Single-cell proteomics reveals decreased abundance of proteostasis and meiosis proteins in advanced maternal age oocytes.

Advanced maternal age is associated with a decline in oocyte quality, which often leads to reproductive failure in humans. However, the mechanisms behind this age-related decline remain unclear. To gain insights into this phenomenon, we applied plexDIA, a multiplexed data-independent acquisition, single-cell mass spectrometry method, to analyze the proteome of oocytes from both young women and women of advanced maternal age. Our findings primarily revealed distinct proteomic profiles between immature fully grown germinal vesicle and mature metaphase II oocytes. Importantly, we further show that a woman's age is associated with changes in her oocyte proteome. Specifically, when compared to oocytes obtained from young women, advanced maternal age oocytes exhibited lower levels of the proteasome and TRiC complex, as well as other key regulators of proteostasis and meiosis. This suggests that aging adversely affects the proteostasis and meiosis networks in human oocytes. The proteins identified in this study hold potential as targets for improving oocyte quality and may guide future studies into the molecular processes underlying oocyte aging.

How effective are the non-conventional ovarian stimulation protocols in ART? A systematic review and meta-analysis.

PURPOSE: To compare the effectiveness of starting the ovarian stimulation on the early follicular phase ("Conventional") with the newer range of non-conventional approaches starting in the luteal phase ("Luteal"), random-start, and studies implementing them in DuoStim ("Conventional"+"Luteal"). METHODS: Systematic review. We searched CENTRAL, PubMed, and Embase, on March 2020. We included randomized and non-randomized controlled trials that compared "Luteal," random-start ovarian stimulation or DuoStim with "Conventional"; we analyzed them by subgroups: oocyte freezing and patients undergoing ART treatments, both, in the general infertile population and among poor responders. RESULTS: The following results come from a sensitivity analysis that included only the low/moderate risk of bias studies. When comparing "Luteal" to "Conventional," clinically relevant differences in MII oocytes were ruled out in all subgroups. We found that "Luteal" probably increases the COH length both, in the general infertile population (OR 2.00 days, 95% CI 0.81 to 3.19, moderate-quality evidence) and in oocyte freezing cycles (MD 0.85 days, 95% CI 0.53 to 1.18, moderate-quality evidence). When analyzing DuoStim among poor responders, we found that it appears to generate a higher number of MII oocytes in comparison with a single "Conventional" (MD 3.35, 95%CI 2.54-4.15, moderate-quality evidence). CONCLUSION: Overall, this systematic review of the available data demonstrates that in poor responders, general infertile population and oocyte freezing for cancer stimulation in the late follicular and luteal phases can be utilized in non-conventional approaches such as random-start and DuoStim cycles, offering similar outcomes to the conventional cycles but potentially with increased flexibility, within a reduced time frame. However, more well-designed trials are required to establish certainty.

Low-dose growth hormone supplementation increases clinical pregnancy rate in poor responders undergoing in vitro fertilisation.

Poor ovarian response (POR) often means low success rates after in vitro fertilisation (IVF). We aim to study the impact of a low-dose growth hormone (GH) supplementation in pregnancy rates in poor responders in a prospective, self-controlled study of 64 poor responders to previous IVF cycles, who failed to achieve pregnancy and were supplemented with low-doses of GH in a subsequent cycle using the same gonadotropin dose and protocol. Our primary endpoint was the clinical pregnancy rate (CPR), considering secondary endpoints, the number of retrieved oocytes, embryos, embryo quality and the proportion of cycles with embryo transfer. CPR in the GH group was 34.4%. Significant differences were observed for the GH group both in the number of top quality embryos (0.64 ± 0.88 versus 1.03 ± 1.17, p < 0.05) and cryopreserved embryos (0.3 ± 0.81 versus 0.85 ± 1.49, p < 0.05). This is, to our knowledge, the first clinical trial to use a low dose of GH as a supplement for IVF in POR patients. Despite this low dose, we achieved excellent success rates in patients with a very poor prognosis, at a reasonable cost and without side effects, which makes this a safe and cost-effective alternative.

Fresh embryo transfer versus frozen embryo transfer in in vitro fertilization cycles: a systematic review and meta-analysis.

