Definition, diagnostic and therapeutic options in recurrent implantation failure: an international survey of clinicians and embryologists.

STUDY QUESTION: What is the global variability in recurrent implantation failure (RIF) definition, investigation and therapy, currently offered to patients undergoing IVF? SUMAMRY ANSWER: Definitions, diagnostic investigations and treatments offered to RIF patients differ widely amongst assisted reproduction healthcare professionals and clinical guidelines on RIF are urgently needed. WHAT IS KNOWN ALREADY: RIF affects around 10% of patients undergoing IVF worldwide. There is no consensus on the definition of RIF, its diagnostic investigations or the therapeutic options, which leads to inconsistencies in clinical practice. STUDY DESIGN, SIZE, DURATION: A cross-sectional study of clinicians and embryologists was conducted between May and June 2020. The survey included 43 questions aimed at understanding participants' background and their current practice with regards to defining, investigating and managing RIF. The questions were designed by the European Society of Human Reproduction and Embryology (ESHRE) Special Interest Group (SIG) on implantation and early pregnancy following three consensus meetings. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 8579 ESHRE members from 6916 IVF centers were invited to participate using two global email calls based on their pre-specified interest in implantation and early pregnancy. SurveyMonkey and SPSS were used for data collection and analysis, respectively. Furthermore, differences were reported in the answers of European and non-European professionals, as well as between public and private settings and among clinicians clustered according to the average number of RIF patients treated per year. MAIN RESULTS AND THE ROLE OF CHANCE: The final data set included 735 clinicians and 300 embryologist or IVF-biologists. The majority defines RIF based on the number of failed embryo transfers (ETs) with the most common threshold adopted being three ETs both fresh and frozen. More than two-thirds take lifestyle factors into account, mainly drugs, smoking and BMI. The highest consensus on which diagnostic investigations should be performed was reached for anatomical malformations and gynecological aspects focusing on hydrosalpinx, Asherman's syndrome, endometrial thickness and endometriosis. Concerning treatment of RIF patients, the highest consensus was reached for preconceptional therapies, including BMI adjustment, smoking and endometritis followed by therapies during IVF procedures. LIMITATIONS, REASONS FOR CAUTION: The response rate was relatively low, but comparable to other surveys. WIDER IMPLICATIONS OF THE FINDINGS: A consensus on definition, diagnosis and treatment of RIF would help to reduce costly, time-consuming and poorly validated approaches. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used. B.T. received support from Bayer for Clinical trials concerning endometriosis and Ferring for clinical trials concerning ovarian stimulation. She received reimbursement for travel expenses from Astropharm, Ferring. Dr Kade and is a shareholder of Reprognostics. She is a board member of the Austrian Society for Obstetrics and Gynecology (OEGGG), the associate head of the 'Reproduktionsmedizinische Zentren Baden-Württemberg' (RZBW), a member of guideline group of the German Society for Obstetrics and Gynecology (DGGG) and an editorial board member of the following journals: American Journal of Reproductive Immunology (AJRI), Archives of Gynecology and Obstetrics. All the other authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Strategies for improving outcome of assisted reproduction in women with polycystic ovary syndrome: systematic review and meta-analysis.

