Endometrial receptivityEndometrial receptivity analysis (ERA) Fresh embryo transfer (ET) Frozen embryo transfer (FET) Personalized embryo transfer (PET) Window of implantation (WOI)

Background Previous evidence indicates associations between the female reproductive tract microbiome composition and reproductive outcome in infertile patients undergoing assisted reproduction. We aimed to determine whether the endometrial microbiota composition is associated with reproductive outcomes of live birth, biochemical pregnancy, clinical miscarriage or no pregnancy. Methods Here, we present a multicentre prospective observational study using 16S rRNA gene sequencing to analyse endometrial fluid and biopsy samples before embryo transfer in a cohort of 342 infertile patients asymptomatic for infection undergoing assisted reproductive treatments. Results A dysbiotic endometrial microbiota profile composed of Atopobium, Bifidobacterium, Chryseobacterium, Gardnerella, Haemophilus, Klebsiella, Neisseria, Staphylococcus and Streptococcus was associated with unsuccessful outcomes. In contrast, Lactobacillus was consistently enriched in patients with live birth outcomes. Conclusions Our findings indicate that endometrial microbiota composition before embryo transfer is a useful biomarker to predict reproductive outcome, offering an opportunity to further improve diagnosis and treatment strategies.

This article summarises and contextualises the accumulated basic and clinical data on the ERA test and addresses specific comments and opinions presented by the opponent as part of an invited debate. Progress in medicine depends on new technologies and concepts that translate to practice to solve long-standing problems. In a key example, combining RNA sequencing data (transcriptomics) with artificial intelligence (AI) led to a clinical revolution in personalising disease diagnosis and fostered the concept of precision medicine. The reproductive field is no exception. Translation of endometrial transcriptomics to the clinic yielded an objective definition of the limited time period during which the maternal endometrium is receptive to an embryo, known as the window of implantation (WOI). The WOI is induced by the presence of exogenous and/or endogenous progesterone (P) after proper oestradiol (E2) priming. The window lasts 30–36 hours and, depending on the patient, occurs between LH + 6 and LH + 9 in natural cycles or between P + 4 and P + 7 in hormonal replacement therapy (HRT) cycles. In approximately 30% of IVF cycles in which embryo transfer is performed blindly, the WOI is displaced and embryo-endometrial synchrony is not achieved. Extending this application of endometrial transcriptomics, the endometrial receptivity analysis (ERA) test couples next-generation sequencing (NGS) to a computational predictor to identify transcriptomic signatures for each endometrial stage: proliferative (PRO), pre-receptive (PRE), receptive (R) and post-receptive (POST). In this way, personalised embryo transfer (pET) may be possible by synchronising embryo transfer with each patient’s WOI. Data are the only way to confront arguments sustained in opinions and/or misleading concepts; it is up to the reader to make their own conclusions regarding its clinical utility.

Background: Previous evidence indicates associations between the female reproductive tract microbiome composition and reproductive outcome in infertile patients undergoing assisted reproduction. We aimed to determine whether the endometrial microbiota composition is associated with reproductive outcomes of live birth, biochemical pregnancy, clinical miscarriage, or no pregnancy. Methods: Here we present a multicentre prospective observational study using 16S rRNA gene sequencing to analyse endometrial fluid and biopsy samples before embryo transfer in a cohort of 342 infertile patients asymptomatic for infection undergoing assisted reproductive treatments. Results: A dysbiotic endometrial microbiota profile composed of Atopobium, Bifidobacterium, Chryseobacterium, Gardnerella, Haemophilus, Klebsiella, Neisseria, Staphylococcus and Streptococcus was associated with unsuccessful outcomes. In contrast, Lactobacillus was consistently enriched in patients with live birth outcomes. Conclusions: Our findings indicate that endometrial microbiota composition before embryo transfer is a useful biomarker to predict reproductive outcome, offering an opportunity to further improve diagnosis and treatment strategies.

This investigation compared the effectiveness of a cognitive-behavioral HIV risk reduction intervention with a standard care (SC) comparison condition in modifying HIV risk related knowledge, beliefs, attitudes, and behavior at 6-month and 12-month follow-ups among 149 HIV seronegative males. The two intervention conditions were administered while participants were in inpatient alcohol and other drug abuse treatment. Global drug abuse severity, as well as injection drug abuse, decreased significantly from preintervention to follow-up across conditions. There were significant increases in the proportions reporting sexual activity and increases in levels of unprotected sex acts between baseline and follow-up across conditions. However, no changes in sex risk behavior were found among those who reported sexual activity both prior to and after intervention across conditions. Participants revealed relatively adequate knowledge regarding HIV and HIV risk reduction practices, strong belief in the utility of safer practices and in their ability to enact such practices, and relatively strong commitment to practice safer sex across conditions at baseline assessment. In general, substantial postintervention improvements over baseline levels in these areas were not found. Relatively modest changes in sexual self-efficacy and in safe-sex guidelines were identified in analyses involving the total sample. Exploratory subgroup analysis suggested increases in knowledge and reductions in susceptibility and anxiety among those who reported sexual activity both prior to and after intervention. Among participants reporting initiation of sexual activity after intervention, those receiving SC revealed changes in perceived susceptibility and in condom attitudes. A discussion is presented of challenges associated with providing meaningful HIV risk reduction intervention when baseline levels of sex risk behavior, perceived HIV infection susceptibility, and HIV anxiety are only moderate and when initial levels of sexual self-efficacy and commitment are relatively high.

