Relación entre parámetros endocrino-metabólicos al nacimiento y la presión arterial durante la pre-adolescencia

Objective: The aim of the present study was to evaluate the relationship between selected hormonal parameters (at birth and at age 8 years) and blood pressure levels at pre-adolescence in a cohort of intrauterine growth retarded (IUGR) and normal birth weight infants (NBW). Methods: A cohort study from early pregnancy to childhood was performed. Seventy-six fetuses/children were evaluated between 1995 and 2004. Cord blood samples were taken at birth and several hormonal and metabolic parameters evaluated. Sixty-four children of the original cohort were available for blood sampling, blood pressure and anthropometric measures at a mean age of 8 years. 27 (42.2%) were IUGR and 37 (57.8%) were NBW. Multiple regression analyses were conducted with cord blood levels of hormonal and metabolic parameters at birth and at 8 years as independent variables and children’s blood pressure as dependent variable adjusted by IUGR status, gender, Body Mass Index and age of the child at the time of blood pressure evaluation. Results: The maternal age (26.6±5.8 vs 26.9±5.8 years old) and the gestational age at birth (39.1±1.4 vs 39.6±1.3 weeks) were similar between the groups. IUGR children were shorter (1.28± 0.09 m vs 1.33± 0.09 m, p=0.04). Growth hormone levels (GH) at birth were negatively associated with systolic blood pressure at 8 years of age (regression coefficients for umbilical cord blood levels: -0.9, 95% CI -2.03 to 0.04 mg/ml, p= 0.04). Conclusion: The alterations on blood pressure can begin in fetal life were levels of GH could have an important role. Objetivo: Evaluar la relación entre parámetros hormonales seleccionados (al nacimiento y a los 8 años de edad) y los niveles de presión arterial a los 8 años de edad en una cohorte de niños con restricción en el crecimiento intrauterino (RCIU) y con peso normal al nacimiento (PNN). Material y métodos: Se realizó un estudio de cohortes desde el inicio del embarazo hasta la infancia (1995-2004). Se tomaron muestras de sangre de cordón umbilical al nacimiento y a los 8 años para evaluar parámetros endocrino-metabólicos seleccionados (variable independiente) y la presión arterial a los 8 años de edad (variable dependiente). Se evaluaron 64 niños de la cohorte original; 27 (42.2%) casos pertenecían al grupo de RCIU y 37 (57.8%) al grupo con PNN. El análisis multivariado se ajustó por RCIU, género, índice de masa corporal y edad del niño en el momento de medir la presión arterial. Resultados: La edad de las madres (26.6±5.8 vs 26.9±5.8 años) y la edad gestacional al parto (39.1±1.4 vs 39.6±1.3 semanas) fueron similares entre los grupos. Los niños de 8 años que nacieron con RCIU fueron más bajos (1.28± 0.09 m vs 1.33± 0.09 m, p=0.04). Los niveles de hormona de crecimiento (GH) al nacimiento fueron asociados negativamente con la presión arterial sistólica del niño (coeficiente de regresión: -0.9, 95% CI -2.03 a 0.04 mg/ml, p=0.04). Conclusión: Las alteraciones de la presión arterial pueden comenzar desde la vida fetal y los niveles de GH fetal pueden jugar un papel importante

Delta and kappa opioid receptors in human endometrium during the menstrual cycle: Expression and localization

Objective Endogenous opioid peptides were reported to be involved in the regulation of reproductive physiology and their precursors and receptors were described in many of the male and female reproductive tissues. Mu opioid receptor (MOR) was described in human endometrial cells and its expression and localization changed during the menstrual cycle. However, there is no data from the distribution of the other opioid receptors: Delta (DOR) and Kappa (KOR). The objective of the present work was to analyze the dynamics of expression and localization of DOR and KOR in human endometrium throughout the menstrual cycle. Study design Human endometrial samples from different menstrual cycle phases were analyzed by immunohistochemistry. Results DOR and KOR were present in all samples analyzed and the protein expression and localization changed throughout the menstrual cycle. Both receptor expression increased during the late proliferative phase and decreased during the late secretory-one, especially in the luminal epithelium. DOR expression was generally higher than KOR expression in all cell compartments. Conclusions The presence of DOR and KOR in human endometrium and their dynamic changes during the menstrual cycle join the results previously obtained in MOR suggesting a possible role of opioids in reproduction events related to the human endometrium.The authors thank Leire Andrés (Cruces University Hospital) and Edurne Alonso (UPV/EHU) for help in the discussion on endometrial histology. This work received financial support from the University of the Basque Country (Grant PPGA19/04). E.O. carried out all the experimentation without any public or private financial help. L.T. acknowledges the financial support given by University of the Basque Country (PIF15/149). The authors also thank Ane Portillo for technical help in analysing the results

