Number Of High-quality Embryos Research Articles

Cai’s prescription inhibits granulosa cell apoptosis through ARHGAP4 on poor ovarian responders

PurposePoor ovarian response (POR) is a big challenge for in vitro fertilization. The traditional Chinese medicine, Cai’s Prescription of Tonifying Kidney and Strengthening Vitals (Cai’s Prescription) has yielded satisfactory results for POR treatment clinically, but systematic scientific research of Cai’s Prescription is not well reported. This study aimed to investigate the clinical effect of Cai’s Prescription on poor ovarian responders and its biological mechanism.MethodsSerum was collected from poor ovarian responders, and IL-1β, INFγ, FSH, E2 and AMH levels were analyzed by ELISA. Ovarian antral follicles were identified and counted using transvaginal ultrasound. The embryo quality grading were done on day 3 after retrieval. We used high-throughput sequencing of granulosa cells to investigate the gene transcription patterns of ovarian granulosa cells in poor ovarian responders after Cai’s Prescription pretreatment. The expression level of ARHGAP4 was analyzed by quantitative real-time PCR and western blot. The effects of ARHGAP4 for granulosa cells were analyzed by CCK-8 assay, annexin-V and PI staining, ELISA and western blot. The effects of Cai’s Prescription on the expression of PI3K-Akt pathway and apoptosis were analyzed by western blot.ResultsIn this study, we found that Cai’s Prescription pretreatment had the tendency to improve the ovarian reserve function and could increase the number of high quality embryos for poor ovarian responders. Through high-throughput sequencing of mRNA in granulosa cells, we discovered ARHGAP4, which is a member of GTPase-activating proteins (GAPs) may be a candidate target for POR treatment. ARHGAP4 was significantly increased in poor ovarian responders and can be recovered after Cai’s Prescription pretreatment. Mechanically, combining the cell line model and clinical tissue samples, we found that ARHGAP4 can accelerate cell apoptosis and inflammation response in granulosa cells via PI3K-Akt signaling pathway. In addition, Cai’s Prescription pretreatment for three months significantly reduced the high level of ARHGAP4 in poor ovarian responders.ConclusionThis study shows that the traditional Chinese medicine, Cai’s Prescription yielded satisfactory results for poor ovarian responders clinically and ARHGAP4 may be a candidate target for POR treatment.

Analysis of use of different rFSHs during IVF/ICSI-assisted conception in elderly population and effect of double trigger on clinical outcomes

Objective To compare the number of oocytes retrieved and clinical outcomes of ovulation induction in an older population treated with in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) (IVF/ICSI) using different rFSH options and the effectiveness of antagonist treatment to induce ovulation using gonadotropin-releasing hormone agonists (GnRH-a) in combination with an human chorionic gonadotropin (HCG) trigger. Methods A total of 132 fresh cycles were selected for this study, which were treated with IVF/ICSI in our hospital from March 2022 to December 2022. Observations were made according to different subgroups and the effects of different triggering methods on the number of oocytes obtained, embryo quality, and clinical outcomes. Results The initial gonadotropin (Gn) dose, the number of oocytes, and the number of MII oocytes were higher in group A than in group B (p < .05), and the clinical pregnancy rate was 29.41% in group A. Group B had a clinical pregnancy rate of 27.5%. The double-trigger group was superior to the HCG-trigger group in terms of the number of 2PN, the number of viable embryos, and the number of high-quality embryos (p < .05). The use of a double-trigger regimen (OR = 0.667, 95%CI (0.375, 1.706), p = .024) was a protective factor for the clinical pregnancy rate, whereas AFC (OR = 0.925, 95%CI (0.867, 0.986), p = .017) was an independent factor for the clinical pregnancy rate. Conclusions The use of a dual-trigger regimen of GnRH-a in combination with HCG using an appropriate antagonist improves pregnancy outcomes in fresh embryo transfer cycles in older patients.

Comparison between the modified long gonadotropin-releasing hormone agonist protocol and the non-downregulation protocol in POSEIDON groups: a propensity score matching retrospective cohort study.

