Day Of Trigger Research Articles

Progesterone peak influences embryonic developmental morphokinetics on trigger day? A retrospective study

ObjectivePremature Progesterone Rise (PPR) is characterized by elevated serum progesterone concentrations either towards the end of the follicular phase or on the trigger day, surpassing a pre-defined threshold value. Aim of the study is to evaluate the impact of PPR exceeding 1.5 ng/ml at the time of hCG-trigger on embryo morphokinetic parameters and to identify predictive biomarkers of in IntraCytoplasmic Sperm Injection (ICSI) cycles outcomes.MethodsIt is a retrospective study including patients underwent ICSI cycles in the period 2020–2023. 58 patients were recruited in the study group showing P levels in the trigger day greater than or equal to 1.5 ng/ml. A matching control group of 58 patients with P levels below 1.5 ng/ml was after selected. The general characteristics of these patients, including age, Body Mass Index (BMI), antral follicle count (AFC), anti-Müllerian hormone (AMH) and follicle-stimulating hormone (FSH) levels, the type of infertility and smoking/non-smoking patients, were recorded on the day of their initial visit. Subsequently, data were collected regarding the number of eggs retrieved, mature eggs, successfully fertilized eggs, and embryos reaching the blastocyst stage. Additionally, the timing of embryonic development and the quality of obtained blastocysts, as assessed by the degree of expansion and the characteristics of the inner cell mass (ICM) and trophectoderm (TE), were evaluated using Time-Lapse technology.ResultsElevated P levels exceeding 1.5 ng/ml on the trigger day were directly associated with a significantly larger number of antral follicles, consequently leading to a higher count of retrieved eggs, mature eggs, successfully fertilized eggs and embryos reaching the blastocyst stage. Furthermore, the analysis of morphokinetic parameters indicated faster division times and a notably greater number of high-grade blastocysts in the study group compared to the control group.ConclusionsP levels ≥ 1.5 ng/ml on the trigger day did not negatively impact embryonic morphokinetic parameters, instead resulting in faster embryo development in the initial stages.

Impact of Omicron Variant Infection on Female Fertility and Laboratory Outcomes: A Self-Controlled Study.

Investigating the impact of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection on female fertility and laboratory outcomes in patients undergoing assisted reproductive technology (ART) treatment who were initially uninfected but later became infected. This self-controlled study included 197 patients who underwent repeated oocyte retrieval before and after SARS-CoV-2 infection between March 2021 and April 2023, of which 117 used the same ovarian stimulation protocol within a consistent age range. We evaluated the ovarian reserve, ovarian response, and laboratory outcomes in patients before and after SARS-CoV-2 infection. The ovarian reserve (follicle-stimulating hormone [FSH], luteinizing hormone [LH], estrogen [E2], anti-Müllerian hormone [AMH], antral follicle count [AFC]), ovarian response (total Gn dosage, duration of Gn administration, number of follicles ≥14mm on trigger day, number of retrieved oocytes), and laboratory outcomes (cleavage stage good-quality embryo rate, blastocyst formation rate, and cycle freezing rate) showed no significant differences before and after SARS-CoV-2 infection in 117 patients (p>0.05). When stratified by age, the ≤ 35years group showed a higher two pronuclei (2PN) fertilization rate post-infection, while the >35years group had increased mature metaphase II (MII) oocyte and blastocyst stage good-quality embryo rates. Additionally, upon stratified by the time interval between SARS-CoV-2 infection and ART treatment, in the ≤ 3months group, there was an increased post-infection MII oocyte rate, 2PN fertilization rate, and blastocyst stage good-quality embryo rate. Meanwhile, no significant differences were found in any indicators when the interval exceeded threemonths. Our study suggested that undergoing IVF/ICSI treatment after recovering from COVID-19 may not adversely affect female fertility and laboratory outcomes.

The progesterone prime protocol: an affordable option for ICSI in Egypt

BackgroundThe two main input indicators needed to assess the success of assisted reproductive technology (ART) strategies are cost-effectiveness and clinical outcome. Therefore, we focused in our study on the direct cost associated with the Progesterone Prime Ovulation Induction Protocol (P-P-OP protocol) compared to other protocols, and the clinical outcomes of this strategy were measured in their effect on implantation and pregnancy rates.MethodsA pilot single-armed study was conducted on 47 infertile women coming for an ICSI cycle. Progesterone priming was started with 10 mg dydrogesterone along with HMG 150–300 IU from the second day of the menstrual cycle and was maintained until the day of ovulation trigger. The primary outcome was the cost per cycle, while the secondary outcome was the clinical pregnancy rate. The cost per cycle, including the cryopreservation cost, was calculated for economic evaluation.ResultsPer each cycle, the number of retrieved oocytes was 14.87 ± 8.09, the number of mature oocytes was 9.81 ± 4.67, the number of total embryos was 8.74 ± 4.28 (grade A = 67.40%, grade B = 11.92%, grade C = 20.68%), and the number of transferred embryos was 2.43 ± 0.68. The clinical pregnancy rate in our study was 42.5%. Economically, the cost of the P-P-OP protocol for each patient was only 56 USD.ConclusionThe P-P-OP protocol is a simplified approach suitable for freeze-only strategies, offering the benefits of positive results, fewer injections, lower costs, and increased patient convenience.

