Age-related miRNome landscape of cumulus oophorus cells during controlled ovarian stimulation protocols in IVF cycles.
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SUBMITTER: Dell'Aversana C
PROVIDER: S-EPMC8058597 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PurposeDoes controlled ovarian stimulation (COS) and progesterone (P) luteal supplementation modify the vaginal and endometrial microbiota of women undergoing in vitro fertilization?MethodsFifteen women underwent microbiota analysis at two time points: during a mock transfer performed in the luteal phase of the cycle preceding COS, and at the time of fresh embryo transfer (ET). A vaginal swab and the distal extremity of the ET catheter tip were analyzed using next-generation 16SrRNA gene sequencing. Heterogeneity of the bacterial microbiota was assessed according to both the Bray-Curtis similarity index and the Shannon diversity index.ResultsLactobacillus was the most prevalent genus in the vaginal samples, although its relative proportion was reduced by COS plus P supplementation (71.5 ± 40.6% vs. 61.1 ± 44.2%). In the vagina, an increase in pathogenic species was observed, involving Prevotella (3.5 ± 8.9% vs. 12.0 ± 19.4%), and Escherichia coli-Shigella spp. (1.4 ± 5.6% vs. 2.0 ± 7.8%). In the endometrium, the proportion of Lactobacilli slightly decreased (27.4 ± 34.5% vs. 25.0 ± 29.9%); differently, both Prevotella and Atopobium increased (3.4 ± 9.5% vs. 4.7 ± 7.4% and 0.7 ± 1.5% vs. 5.8 ± 12.0%). In both sites, biodiversity was greater after COS (p < 0.05), particularly in the endometrial microbiota, as confirmed by Bray-Curtis analysis of the phylogenetic distance among bacteria genera. Bray-Curtis analysis confirmed significant differences also for the paired endometrium-vagina samples at each time point.ConclusionsOur findings suggest that COS and P supplementation significantly change the composition of vaginal and endometrial microbiota. The greater instability could affect both endometrial receptivity and placentation. If our findings are confirmed, they may provide a further reason to encourage the freeze-all strategy.
| S-EPMC7492325 | biostudies-literature
Project description:BackgroundThis secondary analysis aimed to identify predictors of low (<6 oocytes retrieved) and high ovarian response (>18 oocytes retrieved) in IVF patients undergoing controlled ovarian stimulation with corifollitropin alfa in a gonadotropin-releasing hormone (GnRH) antagonist protocol.MethodsStatistical model building for high and low ovarian response was based on the 150 μg corifollitropin alfa treatment group of the Pursue trial in infertile women aged 35-42 years (n = 694).ResultsMultivariable logistic regression models were constructed in a stepwise fashion (P <0.05 for entry). 14.1 % of subjects were high ovarian responders and 23.2 % were low ovarian responders. The regression model for high ovarian response included four independent predictors: higher anti-Müllerian hormone (AMH) and antral follicle count (AFC) increased the risk, and higher follicle-stimulating hormone (FSH) levels and advancing age decreased the risk of high ovarian response. The regression model for low ovarian response also included four independent predictors: advancing age increased the risk, and higher AMH, higher AFC and longer menstrual cycle length decreased the risk of low ovarian response.ConclusionsAMH, AFC and age predicted both high and low ovarian responses, FSH predicted high ovarian response, and menstrual cycle length predicted low ovarian response in a corifollitropin alfa/GnRH antagonist protocol.Trial registration numberNCT01144416 , Protocol P06029.