In vitro fertilization (IVF) is the main technique to address the infertility issue in the patient-oriented strategy encompassing individualized oocyte number (POSEIDON) population. Adopting appropriate protocols for assisted reproduction technologies (ART) cycles in the POSEIDON group may attain more favorable pregnancy outcomes. This study aimed to compare the effectiveness of modified long gonadotropin-releasing hormone agonist protocol and non-downregulation protocol in POSEIDON patients undergoing ART, and to identify the factors affecting the pregnancy outcomes in this group. This study was designed as a propensity score-matched (PSM) retrospective analysis. The study cohort consisted of 910 patients diagnosed with ovarian hyporesponsiveness and treated by IVF from January 2020 to June 2022. They were followed up until the transfer of the last embryo of the IVF cycle and/or pregnancy at 12 weeks. The study was conducted at the Center of Reproductive Medicine, Tongji Medical College, Wuhan Union Hospital, Huazhong University of Science and Technology. The patients were divided into Group I and Group II. Group I was treated with modified long gonadotropin-releasing hormone agonist protocol while Group II was put on a non-downregulation protocol. Propensity score matching (PSM) was used to select patients for each group. The subjects were compared in terms of the baseline level, process of controlled ovarian hyperstimulation, and pregnancy outcomes. Binary logistic regression analysis was performed to assess the difference in the cumulative pregnancy rate between the two groups. Of the 910 POSEIDON patients who underwent IVF, 213 received the modified long gonadotropin-releasing hormone agonist protocol and 697 were subjected to the non-downregulation protocol. From the original cohort, PSM matched 174 pairs of patients. No statistically significant difference was found in total gonadotropin (Gn) dose between the two PSM groups, but the average daily Gn dose was lower in Group I and the duration of Gn lasted longer. The number of retrieved oocytes, the number of metaphase II (MII) ooctyes retrieved, normal fertilization, and normal cleavage embryos was significantly higher in Group I than in Group II, but there existed no significant difference in the number of high-quality embryos between the two groups. The single-cycle CPR (cumulative pregnancy rate) was higher in Group I than in Group II (for Group I: before PSM, CPR = 52.6%; after PSM, CPR = 51.7%; for Group II: before PSM, CPR = 34.0%; after PSM, CPR = 34.5%), and the difference was statistically significant. A binary logistic regression analysis in the unmatched patients showed that the CPR of Group II was 0.486 times that of Group I (95% CI: 0.303 to 0.779). The modified long gonadotropin-releasing hormone agonist protocol can be used as an optimal protocol for IVF or ICSI (Intracytoplasmic sperm injection) in POSEIDON patients. Level III.

Factors influencing clinical pregnancy outcome of in vitro fertilization/intracytoplasmic sperm injection in older women.

To analyse the factors influencing clinical pregnancy outcome of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) in older women, and to establish a risk prediction model. A total of 425 patients receiving IVF/ICSI from March 2018 to March 2020 were divided into pregnancy group (n=194) and non-pregnancy group (n=231). The factors affecting the outcomes of IVF/ICSI were explored by univariate and multivariate logistic regression analyses. A nomogram prediction model was constructed. The two groups had significantly different age, body mass index, dysmenorrhea, parity, times of full-term births, history of cesarean section, basal follicle stimulating hormone, basal antral follicle count (AFC), number of high-quality embryos, and basal estradiol, luteinizing hormone and endometrial thickness on the day of human chorionic gonadotropin (HCG) administration (P<0.05). Age ≥40 years old, dysmenorrhea, history of cesarean section, basal AFC<9, number of high-quality embryos <4, and endometrial thickness on the day of HCG administration <11 mm led to IVF/ICSI failure. The established model exhibited high calibration and discrimination degrees in predicting the outcome of IVF/ICSI. The risk prediction model for the pregnancy outcome of IVF/ICSI in older women helps evaluate the fertility probability and risk, providing references for formulating reasonable assisted reproduction plans.

Season and temperature do not affect cumulative live birth rate and time to live birth in in vitro fertilization.

To explore whether season and temperature on oocyte retrieval day affect the cumulative live birth rate and time to live birth. This was a retrospective cohort study. A total of 14420 oocyte retrieval cycles from October 2015 to September 2019. According to the date of oocyte retrieval, the patients were divided into four groups (Spring(n=3634);Summer(n=4414); Autumn(n=3706); Winter(n=2666)). The primary outcome measures were cumulative live birth rate and time to live birth. The secondary outcome measures included the number of oocytes retrieved, number of 2PN, number of available embryos and number of high-quality embryos. The number of oocytes retrieved was similar among the groups. Other outcomes, including the number of 2PN (P=0.02), number of available embryos (p=0.04), and number of high-quality embryos (p<0.01) were different among the groups. The quality of embryos in summer was relatively poor. There were no differences between the four groups in terms of cumulative live birth rate (P=0.17) or time to live birth (P=0.08). After adjusting for confounding factors by binary logistic regression, temperature (P=0.80), season (P=0.47) and duration of sunshine(P=0.46) had no effect on cumulative live births. Only maternal age (P<0.01) and basal FSH (P<0.01) had an effect on cumulative live births. Cox regression analysis suggested no effect of season(P=0.18) and temperature(P=0.89) on time to live birth. Maternal age did have an effect on time to live birth (P<0.01). Although season has an effect on the embryo, there was no evidence that season or temperature affect the cumulative live birth rate or time to live birth. It is not necessary to select a specific season when preparing for IVF.

