Semen cryopreservation for an oncological reason: a retrospective study.

RESEARCH QUESTION: How do cancer type and treatment affect semen quality before and after treatment, and what effect does it have in their clinical management of infertility? Also, what is the rate of patients using cryopreserved semen samples after treatment? DESIGN: Patients who cryopreserved spermatozoa for oncological reasons between 2000 and 2022 in IVI clinics in Spain were retrospectively reviewed. Semen parameters were analysed before and after treatment, and utilization and destruction rates were calculated. Total motile sperm count (TMSC) was used for assisted reproductive technology (ART) counselling. RESULTS: A total of 724 patients cryopreserved their semen during the study period. The semen parameters of the cancer patients' semen before and after treatment were heterogeneous, with significant differences between cancer type and semen parameters. The utilization rate was relatively low (0.4%), whereas the destruction rate was 23.1%. CONCLUSION: Cancer and antineoplastic treatment affect everyone differently. Therefore, sperm cryopreservation should be offered to all patients before starting treatment to ensure their reproductive future. Furthermore, in addition to considering the semen parameters defined by the World Health Organization, it is important to use TMSC in the diagnosis of men to choose appropriate ART according to type of cancer.

Changes in environmental exposures over decades may influence the genetic architecture of severe spermatogenic failure.

STUDY QUESTION: Do the genetic determinants of idiopathic severe spermatogenic failure (SPGF) differ between generations? SUMMARY ANSWER: Our data support that the genetic component of idiopathic SPGF is impacted by dynamic changes in environmental exposures over decades. WHAT IS KNOWN ALREADY: The idiopathic form of SPGF has a multifactorial etiology wherein an interaction between genetic, epigenetic, and environmental factors leads to the disease onset and progression. At the genetic level, genome-wide association studies (GWASs) allow the analysis of millions of genetic variants across the genome in a hypothesis-free manner, as a valuable tool for identifying susceptibility risk loci. However, little is known about the specific role of non-genetic factors and their influence on the genetic determinants in this type of conditions. STUDY DESIGN, SIZE, DURATION: Case-control genetic association analyses were performed including a total of 912 SPGF cases and 1360 unaffected controls. PARTICIPANTS/MATERIALS, SETTING, METHODS: All participants had European ancestry (Iberian and German). SPGF cases were diagnosed during the last decade either with idiopathic non-obstructive azoospermia (n = 547) or with idiopathic non-obstructive oligozoospermia (n = 365). Case-control genetic association analyses were performed by logistic regression models considering the generation as a covariate and by in silico functional characterization of the susceptibility genomic regions. MAIN RESULTS AND THE ROLE OF CHANCE: This analysis revealed 13 novel genetic association signals with SPGF, with eight of them being independent. The observed associations were mostly explained by the interaction between each lead variant and the age-group. Additionally, we established links between these loci and diverse non-genetic factors, such as toxic or dietary habits, respiratory disorders, and autoimmune diseases, which might potentially influence the genetic architecture of idiopathic SPGF. LARGE SCALE DATA: GWAS data are available from the authors upon reasonable request. LIMITATIONS, REASONS FOR CAUTION: Additional independent studies involving large cohorts in ethnically diverse populations are warranted to confirm our findings. WIDER IMPLICATIONS OF THE FINDINGS: Overall, this study proposes an innovative strategy to achieve a more precise understanding of conditions such as SPGF by considering the interactions between a variable exposome through different generations and genetic predisposition to complex diseases. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the "Plan Andaluz de Investigación, Desarrollo e Innovación (PAIDI 2020)" (ref. PY20_00212, P20_00583), the Spanish Ministry of Economy and Competitiveness through the Spanish National Plan for Scientific and Technical Research and Innovation (ref. PID2020-120157RB-I00 funded by MCIN/ AEI/10.13039/501100011033), and the 'Proyectos I+D+i del Programa Operativo FEDER 2020' (ref. B-CTS-584-UGR20). ToxOmics-Centre for Toxicogenomics and Human Health, Genetics, Oncology and Human Toxicology, is also partially supported by the Portuguese Foundation for Science and Technology (Projects: UIDB/00009/2020; UIDP/00009/2020). The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Artificial Intelligence in Andrology: From Semen Analysis to Image Diagnostics.

Artificial intelligence (AI) in medicine has gained a lot of momentum in the last decades and has been applied to various fields of medicine. Advances in computer science, medical informatics, robotics, and the need for personalized medicine have facilitated the role of AI in modern healthcare. Similarly, as in other fields, AI applications, such as machine learning, artificial neural networks, and deep learning, have shown great potential in andrology and reproductive medicine. AI-based tools are poised to become valuable assets with abilities to support and aid in diagnosing and treating male infertility, and in improving the accuracy of patient care. These automated, AI-based predictions may offer consistency and efficiency in terms of time and cost in infertility research and clinical management. In andrology and reproductive medicine, AI has been used for objective sperm, oocyte, and embryo selection, prediction of surgical outcomes, cost-effective assessment, development of robotic surgery, and clinical decision-making systems. In the future, better integration and implementation of AI into medicine will undoubtedly lead to pioneering evidence-based breakthroughs and the reshaping of andrology and reproductive medicine.

