In Vitro Fertilization-embryo Transfer Research Articles

Assisted reproductive technology in Japan: A summary report for 2020 by the ethics Committee of the Japan Society of obstetrics and gynecology.

Since 1986, the Japan Society of Obstetrics and Gynecology assisted reproductive technology (ART) registry system has collected data on national ART use and outcomes trends in Japan. Herein, we describe the characteristics and outcomes of ART cycles registered during 2020 and compare the results with those from 2019. In 2020, 621 ART facilities participated in the registration. The total number of registered cycles was 449 900, and there were 60 381 live births, which decreased from the previous year (1.79% and 0.36% decrease, respectively). The number of freeze-all in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles increased in 2020, and the number of neonates born was 2282 for IVF-embryo transfer (ET) cycles and 2596 for ICSI cycles, which had decreased from the previous year. Frozen-thawed ET (FET) cycles had slightly increased from 2019 (0.04%). In 2020, 215 285 FET cycles were conducted, resulting in 76 196 pregnancies and 55 503 neonates. Single ET was performed in 81.6% of fresh transfers and 85.1% of frozen-thawed cycles, respectively, resulting in over 97% singleton pregnancies/livebirths rates. Despite the COVID-19 pandemic during 2020, the overall number of ART cycles and neonates born demonstrated only a slight decrease in 2020 compared with 2019.

A retrospective study of pregnancy outcomes when intravenous immunoglobulin is used for the treatment of recurrent spontaneous miscarriages with subchorionic hematoma

Objective: To investigate the incidence of subchorionic hematoma (SCH), pregnancy outcomes and health status of offspring in patients with recurrent spontaneous miscarriage (RSA) treated with intravenous immunoglobulin (IVIg). Methods: The records of 775 patients with RSA were retrospectively reviewed. RSA with SCH were all treated with IVIg. Pregnancy outcomes examined were the rates of miscarriage, stillbirth, pre-term birth, and live birth. The pregnancy complications and comorbidities examined included oligohydramnios, hypertensive disorders, gestational diabetes, premature membrane rupture, placental adhesions, placenta previa, postpartum hemorrhage, placental abruption, and low birth weight. The health status of offspring of RSA patients with SCH was followed up by telephone, record physical and neurodevelopmental performance, and diseases under 5 years old, then compare with common children. Based on the ratio of SCH volume to that of the gestational sac, SCH was divided into small (ratio < 20%), moderate (ratio = 20%–50%), and large (ratio > 50%). Statistical analysis was performed with IBM SPSS Statistics 23.0. Comparison of continuous variables was analyzed using t-test. Categorical variables were compared by using χ2 test or Fisher’s exact test. Multivariable logistic regression was used for adjusting certain confounders. Results: Of the 775 patients with RSA, 110 RSA had a SCH (incidence = 14.2%). SCH was firstly found at 8.29 (5.00–11.58) weeks pregnant. There was no statistical difference in age, number of pregnancies, parity and miscarriages between patients with and without an SCH. The incidence of SCH in in-vitro fertilization embryo transfer (IVF-ET) patients was higher than in natural pregnancy patients (27.9% vs. 13.1%, P < 0.05). RSA with SCH patients with pregnancy outcome data called Group A (n = 94), RSA without SCH patients with pregnancy outcome data called Group B (n = 556), the rates of miscarriage (17.0% vs.12.4%), stillbirth (0 vs. 0.4%), pre-term delivery (9.6% vs. 10.8%), live birth (84.7% vs. 80.9%), and pregnancy complications were not different between Group A and B. The rate of vaginal bleeding in the Group A was higher than in the Group B (P < 0.05). There was no significant difference in the birth weight, the rate of low birth weight infants, neonatal asphyxia, or neonatal pneumonia between the groups. 43 puerpera in the experimental group were willing to receive telephone follow-up, who gave birth from December 2015 to November 2016. A total of 43 live births were delivered. By March 2022, the children were 5 years and 4 months old to 6 years and 3 months old. There is no difference in the physical development compared with common children. A child was diagnosed with neuropsychological delay. The incidence rate of community acquired pneumonia (CAP) was 27.9 per 1000 person-years for children under 5 years. In patients with a SCH and vaginal bleeding, the rate of preterm birth was 16.7%. The rate of preterm birth was highest (36.4%) in RSA patients with a large SCH, and only 5.7% in patients with a small SCH (P < 0.05). Patients treated with IVIg had mild adverse reactions such as hypothermia, dizziness, and rash with rates of 1.8%, 1.8%, and 0.9%, respectively. Conclusion: The incidence of SCH was 14.2% in RSA. Pregnancy outcomes were similar between the RSA patients with a SCH treated with IVIg treatment and RSA patients without a SCH. There is no difference in the physical development between offspring of RSA with SCH and common children, and effect of SCH on neurodevelopment of offspring needs to be further verified by expanding the sample size. RSA patient with a SCH are prone to have vaginal bleeding and abdominal pain. For RSA patients with a SCH and vaginal bleeding, or SCH volume ratio > 50%, even after IVIg, still leads to a significantly higher preterm birth rate.

