Effects of atosiban on clinical outcome in frozen-thawed embryo transfer: a propensity score matching study.

PURPOSE: To evaluate the effects of atosiban on clinical outcomes in patients undergoing frozen-thawed embryo transfer. METHODS: The clinical data of 1093 infertile patients who underwent frozen-thawed embryo transfer in our center from January 2019 to December 2020 were retrospectively analyzed (control, 418; atosiban, 675). Propensity score matching (PSM) analysis identified 400 matched pairs of patients. The implantation rate, clinical pregnancy rate, live birth rate, biochemical pregnancy rate, abortion rate, multiple pregnancy rate, and ectopic pregnancy rate between the two groups were compared. RESULTS: Before PSM, patients differed by infertility factors, number of transferred embryos, and endometrial preparation protocol (P < 0.05). After PSM, characteristics were similar in corresponding patients of the atosiban and control groups. After propensity score matching, we found that there was no significant difference in the implantation rate, clinical pregnancy rate, live birth rate, biochemical pregnancy rate, abortion rate, multiple pregnancy rate, and ectopic pregnancy rate in atosiban and control group (P > 0.05). CONCLUSION: Atosiban did not improve the clinical outcomes of infertile patients with frozen-thawed embryo transfer.

Vasotocin but not isotocin is involved in the emergence of the dominant-subordinate status in males of the weakly electric fish, Gymnotus omarorum.

The establishment of the dominant-subordinate status implies a clear behavioral asymmetry between contenders that arises immediately after the resolution of the agonistic encounter and persists during the maintenance of stable dominance hierarchies. Changes in the activity of the brain social behavior network (SBN) are postulated to be responsible for the establishment and maintenance of the dominant-subordinate status. The hypothalamic nonapeptides of the vasopressin (AVP) and oxytocin (OT) families are known to modulate the activity of the SBN in a context-dependent manner across vertebrates, including status-dependent modulations. We searched for status-dependent asymmetries in AVP-like (vasotocin, AVT) and OT-like (isotocin, IT) cell number and activation immediately after the establishment of dominance in males of the weakly electric fish, Gymnotus omarorum, which displays the best understood example of non-breeding territorial aggression among teleosts. We used immunolabeling (FOS, AVT, and IT) of preoptic area (POA) neurons after dyadic agonistic encounters. This study is among the first to show in teleosts that AVT, but not IT, is involved in the establishment of the dominant-subordinate status. We also found status-dependent subregion-specific changes of AVT cell number and activation. These results confirm the involvement of AVT in the establishment of dominance and support the speculation that AVT is released from dominants' AVT neurons.

Male-specific vasotocin expression in the medaka tuberal hypothalamus: Androgen dependence and probable role in aggression.

Terrestrial vertebrates have a population of androgen-dependent vasotocin (VT)-expressing neurons in the extended amygdala that are more abundant in males and mediate male-typical social behaviors, including aggression. Teleosts lack these neurons but instead have novel male-specific VT-expressing neurons in the tuberal hypothalamus. Here we found in medaka that vt expression in these neurons is dependent on post-pubertal gonadal androgens and that androgens can act on these neurons to directly stimulate vt transcription via the androgen receptor subtype Ara. Furthermore, administration of exogenous VT induced aggression in females and alterations in the androgen milieu led to correlated changes in the levels of tuberal hypothalamic vt expression and aggression in both sexes. However, genetic ablation of vt failed to prevent androgen-induced aggression in females. Collectively, our results demonstrate a marked androgen dependence of male-specific vt expression in the teleost tuberal hypothalamus, although its relevance to male-typical aggression needs to be further validated.

Vasotocin receptor gene genotypes moderate the relationship between cortical thickness and sensory processing.

