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In the management of azoospermia, a combination of testicular sperm extraction and intracytoplasmic sperm injection ( ICSI) is usually the most successful option for fatherhood. However, an outstanding question remains: How can at least a few spermatozoa be obtained from the ejaculate, thus avoiding the need for a surgical procedure? A 36-year-old man presented to Assisted Reproduction Unit with his 26-year-old wife. The ultrasound assessment revealed bilateral microlithiasis. Two spermograms revealed absolute azoospermia. Levels of follicle-stimulating hormone ( FSH) and luteinising hormone were normal-low. The patient underwent 10 months of treatment with clomiphene citrate. A bilateral testicular sperm extraction failed to retrieve spermatozoa and revealed a maturation arrest at spermatocyte/spermatid stages depending on the tubules. Clomiphene citrate was replaced with recombinant FSH ( rFSH). After 9-month treatment with rFSH, motile spermatozoa from droplets of ejaculate pellet were cryopreserved as a single straw. Ovarian stimulation was provided using classic antagonist protocol, and five mature oocytes were collected. Two consecutive fresh semen samples on the day of ICSI yielded seven motile spermatozoa, and fertilisation was achieved in all five oocytes. On day 3, two embryos were transferred, yielding positive beta-human chorionic gonadotropin and a healthy delivery of a boy and a girl. [ABSTRACT FROM AUTHOR]

Background: Maternal psychological distress during pregnancy can negatively impact fetal development, resulting in long-lasting consequences for the offspring. These effects show a sex bias. The mechanisms whereby prenatal stress induces functional and/or structural changes in the placental-fetal unit remain poorly understood. Maternal circulating small extracellular vesicles (sEVs) are good candidates to act as "stress signals" in mother-to-fetus communication. Using a repetitive restraint-based rat model of prenatal stress, we examined circulating maternal sEVs under stress conditions and tested whether they could target placental-fetal tissues., Results: Our mild chronic maternal stress during pregnancy paradigm induced anhedonic-like behavior in pregnant dams and led to intrauterine growth restriction (IUGR), particularly in male fetuses and placentas. The concentration and cargo of maternal circulating sEVs changed under stress conditions. Specifically, there was a significant reduction in neuron-enriched proteins and a significant increase in astrocyte-enriched proteins in blood-borne sEVs from stressed dams. To study the effect of repetitive restraint stress on the biodistribution of maternal circulating sEVs in the fetoplacental unit, sEVs from pregnant dams exposed to stress or control protocol were labeled with DiR fluorescent die and injected into pregnant females previously exposed to control or stress protocol. Remarkably, maternal circulating sEVs target placental/fetal tissues and, under stress conditions, fetal tissues are more receptive to sEVs., Conclusion: Our results suggest that maternal circulating sEVs can act as novel mediators/modulators of mother-to-fetus stress communication. Further studies are needed to identify placental/fetal cellular targets of maternal sEVs and characterize their contribution to stress-induced sex-specific placental and fetal changes., (© 2024. The Author(s).)

