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Objective: To study uterine peristalsis using step-by-step 4-dimensional (4D) ultrasound assessment video, explore its relationship with progesterone levels in a select in vitro fertilization population, and assess the reproducibility of the technique. Design: Four-dimensional uterine ultrasound and a retrospective analysis of outcomes in relation with progesterone levels. The videos were also analyzed by a senior doctor, junior doctor, and a nurse for their reproducibility. Setting: Instituto Bernabeu of Alicante is a private clinic. Patient(s):The study included 197 consecutive patients undergoing in vitro fertilization (from 2018 to 2019) with a history of recurrent implantation failure (defined as unsuccessful implantation of a total number of R3 blastocysts originated from oocyte donation cycles). Because it is known that most failures are attributed to the quality of the embryo, we deemed it important to explore the potential uterine factors explaining the failures in oocyte donation cycles, the use of which decreases the probability of embryo-related factors influencing it. Intervention(s): The participants were evaluated for uterine contractions and serum progesterone levels (10-30 minutes before the embryo transfer procedure). Uterine contractility (UC) was assessed by recording a 6-minute-long video using a 4D mode (Voluson E10; General Electric, Boston, MA), which was performed by a single operator (B.M.). Main Outcomes Measure(s): The contractions were seen like waves going through the endometrial cavity. They were counted on a Â15 accelerated recording video. To define high-frequency UC, we separated uterine peristalsis (contractions per minute [cpm]) into quartiles. The highest quartile defined the hypercontractility group (>1.51 cpm; n ¼ 41), considering the remaining quartiles as the normal contractility group (%1.51 cpm; n ¼ 156). The Mann-Whitney U test was performed. The intraclass correlation coefficient was used to validate variability. P < .05 was considered significant. SPSS version 21.0 was used for the statistical analysis. The institutional review board's approval was obtained. Result(s): Overall, an average of 1.1 cpm was found in the study population. There were no differences between the groups (hypercontractility vs. normal contractility) in terms of patient age and the presence of any uterine factor (adenomyosis, myomas, adhesions, or polyps). An inverse association was observed between UC and progesterone levels. Low progesterone levels (15.9 vs. 19.5 ng/mL; P ¼ .027) were observed in the HUP and NUP group, respectively. The intraclass correlation coefficient to evaluate the interobserver variability was 0.75 (0.63-0.85; P ¼ .000). Conclusion(s):Four-dimensional ultrasound assessment provides a dynamic view of uterine contractions, including their directionality and frequency. Even though recurrent implantation failure is yet a title of obscure definition and probably associated with multiple factors, a subgroup of patients with elevated UC associated with ''low'' progesterone leve...

The factors that cause a preterm birth (PTB) are not completely understood up to date. Moreover, PTB is more common in pregnancies achieved by in-vitro fertilization (IVF) than in spontaneous pregnancies. Our aim was to compare the composition of vaginal microbiome at 12 weeks of gestation between women who conceived naturally or through IVF in order to study whether IVF PTB-risk could be related to vaginal microbiome composition. We performed an observational, prospective and multicentre study among two public hospitals and a fertility private clinic in Spain. Vaginal swabs from 64 pregnant women at 12 weeks of gestation were collected to analyse the microbiome composition by sequencing the V3–V4 region of the 16S rRNA. Our results showed that the vaginal microbiome signature at 12 weeks of pregnancy was different from women who conceived naturally or through IVF. The beta diversity and the genus composition were different between both cohorts. Gardnerella, Neisseria, Prevotella, and Staphylococcus genus were enriched genus in the vaginal microbiome from the IVF group, allowing us to create a balance model to predict both cohorts. Moreover, at species level the L. iners abundance was higher and L. gasseri was lower in the IVF group. As a conclusion, our findings were consistent with a proposed framework in which IVF pregnancy are related to risk for preterm birth (PTB) suggesting vaginal microbiome could be the reason to the relation between IVF pregnancy and risk for PTB.

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Study question Can next generation sequencing (NGS) contribute to diagnoses male idiopathic infertility? Summary answer A male factor gene panel identifies pathogenic variants associated to spermatogenic failure in oligozoospermia and cryptozoospermia patients. What is known already In 50% of cases, infertility is due to a male factor problem. Although the causes of male infertility are heterogeneous, genetic causes account for approximately 30% of cases. Some phenotypes have been associated with specific genetic disorders such as chromosomal abnormalities and chromosome Y microdeletions. However, current genetic studies explain only 4% of cases, whilst most cases of male factor infertility remain without a clear diagnosis. Therefore, new techniques that explain the cause of male infertility are needed. Advances in NGS allowed us to study a large number of genes involved in spermatogenesis process in patients with idiopathic infertility. Study design, size, duration A retrospective study was performed from July 2020 until May 2021. A total of 30 patients with abnormal seminal count parameters (oligozoospermic and cryptozoospermic) were included in the male factor gene panel study. Patients carrying Y-chromosome microdeletions or abnormal karyotype were excluded. The control group included 20 normozoospermic healthy donors selected on the basis of normal semen parameters according to the WHO criteria (2010). Participants/materials, setting, methods Genomic DNA extraction from blood-EDTA of the patients was performed using the commercial MagMax DNA MultiSample Ultra kit and the King-Fisher automated extractor (ThermoFisher®). Next Generation Sequencing (NGS) was done using a panel with 426 genes involved in the spermatogenesis process. Panel sequencing for identification of genetic variants was performed using Nextera Enrichment technology (Illumina®). FASTAQ data were processed using BWA and GATK algorithms. VCF files were analyzed using Variant Interpreter software. Main results and the role of chance After data analysis, we observed that eight of the thirty patients studied were carriers of mutations in least one of the genes included in the panel (8/30, 26.7%). We identified the following pathogenic variants: a missense mutation (Phe1052Val) and a deletion (Phe508del) of CFTR gene (2/30, 6.6%), two frameshifts (Asp128GlufsTer34 and Lys1299Ter) of CEP290 (2/30, 6.6%), a missense mutation (Tyr284Cys) of GNRHR gene (1/30, 3.3%), a missense mutation (Tyr416Cys) of SCN5A gene (1/30, 3.3%), a deletion (Ser83del) of NANOS1 gene (1/30, 3.3%), a stop gained in splice region Arg341Ter of TEX14 gene (1/30, 3.3%), a splicing donor c.362 + 2T&gt;C of ESR2 gene (1/30, 3.3%) and a missense mutation (Ser321Leu) of DNAH5 gene (1/30, 3.3%), which are related to spermatogenesis failure. Additionally, some variants classified as benign have been identified, which are not associated with pathogenicity. All the variants identified are related with male infertility, affecting spermatogenesis process, such as congenital bilateral absence of the vas deferens (CFTR), reproductive system syndrome (CEP190), endocrine disorder (GNRHR, hypogonadotropic hypogonadism), testis expressed (SCN5A), spermatogenic failure (NANOS1, TEX14 and ESR2) and syndromic infertility (DNAH5). Nevertheless, no pathogenic mutations associated to spermatogenic failure were observed in the control group. Limitations, reasons for caution The main limitation of this study is the small number of patients included. Further studies including a higher number of males with idiopathic infertility are warranted to confidently link the genetic variants included in our gene panel to spermatogenic failure. Wider implications of the findings The gene list included in our panel represents a step-forward in the diagnosis screening of males with altered sperm parameters. Our results may add in the knowledge of male factor infertility in order to provide etiologic factors towards a personalized treatment and adequate genetic counselling. Trial registration number Not applicable