Number Of Good Quality Embryos Research Articles

Does growth hormone supplementation of in vitro fertilization/intracytoplasmic sperm injection improve cumulative live birth rates in women with poor embryonic development in the previous cycle?

BackgroundGrowth hormone (GH) has been proposed as an adjunct in in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles, especially in women with poor ovarian response. However, it is unclear whether GH supplementation is effective in women with poor embryonic development in the previous IVF cycle. The aim of this study was to evaluate the effectiveness of GH supplementation in IVF/ICSI cycles in women with poor embryonic development in the previous cycle.MethodsThis is a retrospective cohort study from a public fertility center in China, in which we performed propensity score-matching (PSM) for female age and AFC in a ratio of 1:1. We compared the cumulative live birth rate per started cycle, as well as a series of secondary outcomes. We included 3,043 women with poor embryonic development in the previous IVF/ICSI cycle, of which 1,326 had GH as adjuvant therapy and 1,717 had not. After PSM, there were 694 women in each group.ResultsAfter PSM, multivariate analyses showed the cumulative live birth rate to be significantly higher in the GH group than the control group [N = 694, 34.7% vs. N = 694, 27.5%, risk ratio (RR): 1.4 (95%CI: 1.1–1.8)]. Endometrial thickness, number of oocytes retrieved, number of embryos available, and number of good-quality embryos were significantly higher in the GH group compared to controls. Pregnancy outcomes in terms of birth weight, gestational age, fetal sex, preterm birth rate, and type of delivery were comparable. When we evaluated the impact of GH on different categories of female age, the observed benefit in the GH group did not appear to be significant. When we assessed the effect of GH in different AFC categories, the effect of GH was strongest in women with an AFC5-6 (32.2% versus 19.5%; RR 2.0; 95% CI 1.2–3.3).ConclusionsWomen with poor embryonic quality in the previous IVF/ICSI cycles have higher rates of cumulative live birth with GH supplementation.

The impact and inflammatory characteristics of SARS-CoV-2 infection during ovarian stimulation on the outcomes of assisted reproductive treatment.

Despite the global prevalence of coronavirus disease 2019 (COVID-19), limited research has been conducted on the effects of SARS-CoV-2 infection on human reproduction. The aims of this study were to investigate the impact of SARS-CoV-2 infection during controlled ovarian stimulation (COS) on the outcomes of assisted reproductive treatment (ART) and the cytokine status of patients. This retrospective cohort study included 202 couples who received ART treatment, 101 couples infected with SARS-CoV-2 during COS and 101 matched uninfected couples. The parameters of ovarian stimulation and pregnancy outcomes were compared between the two groups. The All-Human Inflammation Array Q3 kit was utilized to measure cytokine levels in both blood and follicular fluid. No difference was found in the number of good-quality embryos (3.3 ± 3.1 vs. 3.0 ± 2.2, P = 0.553) between the infected and uninfected groups. Among couples who received fresh embryo transfers, no difference was observed in clinical pregnancy rate (53.3% vs. 51.5%, P = 0.907). The rates of fertilization, implantation, miscarriage, ectopic pregnancy and live birth were also comparable between the two groups. After adjustments were made for confounders, regression models indicated that the quality of embryos (B = 0.16, P = 0.605) and clinical pregnancy rate (P = 0.206) remained unaffected by SARS-CoV-2 infection. The serum levels of MCP-1, TIMP-1, I-309, TNF-RI and TNF-RII were increased, while that of eotaxin-2 was decreased in COVID-19 patients. No significant difference was found in the levels of cytokines in follicular fluid between the two groups. Asymptomatic or mild COVID-19 during COS had no adverse effects on ART outcomes. Although mild inflammation was present in the serum, it was not detected in the follicular fluid of these patients. The subsequent immune response needs further investigation.

Pretreatment with oral contraceptive pills in women with PCOS scheduled for IVF: a randomized clinical trial

Abstract STUDY QUESTION What is the effect of pretreatment with oral contraceptive pills (OCPs) on oocyte and embryo quality and pregnancy rates in women with polycystic ovary syndrome (PCOS) scheduled for IVF/ICSI cycles? SUMMARY ANSWER In women with PCOS who underwent a first or second IVF/ICSI cycle with a GnRH antagonist protocol and were randomized to start ovarian stimulation immediately, the quality of cleavage-stage embryos was non-inferior to pretreatment with OCP. WHAT IS KNOWN ALREADY PCOS in Asian populations is characterized by high levels of circulating LH in the early follicular phase. Previous studies indicated that inappropriately high LH levels might affect oocyte maturation and fertilization rates, and impaired embryo quality, consequently resulting in higher rates of impaired pregnancy and miscarriage in women with PCOS. OCPs are frequently used as pretreatment to lower LH levels in PCOS patients. STUDY DESIGN, SIZE, DURATION We performed a randomized controlled trial. After informed consent, women diagnosed with PCOS scheduled for their first or second IVF/ICSI cycle with a GnRH antagonist protocol were randomized to receive OCPs (OCP group) or start ovarian stimulation immediately, regardless of the day of the menstrual cycle (non-OCP group). Using a non-inferiority hypothesis, the sample size was calculated at 242 women. The study lasted from 7 February 2018 to 31 August 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 242 infertility patients with PCOS undergoing the first or second cycle of IVF or ICSI were enrolled and randomized into two groups. In the OCP group, recombinant FSH was started on Day 7 of the washout period after pretreatment with OCP. In the non-OCP group, recombinant FSH was started immediately regardless of the day of the menstrual cycle. All participants received standardized GnRH antagonist ovarian stimulation. The freeze-all strategy was applied to all participants. The primary outcome was the number of good-quality embryos on Day 3 after insemination. Secondary outcomes included the rates of blastocyst formation, implantation, clinical pregnancy, and live birth from the first frozen/warmed embryo transfer cycles and cumulative live birth rates. MAIN RESULTS AND THE ROLE OF CHANCE We randomized 242 women to receive OCP (n = 121) or start immediately with ovarian stimulation (n = 121). The number of good-quality embryos on Day 3 in the OCP group was non-inferior to the non-OCP group (OCP group versus non-OCP group, 6.58 ± 4.93 versus 7.18 ± 4.39, AD −0.61, 95% CI: −1.86 to 0.65, P = 0.34). The rates of blastocyst formation (55.4% versus 52.9%, relative risk (RR) 1.11, 95% CI: 0.96 to 1.28, P = 0.17), implantation (63.0% versus 65.5%, RR 0.90, 95% CI: 0.53 to 1.53, P = 0.79), clinical pregnancy (67.9% versus 68.8%, RR 0.96, 95% CI: 0.54 to 1.71, P = 1.0), and live birth rate (52.8% versus 55.1%, RR 0.92, 95% CI: 0.53 to 1.56, P = 0.79) of the first frozen/warmed embryo transfer cycles were all comparable between the OCP and non-OCP group, respectively. Cumulative live birth rates were also similar in the OCP and non-OCP groups (78.3% versus 83.5%, respectively RR 0.71, 95% CI: 0.36 to 1.42, P = 0.39). LIMITATIONS, REASONS FOR CAUTION Only patients with PCOS in Southern China were recruited. Therefore, caution is necessary when generalizing our results to all such patients with PCOS. Also, since a freeze-only strategy was used, the results of this study are only applicable when infertile women with PCOS undergo the freeze-only method. The obvious treatment difference between the two groups meant that the study was designed as an open-label study for women and doctors. The study had a randomized controlled design that minimized bias. WIDER IMPLICATIONS OF THE FINDINGS Pretreatment with OCPs to lower LH levels in patients with PCOS before ovarian stimulation in IVF or ICSI cycles may not improve the quality of cleavage-stage embryos. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the National Key Research and Development Program of China (No. 2023YFC2705503). This study was supported in part by the Investigator-Initiated Studies Program (grant from MSD and Organon). BWM reports consultancy, travel support, and research funding from Merck. He reports consultancy from Organon and Norgine, and also reports holding stock from ObsEva. No conflicts of interest are declared for the other authors. TRIAL REGISTRATION NUMBER Chinese Clinical Trial Registry (No. chiCTR1800014822). URL: https://www.chictr.org.cn/showproj.html?proj=25280 TRIAL REGISTRATION DATE 7 February 2018. DATE OF FIRST PATIENT’S ENROLLMENT 22 February 2018.