Retrospective analysis for 424 330 first-line screening results of non-invasive prenatal testing in Hebei province

Objective: To evaluate the effect of noninvasive prenatal testing (NIPT) as first-line screening in fetal chromosome aneuploidy screening practice, and to provide evidence for the prevention and control strategy of birth defects. Methods: Since July 2019, Hebei province had carried out the NIPT project providing first-line screening for eligible pregnant women in the area (except for those who were not applicable). Pregnant women with high risk received genetic counseling, prenatal diagnosis and intervention guidance. Low risk and false-positive ones received continuous detection and moved to prenatal diagnosis center for counseling and diagnosis if abnormities were discovered. All pregnant women were followed up to learn about pregnancy outcomes and newborn health status. Detection results and clinical data of pregnant women participating the NIPT project from July 2019 to July 2020 were collected. The detection results and effect of NIPT were analyzed. Results: (1) Basic information of the screened population: A total of 424 330 pregnant women were screened, and 423 596 were successfully detected, with a success rate of 99.83% (423 596/424 330). The age of pregnant women was (28.8±4.5) years old; the gestational age of screening was (16.6±2.3) weeks; the proportion of advanced-age pregnant women (≥35 years old) was 10.18% (43 132/423 596); in vitro fertilization-embryo transfer (IVF-ET) rate was 1.58% (6 713/423 596); the twin rate was 1.38% (5 849/423 596); the proportion of primipara was 34.23% (144 977/423 596). (2) Screening results and detection performance: totally, 325, 73 and 20 pregnant women were diagnosed with trisomy 21, 18 and 13; the sensitivity were 99.39%, 100.00% and 100.00%; the specificity were 99.98%, 99.99% and 99.98%; the positive predictive value were 75.76%, 68.87% and 21.51%, respectively. Besides, 249 190 pregnant women were received supplementary reports as well, and 255, 10 and 9 were confirmed for sex chromosome aneuploidy, other autosomal aneuploidy and deletion/duplication syndrome; the positive predictive value were 37.78%, 6.06% and 32.14%, respectively. The sensitivity of NIPT for target trisomy (trisomy 21, 18 and 13) screening in advanced-age, IVF-ET and twin pregnant women were 99.29%, 100.00% and 90.00%, respectively; the specificity were 99.93% for all; the positive predictive value were 82.25%, 61.54% and 69.23%, respectively. Conclusions: NIPT has a significant effect and good performance in the first-line screening of fetal chromosome aneuploidy in the whole population, which might provide reference for the improvement of birth defect prevention and control strategy.

Assisted reproductive technology treatment and risk of multiple sclerosis – a Danish cohort study

To compare the incidence of multiple sclerosis (MS) among women who had undergone assisted reproductive technology (ART) treatment with the women who had conceived a child without previous ART treatment. A register-based nationwide cohort study. Women with a first ovarian stimulation cycle before invitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) (i.e., ART treatment) recorded in the Danish IVF register between 1996 and 2018; and women recorded in the Danish Medical Birth Register with the birth of their first child where date of conception is between 1996 and 2018. The cohort was observed until March 10,2021. Mainly included IVF, ICSI, and fresh embryo transfer with hormone stimulation. A diagnosis of MS recorded in the Danish Multiple Sclerosis Registry. Crude and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were calculated. A total of 585,716 women were included in the cohort of which 63,791 (11%) were exposed to at least one initiated IVF or ICSI cycle during the study period. Cycles with oocyte donation were excluded. The median follow-up time for the entire cohort was 12.4 years (Q1-Q3= 6.6-18.1). Compared with women conceiving without previous ART, ART treated women were older (31.8 years vs. 27.5 years), more often had a university degree (45% vs. 36%), and more often had received other fertility treatments than IVF or ICSI before cohort entry (26% vs. 3%). We found no association between incident MS and exposure to ART compared with non-ART pregnancy (aHR=1.08; 95 % CI, 0.93-1.25). An analysis following intention-to-treat principle on a propensity score matched sub cohort confirmed our results. In subgroup analysis including all ART cycles among the ART treated women, we found no increased risk of MS within 2 years of ART cycle start for successful ART cycles (pregnancy) compared with failed ART cycles (no pregnancy) (aHR=1.01; 95% CI, 0.58-1.76). We found a non-significant trend toward increased risk of MS with increasing numbers of ART cycles although based on small numbers. Women treated with ART do not seem to be at increased risk of developing MS compared with the women not exposed to ART.

