Superovulation with the gonadotropin-releasing hormone agonist (GnRHa) trigger impaired embryo implantation in mice (RNA-Seq)
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PROVIDER: PRJEB70705 | ENA |
REPOSITORIES: ENA
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Project description:IntroductionSuperovulation is a critical step in assisted reproductive technology, but the use of human chorionic gonadotropin (hCG) as a trigger for superovulation can result in ovarian hyperstimulation. Thus, the use of Gonadotropin-releasing hormone agonist (GnRHa) trigger has been increasingly adopted, although it has been associated with a higher rate of pregnancy failure compared to natural cycles. This study aimed to investigate the effect of GnRHa trigger on embryo implantation in a mouse model.MethodsMice in the superovulation (PG) group were administered 7.5 IU of PMSG, followed by the injection of 3.5 μg of GnRHa (Leuprorelin) 48 h later, while mice in the control group (CTR) mated naturally. We compared the number of oocytes, blastocysts, and corpus luteum between the two groups and the implantation sites after the transfer of natural blastocysts. Ovaries, uterus, and serum 2 and 4 days after mating were collected for qRT-PCR, transcriptome sequencing, and hormone assays.ResultsThe PG group had more oocytes, blastocysts, and corpus luteum after superovulation than the CTR group. However, the mRNA expression of leukemia inhibitory factor (Lif) and the number of implantation sites were reduced in the PG group. The ELISA assay revealed that superovulation increased ovarian estrogen secretion. The transcriptome analysis showed that superphysiological estrogen led to a response of the uterus to a high estrogen signal, resulting in abnormal endometrium and extracellular matrix remodeling and up-regulation of ion transport and inflammation-related genes.ConclusionOur findings suggest that a combination of PMSG and GnRHa trigger impaired embryo implantation in mice, as the excessive uterine response to superphysiological estrogen levels can lead to the change of gene expression related to endometrial remodeling, abnormal expression of uterine ion transport genes and excessive immune-related genes.
| S-EPMC10925639 | biostudies-literature
Project description:ObjectiveTo compare the effect of P on live birth rate between hCG and GnRH agonist (GnRH-a) trigger cycles.DesignRetrospective cohort study.SettingLarge private assisted reproductive technology (ART) practice.Patient(s)A total of 3,326 fresh autologous ART cycles.Intervention(s)None.Main outcome measure(s)Live birth.Result(s)A total of 647 GnRH-a trigger cycles were compared with 2,679 hCG trigger cycles. Live birth was negatively associated with P in both the hCG trigger (odds ratio [OR] 0.62, 95% confidence interval [CI] 0.52-0.76) and the agonist trigger cohorts (OR 0.56, 95% CI 0.45-0.69). Interaction testing evaluating P and trigger medication was not significant, indicating that P had a similar negative effect on live birth rates in both cohorts. Progesterone ≥2 ng/mL occurred more commonly in GnRH-a trigger cycles compared with hCG trigger cycles (5.5% vs. 3.1%) and was negatively associated with live birth in both the hCG trigger (OR 0.28, 95% CI 0.11-0.73) and agonist trigger cohorts (OR 0.35, 95% CI 0.14-0.90). When P ≥2 ng/mL, the live birth rates were poor and similar in the hCG and GnRH-a cohorts (5.9% vs. 14.2%), indicating that P ≥2 ng/mL had a similar negative effect on live birth in both cohorts.Conclusion(s)Elevated serum P on the day of hCG was negatively associated with live birth rates in both hCG and GnRH-a trigger cycles.
