Anal incontinence following obstetric anal sphincter injury: Is there a difference between subtypes? A systematic review.

AIMS: Obstetric anal sphincter injury (OASI) is associated with long-term anal incontinence (AI). We aimed to address the following questions: (a) are women with major OASI (grade 3c and 4) at higher risk of developing AI when compared to women with minor OASI (grade 3a and 3b)? (b) is a fourth-degree tear more likely to cause AI over a third-degree tear? METHODS: A systematic literature search from inception until September 2022. We considered prospective and retrospective cohort studies, cross-sectional and case-control studies without language restrictions. The quality was assessed by the Newcastle-Ottawa Scale and the Joanna Briggs Institute critical appraisal checklist. Risk ratios (RRs) were calculated to measure the effect of different grades of OASI. RESULTS: Out of 22 studies, 8 were prospective cohort, 8 were retrospective cohort, and 6 were cross-sectional studies. Length of follow-up ranged from 1 month to 23 years, with the majority of the reports (n = 16) analysing data within 12-months postpartum. Third-degree tears evaluated were 6454 versus 764 fourth-degree tears. The risk of bias was low in 3, medium in 14 and high in 5 studies, respectively. Prospective studies showed that major tears are associated with a twofold risk of AI for major tears versus minor tears, while retrospective studies consistently showed a risk of fecal incontinence (FI) which was two- to fourfold higher. Prospective studies showed a trend toward worsening AI symptoms for fourth-degree tears, but this failed to reach statistical significance. Cross-sectional studies with long-term (≥5 years) follow-up showed that women with fourth-degree tear were more likely to develop AI, with an RR ranging from 1.4 to 2.2. Out of 3, 2 retrospective studies showed similar findings, but the follow-up was significantly shorter (≤1 year). Contrasting results were noted for FI rates, as only 5 out of 10 studies supported an association between fourth-degree tear and FI. CONCLUSIONS: Most studies investigate bowel symptoms within few months from delivery. Data heterogeneity hindered a meaningful synthesis. Prospective cohort studies with adequate power and long-term follow-up should be performed to evaluate the risk of AI for each OASI subtype.

Evaluating interventions and adjuncts to optimize pregnancy outcomes in subfertile women: an overview review.

BACKGROUND: There is a wealth of information regarding interventions for treating subfertility. The majority of studies exploring interventions for improving conception rates also report on pregnancy outcomes. However, there is no efficient way for clinicians, researchers, funding organizations, decision-making bodies or women themselves to easily access and review the evidence for the effect of adjuvant therapies on key pregnancy outcomes in subfertile women. OBJECTIVE AND RATIONALE: The aim was to summarize all published systematic reviews (SRs) of randomized controlled trials (RCTs) of interventions in the subfertile population, specifically reporting on the pregnancy outcomes of miscarriage and live birth. Furthermore, we aimed to highlight promising interventions and areas that need high-quality evidence. SEARCH METHODS: We searched the Cochrane Database of Systematic Reviews and PubMed clinical queries SR filter (inception until July 2021) with a list of key words to capture all SRs specifying or reporting any miscarriage outcome. Studies were included if they were SRs of RCTs. The population was subfertile women (pregnant or trying to conceive) and any intervention (versus placebo or no treatment) was included. We adopted Grading of Recommendations, Assessment, Development and Evaluation (GRADE) for determining the quality of the evidence. Exclusion criteria were overview reviews, reviews that exclusively reported on women conceiving via natural conception, reviews including non-randomized study designs or reviews where miscarriage or live birth outcomes were not specified or reported. OUTCOMES: The primary outcome was miscarriage, defined as pregnancy loss <24 weeks of gestation. Data were also extracted for live birth where available. We included 75 published SRs containing 121 251 participants. There were 14 classes of intervention identified: luteal phase, immunotherapy, anticoagulants, hCG, micronutrients, lifestyle, endocrine, surgical, pre-implantation genetic testing for aneuploidies (PGT-As), laboratory techniques, endometrial injury, ART protocols, other adjuncts/techniques in the ART process and complementary interventions. The interventions with at least moderate-quality evidence of benefit in reducing risk of miscarriage or improving the chance of a live birth are: intrauterine hCG at time of cleavage stage embryo transfer, but not blastocyst transfer, antioxidant therapy in males, dehydroepiandrosterone in women and embryo medium containing high hyaluronic acid. Interventions showing potential increased risk of miscarriage or reduced live birth rate are: embryo culture supernatant injection before embryo transfer in frozen cycles and PGT-A with the use of fluorescence in situ hybridization. WIDER IMPLICATIONS: This review provides an overview of key pregnancy outcomes from published SRs of RCTs in subfertile women. It provides access to concisely summarized information and will help clinicians and policy makers identify knowledge gaps in the field, whilst covering a broad range of topics, to help improve pregnancy outcomes for subfertile couples. Further research is required into the following promising interventions: the dose of progesterone for luteal phase support, peripheral blood mononuclear cells for women with recurrent implantation failure, glucocorticoids in women undergoing IVF, low-molecular-weight heparin for unexplained subfertility, intrauterine hCG at the time of cleavage stage embryo or blastocyst transfer and low oxygen concentrations in embryo culture. In addition, there is a need for high-quality, well-designed RCTs in the field of reproductive surgery. Finally, further research is needed to demonstrate the integrated effects of non-pharmacological lifestyle interventions.

Development of a salicylic acid inducible minimal sub-genomic transcript promoter from Figwort mosaic virus with enhanced root- and leaf-activity using TGACG motif rearrangement.

In Figwort mosaic virus sub-genomic transcript promoter (F-Sgt), function of the TGACG-regulatory motif, was investigated in the background of artificially designed promoter sequences. The 131bp (FS, -100 to +31) long F-Sgt promoter sequence containing one TGACG motif [FS-(TGACG)] was engineered to generate a set of three modified promoter constructs: [FS-(TGACG)(2), containing one additional TGACG motif at 7 nucleotides upstream of the original one], [FS-(TGACG)(3), containing two additional TGACG motifs at 7 nucleotides upstream and two nucleotides downstream of the original one] and [FS-(TGCTG)(mu), having a mutated TGACG motif]. EMSA and foot-printing analysis confirmed binding of tobacco nuclear factors with modified TGACG motif/s. The transcription-activation of the GUS gene by the TGACG motif/s in above promoter constructs was examined in transgenic tobacco and Arabidopsis plants and observed that the transcription activation was affected by the spacing/s and number/s of the TGACG motif/s. The FS-(TGACG)(2) promoter showed strongest root-activity compared to other modified and CaMV35S promoters. Also under salicylic acid (SA) stress, the leaf-activity of the said promoter was further enhanced. All above findings were confirmed by real-time and semi-qRT PCR analysis. Taken together, these results clearly demonstrated that the TGACG motif plays an important role in inducing the root-specific expression of the F-Sgt promoter. This study advocates the importance of genetic manipulation of functional cis-motif for amending the tissue specificity of a plant promoter. SA inducible FS-(TGACG)(2) promoter with enhanced activity could be a useful candidate promoter for developing plants with enhanced crop productivity.