Impact of progesterone concentration on hCG trigger day on clinical outcomes with cleavage-stage embryo transfer in in vitro fertilization cycles with an antagonist protocol

Objective: To investigate the impact of the progesterone concentration on human chorionic gonadotropin (hCG) trigger day in fresh cycles versus thawed transfer cycles (the freeze-all strategy) with an antagonist protocol, and to compare the differences in clinical outcomes. Methods: This retrospective cohort study included a total of 2 165 cycles conducted at Henan Provincial People's Hospital with cleavage-stage embryo (at least one top-quality) transfer between January 2017 and December 2023, with serum progesterone levels on hCG trigger day all≤6.34 nmol/L (i.e. 2 ng/ml). Multivariate logsitic regression analysis and curve fitting were performed based on different serum progesterone levels on hCG trigger day [≤3.17 nmol/L (i.e. 1 ng/ml) or 1-2 ng/ml]. Results: Multivariate regression analysis, by using cycle type (either fresh or frozen-thawed cycle) as the exposure variable, showed that the clinical pregnancy rate (≤1 ng/ml: OR=0.93, 95%CI: 0.75-1.14; 1-2 ng/ml: OR=1.05, 95%CI: 0.58-1.87) and live birth rate (≤1 ng/ml: OR=0.90, 95%CI: 0.71-1.13; 1-2 ng/ml: OR=1.53, 95%CI: 0.79-3.00) had no statistically significant differences in group of progesterone concentration ≤1 ng/ml or in group of 1-2 ng/ml. Using serum progesterone levels on hCG trigger day as a continuous variable for curve fitting analysis, the clinical pregnancy rate in fresh or thawed cycles showed no significant changes with increasing progesterone levels. Conclusions: In the antagonist protocol with cleavage-stage embryo transfer (at least one top-quality), when the serum progesterone level on hCG day is ≤2 ng/ml, there are no significant differences in clinical outcomes between thawed cycles and fresh cycles, including clinical pregnancy rate and live birth rate. Transferred in fresh cycles or choosing the freeze-all strategy could be selected based on the actual situation of the patients.

Effect of progesterone concentration on hCG trigger day on clinical outcomes after high-quality single blastocyst transfer in GnRH antagonist cycles.

To investigate whether progesterone levels on the human chorionic gonadotropin (hCG) trigger day are associated with clinical outcomes in fresh cycles and the first frozen-thawed cycles (the freeze-all strategy) following the transfer of a high-quality single blastocyst. This single-center retrospective analysis was conducted on patients undergoing in vitro fertilization with the gonadotropin-releasing hormone (GnRH) antagonist protocol from January 2017 to December 2023. The study included the first and second oocyte retrieval cycles with progesterone levels ≤2 ng/ml on hCG trigger day. Clinical pregnancy rates and early miscarriage rates were compared among groups using curve fitting, threshold effect analysis, and multivariable regression. When progesterone levels were between 1 and 2 ng/ml, the pregnancy rate in fresh cycles was only 51% of that in cycles with progesterone levels ≤1 ng/ml (95% CI: 0.33, 0.79, p = 0.0028). And the pregnancy rate decreased by 25% (95% CI: 0.51, 1.09) for frozen cycles, although there was no statistically significant (p = 0.1273). When cycle types were used as a binary variable in multivariate regression analysis, it was found that the clinical pregnancy rate in frozen cycles was 1.84 times higher than in fresh cycles (OR = 1.84, 95% CI: 1.38-2.47). For progesterone levels between 1 and 2 ng/ml, the clinical pregnancy rate in frozen cycles was 2.90 times that of fresh cycles (OR = 2.90, 95% CI: 1.59, 5.29, p = 0.0015). Progesterone levels on hCG day had no impact on the clinical pregnancy rate in thaw cycles, nor did they affect miscarriage rates in fresh or thaw cycles (p > 0.05). When progesterone levels on hCG trigger day were between 1 and 2 ng/ml, the clinical pregnancy rate for frozen-thawed cycles of high-quality single blastocyst transfer using an GnRH antagonist protocol significantly surpasses that of fresh cycles, thus elective frozen embryo transfer after the freeze-all strategy is recommended.

High androgen level during controlled ovarian stimulation cycle impairs endometrial receptivity in PCOS patients

PCOS is one of the most common endocrine disorders among women of reproductive age. While the mechanism involved is not yet fully characterized. Our study aims to examine the pregnancy outcomes of embryo transfers in women with PCOS after pretreatment, and to explore the possible effect of high androgen levels on endometrial receptivity. Retrospective cohort study was conducted to analyze pregnancy outcomes among 2714 infertile women with tubal factor and 452 PCOS women. Endometrium samples were collected from 6 controls and 6 PCOS patients to detect the expression of endometrial receptivity marks. The implantation rate, clinical and ongoing pregnancy rates and live birth rate in women with PCOS followed fresh embryo transfers were obviously decreased even after the pretreatment. Similar pregnancy outcomes were found in frozen-thawed embryo transfer cycles between women with or without PCOS. Strikingly, serum total testosterone (TT) levels on trigger day were significantly higher in PCOS women. Women with high TT levels presented significantly lower clinical and ongoing pregnancy rates, and the expression of insulin-like growth factor binding protein 1 (IGFBP-1), and leukemia inhibitory factor (LIF) in the endometria decreased significantly as well. High doses of testosterone significantly down-regulated the expression of IGFBP-1 and LIF in Ishikawa cells. Although endocrine abnormalities had been improved before the controlled ovarian stimulation (COS) cycle started, higher serum TT levels were detected on the trigger day of the COS cycle in PCOS patients, which may contribute to the decreased fresh embryo implantation by impairing endometrial receptivity.