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.

Screening the predictors for live birth failure in women after the first frozen embryo transfer based on the Lasso algorithm: a retrospective study.

This study aimed to screen factors related to live birth outcomes of women with first frozen embryo transfer (FET). The enrolled women were divided into training and validation cohorts. The least absolute shrinkage and selection operator (Lasso) regression algorithm of machine learning and the multiple regression model were then used to screen factors relevant to live birth failure (LBF) for the training dataset. A nomogram risk prediction model was established on the basis of the screened factors, and the consistency index (C-index) and calibration curve were derived for evaluating the model. The validation cohort was utilized to validate the nomogram model further. In total, 2083 women who accepted the first FET in our hospital were included and 44 factors were initially screened in this study. On the basis of the training cohort, the screened risk factors via multiple regression analysis with odds ratio (OR) values were female age (OR: 3.092, 95%CI: 1.065-4.852), body mass index (BMI; OR: 1.106, 95%CI: 1.015-1.546), caesarean section (OR: 1.909, 95%CI: 1.318-2.814), number of high-quality embryos (OR: 0.698, 95%CI: 0.599-0.812), and endometrial thickness (OR: 0.957, CI: 0.904-0.980). The nomogram model was generated based on five predictors. Furthermore, favourable results with C-indexes and calibration curves close to ideal curves indicated the accurate predictive ability of the nomogram. Female age, BMI, caesarean section, number of high-quality embryos, and endometrial thickness were independent predictors for LBF. The five factors of the risk assessment model may help to identify LBF with high accuracy in women who accept FET.

Retrospective study of influencing factors on the outcomes of luteal phase stimulation in patients with dual stimulation.

Dual/double stimulation (DS) is an ovarian stimulation strategy that has emerged in recent years; it is characterized by two rounds of ovarian stimulation and oocyte retrieval in the same menstrual cycle. DS can greatly shorten the time required to obtain valid embryos in assisted reproduction. For fertility preservation, DS can speed up oocyte storage process. However, factors influencing luteal phase ovarian stimulation (LPS) outcomes in DS have not been elucidated. A total of 156 cycles from 78 cases were studied. Patients were grouped and analyzed according to their follicular phase ovarian stimulation (FPS) types. Female ages, ovarian stimulation protocols, number of oocytes retrieved, embryo quality were recorded. Comparisons of outcomes were conducted between different groups. Our study found that LPS obtained similar outcomes to follicular phase stimulation (FPS), and that the choice of FPS protocol affected the efficiency of LPS, the antagonist protocol and progestin-primed ovarian stimulation (PPOS) protocol resulted in better embryo outcomes in LPS. In LPS of DS, sufficient stimulation duration was the guarantee of embryo quality (number of available embryos: β = 0.145, 95% CI [0.078-0.211], P = 0.000; number of high-quality embryos: β = 0.114, 95% CI [0.057-0.171], P = 0.000). This study provided ideas for the precise use of DS. We suggest to further expand the sample size of DS in the future, conduct prospective controlled studies, unify the sample size of each subgroup, include the ovarian reserve of patients in the grouping basis, and exclude the influence of male factors. We hope that this study will help further refinement of DS so as to maximize patient benefits from it. When the DS strategy is considered in the follicular phase, the antagonist protocol and PPOS protocol are more recommended for better embryo outcomes in LPS. During LPS, adequate ovarian stimulation duration is the most important guarantee for LPS efficiency.

Optimal number of high-quality cleavage-stage embryos for extended culture to blastocyst-stage for transfer in women 38 years and older

Purpose We aimed to evaluate the pregnancy outcomes of cleavage-stage embryo transfers (ETs) for the first time and explore optimal number of high-quality cleavage-stage embryos for extended culture to blastocyst-stage in women of advanced maternal age (AMA). Methods We retrospectively identified 1646 AMA women ≥ age 38 years for the first fresh ETs between January 2014 and December 2020 at our hospital. Double ETs were divided into three groups as follows: DET-HH (two high-quality embryos), DET-HL (one high-quality and one low-quality embryo), and DET-LL (two low-quality embryos) groups. We mainly analyzed the pregnancy outcomes of double cleavage-stage ETs with different embryo grades and blastocyst-stage ETs with different number of high-quality cleavage-stage embryos on day 3. Results Our data indicated that the DET-HH group had significantly higher clinical pregnancy, ongoing pregnancy, and live birth rates than DET-HL and DET-LL groups (p < .05). For extended culture to blastocyst-stage with 2 (D3-2H), 3 (D3-3H), and 4 (D3-≥4H) high-quality cleavage-stage embryos, the D3-≥ 4H group had significantly higher ongoing pregnancy and live birth rates than D3-2H and D3-3H groups (p < .05). We observed that the number of high-quality embryos on day 3 was independently associated with live birth rate for blastocyst transfers (OR: 1.133, 95% CI 1.023–1.256, p = .017). There were no significant differences in the clinical pregnancy, ongoing pregnancy and live birth rates among DET-HH, D3-2H and D3-3H groups (p > .05). Conclusions Extended culture to blastocyst-stage for transfer was safe and recommended for AMA women with ≥ 4 high-quality embryos on day 3.