Failure rate, return-to-sports and magnetic resonance imaging after meniscal repair: 119 patients with 7 years mean follow up.

BACKGROUND: One of the most important factors to consider in relation to meniscal repair is the high failure rate reported in the existing literature. AIM: To evaluate failure rates, return to sports (RTS) rate, clinical outcomes and magnetic resonance image (MRI) evaluation after meniscus suture repair for longitudinal tears at a minimum 2-year-follow-up. METHODS: We conducted a retrospective review of meniscal repairs between January 2004 and December 2018. All patients treated for longitudinal tears associated or not with an anterior cruciate ligament reconstruction (ACL-R) were included. Meniscal ramp lesions, radial and root tears, associated with multiligament injuries, tibial fracture and meniscal allograft transplants were excluded. Surgical details and failure rate, defined as symptomatic patients who underwent a revision surgery, were analyzed. As isolated bucket handle tears (BHTs) were usually associated with higher failure rates, we compared BHTs and not BHTs associated or not with an ACL-R. Since 2014, the inside-out technique using cannulas and suture needles with 2-0 Tycron began to predominate. In addition, the number of stitches per repair was increased. In view of differences in surgical technique, we compared two different cohorts: before and after 2014. We recorded the RTS according to the level achieved and the time to RTS. Lysholm and IKDC scores were recorded. Patients were studied with x-rays and MRI as standard postoperative control. RESULTS: One hundred and nineteen patients were included with a mean follow up of 7 years (SD: 4.08). Overall failure rate was 20.3% at a mean 20.1 mo. No statistically significant differences were found when comparing failure for medial and lateral meniscal repair (22.7% and 15.3%, P = 0.36), BHTs and not BHTs (26% and 17.6%, P = 0.27), isolated or associated with an ACL-R (22.9% and 18%, P = 0.47), or when comparing only BHTs associated with an ACL-R (23% and 27.7%, P = 0.9) or not. When comparing cohorts before and after 2014, we found a significant decrease in the overall failure rate from 26% to 11% (P < 0.03). Isolated lesions presented a decrease from 28% to 6.6% (P = 0.02), BHTs from 34% to 8% (P = 0.09) and those associated with an ACL-R from 25% to 10% (P = 0.09). Mean RTS time was 6.5 mo in isolated lesions and 8.64 mo when associated with an ACL-R. Overall, 56% of patients returned to the same sport activity level. Mean pre and postoperative Lysholm scores were 64 and 85 (P = 0.02), and IKDC 58 and 70 (P = 0.03). Out of 84 asymptomatic patients evaluated with MRI, 39% were classified as "not healed" and 61% as "healed". CONCLUSION: Even though the overall failure rate of our series was 20.3%, we found a statistically significant decrease from 26% to 11%, not only for isolated lesions, but also for BHT's and those associated with an ACL-R when comparing our series in two different cohorts, most probably due to improvements in surgical technique.

Reproductive outcomes of oocyte donation in patients with uterine Müllerian anomalies.

OBJECTIVE: To evaluate live-birth rates per embryo transfer in patients with uterine Müllerian anomalies (UMAs). Secondary objectives were to compare reproductive outcomes between the normal uterus group, the different UMA types, and UMA subgroups with and without required surgery. DESIGN: This retrospective study compared two cohorts, one with UMAs and other with normal uteri of our oocyte donation program at 12 Instituto Valenciano De Infertilidad/Reproductive Medicine Associates University affiliated clinics from January 2000 to 2020. The oocyte donation reduces confounding because of differences in embryo quality. The primary outcome was the live-birth rate per embryo transfer. Secondary outcomes included the rates of implantation, clinical pregnancy, miscarriage, and ongoing pregnancy. We calculated odds ratios with 95% confidence intervals. PATIENTS: Infertile women undergoing oocyte donation with UMAs. INTERVENTION: None. MAIN OUTCOME MEASURES: The rates of implantation, clinical pregnancy, miscarriage, ongoing pregnancy, and live birth. RESULTS: We analyzed 58,337 cycles of oocyte donation: 57,869 patients had no uterine malformation, and 468 women had UMAs. Compared with patients with normal uteri, patients with UMAs had lower rates of live births (36.67% [32.84-40.65] vs. 38.1% [95% confidence intervals {CI}: 37.82-38.42]) and ongoing pregnancy (39.74% [35.93-43.66] vs. 41.5% [41.24-41.83]). The miscarriage rate was higher in patients with UMAs (19.5% [16.55-22.85] vs. 16.6% [16.47-16.92]). Specifically, patients with a unicornuate uterus (n=29) had lower rates of implantation (24.07% [13.49-37.64] vs. 42.85% [95% CI: 42.6-43.09]), pregnancy (41.86% [27.01-57.87] vs. 59.51% [59.22-59.81]), ongoing pregnancy (16.67% [6.97-31.36] vs. 41.54% [41.24-41.83]), and live births (16.67% [6.97-31.36] vs. 38.12% [37.83-38.42]). In addition, patients with a partial septate uterus (n=91) had a higher miscarriage rate (26.50% [18.44-34.89] vs. 16.7% [16.47-16.92]). Compared with the normal uterus group, the live-birth rates were lower in the UMA without surgery group (33.09% [27.59-38.96] vs. 38.12% [37.83-38.42]). CONCLUSION: Among patients who received embryos derived from donated oocytes, live birth and ongoing pregnancy rates were lower in patients with UMAs compared with patients with normal uteri. A higher miscarriage rate was found in patients with UMAs. Patients with a unicornuate uterus had worse reproductive outcomes. Our results show that the uterus is less competent in patients with UMAs. TRIAL REGISTRATION: This study was registered at clinicaltrial.gov (NCT04571671).

