Obstetric and neonatal outcomes after natural versus artificial cycle frozen embryo transfer and the role of luteal phase support: a systematic review and meta-analysis.

BACKGROUND: The number of frozen embryo transfers (FET) has increased dramatically over the past decade. Based on current evidence, there is no difference in pregnancy rates when natural cycle FET (NC-FET) is compared to artificial cycle FET (AC-FET) in subfertile women. However, NC-FET seems to be associated with lower risk of adverse obstetric and neonatal outcomes compared with AC-FET cycles. Currently, there is no consensus about whether NC-FET needs to be combined with luteal phase support (LPS) or not. The question of how to prepare the endometrium for FET has now gained even more importance and taken the dimension of safety into account as it should not simply be reduced to the basic question of effectiveness. OBJECTIVE AND RATIONALE: The objective of this project was to determine whether NC-FET, with or without LPS, decreases the risk of adverse obstetric and neonatal outcomes compared with AC-FET. SEARCH METHODS: A systematic review and meta-analysis was carried out. A literature search was performed using the following databases: CINAHL, EMBASE, and MEDLINE from inception to 10 October 2022. Observational studies, including cohort studies, and registries comparing obstetric and neonatal outcomes between singleton pregnancies after NC-FET and those after AC-FET were sought. Risk of bias was assessed using the ROBINS-I tool. The quality of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. We calculated pooled odds ratios (ORs), pooled risk differences (RDs), pooled adjusted ORs, and prevalence estimates with 95% CI using a random effect model, while heterogeneity was assessed by the I2. OUTCOMES: The conducted search identified 2436 studies, 890 duplicates were removed and 1546 studies were screened. Thirty studies (NC-FET n = 56 445; AC-FET n = 57 231) were included, 19 of which used LPS in NC-FET. Birthweight was lower following NC-FET versus AC-FET (mean difference 26.35 g; 95% CI 11.61-41.08, I2 = 63%). Furthermore NC-FET compared to AC-FET resulted in a lower risk of large for gestational age (OR 0.88, 95% 0.83-0.94, I2 = 54%), macrosomia (OR 0.81; 95% CI 0.71-0.93, I2 = 68%), low birthweight (OR 0.81, 95% CI 0.77-0.85, I2 = 41%), early pregnancy loss (OR 0.73; 95% CI 0.61-0.86, I2 = 70%), preterm birth (OR 0.80; 95% CI 0.75-0.85, I2 = 20%), very preterm birth (OR 0.66, 95% CI 0.53-0.84, I2 = 0%), hypertensive disorders of pregnancy (OR 0.60, 95% CI 0.50-0.65, I2 = 61%), pre-eclampsia (OR 0.50; 95% CI 0.42-0.60, I2 = 44%), placenta previa (OR 0.84, 95% CI 0.73-0.97, I2 = 0%), and postpartum hemorrhage (OR 0.43; 95% CI 0.38-0.48, I2 = 53%). Stratified analyses on LPS use in NC-FET suggested that, compared to AC-FET, NC-FET with LPS decreased preterm birth risk, while NC-FET without LPS did not (OR 0.75, 95% CI 0.70-0.81). LPS use did not modify the other outcomes. Heterogeneity varied from low to high, while quality of the evidence was very low to moderate. WIDER IMPLICATIONS: This study confirms that NC-FET decreases the risk of adverse obstetric and neonatal outcomes compared with AC-FET. We estimate that for each adverse outcome, use of NC-FET may prevent 4 to 22 cases per 1000 women. Consequently, NC-FET should be the preferred treatment in women with ovulatory cycles undergoing FET. Based on very low quality of evidence, the risk of preterm birth be decreased when LPS is used in NC-FET compared to AC-FET. However, because of many uncertainties-the major being the debate about efficacy of the use of LPS-future research is needed on efficacy and safety of LPS and no recommendation can be made about the use of LPS.

The Interaction of Female Age and Active Male Smoking has Negative Influence on Success Rates of the in Vitro Fertilization Treatments.

