Endometrial scratching in women with one failed IVF/ICSI cycle-outcomes of a randomised controlled trial (SCRaTCH)

STUDY QUESTION: Does endometrial scratching in women with one failed IVF/ICSI treatment affect the chance of a live birth of the subsequent fresh IVF/ICSI cycle? SUMMARY ANSWER: In this study, 4.6% more live births were observed in the scratch group, with a likely certainty range between -0.7% and +9.9%. WHAT IS KNOWN ALREADY: Since the first suggestion that endometrial scratching might improve embryo implantation during IVF/ICSI, many clinical trials have been conducted. However, due to limitations in sample size and study quality, it remains unclear whether endometrial scratching improves IVF/ICSI outcomes. STUDY DESIGN, SIZE, DURATION: The SCRaTCH trial was a non-blinded randomised controlled trial in women with one unsuccessful IVF/ICSI cycle and assessed whether a single endometrial scratch using an endometrial biopsy catheter would lead to a higher live birth rate after the subsequent IVF/ICSI treatment compared to no scratch. The study took place in 8 academic and 24 general hospitals. Participants were randomised between January 2016 and July 2018 by a web-based randomisation programme. Secondary outcomes included cumulative 12-month ongoing pregnancy leading to live birth rate. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with one previous failed IVF/ICSI treatment and planning a second fresh IVF/ICSI treatment were eligible. In total, 933 participants out of 1065 eligibles were included (participation rate 88%). MAIN RESULTS AND THE ROLE OF CHANCE: After the fresh transfer, 4.6% more live births were observed in the scratch compared to control group (110/465 versus 88/461, respectively, risk ratio (RR) 1.24 [95% CI 0.96-1.59]). These data are consistent with a true difference of between -0.7% and +9.9% (95% CI), indicating that while the largest proportion of the 95% CI is positive, scratchin

Long-term effects of previous oxandrolone treatment in adult women with Turner syndrome

Objective: Short stature is a prominent feature of Turner syndrome (TS), which is partially overcome by GH treatment. We have previously reported the results of a trial on the effect of oxandrolone (Ox) in girls with TS. Ox in a dose of 0.03 mg/kg per day (Ox 0.03) significantly increased adult height gain, whereas Ox mg/kg per day (0.06) did not, at the cost of deceleration of breast development and mild virilization. The aim of this follow-up study in adult participants of the pediatric trial was to investigate the long-term effects of previous Ox treatment. Design and methods: During the previous randomized controlled trial, 133 girls were treated with GH combined with placebo (Pl), Ox 0.03, or Ox 0.06 from 8 years of age and estrogen from 12 years. Sixty-eight women (Pl, n=23; Ox 0.03, n=27; and Ox 0.06, n=18) participated in the double-blind follow-up study (mean age, 24.0 years; mean time since stopping GH, 8.7 years; and mean time of Ox/Pl use, 4.9 years). We assessed height, body proportions, breast size, virilization, and body composition. Results: Height gain (final minus predicted adult height) was maintained at follow-up (Ox 0.03 10.2 ±4.9 cm, Ox 0.06 9.7±4.4 cm vs Pl 8.0±4.6 cm). Breast size, Tanner breast stage, and body composition were not different between groups. Ox-treated women reported more subjective virilization and had a lower voice frequency. Conclusion: Ox 0.03 mg/kg per day has a beneficial effect on adult height gain in TS patients. Despite previously reported deceleration of breast development during Ox 0.03 treatment, adult breast size is not affected. Mild virilization persists in only a small minority of patients. The long-term evaluation indicates that Ox 0.03 treatment is effective and safe

Determining High-Quality Critical Body Residues for Multiple Species and Chemicals by Applying Improved Experimental Design and Data Interpretation Concepts

Ecotoxicological effect data are generally expressed as effective concentrations in the external exposure medium and do thus not account for differences in chemical uptake, bioavailability, and metabolism, which can introduce substantial data variation. The Critical Body Residue (CBR) concept provides clear advantages, because it links effects directly to the internal exposure. Using CBRs instead of external concentrations should therefore reduce variability. For compounds that act via narcosis even a constant CBR has been proposed. Despite the expected uniformity, CBR values for these compounds still show large variability, possibly due to biased and inconsistent experimental testing. In the present study we tested whether variation in CBR data can be substantially reduced when using an improved experimental design and avoiding confounding factors. The aim was to develop and apply a well-defined test protocol for accurately and precisely measuring CBR data, involving improved (passive) dosing, sampling, and processing of organisms. The chemicals 1,2,4-trichlorobenzene, 1,2,3,4-tetrachlorobenzene, 2,3,4-trichloroaniline, 2,3,5,6-tetrachloroaniline, 4-chloro-3-methylphenol, pentylbenzene, pyrene, and bromophos-methyl were tested on Lumbriculus variegatus (California blackworm), Hyalella azteca (scud), and Poecilia reticulata (guppy), which yielded a high-quality database of 348 individual CBR values. Medians of CBR values ranged from 2.1 to 16.1 mmol/kg wet weight (ww) within all combinations of chemicals and species, except for the insecticide bromophos-methyl, for which the median was 1.3 mmol/kg ww. The new database thus covers about one log unit, which is considerably less than in existing databases. Medians differed maximally by a factor of 8.4 between the 7 chemicals but within one species, and by a factor of 2.6 between the three species but for individual chemicals. Accounting for the chemicals' internal distribution to different partitioning domains and relating effects to estimated concentrations in the target compartment (i.e., membrane lipids) was expected to but did not decrease the overall variability, likely because the surrogate partition coefficients for membrane lipid, storage lipid, protein, and carbohydrate that were used as input parameters did not sufficiently represent the actual partitioning processes. The results of this study demonstrate that a well-designed test setup can produce CBR data that are highly uniform beyond chemical and biological diversity