Background: In the field of male infertility, when sperm is normal/subnormal, a few "add-on" routine tests can complete the basic semen examination., Objectives: The aim of this study was to develop and evaluate a faster, simplified motile sperm organelle morphology examination (MSOME) technique for selected infertile patients with apparently normal/subnormal sperm and, in their background: failure of two or three intrauterine insemination (IUI) cycles, repeatedly fragmented embryos, embryonic development to blastocyst-stage failures, repeated miscarriages, a long period of infertility or 2 or more IVF attempts without pregnancy. Our test results were correlated with IUI, conventional in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI) and intracytoplasmic morphologically selected sperm injection (IMSI) outcomes., Materials and Methods: We validated an adapted version of the MSOME analysis called the pre-IMSI test (PIT), based on vacuole evaluation alone. 248 infertile patients from our assisted reproductive technology (ART) Center were retrospectively selected and split into three PIT score subgroups (patients with ≤8% (score I), 9 to 15% (score II) and ≥16% normal spermatozoa (score III)) based on the correlation between PIT results and each ART technique outcome. The choice of one or another of these ART techniques had been made according to the usual clinico-biological criteria., Results: Clinical outcomes for each of the three PIT subgroups were compared individually for the different ART techniques. For ICSI, the effect of the PIT score subgroup was significant for clinical pregnancies (p = 0.0054) and presented a trend for live births (p = 0.0614). Miscarriage rates of IVF attempts were statistically different depending on the PIT score (p = 0.0348). Furthermore, the odds ratios of clinical pregnancy rates were significantly different according to PIT score subgroup when comparing ICSI vs. IMSI or IVF vs. ICSI attempts., Discussion: IMSI appears to be recommended when sperm belongs to PIT score I, ICSI when it belongs to PIT score II and IVF or IUI when sperm is of PIT score III quality in selected infertile couples. The lack of statistical power in these PIT subgroups means that we must remain cautious in interpreting results., Conclusion: Our results support the interest of this simplified test for certain couples with normal/subnormal sperm to help choose the most efficient ART technique, even as first-line treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sigala et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The live birth rate following embryo transfer is comparable between spontaneous, stimulated and artificial cycles. However, the pregnancy loss rate appears elevated with hormonal therapy, possibly due to luteal insufficiency. This study aimed to determine whether the serum progesterone level on transfer day differed according to the endometrial preparation method for frozen embryo transfer (FET). Twenty spontaneous cycles (SC), 27 ovarian stimulation cycles (OS) and 65 artificial cycles (AC) were retrospectively studied from May to December 2019 in a single French hospital. The primary endpoint was the level of serum progesterone on the day of FET between the three endometrial preparation methods. The mean serum progesterone level on transfer day was 29.47 ng/ml in the OS group versus 20.03 ng/ml in the SC group and 14.32 ng/ml AC group ( P < 0.0001). Progesterone levels remained significantly different after logistic regression on age and anti-Müllerian hormone (AMH) level. There was no significant difference in demographic and hormone characteristics (age, body mass index, embryo stage of embryo, type of infertility, basal follicle stimulating hormone, luteinizing hormone, estradiol and AMH levels), endometrial thickness, number and type of embryos transferred, duration of infertility, pregnancy rate, live birth rate and pregnancy loss rate. No difference was found in serum progesterone levels between clinical pregnancy with fetal heartbeat and no clinical pregnancy (no pregnancy or pregnancy loss, 17.49 ng/ml vs 20.83 ng/ml, respectively, P = 0.07). The lower serum progesterone level found on FET day in the AC group should be further investigated to see whether this difference has a clinical effect on the live birth rate.

Hispanic women living on the US-Mexico border have had higher cesarean delivery rates than other Hispanic women in the US. Using birth certificate and other data, we compared cesarean rates among Hispanic women living in US border counties with rates among other Hispanic women in border states during 2015. Using linear regression, we also determined which medical, hospital, and sociodemographic characteristics accounted for intercounty variations in rates. In border counties the rates were 38.3 percent for all births, 31.3 percent for low-risk nulliparous mothers, 21.0 percent for primary cesareans, and 94.7 percent for repeat cesareans. In nonborder counties the rates were 30.9 percent, 24.4 percent, 15.1 percent, and 90.5 percent, respectively. Maternal medical characteristics explained over 50 percent of the variation for all cesarean outcomes. Other characteristics that were major contributors to higher cesarean rates included for-profit hospital status, delivery by a physician as opposed to a midwife, and residence in a county with a larger Hispanic fraction of the population. Addressing potentially unnecessary cesareans among Hispanic women on the border will likely require a multicomponent strategy.