Aggressive sperm immobilization improves reproductive outcomes in patients with suboptimal semen parameters and previous ICSI fertilization failure

Intracytoplasmic sperm injection (ICSI) is the most effective procedure to resolve male infertility, enhancing overall fertilization and pregnancy outcomes. However, it is important to note that fertilization failure (FF) can still occur in a few cases after ICSI. This study aims to introduce a specialized technique of aggressive sperm immobilization for ICSI and evaluate its impact on reproductive outcomes in cases involving prior fertilization failure. All infertile couples with male partners having suboptimal semen samples and previous ICSI fertilization failure were evaluated using retrospective data from National Taiwan tertiary university hospital (NTUH) between January 2016 and February 2022. Fertilization failure in our study was defined as less than 30% fertilization rate (FR, the number of normally fertilized oocytes divided by the total number of injected mature oocytes). Data involving both standard (routine procedure) and aggressive sperm immobilization (SI) techniques during different ICSI cycles were included in this study. Standard and aggressive SI methods were performed by compressing the distal half tail of the spermatozoa ≦ 5 and 15 times prior to ICSI respectively. Generalized estimating equations analysis were applied to compare the clinical outcomes between two procedures. Overall, data from 23 infertile couples who had undergone 65 ICSI cycles (31 standard SI with low fertilization rate and 34 aggressive SI) were included in the study. The average FR in the ICSI cycles with standard SI and aggressive SI were 23.6 ± 23.1% and 49.5 ± 31.8 respectively (P = 0.0002). The majority of embryos were transferred at the day 3 stage, with an average number transferred of 2.6 ± 0.9 in the aggressive SI group and 1.9 ± 0.9 in the standard group. The number of embryos transferred per transfer cycle was higher in the aggressive SI (P = 0.015), whereas the number of good-quality embryos was similar between the two procedures (P = 0.44). There were one and seven live births from the standard SI cycles and aggressive SI cycles respectively. In conclusion, aggressive SI was associated with a significantly higher FR, resulting in more available embryos for transfer without compromising embryo quality. Therefore, this specialized technique improved pregnancy outcome among infertile couples with a previous ICSI–FF. It can be a safe, economic, and effective method to improve the assisted reproductive technologies outcomes for infertile patients affected by previous ICSI–FF.

A randomized controlled trial to compare the live birth rate of the first frozen embryo transfer following the progestin-primed ovarian stimulation protocol vs. the antagonist protocol in women with an anticipated high ovarian response

ObjectiveTo compare the live birth rate of the first frozen embryo transfer following ovarian stimulation by the progestin-primed ovarian stimulation protocol versus the antagonist protocol in women with anticipated high ovarian response undergoing IVF DesignRandomized controlled trial SettingsA tertiary assisted reproduction center PatientsInfertile women aged <43 years undergoing the first IVF cycle and having antral follicle count >15 InterventionsMedroxyprogesterone 10 mg daily was given from the start of ovarian stimulation until the day of ovulation trigger in the progestin-primed ovarian stimulation protocol. In the antagonist protocol, an antagonist 0.25mg daily was given from 6th day of ovarian stimulation until the day of ovulation trigger. Blinding was not possible for women or physicians but the biostatistician was blinded to the group assignment. Main Outcome MeasuresLive birth rate of the first frozen embryo transfer cycle Results784 women were recruited from June 2020 and October 2021 and randomly assigned in a 1:1 ratio into two groups: progestin-primed ovarian stimulation group (n=392) and antagonist group (n=392). Embryo transfer was either cancelled or postponed in 62 (62/392, 15.8%) women in the progestin-primed ovarian stimulation group and 65 (65/392, 16.6%) in the antagonist group because of no transferable embryos or no frozen embryo transfer within 6 months following randomizaion. The two groups were similar in demographic characteristics and number of oocytes obtained/fertilized, the number of cleaving embryos, number of good quality embryos at day 3, number of blastocysts developed and number of embryo/blastocyst frozen. There was no statistically significant difference in the live birth rate of the first frozen embryo transfer cycle between the progestin-primed ovarian stimulation and antagonist groups based on both intention to treat [37.5.0% (147/392) versus 32.7% (128/392), RR 1.148 (95% CI=0.949–1.390), P=0.16] and per protocol analysis [44.5% (147/330) versus 39.1.% (128/327), RR 1.138 (95%CI = 0.950–1.364), P=0.16]. Both groups showed comparable clinical pregnancy, ongoing pregnancy, miscarriage, multiple pregnancy, ectopic pregnancy and cumulative live birth rates. ConclusionThe live birth rates of the first frozen embryo transfer following the progestin-primed ovarian stimulation and the antagonist protocol were comparable in women with an anticipated high ovarian response.