Decreased CD44v3 expression impairs endometrial stromal cell proliferation and decidualization in women with recurrent implantation failure

BackgroundThe precise pathogenesis of poor endometrial receptivity in recurrent implantation failure (RIF) remains unclear. This study was aimed at exploring the effects of different CD44 isoforms in the mid-secretory phase endometrium on endometrial receptivity in women with RIF.MethodsMid-secretory phase endometrial tissue samples were obtained from the following two groups of women who had undergone IVF: (a) 24 patients with RIF and (b) 18 patients with infertility due to tubal obstruction, who had achieved a successful clinical pregnancy after the first embryo transfer in IVF (control group). Identification of differentially expressed CD44 isoforms in endometrial tissues was assessed using immunohistochemistry, qPCR, and western blotting. Effects of overexpression and knockdown of CD44v3 on proliferation and decidualization of immortalized human endometrial stromal cells (T-HESCs) and primary HESCs were investigated by qPCR and western blot analysis. A heterologous coculture system of embryo implantation was constructed to mimic the process of trophoblast invasion during implantation.ResultsThe expression of CD44v3 was significantly higher in the mid-secretory phase of endometrial stromal cells than in the proliferation phase, but was notably lower in RIF patients. Knockdown of CD44v3 significantly downregulated cell proliferation both in T-HESCs and HESCs. The expression of decidualization markers, prolactin (PRL) and insulin like growth factor binding protein-1 (IGFBP1), was notably decreased following the knockdown of CD44v3, whereas the expression of both PRL and IGFBP1 increased after its overexpression in HESCs. Furthermore, the CD44v3-knockdown HESCs displayed significant deficiency in supporting trophoblast outgrowth in a coculture system of embryo implantation; however, overexpression of CD44v3 in HESCs promoted trophoblast outgrowth.ConclusionThe reduced expression of CD44v3 suppresses the proliferation and decidualization of HESCs, which might play a pivotal role in poor endometrial receptivity in women with RIF.

Effect of transcutaneous electrical acupoint stimulation on pregnancy outcomes in women with in vitro fertilization-embryo transfer: A systematic review and meta-analysis.

Objective: The purpose of this systematic review and meta-analysis was to evaluate the efficacy and safety of transcutaneous electrical acupoint stimulation (TEAS) on pregnancy outcomes in women undergoing in vitro fertilization-embryo transfer (IVF-ET), in order to provide evidence-based medical support. Methods: We searched the Cochrane Library, Embase, PubMed, Web of Science, SinoMed, and CNKI for relevant randomized controlled trials (RCTs) from inception to 31 May 2022, using the search terms "transcutaneous electrical acupoint stimulation," "TEAS," "in vitro fertilization-embryo transfer," "IVF-ET," "randomized controlled trial," and "clinical trials." The experimental group was treated with TEAS or combined with ovulation-inducing medication, and the control group was treated with mock TEAS (mTEAS), ovulation-inducing medication, or no intervention. The main outcome was the clinical pregnancy rate. Secondary outcomes were the embryo implantation rate, live birth rate, biochemical pregnancy rate, and number of oocytes retrieved. Stata15.1 software was used for data summary and analysis. Results: This review involved 15 RCTs and 4,281 participants. TEAS were superior to the control group for improving the clinical pregnancy rate [RR: 1.29, 95% CI: 1.19 to 1.40; p < 0.001; I2 = 23.0%], embryo implantation rate [RR: 1.43, 95% CI: 1.22 to 1.69; p < 0.001; I2 = 35.9%], live birth rate [RR: 1.33, 95% CI: 1.14 to 1.54; p < 0.001; I2 = 47.3%], and biochemical pregnancy rate [RR: 1.15, 95% CI: 1.05 to 1.26; p = 0.003; I2 = 49.1%], without significant heterogeneity. TEAS had no statistically significant effect on the number of oocytes retrieved as compared with the control group, and the heterogeneity was high [SMD: 0.34, 95% CI: -0.04 to 0.72; p = 0.081; I2 = 77.6%]. We performed subgroup analysis based on the sample size, interventions and intervention time-point. The results showed that the sample size had no effect on the results. There was no significant difference between TEAS and ovulation-inducing medication in the clinical pregnancy rate or the embryo implantation rate. In addition, TEAS did not significantly increase the embryo implantation rate or the live birth rate, compared with no intervention. In terms of safety, mild allergic symptoms were found in both the experimental group and the control group. Conclusion: In general, existing evidence supports the potential value of TEAS as an adjunctive treatment for improving pregnancy outcomes. High-quality, large-sample RCTs are needed to further support this conclusion. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=334892, identifier PROSPERO CRD42022334892.