Background: Cesarean delivery occurs in one in three US births and poses risks for mothers and infants. Hispanic cesarean rates were higher than non-Hispanic white rates in the US in 2016. In 2009, cesarean rates among Hispanics on the US-Mexico border exceeded rates among US Hispanics. Since 2009, rates have declined nationwide, but border Hispanic rates have not been studied., Objective: To compare cesarean delivery rates and trends in Hispanics and non-Hispanic whites in border and nonborder counties of the four US border states before and after 2009., Study Design: We used data from birth certificates to calculate percentages of cesarean deliveries among all births and births to low-risk nulliparous women during 2000-2015, and among births to low-risk women with and without a previous cesarean during 2009-2015. We calculated 95% confidence intervals around rates and used regular and piecewise linear regression to estimate trends for four ethnic-geographic subpopulations defined by combinations of Hispanic ethnicity and border-nonborder status., Results: Of the four subpopulations, border Hispanic rates were highest every year for all cesarean outcomes. In 2015 they were 38.3% overall, 31.4% among low-risk nulliparous women, and 21.1% and 94.6% among low-risk women without and with a previous cesarean, respectively. Nonborder Hispanic rates in 2015 were lowest for all outcomes but repeat cesarean. Rates for all four subpopulations rose steadily during 2000-2009. Unlike rates for non-Hispanic whites, border and nonborder Hispanic rates did not decline post-2009. Most of the border Hispanic excess can be attributed to higher cesarean rates in Texas., Discussion: Border Hispanic cesarean rates remain higher than those among other Hispanics and non-Hispanic whites in border states and show no signs of declining. This continuing disparity warrants further analysis using individual as well as hospital, environmental and other contextual factors to help target prevention measures., Competing Interests: The authors have declared that no competing interests exist.

A lower number of metaphase II oocytes eligible for vitrification after controlled stimulation in cancer patients has recently been reported, suggesting that cancer may impair the dynamics and quality of follicular growth. In this prospective, non-interventional study, the pattern of follicular growth and oocyte cohort after ovarian stimulation in cancer patients was analysed. Ninety cancer patients, recruited before starting chemotherapy, were compared with 180 time- and age-matched healthy controls undergoing intracytoplasmic sperm injection. Primary outcome was total number of metaphase II oocytes and metaphase II /total oocytes rate. Basal anti-Müllerian hormone levels (P < 0.05) and antral follicle count (P < 0.0001) were significantly lower in cancer patients. Recombinant FSH total dose was significantly higher in the cancer group (P < 0.0001). No differences were found in duration of stimulation, mean number of mature follicles on day of ovulation induction and total oocyte number after retrieval; the number of metaphase II oocytes retrieved (6.2 ± 4.7 versus 8.8 ± 4.2; P < 0.0001) and number of metaphase II oocytes-total oocytes ratio were significantly lower in cancer patients (56% versus 78%, P < 0.0001). Fewer metaphase II oocytes were eligible for vitrification and lower maturation rate in the cancer group., (Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

The Tau protein (Tubulin Associated Unit) is a phosphoprotein of the microtubule-associated protein family (MAPs). Its role is the regulation of the microtubule polymerization. The Tau protein is naturally present in brain, heart, muscle, lung, kidney, pancreas and liver. An expression of Tau protein and RNA messengers was also highlighted in the testis that is an organ rich in microtubules. The role of microtubules is essential in the stabilization of the cellular shape and in cell divisions. In the testis, Tau protein could be involved in the division process of the spermatogenesis by acting on the microtubular dynamics in the arrangement of the spermatozoon polarity. This review synthesizes the current knowledge, the localization and the main functions of the Tau protein focused on the testis. The localization and the potential roles of the Tau protein during the spermatogenesis are discussed by emphasizing the link with the microtubular structures of seminiferous tubules., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Objective: Although an inhibin B assay may be useful in the assessment of testicular function in a number of genital conditions, reliable reference ranges are still lacking. The present study sought to establish the reference range for serum inhibin B by applying the updated Gen II assay., Design: This prospective study included 818 men referred for semen analysis: 377 were normozoospermic (reference group) and 441 presented at least one abnormal semen parameter (case group)., Methods: Semen parameters were interpreted according to the 2010 World Health Organization manual and David's modified classification for normal morphology. The inhibin B concentration was determined with the current ELISA., Results: In the reference group, the 2.5th percentile for inhibin B was 92 pg/ml and the 97.5th percentile for FSH was 7.8 IU/l. In the overall population, an inhibin B level <92 pg/ml was associated with increased odds ratio (OR; 95% CI) for oligozoospermia (16.93 (9.82-29.18), P<0.0001), asthenozoospermia (4.87 (2.88-8.10), P<0.0001), and teratozoospermia (2.20 (1.31-3.68), P=0.0026). The combination of a FSH >7.8 IU/l and an inhibin B <92 pg/ml was associated with greater OR for oligozoospermia (98.74 (23.99-406.35), P<0.0001) than for each hormone considered separately., Conclusions: A new reference range for serum inhibin B was established by the use of updated immunoassay. The correlations between hormone levels and semen parameters highlighted the importance of establishing these values with respect to the spermogram. When combined with FSH assay, the inhibin B range may be of value in the evaluation of spermatogenesis in a number of male genital conditions., (© 2015 European Society of Endocrinology.)

