Good Quality Embryos Research Articles

EMBRYO GLUE AND CLINICAL PREGNANCY RATES IN ICSI EMBRYO TRANSFER CYCLES: A PROSPECTIVE STUDY

Purpose: One of the reasons for failed implantation after transferring good quality embryos in an intracytoplasmic sperm injection cycle is the failure of creation a viscid layer between the embryo and the endometrium. Many modifications have been made in embryo transfer medium to improve implantation and increase pregnancy rates such as adding albumin as a source of energy and adding hyaluronic acid in high concentrations such as in Embryo Glue medium: a human embryo transfer medium. To investigate whether the use of Embryo Glue had any effect on clinical pregnancy rates in intracytoplasmic sperm injection-fresh embryo transfer cycles.
 Methods: A prospective study included one hundred and twenty-eight infertile Iraqi women who were selected and subjected to a stimulation protocol in an intracytoplasmic sperm injection-fresh embryo transfer cycle. All patients were considered to be eligible for embryo transfer (no visible causes could prevent implantation) and only good quality embryos were transferred to them. Those women were divided randomly into two groups according to type of embryo transfer medium: group A: Embryo Glue medium. group B: Conventional medium. Then group A was subdivided according to age into: AI (34 women with age < 35 years and represented 50.7%) AII (33 women with age ≥ 35 years and represented 49.3%) While group B was subdivided into: BI (41women with age < 35 years and represented 67.3%) BII (20 women with age ≥ 35 years and represented 32.7%).
 Results: Although there was no significant difference between all groups in causes of infertility, the pregnancy rate was significantly higher in subgroup AII (18 pregnant from 33 women) while only 5 patients became pregnant from 20 patients in subgroup BII. In all women no more than four good quality embryos were transferred, and when total number of transferred embryos was significantly more in group B than group A (P=0.013), the significant increase in pregnancy rates was only observed in subgroup AII (P=0.048). Even though a highly significant difference in number of repeated implantation failure was in group A than group B (P=0.027), the pregnancy rates were significantly higher in group A (P=0.038).
 Conclusion: This study concluded that using Embryo Glue has a beneficial effect on old women and increase pregnancy rates, also it has a positive effect on pregnancy rates in repeated implantation failure and increases pregnancy rates even if the women is old.

The relationship between good quality embryo rates and IVF outcomes/embryo transfer policies in extended embryo culture

This study aims to investigate which parameters affect the change in good quality embryo rates during the cleavage stage and whether they have any effect on embryo transfer policies and IVF results. We analysed changes in good quality embryo (grades 1 and 2) rates during the period on days 2, 3 and 5; patients with five or fewer embryos (group 1), 6–10 embryos (group 2) and more than 10 embryos (group 3). The good quality embryo rates decreased in all groups on day 5. When the infertility reasons are studied among all of the groups, ovulatory dysfunction is found to be significantly higher in group 2 compared to group 1 and unexplained infertility was found to be significantly higher in group 2 compared to group 1 and group 3. Total antral follicle, mature oocyte and total oocyte counts were found to be significantly lower in group 1. However, there is no significant difference found among all of the groups for β-HCG levels and clinical pregnancies. Changes in good quality embryo rates at the cleavage stage in extended embryo culture do not have an impact on IVF results. IMPACT STATEMENT What is already known on this subject? The number and quality of embryos in the cleavage stage are important parameters affecting the embryo transfer decision on day 5. There is still insufficient knowledge concerning changes in the percentage of increased good quality embryo transfers associated with IVF outcomes during the second to the third day, and the third to the fifth day. What do the results of this study add? Day 5 embryo transfer is possible in patients with a low number of embryos, according to our results. The good quality embryo rates of patients with a low number of embryos at the cleavage stage are more promising compared to patients having more than five embryos. What are the implications of these findings for clinical practice and/or further research? An extended embryo culture option can be used on patients with a low number of embryos for clinical practice.