Reproductive outcomes in fresh transfer cycles and antagonists with premature luteinizing and/or progesterone surge: a single center retrospective cohort study.

The optimal outcome of assisted reproductive technology is a successful live birth after fresh embryo transfer. However, the success pregnancy rate of fresh embryo transfer cycle in antagonist protocol is lower than that observed in other protocols. Despite the use of antagonists (GnRH-ant), the incidence of luteinizing hormone surge and elevated progesterone levels remain at approximately 5%-38%. Progesterone is widely recognized to exert adverse effects on fresh embryo transfer outcomes. This study aimed to investigate the impact of luteinizing hormone surge and progesterone levels on live birth rate following fresh embryo transfer and explore appropriate progesterone thresholds to enhance pregnancy outcomes. This retrospective cohort study included a total of 1,177 antagonist protocol cycles with fresh embryo transfer. The patients were divided into four groups based on the presence of premature LH surge and progesterone level on trigger day>1.5ng/ml. Then, the relationship between the variables and the pregnancy outcome was analyzed and compared in each group. The transient rise of luteinizing hormone did not impact pregnancy outcomes (P=0.345; P=0.3; P=0.787), in contrast to progesterone levels on the day of hCG administration (P=0.047*; P=0.015*; P=0.021*). In cases with luteinizing hormone surge, elevated progesterone levels were correlated with higher antral follicle count (AFC), and as progesterone levels increased, a greater quantity of oocytes and embryos were obtained. However, there was no statistically significant difference in pregnancy outcomes. In cases without luteinizing hormone surge, elevated progesterone levels led to significantly poorer pregnancy outcomes. Furthermore, the curve-fitting and threshold-effect analysis revealed a notable decline in live birth rates when progesterone exceeded or equaled 1.10ng/ml (OR, 0.25; 95% CI, 0.09-0.66; P = 0.005*). The GnRH-ant dosage addition should be carefully selected in flexible antagonist protocols. The presence of elevated progesterone levels may be associated with improved embryo quality when luteinizing hormone surge occurred. In the absence of a luteinizing hormone surge, progesterone levels showed a larger impact on the pregnancy outcome, and fresh embryo transfer should not be performed if the progesterone level on the day of hCG administration is higher than 1.10ng/ml.

Letrozole co-treatment in an antagonist protocol for overweight women undergoing IVF treatment: a retrospective study

BackgroundOverweight women undergoing IVF treatment have lower success rates. Letrozole, an aromatase inhibitor, has been used as an adjunct for IVF treatment, but its specific effects in overweight women have not been investigated. This study was to explore the effects of letrozole co-treatment in an antagonist protocol for overweight infertile women undergoing IVF treatment.MethodsThis retrospective cohort study included overweight infertile women who underwent IVF/ICSI treatment and fresh embryo transfer (ET), with or without letrozole co-treatment in an antagonist protocol, from 2007 to 2021 at Shanghai Ninth People’s Hospital (Shanghai, China). A total of 704 overweight infertile women were included: 585 women were in the antagonist group, and 119 women were in the letrozole co-treatment group. The primary outcome was the live birth rate after fresh ET. Propensity score-based patient-matching was employed to balance the covariates between the groups. Multivariate logistic regression analysis was also performed to estimate odds ratio (OR) and 95% confidence interval (CI) for association of letrozole co-treatment and the live birth outcome.ResultsLetrozole co-treatment induced significant changes in hormonal profile on the trigger day. The letrozole group exhibited a decrease in the total number of follicles compared to the antagonist group, but a higher proportion of large follicles at oocyte retrieval (P < 0.05). The quantity and quality of embryos were comparable between the two groups (P > 0.05). The letrozole co-treatment group had a significantly higher live birth rate than the control group (38.7% vs. 22.6%, P = 0.026). With multivariate logistic regression analysis, letrozole co-treatment was associated with higher odds of live birth after adjusting for potential confounding factors (adjusted OR = 2.00, 95% CI = 1.17–3.39, P = 0.011). Letrozole presented no significant associations with obstetrical or neonatal complications (P > 0.05).ConclusionLetrozole co-treatment in an antagonist protocol may offer potential benefits for overweight infertile women undergoing IVF treatment. Further research is warranted to validate these findings and explore the broader implications for letrozole co-treatment.

