Prolonged grief disorder, a condition characterized by severe, persistent, and disabling grief, is newly included in ICD-11 and DSM-5-TR. Prolonged grief symptoms can be effectively treated with face-to-face or internet-delivered cognitive behavioral therapy. Traumatic losses may elicit higher prevalence of severe grief reactions. While face-to-face cognitive behavioral therapy appears efficacious in treating prolonged grief symptoms in traumatically bereaved individuals, it is not yet clear if internet-based cognitive behavioral therapy is efficacious for this population. Therefore, we investigated the efficacy of a 12-week internet-delivered cognitive behavioral therapy for people bereaved through traffic accidents in a randomized waitlist-controlled trial (registration number: NL7497, Dutch Trial Register). Forty adults bereaved though a traffic accident were randomized to internet-based cognitive behavioral therapy (n = 19) or a waitlist control condition (n = 21). Prolonged grief, post-traumatic stress, and depression symptoms were assessed at baseline, post-treatment, and 8-week follow-up. Dropout in the treatment condition was relatively high (42%) compared to the control condition (19%). Nevertheless, multilevel analyses showed that internet-based cognitive behavioral therapy strongly reduced prolonged grief, post-traumatic stress, and depression symptoms relative to the control condition at post-treatment and follow-up. We conclude that internet-based cognitive behavioral therapy appears a promising treatment for traumatically bereaved adults.

BACKGROUND: Patients with mosaic Turner syndrome who have normal phenotype and pubertal development may be diagnosed based on karyotype examination which is performed due to recurrent abortion or recurrent implantation failure; but according to the literature review, reproductive and obstetric consequences of these cases are based on case reports. There are contradictory publications on this subject recommending pre-implantation genetic testing (PGT) may be a solution to reduce the high risk for the fetus and perform normal embryo transfer.
OBJECTIVE: In this study, our aim was to evaluate the results of in vitro fertilization and preimplantation genetic diagnosis in patients with low-grade and high-grade mosaic Turner syndrome.
METHODS: We collected data of patients between 2012 and 2018 from a single center retrospectively. The study analyzed 36 mosaic Turner syndrome patients, of whom, 10 patients were evaluated as high, 26 patients were evaluated as low-grade mosaic pattern for Turner syndrome.
RESULTS: Mean age (35,46±0,87 vs. 36,2 ± 1,85) body mass index (25,26±0,74 vs. 30,8 ± 0,63) baseline follicle stimulating hormone (5,73±0,74 vs. 6,70±1,17) basal luteinizing hormone (4,78±0,43 vs. 4,92±0,99) were similar between two groups. In the high-grade mosaic Turner Syndrome patients, duration of stimulation (7,60±0,16 vs. 8,0 ± 0,28, p<0,001), total gonadotrophin dose (1540,0 ± 165,12 vs. 2046,15± 111,47, p<0,001) and the number of normal karyotype embryos was statistically significantly higher (1,58±0,17 vs. 2,00±0,55, p<0,001). The Pregnancy rates in the low-grade and high-grade mosaic Turner syndrome patients\' cycles were 30,8% versus 30%, (p = 0.76) respectively. IVF results were also evaluated by the presence of triploidy were accompanying Turner syndrome or not. In the presence of one or 2 X chromosomes, none of the included in the study could achieve live birth. The most common abnormality in the embryos was monosomy and trisomy of the chromosome13. In 30% of the cases, there were 2 or 3 abnormalities present together. In embryos with 2 abnormal chromosomes, the most common 2 abnormalities were monosomy 13 and trisomy 21, while trisomy 13, trisomy X and monosomy 18 were found in 3 or more abnormalities, respectively.
CONCLUSIONS: In vitro fertilization and Preimplantation genetic diagnose should be considered in the infertility treatment of the patient with mosaic Turner Syndrome.

