Drug use during pregnancy is an important issue that must be investigated due to its adverse effects on maternal and foetal health. This study aimed to determine the embryotoxic and teratogenic effects of in-ovo administered metamizole (dipyrone), which can be used when needed during pregnancy and has potent analgesic, antipyretic, anti-inflammatory, and long bone (tibia and femur) effects. This study used 240 fertile eggs from Atak S breed chickens, divided into eight equal groups: control, vehicle control, and 15.62, 31.25, 62.5, 125, 250 and 500 mg/kg metamizole. The eggs were hatched on the 21st day of incubation, and the chicks\' body weights and mortality rates were determined. The right and left femur and tibia bones were resected from the chicks. Anatomical reference points were determined after removing the soft tissues of the bones, and necessary morphometric measures were taken from these points with a 0.01 mm precision using digital callipers. The 100% lethal dose (LD100) was identified in the highest examined dose (500 mg/kg) in the Chicken Embryotoxicity Screening Test (CHEST)-I stage. The CHEST-II stage determined the 50% lethal dose (LD50). High-dose metamizole affected skeletal development, significantly decreasing tibia and femur lengths and corpus thicknesses and increasing mortality.

Antifungals are a class of drugs that target the treatment of invasive fungal infections. This includes polyenes, triazoles, and echinocadins. Among these, azoles are being extensively used nowadays. Triazoles have become standard for the azoles and have replaced amphotericin B as the first line of defence for fungal infections. With the increased cases of fungal infection, which affect a majority of the population at different stages and situations, one such section of the population is pregnant females. The rate and susceptibility of fungal infections are particularly higher in pregnant females, as the immunity of the mother is highly compromised. Systemic fungal infections like invasive aspergillosis, esophageal candidiasis, and candidemia are being treated with new age triazole antifungals like voriconazole. Prolonged and high concentrations of this drug are associated with various developmental anomalies. With this aim, teratogenic studies were performed on pregnant female mice during gestation and the weaning/lactation period to observe the effects of voriconazole at different dosages (8mg/kg b.w., 10mg/kg b.w., and 20mg/kg b.w.). Pregnant dams were subjected to 20mg/kg b.w. Voriconazole had a small litter size and a high number of resorptions. Craniofacial defects in the form of reduced ossification and widely open sutures, the presence of the 14th rib, asymmetry in the sternebrae, and the absence of ossified distal phalanges were some of the skeletal anomalies which were significant in the foetus and pups subjected to both 10mg/kg b.w. and 20mg/kg b.w. doses of voriconazole.

Detecting the toxic effects of chemicals on reproduction and development without using mammalian animal models is crucial in the exploitation of pharmaceuticals for human use. Zebrafish are a promising animal model for investigating pharmacological effects and toxicity during vertebrate development. Several studies have suggested the use of zebrafish embryos for the assessment of malformations or embryo-fetal lethality (MEFL). However, a reproducible protocol as a standard for the zebrafish MEFL test method that fulfills global requests has not been established based on the International Council of Harmonisation (ICH) S5 (R3) guidelines. To establish such a toxicity test method, we developed a new and easy protocol to detect MEFL caused by chemicals, especially those with teratogenic potential, using fertilized zebrafish eggs (embryos) within 5 days of development. Our toxicity test trials using the same protocol in two to four different laboratories corroborated the high inter-laboratory reproducibility. Our test method enabled the detection of 18 out of 22 test compounds that induced rat MEFL. Thus, the prediction rate of our zebrafish test method for MEFL was almost 82% compared with that of rat MEFL. Collectively, our study proposes the establishment of an easy and reproducible protocol for the zebrafish MEFL test method for reproductive and developmental toxicity that meets ICH guideline S5 (R3), which can be further considered in combination with information from other sources for regulatory use.