Objective: To evaluate the relationship between polycystic ovarian morphology (PCOM) and oocyte quality after controlled ovarian stimulation for intracytoplasmic sperm injection (ICSI)., Design: Prospective, comparative study with concurrently treated and age-matched controls., Setting: Academic IVF unit of the Lille University Hospital., Patient(s): A total of 194 women were prospectively included before their first IVF-ICSI attempt for exclusive male infertility. They were classified into PCOM (n = 97) or control groups (n = 97) according to their follicle number per ovary. The nuclear maturation and morphologic aspects of 1,013 oocytes from PCOM patients were assessed and compared with those of 774 oocytes from controls., Intervention(s): None., Main Outcome Measure(s): Rate of metaphase II (MII) and morphologically abnormal oocytes., Result(s): The mean number of total and MII oocytes retrieved was significantly higher in the PCOM group. The rate of MII and morphologically abnormal oocytes was equivalent between the two groups. The mean number of embryos was significantly higher in the PCOM group. However, the percentage of top-quality embryos on day 3 was similar between the two groups. The implantation and clinical pregnancy rates were significantly higher in the PCOM group., Conclusion(s): Polycystic ovarian morphology does not have a negative impact on the quality of oocytes and embryos or the outcome of IVF-ICSI., (Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Standard protocols for monitoring wastewater treatment efficacy target Escherichia coli and fecal coliforms. This might not accurately describe risks associated with antibiotic resistance in the bacterial population of treated wastewaters. We modified a standard agar recovery method by amending it with various antibiotics. The resulting bacterial colonies were submitted to 454 pyrosequencing; thus we identified the diversity of culturable antibiotic resistant bacteria from treated and raw wastewaters. This approach produced 209,706 high quality reads of >300 bp. Operational taxonomic units (OTUs) within Proteobacteria dominated the system. The Shannon-Wiener H' index showed bacterial populations recovered on ciprofloxacin amended agars to be the least diverse. Principal component analysis of OTU distribution at phylum level showed that Proteobacteria accounted for most of the variability. The same analysis revealed most of the samples to have similar diversities at phylum level being dominated by Proteobacteria, though a few samples, typically recovered from ciprofloxacin or doxycycline amended agars were often dissimilar. Arcobacter spp. or E. coli were dominant in the bacterial communities recovered on agars amended with ciprofloxacin or doxycycline, respectively. Genera containing putative pathogens were mostly representatives of Gamma and Epsilon proteobacteria. Bacterial populations containing multiple antibiotic resistance (MAR) in the final treated effluent was a possibility.