Sensory processing is the process by which the central nervous system gathers, interprets, and regulates sensory stimuli in response to environmental cues. However, our understanding of the genetic factors and neuroanatomical correlations that influence sensory processing is limited. The vasotocin system modulates sensory input responsiveness, making it a potential candidate for further investigation. Additionally, human neuroimaging studies have demonstrated that the ability to modulate sensory stimuli is related to neuroanatomical features such as cortical thickness. Therefore, this study aimed to examine the relationship between functional polymorphisms in vasotocin receptor (VTR) genes, sensory profiles, and neuroanatomical correlations. We used structural magnetic resonance imaging (MRI) and the Adolescent/Adult Sensory Profile (AASP) questionnaire in 98 healthy adult participants to assess sensory processing and identified seven single nucleotide polymorphisms. We found that A-allele carriers of rs1042615 in VTR had higher scores for "sensory sensitivity" and "sensation avoiding". Moreover, higher scores for three AASP subscales were associated with decreased cortical thickness in various regions, including the right precentral, paracentral, and fusiform gyri, as well as bilateral inferior temporal gyri. This study sheds light on the potential role of genetic variations in the VTR in modulating sensory processing and correlation with cortical thickness which has future implications for better understanding sensory abnormalities in neurodevelopmental disorders.

Urban and rural male song sparrows (Melospiza melodia) differ in territorial aggression and activation of vasotocin neurons in response to song challenge.

When living in urban habitats, 'urban adapter' species often show greater aggression toward conspecifics, yet we do not understand the mechanisms underlying this behavioral shift. The neuroendocrine system regulates socio-sexual behaviors including aggression and thus could mediate behavioral responses to urbanization. Indeed, urban male song sparrows (Melospiza melodia), which are more territorially aggressive, also have greater abundance of the neuropeptide arginine vasotocin (AVT) in nodes of the brain social behavior network. Higher abundance of AVT could reflect long-term synthesis that underlies baseline territoriality or short-term changes that regulate aggression in response to social challenge. To begin to resolve the timeframe over which the AVT system contributes to habitat differences in aggression we used immediate early gene co-expression as a measure of the activation of AVT neurons. We compared Fos induction in AVT-immunoreactive neurons of the bed nucleus of the stria terminalis (BSTm) and paraventricular nucleus of the hypothalamus (PVN) between urban and rural male song sparrows in response to a short (< 5 min.) or long (> 30 min.) song playback to simulate territorial intrusion by another male. We found that urban males had a higher proportion of Fos-positive AVT neurons in both brain regions compared to rural males, regardless of the duration of song playback. Our results suggest that AVT neurons remain activated in urban males, independently of the duration of social challenge. These findings that Fos induction in AVT neurons differs between rural and urban male song sparrows further implicate this system in regulating behavioral responses to urbanization.

Knock-out of vasotocin reduces reproductive success in female zebrafish, Danio rerio.

The vertebrate nonapeptide vasotocin/vasopressin is evolutionarily highly conserved and acts as neuromodulator and endocrine/paracrine signaling molecule. Circumstantial and mechanistic evidence from pharmacological manipulations of the vasotocin system in several teleost fishes suggest sex- and species-specific reproductive roles of vasotocin. While effects of vasotocin on teleost reproductive physiology involve both courtship behaviors and the regulation of the hypothalamic-pituitary-gonadal (HPG) axes, comprehensive studies investigating behavioral and physiological reproductive consequences of genetic ablation of vasotocin in a genetically tractable fish model, such as the zebrafish, are currently lacking. Here, we report the generation of homozygous CRISPR/Cas9-based vasotocin gene knock-out zebrafish. Breeding pairs of vasotocin knock-out fish produce significantly fewer fertilized eggs per clutch compared to wildtype fish, an effect coincident with reduced female quivering courtship behavior. Crossbreeding experiments reveal that this reproductive phenotype is entirely female-dependent, as vasotocin-deficient males reproduce normally when paired with female wild-type fish. Histological analyses of vasotocin knock-out ovaries revealed an overall reduction in oocytes and differential distribution of oocyte maturation stages, demonstrating that the reproductive phenotype is linked to oocyte maturation and release. Ovarian hormone quantification and gene expression analysis in mutant fish indicated reduced synthesis of Prostaglandin F2α, a hormone involved in ovarian maturation, egg release and regulation of female courtship behavior in some cyprinids. However, acute injection of vasotocin did not rescue the female mutant reproductive phenotype, suggesting a contribution of organizational effects of vasotocin. Together, this study provides further support for emerging roles of vasotocin in female teleost reproduction in an important teleost model species.