Background: Porcine bile powder (PBP) is a traditional Chinese medicine that has been used for centuries in various therapeutic applications. However, PBP has not previously undergone comprehensive component analysis and not been evaluated for safety through standard in vivo toxicological studies. Methods: In our study, we characterized the component of PBP by liquid chromatography-mass spectrometry. The acute and subchronic oral toxicity, genotoxicity, and teratogenicity studies of PBP were designed and conducted in Kunming mice and Sprague-Dawley (SD) rats. Results: The chemical analysis of PBP showed that the main components of PBP were bile acids (BAs), especially glycochenodeoxycholic acid. There were no signs of toxicity observed in the acute oral test and the subchronic test. In the genotoxicity tests, no positive results were observed in the bacterial reverse mutation test. Additionally, in the mammalian micronucleus test and mouse spermatocyte chromosomal aberration test, no abnormal chromosomes were observed. In the teratogenicity test, no abnormal fetal development was observed. Conclusion: Our findings demonstrate that PBP, composed mainly of BAs, is non-toxic and safe based on the conditions tested in this study.

OBJECTIVE: What is the risk of an undetected natural conception pregnancy during luteal phase ovarian stimulation, and how does it impact the pregnancy\'s course?
CONCLUSIONS: The risk for an undetected, natural conception pregnancy in luteal phase ovarian stimulation is low and it appears that ovarian stimulation is unlikely to harm the pregnancy.
BACKGROUND: Random start ovarian stimulation appears to be similarly effective as early follicular stimulation start; and it allows ovarian stimulation to be started independent of the cycle day and throughout the cycle, in accordance with the patients\' and clinics\' schedule as long as there is no intention of a fresh embryo transfer in the same cycle. Starting ovarian stimulation in the luteal phase bears the possibility of an-at the timepoint of stimulation start-undetected, natural conception pregnancy that has already occurred. There is scarce data on the incidence of this event as well as on the possible implications of ovarian stimulation on the course of an existing pregnancy.
METHODS: This retrospective observational study, performed between June 2017 and January 2024, analyzed luteal phase stimulations, in which a natural conception pregnancy was detected during the ovarian stimulation treatment for IVF/ICSI. Luteal phase stimulation was defined as ovarian stimulation started after ovulation and before the next expected menstrual bleeding, with a serum progesterone (P4) level of >1.5 ng/ml on the day of stimulation start or 1 day before.
METHODS: Women who underwent a luteal phase ovarian stimulation in a tertiary referral ART center.
RESULTS: A total of 488 luteal phase stimulation cycles were included in the analysis. Luteal phase stimulation was only started after a negative serum hCG measurement on the day or 1 day before commencement of ovarian stimulation. Ten patients (2.1%) had an undetected natural conception pregnancy at the time of luteal phase stimulation start. Eight of these patients underwent an ovarian stimulation in a GnRH-antagonist protocol and two in a progestin-primed stimulation protocol (PPOS). Recombinant FSH was used as stimulation medication for all patients, the patients with a PPOS protocol received additional recombinant LH. One pregnancy (0.2%) was detected after the oocyte retrieval, the other nine pregnancies were detected either due to persistent high serum progesterone levels or due to an increasing progesterone level after an initial decrease before oocyte retrieval. In the cycles with an undetected natural conception pregnancy, the median number of stimulation days was 8 days (range: 6-11 days) and median serum hCG at detection of pregnancy was 59 IU hCG (range: 14.91-183.1). From 10 patients with a pregnancy, three patients delivered a healthy baby, two patients had ongoing pregnancies at the time of summarizing the data, three patients had biochemical pregnancies (patient age: 30, 39, and 42 years), one patient had an ectopic pregnancy which required a salpingectomy, and one patient (age: 34 years) had an early pregnancy loss.
CONCLUSIONS: The retrospective study design and the small sample size can limit the accuracy of the estimates.
CONCLUSIONS: Overall, there is a small risk of undetected natural conception pregnancies when luteal phase stimulation is undertaken. It appears that there are no adverse effects through either direct effect on the embryo or indirectly through a detrimental effect on the corpus luteum function on the pregnancy in our cohort.
BACKGROUND: This study did not receive funding. The authors declare that there is no conflict of interest.
BACKGROUND: N/A.