Progesterone elevation on the day of oocyte retrieval and live birth rate after in vitro fertilisation treatment

The objective of this study was to evaluate if progesterone elevation (PE) on the day of oocyte retrieval is associated with IVF outcome. A prospective cohort study of 400 IVF-ICSI cycles, with fresh embryo transfer on day 2–3 was performed. We proposed a serum progesterone (P) level on percentile (p) 90 as a threshold. Pregnancy rates were not affected, however there were more miscarriages (25.7% vs 43.8%) and lower live birth rate (LBR) (28% vs 23.1%) in the PE group (not statistically significant). We also found a positive correlation between P levels and retrieved and mature oocytes, total embryos, and good quality embryos. This is the first study to analyse LBR based on P levels on the day of oocyte retrieval. PE is not associated with the IVF outcome, but there is a trend to lower ongoing pregnancy rate and LBR and more miscarriages. Our results also show that P levels have no negative effects on oocyte and embryo quality. Impact statement What is already known on this subject? The influence of PE during IVF cycle on pregnancy rates remains controversial. What do the results of this study add? This is the first study to analyse LBR based on P levels on the day of oocyte retrieval. What are the implications of these findings for clinical practice and/or further research? We demonstrated that pregnancy rates were not affected by PE at oocyte retrieval, but there is a trend to lower ongoing pregnancy rate and LBR and more miscarriages. Randomised controlled trials are needed to offer more evidence of these relationships.

Growth Hormone Cotreatment for Low-Prognosis Patients According to the POSEIDON Criteria.

BackgroundPoor ovarian response (POR) remains one of the most challenging conditions in assisted reproduction technology. Previous studies seemed to indicate that growth hormone (GH) was a potential solution for the dilemma of POR; however, the role GH played on the low-prognosis patients diagnosed and stratified by the POSEIDON criteria remains indistinct.MethodsThis retrospective study was performed among women with POR according to the POSEIDON criteria who failed a previous in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycle, and the subsequent cycle was under GH cotreatment and conducted within 12 months. These participants were stratified into four groups according to the POSEIDON criteria. The comparison was implemented between the failed cycle and the cycle treated with GH. Generalized estimating equation (GEE) multivariate regression was applied for data analysis.ResultsA total of 428 low-prognosis women were included in this study. GH supplementation improved the live birth rates (47.66%, 28.33%, 45.45%, and 24.07%; in groups 1, 2, 3, and 4, respectively) and the clinical pregnancy rates (OR 19.16, 95% CI 7.87–46.63, p < 0.001; OR 7.44, 95% CI 1.65–33.55, p = 0.009; OR 10.19, 95% CI 2.39–43.52, p = 0.002; OR 27.63, 95% CI 4.46–171.11, p < 0.001; in groups 1, 2, 3, and 4, respectively) in all four POSEIDON groups. The number of oocytes retrieved was significantly elevated in the subgroups with normal ovarian reserve (IRR 1.47, 95% CI 1.36–1.59, p < 0.001; IRR 1.31, 95% CI 1.15–1.49, p < 0.001; in groups 1 and 2, respectively). The number of day-3 good-quality embryos was significantly elevated in the subgroups with either normal ovarian reserve or aged young (IRR 2.13, 95% CI 1.78–2.56, p < 0.001; IRR 1.54, 95% CI 1.26–1.89, p < 0.001; IRR 1.47, 95% CI 1.10–1.98, p = 0.010; in groups 1, 2, and 3, respectively).ConclusionGrowth hormone cotreatment could ameliorate the pregnancy outcome for women with POR under the POSEIDON criteria who failed a previous IVF/ICSI cycle. The application of growth hormone for low-prognosis women who experienced a failed cycle might be considered and further studied.

Impact of L-carnitine supplementation on the in vitro developmental competence and cryotolerance of buffalo embryos.