Increased cytotoxic natural killer cells in the endometrium alone cannot be considered the immunological cause of recurrent miscarriage.

OBJECTIVE: To study the distribution and gene expression of endometrial immune cell populations, especially natural killer (NK) subsets, between assisted reproductive technology patients and healthy donors and explore a possible relationship of these results with patients' killer cell immunoglobulin-like receptor (KIR) genotypes and KIR-human antigen leukocyte-C (HLA-C) binding. DESIGN: Prospective observational cohort study. SETTING: Clinic and university laboratories. PATIENT(S): Participants included 39 women with recurrent miscarriages who had undergone in vitro fertilization cycles with donated oocytes and 21 healthy oocyte donors with proven fertility. INTERVENTION(S): Endometrial biopsy samples were collected from both patients and donors, and the KIR genotypes of the assisted reproductive technology patients were analyzed. MAIN OUTCOME MEASURE(S): Endometrial gene expression (cluster of differentiation [CD] antigens and anti-inflammatory and proinflammatory interleukins) and the number and percentage of regulatory T and NK cell populations in patients and donors were determined. Subsequently, the results obtained were categorized in the group of patients by KIR genotype. Killer cell immunoglobulin-like receptor-HLA-C binding was also examined in patients, considering their KIRs. RESULT(S): A higher percentage of CD56dimCD16+ NK cells were observed in patients than those in healthy donors. Nevertheless, when categorizing patients by KIR genotype and comparing the KIR AA (35.9%), AB (43.6%), and BB (20.5%) groups, no statistically significant difference was observed in either endometrial gene expression or any of the immune cell populations analyzed. Finally, no differences in binding between KIR and HLA-C molecules were registered among these 3 sets of patients. CONCLUSION(S): The reported increase in the number of NK cells with a cytotoxic profile in the endometrium of women with a history of recurrent miscarriages cannot alone explain these events because no relationship is observed between such cellular increase and the KIR genotypes, which individually, and in combination with the different HLA-C alleles, have also been associated, by previous studies, with negative reproductive outcomes. CLINICAL TRIAL REGISTRATION NUMBER: 1405-MAD-025-JG.

Commercial Surrogacy: An Overview / Gestação de substituição comercial: Uma visão global

Abstract Objective Surrogacy is the process in which a woman carries and delivers a baby to other person or couple, known as intended parents. When carriers are paid for surrogacy, this is known as commercial surrogacy. The objective of the present work is to review the legal, ethical, social, and cultural aspects of commercial surrogacy, as well as the current panorama worldwide. Methods This is a review of the literature published in the 21st century on commercial surrogacy. Results A total of 248 articles were included as the core of the present review. The demand for surrogate treatments by women without uterus or with important uterine disorders, single men and same-sex male couples is constantly increasing worldwide. This reproductive treatment has important ethical dilemmas. In addition, legislation defers widely worldwide and is in constant change. Therefore, patients look more and more for treatments abroad, which can lead to important legal problems between countries with different laws. Commercial surrogacy is practiced in several countries, in most of which there is no specific legislation. Some countries have taken restrictive measures against this technique because of reports of exploitation of carriers. Conclusion Commercial surrogacy is a common practice, despite important ethical and legal dilemmas. As a consequence of diverse national legislations, patients frequently resort to international commercial surrogacy programs. As of today, there is no standard international legal context, and this practice remains largely unregulated.