OBJECTIVE: To examine the available evidence to assess if cryopreservation of all embryos and subsequent frozen embryo transfer (FET) results in better outcomes compared with fresh transfer. DESIGN: Systematic review and meta-analysis. SETTING: Centers for reproductive care. PATIENT(S): Infertility patient(s). INTERVENTION(S): An exhaustive electronic literature search in MEDLINE, EMBASE, and the Cochrane Library was performed through December 2011. We included randomized clinical trials comparing outcomes of IVF cycles between fresh and frozen embryo transfers. MAIN OUTCOME MEASURE(S): The outcomes of interest were ongoing pregnancy rate, clinical pregnancy rate, and miscarriage. RESULT(S): We included three trials accounting for 633 cycles in women aged 27-33 years. Data analysis showed that FET resulted in significantly higher ongoing pregnancy rates and clinical pregnancy rates. CONCLUSION(S): Our results suggest that there is evidence that IVF outcomes may be improved by performing FET compared with fresh embryo transfer. This could be explained by a better embryo-endometrium synchrony achieved with endometrium preparation cycles.

First-trimester adiponectin and subsequent development of preeclampsia or fetal growth restriction.

BACKGROUND/AIMS: The evidence regarding the utility of assessing first-trimester adiponectin (ApN) serum levels in early prediction of preeclampsia (PE) and fetal growth restriction (FGR) is contradictory. This study aims to determine the role of maternal serum ApN levels as an early predictor of PE and FGR. METHODS: A prospective case-control study among a pregnant population who attended their 11- to 14-week ultrasound scan at the University of Chile's Clinical Hospital's Fetal Medicine Unit. We included patients who developed PE or FGR (10 cases per group) and 35 healthy controls. We determined ApN levels in blood samples from these 55 patients using a commercial ELISA kit and assessed the relationship of ApN levels with variables like development of PE, FGR, weight at birth and maternal BMI. RESULTS: There were no significant differences among first-trimester ApN serum levels in the groups. Average concentrations were 8, 6.8 and 10.8 ng/ml for the control, PE and FGR groups, respectively. CONCLUSION: In our study, maternal serum ApN levels were not useful in predicting subsequent development of PE and FGR. However, maternal serum ApN concentration adjusted by BMI was significantly higher during the first trimester in women who later developed FGR.

Transmisión vertical de VIHy sida: realidad epidemiológica del Cono Sur / Vertical transmission of HIV/ AIDS: Epidemiologic reality in the Southern Cone

Introducción: En embarazadas seropositivas sintratamiento profiláctico, la transmisión vertical (TV)del virus de la inmunodeficiencia humana (VIH) seproduce en un 30% de los casos, cifra quedisminuye a menos del 2% en gestantes sometidasa un manejo integral de prevención. El objetivo deeste estudio es conocer el comportamientoepidemiológico de la transmisión vertical en elCono Sur americano (Argentina, Bolivia, Brasil,Chile, Perú y Uruguay).Material y métodos: Se analizaron los datosaportados por el Departamento de Epidemiologíade UNASIDA, Organización Mundial de la Salud yMinisterio de Salud de los países en estudio hastael año 2006. Se estudió el comportamientoepidemiológico de la epidemia de VIH/sida porpaís, la tasa de infección en población general yfemenina en edad fértil, la prevalencia en mujeresembarazadas y la TV.Resultados: En el Cono Sur, durante el año 2005,la prevalencia en la población general deseropositivos fue de 60/100.000 habitantes y deéstos el 32% correspondió a mujeres en edad fértil.El VIH 1 y el subtipo B es el predominante en laregión. La razón varón:mujer promedio en laregión fue de 3,15:1. La población femenina queconcentró la mayor tasa de infección por VIH fueentre los 15-24 años y para sida fue entre los 30 ylos 39 años. La tasa de fecundidad globalpromedio en la región fue de 2,3. La tasa deinfección de población femenina en edad fértilpresenta un rango entre 65 y 370/100.000. La tasade infección en embarazadas promedio fue del0,5%. El porcentaje de TV promedio fue del 3%.Conclusiones: La TV del VIH en la región es (..) (AU)