Background and Aim:Despite many trials, buffalo embryos have poor cryosurvivability because of their high lipid content. L-carnitine was found to be a lipid-reducing agent when added to oocyte and embryo culture media. The study aimed to determine the most effective concentration of L-carnitine to improve the oocyte developmental competence and cryotolerance of buffalo embryos.Materials and Methods:In vitro maturation and embryo culture media were supplemented with four concentrations of L-carnitine: 0 (control), 0.25, 0.5, and 1 mM. Good-quality embryos on 7 days were vitrified using mixtures of dimethyl sulfoxide and ethylene glycol at two concentrations (3.5 and 7 M).Results:The result showed that the cleavage and morula rates were significantly (p<0.05) higher in the 0.5 mM group. Blastocyst rates were significantly (p<0.05) higher at both 0.5 and 1 mM. The rates of viable embryos directly after thawing were significantly (p<0.05) increased in the 0.5 mM group. No significant difference was found in embryos cultured for 24 h after warming among all the groups.Conclusion:The addition of L-carnitine at a concentration of 0.5 mM to the culture media improves the oocyte developmental competence and cryotolerance of buffalo embryos directly after warming but not after 24 h of culture. Nevertheless, further studies must identify how L-carnitine exerts its beneficial micromechanisms.

Why double ovarian stimulation in an in vitro fertilization cycle is potentially unsafe.

The occurrence of two antral follicle recruitment waves in a single inter-ovulatory interval has been detected in ovaries of normal women. This data supports the claim that a double ovarian stimulation in the same cycle may benefit poor responder patients with an increased recovery of mature oocytes and good quality embryos per single cycle. The double stimulation protocol was the object of several published studies in which, surprisingly, the mechanism and the safety of the double stimulation in the same cycle were poorly addressed. We propose that in the double stimulation protocol, the first stimulation impacts more committed oocytes progenitors ready to differentiate into mature oocytes. Conversely, the protracted exposure of developmentally earlier less-committed ovarian stem cells to FSH, which occurs in the double stimulation protocol, impacts the less differentiated stem cells which take longer to differentiate into oocytes. The proposed mechanism has broad implications for the safety of the double stimulation strategy.

Pregnancy Outcomes Following the First Frozen Blastocyst Transfer Among Women Aged Less Than 35 Years Old: A Retrospective Cohort Study

Background: Many guidelines have been issued regarding the number of embryos to be transferred after in vitro fertilization (IVF), but patients and clinicians may be reluctant to accept or offer a single embryo transfer due to the expected lower chance of pregnancy or live birth. This study was aimed to provide additional information on cycle outcome according to the number and quality of thawed transferred blastocysts.Methods: A retrospective cohort study was designed to collect the data of 505 patients who performed the first frozen blastocysts transfer at Tam Anh General Hospital from June 2018 to September 2019. One good-quality embryo was transferred for 121 patients (Group 1), two good for 214 patients (Group 2), one good and one poor for 112 patients (Group 3), one good and two poor for 25 patients (Group 4), and one or two poor for 33 patients (Group 5).Results: The pregnancy rate was 71.9%, 74.8%, 69.4%, 84.0%, and 39.4% in Group 1–5, respectively. The multiple pregnancy rate was 36.9%, 16.9%, and 32.0% in Groups 2–4, respectively, higher than Group 1 (4.9%). The live birth rate was 55.6%, 50.9%, and 60.0% in Group 2–4, respectively, but not significantly different from the Group 1 (47.9%).Conclusions: Transferring an additional good or poor embryo, along with a good embryo, does not increase the live birth rate while the incidence of multiple pregnancies rises significantly.

Efficacy of artificial oocyte activation in patients with embryo developmental problems: a sibling oocyte control study.

To explore whether artificial oocyte activation (AOA) can improve embryo developmental potentiality and pregnancy outcomes for patients with a history of embryo developmental problem. This was a retrospective study and candidate patients with embryo development problems were collected. A total of 1422 MII eggs from the enrolled 140 patients were randomized divided equally into 2 groups, half for the AOA group (AOA), and the rest of sibling mature eggs for the control group (non-AOA). The patients were further divided into two subgroups: (1) the rate of good-quality day 3 embryos was 0% (group 1, n = 66); (2) the rate of good-quality day 3 embryos ranged from 1 to 30% (group 2, n = 74). In the early embryonic growth, there were no significant differences in the outcomes of AOA and non-AOA groups in terms of normal fertilization rates, cleavage rates, day 3 good-quality embryo rates and available blastocyst rates (72.7% vs. 79.3%, 97.4% vs. 98.0%, 20.1% vs. 19.7%, 6.6% vs. 8.4% in group 1, respectively; 77.7% vs. 81.9%, 98.1% vs. 97.0%, 25.8% vs. 22.1%, 9.6% vs. 9.3% in group 2, respectively). In the late embryonic growth, no significant differences were found in biochemical and clinical pregnancy rates, implantation rates, miscarriage rates, and live-birth rates (50.0% vs. 45.2%, 45.2% vs. 40.5%, 37.3% vs. 31.3%, 10.5% vs. 11.8%, 40.5% vs. 35.7%, respectively) between two groups. In addition, neonatal outcomes were similar in both the groups as well. Our study demonstrated that the AOA using ionomycin 1h after ICSI did not bring benefits to the early or late development of embryos derived from patients with a history of embryo developmental problems.

