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STUDY QUESTION Is the total number of oocytes retrieved with dual ovarian stimulation in the same cycle (duostim) higher than with two consecutive antagonist cycles in poor responders? SUMMARY ANSWER Based on the number of total and mature oocytes retrieved in women with poor ovarian response (POR), there is no benefit of duostim versus two consecutive antagonist cycles. WHAT IS KNOWN ALREADY Recent studies have shown the ability to obtain oocytes with equivalent quality from the follicular and the luteal phase, and a higher number of oocytes within one cycle when using duostim. If during follicular stimulation smaller follicles are sensitized and recruited, this may increase the number of follicles selected in the consecutive luteal phase stimulation, as shown in non-randomized controlled trials (RCT). This could be particularly relevant for women with POR. STUDY DESIGN, SIZE, DURATION This is a multicentre, open-labelled RCT, performed in four IVF centres from September 2018 to March 2021. The primary outcome was the number of oocytes retrieved over the two cycles. The primary objective was to demonstrate in women with POR that two ovarian stimulations within the same cycle (first in the follicular phase, followed by a second in the luteal phase) led to the retrieval of 1.5 (2) more oocytes than the cumulative number of oocytes from two consecutive conventional stimulations with an antagonist protocol. In a superiority hypothesis, with power 0.8 alpha-risk 0.05 and a 35% cancellation rate, 44 patients were needed in each group. Patients were randomized by computer allocation. PARTICIPANTS/MATERIALS, SETTING, METHODS Eighty-eight women with POR, defined using adjusted Bologna criteria (antral follicle count ≤5 and/or anti-Müllerian hormone ≤1.2 ng/ml) were randomized, 44 in the duostim group and 44 in the conventional (control) group. HMG 300 IU/day with flexible antagonist protocol was used for ovarian stimulation, except in luteal phase stimulation of the duostim group. In the duostim group, oocytes were pooled and inseminated after the second retrieval, with a freeze-all protocol. Fresh transfers were performed in the control group, frozen embryo transfers were performed in both control and duostim groups in natural cycles. Data underwent intention-to-treat and per-protocol analyses. MAIN RESULTS AND THE ROLE OF CHANCE There was no difference between the groups regarding demographics, ovarian reserve markers, and stimulation parameters. The mean (SD) cumulative number of oocytes retrieved from two ovarian stimulations was not statistically different between the control and duostim groups, respectively, 4.6 (3.4) and 5.0 (3.4) [mean difference (MD) [95% CI] +0.4 [−1.1; 1.9], P  = 0.56]. The mean cumulative numbersof mature oocytes and total embryos obtained were not significantly different between groups. The total number of embryos transferred by patient was significantly higher in the control group 1.5 (1.1) versus the duostim group 0.9 (1.1) (P  = 0.03). After two cumulative cycles, 78% of women in the control group and 53.8% in the duostim group had at least one embryo transfer (P  = 0.02). There was no statistical difference in the mean number of total and mature oocytes retrieved per cycle comparing Cycle 1 versus Cycle 2, both in control and duostim groups. The time to the second oocyte retrieval was significantly longer in controls, at 2.8 (1.3) months compared to 0.3 (0.5) months in the duostim group (P  < 0.001). The implantation rate was similar between groups. The cumulative live birth rate was not statistically different, comparing controls versus the duostim group, 34.1% versus 17.9%, respectively (P  = 0.08). The time to transfer resulting in an ongoing pregnancy did not differ in controls 1.7 (1.5) months versus the duostim group, 3.0 (1.6) (P  = 0.08). No serious adverse events were reported. LIMITATIONS, REASONS FOR CAUTION The RCT was impacted by the coronavirus disease 2019 pandemic and the halt in IVF activities for 10 weeks. Delays were recalculated to exclude this period; however, one woman in the duostim group could not have the luteal stimulation. We also faced unexpected good ovarian responses and pregnancies after the first oocyte retrieval in both groups, with a higher incidence in the control group. However, our hypothesis was based on 1.5 more oocytes in the luteal than the follicular phase in the duostim group, and the number of patients to treat was reached in this group (N = 28). This study was only powered for cumulative number of oocytes retrieved. WIDER IMPLICATIONS OF THE FINDINGS This is the first RCT comparing the outcome of two consecutive cycles, either in the same menstrual cycle or in two consecutive menstrual cycles. In routine practice, the benefit of duostim in patients with POR regarding fresh embryo transfer is not confirmed in this RCT: first, because this study demonstrates