Oocyte vitrification for elective fertility preservation: a SWOT analysis.

Oocyte vitrification, also known as egg freezing, is increasingly being used by women as a precautionary measure against the anticipated decline in fertility. In countries where this procedure is allowed, elective oocyte vitrification has become an integral part of the treatment portfolio of fertility clinics. The widespread tendency towards the postponement of motherhood and the advances in laboratory technologies are encouraging women to consider oocyte vitrification and, by doing so, increase their reproductive autonomy. However, elective oocyte vitrification, or elective egg freezing (EEF), still elicits controversy, not only when EEF is appraised from a cost-efficiency point of view, but also in terms of medical and ethical concerns. In general, although the laboratory tool of vitrification has revolutionized the treatment of infertility, the pros and cons need to be clarified when considering EEF.

Variants Ala307Ala and Ser680Ser of 307 and 680 FSHr polymorphisms negatively influence on assisted reproductive techniques outcome and determine high probability of non-pregnancy in Caucasian patients.

PURPOSE: To determine the influence of different genotypes of Ala307Thr and Asn680Ser FSHr polymorphisms on controlled ovarian stimulation (COS) outcome and pregnancy. METHODS: This study collected blood and physiological and clinical parameters of 517 Caucasian patients (Statistical power ≥ 80%) that underwent COS treatment. Genotypes of Ala307Thr and Asn680Ser polymorphisms were determined using PCR amplification followed by Bsu36I and BsrI digestion, respectively. RESULTS: Ala307Ala and Ser680Ser genotypes associated to worse parameters of COS outcome (preovulatory follicles P = 0.05, in both), justifying their lower pregnancy rate than Non-Ala307Ala, P = 0.01 and Non-Ser680Ser, P = 0.004, respectively or together, (P = 0.003). Within the Non-Ala307Ala group, Thr307Thr genotype showed higher number of fertilized oocytes (P = 0.04) and embryos (P = 0.01) than Non-Thr307Thr, but no influence on pregnancy rate. Ala307Ala and Ser680Ser patients doubled probability of non-pregnancy than Non-Ala307Ala (odds ratio = 2.0) and Non-Ser680Ser (odds ratio = 2.11), respectively. Ala307Ala and Ser680Ser genotypes tend to appear together (P < 0.0001), which increases the probability of non-pregnancy. CONCLUSIONS: Ala307Ala and Ser680Ser genotypes of 307 and 680 FSHr polymorphisms associate to worse COS outcome than its respective Non-Ala307Ala and Non-Ser680Ser. Within the Non-Ala307Ala genotypes, Thr307Thr, although shows higher Fertilized Oocytes and Embryos, do not influence on pregnancy rate. Ala307Ala and Ser680Ser genotypes double the probability of Non-Pregnancy than their respective Non-Ala307Ala and Non-Ser680Ser genotypes. Furthermore, the strong tendency of these genotypes to appear together worsens the probability of pregnancy in these patients.

Growth Arrest-Specific Factor 6 (GAS6) Is Increased in COVID-19 Patients and Predicts Clinical Outcome.

BACKGROUND: Growth arrest-specific factor 6 (GAS6) and the Tyro3, AXL, and MERTK (TAM) receptors counterbalance pro-inflammatory responses. AXL is a candidate receptor for SARS-CoV-2, particularly in the respiratory system, and the GAS6/AXL axis is targeted in current clinical trials against COVID-19. However, GAS6 and TAMs have not been evaluated in COVID-19 patients at emergency admission. METHODS: Plasma GAS6, AXL, and MERTK were analyzed in 132 patients consecutively admitted to the emergency ward during the first peak of COVID-19. RESULTS: GAS6 levels were higher in the SARS-CoV-2-positive patients, increasing progressively with the severity of the disease. Patients with initial GAS6 at the highest quartile had the worst outcome, with a 3-month survival of 65%, compared to a 90% survival for the rest. Soluble AXL exhibited higher plasma concentration in deceased patients, without significant differences in MERTK among SARS-CoV-2-positive groups. GAS6 mRNA was mainly expressed in alveolar cells and AXL in airway macrophages. Remarkably, THP-1 human macrophage differentiation neatly induces AXL, and its inhibition (bemcentinib) reduced cytokine production in human macrophages after LPS challenge. CONCLUSIONS: Plasma GAS6 and AXL levels reflect COVID-19 severity and could be early markers of disease prognosis, supporting a relevant role of the GAS6/AXL system in the immune response in COVID-19.

Human intestinal dendritic cell and macrophage subsets in coeliac disease.

