In Vitro Fertilization-embryo Transfer Research Articles

Ultrasound‑assessed endometrial receptivity measures for the prediction of invitro fertilization‑embryo transfer clinical pregnancy outcomes: A meta‑analysis and systematic review.

At present, there are currently no reliable and consistent conclusions regarding transvaginal ultrasound assessment of endometrial receptivity in predicting clinical pregnancy outcomes of in vitro fertilization-embryo transfer (IVF-ET). Thus, in the present study, a meta-analysis was performed on multiple endometrial receptivity indices detected by vaginal ultrasound, aiming to provide a diagnostic basis for clinical practice. PubMed, Embase, and Cochrane Library databases were searched for studies published between the establishment of the databases through to January 2023. Studies that reported infertile women undergoing IVF-ET and undergoing vaginal ultrasound were included, but repeat publication, studies where the full text was not obtainable, studies where there was incomplete information provided or data extraction was not possible, studies on animals, case reports, reviews, and systematic reviews were excluded. STATA 15.1 was used to analyze the data. The pooled results showed that the endometrial thickness [Weighted mean difference (WMD)=0.03, 95% CI: 0.00-0.06; P=0.022] and endometrial volume (WMD=0.41, 95% CI: 0.07-0.74; P=0.017) of the pregnancy group after receiving IVF-ET were all significantly higher than that of the non-pregnancy group. The pooled results also showed that the vascularization index (VI) (WMD=0.79, 95% CI: 0.56-1.03; P=0.000), flow index (FI) (WMD=1.82, 95% CI: 0.83-2.81; P=0.000) and vascularization flow index (VFI) (WMD=1.58, 95% CI: 0.91-2.24; P=0.000) of the pregnancy group after receiving IVF-ET was significantly higher than that of the non-pregnancy group. Systolic/diastolic (S/D) (WMD=-4.92, 95%CI: -8.28- -1.56; P=0.004) of the uterine artery of the pregnancy group after receiving IVF-ET was significantly lower than that of the non-pregnancy group. However, the differences between the resistance index (RI) and pulsatility index (PI) in the pregnancy group vs. the non-pregnancy group after receiving IVF-ET were not statistically significant. Vaginal ultrasound can be used to predict the outcomes of pregnancy in infertile women undergoing IVF-ET by measuring the thickness and volume of the endometrium, combined with the S/D, VI, FI, and VFI of the uterine artery.

Pregnancy and neonatal outcomes in infertile patients with positive tuberculin skin test results

Research questionDo infertile women with positive tuberculin skin test (TST) results have a higher risk of adverse pregnancy outcomes after IVF or intracytoplasmic sperm injection and embryo transfer (ICSI–ET) and does preventive anti-tuberculosis treatment applied to infertile women with positive TST results before IVF/ICSI–ET affect pregnancy and neonatal outcomes? DesignThis was a retrospective cohort analysis of 6283 infertile women who underwent IVF/ICSI–ET treatment for the first time at the Reproductive Hospital affiliated to Shandong University from November 2016 to September 2022. None of the participants had prior tuberculosis or active tuberculosis. According to their TST results, 5947 patients who had never received preventive anti-tuberculosis treatment were divided into a TST-positive group (1704 cases) and a TST-negative group (4243 cases). A total of 504 patients with TST (+++) results (using the 20 mm sclerosis threshold) were divided into a treated TST (+++) group (336 cases) and an untreated TST (+++) group (168 cases) according to whether they received preventive anti-tuberculosis treatment before IVF/ICSI–ET. The outcome measures were pregnancy outcomes and neonatal outcomes. ResultsThere were no significant differences in pregnancy or neonatal outcomes between the TST-positive group and the TST-negative group (P > 0.05). In the TST (+++) group, there were no significant differences in pregnancy or neonatal outcomes between the treated TST (+++) group and the untreated TST (+++) group (P > 0.05). ConclusionsFor infertile women undergoing IVF/ICSI–ET without prior tuberculosis or active tuberculosis, positive TST results and preventive anti-tuberculosis treatments prior to IVF/ICSI–ET do not affect pregnancy or neonatal outcomes.

The effects of chromosome polymorphism on the clinical outcomes of in vitro fertilization/embryo transfer-assisted reproduction