Impact of oxygen tension according to embryo stage of development: a prospective randomized study

Human embryo culture under 2–8% O2 is recommended by ESHRE revised guidelines for good practices in IVF labs. Nevertheless, notably due to the higher costs of embryo culture under hypoxia, some laboratories perform embryo culture under atmospheric O2 tension (around 20%). Furthermore, recent meta-analyses concluded with low evidence to a superiority of hypoxia on IVF/ICSI outcomes. Interestingly, a study on mice embryos suggested that oxidative stress (OS) might only have an adverse impact on embryos at cleavage stage. Hence, we aimed to demonstrate for the first time in human embryos that OS has a negative impact only at cleavage stage and that sequential culture conditions (5% O2 from Day 0 to Day 2/3, then «conventional» conditions at 20% O2 until blastocyst stage) might be a valuable option for human embryo culture. 773 IVF/ICSI cycles were included in this randomized clinical trial from January 2016 to April 2018. At Day 0 (D0), patients were randomized using a 1:2 allocation ratio between group A (20% O2; n = 265) and group B (5% O2; n = 508). Extended culture (EC) was performed when ≥ 5 Day 2-good-quality-embryos were available (n = 88 in group A (20% O2)). In subgroup B, 195 EC cycles were randomized again at Day 2 (using 1:1 ratio) into groups B’ (5% O2 until Day 6 (n = 101)) or C (switch to 20% O2 from Day 2 to Day 6 (n = 94). Fertilization rate, cleavage-stage quality Day 2-top-quality-embryo (D2-TQE), blastocyst quality (Day 5-top-quality-blastocyst (D5-TQB) and implantation rate (IR) were compared between groups A and B (= cleavage-stage analysis), or A(20% O2), B’(5% O2) and C(5%-to-20% O2). Overall, characteristics were similar between groups A and B. Significantly higher rates of early-cleaved embryos, top-quality and good-quality embryos on Day 2 were obtained in group B compared to group A (P < 0.05). This association between oxygen tension and embryo quality at D2 was confirmed using an adjusted model (P < 0.05). Regarding blastocyst quality, culture under 20% O2 from Day 0 to Day 6 (group A) resulted in significantly lower Day 5-TQB number and rates (P < 0.05) compared to both groups B’ and C. Furthermore, blastocyst quality was statistically equivalent between groups B’ and C (P = 0.45). At Day 6, TQB numbers and rates were also significantly higher in groups B’ and C compared to group A (P < 0.05). These results were confirmed analyzing adjusted mean differences for number of Day 5 and Day 6 top quality embryos obtained in group A when compared to those respectively in groups B’ and C (P < 0.05). No difference in clinical outcomes following blastocyst transfers was observed. These results would encourage to systematically culture embryos under hypoxia at least during early development stages, since OS might be detrimental exclusively before embryonic genome activation.

Exploring Epithelial-Mesenchymal Transition Signals in Endometriosis Diagnosis and In Vitro Fertilization Outcomes.