Predictive value of anti-Mullerian hormone for pregnancy outcomes following assisted reproductive techniques (ART) in Southwest China

BackgroundAnti-Müllerian hormone (AMH) is secreted by granulosa cells in preantral follicles and small antral follicles. There is limited information about whether serum AMH levels are related to pregnancy outcomes during in vitro fertilization and embryo transfer (IVF-ET). The aim of this study was to provide a theoretical basis for improving pregnancy outcomes.MethodsA retrospective cohort study was conducted on infertile women who were treated at the Reproductive Centre of the Affiliated Hospital of Southwest Medical University between September 2018 and September 2019. The sample included 518 participants from Southwest China. The participants were divided into 2 groups according to their AMH level. Their data were retrieved from the medical records: days and dosage of gonadotropin (Gn) (one bottle equals 75 IU), the number of oocytes obtained, the number of oocytes in metaphase II (MII) and the number of high-quality embryos. The pregnancy outcomes were followed up and divided into two groups according to whether they were pregnant or not, with statistical analysis of the parameters related to the in vitro fertilization process performed separately.ResultsCompared to a lower AMH level (AMH ≤ 1.1), a higher AMH level (AMH > 1.1) resulted in less total Gn (bottle) (P = 0.00 < 0.05) and a lower starting Gn (IU) (P = 0.00 < 0.05), while the number of oocytes obtained,MII,cleavages and high-quality embryos were higher (P = 0.00 < 0.05). The participants' pregnancy outcomes (ectopic pregnancy, miscarriage, singleton, twin, multiple births) were found to not be predictable by AMH through ROC curves (P = 0.980, 0.093, 0.447, 0.146, 0.526, and 0.868 > 0.05). For participants in the pregnancy group, although AMH was lower in the nonpregnant participants(P = 0.868 > 0.05), the difference was not statistically significant, and the correlation coefficients between the two groups suggested no differences in the IVF process, except for the starting Gn (IU) (P = 0.038 < 0.05).ConclusionAMH has clinical application value in predicting ovarian reserve function, providing guidance and suggestions for the specific formulation of ovulation promotion programs with assisted reproductive technology, but it cannot effectively predict the outcome of clinical pregnancy.

Analysis of factors related to early miscarriage after in vitro fertilization embryo transfer

AimsThis research aims to explore the factors related to early spontaneous miscarriage after in vitro fertilization and embryo transfer (IVF-ET) pregnancy, and to provide guidance for improving pregnancy outcomes. MethodsWe retrospectively analyzed the data for clinical pregnant women (2591 cycles) undergoing IVF-ET at the reproductive center of Peking University People’s Hospital from January 2017 to December 2018; This included 544 ​ET cycles and 2047 frozen embryo transfer cycles. The analysis of factors associated with early miscarriage in the overall population of IVF/intracytoplasmic sperm injection (ICSI) pregnancies (including fresh and thawing cycles) was performed. ResultsThe risk of early miscarriage in the 35–39 age group was 1.35 times higher than that in the <35 age group (OR ​= ​1.35 [1.05,1.73], p ​= ​0.02). In addition, the risk of early miscarriage was 3.88 times higher in the group ≥40 years old than in the group <35 years old (OR ​= ​3.88 [2.68,5.62], p ​< ​0.001). Endometrial thickness also affected the miscarriage rate; the early miscarriage risk with endometrial thickness ≥8.5 ​mm was 0.78 times than that of the <8.5 ​mm group (OR ​= ​0.78 [0.62,0.98], p ​= ​0.03). The early miscarriage rate during frozen embryo transfer was 1.48 times higher than that during fresh embryo transfer (OR ​= ​1.48 [1.08,2.02], p ​= ​0.01), while in the fresh cycle, the risk of early miscarriage with high-quality embryos was 0.5 times lower than that with non-high quality embryos (OR ​= ​0.5 [0.27,0.9], p ​= ​0.02). In the frozen cycle, the risk of early miscarriage in natural cycle transplantation was 0.73 times that in hormone replacement treatment (HRT) cycle transplantation (OR ​= ​0.73 [0.54,0.97], p ​= ​0.03) . ConclusionsAdvanced age is an independent risk factor for early miscarriage, while endometrial thickness at the date of transplantation is an independent protective factor. The risk of early miscarriage in fresh-cycle transplanted embryos is significantly lower than that in frozen embryos, and the number of high-quality embryos in the fresh cycle lowers the miscarriage rate significantly. Natural cycle transplantation has a lower rate of early miscarriage than hormone replacement therapy.