Clinical pregnancy outcomes prediction in vitro fertilization women based on random forest prediction model: A nested case-control study.

The present study aimed to analyze the risk factors influencing the in vitro fertilization embryo transfer (IVF-ET) pregnancy and to construct a prediction model for clinical pregnancy outcome in patients receiving IVF-ET based on the predictors. In this nested case-control study, the data of 369 women receiving IVF-ET were enrolled. Univariate and multivariate Logistic regression analyses were conducted to identify the potential predictors. Ten-fold cross validation method was used to validate the random forest model for predicting the clinical pregnancy. The receiver operating characteristic curve was drawn to evaluate the prediction ability of the model. The importance of variables was shown according to Mean Decrease Gini. The data delineated that age (odds ratio [OR]= 1.093, 95% confidence interval [CI]: 1.036-1.156, P = .0010), body mass index (BMI) (OR = 1.094, 95%CI: 1.021-1.176, P = .012), 3 cycles (OR = 0.144, 95%CI: 0.028-0.534, P = .008), hematocrit (HCT) (OR = 0.865, 95% CI: 0.791-0.943, P = .001), luteinizing hormone (LH) (OR = 0.678, 95%CI: 0.549-0.823, P < .001), progesterone (P) (OR = 2.126, 95%CI: 1.112-4.141, P = .024), endometrial thickness (OR = 0.132, 95%CI: 0.034-0.496, P = .003) and FSH (OR = 1.151, 95%CI: 1.043-1.275, P = .006) were predictors associated with the clinical pregnancy outcome of patients receiving IVF-ET. The results might provide a novel method to identify patients receiving IVF-ET with a high risk of poor pregnancy outcomes and provide interventions in those patients to prevent the occurrence of poor pregnancy outcomes.

Effects of sequential cleavage and blastocyst embryo transfer on pregnancy outcomes in patients with poor ovarian response

The management of patients with poor ovarian response (POR) remains a major challenge for fertility specialists in in vitro fertilization-embryo transfer (IVF-ET). In this retrospective cohort study, we aimed to evaluate the clinical effect of sequential transfer on pregnancy outcomes in patients with POR. A total of 3579 POR patients who underwent the first frozen embryo transfer (FET) cycle were enrolled from January 2018 to April 2021. The patients were divided into three groups according to the embryo transfer (ET) strategy adopted: a study group that included POR patients in whom a cleavage-stage embryo (day 3) and a blastocyst (day 5/6) were transferred (sequential transfer group), and two control groups in whom two cleavage-stage embryos (D3-dET group) or two blastocysts (D5/6-dET group) were transferred. The study group was matched with the control groups at a ratio of 1:4 by propensity score matching (PSM). The main pregnancy outcomes measured were the live birth rate and multiple pregnancy rate. After PSM, the live birth rate in the sequential transfer group was significantly higher than that in the D3-dET group (44.2% vs. 34.3%, P = 0.019), and was similar to that in the D5/6-dET group (44.2% vs. 45.3%; P = 0.90). In addition, there was no increase in the risk of multiple pregnancy among POR patients undergoing sequential transfer compared with both D3-dET (26.7% vs. 25.6%, P = 0.85) and D5/6-dET (26.7% vs. 28.4%, P = 0.97) groups. These findings imply that sequential transfer is an effective option for POR patients and could be utilized after careful consideration.

The impact of sleep on in vitro fertilization embryo transfer outcomes: a prospective study

To prospectively examine the association between sleep quality before embryo transfer with pregnancy outcomes in a population with infertility. Prospective observational cohort study. Center for Reproductive Medicine, Shandong University. From 7,847 women who enrolled from July 2019 to July 2020, 3,183 were eligible. Information about sleep, including sleep quality, sleep duration, and sleep chronology, were collected before embryo transfer using an integrated questionnaire. Sleep quality is quantified by the Pittsburgh Sleep Quality Index (PSQI) with a cut-point of 5 (PSQI >5 identifying poor sleep vs. PSQI ≤5 identifying good sleep). Average weekly sleep duration was calculated and divided into 5 groups (≤7, 7-8, 8-9, 9-10, and >10 h/d). In defining sleep chronotype, women with a sleep midpoint earlier than 2:30 AM were defined as morningness type, whereas those with a sleep midpoint later than 3:30 AM were defined as eveningness type, and the remainder were defined as an intermediate type. Rate of clinical pregnancy and live birth. Compared with those reporting poor sleep quality, those reporting good sleep quality showed higher clinical pregnancy (69.3% vs. 65.1%) and live birth rates (50.5% vs. 45.7%). After adjusting for confounding factors, women who self-reported good sleep had a higher probability of acquiring clinical pregnancy (RR, 1.07; 95% confidence interval, 1.01-1.13) and of live birth (RR, 1.12; 95% confidence interval, 1.02-1.23). Women with the morningness chronotype had the lowest rates of clinical pregnancy and live birth and had the highest rate of miscarriage. Sleep duration was found to have no significant association with any outcomes. In the stratified analyses, the positive associations of good sleep quality with clinical pregnancy and live birth existed only among women younger than 35 years old or who had undergone fresh embryo transfer. Good sleep quality was positively associated with outcomes in invitro fertilization embryo transfer (IVF-ET), particularly with clinical pregnancy and live birth. Poor sleep quality may be a risk factor for adverse IVF-ET outcomes for women <35 years old. Treating sleep disorders and providing sleep behavior guidance to patients receiving IVF-ET may improve pregnancy outcomes.