Endometriosis (EMS) pathogenesis has been related to the release of inflammatory mediators in peritoneal fluid, creating an altered microenvironment that leads to low-grade oocyte/embryos and to the reduction of implantation rates. The Epithelial–Mesenchymal Transition (EMT), an inflammation-related process, can be a further contributing factor to EMS. This study aimed to investigate, among various cytokines and EMT markers (Cadherins, TGF-β, HIF-1α), diagnostic markers of EMS and prognostic factors of in vitro fertilization (IVF) outcomes. Herein, EMS patients manifested higher serum levels of the inflammatory molecules IL-6, IL-8, and IL-12 and a decrease in the concentrations of the anti-inflammatory IL-10. Moreover, biochemical markers associated with the EMT process were more elevated in serum and follicular fluid (FF) of EMS patients than in controls. At the end, the number of good-quality embryos was inversely related to serum IL-6 and EMT markers. Interestingly, serum IL-6 and FF IL-10 concentrations differentiated EMS patients from controls. Finally, serum IL-8 and E-Cadherin levels, as well as FF IL-10, predicted positive IVF outcome with great accuracy. Our data confirm the pivotal role of inflammatory mediators (i.e., IL-6 and IL-10) in EMS pathogenesis and suggest that EMT-related markers are elevated in EMS patients and can be predictive of IVF outcome.

Multifactor Prediction of Embryo Transfer Outcomes Based on a Machine Learning Algorithm.

In vitro fertilization-embryo transfer (IVF-ET) technology make it possible for infertile couples to conceive a baby successfully. Nevertheless, IVF-ET does not guarantee success. Frozen embryo transfer (FET) is an important supplement to IVF-ET. Many factors are correlated with the outcome of FET which is unpredictable. Machine learning is a field of study that predict various outcomes by defining data attributes and using relevant data and calculation algorithms. Machine learning algorithm has been widely used in clinical research. The present study focuses on making predictions of early pregnancy outcomes in FET through clinical characters, including age, body mass index (BMI), endometrial thickness (EMT) on the day of progesterone treatment, good-quality embryo rate (GQR), and type of infertility (primary or secondary), serum estradiol level (E2) on the day of embryo transfer, and serum progesterone level (P) on the day of embryo transfer. We applied four representative machine learning algorithms, including logistic regression (LR), conditional inference tree, random forest (RF) and support vector machine (SVM) to build prediction models and identify the predictive factors. We found no significant difference among the models in the sensitivity, specificity, positive predictive rate, negative predictive rate or accuracy in predicting the pregnancy outcome of FET. For example, the positive/negative predictive rate of the SVM (gamma = 1, cost = 100, 10-fold cross validation) is 0.56 and 0.55. This approach could provide a reference for couples considering FET. The prediction accuracy of the present study is limited, which suggests that there may be some other more effective predictors to be developed in future work.

A short length of gonadotropin hyperstimulation is sufficient to achieve an optimal IVF outcome in advance-aged women

ObjectiveTo analyze the duration of gonadotropin hyperstimulation's impacts on oocyte quality and clinical outcomes in aged in vitro fertilization (IVF) patients. Materials and methodsThis retrospective study was carried out using IVF records of the Chang Gung Memorial Hospital IVF center from January 2017 to December 2019. A total of 308 IVF cycles with patients aged 40–44 years were included. Clinical characteristics of patients who received a short controlled ovarian hyperstimulation (COH) (i.e., 6–7 days; s-COH group) or a long COH treatment (i.e., 9–10 days; l-COH group) were compared. In addition, analysis was conducted using data within two age subgroups: 40–42 years and 42–44 years subgroups. ResultsThe s-COH group received significantly lower total doses of gonadotropin and had smaller leading follicles at the time of ovulation trigger when compared to the l-COH group. The s-COH group also produced a significantly lower number of oocytes, mature metaphase II (MII) oocytes, and 2 PN zygotes compared to the l-COH group. However, there was no significant difference in the number of transferable and good-quality embryos between the two treatment groups. Likewise, the pregnancy rate and live birth rate were comparable in the s-COH and l-COH groups. Similar results were obtained when the analysis was limited to select age subgroups (i.e., 40–42 and 42–44 years subgroups). ConclusionWhile a long COH generates more oocytes per cycle, a 6–7 days COH treatment, which is at the lower end of the recommended window of stimulation, could achieve a pregnancy outcome comparable to that applied 9–10 days of COH in aged patients.