Objective To investigate the effects of chromosome polymorphism on the clinical outcomes of in vitro fertilization/embryo transfer (IVF/ET)-assisted reproductive technology. Methods The case data of 2740 patients treated between January 2018 and January 2019 were retrospectively analyzed. The patients were organized into two groups: a case group and a control group. In the case group (n = 81), one or both parents were characterized by chromosomal polymorphism; in the control group (n = 2659), both parents had normal chromosome karyotyping. The primary outcomes included clinical pregnancy rate (clinical pregnancy rate of fresh transfer cycles = number of clinical pregnancy cycles/number of fresh embryo transfer cycles × 100%) and live birth rate (live birth rate per fresh transfer cycles = number of live births/numbers of fresh embryo transfer cycles × 100%). The propensity score matching (PSM) method was used for statistical analysis. Results After PSM 1:2 matching for the patients in the two groups, 72 patients were successfully matched. The clinical pregnancy rate and live birth rate in the case group were lower than in the control group before PSM (clinical pregnancy rate: 33.30% case group vs. 46.60% control group, p = .020; live birth rate: 30.90% case group vs. 47.90% control group, p = .03). The differences were statistically significant (p < .05). The live birth rate in the case group was also significantly lower than in the control group after PSM (34.98% case group vs. 74.52% control group; p = .028). The correlation coefficient between clinical pregnancy and grouping (i.e. if there was a characteristic chromosome polymorphism) was −.045 (p = .02), while the correlation coefficient between live birth and grouping was −.046. Conclusion Chromosome polymorphism is weakly negatively correlated with live birth in IVF/ET-assisted reproduction and can significantly reduce the live birth rate of patients.

Predicting ovarian responses to the controlled ovarian hyperstimulation in elderly infertile women using clinical measurements and random forest regression

During the past decades, the number of elderly infertile women is obviously increasing in China, and more and more of them are likely to seek medical assisted reproductive technologies. As the in vitro fertilization/embryo transfer (IVF/ET) treatment presents special medical and psychological challenges to elderly infertile women, it is extremely helpful to perform the clinical evaluation and outcome prediction regarding IVF/ET outcomes. In this study, we retrospectively collected 12 clinical measurements in prior to the oocyte recovery for 689 elderly infertile patients (≥35 years of old), and used for predicting ovarian responses to the controlled ovarian hyperstimulation based on random forest regression models. Using different predictor sets and 10-fold cross validation approach, the Mean Square Error (±standard deviation) of prediction models varied from 7.56 ± 0.31 to 13.90 ± 0.37 in the training datasets, and the correlation coefficients between observed and predicted values ranged from 0.86 ± 0.02 to 0.72 ± 0.05 in the testing datasets. Among all clinical measurements involved in this study, the preovulatory follicle count (PFC), antral follicle count (AFC), and anti-Müllerian hormone (AMH) were revealed to be the most important features in prediction models. In conclusion, we successfully established the machine learning approach that could help the elderly infertile patients to better understand the most possible outcomes in subjecting to the controlled ovarian hyperstimulation.

A simple scoring system for the prediction of early pregnancy loss developed by following 13,977 infertile patients after in vitro fertilization

A retrospective study was conducted to investigate a convenient simple scoring system for the prediction of early pregnancy loss (EPL) based on simple demographics. A total of 13,977 women undergoing transvaginal ultrasound scans on Days 27–29 after in vitro fertilization-embryo transfer (IVF-ET) from June 2016 and December 2017 were included. The first trimester pregnancy outcome was recorded at 12 weeks of gestation. The areas under the curve of this scoring system were 0.884 (95% confidence interval (CI) 0.870–0.899) and 0.890 (95% CI 0.878–0.903) in the training set and test set, respectively. The score totals ranged from -8 to 14 points. A score of 5 points, which offered the highest predictive accuracy (94.01%) and corresponded to a 30% miscarriage risk, was chosen as the cutoff value, with a sensitivity of 62.84%, specificity of 98.79%, positive predictive value (PPV) of 88.87% and negative predictive value (NPV) of 94.54% for the prediction of EPL in the training set. In the test set, a score of 5 points had a sensitivity of 64.69%, specificity of 98.78%, PPV of 89.87% and NPV of 93.62%, and 93.91% of the cases were correctly predicted. Therefore, the simple scoring system using conventionally collected data can be conveniently used to predict EPL after ET. However, considering the limitations, its predictive value needs to be further verified in future clinical practice.

Establishment of hysteroscopic scoring system of chronic endometritis and correlative analysis with pregnancy outcomes of in vitro fertilization-embryo transfer in infertile patients

Objective: To establish a hysteroscopic chronic endometritis (hCE) scoring system for patients with chronic endometritis, and observe the correlation of hCE score with in vitro fertilization-embryo transfer (IVF-ET) pregnancy outcomes in infertile women. Methods: The study retrospectively investigated the correlation of morphologic features and hCE score with pregnancy outcomes during IVF-ET in infertile women with CE (n=429) at Yantai Yuhuangding Hospital between January 2017 and September 2018. The clinical pregnancy rate and live birth rate with different score levels (1-3,4-7 and 8-14) after IVF-ET treatment were analyzed. Multivariate regression analysis was performed to adjust for confounding factors. The correlation and regression between hCE score and pregnancy outcomes was analyzed by curve fitting. Results: The age of 429 patients [M(Q1, Q3)] was 31 (29, 35) years. There were 50.6% (217 cases), 35.4% (152 cases), and 14.0% (60 cases) of patients with hCE score of 1-3, 4-7, and 8-14, respectively. The pregnancy rates of the three groups were 60.8% (132 cases), 44.7% (68 cases) and 16.7% (10 cases), P<0.001; The live birth rates were 51.2% (111 cases), 36.8% (56 cases) and 13.3% (8 cases), respectively (P<0.001). Compared with patients with hCE of 1-3, pregnancy rates in those with hCE of 4-7 and 8-14 were lower, and the OR values were 0.521 (0.342-0.793) and 0.129 (0.062-0.268). The live birth rates in patients with hCE of 4-7 and 8-14 were lower than that in patients with hCE of 1-3, and the OR values were 0.570 (0.372-0.873) and 0.162 (0.073-0.360), all P<0.05. Quadratic curve fitting results showed that clinical pregnancy rate and live birth rate decreased with the increase of hCE score. Conclusions: With the increase of hCE score, the clinical pregnancy rate and live birth rate of patients gradually decrease. hCE 4 is an important cut-off threshold significantly affecting the pregnancy outcome.