#295 : Comparison of In Vitro Fertilization in Couples with HIV Infection with Negative Viral Load Versus Non-Infected Couples: A Case-Control Study

Background and Aims: The development of Advanced Reproductive Technology (ART) changes many aspects and perspectives towards reproductive health. Current in vitro fertilization (IVF) protocols reduce the risk of Human Immunodeficiency Virus (HIV) transmission to their partners and offspring. This study compares IVF outcome in couples in which at least one partner is HIV positive with negative viral load versus couples in which neither partner is diagnosed with HIV. Method: A total of 100 couples undergoing IVF were categorized into two groups. HIV-positive with negative viral load group in which at least one partner is infected (n = 50) and non-HIV group in which neither partner is diagnosed with HIV (n = 50) are collected from medical record in our center during the same period. The main outcomes were total oocyte retrieved, normal fertilized egg or 2 pronucleus (2PN) one day after fertilization and good quality embryos based on number of embryos that transferred and frozen for IVF procedure. Differences between groups were determined statistically using the Mann-Whitney test. Results: There is a significant difference between HIV-positive with negative viral load groups compared to non-HIV groups in terms of total oocyte retrieved (p = 0,005) and normal fertilized egg one day after fertilization (p = 0.017). There is no significant difference in the number of good quality embryos (p = 0.076) between two groups. Conclusion: The data suggested that couples with HIV-positive women have poorer total oocyte retrieved and normal fertilized egg outcome compared to non-HIV couple. HIV infection might affect success rates of IVF treatments.

Duphaston as a suitable medication for women taking intracytoplasmic sperm injection to treat infertility

Objective: Duphaston is used as an alternative to gonadotropin-releasing hormone (GnRH) antagonists for suppressing premature luteinizing hormone (LH) surges. This study aimed to compare the efficacy of Duphaston protocols with that of Cetrotide in suppressing the LH surge. Methods: In this retrospective cross-sectional study, 669 infertile women (aged 25–40 years) were administered recombinant follicle-stimulating (rFSH) hormone from the third day of their menstrual cycle. After the follicular diameter reached–13-14 mm, Cetrotide was prescribed orally to the control subjects, also case subjects took Duphaston orally. The retrieved oocytes were fertilized by an intracytoplasmic sperm injection (ICSI). Results: The levels of FSH, LH, and estradiol did not differ significantly between the groups (P &gt;0.05). However, the findings indicated that Duphaston led to greater oocyte retrieval than Cetrotide (P=0.006). However, the number of mature oocytes and viable embryos in the case subjects did not reach a significant difference compared to that in the control subjects (P &gt;0.05). The number of good-quality embryos (stage1) was significantly higher in the case subjects (P =0.04). In addition, there is no significant difference in the chemical, clinical pregnancy, implantation rate, and miscarriage rate between both groups (P &gt;0.05) . Conclusion: Duphaston could be utilized as a suitable medication rather than a GnRH antagonist in women subjected to controlled ovarian hyperstimulation.

Luteinizing Hormone/Human Chorionic Gonadotropin Receptor N312S Single-Nucleotide Polymorphism and Its Impact on Clinical and Reproductive Outcomes in Assisted Reproductive Technology: A Prospective Cohort Study.

Objective The aim of this study was to determine the genotypic distribution of luteinizing hormone/human chorionic gonadotropin receptor (LHCGR) N312S single-nucleotide polymorphism (SNP) and to investigate its impact on clinical and reproductive outcomes in infertile Indian women undergoing assisted reproductive technology (ART). Study design and settings This was a prospective cohort study conducted at a tertiary care university hospital. Subjects and methods Infertile women aged between 21 and 40 years undergoing ART with an antagonist protocol were enrolled in this study. A 2-ml sample of peripheral venous blood was collected from each woman and genotyped for the LHCGR N312S SNP. Participants were divided into three groups based on their SNP: NN, NS, and SS. All subjects underwent controlled ovarian hyperstimulation (COH) through a gonadotropin-releasing hormone (GnRH) antagonist protocol and intracytoplasmic sperm injection (ICSI). Of the 140 women recruited based on selection criteria, 128 underwent embryo transfer. We compared the genotypic distribution of the LHCGR N312S SNP, baseline characteristics, clinical outcomes, and reproductive outcomes in ART among the three groups. Data were analyzed using IBM SPSS Statistics for Windows, Version 29 (Released 2022; IBM Corp., Armonk, New York, United States). The chi-square test and Fisher-Irwin test were employed to evaluate significant differences among the qualitative categorical variables. A p-value of less than 0.05 was considered statistically significant. Results Among the test subjects, 19.3% were homozygous for the LHCGR N312 SNP (NN group), 38.6% were heterozygous (NS group), and 42.1% were homozygous for the LHCGR S312 SNP (SS group). Baseline characteristics were similar among the three groups. In terms of ovarian reserve tests, significantly lower anti-Müllerian hormone (AMH) levels were observed in the SS group compared to the NS and NN groups (2.8 ± 2.1 vs. 3.2 ± 2.5 vs. 4.3 ± 3.3; p=0.03). No significant differences were observed in COH outcomes such as duration of stimulation, total gonadotropin requirement, oocyte yield, or the number of good-quality embryos among the three groups. The cumulative pregnancy rate (82.9% vs. 50.0% vs. 38.2%, p=0.0005), cumulative clinical pregnancy rate (78.8% vs. 44.7% vs. 34.5%, p = 0.0005), and cumulative live birth rate (50.0% vs. 20.2% vs. 20.0%, p=0.005) were significantly higher in the NN group than in the NS and SS groups. Conclusion The study's findings suggest that LHCGR N312 may help predict reproductive outcomes in ART, which may aid in providing better counseling to infertile couples. We need more studies on individualized/personalized COH using pharmacogenomics for follicle-stimulating hormone (FSH) and luteinizing hormone (LH) supplementation based on combined FSH and LH receptor SNP and to assess their effects on ART outcomes.