Carbamazepine is an anticonvulsant medication commonly used to treat epilepsy and other neurological disorders. The purpose of this study was to assess the impact of carbamazepine on prenatal development, including maternal-fetal, external, visceral, and skeletal toxicity. Additionally, the study aimed to investigate the effects of orally administered Carbamazepine at a lower dose range in Wistar rats. Pregnant female rats were randomly distributed into control (G1) group administered with distilled water orally (n=8), low dose (G2) group administered at 25 mg/kg, intermediate dose (G3) group at 50 mg/kg, and high dose (G4) group at 100 mg/kg through oral gavage from gestation day (GD) 5-19. Pregnant female rats were scheduled to necropsy on gestation day (GD) 20. During the evaluation, the uterus was observed for number of live or viable fetuses, dead fetuses, early resorptions, late resorptions, number of corpora lutea and the sex ratio (m/f) per litter. Further, fetuses were subjected to materno-fetal examination which included observation for placenta, amniotic fluid, and umbilical cord followed by external evaluation. Additionally, half of the fetuses were subjected to visceral, craniofacial evaluation and other half of the fetuses were subjected to skeletal evaluation by double staining method using Alcian Blue for cartilages and Alizarin Red S for bones. It was observed that there was a significant decrease in the rate of pregnancy in the intermediate dose (G3) group and in high dose (G4) group when compared with the control group. Moreover, treatment with the Carbamazepine caused significant increase in fetal malformations such as dilation of lateral and third ventricle in brain, in intermediate dose (G3) group and high dose (G4) group when compared with the control (G1) group, dilation of ureters in high dose (G4) group. Fetal skeletal malformations like bent and nodulated ribs were also observed in intermediate dose (G3) group. Existing research substantially supports the claim that carbamazepine can cause teratogenic effects and prenatal development toxicity even at a lower dose range.

Bulk zinc oxide (ZnO-BPs) and its nanoparticles (ZnO-NPs) are frequently used in various products for humans. Helisoma duryi embryos can serve as effective model organisms for studying the toxicity of NPs. This study aimed to compare the teratogenic potency of ZnO-BPs and ZnO NPs in the embryonic stages of H. duryi to evaluate the utility of this snail as a bioindicator for ZnO-NPs in the aquatic environment. The mechanisms of teratogenesis were evaluated by determination of the LC50, studying the effect of sub-lethal concentrations of both ZnO forms on the embryos, and studying their enzyme activity, oxidative stress, and biochemical analysis. The SDS-PAGE electrophoresis was undertaken to assess the effect of ZnO-BPs and ZnO NPs on protein synthesis. The results revealed that the veliger stage of H. duryi is the specific stage for bulk and nano ZnO. ZnO-NPs proved to be more toxic to snails\' embryos than ZnO-BPs. Exposure to ZnO influences specific types of defects in development, which in the case of BPs are far less drastic than those caused by NPs. Thus, the toxicity of ZnO-NPs in embryonic development is due to their unique physicochemical properties. The observed malformations include mainly hydropic malformation, exogastrulation, monophthalmia, shell misshapen, and cell lyses. Almost all tested oxidative biomarkers significantly changed, revealing that ZnONPs display more oxidative stress than ZnO-BPs. Also, the low concentration of ZnO induces many disturbances in the organic substances of veliger larvae, such as a decrease in the total protein and total lipid levels and an increase in the glycogen level. The results indicated that ZnO-BPs increase the number of protein bands. Conversely, ZnO-NPs concealed one band from treated egg masses, which was found in the control group. Embryos of snail are an appropriate model to control freshwater snails. This study demonstrates that H. duryi embryos can serve as effective model organisms to study the toxicity of ZnO-NPs.

