Problem: Expansion of circulating NK cells has been related to pregnancy complications. This study aims at investigating several surface NK cell markers to identify a baseline inflammatory profile in women with recurrent pregnancy loss (iRPL) and recurrent implantation failure (iRIF).Method of study: Expression of NKp30, TIGIT, NKp46, and DNAM-1 on total peripheral blood NK subsets, regulatory (CD56 bright CD16 neg ), and cytotoxic (CD56 dim CD16 pos/neg ) NK cells was measured.Results: Eighty-three women were recruited and classified into two groups, 58 women with RPL and 25 with RIF. A control group of 31 fertile women was included.Expression of NKp30 on cytNK was significantly higher in RPL (p = .019) and RIF (p < .001) than HC. TIGIT on cytNK cells was also higher in both RPL (p < .001) and RIF (p < .01). An optimal cutoff of 70% for NKp30 + cytNK disclosed a sensitivity of 82%, a specificity of 55%, and 83% PPV for RPL diagnosis. A cutoff level of 83% for TIGIT + cytNK was chosen to discriminate between healthy controls and RPL women, with PPV of 84%. Conclusion:Our preliminary data on this RPL and RIF cohorts suggest a simple diagnostic tool by combining NKp30 and TIGIT on cytNK cells to better identify a subgroup of RPL and RIF patients with a baseline inflammatory profile. A more rigorous selection of these patients through phenotyping peripheral cytNK cells may better define patients that could benefit from an immunomodulatory treatment to prevent further pregnancy losses. The performance of these biomarkers requires further investigation and validation in independent cohorts. K E Y W O R D S cytotoxic NK cells, inflammation, NKp30, recurrent implantation failure, recurrent pregnancy loss, T-cell immunoglobulin and ITIM domain How to cite this article: Comins-Boo A, Cristóbal I, Fernández-Arquero M, et al. Functional NK surrogate biomarkers for inflammatory recurrent pregnancy loss and recurrent implantation failure. Am J Reprod Immunol.

Objective:The aim of this study is to analyze the efficacy of the dual trigger (human chorionic gonadotropin (hCG) + GnRH agonists) compared to the conventional trigger (hCG) in terms of oocyte retrieval (number and oocyte maturity), fertilization rate or number of embryos with two pronuclei, number of high-quality embryos, number of transferred embryos, number of cryopreserved embryos, implantation rate, positive β-hCG rate, ongoing pregnancy rate, abortion rate, and live birth rate.Methods: This search performed in this systematic review included all literature published in the PubMed database of studies on controlled ovarian stimulation with dual trigger compared with conventional trigger. The metaanalysis included clinical trials and prospective cohort studies.Results: Statistically significant differences between groups (dual trigger vs. hCG trigger) in terms of number of oocytes retrieved and live birth rate favored the dual trigger protocol. No statistically significant differences were found in the other studied variables. A tend favoring the dual trigger protocol was observed in all studied parameters.Conclusions: Dual trigger seems to be more effective in GnRH antagonist cycles in terms of embryo and pregnancy outcome.

BACKGROUND. Uterine fibroids are common benign uterine neoplasms in women in reproductive age and pregnancy desire. Several surgical approaches for symptomatic fibroids are available, such as surgical or pharmacologic treatments. We report three cases of fibroids treatment in women with primary sterility. CASE PRESENTATION. The first case of a successful in vitro fertilization (IVF) after ulipristal acetate (UPA) as an alternative treatment to reduce the fibroids size in a patient with two previous abdominal myomectomies, resulting in an evolutive pregnancy. The second patient underwent several myomectomies (both abdominal and hysteroscopic) in a long period of time. And the third one of a successful IVF after UPA in a patient with a submucous fibroid which induced myoma migration leading to its prolapse.CONCLUSIONS. Myomectomy appears to be the gold standard treatment for fibroids in women with reproductive desires. Nevertheless, more series are essential for establishing the safety of UPA as a treatment of symptomatic fibroids prior to pregnancy.

