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.