no improvement in the number of oocytes retrieved in the luteal phase after follicular phase stimulation, in contrast to previous non-randomized studies, and second, because the freeze-all strategy avoids a pregnancy with fresh embryo transfer after the first cycle. However, duostim appears to be safe for women. In duostim, the two consecutive processes of freezing/thawing are mandatory and increase the risk of wastage of oocytes/embryos. The only benefit of duostim is to shorten the time to a second retrieval by 2 weeks if accumulation of oocytes/embryos is needed. STUDY FUNDING/COMPETING INTERESTS This is an investigator-initiated study supported by a research Grant from IBSA Pharma. N.M. declares grants paid to their institution from MSD (Organon France); consulting fees from MSD (Organon France), Ferring, and Merck KGaA; honoraria from Merck KGaA, General Electrics, Genevrier (IBSA Pharma), and Theramex; support for travel and meetings from Theramex, Merck KGaG, and Gedeon Richter; and equipment paid to their institution from Goodlife Pharma. I.A. declares honoraria from GISKIT and support for travel and meetings from GISKIT. G.P.-B. declares Consulting fees from Ferring and Merck KGaA; honoraria from Theramex, Gedeon Richter, and Ferring; payment for expert testimony from Ferring, Merck KGaA, and Gedeon Richter; and support for travel and meetings from Ferring, Theramex, and Gedeon Richter. N.C. declares grants from IBSA pharma, Merck KGaA, Ferring, and Gedeon Richter; support for travel and meetings from IBSA pharma, Merck KGaG, MSD (Organon France), Gedeon Richter, and Theramex; and participation on advisory board from Merck KGaA. E.D. declares support for travel and meetings from IBSA pharma, Merck KGaG, MSD (Organon France), Ferring, Gedeon Richter, Theramex, and General Electrics. C.P.-V. declares support for travel and meetings from IBSA Pharma, Merck KGaA, Ferring, Gedeon Richter, and Theramex. M.Pi. declares support for travel and meetings from Ferring, Gedeon Richetr, and Merck KGaA. M.Pa. declares honoraria from Merck KGaA, Theramex, and Gedeon Richter; support for travel and meetings from Merck KGaA, IBSA Pharma, Theramex, Ferring, Gedeon Richter, and MSD (Organon France). H.B.-G. declares honoraria from Merck KGaA, and Gedeon Richter and support for travel and meetings from Ferring, Merck KGaA, IBSA Pharma, MSD (Organon France), Theramex, and Gedeon Richter. S.G. and M.B. have nothing to declare. TRIAL REGISTRATION NUMBER Registration number EudraCT: 2017-003223-30. ClinicalTrials.gov identifier: NCT03803228. TRIAL REGISTRATION DATE EudraCT: 28 July 2017. ClinicalTrials.gov: 14 January 2019. DATE OF FIRST PATIENT'S ENROLMENT 3 September 2018. [ABSTRACT FROM AUTHOR]

Application of the European Water Framework Directive requires Member States to have better understanding of the quality of surface waters in order to improve knowledge of priority pollutants. Xenobiotics in urban receiving waters are an emerging concern. This study proposes a screening campaign of nine molecular species of xenobiotics in a separated sewer system. Five sites were investigated over one year in Toulouse (France) using quantitative monitoring. For each sample, polycyclic aromatic hydrocarbons, polychlorinated biphenyls, nonylphenols, diethelhexylphthalate, linear alkylbenzene sulphonates, methyl tert-butylether, total hydrocarbons, estradiol and ethinylestradiol were analysed. Ground, rain and roof collected water concentrations are similar to treated wastewater levels. Run-off water was the most polluted of the five types investigated, discharged into the aquatic environment. The wastewater treatment plant reduced xenobiotic concentrations by 66% before discharge into the environment. Regarding environmental quality standards, observed concentrations in waters were in compliance with standards. The results show that xenobiotic concentrations are variable over time and space in all urban water compartments. [ABSTRACT FROM AUTHOR]

The contribution of discharge from carwashes to pollutant levels in stormwater was evaluated. Five carwashes and two outlets in the city of Toulouse (France) were selected. Water samples were collected from December 2006 to December 2007. Concentrations and loadings of classical water quality parameters (conductivity, pH, turbidity, chemical oxygen demand, nitrogen, hosphorus, ammonium, nitrate, suspended solid and volatile suspended solid) and five groups of organic compounds (polycyclic aromatic hydrocarbons, polychlorinated biphenyls, lauryl alkyl benzene sulphonates, methyl tert-butyl ether and total hydrocarbons) were determined. The results suggest that the wastewater derived from carwashes was negligible compared to the volume and flow rates within the stormwater network. However, high concentrations of polycyclic aromatic hydrocarbons, phosphorus and lauryl alkyl benzene sulphonates in liquid waste from carwashes, and the impact of these pollutants on stormwater quality could not be neglected. [ABSTRACT FROM AUTHOR]