RESUMENCASO CLÍNICO: la encefalitis anti receptor N-metil D-aspartato (NMDAR) es un trastorno autoinmune con un amplio espectro de síntomas neuropsiquiátricos. Se presenta el caso de una mujer de 22 años con una encefalitis anti-NMDA que cursó con amnesia, crisis parciales complejas y alteraciones del comportamiento asociado a un teratoma ovárico. La evolución fue adecuada con cirugía e inmunosupresores. A los tres años se objetivó un teratoma contralateral, sin recidiva de encefalitis; que fue extirpado tras estimulación ovárica para criopreservación de ovocitos. CONCLUSIONES: el teratoma ovárico debe ser sospechado ante la presencia de una encefalitis atípica. Antes de realizar cirugías ováricas repetidas, debe valorarse la opción de vitrificación ovocitaria si los deseos genésicos de la mujer no están cumplidos.PALABRAS CLAVE: teratoma ovárico, encefalitis anti-NMDA, vitrificación ovocitaria. ABSTRACTCLINICAL CASE: anti-N-methyl-D-aspartate-receptor (NMDAR) encephalitis is an autoimmune disorder with a wide sprectrum of neuropsyquiatric symtoms. A case of a 22 years old woman with NMDAR encephalitis presenting with amnesia, focal complex seizures and behavior disturbances associated with an ovarian teratoma is reported. Three years after the first episode, a contralateral teratoma was observed, with no recurrence of the encephalitis; teratoma excision was performed, after controlled ovarian stimulation for oocyte cryopreservation. CONCLUSIONS: ovarian teratoma must be suspected when atypical encephalitis occurs. Before performing repetead ovarian surgeries, oocyte vitrificaction must be considered as a fertility-sparing option in women who have not completed their childbearing wishes.KEY WORDS: ovarian teratoma, encephalitis anti-NMDA, oocyte vitrification. ANTECEDENTESLa encefalitis anti receptor-N-metil-D-aspartato (NMDAR) es un trastorno autoinmune con un amplio espectro de síntomas neuropsiquiátricos, que fue descrita por primera vez por Vitaliani y Dalmau en 2005 (1). Se producen anticuerpos contra estos receptores, que son proteínas que participan en el control de los impulsos eléctricos en el sistema nervioso central; siendo su concentración más elevada en el cerebro. Afecta en un 80% a mujeres jóvenes y el tumor más frecuentemente asociado es el teratoma ovárico(2) que contiene tejido nervioso atípico y expresa NMDAR. Los síntomas incluyen

Study question We sought to explore the levels of myeloid-derived suppressor cells (MDSCs) in women experiencing recurrent miscarriage (RM) or recurrent implantation failure (RIF) Summary answer MDSCs were significantly expanded in RM patients with respect to fertile healthy women (p = 0.03, 8.25 vs 7.00). What is known already RM and RIF are two distinct disorders that can be associated with a baseline pro-inflammatory state. Different surrogate inflammatory biomarkers have been associated with these disorders in a subgroup of patients, including expanded cytotoxic NK cells, increased pro-inflammatory cytokines or reduced regulatory T cells (TReg). MDSCs are a heterogeneous population of leukocytes, known for their capacity to modulate immune responses. The immunosuppressive function of MDSC in cancer has been well established, while a controversial role in autoimmune diseases has been reported. Typically, there are two major groups of MDSCs in humans: granulocytic/polymorphonuclear MDSCs (PMN-MDSCs) and monocytic MDSCs (M-MDSCs). Study design, size, duration A cross-sectional study to evaluate the levels of MDSCs in women with RM and RIF consecutively referred to our Reproductive Immunology Unit. 55 patients and 23 healthy women were evaluated from 2021 to 2022. RM was defined as the loss of two or more pregnancies and not necessarily consecutive. RIF was defined as the failure to achieve a clinical pregnancy after transferring at least four good-quality embryos. Participants/materials, setting, methods A full fertility screening was performed for all women and their partners as part of routine care. A group of healthy non-pregnant women up to 45 years old with two or more children (proven fertility) and no spontaneous miscarriage was used as control group. Freshly collected blood samples were analyzed by multiparametric flow cytometry using a BD FACS CANTO II. Peripheral blood M-MDSCs were characterized based on HLA-DR, CD14, CD33 and CD45 expression. Main results and the role of chance In this study, we evaluated 55 women, 35 that fulfilled RM criteria and 20 with RIF. In addition, a group of 23 non-pregnant fertile women was included as a control group. We characterized MDSCs as CD14+CD33+CD45+HLA-DR-/LOW, according to previous reports. We observed a significant expansion of peripheral blood MDSCs in RM group compared to the control group (8.25% [6.62-11.9] vs 7.05% [6-7.8], p = 0.03) and RIF group showed a similar increasing trend compared to controls (8.6% [5.65-12.35] vs 7.05% [6-7.8], p = 0.09). We performed ROC curves analysis to evaluate the predictive power. We established an optimal cut-off level of 8.3% in RM group, with a sensitivity of 50% and a specificity of 86.96%. Moreover, women with more than 8.3% had a higher probability of presenting RM compared to the control group (OR: 6.66; CI: 1.68-26.46). MDSCs are characterized by their ability to exert a potent immunosuppressive function. However, recent investigations have shown that MDSCs could act as pro-inflammatory cells under certain inflammatory conditions, such as autoimmune diseases. In this context, MDSCs could worsen the pro-inflammatory state in women, leading to miscarriage or implantation failure. Limitations, reasons for caution In order to validate these results, we should extend our cohort and control group. Moreover, we need to perform a functional evaluation of this subset so we could elucidate their role in these conditions. Wider implications of the findings MDSCs might be a good predictor for RM and RIF patients and with others (as expanded NK cells) may classify a subgroup of patients with a pro-inflammatory profile that can benefit from personalized therapies. Trial registration number Not aplicable