Vasotocin expression is associated with social preference development of the medaka fish.

The neurohypophysial peptide arginine vasotocin (VT) and its mammalian ortholog, arginine vasopressin, function in physiological and behavioral events. These functions have been identified in neuroendocrinological studies using adult animals; however, there is little information on whether VT is associated with social behavior development in fish. Here, we examined social preference in medaka fish of various ages and investigated how VT expression changes during development. The 1-, 2-, 4-, and 8-week post-hatching (wph) larvae, juveniles, and 5-month-old adults were individually introduced to the grouped fish of each age group, and the social preference index (SPI) was compared among ages based on the time spent in the interaction zone near the grouped fish in a test tank. The SPI was significantly higher in the 4-wph larvae, 8-wph juveniles, and adult fish than in the 1- and 2-wph larvae. VT expression increased with age from 1 to 4 wph. Similarly, the expression was high in 4-wph, 8-wph, and adult fish. Furthermore, it was also found that the SPI and the VT expression decreased in the socially isolated larva during the 4 weeks after hatching compared to the levels in the grouped 4-wph larvae. These findings suggest that social preference develops with age and that conspecifics are necessary for social development in medaka larvae. Furthermore, our results suggest that VT is associated with the development of social preferences in medaka.

A case of severe non-cardiogenic pulmonary edema in a woman treated with atosiban for preterm labor.

BACKGROUND: A 27-year-old primigravid woman with a triamniotic pregnancy presented with preterm labor at 29 weeks of gestation and acute severe pulmonary edema after treatment with atosiban. CASE REPORT: The severe symptoms and hypoxemia of the patient led to emergency hysterotomy and intensive care unit hospitalization. CONCLUSIONS: This clinical case prompted us to review the existing literature to examine studies on differential diagnoses in pregnant women with acute dyspnea. The possible pathophysiological mechanisms of this condition and the management of acute pulmonary edema are worth discussing.

Development of a chub mackerel with less-aggressive fry stage by genome editing of arginine vasotocin receptor V1a2.

Genome editing is a technology that can remarkably accelerate crop and animal breeding via artificial induction of desired traits with high accuracy. This study aimed to develop a chub mackerel variety with reduced aggression using an experimental system that enables efficient egg collection and genome editing. Sexual maturation and control of spawning season and time were technologically facilitated by controlling the photoperiod and water temperature of the rearing tank. In addition, appropriate low-temperature treatment conditions for delaying cleavage, shape of the glass capillary, and injection site were examined in detail in order to develop an efficient and robust microinjection system for the study. An arginine vasotocin receptor V1a2 (V1a2) knockout (KO) strain of chub mackerel was developed in order to reduce the frequency of cannibalistic behavior at the fry stage. Video data analysis using bioimage informatics quantified the frequency of aggressive behavior, indicating a significant 46% reduction (P = 0.0229) in the frequency of cannibalistic behavior than in wild type. Furthermore, in the V1a2 KO strain, the frequency of collisions with the wall and oxygen consumption also decreased. Overall, the manageable and calm phenotype reported here can potentially contribute to the development of a stable and sustainable marine product.

Catecholamines modulate differentially nonapeptide precursor mRNA expression in the preoptic area and ovary of the catfish Heteropneustes fossilis: An in vitro study.