Resumo Objetivo A gestação de substituição é o processo no qual uma mulher engravida e entrega um bebê a outra pessoa ou casal, conhecidos como pais pretendidos. Quando as gestantes são pagas, isto é conhecido como gestação de substituição comercial. O objetivo do presente trabalho é rever os aspectos legais, éticos, sociais e culturais da gestação de substituição comercial, bem como o panorama atual em todo o mundo. Métodos Trata-se de uma revisão da literatura publicada no século XXI sobre a gestação de substituição comercial. Resultados Um total de 248 artigos foi incluído nesta revisão. A demanda por tratamentos com gestação de substituição por mulheres sem útero ou com distúrbios uterinos importantes, homens solteiros e casais masculinos está aumentando constantemente em todo o mundo. Este tratamento reprodutivo tem dilemas éticos importantes. Além disso, a legislação é amplamente adiada em todo o mundo e está em constante mudança. Portanto, os pacientes procuram cada vez mais por tratamentos no exterior, o que pode levar a importantes problemas legais entre países com leis diferentes. A gestação de substituição comercial é praticada em vários países, na maioria dos quais não há legislação específica. Alguns países tomaram medidas restritivas contra esta técnica por causa de relatos de exploração destas mulheres. Conclusão A gestação de substituição comercial é uma prática comum, apesar de importantes dilemas éticos e legais. Como consequência de diversas legislações nacionais, os pacientes frequentemente recorrem a programas de gestação de substituição comercial internacionais. Atualmente, não existe um contexto jurídico internacional padrão e esta prática permanece em grande parte não regulamentada.

Relación entre la ubicación de la burbuja de aire en la transferencia embrionaria y las tasas de implantación y gestación evolutiva / Relationship between air bubble location at embryo transfer and implantation and ongoing pregnancy rates

Resumen OBJETIVO: Evaluar la relación entre la ubicación de la burbuja de aire que contiene los embriones y las tasas de implantación y de gestación clínica. El secundario: estudiar la relación entre la posición de la punta de la cánula, el grosor endometrial y el desplazamiento de la burbuja con esos desenlaces reproductivos. MATERIALES Y MÉTODOS: Estudio retrospectivo, observacional y de análisis de imágenes ecográficas de transferencias de embrión único en estadio de blastocisto practicadas por un mismo especialista en la Fundación IVI, Valencia, España, entre septiembre de 2013 y febrero de 2021. Criterios de selección: grosor endometrial ≥ 6 mm en el último control ecográfico, ausencia de miomas, IMC menor de 30 kg/m2, transferencias atraumáticas efectuadas por el mismo especialista. En función de la ubicación de la burbuja de aire se establecieron tres grupos de estudio (alta: mayor de 0.98 cm, media: 0.98 a 1.44 cm y baja: mayor de 1.44 cm) y para evaluar la asociación entre las categorías se aplicó el cálculo de razón de momios (OR) e IC95%. RESULTADOS: Se estudiaron 342 transferencias de embrión único. La edad media de las pacientes fue 39.70 ± 4.5 años. La relación entre la distancia de la burbuja de aire al fondo uterino y la tasa de implantación fue de 61 ± 9% en el grupo de ubicación alta, 64 ± 9% en el grupo de ubicación media, y de 56 ± 1% en el grupo de ubicación baja (p = 0.437). No se observaron diferencias en la tasa de gestación evolutiva analizada mediante probabilidad de ocurrencia entre grupos, con frecuencias de 0.60 en comparación con 0.64 (OR: 1.42; IC95%: 0.83 a 2.44; p: 0.199) y en la ubicación alta con media, y frecuencias de 0.60 en comparación con 0.56 (OR: 1.22; IC95%: 0.72-2.08; p: 0.462) entre alta y baja. CONCLUSIONES: No se encontró asociación entre la ubicación de la burbuja y las tasas de implantación y de gestación evolutiva. El mayor desplazamiento de la burbuja se asoció con mayores tasas de gestación evolutiva.

Abstract OBJECTIVE: To evaluate the relationship between the location of the air bubble containing the embryos and the implantation and clinical gestation rates. Secondary: to study the relationship between the position of the cannula tip, the endometrial thickness and the displacement of the bubble with these reproductive outcomes. MATERIALS AND METHODS: Retrospective, observational, ultrasound image analysis study of single embryo transfers at blastocyst stage performed by the same specialist at the IVI Foundation, Valencia, Spain, between September 2013 and February 2021. Selection criteria: endometrial thickness ≥ 6 mm at the last ultrasound control, absence of fibroids, BMI less than 30 kg/m2, atraumatic transfers, performed by the same specialist. Based on the location of the air bubble, three study groups were established (high: greater than 0.98 cm, medium: 0.98 to 1.44 cm and low: greater than 1.44 cm) and the odds ratio (OR) and 95%CI were used to evaluate the association between the categories. RESULTS: A total of 342 single embryo transfers were studied. The mean age of the patients was 39.70 ± 4.5 years. The relationship between the distance of the air bubble to the uterine fundus and the implantation rate was 61 ± 9% in the high placement group, 64 ± 9% in the medium placement group, and 56 ± 1% in the low placement group (p = 0.437). No differences were observed in the evolutionary gestation rate analyzed by probability of occurrence between groups, with frequencies of 0.60 compared to 0.64 (OR: 1.42; 95%CI: 0.83 to 2.44; p: 0.199) and high to medium location, and frequencies of 0.60 compared to 0.56 (OR: 1.22; 95%CI: 0.72-2.08; p: 0.462) between high and low. CONCLUSIONS: No association was found between the air bubble localization and implantation or ongoing pregnancy rates. However, a greater displacement of the bubble was associated with higher ongoing pregnancy rates.