P-487 Preimplantation genetic testing for aneuploidy for recurrent pregnancy loss: a systematic review and meta-analysis

Abstract Study question Can preimplantation genetic testing for aneuploidy (PGT-A) improve the live rate of recurrent pregnancy loss(RPL)? Summary answer PGT-A can improve the live birth rate and reduce the rate of miscarriages in women with RPL following in vitro fertilization-embryo transfer (IVF-ET). What is known already PGT-A has been widely used in women with RPL over the past decade. However, there is no consensus supporting this approach to the management of RPL. Study design, size, duration Systematic review and meta-analysis according to PRISMA guidelines. The research population was focused on RPL women. The intervention was PGT-A. The comparator was IVF/ICSI without PGT-A or expectant management. The primary outcome was the live birth rate per woman, and the secondary outcomes were the miscarriage rate and clinical pregnancy rate. Participants/materials, setting, methods PubMed, EMBASE, The Cochrane Library, and trial registers were searched for studies on PGT-A and RPL up to October 2022. There were no limitations regarding the year of publication or duration of follow-up but to the English language. The primary outcome was the live birth rate per woman, and the secondary outcomes were the miscarriage rate and clinical pregnancy rate. Main results and the role of chance Out of 1466 search results, 9 studies (including one RCT, one prospective pilot study, and seven retrospective cohort studies) were included in the review. Seven of these studies compared the live birth rate of RPL with PGT-A versus without PGT-A following in vitro fertilization-embryo transfer (IVF-ET). PGT-A significantly increased live birth rate (odds ratio(OR): 2.07; 95% confidence interval: 1.88 to 2.27) and lowered miscarriage rate (OR: 0.21; 95% confidence interval: 0.13 to 0.34). However, PGT-A did not improve the clinical pregnancy rate. In two studies comparing the live birth rate/ongoing pregnancy of RPL with PGT-A versus expectant management, the result shows that PGT-A did not improve the live birth rate (OR: 1.11; 95% confidence interval: 0.74 to 1.67). Limitations, reasons for caution Limitations include the retrospective design and heterogeneity of studies included, limiting comparison and pooling of data. Some studies have limited sample sizes. The data collected in the database could not exclude anatomic or chromosomal abnormalities in women with RPL. Wider implications of the findings PGT-A can improve the live birth rate and reduce the rate of miscarriages in women with RPL following IVF-ET. However, there is no evidence of a beneficial effect of PGT-A if compared with expectant management. It is important to evaluate carefully the application of PGT-A in clinical practice. Trial registration number not applicable

P-520 Risk factors for early pregnancy loss in women undergoing in vitro fertilization-embryo transfer

Abstract Study question What are the risk factors for early pregnancy loss (EPL) in infertility patients undergoing in vitro fertilization-embryo transfer (IVF-ET) cycles? Summary answer The risk factors for EPL were maternal age, 14-day β-human chorionic gonadotrophin(β-hcg) levels and cycle type. What is known already Pregnancy obtained through assisted reproductive technology still has a high risk of spontaneous early pregnancy abortion, and the cause of which is unclear. It not only affects the rate of ongoing pregnancy and live birth, but also increases the psychological and economic burden of patients. At present, there have been many studies on the risk factors of early pregnancy loss in IVF/ICSI-ET at domestic and overseas, but the results are different, which may be related to the selection of different research objects, sample size and statistical methods. Study design, size, duration A retrospective study of 6107 embryo transfer cycles collected from January 2018 to December 2018 was performed. The cycles were divided into the EPL group (n = 987) and the live birth group (n = 5120) according to the cycle outcomes. Participants/materials, setting, methods Baseline data and clinically relevant indicators were compared between the two groups, including maternal age, infertility years, infertility type, body mass index (BMI), tubal factor, ovulatory dysfunction, endometriosis, male factor, antral follicle count (AFC), single gene related genetic disease, follicle-stimulating hormone (FSH), estradiol (E2), luteinizing hormone (LH), 14-day β-hcg levels, prolactin (PRL), progesterone (P), testosterone (T), anti-Müllerian hormone (AMH), cycle type and the number of transplanted embryos. Main results and the role of chance The EPL rate of the infertility patients undergoing fresh/frozen-thaw embryo transfer cycle was 16.16%. Univariate analysis showed that there were statistically significant differences between the two groups in maternal age, AFC, 14-day β-hcg levels, T, AMH, infertility years, cycle type, infertility types, chromosome disease and male factors (P &amp;lt; 0.05). The results of binary logistics regression analysis showed that maternal age, 14-day β-hcg levels and cycle type were related factors to EPL (P &amp;lt; 0.05). Limitations, reasons for caution This study lacked some baseline data, such as adverse pregnancy history, abortion history, and previous transplant failure history, and male factors such as BMI, age, semen results, smoking history. The information about fetal chromosomes was also missing. Wider implications of the findings Clinical prevention and treatment of risk factors can be targeted to improve pregnancy outcomes after transplantation. Trial registration number none