| S-EPMC4628292 | biostudies-literature
Project description:BackgroundSeveral studies have explored which COS protocol yields a higher blastocyst euploidy rate, but findings have been inconsistent. The present study aimed to explore whether controlled ovarian stimulation (COS) protocols was associated with euploid blastocyst rate in pre-implantation genetic testing for aneuploidy (PGT-A) cycles.MethodsThe study was a retrospective study where data were obtained from three reproductive medicine centers. The study included PGT-A cycles with the GnRH-a, GnRH-ant, or PPOS protocols, and the data on patient demographics, protocols, and embryonic outcomes were collected for the PGT-A cycles performed between January 2019 and August 2022.ResultsThis study included 457 PGT-A cycles from three reproductive medicine centers, with 152, 126, and 179 cycles performed using the PPOS, GnRH-a, and GnRH-ant protocols, respectively. The baseline characteristics of the three groups show no significant differences were observed in female BMI, infertility type, and infertility duration among the PPOS, GnRH-a, and GnRH-ant protocol groups. The study found no significant association between Gn dosage, Gn duration, and blastocyst euploidy. The mean number of euploidy blastocysts in PPOS protocol was significantly lower than that of GnRH-a protocol and GnRH-ant protocol (0.75 ± 0.92 vs. 1.79 ± 1.78 vs. 1.80 ± 1.67). The euploidy rate per biopsy blastocyst (48.4% vs. 49.1% vs. 33.1%), per oocyte retrieved (15.0% vs. 14.7% vs. 10.5%), and per MII oocyte (17.7% vs. 16.4% vs. 11.7%) were significantly higher in the cycles using the GnRH-ant and GnRH-a protocols than that of PPOS protocol group. Regression analyses indicated that, compared with the PPOS protocol, the GnRH-ant protocol was positively associated with the euploid blastocyst rate and the mean number of euploid blastocysts, whereas the GnRH-a protocol showed no such relationship.Limitations and reasons for cautionThe main limitation of this study was the retrospective design. Although this study also used other tests to account for confounding factors and reduce potential bias, multiple tests have its own weaknesses.ConclusionsGnRH-ant protocol was the most effective for PGT-A cycles. The findings emphasize the need for personalized treatment strategies, considering patient demographics, and optimizing COS protocols to enhance the chances of successful outcomes in ART procedures.
| S-EPMC10698966 | biostudies-literature
Project description:To compare the two GnRH-a protocols (long GnRH-a protocol and short GnRH-a protocol) for ovarian stimulation in IVF/ICSI cycles in patients of various age ranges.A total of 5662 IVF-ET/ICSI cycles from 2010 to 2013 were retrospectively identified. The cycles were divided into two groups: a long protocol group and short protocol group. In each group, the patients were divided into four age ranges: <31 years, 31 to 35 years, 36 to 40 years, and >40 years. The duration of stimulation, total dose of Gn, implantation rate and pregnancy rate were compared.The total dose of Gn was significantly higher, and the duration of stimulation was significantly longer, in the long protocol group than in the short protocol group for all age ranges (P<0.05). If the patients were of the same age range, the number of oocytes retrieved, MII oocytes, and high-quality embryos in the long protocol group were all significantly greater than those in the short protocol group (P<0.05). In the long protocol group, the clinical pregnancy rates of the four age ranges were 52.76%, 44.33%, 36.15% and 13.33%, respectively, which were significantly higher than those in the short protocol group (33.33%, 24.58%, 22.49% and 8.72%, respectively; P<0.05). The same trend was also found in the implantation rates of the four age ranges. As the age increased, the clinical pregnancy and implantation rates, as well as the number of oocytes retrieved, MII oocytes, and high-quality embryos, of the long protocol group significantly decreased (P<0.05).Our study demonstrated that regardless of patient age, the long protocol was superior to the short protocol in terms of the number of retrieved oocytes, as well as the implantation and pregnancy rates.