In the catfish Heteropneustes fossilis, three nonapeptide hormone genes were identified in the brain preoptic area (POA) and ovary: a pro-vasotocin (pro-vt) and two isotocin gene paralogs viz., a novel pro-ita and conventional pro-itb. In the present study, the regulatory role of catecholamines [CA: dopamine (DA), noradrenaline (NA), adrenaline (AD)] on the expression of these genes were investigated in vitro. DA (1, 10, and 100 ng/mL) inhibited significantly the mRNA expression in both the POA and ovary. NA upregulated the POA mRNA expression in a biphasic manner, the lower concentrations (1 ng and 10 ng) scaled up and the higher concentration (100 ng) scaled down the expression of pro-vt and pro-itb, while only the 1 ng NA scaled up the pro-ita expression. In the ovary, NA upregulated the mRNA expressions at all concentrations; the pro-vt expression was stimulated only at 10 and 100 ng. AD stimulated pro-vt and pro-ita expression in the POA at all concentrations but the pro-itb expression was inhibited at 1 and 10 ng, and stimulated at 100 ng concentrations. In the ovary, AD elicited varied effects; no significant change in pro-vt, a stimulation of pro-ita, and an inhibition of pro-itb at 1 ng, and stimulation of pro-itb at the 10 and 100 ng. The incubation of the POA and ovary with α-methylparatyrosine (MPT, 250 µg/mL, a tyrosine hydroxylase inhibitor) for 8 h downregulated the mRNA expression in the POA but unaltered the expression in the ovary. Pre-incubation with MPT for 4 h, followed by co-incubation with DA, NA or AD for 4 h elicited varied effects. In the POA, the co-incubations with the CAs rescued the inhibition due to MPT. The MPT + DA and MPT + AD treatments reduced the magnitude of the inhibition of pro-vt and pro-itb by MPT. But the pro-ita expression was modestly stimulated in the MPT + AD group. On the other hand, the MPT + NA treatment rescued the MPT effect and elicited 10-folds increase in the expression levels. In the ovary, the changes were: an inhibition in the MPT + DA group, no significant alteration in the MPT + NA group, and a mild stimulation in the MPT + AD group. The results suggest that CAs modulate brain and ovarian nonapeptide gene expression differentially, which is important in the neuroendocrine/endocrine integration of reproduction in the catfish.

Localization of the Neuropeptide Arginine Vasotocin and Its Receptor in the Osmoregulatory Organs of Black Porgy, Acanthopagrus schlegelii: Gills, Kidneys, and Intestines.

The neurohypophysial hormone arginine vasotocin (avt) and its receptor (avtr) regulates ions in the osmoregulatory organs of euryhaline black porgy (Acanthopagrus schlegelii). The localization of avt and avtr transcripts in the osmoregulatory organs has yet to be demonstrated. Thus, in the present study, we performed an in situ hybridization analysis to determine the localization of avt and avtr in the gills, kidneys, and intestines of the black porgy. The avt and avtr transcripts were identified in the filament and lamellae region of the gills in the black porgy. However, the basal membrane of the filament contained more avt and avtr transcripts. Fluorescence double tagging analysis revealed that avt and avtr mRNAs were partially co-localized with α-Nka-ir cells in the gill filament. The proximal tubules, distal tubules, and collecting duct of the kidney all had positive hybridization signals for the avt and avtr transcripts. Unlike the α-Nka immunoreactive cells, the avt and avtr transcripts were found on the basolateral surface of the distal convoluted tubule and in the entire cells of the proximal convoluted tubules of the black porgy kidney. In the intestine, the avt and avtr transcripts were found in the basolateral membrane of the enterocytes. Collectively, this study provides a summary of evidence suggesting that the neuropeptides avt and avtr with α-Nka-ir cells may have functions in the gills, kidneys, and intestines via ionocytes.

Losing a parent in early-life impairs flock size discrimination and lowers oxytocin receptor abundance in a medial amygdala homologue of adult zebra finches.

Experiencing inadequate parental care during early-life diminishes adult social competencies. For example, low parental care impairs adult socio-cognitive abilities (e.g., recognizing familiar conspecifics) and affiliation (e.g., close social proximity); outcomes attributed to diminished medial amygdala nonapeptide functioning in rodents. Whether parental care has effects beyond familiarity, and if siblings have similar effects to parents, is unclear. Here, zebra finches were used to explore if parent and/or sibling number shape adult recognition and preference of small versus large flocks and nonapeptide (oxytocin, vasotocin) receptor expression in an avian homologue of the mammalian medial amygdala. Chicks were raised by single mothers or fathers in small broods or paired parents in small or large broods matched to single parents for chicks per nest or per parent, respectively. Pair-raised birds had preferred flock sizes as adults, but birds raised by single parents had equal preference for either size. Oxytocin receptor expression was lower in birds raised by single parents versus paired parents, but vasotocin receptor levels were unaffected. Such results highlight parents as formative antecedents of their offspring's social competencies related to group size preference and their nonapeptide mechanisms, outcomes that influence an animal's ability to live in social groups.