BACKGROUND: Chromosomal abnormalities affect many children which lead to high rates of morbidity and mortality among them. So, preimplantation genetic testing (PGT) is an evolving technology used to detect a specific genetic disorder in embryos of a couple known to be carriers or affected by a specific mutation. Similarly, it could be used in advanced maternal age which is a high risk of chromosomal abnormalities. Although PGT is a solution for many inherited chromosomal disorders, many ethical dilemmas surround its application. Thus, the aim of this study is to evaluate the community awareness and acceptance of PGT which will eventually lead to a healthier society through disease-free babies in Eastern Province, Kingdom of Saudi Arabia (KSA).
METHODS: A qualitative cross-sectional questionnaire-based study was conducted within the population of the Eastern Province of Saudi Arabia. The questionnaire was designed in Arabic and distributed electronically through social media platforms.
RESULTS: The study included 837 participants, whose ages ranged from 18 to 65 years with the mean age 33.5 ± 11.9 years. Good awareness and acceptance were detected among 53.7% of the old aged group (50 years or more) compared to 39.5% of the young age group. Also, 44.9% of female participants had good awareness in comparison to 34.2% of males (p=.033). Participants with a higher number of children had significantly higher awareness and acceptance of PGT. Also, 44.3% of participants who knew someone in need of assisted reproductive technology, had good awareness and acceptance levels compared to 36.9% of those who did not (p=.033).
CONCLUSIONS: The perception of Eastern Province\'s Saudi citizens toward PGT is found to be low. Increasing their perception toward such technology is needed as it is known that many chromosomal abnormalities are prevalent among this population, particularly sickle cell disease. Achieving this goal will eventually lead to decrease the burden of prevalent inherited diseases. Since Saudis\' opinions are almost influenced by cultural and religious points of view, care should be given to these aspects.

Background: Prolonged grief disorder (PGD) is a chronic and disabling condition that affects approximately 10% of non-traumatically bereaved people. Narrative reconstruction (NR), originally designed for the treatment of posttraumatic stress disorder (PTSD), is a time-limited integrative therapy consisting of exposure to the loss memory, detailed written reconstruction of the loss memory narrative, and an elaboration of the personal significance of that memory for the bereaved. Objective: This pilot study examined the efficacy of NR therapy in reducing symptoms in bereaved people diagnosed with PGD. Method: Ten PGD patients participated in the study and were treated with 16 weekly sessions of NR. PGD, PTSD, and depression symptoms, as well as levels of loss integration, were assessed at pre-treatment, post-treatment, and at a 3-month follow-up. Results: Following NR, participants showed significant reductions in PGD, depression, and PTSD symptoms, and elevated levels of trauma integration. Symptoms showed further improvement at the three-month follow-up. Conclusions: These findings provide preliminary evidence for the feasibility and efficacy of NR in treating PGD. Narrative reconstruction therapy requires further evaluation in randomized controlled trials.
Antecedentes: El trastorno de duelo prolongado (PGD en su sigla en inglés) es una condición crónica y discapacitante que afecta aproximadamente al 10% de las personas que experimentan un duelo no traumático. La reconstrucción narrativa (NR en su sigla en inglés) fue diseñada originalmente para el tratamiento del trastorno de estrés postraumático (TEPT), es una terapia integrativa de tiempo limitado que consiste en la exposición a la memoria de la pérdida, la reconstrucción escrita detallada de la memoria narrativa de la pérdida, y una elaboración del significado personal de esa memoria para la persona experimentando el duelo.Objetivo: Este estudio piloto examina la eficacia de la terapia NR en reducir los síntomas en las personas experimentando duelo que han sido diagnosticadas con el PGD.Método: Diez pacientes con PGD participaron en el estudio y fueron tratados con 16 sesiones semanales de NR. Los síntomas de PGD, TEPT, y depresión, como también los niveles de integración de la pérdida, fueron evaluados previo al tratamiento, luego del tratamiento, y a los 3 meses de seguimiento.Resultados: Siguiendo NR, los participantes mostraron reducciones significativas en los síntomas de PGD, depresión, y TEPT, y niveles elevados de integración del trauma. Los síntomas mostraron mayores mejoras a los tres meses de seguimiento.Conclusión: Estos hallazgos proveen evidencia preliminar para la factibilidad y eficacia del NR en tratar el PGD. La terapia de reconstrucción narrativa requiere mayor evaluación en ensayos controlados aleatorizados.
背景: 延长哀伤障碍 (PGD) 是一种慢性致残性疾病, 大约影响了10％的非创伤性丧亲者。叙述重构 (NR) 最初是为治疗创伤后应激障碍 (PTSD) 设计的, 是一种限时的综合疗法, 包括丧失记忆暴露, 对丧失记忆叙事进行详细的书面重构以及阐述对死者的记忆对于个人的意义。目的: 本前瞻性研究考查了NR治疗减轻诊断为PGD的丧亲者症状的有效性。方法: 十名PGD患者参与了研究, 接受了每周16次的NR治疗。在治疗前, 后以及3个月的随访中评估了PGD, PTSD和抑郁症状以及丧失综合程度。结果: NR后, 参与者表现出PGD, 抑郁和PTSD症状显著减少, 创伤整合水平升高。在3个月的随访中, 症状进一步改善。结论: 这些发现为NR治疗PGD的可行性和有效性提供了初步证据。叙事重构疗法需要在随机对照试验中进行进一步评估。.