The effect of late-follicular phase progesterone elevation on embryo ploidy and cumulative live birth rates.

RESEARCH QUESTION: Does late-follicular phase progesterone elevation have a deleterious effect on embryo euploidy, blastocyst formation rate and cumulative live birth rates (CLBR)? DESIGN: A multicentre retrospective cross-sectional study including infertile patients aged 18-40 years who underwent ovarian stimulation in a gonadotrophin-releasing hormone antagonist protocol and preimplantation genetic testing for aneuploidies (PGT-A) followed by a freeze-all strategy and euploid embryo transfer between August 2017 and December 2019. The sample was stratified according to the progesterone concentrations on the day of trigger: normal (≤1.50 ng/ml) and high (>1.50 ng/ml). Moreover, sensitivity analyses were performed to determine whether different conclusions would have been drawn if different cut-offs had been adopted. The primary outcome was the embryo euploidy rate. Secondary outcomes were the blastocyst formation rate, the number of euploid blastocysts and CLBR. RESULTS: Overall 1495 intracytoplasmic sperm injection PGT-A cycles were analysed. Late-follicular phase progesterone elevation was associated with significantly higher late-follicular oestradiol concentrations (2847.56 ± 1091.10 versus 2240.94 ± 996.37 pg/ml, P < 0.001) and significantly more oocytes retrieved (17.67 ± 8.86 versus 12.70 ± 7.00, P < 0.001). The number of euploid embryos was significantly higher in the progesterone elevation group (2.32 ± 1.74 versus 1.86 ± 1.42, P = 0.001), whereas the blastocyst formation rate (47.1% [43.7-50.5%] versus 51.0% [49.7-52.4%]), the embryo euploidy rate (48.3% [44.9-51.7%] versus 49.1% [47.7-50.6%], the live birth rate in the first frozen embryo transfer (34.1% versus 31.1%, P = 0.427) and CLBR (38.9% versus 37.0%, P = 0.637) were not significantly different between the two groups. CONCLUSIONS: Euploidy rate and CLBR do not significantly differ among PGT-A cycles with and without late-follicular progesterone elevation in a freeze-all approach.

TESE-ICSI outcomes per couple in vasectomized males are negatively affected by time since the intervention, but not other comorbidities.

RESEARCH QUESTION: Does time since vasectomy (as obstructive interval) and the presence of different male comorbidities adversely affect the likelihood of achieving a newborn for vasectomized males undergoing testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI)? DESIGN: This retrospective study included 364 couples with vasectomized males undergoing TESE-ICSI cycles with autologous oocytes at IVI Valencia. The main outcome was live birth rate (LBR). Subjects were divided according to the male risk factor evaluated into quartiles (obstructive interval, body mass index [BMI]) or groups (hypertension, diabetes mellitus, dyslipidaemia). The reproductive outcomes were calculated per embryo transfer, per ovarian stimulation completed, and per couple. RESULTS: The average obstructive interval was 11.3 years. The LBR was 34.4% (95% CI 30.1-38.6) per embryo transfer, 27.8% (95% CI 24.1-31.5) per ovarian stimulation and 46.2% (95% CI 41.8-51.3) per couple. When considering obstructive interval, a significantly lower LBR per couple (P = 0.04) was found in the group with the longest obstruction time: Q1 42.1% (95% CI 33.5-50.7), Q2 49.1% (95% CI 36.1-62.1), Q3 56.3% (95% CI 46.7-65.9) and Q4 37.2% (95% CI 26.5-47.9) but the cumulative live birth rate (CLBR) was not affected (P = 0.63). LBR per ovarian stimulation of males with hypertension was significantly lower (P = 0.04) than healthy males: 13.5% (95% CI 2.5-24.5) and 28.6% (95% CI 24.7-32.5), respectively. The group of diabetic vasectomized males had a significantly higher CLBR (P = 0.02). The remaining risk factors assessed (smoking, dyslipidaemia and a high BMI) did not affect LBR compared with their healthy counterparts. CONCLUSION: Time since vasectomy appears to negatively influence the LBR when assessed per couple. The CLBR was not affected by the obstructive interval or the presence of other male comorbidities apart from diabetes, which had a significant effect.

Different CO2 settings (6.0% vs 7.0%) do have an impact on extracellular pH of culture medium (pHe) and euploidy rates rather than on blastocyst development: a sibling oocyte study.