Reproductive roles of the vasopressin/oxytocin neuropeptide family in teleost fishes.

The vertebrate nonapeptide families arginine vasopressin (AVP) and oxytocin (OXT) are considered to have evolved from a single vasopressin-like peptide present in invertebrates and termed arginine vasotocin in early vertebrate evolution. Unprecedented genome sequence availability has more recently allowed new insight into the evolution of nonapeptides and especially their receptor families in the context of whole genome duplications. In bony fish, nonapeptide homologues of AVP termed arginine vasotocin (Avp) and an OXT family peptide (Oxt) originally termed isotocin have been characterized. While reproductive roles of both nonapeptide families have historically been studied in several vertebrates, their roles in teleost reproduction remain much less understood. Taking advantage of novel genome resources and associated technological advances such as genetic modifications in fish models, we here critically review the current state of knowledge regarding the roles of nonapeptide systems in teleost reproduction. We further discuss sources of plasticity of the conserved nonapeptide systems in the context of diverse reproductive phenotypes observed in teleost fishes. Given the dual roles of preoptic area (POA) synthesized Avp and Oxt as neuromodulators and endocrine/paracrine factors, we focus on known roles of both peptides on reproductive behaviour and the regulation of the hypothalamic-pituitary-gonadal axis. Emphasis is placed on the identification of a gonadal nonapeptide system that plays critical roles in both steroidogenesis and gamete maturation. We conclude by highlighting key research gaps including a call for translational studies linking new mechanistic understanding of nonapeptide regulated physiology in the context of aquaculture, conservation biology and ecotoxicology.

Effect of neonatal isolation on responses to subsequent exposure to isolation stress in young chickens.

The aim of the present study was to investigate effects of isolation at an early age on behavioral and physiological responses of chickens to an isolation challenge at two weeks of age. Birds were assigned to a control group or to one of three treatments where chicks were isolated for 5 min per day. The groups were 1) no isolation (control); 2) early isolation (EI; 2 to 4 days of age); 3) late isolation (LI; 5 to 7 days of age); or 4) full isolation (FI; 2 to 7 days of age). All groups of chicks were challenged with isolation for 5 min at two weeks of age, with distress vocalizations (DV), stepping and jumping behavior measured. Hypothalamic and blood samples were collected at the end of isolation challenges. There were no significant differences between groups in body weight gain at 2 weeks of age. Latency of jump was lower in the LI group compared with the control group, but DV and number of steps were not affected by isolation treatment during the neonatal period. There were no significant differences among groups in plasma glucose or FFA concentrations. Gene expression for hypothalamic corticotropin-releasing hormone, was lower in the EI than the control group, with no differences in expression between control and LI or control and FI groups. There were no significant differences among groups in the expression of arginine vasotocin, thyrotropin-releasing hormone, neuropeptide Y, proopiomelanocortin, and orexin genes. These results suggest that isolation in the first week of life may affect responses to isolation of chicks when they are older, and that there may be a critical period of several days for this effect to occur.

A randomized double blind comparison of atosiban in patients with recurrent implantation failure undergoing IVF treatment.

BACKGROUND: Patients with recurrent implantation failure (RIF) may have more uterine contractions. Several observational studies suggested that atosiban administration around embryo transfer resulted in higher pregnancy rates in RIF patients. This study aimed to evaluate the effect of atosiban given before fresh embryo transfer on pregnancy outcomes of women with RIF. METHODS: A prospective, randomized, double-blind controlled clinical trial was performed in IVF center of Shanghai First Maternity and Infant Hospital. According to a computer-generated randomization list, 194 infertile women with RIF received fresh embryo transfer between July 2017 and December 2019 were randomly allocated into the atosiban (n = 97) and the placebo (n = 97) groups. Women in the treatment group received atosiban intravenously about 30 min before embryo transfer with a bolus dose of 6.75 mg over one minute. Those in the placebo group received only normal saline infusion for the same duration. RESULTS: There was no significant difference in the live birth rate between the atosiban and placebo groups (42.3% vs 35.1%, P = 0.302, RR = 1.206 (0.844-1.723)). No significant differences were found between the two groups in the positive pregnancy test, clinical pregnancy, ongoing pregnancy, miscarriage, multiple pregnancy, ectopic pregnancy and implantation rates. Similar results were found when stratified by the number of embryos previously transferred, number of previous failed embryo transfers, frequency of endometrial peristalsis on embryo transfer day (≥ 3 waves/min) or serum estradiol (E2) on the day of hCG above the median level. And, there was no correlation between the serum E2 level on the day of hCG and the frequency of endometrial peristalsis on embryo transfer day. The frequency of endometrial peristalsis on embryo transfer day, total FSH/HMG dosage and duration were the significant factors which independently predicted the likelihood of a live birth. CONCLUSIONS: These results suggested that atosiban treatment before fresh embryo transfer might not improve the live birth rate in RIF patients. TRIAL REGISTRATION: The study had been approved by the Institutional Review Board of the hospital (2017 ethics No.43) and was registered under Clinicaltrials.gov with an identifier NCT02893722.