Septum Resection Prior to In Vitro Fertilization-Embryo Transfer: A Retrospective Controlled Study.

To investigate the effectiveness of surgery for septate uterus in infertile patients before in vitro fertilization-embryo transfer (IVF-ET). The data of 937 infertile patients with septate uterus and achieved singleton pregnancy after IVF-ET from January 2014 to December 2015 were retrospectively analyzed. Thousand five hundred seventy-eight infertile patients with a normal uterus who achieved singleton pregnancy during the same period were selected as the control group. Patients with septate uterus were divided into two groups according to whether the septum was resected. The pregnancy and perinatal outcomes of the surgical group and the nonsurgical group were compared with the control group. The secondary infertility patients who were surgically corrected septa were also chosen as self-controls and an analysis was performed on their fertility outcomes pre- and post-surgery. Compared with the control group, the surgical group had increased rates of early miscarriage, preterm delivery, and low birthweight and a significantly reduced live birth rate (P < .05). The outcomes of the nonsurgical and control groups were similar. Using secondary infertility patients who were surgically corrected septa as self-controls, after surgery, the rates of miscarriage and ectopic pregnancy were significantly lower and the live birth rate was significantly higher (P ≤ .001); however, perinatal mortality was not significantly different before and after surgery. Patients with a septum depth greater than 10 mm or 5-10 mm associated with a history of unexplained recurrent miscarriage, IVF failure, or infertility might benefit from resection of the uterine septum with hysteroscopic metroplasty.

Elevated serum uric acid level is associated with adverse reproductive outcomes in women with polycystic ovary syndrome undergoing in vitro fertilization or intracytoplasmic sperm injection embryo transfer cycles: a retrospective cohort study

Serum uric acid levels are elevated in polycystic ovary syndrome, however, the relationship between serum uric acid level and reproductive outcomes in women with polycystic ovary syndrome remains unclear. This study aimed to investigate the association between serum uric acid level and the reproductive outcomes in women with polycystic ovary syndrome undergoing invitro fertilization or intracytoplasmic sperm injection embryo transfer cycles. This was a retrospective cohort study performed at a university-affiliated reproductive medicine center. A total of 1903 women with polycystic ovary syndrome undergoing their first invitro fertilization or intracytoplasmic sperm injection embryo transfer cycles between January 2010 and January 2021 were initially included. The trends for reproductive outcomes in polycystic ovary syndrome across quartiles of serum uric acid levels were assessed. A logistic regression analysis was performed to obtain the odds ratios for invitro fertilization outcomes based on the quartiles of serum uric acid with or without adjusting for potential confounding variables. Using generalized additive models, serum uric acid was further treated as its original continuous property to visualize its nonlinear relationship with invitro fertilization outcomes. The live birth rate was the main outcome. After exclusions, a total of 883 women with polycystic ovary syndrome with their first fresh-embryo transfer cycles were included. In quartiles of serum uric acid levels, there was a significant decreasing trend in the live birth rate from the lowest quartile (Q1: 61.8%) to the highest (Q4:45.9%) (Ptrend=.002). The percentage of low birthweight increased from Q1 (22.3%) to Q4 (31.7%) (Ptrend=.049). Compared with those in Q1, women in Q4 showed a significant lower probability of live birth and clinical pregnancy and a higher risk for low birthweight (all P<.05). Both the unadjusted and adjusted generalized additive models indicated that as the serum uric acid level increased, the probability of clinical pregnancy and the live birth rate exhibited an overall decreasing profile, and the risk for low birthweight showed an increasing profile. An elevated serum uric acid level is associated with decreased probabilities of live birth and clinical pregnancy and an increased risk for low birthweight in women with polycystic ovary syndrome. However, these associations may be confounded by other factors and more well-designed studies are needed to confirm these findings in the future.

Correlation of female age with outcome of IVF in a low-resource setting.