Clinical efficacy analysis of oocyte cryopreservation: A propensity score matched study.

To investigate the effectiveness of oocyte thawing cycles in the clinical application of assisted reproductive technology (ART). The clinical data of 78 cases who underwent oocyte thawing cycles in our center were retrospectively analyzed. All patients in this study received oocyte cryopreservation for the husband reason. According to patient age at egg freezing, patients were divided into three observation groups (Group A, <30 years old; Group B, 30-34 years old; Group C, ≥35 years old), and the control groups were selected by propensity score matching with fresh cycles. The clinical outcomes of each group were compared, and the clinical efficacy of oocyte thawing cycles was analyzed. Clinical pregnancy outcomes of oocyte thawing cycles were not significantly different from that of fresh oocytes, but vitrification affected the number of two pronuclei zygotes developing to cleavage stage and the number of high-quality embryos, and the normal fertilization rate after thawing. The cycle cumulative live birth rate in Group C was significantly lower than those in Groups A and B. The live birth rates per egg of Groups A, B, C were 5.03%, 5.61%, and 3.57%, respectively, and the numbers of eggs per live birth were 13.72, 14.43, and 21.0, respectively. The overall clinical outcomes of oocyte vitrification were similar to that of fresh oocytes, but the cleavage rate and embryo quality of frozen oocytes were slightly reduced. Freezing of oocytes in women over 35 years of age affects the clinical efficacy of ART.

P-010 Sperm selection by birefringence: a promising non-invasive tool to improve ICSI outcomes

Abstract Study question Could the sperm selection by birefringence improve ICSI outcomes in couples with different infertility factors? Summary answer Sperm selection by birefringence demonstrated a positive clinical impact on ICSI outcomes in couples with different infertility factors when compared to the conventional sperm selection. What is known already Higher sperm DNA fragmentation may affect ICSI outcomes. However, the utilized sperm selection protocols do not allow the evaluation of this parameter. In this sense, the analysis of sperm’s head birefringence has been suggested as an adjuvant of seminal processing in order to select viable sperm for couples with severe male factor. Nevertheless, considering men with normal seminal parameters may also curse with DNA fragmentation, the impact of birefringence on ICSI outcomes of couples with different infertility factors should be investigated. Study design, size, duration Retrospective case-control study. One hundred eighty-one couples who underwent ICSI from January 2018 to August 2020 [107 submitted to sperm selection by conventional analysis (Nonbirefringence group) and 74 whose sperm were selected by conventional analysis associated to sperm head birefringence evaluation (Birefringence group)] were included in the study. Participants/materials, setting, methods Medical records were assessed for eligibility evaluation and data collection. Clinical characteristics (female age, body mass index, infertility factor, seminal parameters) and ICSI outcomes (eg. fertilization rate, cleavage rate, blastulation rate, number of high quality embryos formed, implantation rate, biochemical pregnancy rate, clinical pregnancy rate per transfer and per initiated cycle) were compared between the groups using (p &amp;lt; 0.05). A multivariate logistic regression model was applied to verify the factors associated with clinical pregnancy. Main results and the role of chance Despite the Birefringence group showed higher female age (p = 0.01), lower seminal sperm concentration (p &amp;lt; 0.01) and higher sperm DNA fragmentation (p &amp;lt; 0.01), those patients cursed with higher cleavage rate (p = 0.04), higher clinical pregnancy rate per transfer (p = 0.03) and higher clinical pregnancy rate per initiated cycle (p = 0.02) than the Nonbirefringence group. The logistic regression showed a positive group (Birefrincence) effect on clinical pregnancy achievement. Limitations, reasons for caution The unequal inclusion of infertility factors between the groups might represent a bias. In logistic regression analysis, none of those factors interfered with clinical pregnancy, which reinforces the impact of the technique on the results. The endpoint analyzed was clinical pregnancy, while live birth would better reflect ICSI success. Wider implications of the findings Sperm selection by birefringence could positively impact ICSI outcomes. Because it is a cheap and easily reproducible technique, it could be combined with conventional ICSI treatments to improve the reproductive chances of those patients. Trial registration number not applicable

P-655 Insulin like growth factor-1 levels in follicular fluids of patients with poor ovarian response undergoing in vitro fertilization