| S-EPMC6499926 | biostudies-literature
Project description:This prospective study aimed to test the ability of follicular GnRH agonist challenge test (FACT) to predict suboptimal response to GnRH agonist trigger, assessed by LH levels post ovulation trigger in non-medical oocyte cryopreservation program. The study included 91 women that underwent non-medical fertility preservation. On day two to menstrual cycle, blood tests were drawn (basal Estradiol, basal FSH, basal LH, Progesterone) and ultrasound (US) was performed. On that evening, the women were instructed to inject 0.2 mg GnRH agonist (FACT) and arrive for repeated blood workup 10-12 h later in the next morning, followed by a flexible antagonist protocol. LH levels on the morning after ovulation trigger were compared to FACT LH levels. The results demonstrated that LH levels following agonist ovulation trigger below 15IU/L occurred in 1.09% of cycles and were predicted by FACT, r = 0.57, p < 0.001. ROC analysis demonstrated that FACT LH > 42.70 IU/L would predict LH post trigger of more than 30 IU/L with 75% sensitivity and 70% specificity, AUC = 0.81. LH levels post trigger also displayed significant positive correlation to basal FSH (r = 0.35, p = 0.002) and basal LH (r = 0.54, p < 0.001). LH levels post ovulation trigger were not associated with total oocytes number or maturity rate. The strongest correlation to the number of frozen oocytes was progesterone levels post agonist trigger (r = 0.746, p < 0.001). We concluded that suboptimal response to agonist trigger, as assessed by post trigger LH levels was a rare event. FACT could serve as an adjunct pre-trigger, intracycle tool to predict adequate LH levels elevation after agonist ovulation trigger. Future studies should focus on optimization of agonist trigger efficacy assessment and prediction, especially in high responders.
| S-EPMC10940571 | biostudies-literature
Project description:In natural cycle or minimal stimulation cycle IVF, buserelin acetate (buserelin), a gonadotropin-releasing hormone agonist, is often used as a maturation trigger; however, its effect on pregnancy outcomes remains unclear. Therefore, in the present study, we compared uterine receptivity in buserelin-administered mice with that in human chorionic gonadotropin (hCG)-administered mice during the peri-implantation period. Implantation, decidualisation, and term-pregnancy were impaired following hCG, but not buserelin administration. hCG stimulated the synthesis and secretion of progesterone and oestradiol, whereas ovarian steroidogenesis in the buserelin-treated group was comparable with that in the control group. Furthermore, similar to the observation in controls, the buserelin-treated group exhibited activation of progesterone receptor signalling and inhibition of oestrogen receptor signalling in the endometrial epithelium on the day of implantation. However, epithelial progesterone signalling was not detected, and a high expression of genes downstream to oestrogen was observed on day 4 following hCG administration. These results suggest that buserelin administration does not impact uterine receptivity as it did not affect ovarian steroidogenesis and endometrial steroid signalling. Therefore, buserelin is preferred as an oocyte maturation trigger to optimise uterine receptivity during treatments involving timed intercourse, intrauterine insemination, or fresh embryo transfer following in vitro fertilisation.
| S-EPMC6715633 | biostudies-literature
Project description:Background:The use of frozen embryo transfer (FET) is increasing worldwide in the treatment of infertility by in vitro fertilization. Different methods of endometrial preparation for FET have been suggested. Objective:The aim of this study was to compare the pregnancy outcomes after treatment with letrozole and those after treatment with the combination of gonadotropin-releasing hormone (GnRH) agonist and estradiol in FET. Materials and Methods:This randomized controlled trial study was conducted on 142 infertile women with a history of previous FET failure. Participants were randomly assigned to two groups (n = 71 each). The GnRH group received 500 µg of buserelin plus 4mg estradiol (which increased to 8 mg if endometrial thickness was less than 5 mm), and the letrozole group received 5 mg of letrozole plus 75 IU of recombinant human follicle-stimulating hormone). At least two high-quality embryos were transferred to each subject in both groups. The outcome measures were clinical pregnancy rate and fetal heart rate detection. Results:Subjects in the study groups had similar demographic characteristics and baseline clinical condition. Mean endometrial thickness in the letrozole and GnRH agonist groups were 8.90 ± 0.88 mm and 8.99 ± 0.85 mm, respectively (p = 0.57). The number of positive results of the beta human chorionic gonadotropin test and detection of fetal heartbeat were not significantly different between the groups (p > 0.05). Conclusion:The administration of letrozole and GnRH may produce similar pregnancy outcomes in FET.