Vasopressin mediates nonapeptide and glucocorticoid signaling and social dynamics in juvenile dominance hierarchies of a highly social cichlid fish.

Early-life social experience can strongly affect adult behavior, yet the behavioral mechanisms underlying developmental trajectories are poorly understood. Here, we use the highly social cichlid, Burton's Mouthbrooder (Astatotilapia burtoni) to investigate juvenile social status and behavior, as well as the underlying neuroendocrine mechanisms. We placed juveniles in pairs or triads and found that they readily establish social status hierarchies, with some group structural variation depending on group size, as well as the relative body size of the group members. Next, we used intracerebroventricular injections to test the hypothesis that arginine vasopressin (AVP) regulates juvenile social behavior and status, similar to adult A. burtoni. While we found no direct behavioral effects of experimentally increasing (via vasotocin) or decreasing (via antagonist Manning Compound) AVP signaling, social interactions directed at the treated individual were significantly altered. This group-level effect of central AVP manipulation was also reflected in a significant shift in whole brain expression of genes involved in nonapeptide signaling (AVP, oxytocin, and oxytocin receptor) and the neuroendocrine stress axis (corticotropin-releasing factor (CRF), glucocorticoid receptors (GR) 1a and 1b). Further, social status was associated with the expression of genes involved in glucocorticoid signaling (GR1a, GR1b, GR2, mineralocorticoid receptor), social interactions with the dominant fish, and nonapeptide signaling activity (AVP, AVP receptor V1aR2, OTR). Together, our results considerably expand our understanding of the context-specific emergence of social dominance hierarchies in juveniles and demonstrate a role for nonapeptide and stress axis signaling in the regulation of social status and social group dynamics.

Identification of neurohypophysial hormones and the role of VT in the parturition of pregnant seahorses (Hippocampus erectus).

Neurohypophysial hormones regulate the reproductive behavior of teleosts; however, their role in the gestation and parturition of ovoviviparous fishes with male pregnancy (syngnathids) remains to be demonstrated. In the present study, the complementary DNA (cDNA) sequences of arginine vasotocin (VT) and isotocin (IT) from the lined seahorse (Hippocampus erectus) were cloned and identified. We observed that the mature core peptides of seahorse VT and IT were conserved among teleosts. In the phylogenic tree, seahorse VT and IT were clustered independently with teleost VT and IT. The tissue distribution patterns of VT and IT were similar, and both were highly expressed in the brain, gills, and gonads. Interestingly, they were also expressed to some extent in the brood pouch. In situ hybridization revealed that VT and IT messenger RNA (mRNA) signals in the brain were mainly located in the preoptic area region of the hypothalamus. Intraperitoneal administration of the VT core peptide to pregnant seahorses induced premature parturition, stimulated gonadotropin release, increased serum estrogen levels, and decreased prolactin secretion. Moreover, VT injection upregulated the mRNA expression of the membrane estrogen receptor in the brood pouch. In summary, neurohypophysial hormones promote premature parturition by regulating estrogen synthesis through the hypothalamus-pituitary-gonad axis.

Teleost Nonapeptides, Isotocin and Vasotocin Administration Released the Milt by Abdominal Massage in Male Catfish, Clarias magur.

