Systematic review and network meta-analysis of hydrosalpinx treatment before in vitro fertilization.

OBJECTIVES: To compare different methods to treat hydrosalpinx, based on both ablative and non-ablative approaches, in infertile patients before undergoing IVF-ET. METHODS: Systematic review and network meta-analysis (NMA) of comparisons between different treatments of hydrosalpinx in infertile patients undergoing IVF. DATA SOURCES: structured searches in common citation databases. Study inclusion criteria: peer-reviewed randomized trials (RCT) or cohort studies comparing effects of salpingectomy, laparoscopic proximal tubal occlusion (LTO), insertion of intratubal device (ITD), sclerotherapy, ultrasound-guided aspiration and no treatment, on live birth, ongoing pregnancy, clinical pregnancy as main outcomes, considering also miscarriage, ectopic pregnancy and complications as secondary outcomes. Principal NMA included RCT, and aggregated NMA of RCT and observational studies was carried out. Pooled effects have been estimated by Odds Ratio (OR) and its 95% confidence interval (CI) for direct and indirect-mixed comparisons, derived from random-effects models. Imprecision and heterogeneity of NMA estimations was assessed by comparison of its 95% CI with predefined intervals for clinically relevant size of effect (OR <0.9 or >1.1). Surface under the cumulative ranking curve (SUCRA) were used to predict treatment rankings for each outcome. RESULTS: Nine RCT were included in main analysis, plus 17 additional observational studies in additional analysis. NMA of RCT did not identify significant differences in the effect of compared treatments on live birth rate, and LTO was the option with the highest value of SUCRA (0.92, mean rank: 1.2). Salpingectomy and US-aspiration associated to a significant increase of ongoing pregnancy rate compared to no treatment, according to NMA results (NMA OR: 4.35; 95% CI: 1.7, 11.14 and 2.8; 95% CI: 1.03, 7.58 respectively). Salpingectomy had the highest SUCRA value (0.88, mean rank: 1.4). NMA estimated significant increase of clinical pregnancy rate for salpingectomy compared with no treatment (NMA OR: 2.24; 95% CI: 1.3, 3.86) as well as for LTO versus no treatment (NMA OR: 2.55; 95% CI: 1.2, 5.41). Both comparisons were affected by a high grade of heterogeneity. For clinical pregnancy, LTO was the intervention with highest SUCRA (0.85; mean rank: 1.6). Regarding secondary outcomes, feasible NMA estimates did not support significant differences between treatments effects. According to aggregated NMA including randomized and observational studies, sclerotherapy showed significant beneficial effects on live birth rate compared to no treatment (NMA (OR: 4.6; 95% CI: 1.21, 17.46). Compared with untreated patients, the aggregated NMA estimates a higher ongoing pregnancy rate in patients treated with salpingectomy (NMA OR: 3.35; 95% CI: 2.12, 5.12), US-aspiration (NMA OR: 2.16; 95% CI: 1.28, 3.65) and LTO (NMA OR: 2.46; 95% CI: 1.11, 5.43). Salpingectomy and LTO produced a higher beneficial effect compared to ITD, based on both direct and indirect comparisons. Salpingectomy obtained the highest SUCRA value in rank of effects on ongoing pregnancy (0.94; mean rank: 1.2). NMA found significant effects on clinical pregnancy for comparisons between the different active management procedures compared with no treatments, with the exception of ITD insertion. LTO had more increasing effect on clinical pregnancy rate compared with US-aspiration (NMA OR: 2.04; 95% CI: 1.05, 3.97), while for the rest of the comparisons between procedures no significant differences were identified. NMA ranked LTO as the treatment with a highest SUCRA value (0.91; mean rank: 1.5). NMA prediction models identified LTO as best intervention to reduce miscarriage (SUCRA value: 0.84; mean rank: 1.8), as sclerotherapy as safer option in terms of ovarian response to IVF stimulation. CONCLUSIONS: The present NMA fails to support the effectiveness of any option to treat hydrosalpinx before IVF in order to improve live birth rates, although the beneficial effect of salpingectomy and US aspirations on ongoing pregnancy rates and of both salpingectomy and LTO on clinical pregnancy rates emerges from our analysis, which reinforces current recommendations. Based on the aggregated analyses, sclerotherapy could be a promising alternative to conventional laparoscopic techniques, combined with a favorable safety profile. This article is protected by copyright. All rights reserved.

Impact of congenital uterine anomalies on obstetric and perinatal outcomes: systematic review and meta-analysis.

