Influence of glucocorticoid and betamimetic therapy on milk secretory IgA concentration produced by mothers delivering preterm infants

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Risks of nonchromosomal birth defects, small-for-gestational age birthweight, and prematurity with in vitro fertilization: effect of number of embryos transferred and plurality at conception versus at birth

PURPOSE: Excess embryos transferred (ET) (> plurality at birth) and fetal heartbeats (FHB) at 6 weeks' gestation are associated with reductions in birthweight and gestation, but prior studies have been limited by small sample sizes and limited IVF data. This analysis evaluated associations between excess ET, excess FHB, and adverse perinatal outcomes, including the risk of nonchromosomal birth defects. METHODS: Live births conceived via IVF from Massachusetts, New York, North Carolina, and Texas included 138,435 children born 2004-2013 (Texas), 2004-2016 (Massachusetts and North Carolina), and 2004-2017 (New York) were classified by ET and FHB. Major birth defects were reported by statewide registries within the first year of life. Logistic regression was used to estimate adjusted odds ratios (AORs) and 95% CIs of the risks of a major nonchromosomal birth defect, small-for-gestational age birthweight (SGA), low birthweight (LBW), and preterm birth (≤36 weeks), by excess ET, and excess ET + excess FHB, by plurality at birth (singletons and twins). RESULTS: In singletons with [2 ET, FHB =1] and [≥3 ET, FHB=1], risks [AOR (95% CI)] were increased, respectively, for major nonchromosomal birth defects [1.13 (1.00-1.27) and 1.18 (1.00-1.38)], SGA [1.10 (1.03-1.17) and 1.15 (1.05-1.26)], LBW [1.09 (1.02-1.13) and 1.17 (1.07-1.27)], and preterm birth [1.06 (1.00-1.12) and 1.14 (1.06-1.23)]. With excess ET + excess FHB, risks of all adverse outcomes except major nonchromosomal birth defects increased further for both singletons and twins. CONCLUSION: Excess embryos transferred are associated with increased risks for nonchromosomal birth defects, reduced birthweight, and prematurity in IVF-conceived births

The relationship between seminal leukocytes, oxidative status in the ejaculate, and apoptotic markers in human spermatozoa

The aim of this study was to investigate the relationship between seminal leukocytes, reactive oxygen species (ROS) production in the ejaculate, and markers of apoptosis in human spermatozoa. Semen samples were collected from 60 patients attending fertility clinics at the Reproductive Biology Unit at Tygerberg Academic Hospital and Vincent Pallotti Hospital, Cape Town, South Africa. The concentration of seminal leukocytes was determined and was correlated with ROS production in the ejaculate, the percentage of superoxide (·O2 )- and hydrogen peroxide (H2O2)-positive spermatozoa, glutathione activation in the ejaculate, and with markers of apoptosis in spermatozoa, namely cysteine-dependent aspartate-directed proteases (caspase)-3/7 activation, mitochondrial membrane potential (ΔΨm), and the percentage of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive sperm. Significant correlations with the concentration of seminal leukocytes were found for ROS production in the ejaculate, the percentage of ·O2 -positive spermatozoa, and caspase-3/7 activation in the ejaculate. Leukocytospermic samples showed significantly higher ROS production, percentage of ·O2 -positive sperm, GSH activation, and caspase-3/7 activation compared to non-leukocytospermic samples. The percentage of ·O2 -positive sperm was significantly correlated with sperm ΔΨm and caspase-3/7 activation in the ejaculate. Sperm ΔΨm and TUNEL-positive sperm did not correlate with seminal leukocyte concentration. Data demonstrate that high seminal leukocyte concentrations that leads to increased seminal ROS production, and is also associated with caspase activation in the male germ cell and increased mitochondrial ROS production. The latter could possibly be a result of disturbed ΔΨm. The activation of caspase-3/7 could then follow the increased intrinsic superoxide levels due to depleted intrinsic glutathione (GSH). These cellular events might not directly and immediately lead to DNA fragmentation as an endpoint of apoptosis because of topological hindrances.Web of Scienc

Assessment of Birth Defects and Cancer Risk in Children Conceived via in Vitro Fertilization in the US