Abstract Study question Does follicular fluid insulin like growth factor level (IGF-1) in poor responders (PR) differ from normoresponders? Is there a correlation between IGF-1 and IVF outcomes? Summary answer Follicular IGF-1 levels are decreased in poor-responders A positive correlation exists between IGF-1 and number of metaphase II (MII) oocytes, fertilized oocytes and transferred embryos What is known already IGFs are mainly synthesized in liver with growth hormone stimulation. IGF-1 component in follicular fluid has been reported to play a crucial role in follicular and embryonic development. In addition to previously reported positive correlation between follicular IGF-I levels and number of high quality embryos, a significant decrease in IGF-1 levels with PR and advanced maternal age has also been reported. GH supplementation in poor responders undergoing IVF has been suggested to improve IVF outcomes. A recent Cochrane analysis reported that GH slightly increases the number of oocytes retrieved and there is an uncertain effect on live birth rates (LBR). Study design, size, duration Study was designed prospectively. A power analysis, of 91% determined a need for 186 patients. Therefore 186 women undergoing IVF between October 2019 and December 2020 were included. 72 (%38,7) patients were assigned to PRs group according to Bologna criteria (BC) and 114 patients (%61.3) were recruited as controls. Antagonist protocol was used for controlled ovarian hyperstimulation. hCG was administered for ovulation trigger. Participants/materials, setting, methods Following the ovarian hyperstimulation follicular fluid samples were collected during oocyte retrieval. When the total desired number of patients was reached, frozen and preserved follicle fluids were thawed at room temperature. IGF-1 levels in samples were measured using hIGF-1 ELISA kit (BT®, China). Follicular IGF-1 levels in PRs were compared to normoresponders and correlation between IGF-1 levels and AMH levels, number of retrieved oocytes, MII and fertilized oocytes, transferred embriyos and LBR were evaluated. Main results and the role of chance Mean IGF-1 levels of normoresponders and Bologna subgroups (B1, B2, B3, B4) were 13.79±14.50 ng/ml vs 5.75±1.86, 5.47±2.83, 5.96±2.16 and 5.03±1.85 ng/ml respectively (p &amp;lt; 0.001). There was no statistically significant difference in clinical pregnancy (CP) per transfer and LBR per transfer between normoresponders and PRs (CPR/ET: 55.1% vs 43.7%, p:0.375; 26.5% vs 12.5% , p: 0.257). In the ROC analysis for the prediction of collection of fewer than 4 oocytes at retrieval (according to BC definition of PR), statistically determined IGF-1 value was 7.02 with a sensitivity of 83% and a specificity of 38.6%. Patients with an IGF-1 value below 7.02 had a higher risk of having an oocyte number less than 4According to the results of Spearman's correlation analysis, IGF-1 levels were negatively correlated with age and number of previous failed cycles (r:-0.250, p:0,001; r:-0.153, p:0,039 respectively). IGF-1 levels were positively correlated with AMH levels, oocyte, MII oocyte, fertilized oocyte numbers and number of transferred embriyos (r: 0.221, p: 0.007; r: 0.283, p &amp;lt; 0.001; r: 0.293, p &amp;lt; 0.001; r: 0.282, p &amp;lt; 0.001; r: 0.194, p: 0.008 respectively). There was a positive correlation between IGF-1 levels and cycle cancellation rates (r: 0.637, p &amp;lt; 0,001). There was no correlation between IGF-1 levels and LBR (p:0.118). Limitations, reasons for caution Small number of patients was the main limitation of study.Results were not interpreted as LBR in all cases, as 21% (n:24) of the cases had still ongoing pregnancies Wider implications of the findings Detecting lower follicular levels of IGF-1 which plays a crucial role in GH activity may highligt the effect of GH supplementation in poor responders undergoing IVF in terms of improved outcomes. However, there is need for more solid data to employ GH in IVF treatment modalities of poor-responders. Trial registration number not applicable

Should Intra Cytoplasmic Sperm Injection (ICSI) be the primary insemination method in women undergoing IVF cycles with donor sperm?

