Follicular flushing during oocyte retrieval in assisted reproductive techniques.
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SUBMITTER: Georgiou EX
PROVIDER: S-EPMC6494433 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Study questionDoes follicular flushing increase the number of mature oocytes in monofollicular IVF?Summary answerFollicular flushing increases the number of mature oocytes in monofollicular IVF.What is known alreadyFlushing increases neither the oocyte yield nor the pregnancy rate in polyfollicular IVF or in poor responder patients. In monofollicular IVF, the effect of flushing has so far been addressed by two studies: (i) a prospective study with minimal stimulation IVF demonstrated an increased oocyte yield, and (ii) a retrospective study with natural cycle (NC)-IVF showed an increased oocyte yield and an increased transfer rate.Study design, size, durationRandomized controlled trial including 164 women who were randomized for either aspiration with or without flushing from 2016 to 2019.Participants/materials, setting, methodsInfertile women 18-42 years of age with an indication for IVF treatment at a university-based infertility unit. Women undergoing monofollicular IVF were randomized to either follicular aspiration only or follicular aspiration directly followed by five follicular flushes at a 1:1 ratio. The intervention was done without anaesthesia, using a gauge 19 single-lumen needle. Flushing volume was calculated (sphere formula) based on the size of the follicle.Main results and the role of chanceA total of 164 women were included; 81 were allocated to 'aspiration only' and 83 to additional 'flushing'. Primary analysis was based on the intention-to-treat: oocyte yield, defined as the collected mature oocyte rate, was higher (n = 64/83, 77.1%) in the flushing group compared to the aspiration only group (n = 48/81, 59.3%, adjusted risk difference (RD): 18.2% (95% CI 3.9-31.7%), P-value = 0.02). In the flushing group, most oocytes were retrieved within the first three flushes (63/83, 75.8%). Fertilization rate was higher in the flushing group (n = 53/83, 63.9% vs n = 38/81, 46.9%; adjusted RD: 16.8% (96% CI 1.5-31.4%), P = 0.045). Transfer rate was also higher in the flushing group (n = 52/83, 62.7% vs n = 38/81, 46.9%; RD: 15.71 (95% CI 0.3-30.3%)), but the difference was not significant (P = 0.06). The clinical pregnancy rate n = 9/83 versus n = 9/81 (RD: -0.3% (95% CI -9.9% to 9.5%)) and live birth rate n = 7/83 versus n = 8/81 (RD: -1.5% (95% CI -10.4% to 7.1%)) were not significantly different between the flushing and the aspiration group. The median duration of the intervention was significantly longer with flushing (2.38 min; quartiles 2.0, 2.7) versus aspiration only (0.43 min; quartiles 0.3, 0.5) (P < 0.01). There was no significant difference in the mean (±SD) visual analogue scales pain score between the follicular flushing (3.4 ± 1.8) and the aspiration group (3.1 ± 1.89).Limitations, reasons for cautionBlinding of the procedure was not possible.Wider implications of the findingsOur study proved that flushing of single follicles in NC-IVF increases the oocyte yield. In contrast to polyfollicular IVF flushing seems to be beneficial in a monofollicular setting if the technique used in our study (single-lumen needle, 5 flushings with flushing volume adaptation) is applied.Study funding/competing interest(s)The study was funded by the financial sources of the division and in part by a research grant provided by NMS Biomedical SA, Switzerland. The company did not have any roles in design or conduct of the study or in the preparation of the manuscript. The authors have no other conflicts of interest.Trial registration numberClinicaltrials.gov NCT02641808.Trial registration date29 December 2015.Date of first patient’s enrolment22 August 2016.
| S-EPMC7518713 | biostudies-literature
Project description:Human infertility can be treated using assisted reproductive technology (ART) such as intracytoplasmic sperm injection (ICSI). But current ART techniques suffer from multiple cumbersome processes requiring technically skilled personnel. Microfluidics technologies offer unique opportunities to streamline ART procedures, reduce stress imposed upon gametes and embryos, and minimize the operator-to-operator variability. However, there have been no automated and continuous processing systems that can reduce the dependence on well-trained embryologists to obtain ICSI-ready oocytes from patients. In this study, using mouse models, we developed a microfluidic device to denude oocytes from the surrounding cumulus-corona cell mass, facilitating the evaluation of oocyte quality and the injection of sperm. Enzyme-treated cumulus-oocyte complexes pass through a series of jagged-surface constriction microchannels of optimized geometries. The jagged inner wall of constriction channels facilitates stripping off of the cumulus-corona cell mass. Oocytes that were denuded by the device showed comparable fertilization and developmental competence compared with mechanical pipetting. The device developed in this study achieves the automation of a manual process for oocyte denudation in a continuous flow, as well as improving standardization and ease-of-use. Our denudation-on-a-chip approach requires inexpensive and simple equipment, which represents one step forward towards improving the accessibility and affordability of assisted reproductive therapy.