In the management of asthenozoospermia, the spermogram-spermocytogram plays an important role during diagnosis. It is of major importance to distinguish between necrozoospermia and sperm vitality. An ultrastructural study of spermatozoa is processed in the case of primary infertility without female implication, severe, unexplained and irreversible asthenozoospermia, sperm vitality at least 50 % and normal concentration of spermatozoa. Ultrastructural flagellar abnormalities are numerous and involve most spermatozoa. ICSI provides a suitable solution for patients with sperm flagellar defects to conceive children with their own gametes but the rate of ICSI success may be influenced by the type of flagellar abnormality. Some fertilization and birth rate failures which are related to some flagellar abnormalities might occur., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

CC chemokine ligand 2 (CCL2) is the most potent monocyte chemoattractant and inter-individual differences in its expression level have been associated with genetic variants mapping to the cis-regulatory regions of the gene. An A to G polymorphism in the CCL2 enhancer region at position -2578 (rs1024611; A>G), was found in most studies to be associated with higher serum CCL2 levels and increased susceptibility to a variety of diseases such as HIV-1 associated neurological disorders, tuberculosis, and atherosclerosis. However, the precise mechanism by which rs1024611influences CCL2 expression is not known. To address this knowledge gap, we tested the hypothesis that rs1024611G polymorphism is associated with allelic expression imbalance (AEI) of CCL2. We used haplotype analysis and identified a transcribed SNP in the 3'UTR (rs13900; C>T) can serve as a proxy for the rs1024611 and demonstrated that the rs1024611G allele displayed a perfect linkage disequilibrium with rs13900T allele. Allele-specific transcript quantification in lipopolysaccharide treated PBMCs obtained from heterozygous donors showed that rs13900T allele were expressed at higher levels when compared to rs13900C allele in all the donors examined suggesting that CCL2 is subjected to AEI and that that the allele containing rs1024611G is preferentially transcribed. We also found that AEI of CCL2 is a stable trait and could be detected in newly synthesized RNA. In contrast to these in vivo findings, in vitro assays with haplotype-specific reporter constructs indicated that the haplotype bearing rs1024611G had a lower or similar transcriptional activity when compared to the haplotype containing rs1024611A. This discordance between the in vivo and in vitro expression studies suggests that the CCL2 regulatory region polymorphisms may be functioning in a complex and context-dependent manner. In summary, our studies provide strong functional evidence and a rational explanation for the phenotypic effects of the CCL2 rs1024611G allele.

Comparative cross-species genomic analysis has served as a powerful tool to discover novel noncoding regulatory regions that influence gene expression in several cytokine loci. In this study, we have identified several evolutionarily conserved regions (ECRs) that are shared between human, rhesus monkey, dog, and horse and that are upstream of the promoter regions that have been previously shown to play a role in regulating CCL2 gene expression. Of these, an ECR that was ~16.5 kb (-16.5 ECR) upstream of its coding sequence contained a highly conserved NF-κB site. The region encompassing the -16.5 ECR conferred TNF-α responsiveness to homologous and heterologous promoters. In vivo footprinting demonstrated that specific nucleotide residues in the -16.5 ECR were protected or became hypersensitive after TNF-α treatment. The footprinted regions were found to bind NF-κB subunits in vitro and in vivo. Mutation/deletion of the conserved NF-κB binding site in the -16.5 ECR led to loss of TNF-α responsiveness. After TNF-α stimulation, the -16.5 ECR showed increased sensitivity to nuclease digestion and loss of histone signatures that are characteristic of a repressive chromatin. Chromosome conformation capture assays indicated that -16.5 ECR physically interacts with the CCL2 proximal promoter after TNF-α stimulation. Taken together, these results suggest that the -16.5 ECR may play a critical role in the regulation of CCL2.

Recent studies have invoked inflammation as a major contributor to the pathogenesis of Parkinson's disease (PD). We determined the role of members of the chemokine system, key inflammatory mediators, in PD pathogenesis. In the MPTP model of murine PD, several chemokines, including CC chemokine ligand 2 (CCL2, Monocyte Chemoattractant Protein-1) and CCL3 (Macrophage Inflammatory Protein-1alpha), were upregulated in the striatum and the ventral midbrain. Astrocytes were the predominant source of CCL2 and CCL3 in the striatum and the substantia nigra, and dopaminergic neurons in the substantia nigra constitutively expressed these two chemokines. MPTP treatment resulted in decreased CCL2 expression and increased CCL3 expression in the surviving dopaminergic neurons. Because we found that CCL2 induced production of TNF-alpha in microglial cells, a cytokine known to play a detrimental role in PD, we anticipated that deletion of the genes encoding CCL2 and CCR2, its major receptor, would confer a protective phenotype. However, MPTP-induced striatal dopamine depletion was comparable in double knockout and wild-type mice. Our results demonstrate that chemokines such as CCL2 are induced following MPTP treatment, but that at least within the context of this PD model, the absence of CCL2 and CCR2 does not protect against striatal dopamine loss.