O-263 Effect of clindamycin and a live biotherapeutic containing lactobacilli on the reproductive outcomes of IVF patients with abnormal vaginal microbiota: a double-blind, placebo-controlled multicentre trial

Abstract Study question Does treatment of abnormal vaginal microbiota improve the reproductive outcomes of IVF patients? Summary answer Data is being analysed and will be presented at ESHRE 2023. What is known already An increasing number of studies reported an association between abnormal genital tract microbiota and adverse reproductive outcomes in IVF patients. One hypothesis could be that vaginal microbiota ascend to the endometrium where the microbiota hampers implantation. To the best of our knowledge, this is the first study powered to investigate causality between abnormal genital tract microbiota - in this study defined by a bacterial vaginosis like vaginal microbiota - and clinical pregnancy rate in IVF patients. Study design, size, duration Double-blind, placebo-controlled multicentre trial in IVF patients diagnosed with abnormal vaginal microbiota and subsequently randomised into three parallel groups 1:1:1. The first group received clindamycin 300 mg ×2 daily for 7 days followed by vaginal Lactobacillus crispatus until the clinical pregnancy scan. The second group received clindamycin and placebo, whereas the third group received placebo/placebo. A total of 1518 patients were screened, and 338 patients were randomised. The study duration was from 2017 to 2023. Participants/materials, setting, methods IVF patients with any cause of infertility embarking on their first, second or third IVF stimulation cycle or embryo transfer were approached for inclusion. At a minimum 12 days prior to embryo transfer, patients were screened for abnormal vaginal microbiota defined by a qPCR assay, targeting high quantitative loads of Fannyhessea vaginae and Gardnerella spp. Patients were excluded if they had intrauterine malformations like polyps, septum, and fibroma. Main results and the role of chance Data and safety monitoring board has decided not to open the randomization code yet. The final dataset is being completed. Data is being analysed and will be presented at ESHRE 2023. Limitations, reasons for caution Data is being analysed and will be presented at ESHRE 2023. Wider implications of the findings The present drug intervention study used clindamycin and a live biotherapeutic containing Lactobacillus crispatus. The results of the study could have a worldwide important clinical impact on daily IVF practice as currently there is no evidence that screening and treating IVF patients with abnormal vaginal microbiota improves the reproductive outcome. Trial registration number EudraCT 2016-002385-31

Treatment effects of laparoscopy versus laparotomy on heterotopic pregnancy after in vitro fertilization and embryo transfer.

To compare the treatment effects of laparoscopy versus laparotomy on heterotopic pregnancy (HP) after in vitro fertilization-embryo transfer (IVF-ET). The retrospective case-control study enrolled 109 patients diagnosed with HP after IVF-ET treatment in our hospital from January 2009 to March 2020. All patients received surgical treatment by either laparoscopy or laparotomy. Data for general characteristics, diagnostic features, surgical parameters, as well as perinatal and neonatal outcomes were collected. Sixty-two patients received laparoscopy and 47 received laparotomy. Significantly lower percentage of large hemoperitoneum (P = 0.001), shorter surgery duration (P < 0.001), less intraoperative blood loss (P = 0.001), higher rates of general anesthesia (P < 0.001), and lower cesarean section rates for singletons (P = 0.003) were found in the laparoscopy group. The perinatal and neonatal outcomes were comparable between the two groups. When interstitial pregnancy was considered alone, the surgical blood loss was significantly reduced in the laparoscopy group (P = 0.021), but there was no significant difference in hemoperitoneum, surgery duration, or perinatal and neonatal outcomes in singletons. Both laparoscopy and laparotomy are effective surgical treatments for HP after IVF-ET. Laparoscopy is minimally invasive but laparotomy can be an alternative in emergency situations.