| S-EPMC6335650 | biostudies-literature
Project description:PurposeThe Uppsala-Stockholm Assisted Reproductive Techniques (UppStART) study is a prospectively recruited sample of couples undergoing assisted reproduction in Stockholm and Uppsala county in Sweden. The study was initiated to (1) investigate possible changes in the epigenetic profile of infants inferred through the ART procedures and their consequence and (2) to assess the impact of lifestyle and health exposures on treatment outcome.ParticipantsRecruitment took place between September 2011 and December 2013, and in vitro fertilisation (IVF) cycles initiated and pregnancies conceived during this time were followed until December 2014. The cohort includes 971 participants (n= 514 women; n= 457 men), and 129 pregnancies were achieved from the first IVF cycle included in the study.Findings to dateSelf-reported demographic, health and lifestyle data were collected from a baseline questionnaire, and to assess changes to lifestyle, a follow-up questionnaire was issued at the time of oocyte retrieval, and at subsequent IVF cycles. Questionnaire data were linked to data extracted from medical records. Biological samples were collected at baseline: blood for extraction of serum, plasma and DNA, morning and evening saliva samples for cortisol measurement and at delivery including samples of maternal blood, placenta and amniotic fluid, and cord blood for epigenetic analysis.Future plansThrough the unique identification number assigned to each Swedish citizen at birth or immigration, UppStART study participants will be linked to the Swedish population-based national and quality registers to provide data from prenatal, obstetrical, neonatal and infant care, and subsequent updates will provide data on childhood health and educational outcomes. Collaboration and use of UppStART data is encouraged, and more information about access can be found at www.ki.se/meb/uppstart.
| S-EPMC6720339 | biostudies-literature
Project description:Egg quality dictates fertility outcomes, and although there is a well-documented decline with advanced reproductive age, how it changes during puberty is less understood. Such knowledge is critical, since advances in Assisted Reproductive Technologies are enabling pre- and peri-pubertal patients to preserve fertility in the medical setting. Therefore, we investigated egg quality parameters in a mouse model of the pubertal transition or juvenescence (postnatal day; PND 11-40). Animal weight, vaginal opening, serum inhibin B levels, oocyte yield, oocyte diameter, and zona pellucida thickness increased with age. After PND 15, there was an age-associated ability of oocytes to resume meiosis and reach metaphase of meiosis II (MII) following in vitro maturation (IVM). However, eggs from the younger cohort (PND 16-20) had significantly more chromosome configuration abnormalities relative to the older cohorts and many were at telophase I instead of MII, indicative of a cell cycle delay. Oocytes from the youngest mouse cohorts originated from the smallest antral follicles with the fewest cumulus layers per oocyte, suggesting a more developmentally immature state. RNA Seq analysis of oocytes from mice at distinct ages revealed that the genes involved in cellular growth signaling pathways (PI3K, mTOR, and Hippo) were consistently repressed with meiotic competence, whereas genes involved in cellular communication were upregulated in oocytes with age. Taken together, these data demonstrate that gametes harvested during the pubertal transition have low meiotic maturation potential and derive from immature follicular origins.
| S-EPMC8244820 | biostudies-literature
Project description:BackgroundAssisted reproductive technology accounts for an increasing proportion of infertility treatments, and assessments to predict clinical pregnancy outcomes are desired. Extracellular vesicles exist in follicular fluid, and small non coding RNAs in extracellular vesicles underline the possibility of reflecting pregnancy potential.MethodsFollicular fluid samples are collected from 20 ovarian follicles of 15 infertile patients undergoing assisted reproductive technology. Extracellular vesicles are isolated by serial centrifugation and small RNA sequencing is performed to investigate the profiles of microRNAs and P-element-induced wimpy testis-interacting RNAs.ResultsSmall extracellular vesicles with a size range of approximately 100 nm are successfully isolated, and the small non coding RNA profiles of pregnant samples (n = 8) are different from those of non-pregnant samples (n = 12). Fourteen dysregulated small non coding RNAs are selected to identify the independent candidates [mean read count >100, area under the curve >0.8]. Among them, we find that a specific combination of small non coding RNAs (miR-16-2-3p, miR-378a-3p, and miR-483-5p) can predict the pregnant samples more precisely using a receiver operating characteristics curves analysis (area under the curve: 0.96). Furthermore, even in the same patients, the three microRNAs are differentially expressed between pregnant and non-pregnant samples.ConclusionsOur results demonstrate that small non coding RNAs derived from small extracellular vesicles in follicular fluid can be potential non-invasive biomarkers for predicting pregnancy, leading to their probable application in assisted reproductive technology. Further large-scale studies are required to validate the clinical usefulness of these small non coding RNAs.