The risk of transmitting HIV frommother to unborn child, without prophylacticintervention, is 30% but can be reduced to lessthan 2% by implementing comprehensivepreventive strategies. The objective of this studywas to assess the epidemiological profile of verticalHIV transmission in the Southern Cone (Argentina,Bolivia, Brazil, Chile, Peru and Uruguay).Material and methods: We analyzed data obtainedfrom the Epidemiology Departments of UNAIDS,WHO and the official Government HealthDepartments and institutions of the abovementionedcountries up to 2006. The study includedassessment of infection rates in the general andfertile female populations, the prevalence amongpregnant women, and vertical transmission rates.Results: The prevalence of HIV in the SouthernCone in 2005 was 60 per 100,000 inhabitants in thegeneral population, 32% of which corresponded towomen of fertile age. The predominant subtype inthe region was HIV-1 B and the gender ratio(male:female) was 3.15:1. Among the femalepopulation, the highest HIV infection and AIDSrates were observed among those in the groupsaged 15-24 years and 30-39 years, respectively. Themean global fecundity rate in the region was 2.3.The infection rate for the fertile female populationranged from 65 to 370 per 100,000. The meaninfection rate in pregnant women was 0.5% andthe mean vertical transmission rate was 3%.Conclusions: Vertical HIV transmission in the regioncauses a small percentage of HIV/AIDS notifications,but accounts for approximately 92% of the infectedchildren. This route of transmission route hasdecreased substantially, reaching prevalence rates ofless than 2%, which may be explained by the wideruse and effectiveness of the health policiesimplemented by governments and health organizationsfor the prevention and treatment of this infection (AU)

Human intoxication with paralytic shellfish toxins: clinical parameters and toxin analysis in plasma and urine.

This study reports the data recorded from four patients intoxicated with shellfish during the summer 2002, after consuming ribbed mussels (Aulacomya ater) with paralytic shellfish toxin contents of 8,066 +/- 61.37 microg/100 gr of tissue. Data associated with clinical variables and paralytic shellfish toxins analysis in plasma and urine of the intoxicated patients are shown. For this purpose, the evolution of respiratory frequency, arterial blood pressure and heart rate of the poisoned patients were followed and recorded. The clinical treatment to reach a clinically stable condition and return to normal physiological parameters was a combination of hydration with saline solution supplemented with Dobutamine (vasoactive drug), Furosemide (diuretic) and Ranitidine (inhibitor of acid secretion). The physiological condition of patients began to improve after four hours of clinical treatment, and a stable condition was reached between 12 to 24 hours. The HPLC-FLD analysis showed only the GTX3/GTX2 epimers in the blood and urine samples. Also, these epimers were the only paralytic shellfish toxins found in the shellfish extract sample.

Gonyautoxin: new treatment for healing acute and chronic anal fissures.

PURPOSE: The mayor symptoms of chronic anal fissure are permanent pain, intense pain during defecation that lasts for hours, blood in the stools, and sphincter cramps. It is subsequent to formation of fibrosis infiltrate that leads to an increased anal tone with poor healing tendency. This vicious circle leads to fissure recurrence and chronicity. This study was designed to show the efficacy of gonyautoxin infiltration in healing patients with anal fissures. METHODS: Gonyautoxin is a paralyzing phytotoxin produced by dinoflagellates. Fifty recruited patients received clinical examination, including proctoscopy and questionnaire to evaluate the symptoms. Anorectal manometries were performed before and after toxin injection. Doses of 100 units of gonyautoxin in a volume of 1 ml were infiltrated into both sides of the anal fissure in the internal anal sphincter. RESULTS: Total remission of acute and chronic anal fissures were achieved within 15 and 28 days respectively. Ninety-eight percent of the patients healed before 28 days with a mean time healing of 17.6 +/- 9 days. Only one relapsed during 14 months of follow-up. Neither fecal incontinence nor other side effects were observed. All patients showed immediate sphincter relaxation. The maximum anal resting pressures recorded after two minutes decreased to 56.2 +/- 12.5 percent of baseline. CONCLUSIONS: Gonyautoxin breaks the vicious circle of pain and spasm that leads to anal fissure. This study proposes gonyautoxin anal sphincter infiltration as safe and effective alternative therapeutic approach to conservative, surgical, and botulinum toxin therapies for anal fissures.