Effect of oral contraceptives pretreatment on cumulative clinical pregnancy of oocyte retrieval cycle in polycystic ovary syndrome women with gonadotropin releasing hormone antagonist protocol

Objective: To investigate the effect of pretreatment with oral contraceptives (OC) on cumulative clinical pregnancy of oocyte retrieval cycle in polycystic ovary syndrome (PCOS) women with gonadotropin releasing hormone (GnRH) antagonist protocol. Methods: A retrospective cohort study was conducted to analyze PCOS women who underwent in vitro fertilization-embryo transfer (IVF-ET)/intracytoplasmic sperm injection (ICSI) treatment with GnRH antagonist in the Reproductive Medical Center of Peking University First Hospital from January 2017 to December 2020. A total of 225 patients were divided into OC pretreatment group (119 patients) and non-pretreatment group (106 patients), according to whether they received OC before GnRH antagonist protocol. The baseline information, IVF, and pregnancy outcomes of the two groups were compared. A multivariate logistic regression model was used to analyze the effect of OC pretreatment on cumulative clinical pregnancy of the oocyte retrieval cycle. Results: The age of 225 patients was (31.1±3.3) years old. The ages of patients in the OC pretreatment group and non-pretreatment group were (31.0±3.3) and (31.2±3.3) years old (P>0.05), respectively. The cumulative clinical pregnancy rate of oocyte retrieval cycle was significantly higher in the OC pretreatment group than that in the non-pretreatment group (79.8%, 95 patients; 67.0%, 71 patients; P=0.029). Age <35 years old (OR=3.199, 95%CI: 1.200-8.531, P=0.020), OC pretreatment (OR=3.129, 95%CI: 1.305-7.506, P=0.011), number of oocytes retrieved (OR=1.102, 95%CI: 1.007-1.206, P=0.035) and number of high-quality embryos (OR=1.536, 95%CI: 1.205-1.957, P=0.001) were related factors for the cumulative clinical pregnancy of oocyte retrieval cycle. Conclusions: OC pretreatment before GnRH antagonist protocol can significantly increase the cumulative clinical pregnancy rate of oocyte retrieval cycle in women with PCOS. Age <35 years old, OC pretreatment, the number of oocytes retrieved, and the number of high-quality embryos were related factors for the cumulative clinical pregnancy of oocyte retrieval cycle.

In vitro fertilization outcomes In infertile women with adenomyosis

Objectives: This study aimed to investigate the efficacy of in vitro fertilization (IVF) in infertile patients with adenomyosis and to identify relevant factors. Subjects and methods: Retrospective descriptive study of infertile cases with adenomyosis who received IVF therapy and embryo transfer from November 2013 to October 2022 at the Center for Reproductive Endocrinology and Infertility, Hue University of Medicine and Pharmacy Hospital, excluding cases of oocyte donation or surrogacy. The β-hCG test was examined two weeks following embryo transfer. Then, women with hCG positive test were followed the pregnancy at 6 weeks, 8 weeks, and 12 weeks, and examined some factors that influence the clinical outcome of pregnancy. Results: Among 61 cycles of IVF treatment for infertile patients with adenomyosis, the average number of retrieved oocytes was 10.9±6.6 oocytes. The percentage of mature oocytes was 82.7%, the fertilization rate was 79.5%, the implantation rate was 16.7%, the clinical pregnancy rate was 19.7%, the miscarriage rate was 6.6%, and the ongoing pregnancy rate was 13.1%. In the group with GnRH agonist administration before embryo transfer, the pregnancy rate was greater than in the group without therapy (29.2% vs. 13.5%), and th e pregnancy rate in the group with &gt; 10 oocytes was higher than in the group with ≤ 10 oocytes (28.0% vs 13.5%). However, these differences were not statistically significant (with p &gt; 0.05). The cut-off point of endometrial thickness on the day of hCG injection, 10.25 mm, had a sensitivity of 58.3%, a specificity of 81.6%, an area under the curve (AUC) of 75.6%, and a p-value of 0.006; the cut-off point of endometrial thickness on the day of embryo transfer, 9.75 mm, had an accuracy of 9.75 mm. sensitivity 75%, specificity 71.4%, AUC 78.50%, p = 0.002 for clinical pregnancy prognosis. Conclusion: The IVF treatment of infertile patients with adenomyosis remains challenging, and additional research is required to explain the influence of this disorder on IVF outcomes. Key words: in vitro fertilization (IVF), adenomyosis, β-hCG.

Cancer risk in children, adolescents, and young adults conceived by ART in 1983-2011.