This study monitors the effect of male smoking and age of the woman on the success of the intracytoplasmic sperm injection (ICSI) fertilization process as part of the assisted reproduction technique (ART). A total of 703 couples in the in vitro fertilization (IVF) program were included. Binary logistic regression analysis was used to study the effect of male smoking on clinical pregnancy rate and live birth rate. The results from the study showed that interaction of male smoking and women's age (>35 years) have significant negative impact on ongoing pregnancy rate and live birth rate.

Erythropoietin reduces cumulative nephrotoxicity from cisplatin and enhances renal tubular cell proliferation.

Cisplatin, a heavy metal complex, is one of the most active drugs used in the treatment of several human malignancies. However, high-dose therapy with cisplatin is limited by its cumulative nephrotoxicity. The main objectives of this study were to determine the role of recombinant human erythropoietin (Epoetin alfa) in the prevention of nephrotoxicity induced experimentally in Wistar rats by long-term administration of cisplatin (2 mg/kg/b.w./week) over eight weeks, and an evaluation of its effect on renal tubular cell proliferation. The animals were randomly assigned into three groups, each including 25 rats. Group 1 (CP) received only cisplatin (2 mg/kg/b.w./week), group 2 (CP+EPO) received cisplatin (2 mg/kg/b.w./week) and epoetin alfa (150 IE/kg/b.w./three times a week), and group 3 (control group) received only saline. During the study, the following tests for the assessment of the renal function and renal damages were performed: determination of concentration of serum creatinine and BUN and determination of total protein quantity in 24-hour urine samples. At the end of the study, the abdomen was opened and both kidneys of the rats were removed and sent for histological and morphometric analysis. Ki-67 was used as a tool to determine a proliferative index. The results obtained have shown that epoetin alfa significantly reduced the functional renal failures and renal damages, and increased toleration of high doses of cisplatin. At the same time, our results with regard to tubular proliferative index have confirmed that one of the possible mechanisms by which erythropoietin accomplishes its renoprotective effect is stimulation of tubular cell proliferation and regeneration.

Association of three isoforms of the meiotic BOULE gene with spermatogenic failure in infertile men.

The complex process of spermatogenesis requires the expression and precise coordination of a multitude of genes. Abnormal function of such genes is frequently associated with male infertility. Among these candidates is the human BOULE gene that is a possible fundamental mediator of meiotic transition. In this study, we describe for the first time the existence of three BOULE transcript variants (B1, B2 and B3). We investigated their tissue specificity and mRNA transcript levels in 23 testis biopsies from infertile men. B1, B2 and B3 differed solely in their N-terminal sequences, which are encoded by three alternatively spliced exons 1. In humans, all three isoforms are exclusively expressed in the testes in a relative proportion of 80:220:1 for B1, B2 and B3, respectively. RT-PCR quantification revealed significantly reduced mRNA expression of all three variants in testicular biopsies with meiotic arrest (MA) compared with those with qualitatively complete spermatogenesis. Alteration of the B1/B2 and B1/B3 transcript ratios was correlated with reduced meiotic capacity of spermatocytes to produce round spermatids as assessed by flow cytometry. Furthermore, BOULE mRNA reduction in biopsies with MA paralleled the absence of BOULE protein as analysed by immunohistochemistry. In conclusion, the relative proportions of B1, B2 and B3 may serve as predictive markers for meiotic efficiency and thus the probability of finding haploid cells in the human testis. Among the three isoforms, B2 might have the major role for meiotic completion.

The changes of ACTH, cortisol, testosterone and testosterone/cortisol ratio in professional soccer players during a competition half-season.