Dendritic cells (DC) and macrophages (Mϕ) constitute the most abundant antigen presenting cells in the human intestinal mucosa. In resting conditions, they are essential to maintain the mechanisms of immune tolerance toward food antigens and commensals, at the time that they keep the capacity to initiate and maintain antigen-specific pro-inflammatory immune responses toward invading pathogens. Nevertheless, this delicate equilibrium between immunity and tolerance is not perfect, like in coeliac disease (CD), where DC and Mϕ drive the development of antigen-specific immune responses toward dietary gluten peptides. In this review, we provide therefore a comprehensive discussion about CD pathogenesis, the human intestinal immune system and the biology of intestinal DC and Mϕ both in resting conditions and in CD. Last, but not least, we discuss about all the remaining issues pending to be studied regarding DC and Mϕ contribution toward CD pathogenesis. This may allow the identification of unique and specific factors which may be useful in the clinical practice, as well as identify new therapeutic targets in order to reestablish the loss intestinal homeostasis in CD.

Pros and cons of implementing a carrier genetic test in an infertility practice.

PURPOSE OF REVIEW: Carrier screening is promptly evolving thanks to the rapid development of new technologies and mutation knowledge. Expanded carrier screening is already being used in assisted reproduction. Medical, ethical, psychological and legal aspects appear from the general public, patients, healthcare providers and scientific societies. Pros and cons of implementing this technique are highlighted. RECENT FINDINGS: Recent publications show the development of wider gene screening panels with lowering cost. Human genome is continually being updated as are the number of mutations and their corresponding phenotype known. Classical criteria established to consider a genetic screening protocol are nowadays overtaken, and scientific societies are developing guidelines and criteria adapted to expanded genetic testing. There is no universal agreement on the mutations that should be included in the panel. Patients' perceptions on carrier genetic testing seem to be positive. Counselling patients is of paramount importance stressing implications when testing positive on their clinical decision making. Gamete donor genetic testing implies a modified approach and blinded matching must be offered. SUMMARY: There are important positive aspects implementing a carrier genetic test in assisted reproductive technique, but controversial issues appear. Reproductive providers must be appropriately aware and follow the new guidelines.

Complicaciones obstétricas y perinatales de la amniocentesis genética del segundo trimestre en las gestaciones gemelares / Obstetrical and perinatal complications of mid-trimester genetic amniocentesis in twin pregnancies

Objetivo: Evaluar el resultado de la amniocentesis del segundo trimestre en las gestaciones gemelares. Diseño: Estudio descriptivo retrospectivo. Institución: Unidad de Diagnóstico Prenatal, Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de la Salud, Zaragoza, España. Participantes: Mujeres con gestaciones gemelares. Métodos: Se realizó un estudio mediante la base de datos informatizada y la revisión de las historias clínicas de las pacientes atendidas entre enero de 2004 y febrero de 2008. Las gestaciones gemelares sometidas a amniocentesis fueron comparadas con las gestaciones simples también sometidas a la técnica y con las gestaciones gemelares no sometidas a amniocentesis. Principales medidas de resultados: Complicaciones obstétricas y perinatales. Resultados: Durante los cuatro años del estudio se realizaron 4 263 amniocentesis, de las cuales 112 casos correspondieron a gestaciones gemelares y 4 151 a gestaciones simples. La edad materna avanzada y la ansiedad fueron las indicaciones más frecuentes de amniocentesis. La pérdida fetal durantelas 4 semanas posteriores al procedimiento fue de 1,78% para las gestaciones gemelares y 0,40% para las gestaciones únicas. Las gestaciones gemelares que se sometieron a una amniocentesis genética no presentaron otras complicaciones obstétricas ni peores resultados perinatales. Conclusiones: Basándonos en nuestros datos y los reflejados por estudios previos podemos decir que las gestaciones gemelares sometidas a una amniocentesis del segundo trimestre tienen un riesgo de pérdida fetal ligeramente superior a las gestaciones simples. No obstante, en manos de operadores experimentados, la amniocentesis es una técnica segura y efectiva para el diagnóstico prenatal en las gestaciones gemelares.

Objectives: To determine genetic mid-trimester amniocentesis outcomes in twin gestations. Design: Descriptive retrospective study. Setting: Prenatal Diagnosis Unit, Hospital Universitario Miguel Servet, Instituto Aragones de Ciencias de la Salud, Zaragoza, España. Patients: Women with twin gestations. Methods: Computerized database and medical records of pregnant women attended from January 2004 to February 2008 were reviewed. Twin pregnancies undergoing amniocentesis were compared with singleton pregnancies also exposed to amniocentesis and with unexposed twin pregnancies. Main outcome measures: Obstetrical and perinatal complications. Results: During the four years study 4 263 amniocentesis were performed, 112 in twin gestations and 4 151 in singleton gestations. Advanced maternal age and anxiety were the most common indications for amniocentesis. Fetal loss within four weeks after the procedure was 1,78% for twin pregnancies and 0,40% for singleton pregnancies.Twin gestations exposed to amniocentesis did not present other obstetrical complications or worse neonatal results. Conclusions: Based on our data and previous studies, we can advise patients undergoing mid-trimester twin amniocentesis that fetal loss rate may be slightly higher than for singleton amniocentesis. Although in hands of experienced operators amniocentesis is a safe and effective technique for prenatal diagnosis in twin gestations.