Effect of basal luteinizing hormone (bLH) level on in vitro fertilization/intra-cytoplasmic injections (IVF/ICSI) outcomes in polycystic ovarian syndrome (PCOS) patients

ObjectiveTo evaluate the effect of basal luteinizing hormone (bLH) levels on In Vitro Fertilization/Intra-Cytoplasmic Injections (IVF/ICSI) outcomes in polycystic ovary syndrome (PCOS).MethodsA total of 256 PCOS patients who underwent IVF/ICSI treatment in our center from January 2018 to January 2022 were analyzed retrospectively. The patients were based on the third quartile (12.455) of the basal LH value was taken as the cut-off value and was divided into high and low LH group: high LH group (LH ≥ 12.455 IU / L) and low LH group (LH < 12.455 IU / L) and the OC group was pretreated with oral contraceptives. The outcomes in ovulation induction and embryo transfer cycles of the three groups were then compared. In addition, factors influencing the number of good quality embryos and the early onset LH peak were analyzed.ResultsAges, infertility duration, body mass index (BMI), and basal follicle-stimulating hormone (FSH), and progesterone (P), testosterone (T) levels were not significantly different among the three groups (p > 0.05). However,there were significant differences in basal LH and basal E2 between low LH group and high LH group, and there were significant differences in basal LH between high LH group and OC group (p < 0.05). LH on the antagonist day was significantly different between low LH group and high LH group and between high LH group and OC group (p < 0.05). LH on the hCG (human Chorionic Gonadotropin) day there were significant differences between low LH group and OC group, high LH group and OC group (p < 0.05). The Mode of triggering between the three groups had significant differences between the two groups (p < 0.05). In addition, the number of days from gonadotropin (Gn) initiation to antagonist addition were significantly different among the three groups (p < 0.05). In addition, total Gn doses,the number of oocytes retrieved, the number of Gn days, 2pronucleus (2PN) numbers, number of good quality embryos, and number of high risk OHSS (Ovarian Hyper-stimulation Syndrome), cases with OHSS occurrences were not significantly different among the three groups (p > 0.05). Moreover, the cycle and clinical pregnancy outcomes and the cumulative clinical pregnancy rate and the cumulative live birth rate were not significantly different among the three groups (p > 0.05). LH levels on the day of antagonist addition affected the number of good-quality embryos (B < 0, p < 0.05). However, LH levels on the day antagonist was added were not significantly correlated with basal LH levels (Pearson correlation coefficient = 0.259), the ROC curve was constructed for the logistic prediction model of the early onset LH peak, and the AUC value was 0.747, indicating that the logistic combined model we constructed had a good ability to predict the early onset LH peak.ConclusionBasal LH levels do not affect the pregnancy outcomes in PCOS patients after antagonist protocols. Besides, LH levels on the day of antagonist addition affect the number of good quality embryos for PCOS patients undergoing IVF /ICSI.

Embryo Quality and Intracytoplasmic Sperm Injection (ICSI) Outcome in Iraqi Women with Polycystic Ovary Syndrome (PCOS): A Cohort Prospective Study

Polycystic ovary syndrome (PCOS) is a major cause of ovulatory dysfunctions among reproductive-aged women. PCOS impairs folliculogenesis leading to suboptimal oocyte maturation, impaired embryonic development and pregnancy failure. Intracytoplasmic sperm injection (ICSI) is a popular option for PCOS patients to attain pregnancy. However, there is no specific determinant to ascertain successful pregnancy outcome in PCOS women undergoing ICSI. The purpose of this study was to determine the influence of PCOS on embryo quality and subsequent pregnancy rate in Iraqi women who had undergone ICSI. Over the course of three months, one hundred and three infertile couples who were referred to Al-Sadr Medical City, Kufa, Iraq between October 2017 and June 2018 were enrolled in this study. The couples were divided into two groups: those with PCOS, and those who did not have PCOS. The amounts of hormones were determined. The evaluation of embryo attributes with grading, as well as the determination of the fertilization rate, cleavage rate, and pregnancy rate, were carried out. The difference in fertility and cleavage rates between the PCOS (P=0.40) and non-PCOS (P=0.59) groups was not statistically significant. When comparing the two groups, the mean number of good quality embryos in the PCOS group was higher (P=0.07), whereas the pregnancy rate in the former was considerably lower (P=0.02) than in the latter. According to our findings, PCOS had no negative impact on the quality of the embryos produced by Iraqi women who underwent ICSI treatment. Because PCOS is a complicated disorder characterized by a variety of endogenous physiological variables that may either directly or indirectly interfere with conception, the low likelihood of pregnancy in these patients suggests that good embryo quality is not the only predictor of successful pregnancy.

O-069 Double vs. single stimulation in young poor prognosis patients followed by a fresh embryo transfer: a randomized controlled trial.

