Environmental exposure to lead and cadmium only minimally affects the redox system of the follicular fluid and the outcome of intracytoplasmic sperm injection.

The purpose of our study was to determine the influence of lead and cadmium in concentrations commonly found in the environment on the redox system of the follicular fluid (FF) and on the results of assisted reproduction. A prospective study of 113 patients with unexplained infertility who qualified for intracytoplasmic sperm injection (ICSI). Patients with moderate or severe endometriosis or poor ovarian reserve were excluded from the study. Biochemical analyses and heavy metal assays of follicular fluid and serum (blood) were followed by statistical analyses of dependencies between lead and cadmium and the components of redox system and results of assisted reproduction. A highly significant linear correlation of lead (Pb) and cadmium (Cd) concentrations in serum and in FF was stated. The number of retrieved oocytes and MII (metaphase II stage) oocytes depended on the malondialdehyde (MDA), catalase (CAT), catalase/g of protein (CAT/g of protein), and glutathione reductase (GR) concentrations. Among biochemical factors, MDA was the only factor that correlated negatively with cadmium concentration in serum and FF and simultaneously influenced the number of retrieved oocytes and MII oocytes. The fertilization rate of MII oocytes was influenced by thiol groups-SH, SH/g of protein, CAT, CAT/g of protein, and glutathione peroxidase/g of protein (GPx/g of protein). The Pb and Cd concentrations in FF did not significantly influence the fertilization rates. Lead as well as cadmium at concentrations commonly found in women of reproductive age despite some adaptive changes in the redox system in follicular fluid do not cause large changes in the ovarian follicular environment as a whole and do not significantly worsen the final results of assisted reproduction.

Open Fetal Surgery for Ventricular-Amniotic Valve Implantation in Aqueductal Stenosis-Dependent Severe Fetal Hydrocephalus: A Case Report with 7-Year Follow-Up.

INTRODUCTION: Fetal ventriculomegaly is one of the most commonly diagnosed central nervous system pathologies of the second trimester, occurring with a frequency of 0.3-0.5/1,000 births. Severe fetal ventriculomegaly (SVM) may necessitate intrauterine intervention. Most such interventions have been made percutaneously with ultrasound guidance insertion of a pigtail catheter, which sadly often became obstructed or migrated. CASE PRESENTATION: Our case report presents the possibility of ventriculo-amniotic valve implantation (VAVI) by classic hysterotomy in isolated severe fetal hydrocephalus (IVSM) due to aqueductal stenosis. The patient was operated on similarly to open fetal surgery MOMS criteria at 24+4/7 GA, with an initial lateral ventricular dimension of 22.5 mm. A female newborn was delivered by elective cesarean section at 31+1/7 GA due to PPROM (Apgar 10' 8 points, birth weight 1,600 g), required CPAP, and removal of the drainage system due to infection and narrow lateral ventricles. Evans index (EI) gradual increase and clinical symptoms of high-pressure hydrocephalus after 10 days required a ventricle-peritoneal shunt (VPS) implantation. The newborn was discharged home after 28 days with stabile hydrocephalus (EI: 0.59-0.6), in good clinical condition. The 7-year follow-up was complicated by epilepsy, VPS shunt infections, delay in motor and intellectual functions (mild to moderate), and symptoms of atypical autism, the phenotype possibly related to a variant in ZEB2 gene. CONCLUSION: Intrauterine VAVI is a one-step procedure that is effective in draining CFS. The limitations of the method remain complications due to preterm labor and infection of the drainage system.

Alternative Hysterotomy Technique for the Reduction of Prenatal Complications of Intrauterine Myelomeningocele Repair.

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.

The Use of Indomethacin with Complete Amniotic Fluid Replacement and Classic Hysterotomy for the Reduction of Perinatal Complications of Intrauterine Myelomeningocele Repair.