Aspiration of excess follicles before intrauterine insemination in high response cycles

Purpose To assess the outcome of excess follicle aspiration before intrauterine insemination (EFABI) in intrauterine insemination (IUI) cycles with 4-6 follicles >= 14 mm. Methods A retrospective case-control study with 1559 patients undergoing IUI (donor and husband's sperm), of whom 86 underwent EFABI. We studied also an historical series of 2213 patients before EFABI implementation. For 3.5 years, all women undergoing IUI developing 4-6 follicles >= 14 mm were offered EFABI on the day of hCG administration. Pregnancy rates (PRs), multiple PRs, and adverse effects were measured. Results EFABI was associated with a similar multiple PR (17.8% vs 17.5% in non-EFABI cases), with no triplets in EFABI patients. Live birth rates were significantly higher in EFABI cycles in IUI overall (25.5% vs 15.2%). When considered separately, the performance of EFABI resulted in significantly increased live birth rates in IUI-donor cycles (32.5% vs 18.5%), whereas the differences in IUI-husband cycles (19.5% vs 12.9%) did not reach statistical significance. The PR was 21.2% during the EFABI implementation period and 19.4% in the pre-EFABI period. Conclusions EFABI in cycles in which 4-6 follicles reach >= 14 mm is a simple option that reduces cycle cancellation rates, results in higher PRs than cycles with 1-3 follicles, and lowers the risk of multiple pregnancy

Meta-Analysis of the Embryo Freezing Transfer Interval

Background The decision of whether frozen embryo transfer (FET) should be performed in the cycle immediately after OPU or at least one cycle later is controversial. FET could improve pregnancy rates in IVF; however, how much time is needed for the endometrium to return to optimal receptivity after ovarian stimulation is not known. Methods Electronic search in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials to identify studies providing data on the influence of the interval between embryo freezing (or OPU) and FET in FET cycles published between January 1, 2007, and February 1, 2020. Main findings Data analyzed indicated that in the immediate FET cycles, there was a trend to an increased biochemical pregnancy rate (RR = 1.08; CI = 1.00-1.18), whereas the clinical pregnancy rate was somewhat higher, but without reaching statistical significance (RR = 1.07; CI = 0.99-1.15). The live birth rate was similar in the two groups (RR = 1.05; CI = 0.95-1.15), as was the implantation rate (RR = 0.98; CI = 0.83-1.16). Stratifying by embryo stage or FET type (freeze-all or FET after failed fresh transfer) showed no differences. Conclusion Systematically delaying FET does not offer benefits to IVF outcomes. In addition, immediate transfer is associated with a nonsignificant trend to better clinical pregnancy rate and it also avoids the psychological effects of prolonging the stress on prospective parents

Asociación entre consumo de calcio, niveles de parathormona y presión arterial en el embarazo

Purpose: To evaluate the association between calcium intake from diet, calciotropic hormones (PTH, PTH-rp), vasoactive regulators (endothelin, nitric oxide) and blood pressure levels during pregnancy, birth and puerperium. Method: In a prospective study 149 healthy normotensive primigravidas were followed-up from 15 weeks of gestation to puerperium. Daily calcium intake, calciuria, PTH, PTH-rp, endothelin, nitrite-nitrate, and Holter Test were assessed. Linear regression models were performed to evaluate the association between calcium intake, blood pressure levels and the laboratory tests. Multivariate regression models were performed to control potential confounders. Results: A significant increase of calcium intake during pregnancy was observed (931±301 mg/day to 1,195±467 mg/day, p<0.001). Plasma PTH-rp, endothelin, and nitrite-nitrate levels did not change during pregnancy. Among the women 38 (25.4%) had low calcium intake (<800 mg/day) with a larger increase of systolic and diastolic blood pressure during pregnancy (p=0.04) birth (p=0.006) and puerperium (p=0.01). After adjusting for other factors the multivariate analyses showed statistical association between low calcium intake, high parathormone levels and high systolic blood pressure levels during pregnancy (p=0.002). Conclusion: Low calcium intake during pregnancy is associated with a larger increase of systolic blood pressure and high parathormone levels. Objetivo: Evaluar la asociación entre la ingesta de calcio en el embarazo, los niveles de presión arterial, las hormonas calciotrópicas (PTH, PTH-rp) y sustancias vasorreguladoras (endotelina, óxido nítrico). Métodos: Se realizó un estudio prospectivo con 149 primigrávidas normotensas que fueron incluidas en la semana 15 de gestación con seguimiento y evaluación hasta el puerperio. Se evaluó la ingesta diaria de calcio, la monitoría Holter de 24 horas, la calciuria, PTH, PTH-rp, la endotelina, nitritos y nitratos. Se siguieron modelos de regresión lineal para evaluar la asociación entre la ingesta de calcio, la presión arterial, las hormonas calciotrópicas y los vasorreguladores. Para controlar las variables de confusión se hicieron modelos de regresión múltiple. Resultados: Durante el embarazo la ingesta de calcio aumentó significativamente (931±301 mg/día a 1,195±467 mg/ día, p<0.001). Entre las embarazadas 38 (25.4%) tuvieron una baja ingesta de calcio (<800 mg/día) asociada con mayores niveles de presión arterial sistólica y diastólica durante el embarazo (p=0.04), en el parto (p=0.006) y en el puerperio (p=0.01). Los mayores niveles de presión arterial sistólica durante el embarazo se asociaron con mayores niveles de paratormona y con menores niveles de ingesta de calcio (p=0.002). Los niveles plasmáticos de PTH-rp, endotelina, nitritos y nitratos no mostraron cambios durante el embarazo. Conclusión: La baja ingesta de calcio en el embarazo se asoció con mayores niveles de paratormona y de presión arterial sistólica durante el embarazo