Abstract: The city of Toulouse with its separate sewer system is ideal for studying stormwater. However, during dry weather, the storm sewer also discharges water into the environment, and it is the impact of these discharges on annual pollution from storm sewer that is the object of this study. Samples have been taken from the outlets of two storm drains located in heavily and moderately urbanized areas. Sampling has been undertaken during wet weather and during dry weather between January 2010 and February 2011. Three dry weather and two wet weather samples have been taken every three months and from each outlet. The overall pollution parameters have been analyzed (chemical oxygen demand, biological oxygen demand, total nitrogen, ammonium, nitrate, total phosphorus, suspended solid matter, volatile suspended matter, pH, conductivity, turbidity). Characterization has been completed by analysis of trace organic compounds: polycyclic aromatic hydrocarbons, total hydrocarbons, methyl tert-butyl ether, diethylhexylphthalate, nonylphenols, hormones (estradiol, ethinylestradiol). For certain parameters, the results obtained did not conform to legislative requirements concerning discharge into the natural environment. Correlations between these parameters have been studied, and identified between several of them using principal component analysis. The most important correlation observed was between conductivity and concentration in total phosphorus for one of the outlet. Results showed that dry weather had an impact on annual pollution load from separate storm sewer and that level of urbanization was also a factor. The effect of season has been studied but no significant impact was found. [Copyright &y& Elsevier]

La douleur est un symptôme majeur chez les patients atteints de polyarthrite rhumatoïde (PR). La douleur est associée à l'activité de la maladie mais pourrait également être liée à des conditions non inflammatoires. La douleur chronique a un impact négatif sur la qualité de vie des patients atteints de PR. Le principal objectif du traitement est le contrôle de la maladie, mais le soulagement de la douleur est une priorité pour le patient. L'objectif de l'étude est d'évaluer au cours d'un suivi de cinq ans l'évolution de la douleur et la proportion de douleurs inacceptables (VASp > 4) chez les patients atteints de PR débutante et d'étudier la corrélation avec la réponse clinique et la qualité de vie. L'âge moyen de la population est de 48,5 ans et l'IMC est de 25,3. 70,5 % des patients sont des femmes. 27,1 % sont fumeurs et 68,8 % sont positifs aux anticorps anti-protéines citrullinées (anti-CCP). L'évolution de la douleur selon l'échelle VASd est : au moment de diagnostic, la douleur moyenne était de 60,2 ± 26,5 mm. La douleur VASd a été réduite de 45 % (moyenne 33,1 ± 28,5 mm) à 6 mois et est restée stable avec une réduction de 51,7 % (moyenne 29,0 ± 27,6 mm) à 5 ans. 78 % des patients (n = 308) ont signalé une douleur inacceptable au moment du diagnostic, qui a été réduite à 40,4 % (n = 163) à 6 mois et à 33 % à 5 ans. Lors du diagnostic, la seule différence significative avec la douleur inacceptable a été observée pour les fumeurs (27,3 % VASd > 4) vs les non-fumeurs (15,6 % VASd > 4). Aucune différence statistique n'a été observée pour l'âge, le sexe ratio, l'IMC, la présence des anti-CCP ou le FR entre les patients ayant ou non une douleur inacceptable ; sauf. Une forte corrélation a été observée entre la diminution de la douleur VASd, des scores DAS28-CRP et HAQ à tous les moments. Parmi les patients présentant une douleur inacceptable à 6 mois, le score HAQ au moment du diagnostic était statistiquement plus élevé (1,30 ± 0,69 vs 1,15 ± 0,67), tandis que les scores DAS28-CRP étaient similaires dans les deux groupes (4,66 ± 1,41 vs 4,67 ± 1,24). Nous avons également identifié 20 patients présentant une douleur inacceptable tout au long des 5 années de suivi ; dans ce groupe les valeurs DAS28-CRP et du HAQ évaluées au moment du diagnostic étaient statistiquement plus élevées (5,4 ± 1,1 vs 4,7 ± 1,4 et 1,41 ± 0,86 vs 1,21 ± 0,62). 31 patients au long des 5 années de suivi ont conservé une rémission complète définie comme une douleur VASd <4 + DAS28- CR P < 3,2 + HAQ< 0,5. Les scores VASd, DAS28-CRP et HAQ évalués au moment du diagnostic étaient statistiquement plus faibles dans ce groupe. (38,9 ± 28,4 contre 61,9 ± 25,7, 4,3 ± 1,1 contre 4,8 ± 1,4 et 0,86 ± 0,60 contre 1,2 ± 0,71). Tous les patients ont été traités selon le schéma standard, principalement avec du méthotrexate. Nous démontrons que le contrôle de la douleur est obtenu chez la majorité des patients atteints de PR. La diminution de la douleur est corrélée avec la diminution du score d'activité de la maladie (DAS28-CRP), ce qui signifie que la douleur dans la PR débutante est principalement lié à l'inflammation. [ABSTRACT FROM AUTHOR]