Do children, adolescents, and young adults born after ART, including IVF, ICSI and frozen-thawed embryo transfer (FET), have an increased risk of cancer compared with children born to subfertile couples not conceived by ART and children from the general population? After a median follow-up of 18 years, the overall cancer risk was not increased in children conceived by ART, but a slight risk increase was observed in children conceived after ICSI. There is growing evidence that ART procedures could perturb epigenetic processes during the pre-implantation period and influence long-term health. Recent studies showed (non-)significantly increased cancer risks after ICSI and FET, but not after IVF. A nationwide historical cohort study with prospective follow-up was carried out, including all live-born offspring from women treated with ART between 1983 and 2011 and subfertile women not treated with ART in one of the 13 Dutch IVF clinics and two fertility centers. Children were identified through the mothers' records in the Personal Records Database. Information on the conception method of each child was collected through the mother's medical record. In total, the cohort comprises 89249 live-born children of subfertile couples, of whom 51417 were conceived using ART and 37832 were not (i.e. conceived naturally, through ovulation induction, or after IUI). Cancer incidence was ascertained through linkage with the Netherlands Cancer Registry for the period 1989-2019. Cancer risk in children conceived using ART was compared with risk in children born to subfertile couples but not conceived by ART (hazard ratio (HR)) and children from the general population (standardized incidence ratios (SIRs)). In total, 358 cancers were observed after a median follow-up of 18 years. Overall cancer risk was not increased in children conceived using ART, when compared with the general population (SIR = 0.96, 95% CI = 0.81-1.12) or with children from subfertile couples not conceived by ART (HR = 1.06, 95% CI = 0.84-1.33). Compared with children from subfertile couples not conceived by ART, the use of IVF or FET was not associated with increased cancer risk, but ICSI was associated with a slight risk increase (HR = 1.58, 95% CI = 1.08-2.31). Risk of cancer after ART did not increase at older ages (≥18 years, HR = 1.26, 95% CI = 0.88-1.81) compared to cancer risk in children not conceived by ART. The observed increased risk among children conceived using ICSI must be interpreted with caution owing to the small number of cases. After a median follow-up of 18 years, children conceived using ART do not have an increased overall cancer risk. Many large studies with prolonged follow-up are needed to investigate cancer risk in (young) adults conceived by different types of ART. In addition, international pooling of studies is recommended to provide sufficient power to study risk of specific cancer sites after ART. This work was supported by The Dutch Cancer Society (NKI 2006-3631) that funded the OMEGA-women's cohort, Children Cancer Free (KIKA; 147) that funded the OMEGA-I-II offspring cohort. The OMEGA-III offspring cohort was supported by a Postdoc Stipend of Amsterdam Reproduction & Development, and the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health under Award Number R01HD088393. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors declare no competing interests. N/A.

Impact of endometriosis on embryo quality and endometrial receptivity in women undergoing assisted reproductive technology.

ART is an important treatment method for infertile patients with endometriosis. However, the effects of endometriosis on embryo quality and endometrial receptivity remain unclear. Thus, we aimed to simultaneously investigate the impact of endometriosis and its stage on embryo quality and endometrial receptivity in women undergoing ART. We retrospectively analyzed the data from patients with and without endometriosis who underwent oocyte retrieval and/or high-quality embryos transfer between July 2015 and December 2020, including 1312 IVF cycles and 608 IVF or frozen-thawed embryo transfer (FET) cycles, respectively. The endometriosis group had a lower percentage of good cleavage-stage embryos and fertilization rates than those in the control group (p=0.038 and 0.008, respectively). The number of retrieved oocytes, MII oocytes, cleavage, blastocysts, and blastulation rates was comparable between two groups. We found no significant difference in clinical pregnancy, implantation, live birth, miscarriage, or multiple pregnancy rates between the two groups among patients who transferred high-quality embryos. Stratification analysis showed that patients with stage III-IV endometriosis had fewer retrieved oocytes than those with stage I-II endometriosis (p=0.012) and marginally fewer retrieved oocytes than the control group (p=0.051). The stage I-II group had the lowest percentage of good cleavage-stage embryos, which was significantly lower than that of the control group (p=0.043). In FET cycles, patients with stage III-IV endometriosis had a higher miscarriage rate than those in the control group (p=0.023). Our results suggest that endometriosis does not alter endometrial receptivity but affects embryo quality, oocyte fertilization ability, and ovarian response.

Risk factors for ovarian hyperstimulation syndrome during IVF embryo transfer based on logistic regression analysis and construction of a forecasting model.

Risk factors for ovarian hyperstimulation syndrome during IVF embryo transfer based on logistic regression analysis and construction of a forecasting model.

Analysis of the relationship between MRI imaging characteristics and clinical symptoms and therapeutic efficacy in adenomyosis patients