Increasing dominant follicular proportion was associated with adverse IVF/ICSI outcomes in low-prognosis women undergoing GnRH antagonist protocol: a retrospective cohort study

PurposeThis study aimed to examine the correlation between different dominant follicle proportions (DFPs) and outcomes of in-vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) among patients classified under POSEIDON Groups 3 and 4, who underwent gonadotropin-releasing hormone antagonist (GnRH-ant) protocols. Additionally, it sought to determine the optimal DFP threshold for trigger timing.MethodsA retrospective analysis was performed on patients classified under POSEIDON Groups 3 (n = 593) and 4 (n = 563) who underwent GnRH-ant protocols for controlled ovarian hyperstimulation (COH) between 2016 and 2022. These patients were categorized into two groups based on their DFPs, defined as the ratio of ≥ 18-mm dominant follicles to ≥ 12-mm follicles on the trigger day (DFP ≤ 40% and DFP ≥ 40%). Statistical analyses, including restricted cubic spline (RCS) and multivariate logistic regression, were employed to assess the relationship between DFP and IVF/ICSI outcomes.ResultsDemographic characteristics of patients were similar across groups. In POSEIDON Groups 3 and 4, DFP > 40 was associated with a significant decrease in the number (No.) of oocytes retrieved, cleaved embryos, and available embryos. Moreover, following the GnRH-ant cycle, the clinical pregnancy and live birth rates in fresh embryo transfer (ET) were notably reduced in the DFP > 40 group compared with the DFP ≤ 40 group, whereas no significant differences were observed in the pregnancy outcomes of the first frozen-thawed embryo transfer (FET) between the groups. In POSEIDON Group 3, the cumulative clinical pregnancy rate (CCPR) and cumulative live birth rate (CLRB) were significantly higher in the DFP ≤ 40 subgroup than in the DFP > 40 subgroup, with a notable decrease in CLRB observed with increasing DFP levels. However, in POSEIDON Group 4, no significant differences in CCPR and CLRB were found between the groups. Logistic regression analysis identified age and the No. of oocytes retrieved as pivotal factors influencing CLRB in Group 4.ConclusionFor patients in POSEIDON Group 3, maintaining a DFP ≤ 40 mm is crucial to achieve optimal laboratory and pregnancy outcomes by avoiding delayed triggering. However, for patients in POSEIDON Group 4, age remains a critical factor influencing CLRB regardless of DFP, although a higher No. of oocytes retrieved and available embryos with DFP ≤ 40 is beneficial.

Effect of LH level on HCG trigger day on clinical outcomes in patients with diminished ovarian reserve undergoing GnRH-antagonist protocol

Research questionDoes luteinizing hormone (LH) levels on human chorionic gonadotropin (HCG) trigger day (LHHCG) affect the clinical outcomes of patients with diminished ovarian reserve (DOR) undergoing gonadotropin-releasing hormone antagonist (GnRH-ant) protocol?MethodsRetrospective analysis fresh embryo transfer cycles of DOR patients who underwent GnRH-ant protocol from August 2019 to June 2023. The participants were divided into different groups according to LHHCG level and age. The clinical data and outcomes were compared between groups.ResultsIn patients with DOR, the HCG positive rate (59.3% versus 39.8%, P = 0.005), embryo implantation rate (34.5% versus 19.7%, P = 0.002), clinical pregnancy rate (49.2% versus 28.4%, P = 0.003), live birth rate (41.5% versus 22.7%, P = 0.005) in LHHCG < 2.58 IU/L group were significantly higher than LHHCG ≥ 2.58 IU/L group. There was no significant correlation between LHHCG level and clinical pregnancy in POSEIDON group 3. In POSEIDON group 4, the HCG positive rate (52.8% versus 27.0%, P = 0.015), embryo implantation rate (29.2% versus 13.3%, P = 0.023), clinical pregnancy rate (45.3% versus 18.9%, P = 0.010) in LHHCG < 3.14 IU/L group were significantly higher than LHHCG ≥ 3.14 IU/L group. Logistic regression analysis indicated that LHHCG level was an independent influencing factor for clinical pregnancy in POSEIDON group 4 patients (OR = 3.831, 95% CI: 1.379–10.643, P < 0.05).ConclusionsLHHCG level is an independent factor affecting pregnancy outcome of fresh embryo transfer in DOR patients undergoing GnRH-ant protocol, especially for advanced-aged women. LHHCG had a high predictive value for POSEIDON group 4 patients, and LHHCG ≥ 3.14 IU/L predicts poor pregnancy outcomes.

GnRH agonist-only trigger, compared to dual trigger, reduces oocyte retrieval rate in high responders without affecting cumulative live birth rate.

This study compared, in high responders undergoing IVF treatment, GnRH agonist-only trigger and dual trigger on oocyte retrieval rate and cumulative live birth rate (LBR). The aim was to determine if the GnRH agonist-only triggers had provided outcomes comparable to dual trigger, while minimizing the risk of ovarian hyperstimulation syndrome (OHSS). A retrospective, matched case-control study was conducted at Taichung Veterans General Hospital, Taiwan, including women who underwent IVF/ICSI between January 1, 2014, and December 31, 2022. Inclusion criteria were: GnRH antagonist protocol and estrogen level >3,000 pg/ml on trigger day. Exclusion criteria were: immune/metabolic diseases, donated oocytes, and mixed stimulation cycles. Propensity score matching was applied to balance age, AMH level, and oocyte number between the GnRH agonist-only and dual trigger groups. Outcomes were analyzed for patients who had complete treatment cycles, focusing on oocyte retrieval rate and cumulative LBR. We analyzed 116 cycles in the agonist-only group, and 232 cycles in the dual trigger group. No inter-group difference was found in their age, BMI, and AMH levels. The dual trigger group had a higher oocyte retrieval rate (93% vs. 80%; p <0.05), while fertilization rates, blastocyst formation rates, and cumulative LBR were comparable. Notably, no OHSS cases had been reported in the GnRH agonist-only group, compared with 7 cases in the dual trigger group. GnRH agonist-only triggers resulted in a lower oocyte retrieval rate compared to dual triggers but did not significantly affect cumulative LBR in high responders. This approach effectively reduces OHSS risk without compromising pregnancy outcomes, making it a preferable option in freeze-all strategies, despite a longer oocyte pick-up duration and a medium cost. GnRH agonist-only trigger, however, may not be suitable for fresh embryo transfers or patients with low serum LH levels on trigger day.

