Centromeric AA motif in KIR as an optimal surrogate marker for precision definition of alloimmune reproductive failure.

Throughout pregnancy, the decidua is predominantly populated by NK lymphocytes expressing Killer immunoglobulin-like receptors (KIR) that recognize human leukocyte antigen-C (HLA-C) ligands from trophoblast cells. This study aims to investigate the association of KIR-HLA-C phenotypes in couples facing infertility, particularly recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF), in comparison to a reference population and fertile controls. This observational, non-interventional retrospective case-control study included patients consecutively referred to our Reproductive Immunology Unit from 2015 to 2019. We analyzed the frequencies of KIR and HLA-C genes. As control groups, we analyzed a reference Spanish population for KIR analysis and 29 fertile controls and their male partners for KIR and HLA-C combinations. We studied 397 consecutively referred women with infertility and their male partners. Among women with unexplained RPL (133 women) and RIF (176 women), the centromeric (cen)AA KIR genotype was significantly more prevalent compared to the reference Spanish population (p = 0.001 and 0.02, respectively). Furthermore, cenAA was associated with a 1.51-fold risk of RPL and a 1.2-fold risk of RIF. Conversely, the presence of BB KIR showed a lower risk of reproductive failure compared to non-BB KIR (OR: 0.12, p < 0.001). Women and their partners with HLA-C1C1/C1C1 were significantly less common in the RPL-Group (p < 0.001) and RIF-Group (p = 0.002) compared to the control group. Moreover, the combination of cenAA/C1C1 in women with C1C1 partners was significantly higher in the control group than in the RPL (p = 0.009) and RIF (p = 0.04) groups, associated with a 5-fold increase in successful pregnancy outcomes. In our cohort, the cenAA KIR haplotype proved to be a more accurate biomarker than the classic AA KIR haplotype for assessing the risk of RPL and RIF, and might be particularly useful to identify women at increased risk among the heterogeneous KIR AB or Bx population. The classification of centromeric KIR haplotypes outperforms classical KIR haplotypes, making it a better indicator of potential maternal-fetal KIR-HLA-C mismatch in patients.

Cumulative live birth rates in egg donor IVF cycles with or without endometrial scratching: Is there a residual effect in subsequent embryo transfers? Follow-up results of a RCT in clinical practice.

INTRODUCTION: Endometrial scratching (ES) is a simple technique that has been claimed to improve pregnancy rates in patients undergoing assisted reproduction techniques. Our objective was to acknowledge the effects of ES in subsequent embryo transfers by assessing the cumulative live birth rates (LBR) in patients undergoing egg-donor in vitro fertilization (IVF). MATERIAL AND METHODS: We performed a follow-up analysis of the cumulative reproductive outcomes of the 352 patients included in the Endoscratch Trial (NCT03108157) during the twelve months following the randomization date. We compared the outcomes of patients who underwent an ES for the second and/or successive embryo transfers versus those who did not have an ES performed, in order to determine a possible carry over effect that could lead to different LBR in these groups. RESULTS: Our analysis reveals that both groups (with and without ES performed before the first embryo transfer) had similar cumulative LBR (69.9% vs 65.9% in group A and B respectively, RR: 1.20, 95% confidence interval (CI): 0.92 - 1.22, p = 0.42). When we analyzed the results comparing patients who had received at least an ES before any of the embryo transfers during that period, we did not find any differences in LBR either (68.0% in patients with at least an ES and 67.8% in patients without ES, RR 1.00, 95%CI 0.87 - 1.16, p = 0.96). CONCLUSION: According to our results, we cannot state that ES has a long term effect on endometrial receptivity of egg recipients as cumulative LBR do not differ from those of patients who do not receive it.

Endometrial microbiota composition is associated with reproductive outcome in infertile patients.

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. Video Abstract.

Is Endometrial Scratching Beneficial for Patients Undergoing a Donor-Egg Cycle with or without Previous Implantation Failures? Results of a Post-Hoc Analysis of an RCT.

