Continuing benefits of the Montreal Protocol and protection of the stratospheric ozone layer for human health and the environment.

The protection of Earth's stratospheric ozone (O3) is an ongoing process under the auspices of the universally ratified Montreal Protocol and its Amendments and adjustments. A critical part of this process is the assessment of the environmental issues related to changes in O3. The United Nations Environment Programme's Environmental Effects Assessment Panel provides annual scientific evaluations of some of the key issues arising in the recent collective knowledge base. This current update includes a comprehensive assessment of the incidence rates of skin cancer, cataract and other skin and eye diseases observed worldwide; the effects of UV radiation on tropospheric oxidants, and air and water quality; trends in breakdown products of fluorinated chemicals and recent information of their toxicity; and recent technological innovations of building materials for greater resistance to UV radiation. These issues span a wide range of topics, including both harmful and beneficial effects of exposure to UV radiation, and complex interactions with climate change. While the Montreal Protocol has succeeded in preventing large reductions in stratospheric O3, future changes may occur due to a number of natural and anthropogenic factors. Thus, frequent assessments of potential environmental impacts are essential to ensure that policies remain based on the best available scientific knowledge.

Oral dydrogesterone versus micronized vaginal progesterone for luteal phase support: a double-blind crossover study investigating pharmacokinetics and impact on the endometrium.

STUDY QUESTION: How do plasma progesterone (P) and dydrogesterone (D) concentrations together with endometrial histology, transcriptomic signatures, and immune cell composition differ when oral dydrogesterone (O-DYD) or micronized vaginal progesterone (MVP) is used for luteal phase support (LPS)? SUMMARY ANSWER: Although after O-DYD intake, even at steady-state, plasma D and 20αdihydrodydrogesterone (DHD) concentrations spiked in comparison to P concentrations, a similar endometrial signature was observed by histological and transcriptomic analysis of the endometrium. WHAT IS KNOWN ALREADY: O-DYD for LPS has been proven to be noninferior compared to MVP in two phase III randomized controlled trials. Additionally, a combined individual participant data and aggregate data meta-analysis indicated that a higher pregnancy rate and live birth rate may be obtained in women receiving O-DYD versus MVP for LPS in fresh IVF/ICSI cycles. Little data are available on the pharmacokinetic (PK) profiles of O-DYD versus MVP and their potential molecular differences at the level of the reproductive organs, particularly at the endometrial level. STUDY DESIGN, SIZE, DURATION: Thirty oocyte donors were planned to undergo two ovarian stimulation (OS) cycles with dual triggering (1.000 IU hCG + 0.2 mg triptorelin), each followed by 1 week of LPS: O-DYD or MVP, in a randomized, cross-over, double-blind, double-dummy fashion. On both the first and eighth days of LPS, serial blood samples upon first dosing were harvested for plasma D, DHD, and P concentration analyses. On Day 8 of LPS, an endometrial biopsy was collected for histologic examination, transcriptomics, and immune cell analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: All oocyte donors were <35 years old, had regular menstrual cycles, no intrauterine contraceptive device, anti-Müllerian hormone within normal range and a BMI ≤29 kg/m2. OS was performed on a GnRH antagonist protocol followed by dual triggering (1.000 IU hCG + 0.2 mg triptorelin) as soon as ≥3 follicles of 20 mm were present. Following oocyte retrieval, subjects initiated LPS consisting of MVP 200 mg or O-DYD 10 mg, both three times daily. D, DHD, and P plasma levels were measured using liquid chromatography-tandem mass spectrometry. Histological assessment was carried out using the Noyes criteria. Endometrial RNA-sequencing was performed for individual biopsies and differential gene expression was analyzed. Endometrial single-cell suspensions were created followed by flow cytometry for immune cell typing. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 21 women completed the entire study protocol. Subjects and stimulation characteristics were found to be similar between groups. Following the first dose of O-DYD, the average observed maximal plasma concentrations (Cmax) for D and DHD were 2.9 and 77 ng/ml, respectively. The Cmax for D and DHD was reached after 1.5 and 1.6 h (=Tmax), respectively. On the eighth day of LPS, the first administration of that day gave rise to a Cmax of 3.6 and 88 ng/ml for D and DHD, respectively. For both, the observed Tmax was 1.5 h. Following the first dose of MVP, the Cmax for P was 16 ng/ml with a Tmax of 4.2 h. On the eighth day of LPS, the first administration of that day showed a Cmax for P of 21 ng/ml with a Tmax of 7.3 h. All 42 biopsies showed endometrium in the secretory phase. The mean cycle day was 23.9 (±1.2) in the O-DYD group versus 24.0 (±1.3) in the MVP group. RNA-sequencing did not reveal significantly differentially expressed genes between samples of both study groups. The average Euclidean distance between samples following O-DYD was significantly lower than following MVP (respectively 12.1 versus 18.8, Mann-Whitney P = 6.98e-14). Immune cell profiling showed a decrease of CD3 T-cell, γδ T-cell, and B-cell frequencies after MVP treatment compared to O-DYD, while the frequency of natural killer (NK) cells was significantly increased. LIMITATIONS, REASONS FOR CAUTION: The main reason for caution is the small sample size, given the basic research nature of the project. The plasma concentrations are best estimates as this was not a formal PK study. Whole tissue bulk RNA-sequencing has been performed not correcting for bias caused by different tissue compositions across biopsies. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study comparing O-DYD/MVP, head-to-head, in a randomized design on a molecular level in IVF/ICSI. Plasma serum concentrations suggest that administration frequency is important, in addition to dose, specifically for O-DYD showing a rapid clearance. The molecular endometrial data are overall comparable and thus support the previously reported noninferior reproductive outcomes for O-DYD as compared to MVP. Further research is needed to explore the smaller intersample distance following O-DYD and the subtle changes detected in endometrial immune cells. STUDY FUNDING/COMPETING INTEREST(S): Not related to this work, C.Bl. has received honoraria for lectures, presentations, manuscript writing, educational events, or scientific advice from Abbott, Ferring, Organon, Cooper Surgical, Gedeon-Richter, IBSA, and Merck. H.T. has received honoraria for lectures, presentations, manuscript writing, educational events, or scientific advice from Abbott, Ferring, Cooper Surgical, Gedeon-Richter, Cook, and Goodlife. S.M. has received honoraria for lectures, presentations, educational events, or scientific advice from Abbott, Cooper Surgical, Gedeon-Richter, IBSA, and Merck and Oxolife. G.G. has received honoraria for lectures, presentations, educational events, or scientific advice from Merck, MSD, Organon, Ferring, Theramex, Gedeon-Richter, Abbott, Biosilu, ReprodWissen, Obseva, PregLem, Guerbet, Cooper, Igyxos, and OxoLife. S.V.-S. is listed as inventor on two patents (WO2019115755A1 and WO2022073973A1), which are not related to this work. TRIAL REGISTRATION NUMBER: EUDRACT 2018-000105-23.