To compare efficacy of Intra Cytoplasmic Sperm Injection (ICSI) with conventional in vitro fertilization (IVF) on treatment outcome in women undergoing in vitro fertilization with donor sperm. We examined retrospectively the outcome data from 203 patients undergoing fresh cycles of conventional IVF (cIVF) or ICSI and an additional 77 frozen-thawed embryo transfer (FET) cycles during 2003-2014, all using donor sperm. Fertilization, cleavage, pregnancy and live birth rates and number of high-quality embryos were compared between cIVF and ICSI. Altogether 185 women underwent 479 transfer cycles of fresh embryos (237 cIVF vs. 224 ICSI and 18 "rescue ICSI" cycles). In addition, 77 FET cycles were compared (24 cIVF vs. 53 ICSI cycles). No differences were found between cIVF and ICSI in fertilization, cleavage, pregnancy and live birth rates (92.6% vs 92.2%, 73.4% vs 72.4%, 25.3% vs 27.2% and 13.1% vs 14.7%, respectively). Pregnancy and life birth rates remained similar even when FET cycles were included (25.8% vs 26.2% and 13.1% vs 13.7%, respectively). The use of ICSI was associated with lower rates of high-quality embryos (52.7% vs. 63.3%, P < 0.0001). A multivariate logistic regression analysis found that patients' age, number of transferred embryos and smoking were independently associated with the chance to conceive. Patient age correlated inversely with fertilization rate (r =-0.13, P < 0.006).Non-smokers were more likely to become pregnant (OR = 2.23, P < 0.012). Our results show that ICSI does not bypass the age-related decrease in oocyte quality in patients using donor sperm for IVF. Use of ICSI was associated with lower rates of high-quality embryos. The findings imply that ICSI should not be the primary method of insemination in patients undergoing IVF with donor sperm.

Analysis of Relevant Factors Affecting the Pregnancy Rate of Frozen-Thawed Embryo Transfer Cycle.

Objective The aim of this study is to explore the relevant factors affecting the pregnancy rate of frozen-thawed embryo transfer cycle. Methods The clinical data of 931 patients who underwent artificial cycle preparation for endometrial FET from April 2017 to November 2020 in the reproductive center of our hospital were retrospectively analyzed. Results According to the pregnancy situation, the patients were divided into 450 cases of pregnancy and 481 cases of biochemical pregnancy. The univariate analysis of FET biochemical pregnancy showed that there were statistically significant differences between pregnancy and biochemical pregnancy in terms of years of infertility, age, endometrial thickness, P level, E2/P, and the number of high-quality embryos (P < 0.05). Multivariate analysis of pregnancy showed that age <30 years was a protective factor for biochemical pregnancy and endometrial thickness <8 mm and E2/P < 0.3 were risk factors (P < 0.05). Conclusion The regulation of endometrial thickness and E2/P serves as the key of treatment for patients undergoing FET using artificial cycle preparation for endometrial transfer, and it contributes to improve the pregnancy rate; also, the patient's age is an important indicator influencing the pregnancy rate.

Antinuclear antibodies in follicular fluid may be a risk factor in vitro fertilization and embryo transfer.

To explore the effect of anti-nuclear antibodies (ANAs) on the outcome of in vitro fertilization-embryo transplantation (IVF-ET) and to study the effect of ANAs in follicular fluid (FF) on embryonic development. The expression of ANAs in FF of patients treated with IVF-ET and healthy group. The patients were divided into ANAs-positive group and ANA-negative group. The age, duration of infertility, body mass index (BMI), basic follicle stimulating hormone (bFSH), anti-Mullerian hormone (AMH), number of retrieved oocytes, portion of metaphase II oocytes (MII), number of embryos in the cleavage stage, bipronuclear (2PN), number of embryos, number of high-quality embryos and the outcome of IVF-ET were compared between the two groups. In vitro, HTR8/SVneo trophoblast cells were cultivated and divided into ANAs-negative group (control group) and ANAs-positive group (ANAs-positive FF was added to cytotrophoblasts). The ANAs titer in the serum and FF of patients who treated with IVF-ET was detected using ELSIA method. CCK-8 assay and flow cytometry (at 24 h and at 48 h) were used to detect the cell proliferation and apoptosis frequency of the two groups, respectively. Among those who underwent IVF-ET treatment, the number of retrieved oocytes, the number of fertilization and the portion of MII oocytes in the FF-positive group were significantly lower than those in the FF-negative group. Furthermore, the implantation rate and the clinical pregnancy rate were decreased, and early miscarriage rate was increased in the FF-positive patients than those in the FF-negative patients. In vitro, the cytotrophoblasts proliferation activity in the ANAs group was significantly lower than that in the control group. Moreover, the cytotrophoblasts apoptosis rate in the ANAs group was significantly higher than that in the control group. Our data suggested that ANAs in FF might become an obstacle to embryonic development through promoting trophoblast apoptosis and inhibiting trophoblast proliferation. ANAs in FF might be an unfavorable factor for the outcome of those who undergo IVF-ET treatment.

Influence of Maternal Age on the Relationship Between Endometrial Thickness and Ongoing Pregnancy Rates in Frozen-Thawed Embryo Transfer Cycles: A Retrospective Analysis of 2,562 Cycles.