OBJECTIVE: This study presented outcomes of classical hysterotomy with modified antiprostaglandin therapy for intrauterine repair of foetal myelomeningocele (fMMC) performed in a single perinatal centre. STUDY DESIGN: Forty-nine pregnant women diagnosed with fMMC underwent classic hysterotomy with anti-prostaglandin management, complete amniotic fluid replacement and high dose indomethacin application. RESULTS: The average gestational age (GA) at delivery was 34.4 ± 3.4 weeks, with no births before 30 weeks GA. There were 2 foetal deaths. Complete reversal of hindbrain herniation (HH), assessed in magnetic resonance imaging at 30-31 weeks GA was found in 72% of foetuses (mostly with HH grade I prior to fMMC repair). Our protocol resulted in rare use of magnesium sulphate (6%), low incidence of chorioamniotic membrane separation - chorioamniotic membrane separation (6%), preterm premature rupture of membranes - preterm premature rupture of membranes (pPROM; 15%) and preterm labour - preterm labour (PTL; 17%). The postoperative wound continuity of the uterus was usually stable (in 72% of patients), with low frequency of scar thinning (23%). CONCLUSION: Our protocol results in rare use of tocolytics, and the low occurrences of CMS, pPROM and PTL in relation to other study cohorts: Management of Myelomeningocele Study, Children's Hospital of Philadelphia, and Vanderbilt University Medical Centre.

Current views on fetal surgical treatment of myelomeningocele - the Management of Myelomeningocele Study (MOMS) trial and Polish clinical experience.

Myelomeningocele (MMC) is the most frequent congenital defect of the central nervous system for which there is no satisfactory alternative to postnatal treatment. On the contrary prenatal MMC surgery is conducting before birth and is aimed at protecting from Chiari II malformation. The main goal of fetal MMC repair is to improve development and life quality of children with Chiari II malformation. Management of Myelomeningocele Study (MOMS) which was published in 2011 clearly confirmed effectiveness of prenatal surgery. In this paper we compare MOMS results with our own clinical experience. Thanks to high effectiveness and significant improvement in safety of maternal-fetal surgery prenatal MMC surgery become a new standard of treatment.

Isolated Fetal Ventriculomegaly: Diagnosis and Treatment in the Prenatal Period.

Fetal ventriculomegaly (VM) is a defect of the central nervous system, typically diagnosed during the second-trimester ultrasound in fetuses with an atrial diameter (AD) of >10 mm. Non-isolated ventriculomegaly (NIVM) is heterogeneous in nature, coexisting with additional intracranial and/or extracranial malformations and genetic syndromes, resulting in an unfavorable prognosis for the further development of the child. Both the pregnancy management and counseling are dependent on the findings of combined ultrasound/MRI, genetic testing, and gestational age at diagnosis. The purpose of this review is to propose a hypothesis that diagnostic advancements allow to define the process of identification of the isolated forms of VM (IVM). Based on the evidence presented in the literature, we consider whether prenatal decompression for severe isolated VM (ISVM) is supported by the experimental trials and whether it might be implemented in clinical practice. Also, we describe the evolution of the diagnostic methods and expert opinions about the previously used prenatal decompression techniques for ISVM. In conclusion, we introduce the idea that fetal surgery centers have either reached or nearly reached the necessary level of expertise to perform such procedures. Endoscopic cystoventriculostomy (ETV) appears to be the most promising, as it is associated with minimal perinatal complications and favorable neurological outcomes in the neonatal period. Randomized trials with long-term neurodevelopmental follow-up of children who underwent prenatal decompression due to ISVM are necessary.

Treatment of parathormone-dependent hypercalcaemia in the third-trimester of pregnancy.

Not required for Clinical Vignette.

Non-Skin Related Symptoms Are Common in Chronic Spontaneous Urticaria and Linked to Active and Uncontrolled Disease: Results From the Chronic Urticaria Registry.