Abstract Study question Does double stimulation, followed by a fresh ET (DUO-STIM fresh) improve outcomes as compared with a single stimulation in young poor prognosis patients? Summary answer Compared to single stimulation, DUO-STIM fresh leads to significantly higher number of good quality embryos, without hindering fresh embryo transfer outcomes. What is known already Dual Stimulation (ovarian stimulation both in the follicular and luteal phase of the same cycle) is an innovative strategy to retrieve higher number of oocytes in a shorter time frame, thus it is particularly appealing for poor ovarian responders. Three current limitations of Dual-Stimulation are: (1) it is unclear whether outcomes of the second (luteal) wave results from the second stimulation, or a carry-over effect from previous follicular stimulation; (2) the desynchronization between endometrium and ovaries and, (3) lack of robust evidence. No previous studies explored Dual Stimulation starting from the luteal phase, and with a fresh embryo transfer (DUOSTIM-fresh). Study design, size, duration This study is a prospective, randomized, controlled, single-center, superiority clinical trial comparing two different ovarian stimulation protocols: a double stimulation cycle vs. a single stimulation cycle followed by fresh ET. The primary outcome was the number of good quality embryos obtained, while secondary outcomes included results from fresh embryo transfer (clinical pregnancy, miscarriage). A total of 120 women were enrolled in this study between October 2020 and October 2022, with a 1:1allocation. Participants/materials, setting, methods Only young (&amp;lt;40 years old) poor-prognosis (AMH&amp;lt;1.2 ng/mL) patients were recruited in the Fertility Clinic within a tertiary University Hospital. In the investigational group, DUOSTIM-fresh, the 1st stimulation was initiated in the luteal phase followed by a 2nd stimulation 5 days post first OPU, initiated in the follicular phase and a fresh ET of the best embryo generated (1st or 2nd cycle). The control group performed a follicular phase single stimulation cycle with fresh ET. Main results and the role of chance Overall, 107 patients were randomized, 53 in the investigational (DUO-STIM fresh) and 54 in the control arm (single stim). DUO-STIM fresh resulted in a significantly higher number of good quality embryos as compared to single stim (difference of mean 0.81, 95% CI 0.12-1.49). The mean percentage of embryo transfer was comparable (62.3 and 51.9, respectively for double vs single stimulation). No significant differences were found for fresh embryo transfer outcomes (ongoing pregnancy rates: 24.5 and 22.2, respectively for DUO-STIM fresh vs conventional IVF). Of interest comparisons between different stimulation cycles (A: luteal phase DUOSTIM-fresh, B: follicular phase DUOSTIM-fresh and C: single stim didn’t demonstrate any significant difference in terms of ovarian response with the mean (SD) number of mature oocytes being (A: 3.3 (2.9) B: 3.4 (3.4) C: 3.5 (2.9), respectively). Limitations, reasons for caution Study sample size was calculated to detect differences on the mean number of good-quality embryos. Therefore, results for secondary outcomes (embryo transfer rates and clinical pregnancy rates) should be interpreted with caution as exploratory findings that warrant future investigations. Wider implications of the findings Although DUOSTIM-fresh results in higher number of blastocysts as compared with a single stimulation in young poor-prognosis patients, the decision of performing dual stim should be evaluated with caution considering that whether this may improve embryo transfers rate and pregnancy outcomes is still unclear. Results on Cumulative-Live-Birth-Rate are warranted. Trial registration number NCT04446845

P-218 Does Artificial Oocyte Activation (AOA) improve the outcome beyond fertilization rate in ICSI cycles?

Abstract Study question Does CultActive© improve reproductive outcomes of ICSI cycles in cases of low fertilization rate and normal fertilization rate? Summary answer The application of CultActive© after ICSI improves fertilization rates only in clinical indication of fertilization failure. What is known already Oocyte activation deficiency is attributed in the majority of cases to fertilization failure in ICSI cycles, and these can be corrected by increasing initial levels of calcium (Ca2+) using assisted oocyte activation techniques (AOA), such as the use of Ca2+ ionophores. These agents enhance intracellular calcium release and increase the membrane permeability facilitating the influx of extracellular Ca2+, which initiates the activation cascade. Previous results suggest that Ca2+ ionophore treatment can increase the live birth rate after failed ICSI cycles in couples with poor fertilization rates, embryo developmental arrest, and also increase the number of good quality embryos. Study design, size, duration This was a retrospective observational study. There were 30 patients included and the first group consisted of 30 ICSI cycles, 231 oocytes and 56 embryos (without AOA). The second group consisted of the same patients (n = 30) with 30 ICSI cycles using AOA, 219 oocytes and 47 embryos. Subgroups were defined according to clinical indications (normal fertilization rate group: ≥ 65 % and low fertilization rate group: &amp;lt;65% ). All data was collected from January-December 2022. Participants/materials, setting, methods 450 oocytes were assessed in the study. 231 oocytes belonged to the pre-AOA and 219 belonged to the AOA. The oocytes were exposed for 15 minutes after ICSI in a solution containing the Ca2+ ionophore A23187, CultActive© (Gynemed, Germany). Fertilization, good quality blastocyst formation and pregnancy rate were analyzed.Good quality blastocyst were defined as ≥ 3BB. Statistical significance was analyzed using the Paired Student T test (p &amp;lt; 0.05 was considered statistically significant). Main results and the role of chance The cohort of patients with normal fertilization rate (without clinical indications),was not significantly different. The AOA treatment gave a fertilization rate of 61% compared to 71% of the control cycles (p = 0.1398). There was no increase in the number of good quality blastocysts formation when the study group was compared to the control (p = 0.1660). In the cohort of patients with an indication of low fertilization, a significantly higher fertilization rate was recorded compared to the control (51% and 37%, respectively p = 0.0238). There were no significant difference in the quantity of good quality blastocysts compared with the control (p = 0.3328). Regardless of normal or low fertilization rates there was no significant difference in pregnancy rate when CultActive© was used in treatment (p &amp;gt; 0.05). Limitations, reasons for caution There are limitations in our study. First, the retrospective design and limited study population are major limitations. The data should be interpreted cautiously in the subgroup analyses due to potential bias, specifically the small population in the group without clinical indication. Wider implications of the findings AOA was only beneficial for couples with poor fertilization. Embryo quality and pregnancy rate did not improve with CultActiveive©. External variation was minimized by using the same patients in each cohort. This suggests AOA should not be used without clinical indication or for poor embryo quality/blastulation rate. Trial registration number not applicable

Effectiveness, Flexibility and Safety of Switching IVF to IVM as a Rescue Strategy in Unexpected Poor Ovarian Response for PCOS Infertility Patients

According to the latest practice committee document, in vitro maturation (IVM) is a simple and safe procedure, especially in patients with polycystic ovary syndrome (PCOS). Does switching from in vitro fertilization (IVF) to IVM (IVF/M) help as a rescue infertility treatment for PCOS patients with an unexpected poor ovarian response (UPOR) tendency? This retrospective cohort study included 531 women with PCOS who had undergone 588 natural IVM cycles or had switched to IVF/M cycles from 2008 to 2017. Natural IVM was performed in 377 cycles, and switching IVF/M was performed in 211 cycles. The primary outcome measure was the cumulative live birth rates (cLBRs), and the secondary outcomes included laboratory and clinical outcomes, maternal safety, and obstetric and perinatal complications. No significant difference was found in the cLBRs between the natural IVM and switching IVF/M groups (23.6% vs. 17.4%, p = 0.05). Meanwhile, the natural IVM group had a higher cumulative clinical pregnancy rate (36.0% vs. 26.0%, p = 0.01), and a decrease in the number of oocytes was obtained in the switching IVF/M group (13.5 vs. 12.0, p < 0.01). The number of good quality embryos in the natural IVM group was 2.2 ± 2.5, and 2.1 ± 2.3 (p = 0.64) in the switching IVF/M group. No statistically significant differences were observed in the number of 2 pronuclear (2PN) and available embryos. Ovarian hyperstimulation syndrome (OHSS) did not occur in the switching IVF/M and natural IVM groups, indicating a highly favorable outcome. In PCOS infertile women with UPOR, timely switching IVF/M is a viable option that markedly reduces the canceled cycle, results in reasonable oocyte retrieval, and leads to live births.