To determine the effect of female age on pregnancy outcome after in vitro fertilization/embryo transfer (IVF-ET). A prospective study was conducted involving 266 women who had IVF-ET at Nisa Fertility and Genetic Center, Abuja, Nigeria. All eligible consenting women were recruited to the study. The main outcome measure was clinical pregnancy. Data were analyzed using IBM SPSS Statistics version 25. P< 0.05 at 95% confidence intervals was taken as significant. A total of 266 patients were recruited and included in the study; 104 pregnancies were recorded, giving an overall pregnancy rate of 39.1%. The age range of the patient was 26-43 years (mean age 33.9± 2.41 years) while the mean number of embryo transfers per patient was 2.2. The clinical pregnancy rate for women aged below 30 years was 69.4% while the pregnancy rate for patients aged 30-34 years, 35-39 years, and 40-43 years was 52.6%, 24.7%, and 9.4%, respectively (P< 0.0001). The study found that the success rate of IVF-ET decreases significantly in women aged over 34 years. Women should be counseled about the age-related risk of infertility and referred to a fertility center as early as possible.

Effects of intrauterine human chorionic gonadotropin administration on endometrial receptivity and embryo implantation

AimsEven though major advances have occurred in in vitro fertilization-embryo transfer (IVF-ET) techniques in recent years, low efficacy of embryo implantation rates after fresh cycle of IVF-ET around 25–30 % is still a biggest challenge to physicians. To address this, clinicians have used intrauterine administration of human chorionic gonadotropin (hCG), one of the initial arrays of molecular crosstalk occurred at maternal-fetal interface. However, many reports have demonstrated the conflicting outcomes with various efficacy. This study aims to provide evidence of the optimal timing of hCG administration to enhance the rates of embryo implantation via improving the uterine environment. Main methodshCG was administered into one side of mouse uterine horns and saline was infused into the other side of horns as a control. Alterations in the endometrial thickness, endometrial receptivity and angiogenesis-related gene expression, responses of progesterone receptor, and subsequent in vitro fertility assessment were evaluated in hCG-treated endometrium in mice. Key findingshCG administration induced a serial induction of endometrial receptivity and angiogenesis-related genes and maximally enhanced their expression levels around 72 h after treatment with no significant morphological alterations in the numbers of endometrial glands and thickness. Moreover, using an in vitro model of embryo attachment, hCG treatment significantly promoted the stability of attached embryos, supporting the positive effect of hCG on the initial stage of embryo implantation. SignificanceOur findings suggest a new consensus criteria providing a potential strategy of clinical use of hCG for the cleavage-stage ET rather than blastocyst-stage ET to achieve maximal effects of IVF-ET.

The cytokine profiles in follicular fluid and reproductive outcomes in women with endometriosis.

Endometriosis patients undergoing in vitro fertilization-embryo transfer (IVF-ET) treatment suffer from poor oocyte quality, a reduced likelihood of the fertilization rate, and low embryo quality. The dysregulation of immune cells and cytokine profiles in the follicular fluid (FF) may play an important role in the competence of the oocyte and the development of the embryo, but the mechanism remains largely unknown. A total of 40 proved advanced staged endometriosis patients were enrolled in this study. The pregnancy results were followed until all the embryos collected by the first oocyte retrieval cycle were used up. The immune cells subtypes in FF and serum collected on the day of oocyte retrieval were detected by flow cytometry and 27 cytokines were determined using the Bio-Plex Pro Human Cytokine 27-Plex Immunoassay. The specific effect of cytokine on the gene expression of human granulosa cells was determined by RT-qPCR. The fertilization rate and the cumulative live birth rate were significantly lower in the endometriosis group. The ratio of CD4+ /CD8+ T cells in FF was significantly lower, while the level of IP-10, RANTES and G-CSF were statistically higher in the endometriosis group. The level of IP-10 correlated with the IVF outcome. Moreover, treated by IP-10, the mRNA level of FSHR and CYP19A1 the human granulosa cells were downregulated in vitro. These results suggest that alterations of the lymphocyte subsets and cytokines in women with advanced endometriosis may have an impact on the oocyte development and resulting in poorer IVF outcomes.

Efficacy of Acupoint Application on In Vitro Fertilization Outcome in Patients with Polycystic Ovary Syndrome: A UHPLC-MS-Based Metabolomic Study.