Endometrial scratching (ES) has been proposed as a useful technique to improve outcomes in in vitro fertilization (IVF) cycles, particularly in patients with previous implantation failures. Our objective was to determine if patients undergoing egg-donor IVF cycles had better live birth rates after ES, according to their previous implantation failures. Secondary outcomes were pregnancy rate, clinical pregnancy rate, ongoing pregnancy rate, miscarriage rate, and multiple pregnancy rate. We analysed the results of 352 patients included in the Endoscratch Trial (NCT03108157). A total of 209 were patients with one or no previous implantation failures (105 with an ES done in the previous cycle, group A1, and 104 without ES, group B1), and 143 were patients with at least two previous failed implantations (71 patients with ES, group A2, and 72 without ES, group B2). We found an improvement in pregnancy rates (62.9% in group A1 vs. 55.8% in group B1 vs. 70.4% in group A2 vs. 76.4% in group B2, p = 0.028) in patients with at least two previous implantation failures, but this difference was not statistically different when we compared clinical pregnancy rates (59.1% vs. 51.0% vs. 64.8% vs. 68.1% in groups A1, B1, A2 and B2, respectively, p = 0.104) and live birth rates (52.4% vs. 43.3% vs. 57.8% vs. 55.6% in groups A1, B1, A2 and B2, respectively, p = 0.218). According to these results, we conclude that there is no evidence to recommend ES in egg-donor IVF cycles, regardless of the number of previous failed cycles.

A 5-year multicentre randomized controlled trial comparing personalized, frozen and fresh blastocyst transfer in IVF.

RESEARCH QUESTION: Does clinical performance of personalized embryo transfer (PET) guided by endometrial receptivity analysis (ERA) differ from frozen embryo transfer (FET) or fresh embryo transfer in infertile patients undergoing IVF? DESIGN: Multicentre, open-label randomized controlled trial; 458 patients aged 37 years or younger undergoing IVF with blastocyst transfer at first appointment were randomized to PET guided by ERA, FET or fresh embryo transfer in 16 reproductive clinics. RESULTS: Clinical outcomes by intention-to-treat analysis were comparable, but cumulative pregnancy rate was significantly higher in the PET (93.6%) compared with FET (79.7%) (P = 0.0005) and fresh embryo transfer groups (80.7%) (P = 0.0013). Analysis per protocol demonstrates that live birth rates at first embryo transfer were 56.2% in PET versus 42.4% in FET (P = 0.09), and 45.7% in fresh embryo transfer groups (P = 0.17). Cumulative live birth rates after 12 months were 71.2% in PET versus 55.4% in FET (P = 0.04), and 48.9% in fresh embryo transfer (P = 0.003). Pregnancy rates at the first embryo transfer in PET, FET and fresh embryo transfer arms were 72.5% versus 54.3% (P = 0.01) and 58.5% (P = 0.05), respectively. Implantation rates at first embryo transfer were 57.3% versus 43.2% (P = 0.03), and 38.6% (P = 0.004), respectively. Obstetrical outcomes, type of delivery and neonatal outcomes were similar in all groups. CONCLUSIONS: Despite 50% of patients dropping out compared with 30% initially planned, per protocol analysis demonstrates statistically significant improvement in pregnancy, implantation and cumulative live birth rates in PET compared with FET and fresh embryo transfer arms, indicating the potential utility of PET guided by the ERA test at the first appointment.

Endometrial scratch vs no intervention in egg donation cycles: the ENDOSCRATCH trial protocol.