Ganirelix and the prevention of premature luteinizing hormone surges

Ganirelix is a gonadotropin-releasing hormone (GnRH) antagonist with high antagonistic activity that blocks the GnRH receptor by competitive binding. A daily dose of 0.25 mg of ganirelix was sel5ected after a phase II study because it was the minimal, effective daily dose to prevent premature luteinizing hormone surges and this dose yielded the highest ongoing pregnancy rate per started cycle. After subcutaneous administration, ganirelix is rapidly absorbed, reaching peak levels within 1-2 hours (tmax), and has a high absolute bioavailability (>90%). Prospective, comparative studies have demonstrated the advantages of GnRH antagonists over long GnRH agonist treatment in assisted reproduction, including the immediate reversibility of drug effects, a requirement for less follicle-stimulating hormone, a shortened duration of stimulation, a reduced incidence of ovarian hyperstimulation syndrome, and reduced patient burden. Combined analyses concluded that in the general invitro fertilization population, there is a trend for a slightly lower ongoing pregnancy rate and a lower risk of ovarian hyperstimulation syndrome that is largely eliminated when considering triggering with GnRH agonist instead of human chorionic gonadotropin. Regardless of all the research, it is still not fully elucidated why the long GnRH agonist protocol has a trend for higher pregnancy rates after fresh transfer of the same number of good-quality embryos.

Rescue in vitro maturation may increase the pregnancy outcomes among women undergoing intracytoplasmic sperm injection.

To investigate whether rescue in vitro maturation (R-IVM) improves the reproductive outcomes among women undergoing intracytoplasmic sperm injection (ICSI) after one oocyte retrieved cycle. Between January 2019 and December 2020, 2602 women who underwent ICSI in the Reproductive Medicine Center of Tongji Hospital, Wuhan, China, were included in our retrospective cohort study. There were 2112 women undergoing only ICSI and 490 women with R-IVM followed by ICSI. The intermediate reproductive outcomes and pregnancy outcomes were assessed, including the number of normally fertilized embryos, number of cleaved embryos, number of good-quality embryos, number of day-3 available embryos, number of embryos cultured past day-3, number of blastocysts, number of available blastocysts, biochemical pregnancy, miscarriage, clinical pregnancy and live birth. The perinatal outcomes were also assessed, including preterm birth and birth weight. The abovementioned outcomes were also calculated for in vivo matured and R-IVM oocytes separately in women undergoing ICSI with R-IVM group. Compared with the women who underwent only ICSI, those who underwent ICSI with R-IVM had higher numbers of MII oocytes, normally fertilized embryos, cleaved embryos, day-3 available embryos, embryos cultured past day-3, and higher oocyte maturation rate, available embryo rate than women undergoing only ICSI. Additionally, we found that women undergoing ICSI with R-IVM had an increased chance of clinical pregnancy (adjusted OR=1.50, 95% CI: 1.17-1.93) and cumulative live birth (adjusted OR=1.35, 95% CI: 1.07-1.71). After propensity score matching (PSM), the cumulative live birth rate was 60.1% for women undergoing ICSI with R-IVM versus 54.9% for women undergoing only ICSI (OR=1.24, 95% CI: 0.94-1.63). The reproductive outcomes were also significantly different when calculated for in vivo matured and R-IVM oocytes separately in women undergoing ICSI with R-IVM group. All live births from R-IVM embryos were healthy and without malformations or complications. R-IVM may improve the reproductive outcomes of women undergoing ICSI. It may also provide a reference for the safety of R-IVM. This study maybe support a routine application of R-IVM among patients who intend to undergo ICSI.

Effects of autologous Platelet-Rich Plasma treatment on thin endometrium in patients undergoing frozen-thawed embryo transfer cycles

ObjectiveThe objective of this study is to determine whether the treatment of a thin endometrium with autologous platelet-rich plasma (PRP) prior to an embryo transfer increases positive reproductive outcomes in cycles where implantation failure is attributable to a thin endometrium, during the endometrial preparation cycles.Material and MethodsThis is a cohort, prospective and interventional study, carried out in a private facility. Women between 32 and 45 years old were included, with a history of two or more failed IVF/ICSI (In vitro fertilization/Intracytoplasmic sperm injection) cycles and a thin endometrium (&lt;7 mm), the cycles were with their own ovules or from donors not older than 28 years, with or without alterations in the seminal samples of their partners.Twenty-five women were enrolled in this study, the patients were treated with an intrauterine infusion of autologous PRP 2 or 3 times during the menstrual cycle on days 8, 10 and 12 of endometrial preparation for their frozen-thawed embryo transfer (FET) cycle, and Embryo Transfer (ET) was performed 3 to 5 days after the final autologous PRP infusion. A total of 25 patients underwent FET.ResultsOf 25 patients included in this study, the mean endometrial thickness after PRP treatment was 8.6 mm. The average increase in endometrial thickness was 1.76 mm this difference was statistically significant when compared with the previous cycles for each patient, respectively. The results of the cycles with PRP infusion treatment were compared with the previous results obtained in the same group of patients. The implantation, clinical pregnancy, and live birth rates (LBR) in the PRP treatment cycle were 24.59, 56, and 48%, respectively. Implantation, clinical pregnancy, and LBR in the control cycle were 0%. Implantation, clinical pregnancy, and LBR were significantly higher in the PRP treatment cycle than in the control cycle. Age, BMI, number of embryos transferred, and number of good quality embryos transferred were not significantly different.&#x0D; ConclusionsThe present study revealed a noticeable improvement in endometrial thickness after the PRP treatment considering the history of the patients, however, more studies are needed to elucidate the molecular basis of the PRP action mechanism on the endometrium and to support the results obtained and generate more solid evidence on the beneficial effect of autologous PRP treatment on the thin endometrium.

Luteinizing hormone-based modified GnRH antagonist protocol in normal responders undergoing in vitro fertilization treatment: A multi-center randomized controlled trial.