Based on prior data, the current authors hypothesised that beneficial pronation effects on gas exchange and respiratory mechanics might be maximised in severely hyperinflated chronic bronchitis patients. The current authors also sought to elucidate underlying mechanisms and to determine whether pronation effects are reflected by postural changes in inspiratory pressure-volume (P-V) curve characteristics. A total of 16 mechanically ventilated patients (for 16-36 h) with chronic bronchitis exacerbation were studied in pre-prone semirecumbent (SREC), prone and post-prone SREC postures. Static respiratory system intrinsic positive end-expiratory pressure (PEEPi,rs) was >12 cmH2O. Haemodynamics, partitioned respiratory mechanics, gas exchange, and lung volumes were determined at zero external positive end-expiratory pressure. P-V curves were constructed from functional residual capacity. End-expiratory lung volume exceeded opening volume. Prone position versus pre-prone SREC resulted in 20% reduced pressure at the lower inflection point (LIP) and 17% increased volume at the upper inflection point of the lung P-V curve, improved lung mechanics and volumes, oxygenation, and carbon dioxide arterial tension (Pa,CO2). In multiple linear regression, postural decreases in PEEPi,rs and additional lung resistance independently predicted postural decreases in lung LIP pressure and Pa,CO2), respectively. In conclusion, in severely hyperinflated patients, pronation reduces lung lower inflection point pressure and increases lung upper inflection point volume. Pronation effects on ventilation homogeneity and carbon dioxide arterial tension are maximised, implying that pronation can be useful during early controlled ventilation.

Most reports on the effectiveness and side effects of oral versus parenteral calcitriol or alfacalcidol in hemodialysis patients with secondary hyperparathyroidism show no advantage of parenteral treatment. The efficacy and safety of intravenous doxercalciferol (1alphaD(2)) were studied in hemodialysis patients with secondary hyperparathyroidism (plasma intact parathyroid hormone [iPTH]: range, 266 to 3,644 pg/mL; median, 707 pg/mL). These results were compared with those of a previous trial using intermittent oral 1alphaD(2); the same 70 patients were entered onto both trials, and 64 patients completed both trials per protocol. Twelve weeks of open-label treatment in both trials were preceded by identical 8-week washout periods. Degrees of iPTH suppression from baseline were similar in the two trials, with iPTH level reductions less than 50% in 89% and 78% of patients during oral and intravenous treatment, respectively. Grouping patients according to entry iPTH levels (<750 and >/=750 pg/mL) showed similar but more rapid iPTH suppression in the low-iPTH groups, whereas longer treatment and larger doses were required by the high-iPTH groups. Highest serum calcium levels averaged 9.82 +/- 0.14 and 9.67 +/- 0.11 mg/dL during oral and intravenous 1alphaD(2) treatment, respectively (P: = not significant [NS]). Prevalences of serum calcium levels greater than 11.2 mg/dL during oral and intravenous treatment were 3.62% and 0.86% of calcium measurements, respectively (P: < 0.001). Highest serum phosphorus levels during oral and intravenous treatment averaged 5.82 +/- 0.21 and 5.60 +/- 0.21 mg/dL, respectively (P: = NS). The percentage of increments in serum phosphorus levels during oral treatment exceeded that during intravenous treatment during 5 of 12 treatment weeks. Thus, intermittent oral and intravenous therapy with 1alphaD(2) reduced iPTH levels effectively and similarly, hypercalcemia was less frequent, and serum phosphorus levels increased less during intravenous than oral 1alphaD(2) therapy, suggesting that intravenous 1alphaD(2) therapy may be advantageous in patients prone to hypercalcemia or hyperphosphatemia.