Parameters to identify good quality oocytes and embryos in cattle

Oocyte/embryo selection methodologies are either invasive or noninvasive and can be applied at various stages of development from the oocyte to cleaved embryos and up to the blastocyst stage. Morphology and the proportion of embryos developing to the blastocyst stage are important criteria to assess developmental competence. Evaluation of morphology remains the method of choice for selecting viable oocytes for IVP or embryos prior to transfer. Although non-invasive approaches are improving, invasive ones have been extremely helpful in finding candidate genes to determine oocyte/embryo quality. There is still a strong need for further refinement of existing oocyte and embryo selection methods and quality parameters. The development of novel, robust and non-invasive procedures will ensure that only embryos with the highest developmental potential are chosen for transfer. In the present review, various methods for assessing the quality of oocytes and preimplantation embryos, particularly in cattle, are considered. These methods include assessment of morphology including different staining procedures, transcriptomic and proteomic analyses, metabolic profiling, as well as the use of artificial intelligence technologies.

An Intelligent Model for Prediction of In-Vitro Fertilization Success using MLP Neural Network and GA Optimization

In Vitro Fertilization (IVF) is one of the scientifically known methods of infertility treatment. This study aimed at improving the performance of predicting the success of IVF using machine learning and its optimization through evolutionary algorithms. The Multilayer Perceptron Neural Network (MLP) were proposed to classify the infertility dataset. The Genetic algorithm was used to improve the performance of the Multilayer Perceptron Neural Network model. The proposed model was applied to a dataset including 594 eggs from 94 patients undergoing IVF, of which 318 were of good quality embryos and 276 were of lower quality embryos. For performance evaluation of the MLP model, an ROC curve analysis was conducted, and 10-fold cross-validation performed. The results revealed that this intelligent model has high efficiency with an accuracy of 96% for Multi-layer Perceptron neural network, which is promising compared to counterparts methods.

The Effects of Autologous Platelet-Rich Plasma on Pregnancy Outcomes in Repeated Implantation Failure Patients Undergoing Frozen Embryo Transfer: A Randomized Controlled Trial.

Repeated implantation failure (RIF) is a disorder in which good-quality embryos fail to implant in the endometrium following several in vitro fertilization (IVF) cycles. This study aimed to evaluate the efficiency and safety of intrauterine infusion of platelet-rich plasma (PRP) in improvement of pregnancy outcomes in RIF patients undergoing frozen embryo transfer (FET). A total of 438 women with a history of RIF undergoing FET were assessed for eligibility to enter the study. Patients were randomly assigned to the intervention (PRP) and control groups. The intervention group received an intrauterine infusion of 0.5 ml PRP 48 h before embryo transfer while the control group received standard treatment. The rates of chemical and clinical pregnancy were defined as the primary outcome values. All women were followed up until the study endpoints that included the number of neonates born and pregnancy-related complications. Three hundred and ninety-three participants accomplished the study and their data were analyzed. The chemical pregnancy, clinical pregnancy, and live birth rates were higher in the PRP group than control group (p value: <0.0001; p value: <0.0001; p value: <0.0001 respectively). However, there were no significant differences between the two groups in terms of multiple pregnancies and pregnancy complications except for spontaneous abortion. The spontaneous abortion rate was significantly higher in the control group compared to the PRP group (p value = 0.0262). These results suggest that intrauterine infusion of PRP is an effective and safe route to improve pregnancy outcomes in RIF patients undergoing FET.

Evaluation of GnRH antagonist pretreatment before ovarian stimulation in a GnRH antagonist protocol in normal ovulatory women undergoing IVF/ICSI: a randomized controlled trial