Background: Congenital uterine anomalies (CUA) can be associated with impairments of early and late pregnancy events. Objective: To assess the impact of CUA on reproductive outcomes in pregnancies conceived spontaneously or after assisted reproduction. Materials and Methods: Systematic review and meta-analysis of cohort studies comparing patients with CUA versus women with normal uterus. A structured literature search was performed in leading scientific databases to identify prospective and retrospective studies. The Newcastle-Ottawa scale, adapted to AHRQ standards, was used to assess the risk of bias. Pooled odds ratios (OR) were calculated. Publication bias and statistical heterogeneity were assessed, and meta-regression was used to analyse the heterogeneity. Main outcome measures: Miscarriage, ectopic pregnancy, placental abruption, term, and premature rupture of membranes (PROM), malpresentation at delivery, preterm delivery prior to 37, 34 and 32 weeks, caesarean delivery, intrauterine growth restriction/small for gestational age, foetal mortality and perinatal mortality. Results: 32 studies were included. CUAs increased significantly the risk of first/second trimester miscarriage (OR:1.54;95%CI:1.14-2.07), placental abruption (OR:5.04;3.60-7.04), PROM (OR:1.71;1.34-2.18), foetal malpresentation at delivery (OR:21.04;10.95-40.44), preterm birth (adjusted OR:4.34;3.59-5.21), a caesarean delivery (adjusted OR:7.69;4.17-14.29), intrauterine growth restriction/small for gestational age (adjusted OR:50;6.11-424), foetal mortality (OR:2.07;1.56-2.73) and perinatal mortality (OR:3.28;2.01-5.36). Conclusions: CUA increases the risk of complications during pregnancy, delivery, and postpartum. Complications most frequent in CUA patients were preterm delivery, foetal malpresentation, and caesarean delivery. What is new?: Bicornuate uterus was associated with the highest number of adverse outcomes, followed by didelphys, subseptate and septate uterus.

Diagnosis and management of isthmocele (Cesarean scar defect): a SWOT analysis.

The purpose of this State-of-the-Art Review was to provide a strategic analysis, in terms of strengths, weaknesses, opportunities and threats (SWOT analysis), of the current evidence regarding the management of uterine isthmocele (Cesarean scar defect). Strengths include the fact that isthmocele can be diagnosed on two-dimensional transvaginal ultrasound, and that surgical repair may restore natural fertility potential and prevent secondary infertility, as well as reduce the risk of miscarriage and other obstetric complications. However, there is a lack of high-quality evidence regarding the best diagnostic method and criteria, as well as the potential benefits of surgical repair with respect to fertility. There is a need for experienced surgeons skilled in the various isthmocele repair techniques. Isthmocele repair does not prevent the need for Cesarean delivery in subsequent pregnancies. There is increasing awareness regarding the accuracy of transvaginal ultrasound in diagnosing isthmocele. This may lead to surgical correction and prevention of obstetric and perinatal complications in subsequent pregnancies, including Cesarean scar pregnancy. Regarding threats, the existence of different surgical techniques means that there is a risk of selecting an inadequate approach if the type of isthmocele and the patient's characteristics are not considered. There is a risk of overtreatment when asymptomatic defects are repaired surgically. Finally, there is an absence of cost-effectiveness analyses to justify routine repair. Thus, while there are many data suggesting that isthmocele has an adverse effect on both natural fertility and the outcome of assisted reproduction techniques, high-quality evidence to support surgical isthmocele repair in all asymptomatic patients desiring future fertility are lacking. There is increasing agreement to recommend hysteroscopic repair of isthmocele as a first-line approach as long as the residual myometrial thickness is at least 2.5-3.0 mm. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Vaginal neutrophil infiltration is contingent on ovarian cycle phase and independent of pathogen infection.

The mucosa of the female reproductive tract must reconcile the presence of commensal microbiota and the transit of exogenous spermatozoa with the elimination of sexually transmitted pathogens. In the vagina, neutrophils are the principal cellular arm of innate immunity and constitute the first line of protection in response to infections or injury. Neutrophils are absent from the vaginal lumen during the ovulatory phase, probably to allow sperm to fertilize; however, the mechanisms that regulate neutrophil influx to the vagina in response to aggressions remain controversial. We have used mouse inseminations and infections of Neisseria gonorrhoeae, Candida albicans, Trichomonas vaginalis, and HSV-2 models. We demonstrate that neutrophil infiltration of the vaginal mucosa is distinctively contingent on the ovarian cycle phase and independent of the sperm and pathogen challenge, probably to prevent sperm from being attacked by neutrophils. Neutrophils extravasation is a multi-step cascade of events, which includes their adhesion through selectins (E, P and L) and integrins of the endothelial cells. We have discovered that cervical endothelial cells expressed selectin-E (SELE, CD62E) to favor neutrophils recruitment and estradiol down-regulated SELE expression during ovulation, which impaired neutrophil transendothelial migration and orchestrated sperm tolerance. Progesterone up-regulated SELE to restore surveillance after ovulation.

Graham Little-Piccardi-Lassueur syndrome associated with androgen insensitivity syndrome (testicular feminization).

Graham Little-Piccardi-Lassueur syndrome is characterized by the presence of cicatricial alopecia on the scalp, keratosis pilaris in the skin of trunk and extremities, and non-cicatricial hair loss in pubis and axillae. A frequent form of male pseudohermaphroditism is complete androgen insensitivity syndrome (CAIS), also known as testicular feminization syndrome. It refers to genetic males with XY karyotype who, owing to a lack of sensitivity in the peripheral androgenic receptors, develop a female phenotype. Axillary and pubic hair is typically scarce or absent. To our knowledge, this is the first case describing the association of the two processes. The presence of both processes in the same patient furthers our understanding of Graham Little-Piccardi-Lassueur syndrome as it rejects the influence of androgens in the alopecias accompanying this syndrome. The coincidence of non-cicatricial alopecia in axillary and pubic hair in both processes is also remarkable.