| S-EPMC4514806 | biostudies-literature
Project description:Although it is well appreciated that ovarian stimulation protocols for in vitro fertilization (IVF) alter endometrial receptivity, the precise cellular mechanisms are not known. To gain insights into potential mechanisms by which different ovarian stimulation protocols alter the endometrium, we compared histologic and gene expression profiles of endometrium from women undergoing conventional ovarian stimulation for IVF (C-IVF) with those undergoing minimal stimulation with clomiphene citrate (MS-IVF). Sixteen women undergoing MS-IVF (n = 8) or C-IVF (n = 8) were recruited for endometrial biopsy at the time of oocyte retrieval. Endometrial glands were large, tortuous, and secretory with C-IVF but small and undifferentiated with MS-IVF. Whereas RNA sequencing did not reveal changes in estrogen receptor or its co-regulators or classic proliferation associated genes in MS-IVF, together with immunohistochemistry, Wnt signaling was disrupted in endometrium from MS-IVF cycles with significant upregulation of Wnt inhibitors. Secreted frizzled-related protein 1 (sFRP1) was increased fourfold (p < 0.01), and sFRP4 was upregulated sixfold (p < 0.01) relative to C-IVF. Further these proteins were localized to subepithelial endometrial stroma. These data indicate that MS-IVF protocols with CC do not seem to impact endometrial estrogen signaling as much as would be expected from the reported antiestrogenic properties of CC. Rather, the findings of this study highlight Wnt signaling as a major factor for endometrial development during IVF cycles.
| S-EPMC7539809 | biostudies-literature
Project description:BackgroundEvaluation of patients' experiences and satisfaction is vital for assessing the quality of healthcare service, including in fertility clinics. One promising concept that has recently been widely used to increase efficiency and service quality in hospitals is the lean concept. Lean is a form of philosophy that focuses on reducing waste of a process and continuous improvement so that consumers receive greater value. This study aims to identify waste and improve efficiency using lean management methods in the controlled ovarian stimulation (COS) monitoring process during in vitro fertilization (IVF) treatment in a fertility clinic.MethodsThis study used an action research approach by observing the total service time of monitoring ovarian stimulation in IVF patients (n = 40). The identified waste and solutions were then compiled for use in a focus group discussion (FGD). From the FGD, a priority plan was obtained for the implementation of lean management. This study uses the PDCA cycle for improvement.ResultsThree priority solutions were chosen, which are as follows: (1) evaluating ovarian stimulation via USG only; (2) allocating more time during doctor's counselling; and (3) increasing counselling time by nurses in the injection room. The total patient wait time was reduced to 6 hours 32 minutes over the three visits, 13 hours 35 minutes decrease from before the intervention. In addition, the value-added ratio (VAR) was increased from 9% to 22% after the intervention.ConclusionThis research provides theoretical and practical contributions for the lean management principles in IVF treatment. The findings of this study will contribute to the pursuit of knowledge and dissemination of lean principles in the management of healthcare, including IVF clinics.
| S-EPMC8942643 | biostudies-literature
Project description:The oocyte and the surrounding cumulus cells (CCs) are deeply linked by a complex bidirectional cross-talk. In this light, the molecular analysis of the CCs is nowadays considered to be precious in providing information on oocyte quality. It is now clear that miRNAs play a key role in several ovarian functions, such as folliculogenesis, steroidogenesis, and ovulation. Thus, in this study, specific miRNAs, together with their target genes, were selected and investigated in CCs to assess the response of patients with normal (NR) and low (LR) ovarian reserve to two different controlled ovarian stimulation (COS) protocols, based on rFSH and hMG. Moreover, a Fourier transform infrared microspectroscopy (FTIRM) analysis was performed to evaluate DNA conformational changes in CCs and to relate them with the two COS protocols. The results evidenced a modulation of the expression of miRNAs and related target genes involved in CCs' proliferation, in vasculogenesis, angiogenesis, genomic integrity, and oocyte quality, with different effects according to the ovarian reserve of patients. Moreover, the COS protocols determined differences in DNA conformation and the methylation state. In particular, the results clearly showed that treatment with rFSH is the most appropriate in NR patients with normal ovarian reserve, while treatment with hMG appears to be the most suitable in LR patients with low ovarian reserve.