Importance: Children with birth defects have a greater risk of developing cancer, but this association has not yet been evaluated in children conceived with in vitro fertilization (IVF). Objective: To assess whether the association between birth defects and cancer is greater in children conceived via IVF compared with children conceived naturally. Design, Setting, and Participants: This cohort study of live births, birth defects, and cancer from Massachusetts, New York, North Carolina, and Texas included 1000639 children born to fertile women and 52776 children conceived via IVF (using autologous oocytes and fresh embryos) during 2004-2016 in Massachusetts and North Carolina, 2004-2015 in New York, and 2004-2013 in Texas. Children were followed up for an average of 5.7 years (6008985 total person-years of exposure). Data analysis was conducted from April 1 to August 31, 2020. Exposures: Conception by IVF for state residents who gave birth to liveborn singletons during the study period. Birth defect diagnoses recorded by statewide registries. Main Outcomes and Measures: Cancer diagnosis as recorded by state cancer registries. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs for birth defect-cancer associations separately in fertile and IVF groups. Results: A total of 1000639 children (51.3% boys; 69.7% White; and 38.3% born between 2009-2012) were in the fertile group and 52776 were in the IVF group (51.3% boys; 81.3% White; and 39.6% born between 2009-2012). Compared with children without birth defects, cancer risks were higher among children with a major birth defect in the fertile group (hazard ratio [HR], 3.15; 95% CI, 2.40-4.14) and IVF group (HR, 6.90; 95% CI, 3.73-12.74). The HR of cancer among children with a major nonchromosomal defect was 2.07 (95% CI, 1.47-2.91) among children in the fertile group and 4.04 (95% CI, 1.86-8.77) among children in the IVF group. The HR of cancer among children with a chromosomal defect was 15.45 (95% CI, 10.00-23.86) in the fertile group and 38.91 (95% CI, 15.56-97.33) in the IVF group. Conclusions and Relevance: This study found that among children with birth defects, those conceived via IVF were at greater risk of developing cancer compared with children conceived naturally

Synthesis and characterisation of organo-platinum(II) complexes of the N,O-donor ligands hippuric acid (N-benzoylglycine) and N-phenylanthranilic acid

Reaction of [PtCl₂(cod)] (cod = cyclo-octa-1,5-diene) with either hippuric acid [PhC(O)NHCH₂COOH] or N-phenylanthranilic acid (ortho-PhNHC₆H₄COOH) in refluxing dichloromethane in the presence of silver(I) oxide gave the new organoplatinum derivatives [Pt{N(COPh)CH₂COO}(cod)] and [Pt{N(Ph)C₆H₄COO}(cod)] respectively. Ligand substitution reactions of the cod ligand in [Pt{N(COPh)CH₂COO}(cod)] provided a facile route to a selection of phosphine-substituted analogues [Pt{N(COPh)CH₂COO}L₂] [L = phosphatriazaadamantane (pta), PPh3, or L₂ = Ph₂PCH₂CH₂PPh₂ or Fe(η⁵-C₅H₄PPh₂) ₂] via displacement of the labile cod ligand. The complexes were characterised using NMR spectroscopy, IR spectroscopy, and ESI mass spectrometry. The X-ray structure of [Pt{N(COPh)CH₂COO}(cod)] is also reported

The interaction between human spermatozoa and its homologous zona pellucida : scientific advances and clinical significance

Thesis (PhD)--Stellenbosch University, 2002.ENGLISH ABSTRACT: Infertility is a very common problem worldwide. Recent data have shown that disorders of the male represent the most common single defined cause of infertility. This proposal examines the clinical significance and fundamental physiological aspects of human gamete interaction. These studies are focused on the assessment of the cellular-molecular mechanisms involved in human sperm binding to its homologous zona pellucida resulting in the physiologic induction of the acrosome reaction. We have developed and validated in vitro bioassays that assess specific steps of the fertilization process that are critical for early embryo development. The results of our translational research have already had a significant impact on the overall evaluation of male infertility and on the clinical management of the infertile man in the assisted reproduction arena. Furthermore, the unveiling of the basic mechanisms involved in human gamete interaction will ultimately allow for both (i) the development of new male reproductive diagnostic capabilities and (ii) the design of improved and safer therapies aiding conception in childless couples suffering from male infertility.AFRIKAANSE OPSOMMING: Menslike onvrugbaarheid is 'n algemene wêreldwye probleem en onlangse data toon aan dat die manlike factor die grootste enkel bydraende factor tot hierdie toestand is. Die werk loods 'n intensiewe ondersoek na die kliniese betekenis en basiese fisiologiese aspekte wat 'n rol tydens spermsel en eisel interaksie speel. Hoofstuk 3 fokus op die sellulêre en molekulêre meganismes wat betrokke is tydens spermsel en eisel binding wat gevolglik lei tot akrosoomreaksie van die spermsel. Die werk verteenwoordig die resultate van 10 jaar se navorsing tussen die kandidaat en die promoter. Dit gee oorsprong aan 'n reeks bio-toetse wat die bevrugtingsproses koriografiese ontleed en verskaf dus 'n stap-vir-stap uiteenseting van menslike bevrugting en gevolglike embrio ontwikkeling. Die resultate in Hoostuk 4 bring vernuwing in die begrippe van die manlike faktor en die rol in die kinderlose huwelik. Die resulate soos in Hoofstuk 3 en 4 uiteengesit, vorm nie net die basis vir die moontlike ontwikkeling van nuwe diagnostiese benaderings tot die hantering van die man nies maar speel oojk 'n rol die daarstelling van verbeterde terapeutiese hantering van die kinderlose egpaar. Hoofstuk 5 gee kortliks riglyne en aanbevelings tot opsigte van die gebruik van die spermsel-zona pellucida bindingstoets en akrosomreaksie. Die kandidaat bevel aan dat die genoemde twee bio-toetse deel van die laboratorium ondersoeke van die man gebruik moet word