BACKGROUND: The following up of some hormonal parameters during the professional soccer training process could be one of the indicators of the training effects. On the other hand, overreaching and overtraining as an opposite adaptation of supercompensation could be detected by following up some hormonal changes. OBJECTIVES: The aim of this study is to evaluate the changes in some hormonal parameters in professional soccer players during a half-season competition. METHODS: We included 30 professional soccer players from a soccer club of our National Soccer League in this study. All sport medical examinations were conducted tree times: before the preparation phase, before the competition phase (after previous phase) and after finishing the competition phase. RESULTS: There were significant differences in all evaluated hormones between three phases of soccer training process, including significant decrease in T/C of more than 30% at the end of the competition phase (phase III). The decrease in muscle mass after the preparation phase and the increase in fat mass at the end of competition phase were insignificant. CONCLUSIONS: The hormonal changes indicated that some indices could indicate overreaching and overtraining at the end of professional soccer competition season. Although insignificant, the decrease in muscle mass after the preparation phase and the increase in fat mass at the end of competition phase were undesirable effects for us (Tab. 4, Fig. 2, Ref. 19).

Dual inhibition of angiotensin converting enzyme and neutral endopeptidase produces effective blood pressure control in spontaneously hypertensive rats.

BACKGROUND: The synergistic effects of the combined ACE and NEP inhibition is based both on the blockade of angiotensin II synthesis and degradation of vasoactive peptides and NEP substrates (ANP, arginine, endothelial cells, guanylat cyclase etc.), including bradykinine and the natriuretic peptides, which contribute to vasodilatation, diuresis and improvement of myocardial function. OBJECTIVES: This study was undertaken to asses the hypotensive effect of a dual ACE/NEP inhibitor (omapatrilat) in comparison to a NEP inhibitor (candoxatril) and ACE inhibitor (enalapril) in SHRS. METHODS: The study was performed in 130 male spontaneously hypertensive rats (SHRS) that were divided into 4 groups and treated orally by a gastric tube for 14 days according to the following dosage regimen: omapatrilat (40 mg/kg b.w./24 h); candoxatril (30 mg/kg b.w./24 h); enalapril (20 mg/kg b.w./ 24 h) and control (water). Systolic blood pressure values were determined at the beginning of the study by the tail-cuff pletysmographic method, at the 7th and 14th day of the treatment, as well as 14 days after the end of the drug administration. For evaluation of the effect of omapatrilat, candoxatril and enalapril on the investigated parameters (plasma atrial natriuretic peptide and serum ACE), 10 animals from the control group were sacrificed at the beginning of the study, and afterwards 10 animals from each group were also sacrificed on the 7th and 14th day of the treatment, as well as 14 days after the end of the drug administration (28th day). RESULTS: The dual ACE/NEP inhibitor, omapatrilat and the ACE inhibitor, enalapril lowered SBP more effectively than the NEP inhibitor, candoxatril at all time points of the experiment (p < 0.01). Omapatrilat was slightly more effective than the enalapril treatment. CONCLUSIONS: Two-week treatment with the dual ACE/NEP inhibitor omapatrilat caused a significant decrease of the SBP, inhibition of the serum ACE activity and increase of the plasma ANP values, and therefore it should be considered as a new potential therapeutic agent in blood pressure management (Tab. 3, Fig. 2, Ref. 20).

Case report: natural transmission of an AZFc Y-chromosomal microdeletion from father to his sons.

Y-chromosomal microdeletions, associated with oligozoospermia or azoospermia, are usually de novo deletions in the affected patients. We report here the rare case of an affected father who transmitted a Y-chromosomal microdeletion to at least two of his three sons naturally and who also fathered a daughter. The extent of the deletion, which was determined with new STS-primers and covers 3.5 Mb, was identical in the father and his azoospermic sons. To determine any possibly modifying influence of other genes involved in spermatogenesis, we analysed two polymorphisms of the DAZL gene, the autosomal homologue of the deleted DAZ gene. DAZL and DAZ might be functionally related to each other. However, we found identical polymorphisms in exon 2 and 3 of the DAZL gene, in both father and his sons, corresponding to the most prevalent genotype in fertile men. Thus, other genes or environmental factors must modify spermatogenesis in men with identical Y-chromosomal microdeletions.

Effect of angiotensin II type 1 (AT1) receptor antagonist on the endothelial dysfunction in spontaneously hypertensive rats in correlation with the nitric oxide system.