ObjectiveTo study the clinical efficacy and cost-effectiveness of a modified gonadotrophin-releasing hormone (GnRH) antagonist protocol based on luteinizing hormone (LH) levels through one complete assisted reproductive technology (ART) cycle in normal responders.DesignNon-inferiority, multicenter randomized controlled trial.SettingUniversity-based hospitals and an academic medical center.PatientsA total of 372 patients fulfilled the inclusion criteria and were eligible to participate.Intervention(s)Participants were randomized at a 1:1 ratio and stimulated with the conventional flexible GnRH antagonist protocol (control group) or LH-based modified GnRH antagonist protocol (study group).Main Outcome MeasuresThe primary outcome was the cumulative ongoing pregnancy rate per aspiration. The secondary outcomes were number of oocytes retrieved, number of good quality embryos, cumulative positive βhCG rate, cumulative clinical pregnancy rate, pregnancy loss rate, moderate and severe ovarian hyperstimulation syndrome (OHSS), and financial expenditure.ResultsThe cumulative ongoing pregnancy rate was 65.1% in the study group and 70.1% in the control group (odds ratio, 0.79; 95% confidence interval, 0.50–1.26; P = 0.33). The multivariate regression analyses results showed that the number of retrieved oocytes was positively associated with the odds for a higher cumulative ongoing pregnancy rate (adjusted odds ratio, 1.11, 95% confidence interval, 1.06–1.17, P < 0.001). The treatment protocol, female age, and body mass index were not independent predictors. The incremental cost-effectiveness ratio for luteinizing hormone-based gonadotrophin releasing hormone antagonist protocol versus the conventional flexible gonadotrophin releasing hormone antagonist protocol was estimated at 3568.6 USD for each additional ongoing pregnancy.ConclusionThe luteinizing hormone-based gonadotrophin releasing hormone antagonist protocol had clinical efficacy similar to the conventional flexible gonadotrophin releasing hormone antagonist protocol in normal responders undergoing in vitro fertilization treatment but was more cost-effective considering the cumulative ongoing pregnancy rate in the entire assisted reproductive technology cycle.Clinical Trial Registration www.chictr.org.cn, identifier: ChiCTR1800018077URL of the registration site http://www.chictr.org.cn/edit.aspx?pid=27389&htm=4.Trial registration date29 August 2018.Date of first patient enrollment1 September 2018.

O-069 Does dual stimulation with continuous FSH administration increase the total number of metaphase II oocytes in poor responders?

Abstract Study question Is there an increase in the total number of metaphase II (MII) oocytes between a conventional ovarian stimulation and a dual uninterrupted stimulation? Summary answer Dual stimulation with continuous follicle stimulating hormone (FSH) administration is not superior to conventional stimulation in terms of number of MII oocytes. What is known already In the last decade, the concept of multiple follicular waves during one menstrual cycle has gained a lot of interest. Translated into clinical practice, combining two stimulations in the same ovarian cycle has appeared beneficial with regard to the number of retrieved oocytes, without affecting the embryo quality or ploidy status. Usually, this so-called dual stimulation approach is characterized by a discontinuation of FSH administration for approximately 5 days between two consecutive stimulations. The role of dual uninterrupted ovarian stimulation has not yet been studied. Study design, size, duration This was an open-label randomized controlled trial (RCT) with superiority design, performed in a single tertiary center. Power analysis indicated a required sample of 46 patients to detect superiority (defined as two surplus MII oocytes) of the dual stimulation group. Between October 2020 and September 2021, 70 patients were screened, 48 were randomized and 46 completed the study. Participants/materials, setting, methods Women aged 25-40 with a serum anti-Müllerian hormone (AMH) level of ≤ 1.5 ng/mL, antral follicle count (AFC) of ≤ 6, or ≤ 5 oocytes after a previous stimulation, were eligible for inclusion. Randomization occurred only in case of ≤ 9 follicles of ≥ 11mm on the trigger day. In the control group, patients underwent one round of ovarian stimulation and oocyte retrieval only, while the study group had two uninterrupted rounds of ovarian stimulation and two retrievals. Main results and the role of chance Baseline characteristics were similar between both groups. The cumulative number of COC and MII oocytes after completion of the second oocyte retrieval was similar in the control and study group [5.3 ± 2.7 versus 5.3 ± 3.1 [difference 95%CI (-1.7 to 1.7), p = 0.92] and 4.1 ± 2.5 versus 4.3 ± 2.7 [difference 95%CI (-1.7 to 1.3), p = 0.82]. Likewise, a comparable number of good quality embryos at day 3 was available (3.0 ± 2.0 versus 2.7 ± 2., p = 0.63). In the study group, the cancellation rate due to insufficient response to the second round of stimulation was 39.1%. When focusing on the first stimulation in both groups, there were no significant differences regarding basal FSH, FSH consumption and the number of preovulatory follicles. After the first oocyte retrieval, the mean number of COC and MII oocytes was significantly higher in the control group (who had human chorionic gonadotropin (hCG) triggering), compared to the study group (who had Gonadotropin Releasing Hormone (GnRH) agonist triggering) (5.3 ± 2.7 versus 3.3 ± 2.2, p = 0.004 and 4.2 ± 2.4 versus 2.9 ± 2.2, p = 0.05). Likewise, the number of good quality embryos on day 3 was significantly higher (3.0 ± 2.0 versus 1.9 ± 1.7, p = 0.04). Limitations, reasons for caution This study was powered to demonstrate superiority for number of MII oocytes. Investigating the impact of dual stimulation on pregnancy rates would have required a larger sample size. Wider implications of the findings The observed suboptimal oocyte yield after agonist triggering in poor responders is a reason for concern and further scrutiny, given that previous RCTs have shown similar outcomes in normal and high responders after hCG and GnRH agonist trigger. Trial registration number NCT03846544

P-652 Contribution of the D19S884 allele 8 of the FBN3 gene and the Hippo signaling to the reproductive and metabolic phenotype of PCOS patients