OBJECTIVE: To determine whether euploidy rates and blastocyst development differ in a continuous culture medium under different CO2 concentrations. DESIGN AND METHOD: A single-center retrospective study was performed from July 2018 to October 2019 including 44 fresh cycles with at least four fresh mature oocytes (MII) without severe male factor infertility. Sibling MII were injected and cultured in Global®Total®LP under 6.0% (pHe = 7.374 ± 0.014) or 7.0% (pHe = 7.300 ± 0.013) CO2, 5.0% O2, and 89.0% or 88.0% N2. Analyzed variables were normally fertilized oocytes (2PN), cleavage rate, blastulation rate on day 5/2PN, usable blastocyst (blastocysts biopsied/2PN), and euploidy rates. Blastocyst's trophectoderm biopsy was performed on day 5, 6, or 7 for genetic testing and mitochondrial DNA (mtDNA) quantification by next-generation sequencing. RESULTS: Women's mean age was 33.0 ± 6.6 years old. From a total of 604 MII, no differences were found in normal fertilization and cleavage rates on day 3 between 6.0 and 7.0% CO2 (72.3% vs 67.1%, p = 0.169 and 96.6% vs 96.3%, p = 0.897, respectively). Blastulation rate on day 5/2PN was comparable between 6.0 and 7.0% CO2 (68.1% vs 64.2%, p = 0.409). Although usable blastocyst rate was not different (54.3% vs 55.3%, p = 0.922), total euploidy rates differed significantly (58.7% vs 42.8%, p = 0.016) between 6.0% and 7.0% CO2, respectively. The mean blastocyst mtDNA content was significantly lower in 6.0% CO2 (30.4 ± 9.1 vs 32.9 ± 10.3, p = 0.037). CONCLUSION: Blastocyst development is not affected when embryos are cultured in vitro at 6.0% or 7.0% CO2, while euploidy rates are significantly decreased at a higher CO2 concentration, therefore at a lower pHe.

Minimal ovarian stimulation is an alternative to conventional protocols for older women according to Poseidon's stratification: a retrospective multicenter cohort study.

OBJECTIVE: To investigate whether minimal ovarian stimulation (mOS) is as effective as conventional ovarian stimulation (cOS) for older women belonging to different groups according to the Poseidon criteria. MATERIAL AND METHODS: Observational retrospective multicentre cohort including women from Poseidon's groups 2 and 4 that underwent in vitro fertilization (IVF). We performed a mixed-effects logistic regression model, adding as a random effect the patients and the stimulation cycle considering the dependence of data. Survival curves were employed as a measure of the cumulative live birth rate (CLBR). The primary outcomes were live birth rate per embryo transfer and CLBR per consecutive embryo transfer and oocyte consumed until a live birth was achieved. RESULTS: A total of 2002 patients underwent 3056 embryo transfers (mOS = 497 and cOS = 2559). The live birth rates per embryo transfer in mOS and cOS showed no significant difference in both Poseidon's groups. Likewise, the logistic regression showed similar live birth rates between the two protocols in Poseidon's groups 2 (OR 1.165, 95% CI 0.77-1.77; p = 0.710) and 4 (OR 1.264 95% CI 0.59-2.70; p = 0.387). However, the survival curves showed higher CLBR per oocyte in women that received mOS (Poseidon group 2: p < 0.001 and Poseidon group 4: p = 0.039). CONCLUSIONS: Minimal ovarian stimulation is a good alternative to COS as a first-line treatment for patients belonging to Poseidon's groups 2 and 4. The number of oocytes needed to achieve a live birth seems inferior in mOS strategy than cOS.

Euploidy rates are not affected when embryos are cultured in a continuous (CCM) or sequential culture medium (SCM): a sibling oocyte study.

PURPOSE: To determine if euploidy rates and embryo development differ when blastocysts are cultured in CCM or SCM. METHOD: A single-center retrospective observational study was performed from September 2018 to March 2019. Patients [23-46 years] with at least four fresh mature oocytes (MII) without severe male factor infertility were included. Sibling MII were injected and cultured in Global®Total®LP (CCM) or Sage Quinn's Advantage® Cleavage and Blastocyst media (SCM) under 6% CO2, 5% O2, and 89% N2. Fertilization, cleavage, day (D) 5 blastulation, usable blastocyst (blastocysts biopsied/normally fertilized oocytes), and euploidy rates were recorded. Blastocysts were graded prior to trophectoderm (TE) biopsy on D5, 6, or 7 for genetic testing and mitochondrial DNA (mtDNA) quantification. RESULTS: According to clinical practice, 1452 MII were randomly distributed: 751 in CCM and 701 in SCM. No differences were observed in fertilization and cleavages rates for CCM and SCM (77.4% vs 75.5%, p = 0.429 and 97.6% vs 99.1%, p = 0.094, respectively). Blastulation rate on D5 was higher in CCM (70.6% vs 62.2, p = 0.009); however, usable blastocyst rates were comparable (CCM: 58.3% vs SCM: 56.7%, p = 0.625). From a Poisson regression model adjusted for confounding factors, euploidy rates were not different between media (aOR = 1.18, [0.94-1.48], p = 0.157). Euploid blastocyst's mtDNA values were similar (CCM: 32.2, [30.5, 34.1] and SCM: 33.5, [31.8, 35.2], p = 0.345) and top-quality blastocysts (AA/BA) were increased in SCM (OR=1.04, [1.00-1.09], p = 0.037). CONCLUSION: Under controlled in vitro conditions, euploidy rates and embryo development are comparable when embryos are cultured in CCM or SCM.