Objective To explore the clinical effect of acupoint application on the outcome of in vitro fertilization-embryo transfer (IVF-ET) in patients with polycystic ovary syndrome (PCOS) of the phlegm-dampness type and elucidate its possible mechanism of action from the perspective of follicular fluid metabolomics. Methods A total of 90 patients undergoing IVF-ET due to infertility were selected and divided into three groups: the treatment group (PCOS with acupoint application, n = 30), the control group (PCOS without acupoint application, n = 30), and the normal group (non-PCOS, n = 30). All patients received a gonadotropin-releasing hormone agonist (GnRH-a) long protocol for controlled ovarian hyperstimulation (COH). Among them, the treatment group was also given the acupoint application from the day of pituitary downregulation to the day of the human chorionic gonadotrophin (hCG) trigger. Ultrahigh-performance liquid chromatography connected with quadrupole time-of-flight mass spectrometry (UHPLC-MS) was adopted for untargeted metabolomic analysis of follicular fluid collected from the three groups of patients on the day of oocyte pick-up (OPU). The significantly differential metabolites were screened using univariate and multivariate statistical analysis, and the related metabolic pathways were identified by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Results Metabolomic analysis showed that the treatment group's follicular fluid samples were aggregated with the normal group and separated from the control group. A total of 34 significantly differential metabolites were found in the follicular fluid of patients with phlegm-dampness PCOS and normal people. With the intervention of acupoint application, seven metabolites (pseudouridine, phenol, 2-oxoadipic acid, 9R,10S-EpOME, DL-lactate, nicotinamide, and DL-indole-3-lactic acid) were all downregulated, mainly involving the pathways of pyruvate metabolism, nicotinate and nicotinamide metabolism, protein digestion and absorption, biosynthesis of amino acids, and pyrimidine metabolism. Conclusions Acupoint application can effectively improve the clinical symptoms and the outcome of IVF-ET treatment in patients with PCOS of the phlegm-dampness type, and its mechanism of action may be related to the regulation of the pathways of pyruvate metabolism, nicotinate and nicotinamide metabolism, protein digestion and absorption, biosynthesis of amino acids, and pyrimidine metabolism.

IS AN AGING ENDOMETRIUM MORE LIKELY TO SHOW AN ADVERSE INFERTILITY FACTOR, I.E., A TRIPLE-LINE (TL) ENDOMETRIAL ECHO PATTERN IN MID-LUTEAL PHASE, WHEN TRANSFERRING FROZEN-THAWED EMBRYOS?

The presence of a TL endometrial echo pattern and the mid-luteal phase has been associated with decreased fecundity in women trying to conceive in natural cycles or in vitro fertilization-embryo transfer (IVF-ET) with fresh embryos or even following frozen ET. The objective of this study was to compare the frequency of a TL mid-luteal phase echo pattern as age advances and whether the presence of a TL pattern has a more negative effect on fertility as age advances in frozen ET cycles.

OBESITY IS ASSOCIATED WITH INCREASED MISCARRIAGE RATES IN PAIRED SIBLING DONOR OOCYTE RECIPIENT CYCLES

Obesity rates in the United States have increased over the past several decades. Obesity has many known adverse consequences on fertility and obstetrical outcomes. This study aimed to determine whether body mass index (BMI) adversely affects pregnancy outcomes following donor egg IVF embryo transfer, by analyzing donor oocyte recipient cycles using paired sibling oocytes.

Effect of weight loss on pregnancy outcomes, neuronal-reproductive-metabolic hormones and gene expression profiles in granulosa cells in obese infertile PCOS patients undergoing IVF-ET.

ObjectiveTo investigate the effect of weight loss on pregnancy outcomes, PCOS related neuronal-reproductive-metabolic hormones and ovarian granulosa cell gene expression profiles in obese PCOS infertile patients undergoing in vitro fertilization-embryo transfer (IVF-ET).Methods75 patients undergoing IVF-ET due to tubal factors alone collected as the control group (group A), and 352 patients with obese PCOS infertility were divided into four groups according to the amount of weight loss before IVF: 0 kg (group B), 1-5 kg (group C), 5-10 kg (group D), and >10 kg (group E). Six cases of ovarian granulosa cells were collected randomly with the random number table method in each group for detecting mRNA profiling. Pathway networks and biological functions of the differentially expressed genes were analyzed. Validation by RT-PCR was performed.Results(1) The levels of luteinizing hormone(LH), testosterone(T) and homeostasis model assessment insulin resistance(HOMA-IR) in group E were significantly lower than those in groups B and C (P<0.05). (2) Compared with groups A and E, groups B and C showed increased total gonadotropin (Gn) and days of Gn stimulation (P<0.05), and the E2 level on trigger day and number of oocytes obtained in group B was significantly less than that in group E (P<0.05 or 0.01). Embryo implantation rate, clinical pregnancy rate and live birth rate were increased and miscarriage rate was decreased in groups A, D and E compared with group B (P<0.05 or 0.01). (3) There were significant differences among the control group and PCOS groups in some genes that are involved in neuronal-reproductive-metabolic endocrine, transcriptional regulation, cell proliferation and differentiation, etc (P<0.05). RNA-Seq results were validated by real time PCR analysis for the expression of follicle stimulating hormone receptor (FSHR), drosophila mothers against decapentaplegic protein 7(Smad7) and glutathione peroxidase 3(GPX3) genes that are known to have an important role in follicular development. Functional alterations were confirmed by the improvement in the ovarian responsiveness to Gn and embryo quality.ConclusionWeight loss more than 5kg may regulate the neuroreproductive endocrine hormone secretion, insulin resistance and gene expression profiles of ovarian granulosa cells, so as to improve the ovarian responsiveness to Gn, the embryo quality, embryo implantation rate, clinical pregnancy rate, live birth rate, and reduce the spontaneous abortion rate in obese infertile PCOS patients undergoing IVF-ET.Clinical trial registration www.chictr.org.cn, identifier ChiCTR1800018298.