BACKGROUND: Chronic spontaneous urticaria (CSU) can present with non-skin related symptoms (NSRS), including recurrent unexplained fever, joint, bone, or muscle pain (JBMP), and malaise, which also occur in other conditions that manifest with wheals (eg, urticarial vasculitis or autoinflammatory disorders) or without wheals (eg, infection). OBJECTIVE: We sought to determine the rate of patients with CSU affected by fever, JBMP, and malaise, their trigger factors, links with clinical and laboratory characteristics, and their impact on everyday life and treatment responses. METHODS: We analyzed baseline data from the Chronic Urticaria Registry of 2,521 patients with CSU who were aged 16 years or older. RESULTS: One third of CSU patients (31.2%; 786 of 2,521) had one or more NSRS, including recurrent fever (5.3%), JBMP (19.1%), and/or malaise (18.6%). In a multivariable analysis, having one or more of these NSRS correlated with food and infection as trigger factors of urticaria (adjusted odds ratio [aOR] = 1.7 and 1.5), wheals of 24 hours or greater duration (aOR = 2.5), sleep disturbance (aOR = 2.4), anxiety (aOR = 2.8), comorbid atopic dermatitis (aOR = 2.1), gastrointestinal disease (aOR = 1.8), elevated leukocytes (aOR = 1.7) and erythrocyte sedimentation rate (aOR = 1.5). In a bivariate analysis, these NSRS were additionally associated with higher disease activity (weekly Urticaria Activity Score, median: 21 vs 14; P = .009), longer disease duration (years, median: 2 vs 1; P = .001), the presence of angioedema (74.6% vs 58.7%; P < .001), worse quality of life (Chronic Urticaria Quality of Life Questionnaire, median: 42 vs 29; P < .001) and more frequent poor control of CSU (78% vs 69%; P < .001). CONCLUSIONS: The presence of NSRS in a subpopulation of patients with CSU points to the need for better control of the disease, exclusion of comorbid conditions, and/or exclusion of urticarial vasculitis and urticarial autoinflammatory diseases.

Patient-Reported Outcome Measures in Atopic Dermatitis and Chronic Urticaria Are Underused in Clinical Practice.

BACKGROUND: Patient-reported outcome measures (PROMs) are validated and standardized tools that complement physician evaluations and guide treatment decisions. They are crucial for monitoring atopic dermatitis (AD) and chronic urticaria (CU) in clinical practice, but there are unmet needs and knowledge gaps regarding their use in clinical practice. OBJECCTIVE: We investigated the global real-world use of AD and CU PROMs in allergology and dermatology clinics as well as their associated local and regional networks. METHODS: Across 72 specialized allergy and dermatology centers and their local and regional networks, 2,534 physicians in 73 countries completed a 53-item questionnaire on the use of PROMs for AD and CU. RESULTS: Of 2,534 physicians, 1,308 were aware of PROMs. Of these, 14% and 15% used PROMs for AD and CU, respectively. Half of physicians who use PROMs do so only rarely or sometimes. Use of AD and CU PROM is associated with being female, younger, and a dermatologist. The Patient-Oriented Scoring Atopic Dermatitis Index and Urticaria Activity Score were the most common PROMs for AD and CU, respectively. Monitoring disease control and activity are the main drivers of the use of PROMs. Time constraints were the primary obstacle to using PROMs, followed by the impression that patients dislike PROMs. Users of AD and CU PROM would like training in selecting the proper PROM. CONCLUSIONS: Although PROMs offer several benefits, their use in routine practice is suboptimal, and physicians perceive barriers to their use. It is essential to attain higher levels of PROM implementation in accordance with national and international standards.

Absence of a Hernia Sack in Patients Undergoing Prenatal Repair of Spina Bifida Increases the Risk of Developing Shunt-Dependent Hydrocephalus.