To assess differences in prolonged grief, depression, posttraumatic stress, and sleep disturbances in bereaved parents across years since loss (1-5 years) and by gender and to assess potential interactive effects of time since loss and gender on bereavement outcomes.
This study examined symptom levels of prolonged grief disorder, depression, posttraumatic stress, and insomnia in bereaved parents. A sample, including 133 mothers and 92 fathers who had lost a child to cancer 1 to 5 years previously, subdivided to five subsamples, one for each year since loss. Analysis of variance (ANOVA) was used to assess differences in symptom levels, related to years since loss, and gender.
Regardless of how many years had passed since the loss, symptom levels of prolonged grief, depression, posttraumatic stress symptoms, and insomnia were elevated in all subsamples. Mothers showed higher symptom levels of prolonged grief, depression, and posttraumatic stress than fathers. However, no significant interaction effects were found between years since loss and gender on any of the symptom levels.
Cancer-bereaved mothers and fathers are vulnerable to prolonged grief and psychological symptoms up to 5 years after the death of their child. Findings highlight that bereaved parents may need long-term support, and the results deserve further attention in research and clinical care.

OBJECTIVE: Does Day 3 embryo biopsy for pre-implantation genetic testing for monogenic (PGT-M) and structural chromosomal aberrations (PGT-SR) affect body composition and blood pressure readings of 6-year-old singletons?
CONCLUSIONS: This study of 87 PGT-M and PGT-SR conceived singletons showed no differences in anthropometric measurements and blood pressure readings in comparison with a matched cohort of peers born after ICSI without embryo biopsy.
BACKGROUND: While neonatal outcomes after PGT conception have been found comparable to those after ICSI without embryo biopsy, only a few studies have reported outcomes after PGT at older ages. Moreover, embryo biopsy is also applied in couples who opt for PGT-M and PGT-SR and hence are not necessarily infertile. Health parameters and in particular body composition data in this group of children are lacking.
UNASSIGNED: This single-centre matched-pair cohort study evaluated body composition of 6-year-old children born after fresh blastocyst embryo transfer with or without embryo biopsy performed at Day 3 for the purpose of PGT-M and PGT-SR. For each child born after embryo biopsy, a singleton born after transfer of a fresh ICSI embryo at the blastocyst stage and reaching the age of 6 years between May 2011 and June 2017 was matched as closely as possible for gender, age, maternal educational level and birth order.
METHODS: Anthropometry (weight, height, BMI, skinfold thickness, waist and mid-upper arm circumference) and blood pressure readings in a longitudinally followed cohort of 87 singletons conceived by PGT-M and PGT-SR and a pairwise matched sample of 87 children conceived by ICSI are described. Results are adjusted for current, neonatal and parental characteristics.