OBJECTIVES: To identify, appraise and summarize the current evidence regarding the efficacy of strategies aimed at improving assisted reproductive techniques in women with polycystic ovary syndrome (PCOS). METHODS: A comprehensive literature search of the standard medical databases was performed. The last electronic search was run in July 2015. The primary outcome measures were live birth/ongoing pregnancy and ovarian hyperstimulation syndrome (OHSS). The secondary outcome measures were clinical pregnancy and miscarriage. RESULTS: We screened 1021 records and completely assessed 173, finally including 66 studies in the quantitative analysis. Many different interventions were assessed, however the overall quality of the studies was low. We observed moderate-quality evidence that there is no clinically relevant difference in live birth/ongoing pregnancy rates (relative risk (RR), 0.95 (95% CI, 0.84-1.08)), or clinical pregnancy (RR, 1.02 (95% CI, 0.91-1.15)) when comparing antagonist and agonist protocols for ovarian stimulation. Additionally, we found low-quality evidence that metformin improves live birth/ongoing pregnancy (RR, 1.28 (95% CI, 1.01-1.63)) and clinical pregnancy rates (RR, 1.26 (95% CI, 1.04-1.53)) when compared with placebo or no intervention. We further found low-quality evidence that there is no clinically relevant difference in live birth/ongoing pregnancy rates (RR, 1.03 (95% CI, 0.80-1.34)) and clinical pregnancy rates (RR, 0.99 (95% CI, 0.81-1.22)) when comparing human menopausal gonadotropin for inducing ovulation and artificial preparation with estradiol valerate for endometrial preparation for frozen embryo transfer (FET). Low-quality evidence suggests that mannitol compared with no intervention (RR, 0.54 (95% CI, 0.39-0.77)) and antagonist protocols compared with agonist protocols (RR, 0.63 (95% CI, 0.49-0.80)) reduce rates of OHSS. CONCLUSION: There is low- to moderate-quality evidence suggesting that antagonist protocols are preferable to agonist ones, because they reduce the incidence of OHSS without interfering with clinical pregnancy and live birth for women with PCOS. Additionally there is low-quality evidence pointing to a benefit of metformin supplementation on clinical pregnancy and live birth; and that ovulation induction and administration of estradiol seem to be equally effective for endometrial preparation before FET for women with PCOS. For all other interventions, the evidence is of very low quality, not allowing any meaningful conclusions to be drawn. Estrategias para mejorar el resultado de la reproducción asistida en mujeres con síndrome de ovario poliquístico: revisión sistemática y metaanálisis RESUMEN OBJETIVOS: Identificar, evaluar y resumir la evidencia actual sobre la eficacia de las estrategias para mejorar las técnicas de reproducción asistida en mujeres con síndrome de ovario poliquístico (SOP). MÉTODOS: Se realizó una búsqueda exhaustiva de literatura en las bases de datos médicas estándar. La última búsqueda electrónica se realizó en julio de 2015. Las medidas de resultado primarias fueron los nacimientos vivos/embarazos en curso y el síndrome de hiperestimulación ovárica (SHO). Las medidas de resultado secundarias fueron el embarazo confirmado ecográficamente y el aborto. RESULTADOS: Se cribaron 1021 registros, de los que se evaluaron por completo 173, para finalmente incluir 66 estudios en el análisis cuantitativo. Aunque se evaluaron muchas intervenciones diferentes, en general la calidad de los estudios fue baja. Se observó evidencia de calidad moderada de que no hay diferencias relevantes clínicamente en las tasas de nacimientos vivos/embarazos en curso (riesgo relativo (RR): 0,95 (IC 95%, 0,84-1,08)), o de embarazos confirmados ecográficamente (RR: 1,02 (IC 95%, 0,91-1,15)), cuando se comparan los protocolos de antagonistas y agonistas para la estimulación ovárica. Además, se encontró evidencia de baja calidad en que la metformina mejora las tasas de nacimientos vivos/embarazos en curso (RR: 1,28 (IC 95%, 1,01-1,63)) y de embarazos confirmados ecográficamente (RR: 1,26 (IC 95%, 1,04-1,53)) en comparación con un placebo o la no intervención. Se encontró también evidencia de baja calidad en que no hay diferencias relevantes clínicamente en las tasas de nacimientos vivos/embarazos en curso (RR: 1,03 (IC 95%, 0,80-1,34)) y las tasas de embarazos confirmados ecográficamente (RR: 0,99 (IC 95%, 0.81-1,22)) al comparar la gonadotropina menopáusica humana para la inducción de la ovulación y la preparación artificial con el valerato de estradiol para preparar el endometrio para la transferencia de embriones congelados (TEC). La baja calidad de la evidencia sugiere que el manitol, en comparación con la no intervención (RR: 0,54 (IC 95%, 0,39-0,77)), y los protocolos de antagonistas, en comparación con los protocolos de agonistas (RR: 0,63 (IC 95%, 0,49-0,80)), reducen las tasas de SHO. CONCLUSIÓN: Hay evidencia de calidad baja a moderada que sugiere que los protocolos de antagonistas son preferibles a los de agonistas, ya que reducen la tasa de SHO sin interferir con el embarazo confirmado ecográficamente y los nacimientos vivos en las mujeres con SOP. Además, existe evidencia de baja calidad que indica un beneficio del uso de metformina como aporte suplementario en embarazos confirmados ecográficamente y en nacimientos vivos; y que la inducción de la ovulación y la administración de estradiol parecen ser igualmente eficaces para la preparación del endometrio antes de la TEC en mujeres con SOP. Para el resto de procedimientos, la evidencia es de muy baja calidad, y por ello no permite extraer conclusiones importantes.

Maternal and neonatal outcomes in pregnant women with PCOS: comparison of different diagnostic definitions.

