P–362 The effect of nolasiban on uterine contractility at the time of embryo transfer in in vitro fertilisation patients

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
C Rees ◽  
Y Huang ◽  
M Akhtar ◽  
M Mischi ◽  
A Humberstone ◽  
...  

Abstract Study question What is the effect of nolasiban on the uterine contractility of in-vitro fertilisation (IVF) patients prior to embryo transfer (ET) ? Summary answer A single oral dose of nolasiban 900 mg administered 4 h before ET significantly decreased contraction frequency and increased coordination compared to placebo. What is known already Nolasiban is an investigational oral oxytocin receptor antagonist (OTRa) being developed to improve the chance of pregnancy following ET. Increased uterine contraction frequency can influence embryo implantation, and the coordination of these uterine contractions is equally important. OTRa have been shown to decrease uterine contractions and increase endometrial perfusion. Recently, an automated and quantitative measurement tool using transvaginal ultrasound (TVUS) to better characterise uterine contractility has been developed which can be used to quantify the effect of nolasiban on uterine contractility. Study design, size, duration This study is part of a completed multi-centre randomised placebo-controlled trial (IMPLANT 1 – NCT02310802) in IVF patients (n = 247) carried out in 2015. Our study retrospectively assessed a sub-set of patients with good quality TVUS recordings to evaluate their mechanical uterine motion that were randomised to receive either nolasiban 900mg (n = 39) or placebo (n = 42). Participants/materials, setting, methods Subjects were < 37 years, undergoing ET on Day 3 following IVF/ICSI and with evidence of uterine contractions 4 h before ET. Nolasiban was administered 4 h before ET. Patients underwent TVUS immediately before drug administration and again immediately before ET. Uterine contraction frequency, amplitude, power and coordination were measured by applying dedicated speckle tracking and strain analysis. The Shapiro–Wilk test, followed by the Wilcoxon rank-sum test were applied to compare features between treatment groups. Main results and the role of chance The mean (SD) frequency of uterine contractions was 1.54 (0.25) in the nolasiban group versus 1.57 (0.12) in the placebo group (p = 0.016). The mean (SD) coordination was 0.10 (0.17) in the nolasiban group versus 0.02 (0.16) in the placebo group (p = 0.034). The coordination feature was measured by assessing the presence of simultaneous movements of the anterior and posterior uterine walls, a higher value reflects increased coordination. There was no difference in contraction amplitude or power. Limitations, reasons for caution This was a retrospective analysis of TVUS videos. The small sample size limits the generalisability of the findings. Furthermore, our initial results do not show how the changes in uterine motion may affect pregnancy rate after ET, meaning that the clinical relevance of our results remains to be proven. Wider implications of the findings: Our results show that in patients taking one 900mg dose of nolasiban prior to ET, beneficial uterine contractions are seen, which could be promising for embryo implantation and pregnancy in IVF patients. Our quantitative TVUS measurement tool can be applied to different patient populations to accurately quantify uterine motion. Trial registration number NCT02310802

2012 ◽  
Vol 108 (12) ◽  
pp. 1192-1197 ◽  
Author(s):  
Shlomo Berliner ◽  
David Steinberg ◽  
David Zeltser ◽  
David Levran ◽  
Orit Shimron ◽  
...  

SummaryAssisted reproductive technology (ART) is extensively used as a tool for pregnancy achievement in subfertile couples. Congenital and acquired thrombophilias have been suggested by some investigators to play a role in abnormal embryo implantation and placentation. The objective of this study was to assess the role of common thrombophilias in women with unexplained infertility undergoing <i>in vitro</i>fertilisation (IVF). We retrospectively analysed 594 women from a large healthcare maintenance organisation going through IVF and who had a thrombophilia workup, and compared them for prevalence of thrombophilia to two reference groups consisting of 637 fertile women from previous work and 17,337 women members of the same healthcare organisation with no history of venous thromboembolism. The mean age of the women at the first cycle of IVF was 30.9 years (SD: 4.1).The mean number of IVF cycles was 7.3 (SD: 5.0), and the mean fertility success rate per woman was 14.6% (SD: 19.0%). None of the common thrombophilias tested was found to be significantly associated with the number of IVF cycles or with lower fertility success rate. Rather, women who had APCR and /or factor V Leiden and lupus anticoagulant had significantly higher live birth rates (12.3% and 12.6%, respectively) in comparison to women who were tested negative (9.0% and 9.7%, respectively). Thus, hypercoagulability is not associated with failure to achieve pregnancy. These data suggest that neither screening for thrombophilia nor anticoagulant treatment is indicated in cases with unexplained reproductive failure.