BACKGROUND: The effects of endometrial scratching (ES) on embryo implantation have been studied for many years. Several studies have shown better outcomes when performed on patients undergoing intrauterine insemination and in vitro fertilization (IVF) cycles, but many other reports have not been able to find these differences. As far as cycles with donor eggs are concerned, reported evidence is scarce. Our aim in this trial is to determine if ES is useful for those patients undergoing IVF cycles with donor eggs, in order to assure a greater homogeneity in embryo quality and endometrial preparation. METHODS: This single centre randomized controlled trial will include patients undergoing an egg donation cycle, meeting the inclusion criteria and who accept to participate in the study. Once informed consent is signed, patients will be randomly allocated to the study arm (group A) and then receive ES in the luteal phase of the cycle prior to embryo transfer, or the control arm (group B) without any intervention. All cycle data will be collected and analyzed to obtain the clinical pregnancy and the live birth rates in the two groups. DISCUSSION: Several studies have tried to determine the effectiveness of an ES in IVF cycles, but it is still unclear due to the heterogeneity of these reports. The aim of this study is to determine if there are differences in clinical pregnancy rate and live birth rate in egg donor cycles, when comparing an ES performed in the preceding luteal phase versus no intervention, given that embryo quality and endometrial preparation protocols will be comparable. TRIAL REGISTRATION: Ethical approval of version 2.0 of this trial was obtained on the 13th January 2017. It was retrospectively registered on the 5th April 2017 as the ENDOSCRATCH Trial (NCT03108157) in ClinicalTrials.gov.

Evaluation of the degree of satisfaction in oocyte donors using sustained-release FSH corifollitropin α.

Ovarian stimulation treatment is recognized as placing a physical and psychological burden on patients and oocyte donors. The introduction of sustained follicle stimulants will reduce the number of injections and may improve the overall patient experience. This study aimed to evaluate the degree of satisfaction in oocyte donors undergoing treatment with corifollitropin α, a synthetic recombinant rFSH which replaces daily FSH injections for the first week of ovarian stimulation. The results showed no significant differences in clinical parameters between the two protocols (recombinant FSH versus corifollitropin α). Implantation rates for the corifollitropin α and daily FSH protocol groups were 39.1% and 38.4%, respectively, while ongoing pregnancy rates were 45.9% and 44.4%. There were no statistical between-group differences in the responses to the questionnaires. However, donors treated with corifollitropin α who had undergone a previous cycle with daily FSH reported greater satisfaction with the corifollitropin α protocol. In conclusion, no significant differences were found in any analysed parameters between treatments. However, when donors who had undergone both treatments chose which treatment they preferred, the results clearly showed a positive trend towards choosing corifollitropin α, confirming that this protocol may reduce treatment burden and increase donor compliance.

Lesión urológica compleja y gestación. Técnica de Mitrofanoff / Complex urological damage and pregnancy. Mitrofanoff’s technique

Se expone el caso de una mujer primigesta, de 31 años, con lesión traumática uretral 10 años atrás, sometida a derivación urinaria de Mitrofanoff, consistente en la creación de una comunicación cateterizable de la vejiga con el exterior (generalmente se emplea el apéndice cecal). El control gestacional realizado fue el habitual, además de urocultivos mensuales, en los que se detectan infecciones del tracto urinario (ITU) de repetición resueltas con antibioticoterapia oral.En la semana 31 se produjo un prolapso de cordón que obligó a la realización de una cesárea urgente.A propósito de éste, presentamos los 14 casos publicados sobre gestación en pacientes con derivación urinaria de Mitrofanoff, circunstancia en la que se recomienda la cesárea programada como vía de finalización del embarazo (AU)

We report the case of a 31-year-old primigravida who had sustained irreversible urethral damage in a traffic accident 11 years previously. The lesion required the application of Mitrofanoff’s technique, consisting of the creation of a catheterizable urinary conduit from the urinary bladder to the abdominal wall (the cecal appendix is generally used). In addition to routine prenatal care, monthly urine cultures were performed, revealing recurrent urinary tract infections, which were resolved with oral antibiotics.At 31 weeks of pregnancy, emergency cesarean section was performed due to umbilical cord prolapse. We review the 14 cases published on pregnant women with Mitrofanoff’s technique, in whom elective cesarean section is the recommended form of delivery (AU)