Effect of prematurely elevated late follicular progesterone on pregnancy outcomes following ovarian stimulation-intrauterine insemination for unexplained infertility: secondary analysis of the AMIGOS trial.

What is the relationship between late follicular phase progesterone levels and clinic pregnancy and live birth rates in couples with unexplained infertility undergoing ovarian stimulation with IUI (OS-IUI)? Late follicular progesterone levels between 1.0 and <1.5 ng/ml were associated with higher live birth and clinical pregnancy rates while the outcomes in groups with higher progesterone levels did not differ appreciably from the <1.0 ng/ml reference group. Elevated late follicular progesterone levels have been associated with lower live birth rates after fresh embryo transfer following controlled ovarian stimulation and egg retrieval, but less is known about whether an association exists with outcomes in OS-IUI cycles. Existing studies are few and have been limited to ovarian stimulation with gonadotrophins, but the use of oral agents, such as clomiphene citrate and letrozole, is common with these treatments and has not been well studied. The study was a prospective cohort analysis of the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) randomized controlled trial. Frozen serum was available for evaluation from 2121 cycles in 828 AMIGOS participants. The primary pregnancy outcome was live birth per cycle, and the secondary pregnancy outcome was clinical pregnancy rate per cycle. Couples with unexplained infertility in the AMIGOS trial, for whom female serum from day of trigger with hCG was available in at least one cycle of treatment, were included. Stored frozen serum samples from day of hCG trigger during treatment with OS-IUI were evaluated for serum progesterone level. Progesterone level <1.0 ng/ml was the reference group for comparison with progesterone categorized in increments of 0.5 ng/ml up to ≥3.0 ng/ml. Unadjusted and adjusted risk ratios (RR) and 95% CI were estimated using cluster-weighted generalized estimating equations to estimate modified Poisson regression models with robust standard errors. Compared to the reference group with 110/1363 live births (8.07%), live birth rates were significantly increased in cycles with progesterone 1.0 to <1.5 ng/ml (49/401 live births, 12.22%) in both the unadjusted (RR 1.56, 95% CI 1.14, 2.13) and treatment-adjusted models (RR 1.51, 95% CI 1.10, 2.06). Clinical pregnancy rates were also higher in this group (55/401 clinical pregnancies, 13.72%) compared to reference group with 130/1363 (9.54%) (unadjusted RR 1.46, 95% CI 1.10, 1.94 and adjusted RR 1.42, 95% CI 1.07, 1.89). In cycles with progesterone 1.5 ng/ml and above, there was no evidence of a difference in clinical pregnancy or live birth rates relative to the reference group. This pattern remained when stratified by ovarian stimulation treatment group but was only statistically significant in letrozole cycles. The AMIGOS trial was not designed to answer this clinical question, and with small numbers in some progesterone categories our analyses were underpowered to detect differences between some groups. Inclusion of cycles with progesterone values above 3.0 ng/ml may have included those wherein ovulation had already occurred at the time the IUI was performed. These cycles would be expected to experience a lower success rate but pregnancy may have occurred with intercourse in the same cycle. Compared to previous literature focusing primarily on OS-IUI cycles using gonadotrophins, these data include patients using oral agents and therefore may be generalizable to the wider population of infertility patients undergoing IUI treatments. Because live births were significantly higher when progesterone ranged from 1.0 to <1.5 ng/ml, further study is needed to clarify whether this progesterone range may truly represent a prognostic indicator in OS-IUI cycles. Oklahoma Shared Clinical and Translational Resources (U54GM104938) National Institute of General Medical Sciences (NIGMS). AMIGOS was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development: U10 HD077680, U10 HD39005, U10 HD38992, U10 HD27049, U10 HD38998, U10 HD055942, HD055944, U10 HD055936, and U10HD055925. Research made possible by the funding by American Recovery and Reinvestment Act. Dr Burks has disclosed that she is a member of the Board of Directors of the Pacific Coast Reproductive Society. Dr Hansen has disclosed that he is the recipient of NIH grants unrelated to the present work, and contracts with Ferring International Pharmascience Center US and with May Health unrelated to the present work, as well as consulting fees with May Health also unrelated to the present work. Dr Diamond has disclosed that he is a stockholder and a member of the Board of Directors of Advanced Reproductive Care, Inc., and that he has a patent pending for the administration of progesterone to trigger ovulation. Dr Anderson, Dr Gavrizi, and Dr Peck do not have conflicts of interest to disclose. N/A.