| S-EPMC10902298 | biostudies-literature
Project description:MicroRNAs (miRNAs) are important regulators of many biological functions, including embryo implantation and development. Recently, it is reported that miRNAs in biofluids are predictive for physiological and pathological processes. In this study, we aim to investigate whether the miRNAs secreted by human embryos in culture medium can be used as embryonic biomarkers. The culture media were prospectively collected from embryos of patients who underwent routine in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) at reproductive medicine center with informed consent. A high-throughput miRNA sequencing method was applied to detect the miRNAs profiles in culture media of embryos with different reproductive outcomes. Compared with embryos with failed pregnancy, the embryos with successful pregnancy secreted different miRNA profiles into the culture media. These differentially expressed miRNAs were predicted to be involved in multiple biological processes, cellular components and molecular functions. After bioinformatics analysis, 18 miRNAs were selected for validation by quantitative real-time polymerase chain reaction (qRT-PCR) and droplet digital PCR (ddPCR). We found that the cleavage embryos with successful pregnancy presented decreased expression of hsa-miR-26b-5p and hsa-miR-21-5p in the culture media. Moreover, the Receiver Operating Characteristic (ROC) curve analysis indicated that hsa-miR-26b-5p and hsa-miR-21-5p could serve as potential biomarkers for reproductive outcomes. Together, our findings highlight the important predictive potential of miRNAs secreted by human embryos in culture media, which is meaningful for noninvasive embryo selection during IVF cycles.
2020-02-28 | GSE142824 | GEO
Project description:BackgroundA Delphi consensus was conducted to evaluate global expert opinions on key aspects of assisted reproductive technology (ART) treatment.MethodsTen experts plus the Scientific Coordinator discussed and amended statements plus supporting references proposed by the Scientific Coordinator. The statements were distributed via an online survey to 35 experts, who voted on their level of agreement or disagreement with each statement. Consensus was reached if the proportion of participants agreeing or disagreeing with a statement was >66%.ResultsEighteen statements were developed. All statements reached consensus and the most relevant are summarised here. (1) Follicular development and stimulation with gonadotropins (n = 9 statements): Recombinant human follicle stimulating hormone (r-hFSH) alone is sufficient for follicular development in normogonadotropic patients aged <35 years. Oocyte number and live birth rate are strongly correlated; there is a positive linear correlation with cumulative live birth rate. Different r-hFSH preparations have identical polypeptide chains but different glycosylation patterns, affecting the biospecific activity of r-hFSH. r-hFSH plus recombinant human LH (r-hFSH:r-hLH) demonstrates improved pregnancy rates and cost efficacy versus human menopausal gonadotropin (hMG) in patients with severe FSH and LH deficiency. (2) Pituitary suppression (n = 2 statements): Gonadotropin releasing hormone (GnRH) antagonists are associated with lower rates of any grade ovarian hyperstimulation syndrome (OHSS) and cycle cancellation versus GnRH agonists. (3) Final oocyte maturation triggering (n=4 statements): Human chorionic gonadotropin (hCG) represents the gold standard in fresh cycles. The efficacy of hCG triggering for frozen transfers in modified natural cycles is controversial compared with LH peak monitoring. Current evidence supports significantly higher pregnancy rates with hCG + GnRH agonist versus hCG alone, but further evidence is needed. GnRH agonist trigger, in GnRH antagonist protocol, is recommended for final oocyte maturation in women at risk of OHSS. (4) Luteal-phase support (n = 3 statements): Vaginal progesterone therapy represents the gold standard for luteal-phase support.ConclusionsThis Delphi consensus provides a real-world clinical perspective on the specific approaches during the key steps of ART treatment from a diverse group of international experts. Additional guidance from clinicians on ART strategies could complement guidelines and policies, and may help to further improve treatment outcomes.