| S-EPMC7097171 | biostudies-literature
Project description:BackgroundThe main objective of the present work was to compare the effects of the gonadotropin-releasing hormone agonist (GnRH-a) and GnRH antagonist (GnRH-ant) on the gene expression profiles of oocytes obtained from Iranian infertile couples undergoing in vitro fertilization (IVF).MethodsFifty infertile couples who underwent IVF between June 2012 and November 2013 at the Infertility Center of Tehran Women General Hospital, Tehran University of Medical Sciences, were included in this study. We included women that had undergone IVF treatment because of male factor, tubal factor, or unexplained infertility. The women randomly underwent controlled ovarian stimulation (COS) with either the GnRH-a (n = 26) or the GnRH-ant (n = 24). We obtained 50 germinal vesicle (GV) oocytes donated by women in each group. After the sampling, pool of 50 GV oocytes for each group was separately analyzed by quantitative polymerase chain reaction (qPCR).ResultThe expression levels of Adenosine triphosphatase 6 (ATPase 6), Bone morphogenetic protein 15 (BMP15), and Neuronal apoptosis inhibitory protein (NAIP) genes were significantly upregulated in the GnRH-ant group compared to the GnRH-a group, with the fold change of 3.990 (SD ± 1.325), 6.274 (SD ± 1.542), and 2.156 (SD ± 1.443), respectively, (P < 0.001). Growth differentiation factor 9 (GDF9) mRNA did not have any expression in the GnRH-a group; however, GDF9 mRNA was expressed in the GnRH-ant group. Finally, it was found that the genes involved in the DNA repairing and cell cycle checkpoint did not have any expression in either group.ConclusionThe present study showed, for the first time, the expression levels of genes involved in the cytoplasmic maturity (BMP15, GDF9), adenosine triphosphate production (ATPase 6), and antiapoptotic process (NAIP), in human GV oocytes were significantly higher in the GnRH-anta group than in the GnRH-a group in COS. Higher expression level of these genes when GnRH-ant protocol is applied, this protocol seems to be a more appropriate choice for women with poly cystic ovarian syndrome, because it can probably improve the expression of the aforementioned genes.Trial registrationCurrent Controlled Trials: IRCT 2014031112307 N3.
| S-EPMC4197229 | biostudies-literature
Project description:GnRH agonists (GnRHa) are a useful tool for pretreatment before artificial endometrial preparation for frozen-thawed embryo-transfer (FET). Their prolonged administration has been associated with thyroid dysfunction, both hyper and hypothyroidism. The aim of this study is to investigate the impact of GnRHa administration on thyroid function in women undergoing artificial endometrial preparation. Seventy-eight euthyroid women undergoing endometrial preparation with hormone replacement for FET were retrospectively reviewed. They were divided into two groups according to pretreatment with GnRHa (group A, 42 women) or with an oral contraceptive (group B, 36 women). Group A was subsequently divided into two subgroups according to thyroid autoimmunity presence. Thyroid function has been evaluated and compared among groups and subgroups. Our results did not show any statistically significant differences in age, body mass index, and basal thyroid stimulating hormone (TSH). Total estradiol dosage, duration of treatment, and endometrial thickness were comparable among groups. When TSH was measured 14 days after embryo transfer, no significant differences between the two groups were reported. Among women of group A, TSH was significantly higher only in women with thyroid autoimmunity. GnRHa seems to be associated with thyroid dysfunction in women with thyroid autoimmunity undergoing hormone replacement therapy for FET.
| S-EPMC9019438 | biostudies-literature
Project description:In vitro fertilization (IVF) and embryo transfer and intracytoplasmic sperm injection (ICSI) have allowed millions of infertile couples to achieve pregnancy. As an essential part of IVF/ICSI enabling the retrieval of a high number of oocytes in one cycle, controlled ovarian stimulation (COS) treatment mainly composes of the standard long gonadotrophin-releasing hormone agonist (GnRH-a) protocol and the gonadotrophin-releasing hormone antagonist (GnRH-ant) protocol. However, the effectiveness of GnRH-ant protocol is still debated because of inconsistent conclusions and insufficient subgroup analyses. This systematic review and meta-analysis included a total of 52 studies, encompassing 5193 participants in the GnRH-ant group and 4757 in the GnRH-a group. The findings of this study revealed that the GnRH-ant protocol is comparable with the long GnRH-a protocol when considering live birth as the primary outcome, and it is a favourable protocol with evidence reducing the incidence of ovarian hyperstimulation syndrome in women undergoing IVF/ICSI, especially in women with polycystic ovary syndrome. Further research is needed to compare the subsequent cumulative live birth rate between the two protocols among the general and poor ovarian response patients since those patients have a lower clinical pregnancy rate, fewer oocytes retrieved or fewer high-grade embryos in the GnRH-ant protocol.