Reproductive and transcriptome characteristics of endometrium at the window of im-plantation in patients after fertility-sparing treatment of endometrial intraepithelial neoplasm or cancer

BackgroundProgestin therapy is an option for patients with endometrial carcinoma (EC) or endometrial intraepithelial neoplasm (EIN) who fit specific criteria of fertility-sparing treatment. However, the implantation rate remains low among females receiving in vitro fertilization (IVF) even after the complete reversal of endometrial lesions. MethodsHere, ten patients with EC/EIN achieved complete regression (CR) in histology. Their relevant metabolic and IVF parameters were collected. An endometrial sampling at the window of implantation (WOI) and transcriptome analysis were conducted among them, and four healthy controls were analyzed to analyze endometrial receptivity. ResultsOn average, it took ten patients five months to achieve CR after four curettage procedures. The interquartile range of endometrium thickness on trigger day was between 8.8 and 10.0 mm, while the range was 15.2–18.5 mm for controls. Five patients got pregnant after a frozen-embryo transfer. According to ERA analysis, the endometrial sampling at WOI showed pre-receptive status in four cases. In total, 1458 differential expression genes were identified, and 70 belonged to the ERA genes. ImmuneScore indicated decreased NK cells in the endometrium, affecting endometrial receptivity. ConclusionsEven after EC/EIN reversal in histology, endometrial receptivity has already been compromised regarding altered WOI and immune microenvironment, leading to a low pregnancy rate.

Using progesterone to follicular index ratio is better correlated with intracytoplasmic sperm injection outcome than using serum progesterone level alone.

to investigate the possibility of using the ratio of serum progesterone level to the number of follicles, according to ovarian response in the day of human chorionic gonadotrophin trigger, as a predictor of cycle outcome. A prospective intervensional study was conducted at Kamal Al-Samarai Hospital for Infertility Treatment and IVF during the period from December 2020 to September 2021. Ninety infertile women underwent intracytoplasmic sperm injection (ICSI) cycles using antagonist protocol. Moreover, once the patient reached triggering criteria, meticulous recording of follicular index together with serum estrogen level and serum progesterone level are measured. Fresh embryo transfer of cleavage stage embryo is done once serum progesterone level was less than 1.5 ng/mL. A follow-up to confirm pregnancy rate and cycle outcome was done. The study showed a positive pregnancy rate of 28.9%. The relationship between progesterone follicular index (Prog/FI) ratio and (ICSI) outcome was highly significant with a p value of 0.001. Additionally, an inverse relationship, as the ratio was lower the pregnancy rate was improved, was documented. The receiver operating characteristic (ROC) curve for progesterone follicular index ratio was 0.711 with a cut off value of 0.0354 ng/mL in addition to a sensitivity of 65.6 and a specificity of 65.4. The serum progesterone level is an independent factor for the prediction of intracytoplasmic sperm injection (ICSI) outcome, whereas the progesterone follicular index ratio can be used as a potential marker for predicting ICSI outcome in fresh embryo transfer.

Can We Harvest More Mature Oocytes by Repeating Gonadotropin-Releasing Hormone Agonist Doses in Polycystic Ovarian Syndrome Patients at Risk of OHSS in Antagonist Cycles? A Randomised Clinical Trial.

There is an ongoing debate about the optimal dosage of gonadotropin-releasing hormone (GnRH) agonist for oocyte triggering in polycystic ovarian syndrome (PCOS) patients at risk for ovarian hyperstimulation syndrome (OHSS). In this study, we intend to ascertain whether the use of repeated doses of a GnRH agonist for oocyte triggering in these patients can enhance the outcomes of controlled ovarian stimulation (COS) for in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI) cycles. This randomised clinical trial enrolled 70 PCOS women candidates for IVF/ICSI with the standard antagonist protocol at Royan Institute (Tehran, Iran) from May 2020 to June 2022. Patients at risk of OHSS with oestradiol (E2) levels >3000 pg/ml on the day of trigger were randomly assigned to a control or experimental group. Group A (control group) patients received 0.2 mg triptorelin (Decapeptyl®) for final oocyte maturation. Group B (experimental group) patients received a second dose of 0.1 mg Decapeptyl®12 hours after their first dose, for a total dose of 0.3 mg. IVF/ICSI outcomes were compared between the groups. Ultimately, 35 women from the study group and 33 from the control group completed the treatment cycle. Both groups were comparable in terms of demographic characteristics, baseline hormonal profiles, and PCOS phenotypes. The dosage of gonadotropin, stimulation duration, number of retrieved oocytes, oocyte maturation rate, and oocyte recovery ratio did not significantly differ between the groups. No significant differences were found in terms of the number of blastocyst and cleavage embryos, nor the quality of obtained embryos between the groups. The mild to moderate OHSS rate was significantly lower in the study group (P=0.038). A second dose of GnRH agonist 12 hours after the first dose did not improve the number and maturity of oocytes, or pregnancy outcomes in PCOS patients (registration number: NCT04600986).

