducted to estimate the prevalence of symptomatic tracheal complications in infants who underwent FETO for CDH. Presence of one or more of the following was considered as tracheal complication: tracheomalacia, stenosis, laceration or tracheomegaly with symptoms such as stridor, effort-induced barking cough, recurrent chest infections or the need for tracheostomy, tracheal suturing, or stenting. Isolated tracheomegaly on imaging or routine bronchoscopy without clinical symptoms was not considered as tracheal morbidity. Statistical analysis was performed using the metaprop command on Stata V.16.0.ResultsA total of 10 studies (449 infants) were included (6 retrospective cohort, 2 prospective cohort and 2 randomised controlled trials). There were 228 infants who survived to discharge. Prevalence rates of tracheal complications in infants born alive were 6% (95% CI 2% to 12%) and 12% (95% CI 4% to 22%) in those who survived to discharge. The spectrum of severity ranged from relatively mild symptoms such as effort-induced barking cough to the need for tracheostomy/tracheal stenting.ConclusionA significant proportion of FETO survivors have symptomatic tracheal morbidities of varying severity. Units that are planning to adopt FETO for managing CDH should consider ongoing surveillance of survivors to enable early identification of upper airway issues. Inventing FETO devices that minimise tracheal injury is needed.

Introduction Preterm prelabor rupture of membranes (PPROM) remains a major complication of fetal laser surgery in the treatment of twin‐to‐twin transfusion syndrome (TTTS). The aim of the study was to determine the impact of cannula size on pregnancy outcomes, with a particular focus on PPROM. Material and methods The protocol was developed and registered in the PROSPERO database under registration number CRD42022333630. The PubMed, Web of Science, and EMBASE databases were searched electronically on May 18, 2022, and updated on March 2, 2023, utilizing a combination of the relevant MeSH terms, keywords, and word variants for “TTTS” and “laser”. Randomized controlled trials, prospective and retrospective cohorts, case–control studies, and case reports/series with more than five participants were considered eligible for inclusion. Studies reporting the cannula diameter and PPROM rate after laser surgery in the treatment of monochorionic pregnancies affected by TTTS between 16‐ and 26 weeks' gestation were included. Data was extracted independently, and when appropriate, a random‐effects meta‐analysis was undertaken to calculate pooled estimates and their confidence intervals. Heterogeneity in the effect estimates of the individual studies was calculated using the I2 statistic. The primary outcome was PPROM rate. Secondary outcomes were survival rate, preterm birth, and incomplete surgery. The quality of the included studies was assessed using a modified quality in prognosis study tool. Results We included a total of 22 studies, consisting of 3426 patients. Only one study was scored as low quality, seven as moderate quality, and the remaining 14 as high quality. The mean PPROM rate after laser surgery treating TTTS was 22.9%, ranging from 11.6% for 9 French (Fr) to 54.0% for 12 Fr. Subsequent meta‐regression for the clinically relevant PPROM rate before 34 weeks of gestation, showed increased PPROM rates for increased cannula size (p‐value 0.01). Conclusions This systematic review confirmed PPROM as a frequent complication of fetal laser surgery, with a mean PPROM rate of 22.9%. A larger cannula diameter relates to a significant higher PPROM risk for PPROM before 34 weeks gestation. Hence, the ideal balance between optimal visualization requiring larger port diameters and shorter operation time and more complete procedures that benefit from larger diameters is crucial to reduce iatrogenic PPROM rates. Iatrogenic PPROM is a frequent complication of fetal laser surgery, with a mean PPROM rate of 22.9%. Larger cannula diameter relates to a higher PPROM risk, with a statistical significant effect for PPROM before 34 weeks gestation.

Objective: To determine predictors of survival in monochorionic diamniotic twins with selective fetal growth restriction type II (sFGR-II), with or without twin-to-twin transfusion syndrome (TTTS), treated by endoscopic placental laser coagulation. Methods: Laser surgery was performed at 20 (15-27) weeks' gestation in 405 cases of sFGR-II with and 142 without coexisting TTTS. Multivariable logistic regression analysis was performed to determine significant predictors of survival to discharge from hospital. Results: There was survival of the small twin in 216 (39.5%) and of the large twin in 379 (69.3%) cases. Significant predictors of survival of both the small and larger twin were ductus venosus Doppler findings in the small twin, gestational age at laser and cervical length, but not the presence of TTTS or Doppler findings in the large twin. Conclusions: In sFGR-II, survival after laser surgery is primarily dependent on the condition of the small twin.

Background Fetoscopic laser photocoagulation (FLP) has been performed as first-line approach for twin-to-twin transfusion syndrome (TTTS) in monochorionic twin pregnancies. The majority of researches are focusing on advances in fetal treatment and long-term outcome, few researches on maternal surgery-related complications are reported. This study is to compare the maternal blood dynamic changes in women with and without persistent compression on the uterine insertion after the FLP procedure. Methods This was a retrospective study conducted at two tertiary referral centers in China between November 2018 and July 2023. TTTS-cases undergoing FLP surgery were enrolled and divided into two groups upon whether having compression on the uterine insertion after FLP. The changes of maternal hemoglobin, hematocrit before and after the procedure were compared between the two groups. Results A total of 111 TTTS-cases were finally analyzed including 46 cases with persistent compression and 65 cases without persistent compression. The two groups had similar values of hemoglobin (10.7 ± 1.1 versus 10.5 ± 1.2 g/dl, p  = 0.513) and hematocrit (32.3 ± 3 versus 31.3 ± 3.2, p  = 0.099) before FLP. A similar volume of amniodrainage during the surgery was observed in the two groups (710 ml versus 850 ml, p  = 0.255). The decrease in hemoglobin in TTTS-cases with persistent compression was significantly lower than that in TTTS cases without continuous compression (1.1 g/dL versus 1.5 g/dL, p  = 0.014). A decrease trend in change of hematocrit was observed between cases with persistent compression (3.1%) and those without persistent compression (4.0%), while it did not achieve a significant difference ( p  = 0.050). The blood transfusion rate in TTTS-cases with and without compression was 2.2% and 7.7% respectively ( p  = 0.205). Conclusion The decrease in hemoglobin and hematocrit could be mitigated by persistent compression on the uterine insertion site after FLP, which is an economical, simple and convenient method.

In this randomized trial involving fetuses with moderate left congenital diaphragmatic hernia, fetoscopic endoluminal tracheal occlusion at 30 to 32 weeks of gestation did not significantly increase survival to discharge from a NICU or reduce the need for oxygen supplementation at 6 months, and it increased the risks of preterm, prelabor rupture of membranes and preterm birth. The surgical technique is shown in an animated video.