| S-EPMC10941349 | biostudies-literature
Project description:Sleep interruption is often reported by women with hot flashes and night sweats (or vasomotor symptoms, VMS). Although women report that VMS awaken them, polysomnography (PSG) studies have not consistently supported this contention.We mimicked menopause using a gonadotropin-releasing hormone agonist (GnRHa) to investigate whether VMS increase awakenings and wake after sleep onset (WASO). VMS, serum estradiol, and at-home PSGs (two pretreatment, two posttreatment) were measured before and after 4 weeks on GnRHa. Regression models were used to determine the effect of increasing VMS frequency on awakenings and WASO, as measured objectively and subjectively.Twenty-nine healthy women (mean 27.3 y).Academic medical center.Depot GnRHa (leuprolide 3.75-mg).Serum estradiol was rapidly and uniformly suppressed on GnRHa. Persistent VMS were reported by 69% of women. The number of nighttime VMS correlated directly with the degree of sleep disturbance. Each additional reported nighttime VMS was associated with a 62% increase from baseline in PSG-measured WASO (P = 0.007), a 3% increase in awakenings (P = 0.05), and 6% increase in %N1 sleep (P = 0.02). Nighttime VMS were also associated with increased perceived WASO (312%; P = 0.02), awakenings (16%; P = 0.007), Insomnia Severity Index (P = 0.03), and Pittsburgh Sleep Quality Index (P = 0.03) scores, and decreased perceived sleep efficiency (P = 0.01). Objectively recorded nighttime VMS correlated with PSG-measured WASO (rs = 0.45, P = 0.02).This menopause model demonstrates that nighttime vasomotor symptoms correlate with increased sleep fragmentation. These findings are consistent with a specific contribution of vasomotor symptoms to polysomnography-measured sleep interruption suggesting that nighttime vasomotor symptoms interrupt sleep in the setting of menopause.
| S-EPMC3825449 | biostudies-literature
Project description:ContextChildren with congenital adrenal hyperplasia (CAH) are at risk for early puberty. Gonadotropin-releasing hormone analog (GnRHa) is frequently used and can decrease bone mineral density (BMD).ObjectiveOur aim was to investigate the effect of GnRHa therapy on BMD in a longitudinal study of patients with CAH spanning both childhood and adulthood.Design and settingSixty-one patients with classic CAH due to 21-hydroxylase deficiency (20 treated with GnRHa) were followed with dual-energy X-ray absorptiometry (DXA) scans at puberty onset, attainment of adult height, and during early adulthood.Main outcome measuresWhole body, lumbar spine, femoral neck, total hip, and distal radius BMD z-score at adult height. Longitudinal BMD and adult height were also assessed.ResultsTwenty patients received GnRHa for an average of 4.5 ± 2 years. There were no differences in BMD between GnRHa-treated and -untreated groups at adult height for all sites. Overall, the follow-up DXA during early adulthood showed decreases in BMD z-scores for whole body (P = .01), lumbar spine (P < .0001), femoral neck (P = .06), total hip (P = .009), and distal radius (P = .05). GnRHa treatment correlated with improved height outcomes compared to predicted height at puberty onset after adjusting for midparental height (P = .02). Patients in both groups achieved similar adult height.ConclusionIn children with CAH, GnRHa does not compromise BMD. However, BMD decreases with time and during the second and third decades of life is a possible effect of chronic supraphysiologic glucocorticoids. Children with CAH who experience early puberty benefit from GnRHa treatment as evidenced by the positive effect on height.
| S-EPMC10795903 | biostudies-literature