P-706 The pregnancy rates in a large cohort of patients with thin endometrium when stratified according to estradiol levels on the day of triggering

Abstract Study question Is there any difference in ongoing pregnancy rate in women with thin endometrium (&amp;lt;8 mm) when scrutinized based on estradiol levels on triggering day? Summary answer Either with a low, moderate, or high estradiol level on the day of triggering, ongoing pregnancy rates do not change in patients with thin endometrium. What is known already Endometrial thickness has been argued to be one of the proxy determinants of endometrial receptivity. In that context, although the optimal thickness has been widely stated to be between 8-14 mm, the negative effect of thin endometrium on pregnancy outcome is still controversial in in-vitro-fertilization (IVF) cycles. Nevertheless, particularly lack of large sample size of women with thin endometrium among the available literature, is the leading factors that avoids to solid conclusion.Furthermore, it might be hypothesized that patients with thin endometrium and accompanying low estradiol might be distinct from women with thin endometrium despite relatively high estradiol level. Study design, size, duration A retrospective cohort study was designed among patients that has undergone in-vitro fertilization (IVF) treatment between January-2018 and June-2023 in Bahceci Health Group. Only patients having an endometrial thickness &amp;lt;8 mm on the day of triggering were recruited. Other inclusion criteria was having at least one blastocyst to be transferred. All frozen-thawed embryo transfer cycles were excluded. Female age and body mass index were not considered as an exclusion criterion. Participants/materials, setting, methods During the study period, a total of 3076 IVF cycles with fresh ET were employed. Of them, 814 had an endometrial thickness of &amp;lt; 8 mm on the day of triggering. Among 814 IVF cycles, 25th, 50th and 75th quartiles of estradiol levels on the day of triggering referred to 322.8, 755.7 and 1310.5 pg/ml, respectively. The number of IVF-ET cycles in the 1st, 2nd, 3th and 4th quartiles were 203, 204, 204 and 203. Main results and the role of chance The mean (SD) age of women recruited in the final analyses was 36.5 (5.5) years and endometrial thickness was 7.2 (0.8) mm. The pregnancy rates per ET with regard to 1st, 2nd, 3th and 4th quartiles were 37.6%, 33.0%, 37.3% and 44.3%, respectively without any statistical significance (p = 0.134). However, the respective ongoing pregnancy rates were 26.1%, 18.1%, 22.1%, 31.0 % and the highest quartile had a statistically superior ongoing pregnancy rates than the second (p = 0.003) and third quartiles (p = 0.022). When binary logistic regression analysis was performed by inserting the female age, body-mass index, duration of infertility and quartiles of estradiol levels on the day of triggering, only female age remained as an independent factor for the prediction of an ongoing pregnancy (RR: 0.92 CI95%: 0.87 to 0.98, p = 0.008). Utilization of estradiol level as a continuous variable in the same model also failed to present the independent validity of it to predict an ongoing pregnancy. Notably, the lowest thickness of a positive pregnancy resulting with an ongoing pregnancy was 4.7 mm. Limitations, reasons for caution The inherent risks cannot be excluded due to the retrospective nature of the current study, which had been efforted to overcome with regression analysis. Wider implications of the findings The current study includes one of the largest numbers of experience particularly with thin endometrium on the day of triggering. However, having a thin endometrium despite low or relatively high estradiol level does yield any prediction for the pregnancy outcome. Trial registration number Not Applicable

O-219 Explainable artificial intelligence (XAI) to determine the follicle sizes on trigger day that maximize mature oocyte yield

Abstract Study question Which follicle sizes on trigger day (TD) are key to obtaining mature oocytes, embryos, and blastocysts, thereby enhancing live birth rates? Summary answer Follicles sized 13-18mm are most likely to yield mature oocytes. Live birth rate (LBR) was increased with a greater proportion of follicles in this range. What is known already At the time of oocyte retrieval, follicles that are either too small or too large are less likely to yield mature oocytes. However, there is only limited data examining which follicle sizes on TD administration are optimally sized to yield mature oocytes, nor any data examining whether live birth rates are impacted. Explainable artificial intelligence (XAI) offers a valuable opportunity to leverage clinical data to determine the range of follicle sizes that are most likely to yield mature oocytes and lead to improved downstream outcomes. Study design, size, duration A retrospective study incorporating 19,082 patients undergoing their first IVF/ICSI cycle (2005-2023) across 11 European clinics. Follicle sizes on TD were related to oocyte maturity (14,140 patients), fertilization (17,822 patients), high-quality blastocyst development (17,488 patients), and pregnancy outcomes (12,672 patients). Secondary analyses included stratification by age (&amp;gt;35 years: 4,717 patients; ≤35 years: 5,707), and suppressant protocol (GnRH agonist: n = 5,420 patients; GnRH antagonist: n = 3,982). Participants/materials, setting, methods An ensemble-based XAI model, developed through ‘internal-external validation’, was trained, Bayesian optimized, and independently iteratively tested on hold-out clinic datasets. The model determined follicle sizes contributing most to successful laboratory outcomes by harnessing permutation importance and ‘SHAP’ values. Model performance was evaluated and optimized for mean absolute error (MAE). The top 50% contiguous cohort of influential follicle sizes on TD were identified, and further validated through analysis of follicle sizes on preceding days. Main results and the role of chance XAI analysis revealed that follicles sized 13-18mm on TD were most influential in yielding mature oocytes, especially those sized 15-18mm (MAE: 3.60 ±0.35). Predictive follicle sizes from scans 1-2 days preceding TD administration were consistent with expected mean follicle growth rates. For high-quality blastocysts, follicles sized 14-20mm were contributory, narrowing to 15-18mm in the subset of patients where oocytes had been confirmed to be mature. In hCG-triggered cycles, follicles sized 12-19mm were most likely to yield mature oocytes in GnRH antagonist cycles, whereas follicles sized 14-20mm were most contributory in GnRH agonist cycles. In patients ≤35 years, follicles 13-18mm were most contributory, whereas a wider range of follicles (11-20mm) were contributory in patients &amp;gt;35 years. In line with current practice, having three lead follicles ≥17mm on TD was associated with a median improvement in mature oocyte yield of 10% versus those that did not (p &amp;lt; 0.0001). By comparison, maximizing the proportion of follicles on TD within the optimal size range could better improve mature oocyte yield, for example, by 42% when at least 70% of follicles were sized 15-18mm (p &amp;lt; 0.0001). Likewise, LBR improved as the proportion of follicles sized 13-18mm was increased (&amp;lt;10%: 23.3%; 10-20%: 25.7%; 20-30%: 28.8%; 30-40%: 31.6%). Limitations, reasons for caution These data could help guide when to administer the trigger to optimize clinical outcomes, however prospective assessment of different TD strategies based on the proportion of follicles within the optimal follicle size ranges identified in comparison to current practice based on lead follicle size is required prior to clinical adoption. Wider implications of the findings These findings provide a data-driven approach to personalizing ovarian stimulation in IVF. The findings generated by applying an XAI model could assist clinicians in optimizing TD timing, potentially enhancing clinical outcomes by moving beyond the conventional focus on lead follicle size. Trial registration number not appicable