| S-EPMC8836191 | biostudies-literature
Project description:The predictive value of anti-Müllerian hormone (AMH) in Chinese women undergoing in vitro fertilization (IVF) treatment is data deficient. To determine the attributes of AMH in IVF, oocyte yield, cycle cancellation, and pregnancy outcomes were analyzed. All patients initiating their first IVF cycle with gonadotropin-releasing hormone agonist treatment in our center from October 2013 through December 2014 were included, except patients diagnosed with polycystic ovarian syndrome. Serum samples collected prior to IVF treatment were used to determine serum AMH levels. A total of 4017 continuous cycles were analyzed. The AMH level was positively correlated with the number of oocytes retrieved. Overall, AMH was significantly correlated with risk of cycle cancellation, poor ovarian response (POR, 3, or fewer oocytes retrieved) and high response (>15 oocytes), with an area under the curve (AUC) of 0.83, 0.89, and 0.82 respectively. An AMH cutoff of 0.6 ng/mL had a sensitivity of 54.0% and a specificity of 90.0% for the prediction of cycle cancellation, and cutoff of 0.8 ng/mL with a sensitivity of 55.0% and a specificity of 94.0% for the prediction of POR. Compared with AMH >2.0 ng/mL, patients with AMH < 0.6 ng/mL had a 53.6-fold increased risk of cancellation (P < 0.001), and AMH <0.80 ng/mL were 17.5 times more likely to experience POR (P < 0.001). However, AMH was less predictive of pregnancy and live birth, with AUCs of 0.55 and 0.53, respectively. Clinical pregnancy rate, ongoing pregnancy rate, and live birth rate per retrieval according to the AMH level (≤0.40, 0.41-0.60, 0.61-0.80, 0.81-1.00, 1.01-1.50, 1.51-2.00, and >2.00 ng/mL) showed no significant differences. Even with AMH≤0.4 ng/mL, 50.0% of all the patients achieved pregnancy and 34.8% of patients achieved live birth after transfer. Our results suggested that AMH is a fairly robust metric for the prediction of cycle cancellation and oocyte yield for Chinese women, but it is a relatively poor test for prediction of pregnancy outcomes. Patients with low levels of AMH still can achieve reasonable treatment outcomes and low AMH levels in isolation do not represent an appropriate marker for withholding fertility treatment.
| S-EPMC5380281 | biostudies-literature
Project description: Not available
| S-EPMC10769816 | biostudies-literature
Project description:PurposeTo evaluate the impact of preimplantation genetic testing for aneuploidy (PGT-A) on cumulative live birth rate (CLBR) in IVF cycles.MethodsRetrospective cohort study of the SART CORS database, comparing CLBR for patients using autologous oocytes, with or without PGT-A. The first reported autologous ovarian stimulation cycle per patient between January 1, 2014, and December 31, 2015, and all linked embryo transfer cycles between January 1, 2014, and December 31, 2016, were included in the study. Exclusion criteria were donor oocyte cycles, donor embryo cycles, gestational carrier cycles, cycles which included both a fresh embryo transfer (ET) combined with a thawed embryo previously frozen (ET plus FET), or cycles with a fresh ET after PGT-A.ResultsA total of 133,494 autologous IVF cycles were analyzed. Amongst patients who had blastocysts available for either ET or PGT-A, including those without transferrable embryos, decreased CLBR was noted in the PGT-A group at all ages, except ages > 40 (p < 0.01). A subgroup analysis of only those patients who had PGT-A and a subsequent FET, excluding those without transferrable embryos, demonstrated a very high CLBR, ranging from 71.2% at age < 35 to 50.2% at age > 42. Rates of multiple gestations, preterm birth, early pregnancy loss, and low birth weight were all greater in the non-PGT-A group.ConclusionsPGT-A was associated with decreased CLBR amongst all patients who had blastocysts available for ET or PGT-A, except those aged > 40. The negative association of PGT-A use and CLBR per cycle start was especially pronounced at age < 35.
| S-EPMC9840738 | biostudies-literature