Antibacterial and antifungal activity of the human endometrial fluid during the natural cycle

[EN] Purpose. Some microbiota patterns have been associated with favorable IVF prognosis and others with pathological conditions. The endometrial fluid aspirate (EFA) contains antibacterial proteins that are enriched in implantative IVF cycles, but the antimicrobial effect of EFA has not been addressed. We aimed to evaluate the antimicrobial activity of the human endometrial fluid during the natural cycle. Methods. EFA was obtained through an embryo transfer catheter in 38 women, aged 18-40 years, with regular cycles attending to a fertility clinic. The antimicrobial activity of EFAs was tested against two strains of Staphylococcus aureus; one strain each of Streptococcus agalactiae, Enterococcus faecalis, Escherichia coli, and Klebsiella pneumoniae; and three yeasts (Candida albicans, Candida glabrata, and Candida krusei). Results. All samples exhibited antibacterial activity against S. aureus. In addition, 32.4% of EFAs were active against one of the other microorganisms assayed, 16.2% against two, and 5.4% against four of them. In contrast, none exhibited antibacterial activity against E. coli or K. pneumoniae. The antimicrobial activity differs considerably between EFA samples, and we failed to observe a cycle-related pattern. Conclusions. EFA presented two antimicrobial activity patterns: (a) one common to all the samples, exhibiting activity against S. aureus and lack of activity against E. coli and K. pneumoniae, and (b) an individualized pattern, showing activity against some of the other microorganisms tested. The intensity of antibacterial activity differs between EFA samples. Our data suggest that the uterine microbiota is controlled by means of endometrial fluid components.This study was partially supported by a Grant for Fertility Innovation (GFI, 2011) from Merck, Darmstadt, Germany. M. Bregón-Villahoz is recipient of a predoctoral grant from the Universidad del País Vasco-Euskal Herriko Unibertsitatea (UPV/EHU) (PIF19/316). The authors thank the technical and human support provided by DNA Bank Service (SGIker) of the University of the Basque Country (UPV/EHU) and European funding (ERDF and ESF). CIC bioGUNE is accredited with the Severo Ochoa Excellence award by the Spanish Ministerio de Economía y Competitividad, MINECO (SEV-2016-0644)

Cell-cell interactions during the formation of primordial follicles in humans

Gametogenesis is a complex and sex-specific multistep process during which the gonadal somatic niche plays an essential regulatory role. One of the most crucial steps during human female gametogenesis is the formation of primordial follicles, the functional unit of the ovary that constitutes the pool of follicles available at birth during the entire reproductive life. However, the relation between human fetal germ cells (hFGCs) and gonadal somatic cells during the formation of the primordial follicles remains largely unexplored. We have discovered that hFGCs can form multinucleated syncytia, some connected via interconnecting intercellular bridges, and that not all nuclei in hFGC-syncytia were synchronous regarding meiotic stage. As hFGCs progressed in development, pre-granulosa cells formed protrusions that seemed to progressively constrict individual hFGCs, perhaps contributing to separate them from the multinucleated syncytia. Our findings highlighted the cell-cell interaction and molecular dynamics between hFGCs and (pre)granulosa cells during the formation of primordial follicles in humans. Knowledge on how the pool of primordial follicle is formed is important to understand human infertility.</p