Study question Is there an association between the composition of the endometrial microbiota and the reproductive outcomes in infertile patients undergoing in vitro fertilization (IVF)? Summary answer The composition of the endometrial microbiota (EM) prior to embryo transfer is associated with the different reproductive outcomes: live birth, no pregnancy or clinical miscarriage. What is known already The investigation of bacterial communities in the female reproductive tract using molecular methods has revealed the existence of a continuum microbiota that extends from the vagina to the upper genital tract. Previous evidence suggests the existence of an association between the vaginal and endometrial microbiome composition with reproductive and obstetrical outcomes. Specifically, the presence of specific pathogens together with low abundance of Lactobacilli has been associated with poor IVF outcomes. Study design, size, duration Multicentre prospective observational clinical study analysing the EM of infertile patients undergoing IVF (with maternal age ≤40) or ovum donation (≤50 years). A total of 452 infertile patients undergoing IVF/ovum donation were assessed for eligibility in 13 reproductive clinics in Europe, America, and Asia. The duration of the study was 30 months and the recruitment period extended between August 2017 and February 2019 (ct.gov 03330444). Participants/materials, setting, methods Endometrial fluid and endometrial biopsy were collected during a hormonal replacement therapy cycle after 5 days of progesterone (P) administration prior to a frozen embryo transfer cycle. Endometrial microbiota (EM) composition was analyzed using 16S rRNA gene sequencing using compositional data to transform scale-invariant values in both sample types. The EM in fluid and biopsy was associated with live birth, biochemical pregnancy, clinical miscarriage, or no pregnancy. Main results and the role of chance Of the 452 patients assessed, 44 did not meet the selection criteria and were excluded for the study and 66 patients were lost to follow-up. Of the 342 remaining patients, 198 (57.9%) became pregnant [141 (41.2%) had a live birth, 27 (7.9%) had a biochemical pregnancy, 2 (0.6%) had an ectopic pregnancy, and 28 (8.2%) a clinical miscarriage], while 144 (42.1%) did not become pregnant. The baseline characteristics, clinical and embryological variables were homogeneous and no bias toward the clinical outcome categories was observed. Our association study showed that the composition of the EM was associated with the reproductive outcome in both endometrial fluid and biopsy. A dysbiotic endometrial microbiota profile composed of Atopobium, Bifidobacterium, Chryseobacterium, Gardnerella, Haemophilus, Klebsiella, Neisseria, Staphylococcus and Streptococcus was significantly associated with unsuccessful outcomes, especially no pregnancy and clinical miscarriage. In contrast, Lactobacillus was consistently enriched in patients with live birth outcomes. The EM in endometrial fluid did not fully reflect that in endometrial biopsy, although their association with clinical outcome was consistent. Limitations, reasons for caution The main limitation was the small number of biochemical pregnancy and clinical miscarriage analysed. During transcervical collection of endometrial samples caution was taken to avoid contamination with the cervix although cervical contamination cannot be fully discarded. Wider implications of the findings Our data indicate that EM dysbiosis is associated with poor clinical outcome in ART. Thus, the EM composition before embryo transfer could be a useful biomarker to consider offering an opportunity to further improve diagnosis and treatment strategies. Trial registration number Clinical trials.gov 03330444

EBL). Spearman's correlation was used to evaluate the correlation between leiomyomata volume and operative outcomes. Receiver-operator-characteristic (ROC) curves were constructed for outcomes showing statistical significance.RESULTS: A total of 117 patients were included; there was no difference in the demographics or leiomyomata characteristics of patients undergoing MRI or US in the AM (n¼69), LM (n¼13) or RALM (n¼35) groups. The mean age and leiomyomata volume of patients undergoing LM was 36.7AE7.1 years and 152.1AE90.9 mL, respectively. The was a strong positive correlation between MRI leiomyomata volume and operating time (rho¼0.90; P<0.001) and leiomyomata weight (rho¼0.89; P¼0.02). Patients in the RALM group had a mean age and leiomyomata volume of 36.9AE4.1 years and 242.4AE136.1 mL, respectively. A significant positive correlation between MRI leiomyomata volume and operating time (rho¼0.83; P¼0.03) and leiomyomata weight (rho¼0.79; P¼0.01) was noted in the RM group as well. These correlations were non-significant in the LM and RALM groups when using US leiomyomata volume. MRI leiomyomata volume was also predictive of LM and RALM conversion to laparotomy (area-under-the-curve¼0.92).

multicentre randomized controlled trial comparing personalized, frozen and fresh blastocyst transfer in IVF. Reprod. Biomed. 2020