| S-EPMC8142593 | biostudies-literature
Project description:Mitochondria change their shape through fusion and fission in order to adapt to their metabolic milieu. Mitofusin-2 (MFN2) is a key regulatory protein in this process, mediating mitochondrial fusion and interaction with endoplasmic reticulum. Targeted deletion of Mfn2 in oocytes resulted in mitochondrial dysfunction and female subfertility associated with impaired oocyte maturation and follicle development. Oocytes lacking MFN2 showed shortened telomeres and increased apoptosis, resulting in compromised oocyte quality and accelerated follicular depletion, consistent with a reproductive aging phenotype.
| S-EPMC6628992 | biostudies-literature
Project description:ObjectiveAlthough there are substantial data linking thyroid autoimmunity (TAI) and infertility, data regarding assisted reproductive technology (ART) outcomes and TAI markers in follicular fluid (FF) of women undergoing ART are scarce. Objective of the study was to assess the association of the levels of thyroid autoantibodies in FF and ART outcome expressed as the achieved pregnancies.MethodsThis study enrolled 52 women undergoing ART (26 TAI positive subjects and 26 age and body mass index matched TAI negative controls). Blood samples were drawn before the initiation of protocol for controlled ovarian stimulation, and thyrotropin (TSH), free triiodothyronine (fT3), free thyroxine (fT4), thyroid peroxidase antibodies (TPOAbs) and thyroglobulin antibodies (TgAbs) levels were measured. TSH, fT4, TPOAbs, TgAbs and progesterone levels were also measured in FF.ResultsThere were no significant differences between the groups regarding mean levels of FF TSH and FF fT4. Statistically significant correlation was discovered regarding the levels of serum and FF TPOAbs (0,961, p<0.001 in TAI positive, 0,438, p = 0.025 in TAI negative group) and TgAbs (0,945, p<0.001 in TAI positive, 0,554, p = 0.003 in TAI negative group). Pregnancies rates per initiated cycle and per embryotransfer cycle were significantly different between TAI positive and TAI negative group, (30.8% vs 61.5%), p = 0.026 and (34.8% vs 66.7%), p = 0.029, respectively. Multivariate analysis showed that TAI positive women had less chance to achieve pregnancy (p = 0.004, OR = 0.036, 95% CI 0.004-0.347).ConclusionsHigher levels of thyroid autoantibodies in FF of TAI positive women are strongly correlated with serum levels and may have effect on the post-implantation embryo development.
| S-EPMC6205652 | biostudies-literature
Project description:ObjectiveTo study pain in women undergoing oocyte retrieval with a reduced needle (20/17 gauge) compared to a standard needle (16 gauge).DesignSingle-center randomized controlled trial.SettingFertility clinic.PatientsWomen undergoing their first oocyte retrieval for in vitro fertilization or intracytoplasmic sperm injection.InterventionsOocyte retrieval with a reduced needle (20/17 gauge) or with a standard needle (16 gauge).Main outcome measuresThe primary outcome measure was intraoperative pain on an 11-point visual analogue scale (VAS). Secondary outcome measures included the following: dosage of fentanyl requested; pain at 5, 15 and 30 minutes after retrieval; and pain and analgesia until 4 days after retrieval.ResultsA total of 47 women were randomized for the reduced needle (RN) and 48 for the standard needle (SN). Pain scores were significantly lower during and after retrieval with the RN. During retrieval, mean VAS scores in the RN group were 4.3 versus 6.3 in the SN group. Pain remained significantly lower in the RN group after retrieval, with VAS-scores of 1.2 vs. 2.1 directly after retrieval, 0.0 versus 2.0 5 minutes after retrieval, and 0.0 versus 1.0 30 minutes after retrieval. In the RN group, three patients (6.4%) requested more fentanyl during the procedure, versus 16 (33.3%) in the SN group. A total of 79 patients submitted their follow-up questionnaire (response rate 83%). Pain on the first 2 days following retrieval was significantly less in the RN group, with VAS scores of 1.6 versus 2.4 in the SN group, and 1.2 versus 2.5. In line with this finding, fewer patients in the RN group took analgesia on the days after the procedure. This difference was statistically significant only on day 3.ConclusionUse of a thinner needle results in significantly and clinically relevant lower pain scores during oocyte retrieval, and patients in the reduced needle group requested significantly less analgesia during oocyte retrieval than patients in the standard needle group. Pain scores remained significantly lower up until 2 days after the procedure.Dutch trial registration numberNTR6064 (www.trialregister.nl).
| S-EPMC7563574 | biostudies-literature