Estimation of preterm labor immediacy by nonlinear methods

Preterm delivery affects about one tenth of human births and is associated with an increased perinatal morbimortality as well as with remarkable costs. Even if there are a number of predictors and markers of preterm delivery, none of them has a high accuracy. In order to find quantitative indicators of the immediacy of labor, 142 cardiotocographies (CTG) recorded from women consulting because of suspected threatened premature delivery with gestational ages comprehended between 24 and 35 weeks were collected and analyzed. These 142 samples were divided into two groups: the delayed labor group (n = 75), formed by the women who delivered more than seven days after the tocography was performed, and the anticipated labor group (n = 67), which corresponded to the women whose labor took place during the seven days following the recording. As a means of finding significant differences between the two groups, some key informational properties were analyzed by applying nonlinear techniques on the tocography recordings. Both the regularity and the persistence levels of the delayed labor group, which were measured by Approximate Entropy (ApEn) and Generalized Hurst Exponent (GHE) respectively, were found to be significantly different from the anticipated labor group. As delivery approached, the values of ApEn tended to increase while the values of GHE tended to decrease, suggesting that these two methods are sensitive to labor immediacy. On this paper, for the first time, we have been able to estimate childbirth immediacy by applying nonlinear methods on tocographies. We propose the use of the techniques herein described as new quantitative diagnosis tools for premature birth that significantly improve the current protocols for preterm labor prediction worldwide.Work by the first author was supported by the Basque Government grant PRE-2015-1-194,and work by the first and second authors by the Basque Government grant IT974-16. This work was also supported in part by FERRING laboratories Madrid, Spain (RM), https://www.ferring.com/en/home/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Effect of vitamin E administered to men in infertile couples on sperm and assisted reproduction outcomes: a double-blind randomized study

Objective: To evaluate the influence on sperm parameters and invitro fertilization (IVF) outcomes of the administration of 400 mg/day of vitamin E for 3 months to men from infertile couples who are undergoing IVF. Design: Double-blind, placebo-controlled, randomized study. Setting: Human reproduction unit of a university hospital. Patients: A total of 101 couples, 50 in the vitamin E group and 51 in the placebo group, undergoing IVF, among whom 64.4% of cases had an abnormal spermiogram according to World Health Organization (WHO) criteria. Interventions: Vitamin E (alpha-tocopherol), 400 mg daily by mouth for 3 months, with sperm analysis performed immediately before starting the treatment and 3 months later on the day of IVF. Main Outcome Measures: WHO sperm parameters and IVF outcomes. Results: Although there was a statistically significant increase in progressive motility in the vitamin E group compared with before-treatment values, a similar increase occurred in the placebo group. Normal morphology was even better in the placebo group. Regarding IVF outcomes, better fertilization rates were observed in the placebo group, but the live-birth rate per transfer was statistically significantly higher in the vitamin E group: 17 (41.46%) of 41 versus 9 (20.46%) of 44 in the placebo group. Although the clinical pregnancy rates (both per transfer and per cycle started) and the implantation rate were somewhat higher in the vitamin E group (43.9% and 25%; 36.0% and 22.0%; and 24.7% and 14.1%, respectively), the increase was not statistically significant. Conclusions: The effect of vitamin E on classic sperm parameters was not an improvement over placebo. Nonetheless, vitamin E administration was associated with a statistically significantly higher live-birth rate, and there was a trend toward better results in other IVF parameters

Cervical pregnancy in assisted reproduction: an analysis of risk factors in 91,067 ongoing pregnancies

OBJECTIVE: To assess the frequency of cervical pregnancy (CP) in women undergoing assisted reproductive techniques (ART) and to ascertain its risk factors DESIGN: Case-control study. Two control groups were established: tubal ectopic pregnancies and intrauterine pregnancies. SETTING: 25 private assisted reproduction clinics run by the same group in Spain PATIENT(S): Women undergoing ART (artificial insemination, or IVF with own or donor oocytes). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Frequency of CP. Ascertainment of demographic and clinical risk factors. Assessment of the influence of IVF parameters on CP risk. RESULT(S): There were 32 CPs out of 91,067 ongoing pregnancies, yielding a rate of 3.5/10,000. CPs represented 2.02% of all ectopic pregnancies (32/1582). The main risk factors were: ≥ 2 previous pregnancies (OR= 2.68; CI=1.18-6.07), ≥2 previous miscarriages (OR= 4.21, CI=1.7- 10.43), ≥ 2 previous curettages (OR=4.71; CI= (1.19-18.66) and smoking (OR= 2.82 (1.14-6.94). History of cesarean sections and tubal pregnancy were not associated with an elevated CP risk. Infertility conditions and endometrial thickness were similar across the three groups. The proportion of women from whom < 10 oocytes were retrieved was higher in the CP group than in either of the control groups. CONCLUSION(S): In ART, the main risk factors for ectopic pregnancy are a history of at least 2 pregnancies/miscarriages/curettages, and smoking. IVF parameters do not seem to influence the development of CP. CP is less common in ART than previously reported, likely attributable to improvements in ART, although a publication bias cannot be ruled out in early IVF reports