2010 ◽  
Vol 17 (01) ◽  
pp. 84-90
Author(s):  
FARZANA LATIF ◽  
BUSHRA BANO ◽  
UZMA HUSSAIN

Objective: To compare the efficacy of Glyecryl trinitrate patch for prolonging gestation for more than 48 hours, 7 days or upto 37 weeks of gestation with Salbutamol in preterm labour. Study Design: Compartive descriptive study. Setting: Fatima Memorial HospitalLahore. Period: Dec 2003 to Jan 2005. Patients & Methods: The study was carried out on 60 pregnant patients admitted in hospital with thesymptoms and signs of preterm labour. The results were statistically analyzed using SPSS version 8.0. Results: Two groups (TransdermalGlyceryl Trinitrate group and Salbutamol) comprising 30 patients each were made. In Glyceryl Trinitrate group, transdermal patch was appliedand in Salbutamol group,. Intravenous infusion titrated according to frequency, duration and intensity of uterine contractions. All the patientsin each group were evaluated for prolongation of gestation for 48 hours till 37th week of gestation. The mean prolongation of pregnancy was26 days in GTN group and 32 days in Salbutamol group. The decrease in frequency of uterine contractions by 67.51 ± 7.74% in first 48 hoursof applying transdermal Glyceryl Trinitrate patch and by 80.14 ± 8.43 % in Salbutamol group which was statistically significant. Conclusion:Trinitrate appears to be a safe, well tolerated and non-invasive but less effectives method of suppressing uterine contraction in preterm labouras compared to Salbutamol.


GYNECOLOGY ◽  
2021 ◽  
Vol 23 (4) ◽  
pp. 346-353
Author(s):  
Natalya I. Tapilskaya ◽  
Mikhail S. Nekrasov ◽  
Inna O. Krikheli ◽  
Ksenia V. Ob'edkova ◽  
Alexander M. Gzgzyan ◽  
...  

Aim. To study a stress-protective efficacy of micronized progesterone (MP) in pregnant women with anxiety disorders after in vitro fertilisation (IVF). Materials and methods. We conducted a prospective, comparative open-label randomized trial in two IVF-clinics. A total of 98 pregnant women after IVF with anxiety disorders were recruited at the 9th week of pregnancy. Progesterone supplementation after IVF for luteal phase support was administered out until 9 weeks gestation. Then, after randomization, group 1 (n=35) received 400 mg per day of MP vaginally, group 2 (n=33) received 400 mg of MP orally, group 3 (n=30) was comparative for the other groups. The duration of progesterone treatment was 12 weeks. The Spielberger State Trait Anxiety Inventory (STAI), the Montgomerysberg depression rating scale (MADRS), Hospital Anxiety and Depression Scale (HADS), and the Epworth Sleepiness Questionnaires (ESQ) were used to compare maternal mood at 9 weeks (day of randomization) after delivery and at 283, 565, 847 days after randomization. Results. The mean STAI sumscore in MP-groups was significantly lower than in group 3 starting from day 565 and continued until the end of the study. There were no significant differences between vaginal and oral administration of progesterone. There were no significant differences between the mean sumscores when questioning on the HADS, MADRS and ESQ. Conclusion. Prolonged use of MP in pregnant women with anxiety disorders led to the prevention of manifestations of an increase in anxiety and depression. The stress-protective and neuromodulating properties of MP can determine additional indications for its prolonged administration in women with anxiety disorders and/or premorbid history.