Human intoxication with paralytic shellfish toxins: clinical parameters and toxin analysis in plasma and urine

This study reports the data recorded from four patients intoxicated with shellfish during the summer 2002, after consuming ribbed mussels (Aulacomya ater) with paralytic shellfish toxin contents of 8,066 n 61.37 mg/100 gr of tissue. Data associated with clinical variables and paralytic shellfish toxins analysis in plasma and urine of the intoxicated patients are shown. For this purpose, the evolution of respiratory frequency, arterial blood pressure and heart rate of the poisoned patients were followed and recorded. The clinical treatment to reach a clinically stable condition and return to normal physiological parameters was a combination of hydration with saline solution supplemented with Dobutamine (vasoactive drug), Furosemide (diuretic) and Ranitidine (inhibitor of acid secretion). The physiological condition of patients began to improve after four hours of clinical treatment, and a stable condition was reached between 12 to 24 hours. The HPLC-FLD analysis showed only the GTX3/GTX2 epimers in the blood and urine samples. Also, these epimers were the only paralytic shellfish toxins found in the shellfish extract sample.

The gonyautoxin 2/3 epimers reduces anal tone when injected in the anal sphincter of healthy adults.

The primary clinical symptom of Paralytic Shellfish Poisoning is acute paralytic illness produced by paralyzing toxins. Paralytic shellfish poison is formed by a mixture of phycotoxins and their toxicity is due to its reversible binding to a receptor site on the voltage-gated sodium channel on excitable cells, thus blocking neuronal transmission. We studied the effect of the gonyautoxin 2/3 epimers by local infiltration in the anal internal sphincter of healthy voluntary adults in order to reduce anal tone. The toxin was injected after prior clinical evaluation, anoscopy and anorectal manometry. Post injection clinical examination, electromyography and anorectal manometry were performed. Resting and voluntary contraction pressures were measured and the anorectal inhibitory and anocortical reflexes were tested by manometry. Blood and urine samples were obtained from each participant, and hemogram, basic metabolic panel, and urinalysis were done both before and one week after the injection. This study shows, for the first time, that gonyautoxin 2/3 reduces the anal tone by relaxing the anal sphincters in 100 % of the participants. Manometric recordings showed a significant decrease in anal maximal voluntary contraction pressure after the toxin injection, dropping to 55.2+/-6.2 % and 47.0+/-6.8% (Mean Value+/-Std.Dev.) of the baseline values at 2 minutes and at 24 hours respectively after the injection. Post-injection electromyography showed that activity of the muscle was abolished. We conclude that local administration of gonyautoxin 2/3 to the anal sphincter produces immediate relaxation and a statistically significant decrease in the anal tone (p <0.001).

The Gonyautoxin 2/3 epimers reduces anal tone when injected in the anal sphincter of healthy adults

The primary clinical symptom of Paralytic Shellfish Poisoning is acute paralytic illness produced by paralyzing toxins. Paralytic shellfish poison is formed by a mixture of phycotoxins and their toxicity is due to its reversible binding to a receptor site on the voltage-gated sodium channel on excitable cells, thus blocking neuronal transmission. We studied the effect of the gonyautoxin 2/3 epimers by local infiltration in the anal internal sphincter of healthy voluntary adults in order to reduce anal tone. The toxin was injected after prior clinical evaluation, anoscopy and anorectal manometry. Post injection clinical examination, electromyography and anorectal manometry were performed. Resting and voluntary contraction pressures were measured and the anorectal inhibitory and anocortical reflexes were tested by manometry. Blood and urine samples were obtained from each participant, and hemogram, basic metabolic panel, and urinalysis were done both before and one week after the injection. This study shows, for the first time, that gonyautoxin 2/3 reduces the anal tone by relaxing the anal sphincters in 100 % of the participants. Manometric recordings showed a significant decrease in anal maximal voluntary contraction pressure after the toxin injection, dropping to 55.2 ± 6.2 % and 47.0 ± 6.8 % (Mean Value ± Std.Dev.) of the baseline values at 2 minutes and at 24 hours respectively after the injection. Post-injection electromyography showed that activity of the muscle was abolished. We conclude that local administration of gonyautoxin 2/3 to the anal sphincter produces immediate relaxation and a statistically significant decrease in the anal tone (p <0.001)..