Nivel de actividad física según GPAQ en mujeres embarazadas y postparto que asisten a un centro de salud familiar / Physical activity levels using the GPAQ in women during pregnancy and postpartum

Antecedentes: Durante el embarazo y postparto las mujeres disminuyen el nivel de actividad física (AF). Objetivo: Determinar el nivel de AF y conducta sedentaria en mujeres embarazadas y postparto. Métodos: Participaron mujeres embarazadas y postparto entre 18 y 40 años de edad de un Centro de Salud Familiar. La AF y conducta sedentaria se midió utilizando el Global Physical Activity Questionnaire. Resultados: Se analizó la información de 47 mujeres embarazadas y 12 en postparto. La edad P50=25 años (rango: 18-40 años). El 61 por ciento presentó exceso de peso. El tiempo de AF diaria fue P50=154 (rango: 0-960 min/día) en embarazadas y P50=190 (rango: 24-411 min/día) en postparto. La AF en la dimensión tiempo libre en embarazadas fue P50=0 (rango: 0-540 min/día) y P50=3 (rango: 0-86 min/día) en el grupo de postparto. La conducta sedentaria para todo el grupo fue P50=180 (rango: 0-720 min/día). El 20,3 por ciento de las mujeres clasifica como suficientemente activo según criterio OMS, al corregir la AF reportada por GPAQ según IMC y nivel educacional. No hubo asociación entre las variables edad, estado nutricional, nivel educacional e ingreso familiar con el nivel de AF reportado. Conclusión: La AF de tiempo libre es una dimensión susceptible a intervenciones de promoción de la AF. El nivel de AF reportado por el grupo es mayor a resultados de estudios similares en otros países. Estudios de validación en esta población son necesarios para determinar la posible sobreestimación de los resultados por un sesgo de medición.

Background: During pregnancy and postpartum, women decrease physical activity (PA) levels despite the health benefits reported in the literature for women and the fetus. Aims: To determine PA levels and sedentary behaviour in women during pregnancy and postpartum. Methods: Pregnant and postpartum women between 18 and 40 years old attending to primary care center participated. Sedentary behaviour and PA were measured using the Global Physical Activity Questionnaire (GPAQ). Results: Information was collected from 47 pregnant and 12 postpartum women. Age was P50=25 (range: 18-40 years). 61 percent were overweight. Daily PA time was P50=154 (range: 0-960 min/day) for pregnant women and P50=190 (range: 24-411 min/day) during postpartum. Leisure time PA was P50=0 (range: 0-540 min/day) for pregnant women and P50=3 (range: 0-86 min/day) during postpartum. Sedentary behaviour was P50=180 min/day (range: 0-720 min/day) for all women. According to WHO criteria, only 20.3 percent of women are physically active, adjusting by BMI and educational level the reported PA in GPAQ. There was no association between the variables age, nutritional status, educational level, family income and reported level of PA. Conclusion: Leisure time PA could be susceptible to PA promotion interventions. The reported level of PA is higher than those from similar studies in other countries. Validation studies are needed to determine possible overestimation of the results due to measurement bias.