2018 ◽  
Vol 29 (6) ◽  
pp. 593-598 ◽  
Author(s):  
Hemlata Gupta ◽  
Shripad B. Deshpande

Abstract Background: Bisphenol A (BPA), a chemical used in the manufacture of plastics, has toxic effects on various systems of the human body including the reproductive system. BPA possesses estrogenic activity and is implicated in altering oogenesis, ovulation, and fertility. In addition to ovulatory changes, uterine contractility is an important factor for fertility. However, the effects of BPA on myometrial contractions are not known. Therefore, we examined the effect of BPA on rat uterine contractions. Methods: The uterus was isolated from adult rats showing estrous phase, and spontaneous in vitro contractions were recorded (35±1 °C). The effect of cumulative concentrations of BPA was determined. Further, the involvement of nitric oxide (NO) and guanylyl cyclase (GC) for the BPA-induced changes on uterine contractility was evaluated using the NO synthase inhibitor (L-NAME) or GC inhibitor (methylene blue). Results: BPA decreased the amplitude and frequency of spontaneous uterine contractions in a concentration-dependent manner. A decrease of 50% occurred at 1 and 3 μM for amplitude and frequency, respectively. L-NAME (N-ω-nitro-l-arginine methyl ester) blocked the BPA-induced decrease in amplitude at all concentrations but antagonized the frequency only at the maximum concentration (10 μM). Methylene blue (a GC inhibitor) did not block the BPA-induced responses but for the frequency at 10 μM of BPA. Conclusions: The results indicate that BPA decreased the amplitude and frequency of spontaneous uterine contractions by involving the nitrergic mechanism; however, the GC mechanism is not involved in the depression.


2019 ◽  
Vol 09 (02) ◽  
pp. e177-e184
Author(s):  
Annemaria De Tina ◽  
Jeremy Juang ◽  
Thomas F. McElrath ◽  
Jack D. Baty ◽  
Arvind Palanisamy

Objective To investigate differences in oxytocin (OXT) biodistribution between nonobese and obese parturients during labor. Study Design Patients with body mass index (BMI) of either ≥ 18 ≤ 24.9 kg/m2 (“nonobese”) or ≥ 30 kg/m2 (“obese”) undergoing elective induction of labor were included (N = 25 each). Blood samples were collected at baseline (T0), and 20 minutes after maximal OXT augmentation or adequate uterine contractions (T1) for OXT and oxytocinase assays. A mixed-model repeated-measures analysis of variance was used to test for group versus time interaction and analysis of covariance to detect a difference in OXT level at T1. Data presented as mean ± standard deviation or median (interquartile range), with p < 0.05 considered significant. Results The mean BMIs (kg/m2) were 22.1 ± 1.6 and 35.9 ± 5.1 in the nonobese and obese groups, respectively. No differences were observed in either the duration of OXT infusion, total dose of OXT, or plasma OXT (pg/mL) either at T0 or T1. However, plasma oxytocinase (ng/mL) was significantly lower at T0 (1.41 [0.67, 3.51] vs. 0.40 [0.29, 1.12]; p = 0.03) in the obese group. Conclusion We provide preliminary evidence that the disposition of OXT may not be different between obese and nonobese women during labor.


2010 ◽  
Vol 88 (9) ◽  
pp. 880-887
Author(s):  
Enitome Evi Bafor ◽  
Lucky Osaro Okunrobo

This study investigated the effect on the uterus of the aqueous fraction of the partitioned methanol crude extract of the leaves of Anthocleista djalonensis (AD) and the possible mechanism of AD activity. AD inhibited the concentration–response curves induced by oxytocin and CaCl2 on the rat uterus in vitro and significantly reduced the EC50 in a concentration-dependent manner (p < 0.05). A similar effect was observed with salbutamol and verapamil on the concentration–response curves obtained for oxytocin and CaCl2. The inhibitory effect of AD was not attenuated in the presence of propranolol. AD, salbutamol, and verapamil also produced a concentration-dependent relaxation on K+-induced sustained uterine contraction. In Ca2+-free medium, AD and salbutamol similarly inhibited oxytocin-induced contraction, but verapamil failed to produce this effect. The present results suggest that AD, being a mixture of phytochemicals, probably exerts inhibitory activity on in vitro uterine contractions of the nonpregnant, diethylstilboestrol-treated rat by multiple mechanisms that do not involve interaction with β-adrenergic receptors and do not solely depend on inhibition of calcium influx.