STUDY QUESTION: Does the prevalence of adverse maternal and neonatal outcomes vary in women diagnosed with polycystic ovary syndrome (PCOS) according to different definitions? SUMMARY ANSWER: A comparison of different criteria revealed that there is a substantial risk for perinatal complications in PCOS women, regardless of the used definition. WHAT IS KNOWN ALREADY: Pregnant women with PCOS are susceptible to perinatal complications. At present, there are three main definitions for PCOS. So far, we are aware of only one study, which found that the elevated risk for complications varied widely depending on the different phenotypes and features but only considered a relatively small sample size for some of the phenotypes. STUDY DESIGN, SIZE, DURATION: Retrospective matched cohort study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data of primiparous women with PCOS according to ESHRE/ASRM 2003 criteria and healthy controls giving birth to neonates ≥500 g were included. A total of 885 women were analysed: out of 177 women with PCOS, 85 (48.0%) met the National Institutes of Health (NIH) 1990 criteria, another 14 (7.9%) featured the additional phenotypes defined by The Androgen Excess and PCOS Society (AE-PCOS) 2006 criteria, 78 (44.1%) were classified as PCOS exclusively by the ESHRE/ASRM 2003 definition, and 708 represented the control group. MAIN RESULTS AND THE ROLE OF CHANCE: The prevalence of adverse maternal (49.4 versus 64.3 versus 60.3%, P = 0.313) and neonatal (27.1 versus 35.7 versus 23.1%, P = 0.615) outcomes did not differ within the three PCOS groups (ESHRE/ASRM, NIH, AE-PCOS, respectively). Compared with healthy controls, the risk for maternal complications was increased in PCOS patients [odds ratio (OR) 2.57; 95% confidence interval (CI) 1.82-3.64; P < 0.001] while there was no difference in neonatal complications (OR 0.83; 95% CI 0.56-1.21; P = 0.343). LIMITATIONS, REASONS FOR CAUTION: A limitation of our study is its retrospective design and the relatively small sample size, particularly in the AE-PCOS subgroup. WIDER IMPLICATIONS OF THE FINDINGS: Since women with PCOS have, regardless of the used definition, a high risk of maternal and neonatal complications they should be informed and advised to follow regular checks in units where problems can be detected early to allow specialized care. STUDY FUNDING/COMPETING INTERESTS: Marietta Blau Grant (Austrian Agency for International Cooperation in Education and Research; OeAD-GmbH) and mobility scholarship (Medical University of Graz).

A literature review of the current evidence for routine antibiotic prophylaxis after cervical tissue excisions.

Consistent data are available on supporting the routine use of prophylactic antibiotics for several obstetrical and gynaecological procedures. According to the Surgical Wounds Classification scheme, operations involving the vagina are included in the clean-contaminated category of procedures, and guidelines recommend the routine use of prophylactic antibiotics. The objective of this paper is to review the current evidence regarding prophylactic antibiotics for cervical tissue excisions. We performed a systematic search of medical databases to March 2014 and we found three randomised controlled trials reporting on the role of prophylactic antibiotics in 683 patients who underwent cervical excisions. When compared with controls, the prophylactic antibiotics group was similar in terms of postoperative bleeding, vaginal discharge, pain, incidence of adverse events, requirement of antibiotics and readmission rate secondary to bleeding. This systematic review based on three randomised controlled trials suggests that current evidence does not support the routine prophylactic antibiotics for cervical tissue excisions.

Chewing gum in preventing postoperative ileus in women undergoing caesarean section: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: The incidence of postoperative ileus (POI) after gynaecological surgery is 10-15% Chewing gum following general surgery improves outcomes, including early flatus, early bowel sounds, and shortening of hospitalisation periods. There is currently no guideline that supports the use of chewing gum after caesarean sections. OBJECTIVES: To systematically analyse the published randomised controlled trials regarding the effectiveness of chewing gum in preventing POI in women undergoing caesarean sections. SEARCH STRATEGY: Systematic search of medical databases up to March 2013. SELECTION CRITERIA: Randomised controlled trials that reported the role of chewing gum in preventing POI in women undergoing caesarean sections. DATA COLLECTION AND ANALYSIS: Two authors independently identified the relevant studies for inclusion, extracted outcome-related data, and analysed it systematically using REVMAN(®). The combined outcome was expressed as an odds ratio and standardised mean difference. MAIN RESULTS: Seven randomised controlled trials involving 1462 women (728 in the chewing gum group, 734 controls) were systematically analysed. There was significant heterogeneity (χ(2) = 29.02, df = 7; P < 0.0001; I(2) = 76%) among the included trials. Among women undergoing caesarean sections, chewing gum reduced the risk of POI (odds ratio 0.36; 95% confidence interval 0.19-0.69; z = 3.08; P < 0.002) but did not affect duration of hospitalisation (P = 0.32). CONCLUSIONS: Chewing gum for 30-60 minutes at least three times a day appears to be effective in reducing the incidence and consequences of POI following caesarean sections.