RESULTS: From the 124 eligible PGT-M and PGT-SR families, 110 could be reached of whom 23 refused and 87 (87/110 = 79%) participated. All anthropometric measurements, including z-scores of BMI, waist and mid-upper arm circumference, were comparable between the PGT-M and PGT-SR (-0.23; 0.27; 0.17, respectively) and ICSI (-0.29; 0.11; 0.11, respectively) groups (all P > 0.05). Furthermore, indices of peripheral (triceps) and central (subscapular) adiposity derived from skinfold thickness were comparable (PGT-M and PGT-SR: 14.7 mm; 11.6 mm and ICSI: 15.5 mm; 11.5 mm) as well as the percentage total body fat mass derived from these (PGT-M and PGT-SR: 13.7% and ICSI: 13.9%) (all P > 0.05). Z-scores for blood pressure were also comparable between the PGT and ICSI groups (all P > 0.05). Results did not change when adjusted for neonatal (birthweight, birth order), current (age) and parental (smoking during pregnancy, parental BMI) characteristics. Hospitalization rate and surgical intervention rate were not different for PGT-M and PGT-SR children compared to matched peers born after ICSI.
CONCLUSIONS: Although our study describes the largest cohort of singletons born after embryo biopsy worldwide, we were only able to detect moderate differences in anthropometrics and blood pressure with our sample size.
CONCLUSIONS: Although Day 3 embryo biopsy followed by blastocyst transfer is not associated with adverse outcomes regarding anthropometry and blood pressure, future studies should focus on outcomes in children born after trophectoderm biopsy and/or transfer of warmed embryos after vitrification.
BACKGROUND: This study was supported by Methusalem grants and by grants from Wetenschappelijk Fonds Willy Gepts; all issued by the Vrije Universiteit Brussel (VUB). All co-authors, except M.B. declared no conflict of interest. M.B. has received consultancy fees from MSD, Serono Symposia and Merck. The Universitair Ziekenhuis Brussel (UZ Brussel) and the Centre for Medical Genetics have received several educational grants from IBSA, Ferring, Organon, Shering-Plough, Merck for establishing the database for follow-up research and organizing the data collection.

The use of GnRH analogue medication is essential in reproductive medicine to avoid premature ovulation by pituitary suppression for the duration of ovarian stimulation by gonadotrophins. The type of pituitary suppression by either GnRH agonist analogues versus GnRH antagonist analogues may result in different embryological hence clinical results. Preimplantation genetic diagnosis is a subtype of IVF in which embryos are created for genetic diagnosis of hereditary disorders in order to avoid genetically affected children. Embryological quality hence ovarian stimulation in preimplantation genetic diagnosis is crucial as genetic selection will reduce the number of available embryos to a fraction of the total.
The aim of this study was to assess the efficiency of GnRH antagonist versus GnRH agonist treatment for pituitary suppression in ovarian stimulation for PGD, by proxy of number and quality of embryos at cleavage stage available for biopsy.
We conducted a prospective randomised controlled trial comparing pituitary suppression by GnRH antagonist versus GnRH agonist in ovarian stimulation for PGD. The primary outcome measure was the number of embryos of sufficient quality for biopsy at cleavage stage. Secondary outcome parameters were the number of blastocysts available of top quality, and clinical pregnancy rate.
There was no difference in number of oocytes retrieved, embryos at cleavage stage available for biopsy or embryo quality. The clinical pregnancy rate was higher in the GnRH agonist group; however the sample size was insufficient to allow conclusions.
The use of GnRH agonist versus antagonist treatment does not result in differences in a number of oocytes, embryos or embryo quality in ovarian stimulation for preimplantation genetic diagnosis.