2013 ◽  
Vol 31 (2) ◽  
pp. 157-161 ◽  
Author(s):  
Daniela Isoyama Manca di Villahermosa ◽  
Lara Guercio dos Santos ◽  
Mariana Balthazar Nogueira ◽  
Fabia Lima Vilarino ◽  
Caio Parente Barbosa

Objective To evaluate the effectiveness of acupuncture and moxibustion as an adjuvant treatment in women undergoing in vitro fertilisation (IVF) when embryo implantation has failed. Methods A prospective, randomised controlled clinical trial was conducted with 84 infertile patients who had had at least two unsuccessful attempts of IVF. The patients were randomised in three groups: control (n=28), sham (n=28) and acupuncture (n=28). The sample size was calculated by assuming a pregnancy rate of 10% when embryo implantation had failed. The pregnancy rates of the current IVF cycle were evaluated by measurement of blood β human chorionic gonadotrophin (βhCG) and subsequent transvaginal ultrasound. Acupuncture was performed on the first and seventh day of ovulation induction, on the day before ovarian puncture and on the day after embryo transfer. In the acupuncture group, patients were treated with moxibustion at nine acupuncture points (BL18, BL22, BL23, BL52, CV3, CV4, CV5, CV7, GV4) and needling at 12 points. In the sham group needles were inserted in eight areas that did not correspond to known acupuncture points. Results The clinical pregnancy rate in the acupuncture group was significantly higher than that in the control and sham groups (35.7% vs 7.1% vs 10.7%; p=0.0169). Conclusions In this study, acupuncture and moxibustion increased pregnancy rates when used as an adjuvant treatment in women undergoing IVF, when embryo implantation had failed.


Reproduction ◽  
2002 ◽  
pp. 429-434 ◽  
Author(s):  
C Veitch ◽  
L Brown ◽  
C Sernia ◽  
RT Gemmell

Maturation of the fetal pituitary and adrenal glands allows the secretion of cortisol, which in turn leads to an increase in prostaglandin and mesotocin production. The production of prostaglandin and mesotocin results in an increase in uterine contractions and initiates birth in marsupials. The major metabolite of PGF(2alpha), 13,14-dihydro-15-keto-prostaglandin F(2alpha) (PGFM), has been found in the plasma of the possum at the time of birth and administration of PGF(2alpha) to female possums induced the adoption of the birth position. Evidence that mesotocin is an integral hormone of birth in the tammar wallaby indicates that both PGF(2alpha) and mesotocin or oxytocin are required for marsupial birth. The presence of PGF(2alpha) receptors in the uterus and corpus luteum of the possum, and the in vitro uterine responsiveness to PGF(2alpha) or oxytocin, were examined. PGF(2alpha) receptors were not observed in possum uteri and the inability of PGF(2alpha) to cause contractions indicates that PGF(2alpha) is not involved directly in contraction of the uterus at parturition. The presence of oxytocin and mesotocin receptors in the uterus of possoms and the ability of oxytocin to induce uterine contraction in vitro supports the view that mesotocin is required for expulsion of the young from the uterus. Low numbers of PGF(2alpha) receptors were found in the possum corpus luteum at birth, indicating an involvement of PGF(2alpha) in regression of the corpus luteum.


Medicina ◽  
2021 ◽  
Vol 57 (11) ◽  
pp. 1251
Author(s):  
Rafał Adamczak ◽  
Natalia Ukleja-Sokołowska ◽  
Kinga Lis ◽  
Mariusz Dubiel

A balance within the immune system is necessary for the proper development of ovarian follicles. Numerous cytokines were detected in follicular fluid, the role of which in reproductive physiology seems crucial. They influence the development and maturation of the follicle, ovulation, and corpus luteum formation, as well as embryo implantation and maintenance of pregnancy. The analysis of follicular fluid requires its collection by puncturing of the ovary, which is usually executed in connection with various gynaecological procedures. When interpreting such test results, clinical indications for a given procedure and the method of patient preparation should be taken into account. This review revealed the results of currently available studies on the concentration of pro-inflammatory cytokines in follicular fluid in various forms of infertility. Additionally, it presented cytokines, whose concentration has a significant impact on the size of ovarian follicles, their number, the effectiveness of in vitro fertilisation, development of the embryo, and chances of correct implantation. Despite the many recent publications, the knowledge of follicular fluid immunology in the context of reproductive pathology is superficial and further research is required to extensively understand the roles of individual cytokines in reproductive pathology. In the future, this knowledge may enable patients’ individual qualifications to individual methods of infertility treatment, as well as the possible adjustment of the treatment regimen to the patient’s immune profile.


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