BACKGROUND: Hypertension is associated with impaired endothelial function, which can be explained by a decrease in nitric oxide (NO) generation or by an enhanced inactivation of NO after its release from endothelial cells. OBJECTIVES: The aim of this study was to investigate the effect of long-term treatment with losartan, an angiotensin II (AT1) receptor antagonist, on endothelial dysfunction in an animal model of hypertension in relation to the nitric oxide system. METHODS: Losartan was administered to 48 sixteen-week-old spontaneously hypertensive rats, in a dose of 10 mg/kg bw/daily in drinking water, for 12 weeks. Systolic blood pressure (SBP) was measured at the beginning, after 4, 8 and 12 weeks of treatment, by the tail-cuff plethysmographic method. At each mentioned time point, a group of 12 animals was sacrificed and blood was withdrawn from the abdominal aorta. Plasma samples were used for determination of total nitrate/nitirite levels, cyclic guanosine monophosphate (cGMP) and endothelin (ET) 1 levels. Statistical evaluation of the results was performed by the use of a computer statistical programme Statistica for Windows 5.0. RESULTS: Losartan produced a significant decrease of SBP at all time points. On the other hand, long-term treatment with this AT1 receptor antagonist produced a significant increase of nitrate/nitrite and cGMP plasma levels. When we compared the values of SBP with plasma nitrate/nitrite as well as with cGMP values, a statistically significant correlation was established. A statistically significant decrease in plasma endothelin 1 values was found during the whole study period. Also, a positive correlation between SBP and plasma endothelin 1 concentrations was observed. CONCLUSIONS: Long-term losartan (AT1 receptor antagonist) treatment, apart from its blood pressure lowering effect in hypertension, has beneficial effects on the endothelial dysfunction which is at least partially due to the activation of the nitric oxide system. (Tab. 1, Fig. 2, Ref. 33.)

Ancient evidence for the origin and early development of chronobiology and biometeorology in Bulgaria.

Chronobiology and biometeorology have developed since ancient times of world history (China, Greece, etc.). Different authors have studied the origin and early development of medicine and related sciences in Bulgaria (Apostolov et al 1982, Georgiev 1987, etc.). They have reported that early medical postulates have incorporated the notion of temporal patterns of health and disease and their dependence on the environment. However, these authors have neither emphasized the above relationships nor considered them possible origins of both chronobiology and biometeorology in Bulgaria. The aim was to present evidence for the possible origin and early development of chronobiological and biometeorological perceptions in ancient Bulgaria. Different sources from ancient Bulgarian history were searched and analyzed. Ancient sources from Bulgarian history, relevant to the aim of this study, were reviewed. The evidence on chronobiological and biometeorological understandings in ancient times was obtained from the "Protobulgarian Calendar", Preslav's Rosette, etc. Here, only the most important of Protobulgarian, Thracian and Slavonic sources were presented. It was concluded that chronobiology and biometeorology had also their origin and early development in ancient Bulgarian times.

Importance of interfacial water in permeabilization of ceramide bilayers.

The role of structured water at the membrane-aqueous interface in regulating the water permeability functions of the epidermal horny layer (Stratum corneum) is not clear at present. The subject of this review is the effect of perturbed interfacial water structure on the relative water permeability properties in shrinkage experiments of reconstituted vesicle suspensions of ceramides and cholesterol in the gel phase. Water structure was perturbed by a series of reagents known to affect the phase equilibrium of lipid assemblies. Multilamellar bilayers containing synthetic ceramides N-palmitoyl-D-L-dihydrosphingosine, and N-oleoyl-D-sphingosine were used as model membranes. The reagent binding to the ceramide membrane was determined by fluorescence measurements with 1-anilino, 8-naphtalene sulphonate (ANS). A dependence of number of binding sites for ANS on the type of reagent was found. The change of relative water permeability with concentration of reagents was studied. Analysis of these data reveals that the anomalous behaviour of relative water permeability with the concentration of reagents used is due to concentration-dependent structural transitions of the bound water at the membrane-aqueous interface. Different possibilities of interaction of the reagents with the interface are discussed. At the end, it is suggested that the interfacial water in multilamellar ceramide structures may also contribute to the water holding and permeability barrier functions of cell membrane complex within the stratum corneum.

