Oral micronized progesterone versus vaginal progesterone for luteal phase support in fresh embryo transfer cycles: a multicenter, randomized, non-inferiority trial.

STUDY QUESTION: Does oral micronized progesterone result in a non-inferior ongoing pregnancy rate compared to vaginal progesterone gel as luteal phase support (LPS) in fresh embryo transfer cycles? SUMMARY ANSWER: The ongoing pregnancy rate in the group administered oral micronized progesterone 400 mg per day was non-inferior to that in the group administered vaginal progesterone gel 90 mg per day. WHAT IS KNOWN ALREADY: LPS is an integrated component of fresh IVF, for which an optimal treatment regimen is still lacking. The high cost and administration route of the commonly used vaginal progesterone make it less acceptable than oral micronized progesterone; however, the efficacy of oral micronized progesterone is unclear owing to concerns regarding its low bioavailability after the hepatic first pass. STUDY DESIGN, SIZE, DURATION: This non-inferiority randomized trial was conducted in eight academic fertility centers in China from November 2018 to November 2019. The follow-up was completed in April 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 1310 infertile women who underwent their first or second IVF cycles were enrolled. On the day of hCG administration, the patients were randomly assigned to one of three groups for LPS: oral micronized progesterone 400 mg/day (n = 430), oral micronized progesterone 600 mg/day (n = 440) or vaginal progesterone 90 mg/day (n = 440). LPS was started on the day of oocyte retrieval and continued till 11-12 weeks of gestation. The primary outcome was the rate of ongoing pregnancy. MAIN RESULTS AND THE ROLE OF CHANCE: In the intention-to-treat analysis, the rate of ongoing pregnancy in the oral micronized progesterone 400 mg/day group was non-inferior to that of the vaginal progesterone gel group [35.3% versus 38.0%, absolute difference (AD): -2.6%; 95% CI: -9.0% to 3.8%, P-value for non-inferiority test: 0.010]. There was insufficient evidence to support the non-inferiority in the rate of ongoing pregnancy between the oral micronized progesterone 600 mg/day group and the vaginal progesterone gel group (31.6% versus 38.0%, AD: -6.4%; 95% CI: -12.6% to -0.1%, P-value for non-inferiority test: 0.130). In addition, we did not observe a statistically significant difference in the rate of live births between the groups. LIMITATIONS, REASONS FOR CAUTION: The primary outcome of our trial was the ongoing pregnancy rate; however, the live birth rate may be of greater clinical interest. Although the results did not show a difference in the rate of live births, they should be confirmed by further trials with larger sample sizes. In addition, in this study, final oocyte maturation was triggered by hCG, and the findings may not be extrapolatable to cycles with gonadotropin-releasing hormone agonist triggers. WIDER IMPLICATIONS OF THE FINDINGS: Oral micronized progesterone 400 mg/day may be an alternative to vaginal progesterone gel in patients reluctant to accept the vaginal route of administration. However, whether a higher dose of oral micronized progesterone is associated with a poorer pregnancy rate or a higher rate of preterm delivery warrants further investigation. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by a grant from the National Natural Science Foundation of China (82071718). None of the authors have any conflicts of interest to declare. TRIAL REGISTRATION NUMBER: This trial was registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/) with the number ChiCTR1800015958. TRIAL REGISTRATION DATE: May 2018. DATE OF FIRST PATIENT'S ENROLMENT: November 2018.

Recirculation of reject water in deep-dewatering process to influent of wastewater treatment plant and dewaterability of sludge conditioned with Fe2+/H2O2, Fe2+/Ca(ClO)2, and Fe2+/Na2S2O8: From bench to pilot-scale study.

Deep dewatering of sewage sludge pretreated with advanced oxidation processes (AOPs) is a strategy for efficient sludge reduction and subsequent disposal. The pretreatment and dewatering performance of sludge conditioned with three types of AOPs (Fe2+/H2O2, Fe2+/Ca(ClO)2, and Fe2+/Na2S2O8), compared with sludge conditioned with traditional conditioner (Fe3+/CaO), were investigated in both bench and pilot-scale tests. All of those conditioner systems could reduce the water content of dewatered sludge cake to below 60 wt% in bench-scale (about 16 kg raw sludge per round) and pilot-scale (approximate 800 kg raw sludge per round) diaphragm filter press dewatering. Compared with raw sludge, the deep-dewatering filtrate after different conditioning and dewatering processes had higher ammonia nitrogen (NH4+-N) and chemical oxygen demand (COD) contents due to the degradation of organic matter, and much lower total phosphorus (TP) content due to the formation of iron phosphate precipitate. A better biodegradability (i.e. higher BOD5/COD ratio) was found in the deep-dewatering filtrate of sludge conditioned with Fe2+/H2O2 (25.2 %) and Fe2+/Ca(ClO)2 (17.4 %). Most of the heavy metals (Cr, Cu, Ni, and Pb) (>79 wt%) have remained in the dewatered sludge cake, and most of the Cl element (>90 wt%) in the sludge pretreated by Fe2+/Ca(ClO)2 and Fe3+/CaO was kept in the filtrate, rather than the dewatered sludge cake. Based on the pilot-scale experimental results, if all the filtrate in the deep-dewatering process returned to the influent of WWTP, the loading ratios of TP, NH4+-N, COD in the four conditioner systems were less than 3 wt%. The above results proved that the AOPs conditioned sludge could achieve deep-dewatering in pilot-scale and the direct recirculation of deep-dewatering filtrate to the influent of wastewater treatment plant was feasible.

Unraveling oxidation behaviors for intracellular and extracellular from different oxidants (HOCl vs. H2O2) catalyzed by ferrous iron in waste activated sludge dewatering.

Cell lysis in sludge pretreatment by advanced oxidation process (AOP) has a great effect on sludge dewaterability. Cell lysis caused by reactive radicals (e.g. hydroxyl radical) was dependent on the reaction site of AOP. However, little is known about the accurate radical generation site of AOP in sludge pretreatment. In this study, two kinds of oxidation behaviors from different oxidants (HOCl vs. H2O2) catalyzed by ferrous iron were comparatively investigated. Higher amount of living cells (84.3%) and hydroxyl radicals (9.86 × 10-5 M), and more fragmentized sludge flocs (particle sizes of D50 was 50.1 vs. 57.3 µm of RS) were detected in sludge conditioned by Fe2+/H2O2, which implied that Fenton reaction mainly happened at surface and outside of sludge flocs (such as EPS layer and liquid phase). Thus, it could be regarded as "extracellular oxidation". Fewer living cells (undetectable), fewer amount of hydroxyl radicals (undetectable in sludge), and more integrated sludge flocs (particle size of D50 was 56.1 vs. 57.3 µm of RS) were determined in sludge conditioned by Fe2+/Ca(ClO)2. Hence, it could be regarded as "Intracellular oxidation". In addition, sludge pretreatment based on Fe2+/Ca(ClO)2 could achieve simultaneous deep-dewatering performance and total coliforms inactivation. Based on response surface methodology, the optimal dosages of Fe2+ and Ca(ClO)2 were proposed as 106.1 and 234.5 mg/g volatile solids respectively, without any acidification of sludge. Under these optimal dosages, the water content of dewatered sludge cake was 51.9 ±â€¯0.1 wt% and the pH of the final filtrate was 5.8 ±â€¯0.2. Total coliforms of sludge could be inactivated in 10 s after Fe2+/Ca(ClO)2 addition.