Ефективність програм екстракорпорального запліднення (IVF/ICSI) у пацієнток із прогнозованою слабкою відповіддю яєчників

Purpose - to show the effectiveness of in vitro fertilization (IVF) programs in infertile women with a predicted poor ovarian response to stimulation with various gonadotropins and to study the course of pregnancy, childbirth and the condition of their newborns. Materials and methods. The Group І is 75 women, the controlled stimulation of superovulation in which by urinary gonadotropins was performed in the protocol with the use of gonadotropin-releasing hormone antagonist. The Group ІІ (comparison) is 65 women, the stimulation of superovulation in which was carried out according to an analogical scheme with recombinant gonadotropins. Confirmation or exclusion of biochemical pregnancy was carried out by determining the level of total human chorionic gonadotropin in blood serum 14 days after embryo transfer. Data processing was carried out using the Stat Soft Statistica 8.0 software package. Results. The frequency of cancellation of IVF cycle (IVF/ICSI) in the patients of the Group І was reliably lower than among the patients of the Group ІІ: in the Group І it was 2 (2.7%) cases against 8 (12.3%) cases in the Group ІІ (p&lt;0.05). IVF cycle cancellations among the patients of the Group І was reliably lower than among the women of the Group ІІ (OR=0.205; 95% СІ: 0.048-0.87; p&lt;0.05). Embryo transfer procedure was performed for 73 women of the Group І and 57 patients of the Group ІІ. The frequency of pregnancy on the IVF protocol and embryo transfer was 41.1% (30/73) and 36.8% (21/57), respectively. Absence of the further embryo development after implantation (biochemical pregnancy) was registered in 1 (3.3%) woman of the Group І and 1 (4.8%) patient of the Group ІІ. Non-developing pregnancy up to 12 weeks was diagnosed in 2 (6.6%) women of the Group І and 3 (14.2%) patients of the Group ІІ. Pregnancy that occurred after the IVF/ICSI program resulted in childbirth in 24 (32.9%) women out of 73 of the Group І and 13 patients out of 57 (22.8%) of the Group ІІ. Conclusions. In women who underwent the controlled stimulation of superovulation by urinary gonadotropins in the protocol using gonadotropin-releasing hormone antagonist compared to women who underwent the stimulation of superovulation with recombinant gonadotropins according to an analogical scheme, the frequency of pregnancy and completion of pregnancy by childbirth was reliably higher. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the author.

The effect of adenomyosis types on clinical outcomes of IVF embryo transfer after ultra-long GnRH agonist protocol

Research questionWhat is the effect of adenomyosis types on IVF and embryo transfer (IVF-ET) after ultra-long gonadotrophin-releasing hormone (GnRH) agonist protocol? DesignPatients who underwent the first cycle of IVF-ET with ultra-long GnRH agonist protocol were included in this retrospective cohort study. They were divided into three groups: (A) 428 patients with diffuse adenomyosis; (B) 718 patients with focal adenomyosis; and (C) 519 patients with tubal infertility. Reproduction outcomes were analysed. ResultsLogistic regression analysis revealed that, compared with focal adenomyosis and tubal infertility, diffuse adenomyosis was negatively associated with clinical pregnancy and live birth (clinical pregnancy: A versus B: OR 0.708, 95% CI 0.539 to 0.931, P = 0.013; A versus C: OR 0.663, 95% CI 0.489 to 0.899, P = 0.008; live birth: A versus B: OR 0.530, 95% CI 0.385 to 0.730, P < 0.001; A versus C: OR 0.441, 95% CI 0.313 to 0.623, P < 0.001), but positively associated with miscarriage (A versus B: OR 1.727, 95% CI 1.056 to 2.825, P = 0.029; A versus C: OR 2.549, 95% CI 1.278 to 5.082, P = 0.008). Compared with patients with tubal infertility, focal adenomyosis was also a risk factor for miscarriage (B versus C: OR 1.825, 95% CI 1.112 to 2.995, P = 0.017). ConclusionsCompared with patients with focal adenomyosis or tubal infertility, the reproduction outcomes of IVF-ET in patients with diffuse adenomyosis seems to be worse.