A global approach to addressing the policy, research and social challenges of male reproductive health.

Male infertility is a global health issue; yet to a large extent, our knowledge of its causes, impact and consequence is largely unknown. Recent data indicate that infertile men have an increased risk of somatic disorders such as cancer and die younger compared to fertile men. Moreover, several studies point to a significant adverse effect on the health of the offspring. From the startling lack of progress in male contraception combined with the paucity of improvements in the diagnosis of male infertility, we conclude there is a crisis in male reproductive health. The Male Reproductive Health Initiative has been organized to directly address these issues (www.eshre.eu/Specialty-groups/Special-Interest-Groups/Andrology/MRHI). The Working Group will formulate an evidence-based strategic road map outlining the ways forward. This is an open consortium desiring to engage with all stakeholders and governments.

SARS-CoV-2 pandemic and repercussions for male infertility patients: A proposal for the individualized provision of andrological services.

The prolonged lockdown of health facilities providing non-urgent gamete cryopreservation-as currently recommended by many reproductive medicine entities and regulatory authorities due to the SARS-CoV-2 pandemic will be detrimental for subgroups of male infertility patients. We believe the existing recommendations should be promptly modified and propose that the same permissive approach for sperm banking granted for men with cancer is expanded to other groups of vulnerable patients. These groups include infertility patients (eg, azoospermic and cryptozoospermic) undergoing medical or surgical treatment to improve sperm quantity and quality, as well as males of reproductive age affected by inflammatory and systemic auto-immune diseases who are about to start treatment with gonadotoxic drugs or who are under remission. In both scenarios, the "fertility window" may be transitory; postponing diagnostic semen analysis and sperm banking in these men could compromise the prospects of biological parenthood. Moreover, we provide recommendations on how to continue the provision of andrological services in a considered manner and a safe environment. Our opinion is timely and relevant given the fact that fertility services are currently rated as of low priority in most countries.

Correlación y comparación entre el nivel de actividad física y flexibilidad en niños y niñas de 10 a 11 años de edad de un colegio de Concepción. Chile / Correlation and comparison between the level of physical activity and flexibility in boys and girls from 10 to 11 years of age from a school in Concepción. Chile

RESUMEN. El estudio se centró en determinar los niveles de actividad física que presentan los escolares de 10 a 11 años que asisten a un Colegio de la Ciudad de Concepción, relacionarlo y compararlo con la flexibilidad. La metodología utilizada corresponde a un estudio cuantitativo, transversal, descriptivo-correlacional; con muestreo intencionado, se evaluó a 49 escolares, para medir el nivel de actividad física se utilizó la encuesta INTA y para medir la flexibilidad se utilizó el test de V-Sit And Reach. Se utilizó la prueba de Shapiro Wilk arrojando la normalidad de los datos, la prueba Z score para establecer medias, la prueba t de Student para el nivel de significancia entre grupo, y, por último, en la relación de las variables se empleó la correlación de Pearson. Los resultados muestran que las niñas tienen un nivel de flexibilidad mayor a los niños siendo estadísticamente significativa, en cambio en el nivel de actividad física se obtiene un nivel regular no existiendo diferencias significativas. No existe correlación entre las variables estudiadas.

ABSTRACT. The study focuses on determining levels of physical activity presented by children between the ages 10 and 11, attending a school in the City of Concepción, relating it and comparing it with flexibility. The methodology used corresponds to a quantitative, cross-sectional, descriptive-correlational study; with intentional sampling, 49 students were evaluated, the INTA survey was used to assess the level of physical activity, and the V-Sit And Reach test were used to measure flexibility. The Shapiro-Wilk test was used, yielding the normality of the data, the Z score test to establish means, the Student's T test for the level of significance between the groups, and, finally, for the relationship of the variables, Pearson's correlation was used. The results show that girls have a higher level of flexibility than boys, being statistically significant, while in the level of physical activity a regular level is obtained, without significant differences. There is no correlation between the variables studied.

Evaluation of the endometrial receptivity assay and the preimplantation genetic test for aneuploidy in overcoming recurrent implantation failure.