Systematic review and meta-analysis of published, randomized, controlled trials comparing suture anastomosis to stapled anastomosis for ileostomy closure.

The objective of this article is to systematically analyze the randomized, controlled trials comparing the effectiveness of suture anastomosis (SUA) versus stapled anastomosis (STA) in patients undergoing ileostomy closure. Randomized, controlled trials comparing the effectiveness of SUA versus STA in patients undergoing ileostomy closure were analyzed using RevMan(®), and combined outcomes were expressed as odds risk ratio (OR) and standardized mean difference (SMD). Four randomized, controlled trials that recruited 645 patients were retrieved from electronic databases. There were 327 patients in the STA group and 318 patients in the SUA group. There was significant heterogeneity among included trials. Operative time (SMD -1.02; 95 % CI -1.89, -0.15; z = 2.29; p < 0.02) was shorter following STA compared to SUA. In addition, risk of small bowel obstruction (OR 0.54; 95 % confidence interval (CI), 0.30, 0.95; z = 2.13; p < 0.03) was lower in the STA group. Risk of anastomotic leak (OR 0.87; 95 % CI 0.12, 6.33; z = 0.14; p = 0.89), surgical site infection, reoperation and readmission were similar following STA and SUA in patients undergoing ileostomy closure. Length of hospital stay was also similar between STA and SUA groups. In ileostomy closure, STA was associated with shorter operative time and lower risk of postoperative small bowel obstruction. However, STA and SUA were similar in terms of anastomotic leak, surgical site infection, readmission, reoperations and length of hospital stay.

Use of antibacterial sutures for skin closure in controlling surgical site infections: a systematic review of published randomized, controlled trials.

OBJECTIVE: The objective of this article is to systematically analyse the randomized, controlled trials that compare the use of antibacterial sutures (ABS) for skin closure in controlling surgical site infections. METHODS: Randomized, controlled trials on surgical patients comparing the use of ABS for skin closure in controlling the surgical site infections were analysed systematically using RevMan® and combined outcomes were expressed as odds ratios (OR) and standardized mean differences (SMD). RESULTS: Seven randomized, controlled trials evaluating 1631 patients were retrieved from electronic databases. There were 760 patients in the ABS group and 871 patients in the simple suture group. There was moderate heterogeneity among trials (Tau(2) = 0.12; chi(2) = 8.40, df = 6 [P < 0.01]; I(2) = 29%). Therefore in the random-effects model, the use of ABS for skin closure in surgical patients was associated with a reduced risk of developing surgical site infections (OR, 0.16; 95% CI, 0.37, 0.99; z = 2.02; P < 0.04) and postoperative complications (OR, 0.56; 95% CI, 0.32, 0.98 z = 2.04; P = 0.04). The durations of operation and lengths of hospital stay were similar following the use of ABS and SS for skin closure in patients undergoing various surgical procedures. CONCLUSION: Use of ABS for skin closure in surgical patients is effective in reducing the risk of surgical site infection and postoperative complications. ABS is comparable with SS in terms of length of hospital stay and duration of operation.

Open transinguinal preperitoneal mesh repair of inguinal hernia: a targeted systematic review and meta-analysis of published randomized controlled trials.

OBJECTIVE: The objective of this article is to systematically analyse the randomized, controlled trials comparing transinguinal preperitoneal (TIPP) and Lichtenstein repair (LR) for inguinal hernia. METHODS: Randomized, controlled trials comparing TIPP vs LR were analysed systematically using RevMan® and combined outcomes were expressed as risk ratio (RR) and standardized mean difference. RESULTS: Twelve randomized trials evaluating 1437 patients were retrieved from the electronic databases. There were 714 patients in the TIPP repair group and 723 patients in the LR group. There was significant heterogeneity among trials (P < 0.0001). Therefore, in the random effects model, TIPP repair was associated with a reduced risk of developing chronic groin pain (RR, 0.48; 95% CI, 0.26, 0.89; z = 2.33; P < 0.02) without influencing the incidence of inguinal hernia recurrence (RR, 0.18; 95% CI, 0.36, 1.83; z = 0.51; P = 0.61). Risk of developing postoperative complications and moderate-to-severe postoperative pain was similar following TIPP repair and LR. In addition, duration of operation was statistically similar in both groups. CONCLUSION: TIPP repair for inguinal hernia is associated with lower risk of developing chronic groin pain. It is comparable with LR in terms of risk of hernia recurrence, postoperative complications, duration of operation and intensity of postoperative pain.