The aim of this pilot study was to assess if array comparative genomic hybridization (aCGH), non-invasive preimplantation genetic screening (PGS) on blastocyst culture media is feasible. Therefore, aCGH analysis was carried out on 22 spent blastocyst culture media samples after polar body PGS because of advanced maternal age. All oocytes were fertilized by intracytoplasmic sperm injection and all embryos underwent assisted hatching. Concordance of polar body analysis and culture media genetic results was assessed. Thirteen out of 18 samples (72.2%) revealed general concordance of ploidy status (euploid or aneuploid). At least one chromosomal aberration was found concordant in 10 out of 15 embryos found to be aneuploid by both polar body and culture media analysis. Overall, 17 out of 35 (48.6%) single chromosomal aneuploidies were concordant between the culture media and polar body analysis. By analysing negative controls (oocytes with fertilization failure), notable maternal contamination was observed. Therefore, non-invasive PGS could serve as a second matrix after polar body or cleavage stage PGS; however, in euploid results, maternal contamination needs to be considered and results interpreted with caution.

OBJECTIVE: We aim to present a case of a healthy infant born after intracytoplasmic sperm injection-in vitro fertilization (ICSI-IVF) with a preimplantation genetic diagnosis (PGD) for pantothenate kinase-associated neurodegeneration (PKAN) due to PANK2 mutation.
METHODS: ICSI-IVF was performed on a Thai couple, 34-year-old female and 33-year-old male, with a family history of PKAN in their first child. Following fertilization, each of the embryos were biopsied in the cleavage stage and subsequently processed for whole-genome amplification. Genetic status of the embryos was diagnosed by linkage analysis and direct mutation testing using primer extension-based mini-sequencing. Comprehensive chromosomal aneuploidy screening was performed using a next-generation sequencing-based strategy.
RESULTS: Only a single cycle of ICSI-IVF was processed. There were seven embryos from this couple-two were likely affected, three were likely carriers, one was likely unaffected, and one failed in target genome amplification. Aneuploidy screening was performed before making a decision on embryo transfer, and only one unaffected embryo passed the screening. That embryo was transferred in a frozen thawed cycle, and the pregnancy was successful. The diagnosis was confirmed by amniocentesis, which presented with a result consistent with PGD. At 38 weeks of gestational age, a healthy male baby was born. Postnatal genetic confirmation was also consistent with PGD and the prenatal results. At the age of 24 months, the baby presented with normal growth and development lacking any neurological symptoms.
CONCLUSIONS: We report the first successful trial of PGD for PKAN in a developing country using linkage analysis and mini-sequencing in cleavage stage embryos.

OBJECTIVE: To study whether women conceiving after preimplantation genetic diagnosis (PGD) and their children have greater risks of adverse pregnancy and birth outcomes compared with children conceived spontaneously or after IVF with or without intracytoplasmic sperm injection (ICSI).
METHODS: Historical cohort study.
METHODS: Not applicable.
METHODS: All deliveries following PGD treatment for single gene and sex-linked disorders or structural chromosomal aberrations (n = 126 deliveries/149 children), IVF/ICSI treatment (n = 30,418 deliveries/36,115 children), and spontaneous conception (n = 896,448 deliveries/909,624 children).
METHODS: None.
METHODS: Adverse obstetric and neonatal outcomes, such as pre-eclampsia, preterm primary rupture of membranes, placenta previa, abruption of placenta, preterm birth, low birth weight, malformations, and neonatal admission.
RESULTS: Compared with spontaneously conceived pregnancies, PGD pregnancies were at significantly increased risk of placenta previa (adjusted odds ratio [ORa] 9.1; 95% confidence interval [95% CI] 3.4, 24.9), cesarean section (ORa 2.0; 95% CI 1.3, 2.9), preterm birth (ORa 1.6; 95% CI 1.0, 2.7), shorter gestation (mean difference -3.4 days; 95% CI -5.7, -1.1 days), and longer neonatal admission (mean difference 21 days; 95% CI 15, 28 days). The risks were comparable to that of pregnancies following IVF/ICSI. In subanalyses, adverse outcomes were only present in children conceived by PGD owing to parental monogenetic disorder and comparable to those of children born to parents with monogenic disorders conceiving without PGD, except for a higher risk of placenta previa.
CONCLUSIONS: In this cohort study, the risk of adverse obstetric and neonatal outcomes was mainly related to the underlying parental condition rather than the PGD procedure.