PURPOSE: To evaluate the clinical usefulness of the endometrial receptivity array (ERA) and the preimplantation genetic test for aneuploidy (PGT-A) in patients with severe and moderate recurrent implantation failure (RIF). DESIGN: A retrospective multicenter cohort study was conducted in patients who failed to achieve implantation following transfer of 3 or more or 5 or more embryos in at least three single embryo transfers; patients were classified as moderate or severe RIF, respectively. Patients with previous RIF were compared based on the testing they received: PGT-A, ERA, or PGT-A+ERA versus a control group with no testing. Mean implantation rate and ongoing pregnancy rates per embryo transfer were considered primary outcomes. Multiple logistic regression analysis was performed and adjusted ORs were calculated to control possible bias. RESULTS: Of the 2110 patients belonging to the moderate RIF group, those who underwent transfer of euploid embryos after PGT-A had a higher implantation rate than those who did not. Additionally, the PGT-A group had a significantly higher rate of ongoing pregnancy. The same outcomes measured for the 488 patients in the severe RIF group did not reveal any statistically significant improvements. The use of the ERA test did not appear to significantly improve outcomes in either group. CONCLUSIONS: PGT-A may be beneficial for patients with moderate recurrent implantation failure but not for severe cases. At its current level of development, ERA does not appear to be clinically useful for patients with RIF.

Descripción morfológica e histológica del tejido hepático de Gambusia holbrooki (Pisce: Poeciliidae) que habita en la Provincia de Arica - Chile / Morphological and histological description of the liver tissue of Gambusia holbrooki (Pisce: Poeciliidae) inhabiting the Province of Arica - Chile

Gambusia holbrooki es el pez de agua dulce con mayor distribución en Chile y el mundo, pero los estudios que abordan la morfología e histología hepática del pez son escasos. El hígado es utilizado para evidenciar efectos subletales de contaminantes ambientales y es preciso contar con una descripción histomorfológica del hígado para futuros estudios comparativos. El presente estudio tiene como objetivo describir patrones histomorfológicos del hígado de Gambusia holbrooki, para ello se colectaron 97 individuos adultos de los sistemas límnicos de los valles de Lluta y Azapa (Extremo norte de Chile), para observar patrones morfológicos comunes en ambas poblaciones, se utilizó técnicas histológicas de rutina e histoquímica. Las evidencias demostraron que el hígado contiene tejido pancreático y su arquitectura tisular es trabecular con mayor presencia de capilares sinusoides.

Gambusia holbrooki is the freshwater fish with the greatest distribution in Chile and the world. However, studies dealing with morphology and liver histology of fish are scarce. The liver commonly shows the sublethal effects of environmental pollutants and there should be a histomorphological description of the liver for further comparative studies. The present study aims to describe histomorphological patterns of the liver of Gambusia holbrooki. A total of 97 adult individual specimens were collected from the ecosystems in the valleys of Lluta and Azapa (Region of Arica and Parinacota), to observe patterns morphologically common in both populations. Routine histological and histochemical techniques were used for analysis. The evidence showed that the liver contains pancreatic tissue, and that tissue architecture is trabecular with greater presence of capillary sinusoids.

Therapy with probiotics and synbiotics for polycystic ovarian syndrome: a systematic review and meta-analysis.

OBJECTIVE: Several randomized controlled trials (RCTs) have investigated the use of probiotic/synbiotic in PCOS patients, without clarifying the real use in clinical practice. The aim of this meta-analysis was to evaluate the effectiveness of probiotics and synbiotics on metabolic, hormonal and inflammatory parameters of PCOS. METHODS: Electronic databases (MEDLINE, Scopus, EMBASE, ScienceDirect, The Cochrane Database of Systematic Reviews and ClinicalTrials.gov) were searched from their inception until May 2019. The study protocol was registered in PROSPERO with number CRD42018111534. Randomized controlled trials (RCTs) of PCOS's women undergoing therapy at least 8 weeks with probiotics or synbiotics or without therapy were included. The primary outcomes were changes in anthropometric parameters, glucose/insulin metabolism, lipid profile, sex hormones profile, inflammation markers. RESULTS: 587 patients were included in nine RCT. The administration of probiotic/synbiotic were associated with a significant improvement in FPG, FBI, HOMA I-R, BMI. It also modified Ferriman-Gallway, serum triglycerides, serum testosterone, hs-CRP, NO, TAC, GSH, and MDA. Subgroup analysis of the type of intervention showed that probiotics were associated with greater testosterone and FPG reduction; synbiotics administration resulted in a more pronounced decrease of the FBI. Subgroup analyses on the duration of therapy showed that, probiotic/synbiotic administration had a significantly greater effect on QUICK-I in the case of women with 12-weeks of therapy than in the 8-weeks therapy group. Nevertheless, we did not observe any significant difference was observed in terms of FBI, HOMA-IR, and FPG. CONCLUSIONS: Probiotics and synbiotics seem to either an effect on/influence metabolic, hormonal and inflammatory parameters, or can influence them. Consequently, it could lead to an improvement of fertility in PCOS.