Kinetics and role of alpha 1-acid glycoprotein-dependent osmotic transport of water and ions in palmitoyl-L-oleoyl phosphatidylcholine liposomes.

alpha 1-Acid glycoprotein isolated from human blood plasma is known to influence cell permeability, although the mechanisms of this process are unclear. Here, the glycoprotein effects on the permeability of osmotically stressed phospholipid liposomes are studied as a model of membrane permeability. Liposomes containing glycoprotein were found to be osmotically sensitive to water and chloride salts of some monovalent (Na+, K+) and bivalent (Mg2+, Ca2+) ions. The permeations of these substances were determined by light-scattering measurements of the volume changes in liposomes after mixing with hyperosmotic solutions of chloride salts. The time courses of scattered light were recorded by means of stopped-flow spectrophotometry. Two processes were studied: the fast water outflow from liposomes and slower ion permeations through the lipid membrane. The second order permeation rate constants were determined at different glycoprotein concentrations for both processes. Values from 66 to 250 x 10(3) for water outflow and 2-500 M-1 sec-1 for the different ion permeations were obtained in order to characterize the permeations of solutes across the lipid membrane. The apparent activation energies also were calculated between 18 and 33 degrees C. The mercurial sulphydryl reagent pCMBS inhibited the ion permeations in the slow phase. When pCMBS was present in this phase, higher activation energies were obtained, indicating more difficult permeations. An interpretation of these results is that membrane permeability is mediated by aqueous pores. Membrane selectivity to monovalent metal ions also was demonstrated, but no correlation was observed between the ion radius of the corresponding metal cation and permeation rate constants. The discovery of non-specific pores in liposomes containing glycoprotein shows that they can serve as vehicles for the water and ions in the processes of passive transport through lipid membranes.

[Systemic immunity of experimental animals immunized with cholera vaccines]. / Sostoianie sistemnogo immuniteta u éksperimental'nykh zhivotnykh pri immunizatsii kholernymi vaktsinami.

The levels of antitoxic and vibriocidal antibodies in the sera of suckling rabbits after their parenteral immunization with cholera vaccine, cholera toxoid and a combination of cholera vaccine and toxoid were examined. Cholera vaccine induces intensive production of vibriocidal antibodies, and cholera toxoid, of antitoxic antibodies. The parenteral administration of the serum of rabbits immunized with cholera toxoid neutralized the action of cholera toxin in the small intestine of suckling rabbits. The complex preparation combines the properties of the corpuscular vaccine and the toxoid, inducing the production of both vibriocidal and antitoxic antibodies.

[Experimental research on cholera vaccines. Local immunity]. / Eksperimental'nye issledovaniia kholernykh vaktsin. Mestnyi immunitet.

Parenteral immunization of rabbits with cholera vaccine decreased the number of Vibrio cholerae adhering to the mucous membrane of the small intestine. Cholera toxoid and the complex preparation ensure protection from the local action of cholera toxin on the ligated loop of the rabbit intestine, while cholera vaccine produces no effect under the same conditions. The use of three preparations under study leads to the decrease of exudative reaction to the introduction of live V. cholerae, the effectiveness of these vaccines growing in the following order: cholera vaccine, cholera toxoid, the complex preparation.

[Effect of halothane (narcothane) on intrauterine fetal development]. / Vliianie na khalotan (narkotan) vurkhu intrauterinnoto razvitie na ploda.

The authors examined the effect of chalotane (narcotann ne-Spofa) on the development of a rat fetus. The rats were divided into groups and were narcotised for a period of 4 hours as well as 4.5 days. One of the group was narcotised from the 8 to the 13 day of gestation. Narcosis was made in chambers with dynamic inhalatory regimen at concentration of narcotane of 10 mg/m3 and 250 mg/m3. There was blastopathogenic effect of narcotane, manifested by an early resorption of nidaded ova, by nonspecific action on the fetus, which inhibited growth and development of the fetus and raised the mortality of the fetuses. The amount of estriol was diminished in mothers, treated with 250 mg/m3 of the drug.