Spina bifida aperta (SBA), with (myelomeningocele) or without (myeloschisis) a hernia sack, is the most common congenital defect of the central nervous system. Prenatal surgical closure of SBA lowers the risk for developing shunt-dependent hydrocephalus, which offers a chance at improved motor, urinary, and gastrointestinal function. A total of 96 patients who had undergone open surgery prenatal repair for SBA were analyzed. The patients were divided into two groups: Group I-12 patients (12.5%)-without a hernia sack (myeloschisis) and Group II-84 patients (87.5%)-with a hernia sack (myelomeningocele). In this study, we demonstrated that prenatal SBA repair was statistically significantly less often associated with the need for ventriculoperitoneal shunting (p > 0.00001). The shunting was statistically significantly more often required in patients from Group I (p > 0.004). The absence of a hernia sack increases the risk for developing shunt-dependent hydrocephalus in patients after prenatal SBA repair. However, as prenatal SBA repair is associated with better motor, urinary, and gastrointestinal function, increased risk of developing shunt-dependent hydrocephalus in fetuses without a hernia sack should not be treated as a contraindication to prenatal intervention.

Decreased Maternal Morbidity and Improved Perinatal Results of Magnesium-Free Tocolysis and Classical Hysterotomy in Fetal Open Surgery for Myelomeningocele Repair: A Single-Center Study.

Fetal and maternal risks associated with open fetal surgery (OFS) in the management of meningomyelocele (MMC) are considerable and necessitate improvement. A modified technique of hysterotomy (without a uterine stapler) and magnesium-free tocolysis (with Sevoflurane as the only uterine muscle relaxant) was implemented in our new magnesium-free tocolysis and classical hysterotomy (MgFTCH) protocol. The aim of the study was to assess the introduction of the MgFTCH protocol in reducing maternal and fetal complications. The prospective study cohort (SC) included 64 OFS performed with MgFTCH at the Fetal Surgery Centre Bytom (FSCB) (2015-2020). Fetal and maternal outcomes were compared with the retrospective cohort (RC; n = 46), and data from the Zurich Center for Fetal Diagnosis and Therapy (ZCFDT; n = 40) and the Children's Hospital of Philadelphia (CHOP; n = 100), all using traditional tocolysis. The analysis included five major perinatal complications (Clavien-Dindo classification, C-Dc) which developed before the end of 34 weeks of gestation (GA, gestational age). None of the newborns was delivered before 30 GA. Only two women presented with grade 3 complications and none with 4th or 5th grade (C-Dc). The incidence of perinatal death (3.3%) was comparable with the RC (4.3%) and CHOP data (6.1%). MgFTCH lowers the risk of major maternal and fetal complications.

Alternative technique of intrauterine myelomeningocele repair to decrease the incidence of unfavorable maternal and fetal outcomes.

OBJECTIVES: The aim of the study was to determine the effectiveness of an alternative method of open fetal surgery to prevent severe unfavorable prenatal events, both for the mother and the fetus. MATERIAL AND METHODS: In this study, the previously published results for a cohort of 46 patients, who had undergone intrauterine myelomeningocele repair (IUMR) at our Center by 2014, constituted the retrospective control group (CG). The MOMS protocol had been applied for hysterotomy, with an automatic uterine stapling device. The study group (SG) n = 57 was assembled during a prospective observation. IUMR was performed using an alternative method of hysterotomy, with the typical opening and closure of the uterus, without automatic stapling device, as described by Moron et al. Additionally, our single-center results were compared with the post-MOMS findings of other centers: CHOP (Children' S HOSPITAL OF PHILADELPHIA: ) and VUMC (Vanderbilt University Medical CENTER: ). RESULTS: No cases of delivery before 30 weeks of gestation (0%, 0/55) were observed in the study group, which is a statistically significant difference (p < 0.05) as compared to controls (15/44). Statistically significantly lower incidence of chorioamniotic separation (5.4% (3/55) vs CHOP 22.9% (22/96), p < 0.001) and contractile activity resulting in preterm labor (16.3% (9/55) vs CHOP 37.5% (36/96), p < 0.05) was found in the study group. Premature rupture of the membranes was statistically significantly less common in the study group as compared to controls, CHOP and VUMC (SG 12.7% (7/55) vs CG 52.2% (24/46), p < 0.001; vs CHOP 32.3% (31/96), p < 0.001; vs VUMC 22% (9/43), p < 0.01, respectively). CONCLUSIONS: The presented IUMR method is associated with improved perinatal outcomes, i.e., lower rates of preterm delivery at < 30 weeks of gestation, preterm premature rupture of membranes, and uterine contractility resulting in preterm delivery. That, in turn, results in lower prematurity rates and, consequently, more favorable neonatal outcomes.