In the present work the nonapeptides i.e., isotocin and vasotocin alone or in a combination were tested in C. magur to evaluate their effect on stripping by abdominal massage. Also, we used chitosan-carbon nanotube nanocomposites to conjugate the nonapetides isotocin (abbreviated as COOH-SWCNTCSPeP) and isotocin and vasotocin (COOH-SWCNTCSPePs) with the aim of sustaining the effect for a longer duration. The conjugation of nonapeptides with nanocomposites was confirmed by Fourier-transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM), Transmission electron microscopy (TEM), Thermogravimetric analysis (TGA) and X-ray photoelectron spectroscopy (XPS). Two experiments were conducted to study the effect of naked (without nanoparticles) and conjugated nonapeptides on the milt release by stripping. Both the experiments consisted of eight treatments which included four naked groups two nanoconjugated groups and two controls. Both naked and nonconjugated formulations were successful in stripping the male catfish. The mRNA expression of selected reproductive genes was analysed to decipher the effect of nanopeptides at the molecular level. Nonapeptide treatment either naked or nanoconjugated, resulted in the upregulation of the transcript level of genes. Histological analysis revealed the concentration of spermatozoa was more in peptide injected groups than in the controls. The synergistic effects of nonapeptides and Ovatide had a positive impact on GSI. Thus, the present formulations were successful in stripping the male catfish to obtain the milt with significant reproductive success. Even though the naked groups perform better but the number of males required to fertilize the eggs in nanoconjuagted groups was smaller making it worth using for the delivery of nonapeptides.

Tocolysis with nifedipine versus atosiban and perinatal outcome: an individual participant data meta-analysis.

BACKGROUND: Worldwide, nifedipine and atosiban are the two most commonly used tocolytic agents for the treatment of threatened preterm birth. The aim of this study was to evaluate the effectiveness of nifedipine and atosiban in an individual participant data meta-analysis (IPDMA). METHODS: We investigated the occurrence of adverse neonatal outcomes in women with threatened preterm birth by performing an IPDMA, and sought to identify possible subgroups in which one treatment may be preferred. We searched PubMed, Embase, and Cochrane for trials comparing nifedipine and atosiban for treatment of threatened preterm birth between 240/7 and 340/7 weeks' gestational age. Primary outcome was a composite of perinatal mortality and neonatal morbidities including respiratory distress syndrome, intraventricular haemorrhage, periventricular leucomalacia, necrotising enterocolitis, and sepsis. Secondary outcomes included NICU admission, prolongation of pregnancy and GA at delivery. For studies that did not have the original databases available, metadata was used. This led to a two-stage meta-analysis that combined individual participant data with aggregate metadata. RESULTS: We detected four studies (N = 791 women), of which two provided individual participant data (N = 650 women). The composite neonatal outcome occurred in 58/364 (16%) after nifedipine versus 69/359 (19%) after atosiban (OR 0.76, 95%CI 0.47-1.23). Perinatal death occurred in 14/392 (3.6%) after nifedipine versus 7/380 (1.8%) after atosiban (OR 2.0, 95%CI 0.80-5.1). Nifedipine results in longer prolongation of pregnancy, with a 18 days to delivery compared with 10 days for atosiban (HR 0.83 (96% CI 0.69-0.99)). NICU admission occurred less often after nifedipine (46%) than after atosiban (59%), (OR 0.32, 95%CI 0.14-0.75). The sensitivity analysis revealed no difference in prolongation of pregnancy for 48 hours (OR 1.0, 95% CI 0.73-1.4) or 7 days (OR 1.3, 95% CI 0.85-5.8) between nifedipine and atosiban. There was a non-significant higher neonatal mortality in the nifedipine-exposed group (OR 1.4, 95% CI 0.60-3.4). CONCLUSIONS: In this IPDMA, we found no differences in composite outcome between nifedipine and atosiban in the treatment of threatened preterm birth. However, the non-significant higher mortality after administering nifedipine warrants further investigation of the use of nifedipine as a tocolytic drug. STUDY REGISTRATION: We conducted this study according to a prospectively prepared protocol, registered with PROSPERO (the International Prospective Register of Systematic Reviews) under CRD42016024244.