BackgroundSynchronization of follicles is key to improving ovulation stimulation with the gonadotropin-releasing hormone (GnRH) antagonist protocol. GnRH antagonist administration in the early follicular phase can quickly decrease gonadotrophin (Gn) levels and achieve downregulation before stimulation, which may improves synchronization. A previous small randomized controlled study (RCT) showed that pretreatment with a GnRH antagonist for 3 days before stimulation may increase oocyte retrieval but cannot increase the pregnancy rate. This study investigated whether the GnRH antagonist pretreatment protocol in ovulatory women can increase the synchronization of follicles and pregnancy outcomes compared with the conventional GnRH antagonist protocol.MethodsThis RCT included 136 normal ovulatory women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Both groups were treated with recombinant follicle-stimulating hormone (r-FSH) and a flexible GnRH antagonist protocol. The women were randomized into two equal groups with or without GnRH antagonist administration from day 2 of the menstrual cycle for 3 days before stimulation. Our primary outcome was the number of retrieved oocytes. Secondary outcomes included the pregnancy rate and live birth rate.ResultsBoth groups had similar baseline characteristics. The number of retrieved oocytes in the study group was comparable to that in the control group (9.5 [8.0–13.0] vs. 11.0 [7.0–14.8], P = 0.469). There was no significant difference in the follicle size. The fertilization rate, number of good-quality embryos, implantation rate, pregnancy rate, ongoing pregnancy rate, live birth rate per embryonic transfer cycle, and miscarriage rate were similar between the two groups.ConclusionThis large RCT analysed GnRH antagonist pretreatment with the GnRH antagonist protocol applied to normal ovulatory women undergoing IVF/ICSI. The number of retrieved oocytes and pregnancy outcomes did not significantly vary.Trial registrationChinese Clinical Trial Registry, ChiCTR1800019730. Registered 26 November 2018.

Alterations of miR-16, miR-let-7a and their target genes expression in human blastocysts following vitrification and re-vitrification

Embryo cryopreservation is a widely used technique in infertility management and today is an essential part of assisted reproductive technology (ART). In some cases, re-vitrification can be applied to good quality supernumerary warmed embryos that have not been transferred in the present cycle. However, there is no study about re-vitrification impact on microRNA and gene expression in human embryos. The purpose of this study is to evaluate miR-16, miR-let7a and target genes expression in in vitro produced human blastocysts following re-vitrification.Day3 embryos obtained from ICSI cycles of fertile couples referring for family balancing program were biopsied and cultured individually. On the fourth day (post-ICSI) male ones (choices of their parents) were transferred and the females (good quality embryos) were donated for research. Donated embryos were cultured to blastocyst stage and assigned to three groups: fresh, vitrified and re-vitrification. Embryos were vitrified on Cryotech carriers. Then blastocysts of three groups were individually assessed for expression of miR-16, miR-let7a and target genes.The results showed that re-vitrification of human blastocysts did not affect the ability to re-expand in culture. In addition, significant decrease was observed in miR-16 and miR-let7a expression in re-vitrified group compared to fresh (p < 0.05). A significant upregulation of the target genes ITGβ3 and BCL-2 in re-vitrified and vitrified embryos was observed compared to the fresh group (p < 0.05). The expression of BAX as a pro-apoptotic gene showed a significant decrease in re-vitrification group comparing with the fresh one (P < 0.05).The results of this research indicated that re-vitrification of embryos changes the expression of miR-16, miR-let-7a and their target genes. These alterations include increased expression of BCl-2 and ITGβ3 genes which play important roles in embryo survival and implantation, respectively. Clinical proof of these effects requires further research.

Effectiveness the perfusion of Endometrial and Subendometrial and Endometrial volume on the endometrial receptivity of FET Cycles

Objective: this study was effects of endometrial and subendometrial blood perfusion and endometrial volume on endometrial receptivity in frozen embryo transfer (FET) cycles. Materials and methods: This prospective observational cohort study, that on infertile women who referred for FET to Shariati Hospital and Omid Infertility Clinic in Tehran (Iran) .112 patients selected among eligible women with good quality embryos. After homogenization, participants underwent endometrial preparation for hormone replacement therapy (HRT) according to a similar routine protocol. On the day of the FET, they underwent a thorough ultrasound examination for possible effective parameters. Subsequently, one to two good quality blastocysts were transferred, and the pregnancy outcomes were monitored. Results: In vitro fertilization (IVF) was performed on 112 patients with a mean age of 33.93±4.93 years. Although, serum β-HCG level was used to confirm pregnancy. Accordingly, out of 112 participating patients, 50 (44.6%) became pregnant after IVF. Based on the results of this study, the endometrial blood flow was significantly different between the two groups of pregnant and non-pregnant women, so that a higher pregnancy rate was observed in participants with multi-focal and spare endometrial blood flows (P&lt;0.05). Additionally, a significant relationship between endometrial blood flow and pregnancy outcome so that there was more ongoing pregnancy rates in those with multi-focal and spare endometrial blood flows (P&lt;0.05). But the endometrial variables of volume, length, width, thickness and pattern were not significantly different between the two groups of pregnant and non-pregnant women. Moreover, contextual parameters had no significant relationship with pregnancy outcome (P&gt;0.05). Endometrial measurement indices were also ineffective on pregnancy outcomes and no significant difference was there between the groups (P&gt;0.05). Conclusion: Collectively, the endometrial blood flow can play an effective role in improving pregnancy event and its stability after IVF, but the endometrial volume was unable to predict pregnancy event and its stability after IVF.