Abstract Study question Does exist a correlation between the presence of D19S884 allele 8 (A8) and Hippo pathway dysregulation with the metabolic and ovarian PCOS profiles? Summary answer The presence of the A8 allele affects insulin resistance and hyperandrogenism. Moreover, PCOS ovarian phenotype could be related to a dysregulation of Hippo pathway genes. What is known already The specific D19S884 A8 allele of the FBN3 gene has been associated with an increased probability of polycystic ovarian syndrome (PCOS). D19S884 participates in FBN3 alternative splicing and produces Asprosin-3 and Fibrilin-3 proteins that may be related to PCOS clinical manifestations. Asprosin-3 has been recently identified as a glucose modulator and could be related to metabolic profiles of PCOS. Fibrilin-3 is an extracellular matrix protein, and together with a dysregulation of the Hippo pathway, could be responsible for constraining follicular growth in the PCOS ovaries. Study design, size, duration Descriptive and cross-sectional study with 93 women (25-37 years old) undergoing an IVF cycle between 2019 and 2021 at Hospital la Fe (Valencia, Spain). Thirty patients were considered PCOS while the remaining sixty-three were non-PCOS controls. After recruitment women were screened for A8 allele, metabolic status, hormone profile and Hippo pathway genes. The IVF cycle parameters were recorded to determine their relationship with study variables. Participants/materials, setting, methods Patients with two or more Rotterdam-criteria or with polycystic ovarian morphology (PCOM) were considered as PCOS. After signed informed consent, blood samples and cumulus cells were obtained at egg retrieval. Hormone and metabolic parameters were analyzed and the homeostasis model assessment of insulin resistance (HOMA-IR) established. Genomic DNA was isolated to assess the presence of A8 allele by capillary electrophoresis. The expression of Hippo pathway genes, BIRC1 and CCN2, was analyzed by Taqman qPCR assay. Main results and the role of chance PCOS patients showed increased body mass index (Control:23.2±3.7; PCOS:25.3±4.5, p = 0.04) antimüllerian hormone levels (Control:17.7±7.7pmol/L; PCOS:39.7±22.9pmol/L, p = 0.00), antral follicle count (Control:15±7; PCOS:27±13, p = 0.001) and a reduced number of good quality embryos (Control:1.3±0.9; PCOS:0.8±1.0, p = 0.02). The A8 allele was detected in 15% of the recruited patients, with a 13% incidence in controls and 19% in PCOS. Interestingly, PCOS A8+ patients presented the PCOM phenotype. Women with the A8 allele (A8+) showed higher DHEAS levels (A8-:1899.7±1256.9; A8+:2642.5±555.2, p = 0.046) and free androgen index (A8-:1.1±0.8; A8+:2.0±1.2, p = 0.046) when compared to A8- ones. Similar results were obtained when the comparison was made according to clinical diagnose (Control A8+ vs. Control A8- and PCOS A8+ vs PCOS A8-). Moreover, the overall A8+ patients associated an increase in glucose levels (A8-:85.7±10.9mg/dL; A8+:93.0±6.01mg/dL, p = 0.02) and HOMA-IR (A8-:1.7±1.1; A8+:2.5±1.2). These metabolic findings were observed in control women with the allele but not in PCOS. The PCOS group showed a downregulation of CCN2 (Fold-change (FC): -3.8±9.1, p = 0.02) in cumulus cells. Interestingly, those women with the A8 allele showed downregulated BIRC1 levels (FC A8+: -2.7±4.8 and A8-: 0.2±2.7; p = 0.04). These gene dysregulations could be related with a deficient oocyte-cumulus communication, abnormal follicular growth and an ovarian stroma stiffness alteration. Limitations, reasons for caution These promising results need to be confirmed in a larger population of PCOS to allow validation of the observed effects according to PCOS sub-phenotypes. Moreover, transcriptomic analysis and functional enrichment assays should be carried out to clarify the contribution of Hippo pathway and A8 allele to PCOS pathogenesis. Wider implications of the findings The obtained results suggest that the presence of the A8 allele influences the metabolic profile related to insulin resistance and androgen levels, as well as the activation status of Hippo pathway. Moreover, this signaling pathway seems to be dysregulated in PCOS patients, suggesting its possible role in the ovarian phenotype. Trial registration number Not applicable

P-359 Effect of estradiol pretreatment on antagonist ICSI cycles outcome

Abstract Study question Does estrogen pretreatment in antagonist ICSI cycles improves the outcome? Summary answer Pretreatment with estrogen in antagonist cycles reduced the days of stimulation, the number of hMG ampoules and enhanced the implantation rate. What is known already It has been previously reported that, programming of antagonist cycles with E2 only, started in the luteal phase and continued beyond the menses till the first day of stimulation, yielded similar results as the long agonist protocol. E2 pre-treatment in the luteal phase has an inhibiting role on follicular growth through its negative feedback on the FSH increase during the luteal follicular transition phase. This effect stops as soon as E2 administration is terminated. Study design, size, duration This was a prospective randomized controlled trial performed in a private IVF centers from June 2020 to February 2021. One hundred and fourteen infertile couples undergoing intracytoplasmic sperm injection embryo transfer cycles (ICSI-ET) were included. Participants/materials, setting, methods Group A includes 57 patients were pretreated with a dose of 4 mg estradiol valerate (progynova 2 mg; Bayer) once daily starting 10days before expected menses. Ovarian stimulation was started one day after the last estradiol dose, in a dose ranging from 225 to 375 IU of hMG. While in group B , 57 patients received stimulation in a dose of 225 to 375 IU of hMG starting on cycle day 2 without estradiol pretreatment. Main results and the role of chance The daily dose of hMG was significantly lower in The study group (P = 0.048), the stimulation days were significantly higher in the control group (P = 0.049), the total number of hMG ampoules was significantly higher in the control group (P = 0.041), and the implantation rate was higher in the study group (P = 0.045) , also the pregnancy rate (positive pregnancy test) was higher in the study group (p = 0.044) but there was no significant statistical difference detected as regards the clinical pregnancy rate between both groups (P = 0.180) , the serum estradiol on day of hCG ( p = 0.055), serum progesterone level on hCG day (P = 0.71) and the endometrial thickness (p = 0.780) . Also there is no significant statistical difference between the two groups as regarding number of follicles on day of hCG. (P = 0.803), the number of mature oocytes (P = 0.703) and no significant difference in the number of good quality embryos (p = 0.532) and the ratio of mature oocytes to number of follicles on day of hCG (P = 0.835), with no significant statistical difference between both groups. Limitations, reasons for caution The limitation of this study is the small number of patients as we included only 114 patients. Wider implications of the findings Luteal estradiol in antagonist cycles improved the outcomes of ICSI procedure by reducing the number of gonadotropin ampoules used for COH and reduced duration of stimulation, also the implantation rate is improved by luteal estradiol administration. Trial registration number NCT05197374