BackgroundIn frozen–thawed embryo transfer (FET) cycles, endometrial thickness (EMT) has been used routinely as the main clinical monitoring index. However, the current findings are conflicting.MethodThis was a single-center retrospective study of 2,054 couples (2,562 cycles) who underwent FET (including cleavage stage embryos and blastocysts) between January 2017 and August 2020 in the reproductive centers of First Affiliated Hospital of Xinjiang Medical University. The primary outcome measure was the ongoing pregnancy rate (OPR); the secondary outcome was the clinical pregnancy rate.ResultsAfter stratified analysis and adjusting for confounders such as maternal age, duration of infertility, number of high-quality embryos transferred, endometrial preparation protocol, number of transfer cycles, and stages of embryo transferred, we found a curvilinear relationship between EMT and the OPR in women < 35 years of age. For women with EMT ≤ 8 mm, the OPR increased by 150% for cleavage stage embryo transfer for every 1 mm increase in the EMT; similarly, it increased by 97% for blastocyst stage FET. However, there was a linear relationship between EMT and OPR in women aged ≥ 35 years. When blastocysts were transferred, for every 1 mm increase in the EMT the OPR increased significantly by 12%. But OPR after frozen-thawed cleavage stage embryos transfer did not increase significantly with increased EMTConclusionsOur study showed that the OPR increased significantly with increased EMT between young women aged < 35 years with EMT ≤ 8 mm and older women who underwent transfer of blastocysts.

The effect of flexible low-dose GnRH antagonist on pregnancy outcome in the fresh embryo transfer cycle of IVF-ET: a randomized controlled trial

ObjectiveTo explore the practicality and effectiveness of a flexible low-dose protocol in the fresh embryo transfer cycle: reducing the total amount of antagonist by increasing the interval between administrations of Cetrotide.MethodsA total of 211 patients with normal ovarian reserve who accepted GnRH-ant protocol for IVF-ET were selected, and they were randomized to the flexible low-dose antagonist group (test group, n = 101) or the conventional dose antagonist group (control group, n = 110). The initial dose of Cetrotide in the test group was 0.25 mg every other day, and then the dose was adjusted to 0.25 mg every day based on the subsequent luteinizing hormone (LH) levels. The dosage of Cetrotide in the control group was 0.25 mg per day. The primary outcome was the clinical pregnancy rate. Secondary outcomes included the incidence of premature LH rise, total dosage of Cetrotide, number of oocytes retrieved, number of fertilized oocytes, number of high-quality embryos, biochemical pregnancy rate and ongoing pregnancy rate.ResultsThere was no significant difference in the general condition of the two groups. There was no significant difference in the clinical pregnancy rate (51.49% vs. 48.18%, p = 0.632) or the incidence of premature LH rise (18.81% vs. 15.45%, p = 0.584) between the two groups. However, the amount of Cetrotide used in the test group was significantly lower than that in the conventional dose antagonist group (1.13 ± 0.41 vs. 1.61 ± 0.59 mg, p < 0.001).ConclusionThe flexible low-dose antagonist protocol and the conventional dose antagonist protocol were equally effective in people with a normal ovarian reserve in the fresh embryo transfer cycle of IVF-ET.

Improved pregnancy outcomes of cyclosporine A on patients with unexplained repeated implantation failure in IVF/ICSI cycles: A retrospective cohort study.

Repeated implantation failure (RIF) is a daunting obstacle restricting the further improvement of embryo implantation rate (IR) and live birth rate (LBR). The beneficial effect of cyclosporine A (CsA) on reproductive outcomes of unexplained RIF(URIF) was explored after de novo embryo transfer (ET). A retrospective cohort study was conducted, comparing pregnancy outcomes of 146 cycles (CsA group, n=62; control group, n=84) at the IVF center of Suzhou Municipal Hospital from April 2016 to March 2020. Baseline and transfer cycle characteristics of participants were comparable between groups. Overall, CsA exerted obvious improvement on IR (51.16% vs 31.97%, P=.006), clinical pregnancy rate (CPR) (58.06% vs 38.10%, P=.017), and LBR (48.39% vs 32.14%, P=.047). Especially, CsA showed remarkably enhancement on IR (41.38% vs 14.63%, P=.012), CPR (47.62% vs 17.24%, P=.021) of non-high quality embryos. No difference in obstetric and pediatric complications was observed, and no birth defects were reported under CsA application. CsA was found to be a predictor of clinical pregnancy [fine adjusted OR 2.360, 95 % CI 1.165-4.781; P=.017] and live birth [fine adjusted OR 2.339, 95% CI 1.124-4.867; P=.023] for multivariate logistic regression. Not surprisingly, the number of high quality embryos should also be considered as an independent predictor for clinical pregnancy [fine adjusted OR 1.637,95%CI 1.027-2.609; P=.038] and live birth [fine adjusted OR 1.890, 95% CI 1.165-3.068; P=.010]. CsA application in patients with URIF promotes the pregnancy outcomes and does not increase the risk of obstetric and pediatric complications.