The Impact of Ethanol Sclerotherapy on ICSI Outcomes in Infertile Patients with Endometriomas Undergoing Controlled Ovarian Stimulation

Objective: the aim of the study was to determine whether endometrioma aspiration and alcohol sclerotherapy performed prior to controlled ovarian stimulation has any beneficial effects on ICSI outcomes in patients with endometriomas.&#x0D; Methods: The cycle characteristics and pregnancy outcomes of 103 patients with endometriomas who underwent ethanol sclerotherapy on day 2 of the controlled ovarian stimulation with a gonadotropin antagonist protocol were retrospectively compared with the cycle characteristics of 405 patients with endometriomas who did not receive scleroterapy before stimulation.&#x0D; Results: No statistically significant difference was observed in the number of retrieved oocytes, metaphase II oocytes, fertilization and good quality embryo rates between the two groups. The clinical pregnancy rate, implantation rate and live birth rates were similar among the two groups. No major complications including intraperitoneal haemorrhage, peritonitis, ovarian abscess or intestinal perforation were recorded.&#x0D; Conclusion: The results of the present study indicate that ethanol sclerotherapy does not improve ICSI outcomes when performed right before ovarian stimulation and without concomittant GnRH analogue administration. Since it is a simple outpatient procedure without significant complications, ethanol sclerotherapy may be performed prior to IVF as an alternative to surgery to improve the accessibility of follicles and monitoring of follicle growth in patients with large endometriomas and for those patients with intractable pain symptoms, without decreasing the ovarian reserve.

Expression and significance of miR-30d-5p and SOCS1 in patients with recurrent implantation failure during implantation window

BackgroundPoor endometrial receptivity is a major factor that leads to recurrent implantation failure. However, the traditional method cannot accurately evaluate endometrial receptivity. Various studies have indicated that microRNAs (miRNAs) are involved in multiple processes of embryo implantation, but the role of miRNAs in endometrial receptivity in patients with recurrent implantation failure (RIF) remains elusive. In the present study, we investigated the presence of pinopodes and the roles of miR-30d-5p, suppressor of cytokine signalling 1 (SOCS1) and the leukaemia inhibitory factor (LIF) pathway in women with a history of RIF during the implantation window.MethodsEndometrial tissue samples were collected between January 2018 to June 2019 from two groups of women who underwent in vitro fertilisation and embryo transfer (IVF-ET) or frozen ET. The RIF group included 20 women who underwent ≥ 3 ETs, including a total of ≥ 4 good-quality embryos, without pregnancy, whereas the control group included 10 women who had given birth at least once in the past year. An endometrial biopsy was performed during the implantation window (LH + 7). The development of pinopodes in the endometrial biopsy samples from all groups was evaluated using scanning electron microscopy (SEM). Quantitative reverse transcription-polymerase chain reaction and western blotting were used to investigate the expression levels of miR-30d-5p, SOCS1, and the LIF pathway.ResultsThe presence of developed pinopodes decreased in patients with RIF on LH + 7. The expression level of miR-30d-5p decreased in the endometria during the implantation window of patients with RIF, whereas the mRNA and protein levels of SOCS1 were significantly higher in the RIF group than in the control group. Furthermore, a negative correlation was observed between the expression of miR-30d-5p and SOCS1 (r2 = 0.8362). In addition, a significant decrease in LIF and p-STAT3 expression was observed during the implantation window in patients with RIF.ConclusionsMiR-30d-5p and SOCS1 may be potential biomarkers for endometrial receptivity. Changes in pinopode development and abnormal expression of miR-30d-5p, SOCS1 and LIF pathway in the endometrium could be the reasons for implantation failure.