Fetoscopic Myelomeningocele Repair with Complete Release of the Tethered Spinal Cord Using a Three-Port Technique: Twelve-Month Follow-Up-A Case Report.

Open spina bifida is one of the most common congenital defects of the central nervous system. Open fetal surgery, which is one of the available therapeutic options, remains the gold standard for prenatal repairs. Fetoscopic closure may lower the number of maternal complications associated with open fetal surgery. Regardless of the approach, the outcome may be compromised by the development of tethered spinal cord (TSC) syndrome. At 24.2 weeks of gestation, a primipara was admitted due to fetal myelomeningocele and was deemed eligible for fetoscopic repair. Fetal surgery was performed at 25.0 weeks of gestation. It was the first complete untethering of the spinal cord and anatomic reconstruction (dura mater, spinal erectors, skin) achieved during a fetoscopic repair of spina bifida. Cesarean section due to placental abruption was performed at 31.1 weeks of gestation. VP shunting, with no need for revision, was performed at 5 weeks postdelivery due to progressing ventriculomegaly. No clinical or radiological signs of secondary tethering were observed. Neurological examination at 11 months postdelivery revealed cranial nerves without any signs of damage, axial hypotonia, decreased muscle tone in the lower extremities, and absent pathological reflexes. Motor development was slightly retarded. Complete untethering of the neural structures should always be performed, regardless of the surgical approach, as it is the only course of action that lowers the risk for developing secondary TSC.

Open fetal surgery for myelomeningocele - is there the learning curve at reduction mother and fetal morbidity?

OBJECTIVES: We aimed to show how increased experience of a surgery team in fMMC repair influences maternal and fetal/neonatal outcomes. MATERIAL AND METHODS: We compare perinatal results of fMMC repair in our Fetal Surgery Center (FSC) in cohort groups for the 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 and MOMS. 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 in all 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.

Comparison of prenatal and postnatal treatments of spina bifida in Poland--a non-randomized, single-center study.

OBJECTIVE: The aim of this study was a comparison of the outcomes of intrauterine myelomeningocele (MMC) repairs (IUMR) in type II Chiari malformation (II CM) fetuses with clinical data of newborns and infants operated on postnatally. METHODS: The study group (SG) comprised 46 pregnant women whose type II CM children underwent IUMR, while 47 pregnant women whose type II CM children were operated on postnatally constituted the control group (CG). A total of 24 SG and 20 CG patients reached the endpoint of the study. RESULTS: High incidence of prelabor rupture of membranes (24 (52.2%), CI: 3.74 (1.69-8.26) (p < 0.001) was noted in the group of prenatal surgeries as compared to controls. The need for ventriculoperitoneal shunt implantation was statistically significantly lower (p < 0.008) in the group of children after IUMR as compared to controls (5 (27.8%) and 16 (80%), respectively, CI: 0.35 (0.16-0.75). None of the postnatally treated CG children can walk without adaptive equipment. In contrast, two children from the SG (2 (11.1%) CI: 1.86 (1.00-3.48) p < 0.05) are able to walk independently. CONCLUSIONS: Prenatal MMC closure significantly lowers further adverse evolution of the II CM. Further studies are needed, especially on preventive measures for preterm labor and iatrogenic preterm prelabor rupture of membranes (iPPRM) in the postoperative course of IUMR.