Previous studies examining antidepressants and congenital-malformations were primarily conducted in western countries, and many were constrained by important methodological limitations. This population-based study identified 465,069 women (including 1,705 redeemed ≥1 prescription of antidepressants during first-trimester) aged 15-50 years who delivered their first and singleton child between 2003 and 2018 in a predominantly-Chinese population in Hong Kong, using territory-wide medical-record database of public-healthcare services, and employed propensity-score fine-stratification-weighted logistic-regression analyses to evaluate risk of any major and organ/system-specific congenital-malformations following first-trimester exposure to antidepressants. Major malformation overall was not associated with any antidepressant (weighted-odds-ratio wOR, 0.88 [95 %CI, 0.44-1.76]), specific drug-class, or individual antidepressants. Exposure to any antidepressant was associated with increased risk of cardiac (wOR, 1.82 [95 %CI, 1.07-3.12]) and respiratory anomalies (wOR,4.11 [95 %CI, 1.61-10.45]). Exposure to selective-serotonin-reuptake-inhibitors (SSRI) and multiple-AD-classes were associated with respiratory and cardiac anomalies, respectively. However, these identified associations were not consistently affirmed across sensitivity analyses, precluding firm conclusion. Observed associations of specific cardiac defects with serotonin-norepinephrine-reuptake-inhibitors (SNRI), tricyclic-antidepressants (TCA) and multiple-AD-classes were noted with wide confidence-intervals, suggesting imprecise estimation. Overall, our findings suggest that first-trimester antidepressant exposure was not robustly associated with increased risk of congenital-malformations. Further research clarifying comparative safety of individual antidepressants on specific malformations is warranted.

UNASSIGNED: Approximately 1-2% of pregnant women undergo non-obstetric surgery under anaesthesia during their pregnancy. This review specifically targets anaesthesia management for pregnant women undergoing non-obstetric surgery in resource-limited settings.
UNASSIGNED: Following the delineation of primary questions, scope, and inclusion criteria, a comprehensive search strategy utilizing advanced techniques was implemented across electronic sources, databases, and websites to identify relevant articles. A rigorous screening process was applied during the literature evaluation. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement guided the conduct of this review, ensuring adherence to standardized reporting practices.
UNASSIGNED: A total of 240 articles were initially identified from databases and websites. After screening titles and abstracts, 85 papers were excluded, and an additional 43 were removed due to duplication. Subsequently, 68 items were subjected to eligibility screening. Finally, 30 papers that specifically addressed anaesthetic considerations for pregnant women undergoing non-obstetric operations were reviewed.
UNASSIGNED: Thorough preoperative evaluation is essential for all patients, with particular attention to modifications in anaesthetic management to accommodate physiological changes during pregnancy. Urgent and emergent surgeries should proceed promptly during pregnancy to optimize outcomes for both the mother and foetus. Maintaining uteroplacental perfusion generally involves avoiding maternal hypoxaemia, hypotension, hyper- and hypocapnia, temperature extremes, and stress. When deemed safe, regional anaesthesia may offer favourable outcomes for both the mother and foetus.

Following two requests from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the revision of the tolerable upper intake level (UL) for preformed vitamin A and β-carotene. Systematic reviews of the literature were conducted for priority adverse health effects of excess vitamin A intake, namely teratogenicity, hepatotoxicity and endpoints related to bone health. Available data did not allow to address whether β-carotene could potentiate preformed vitamin A toxicity. Teratogenicity was selected as the critical effect on which to base the UL for preformed vitamin A. The Panel proposes to retain the UL for preformed vitamin A of 3000 μg RE/day for adults. This UL applies to men and women, including women of child-bearing age, pregnant and lactating women and post-menopausal women. This value was scaled down to other population groups using allometric scaling (body weight0.75), leading to ULs between 600 μg RE/day (infants 4-11 months) and 2600 μg RE/day (adolescents 15-17 years). Based on available intake data, European populations are unlikely to exceed the UL for preformed vitamin A if consumption of liver, offal and products thereof is limited to once per month or less. Women who are planning to become pregnant or who are pregnant are advised not to consume liver products. Lung cancer risk was selected as the critical effect of excess supplemental β-carotene. The available data were not sufficient and suitable to characterise a dose-response relationship and identify a reference point; therefore, no UL could be established. There is no indication that β-carotene intake from the background diet is associated with adverse health effects. Smokers should avoid consuming food supplements containing β-carotene. The use of supplemental β-carotene by the general population should be limited to the purpose of meeting vitamin A requirements.