Objective: To investigate the relationship between magnetic resonance imaging (MRI) imaging characteristics and clinical symptoms and therapeutic efficacy in adenomyosis patients. Methods: The clinical characteristics of the adenomyosis questionnaire was self-designed. This was a retrospective study. From September 2015 to September 2020, totally 459 patients were diagnosed with adenomyosis and underwent pelvic MRI examination at Peking University Third Hospital. Clinical characteristics and treatment were collected, MRI was used to determine the lesion location, and to measure the maximum lesion thickness, the maximum myometrium thickness, uterine cavity length, uterine volume, the minimum distance between the lesion and serosa or endometrium, and whether combined with ovarian endometrioma. The difference of MRI imaging characteristics in patients with adenomyosis and its relationship with clinical symptoms and therapeutic efficacy were analyzed. Results: (1) Among the 459 patients, the age was (39.1±6.4) years. There were 376 patients (81.9%, 376/459) with dysmenorrhea. Whether patients had dysmenorrhea were related to uterine cavity length, uterine volume, ratio of the maximum lesion thickness to the maximum myometrium thickness, and whether patients had ovarian endometrioma (all P<0.001). Multivariate analysis suggested that ovarian endometrioma was the risk factor for dysmenorrhea (OR=0.438, 95%CI: 0.226-0.850, P=0.015). There were 195 patients (42.5%, 195/459) with menorrhagia. Whether patients had menorrhagia were related to age, whether patients had ovarian endometrioma, uterine cavity length, the minimum distance between lesion and endometrium or serosa, uterine volume, ratio of the maximum lesion thickness to the maximum myometrium thickness (all P<0.001). Multivariate analysis suggested that ratio of the maximum lesion thickness to the maximum myometrium thickness was the risk factor for menorrhagia (OR=774.791, 95%CI: 3.500-1.715×105, P=0.016). There were 145 patients (31.6%, 145/459) with infertility. Whether the patients had infertility were related to age, the minimum distance between lesion and endometrium or serosa, and whether patients had ovarian endometrioma (all P<0.01). Multivariate analysis suggested that young and large uterine volume were risk factors for infertility (OR=0.845, 95%CI: 0.809-0.882, P<0.001; OR=1.001, 95%CI: 1.000-1.002, P=0.009). (2) The success rate of in vitro fertilization-embryo transfer (IVF-ET) was 39.2% (20/51). Dysmenorrhea, high maximum visual analogue scale score and large uterine volume affected the success rate of IVF-ET (all P<0.05). The smaller the maximum lesion thickness, the smaller the distance between the lesion and serosa, the larger the distance between the lesion and endometrium, the smaller the uterine volume, and the smaller the ratio of the maximum lesion thickness to the maximum myometrium thickness, the better the therapeutic efficacy of progesterones (all P<0.05). Conclusions: Concomitant ovarian endometrioma increases the risk of dysmenorrhea in patients with adenomyosis. The ratio of the maximum lesion thickness to the maximum myometrium thickness is an independent risk factor for menorrhagia. Young and large uterine volume may increase the risk of infertility. Severe dysmenorrhea and large uterine volume affect the success rate of IVF-ET. The therapeutic efficacy of progesterones is relatively better when the lesion is small and far away from the endometrium.

Expression of Apoptotic and Ubiquitin-Proteasome Genes Are Altered in Blastocoel Fluid From Preimplantation Euploid IVF Embryos That Result in Miscarriage [ID: 1365769

INTRODUCTION: Infertility is one of the leading causes of recurrent miscarriage, affecting approximately 14% of reproductive-aged patients. Recurrent miscarriages are presumed to be the result of embryonic chromosomal abnormalities such as aneuploidy. Literature has indicated that apoptotic mechanisms may play a role in selective elimination of aneuploid cells during preimplantation embryo development. This study aims to identify the expression patterns of an apoptotic gene and a gene encoding a ubiquitin ligase within blastocoel fluid-conditioned media from preimplantation euploid in vitro fertilization (IVF) embryos that resulted in miscarriage to identify specific genes associated with poor implantation outcomes. METHODS: Candidate genes were identified through whole-transcriptome (RNA-seq) analysis of blastocoel fluid from euploid IVF embryos that resulted in successful or unsuccessful implantation. Blastocoel fluid from euploid IVF embryos resulting in miscarriage or successful implantation was selected for specific gene expression analysis using RT-qPCR and Taqman-specific primers. BCL2L12 and SHARPIN gene expression was assessed, compared to GAPDH control. RESULTS: Expression of BCL2L12, an antiapoptotic gene, and SHARPIN, a gene that encodes an ubiquitin ligase, was altered in blastocoel fluid samples associated with miscarriage. Initial studies indicate that SHARPIN has a higher expression in blastocoel fluid from samples associated with negative implantation outcomes. CONCLUSION: Identification of gene expression patterns during preimplantation development that are associated with miscarriage may allow for an additional embryo quality metric to improve the success of each IVF embryo transfer potentially reducing the number of miscarriages. Additionally, these metrics could be expanded to allow for the identification of potential high-risk pregnancies soon after implantation, without any harm to the fetus.

Effects of electroacupuncture on pregnancy outcome in poor ovarian response patients of kidney essence deficiency and undergoing in vitro fertilization-embryo transfer

To observe the effects of electroacupuncture (EA) on ovarian reaction, egg and embryo quality, as well as pregnancy rate in poor ovarian response (POR) patients of kidney essence deficiency and undergoing in vitro fertilization-embryo transfer (IVF-ET). Ninety-six patients who met the inclusion criteria were randomly divided into an EA group and a control group, with 48 cases in each group. Before IVF-ET, the patients in the EA group received EA, once daily, 2 or 3 treatments a week for 12 weeks. Before and after the treatment, traditional Chinese medicine (TCM) syndrome score and clinical pregnancy rate were assessed in two groups. The concentrations of serum follicle-stimulating hormone (FSH), luteinsing hormone, estradiol, progesterone and anti-mullerian hormone were detected by chemiluminescence; the contents of serum insulin-like growth factor-1, serum inhibin B (INHB) and Kisspeptin in follicular fluid were determined by enzyme linked immunosorbent assay (ELISA); the antral follicle counting (AFC) was detected by color Doppler ultrasonography; and the egg and embryo conditions were observed under microscope. Fourteen days after embryo transfer, the positive rate of serum hemchoriconic gonadotropin (HCG) and clinical pregnancy rate were calculated. After the treatment, the TCM syndrome score and level of serum FSH were reduced (P<0.05); the INHB in serum and AFC were increased (P<0.05) when compared with those before the treatment in the EA group. After the treatment, in comparison with the control group, the TCM syndrome score and level of serum FSH were lower (P<0.05); and the contents of serum INHB, AFC, the numbers of MⅡ eggs and high-quality embryos, as well as serum HCG positive rate were all increased (P<0.05) in the EA group. EA can relieve the clinical symptoms of TCM in POR patients of kidney essence deficiency and undergoing IVF-ET, increase the ovarian reserve, reduce the serum FSH level, and improve the content of serum INHB, and the quality of eggs and embryos. This therapy tends to improve the clinical pregnancy rate and clinical pregnancy outcome.

Application value of tumor necrosis factor inhibitors in in vitro fertilization-embryo transfer in infertile women with polycystic ovary syndrome

BackgroundClinical value of tumor necrosis factor (TNF) inhibitors in in vitro fertilization-embryo transfer (IVF-ET) in infertile women with polycystic ovary syndrome (PCOS) was investigated in this study.MethodsA retrospective analysis was performed on the clinical data of 100 PCOS patients who received IVF-ET for the first time at Hebei Institute of reproductive health science and technology from January 2010 to June 2020. The patients were divided into Inhibitor group and Control group according to whether they were treated with or without TNF inhibitors. Next, the two groups were subject to comparison in terms of the days of gonadotropin (Gn) use, total dosage of Gn, trigger time, hormone level and endometrial condition on the day of human chorionic gonadotropin (HCG) injection, the effects of two different regimens on controlled ovarian hyperstimulation (COH) and pregnancy outcomes.ResultsThere were no significant differences in baseline characteristics between the two groups, including age, duration of infertility, body mass index (BMI), ovarian volume, antral follicle count, and basal hormone levels. Compared with the Control group, the days of Gn use and trigger time of patients in the Inhibitor group were significantly shortened, and the total Gn dosage was notably reduced. In terms of sex hormone levels on the HCG injection, the Inhibitor group displayed much lower serum estradiol levels while higher serum luteinizing hormone and progesterone (P) levels than the Control group. Notably, the high-quality embryo rate was also significantly increased with the use of TNF inhibitors. However, significant differences were not observed in endometrial thickness (on the day of HCG injection), proportion of endometrial A, B and C morphology (on the day of HCG injection), cycle cancellation rate, number of oocytes retrieved, fertilization rate, and cleavage rate between the two groups. Importantly, the clinical pregnancy rate in the Inhibitor group was significantly higher than that in the Control group, but there was no significant difference in the biochemical pregnancy rate, early abortion rate, multiple birth rate, ectopic pregnancy rate and number of live births between the two groups.ConclusionCollectively, after application of TNF-α inhibitor regimen, superior overall treatment effect can be observed in infertile PCOS patients receiving IVF-ET. Therefore, TNF inhibitors have certain application value in IVF-ET in infertile women with PCOS.

Predictive value of endometrial receptivity evaluated by three-dimensional ultrasound in ectopic pregnancy after in vitro fertilization-embryo transfer.

The aim of this study was to use three-dimensional (3D) ultrasound to detect ultrasound parameters related to the uterine artery and endometrium, evaluate endometrial receptivity, and investigate the predictive value of each parameter for ectopic pregnancy (EP) after in vitro fertilization-embryo transfer (IVF-ET). Fifty-seven cases of pregnancy following IVF-ET in our institution were collected and split into EP and intrauterine pregnancy (IP) groups based on the location of pregnancy, with 27 cases in EP and 30 cases in IP. Endometrial thickness, type, volume, endometrial blood flow parameters, and uterine artery blood flow parameters were all measured one day before transplantation in both groups, and the differences between the two groups were examined. There were differences in endometrial blood flow typing between the two groups, with type III endometrium accounting for the highest proportion in both; the uterine spiral artery pulsatility index PI was significantly higher in the EP group than in the IP group; there were no statistical differences in uterine volume, uterine artery resistance index mRI, or uterine artery resistance index S/D between the two groups; there were no statistical differences in uterine volume, or uterine artery. Intracavitary 3D ultrasound can assess endometrial tolerance and may predict pregnancy outcome after IVF-ET.