P-645 A machine learning model for optimal trigger day recommendation

Abstract Study question Could AI be used for trigger day recommendations to improve the number of M2 oocytes retrieved in IVF processes? Summary answer The use of AI for trigger day recommendations can improve the number of M2 oocytes retrieved in IVF processes by 1 on average. What is known already One of the most important decisions during ovarian stimulation during IVF cycles is when to trigger follicular maturation. Optimally timed trigger injection should maximize the number of retrieved high-quality oocytes. While these decisions are commonly made based on follicle sizes, hormone levels, and patient parameters, they are subjective and the criteria vary across medical centers and physicians. Numerous research studies are exploring how follicle sizes and other parameters translate to stimulation outcomes, but only in recent years, the use of artificial intelligence in decisions about the day of the trigger has become one of the main fields of interest. Study design, size, duration A retrospective study was made on 1085 IVF cycles conducted between 2019 and 2021 at 6 IVF centers in Poland. Processes were selected to have at least one set of ultrasound cine-loop videos for both ovaries from a maximum of three days before trigger day. Additionally, data on age, AMH, estradiol level, endometrium thickness, and the process outcome (MII oocytes number) was collected. Follicles were measured using the FOLLISCAN system. Participants/materials, setting, methods The recommendation algorithm uses a model predicting the number of MII oocytes retrieved if the trigger was applied on each of the three days following examination. The day with a maximum expected number of oocytes is recommended. The average number of retrieved MII oocytes was compared between two groups: cycles where the recommendation was the same as the actual physician decision, and cycles where it was different. Ten-fold cross-validation and propensity score matching were performed. Main results and the role of chance The model predicting MII oocyte numbers had an R2 of 0.56 and errors of 3.5 (RMSE), and 2.54 (MAE) overall. For the trigger on the day of the USG examination, it was RMSE: 3.33, MAE: 2.39, and later (+1, +2, +3 days respectively) RMSE: 3.6, 3.67, 3.44, MAE: 2.57, 2.71, 2.56. On average, 1.98 more MII oocytes (95% Confidence Interval: 1.22-2.77) were retrieved from processes where the model recommendation was the same as the actual physician decision (on time) compared to those where the model recommendation differed (not on time). Because this was not a randomized trial, and patient parameters vary across compared groups, propensity matching was used to ensure their homogeneity. After this, there were 1.11 more MII oocytes (CI: 0.22-1.99) retrieved on average in the “on time” group than in the “not on time” group. For patients with less than 10 follicles, there were on average 0.3 more MII oocytes in the “on time” group. For patients with 10-20 follicles, on average 0.72 more MII oocytes were observed, and for those with at least 20 follicles 1.32 more on average. Limitations, reasons for caution The study was limited to a few IVF centers in Poland, and its retrospective findings do not necessarily generalize to different centers. Additional evaluation of the model on data from multiple centers should be performed. Also, randomized control trials could be used to evaluate its effectiveness. Wider implications of the findings Results show the potential of using machine learning to optimize ovarian stimulation outcomes. An increased number of MII oocytes results in a higher success rate of in vitro fertilization. Trial registration number Project support was provided by the Polish National Center for Research and Development no. POIR.01.01.01-00-1634/20-00 and ERC Consolidator Grant TUgbOAT no. 772346.

P-494 Empowering women’s comfort! Sedation experts provide enhanced oocyte retrieval experiences with deep sedation

Abstract Study question What are the patient-reported-outcomes (PROs) and patient-reported-experiences (PREs) of deep sedation performed by sedation practitioners during oocyte retrievals compared to light-sedation by the fertility nurse? Summary answer Women undergoing oocyte retrievals with deep sedation by a sedation practitioner had a better experience and classified sedation the preferred method compared to light-sedation. What is known already Vaginal oocyte retrieval is a key step in modern IVF. The procedure is painfull, requiring systemic analgesics and anxiolytics which is called sedation. Light sedation is still the norm in the Netherlands although women prefer stronger analgesia, less anxiety, and less side effects such as nausea and vomiting from the opiods. From a safety point of view, the ministry of health (IGJ) recommends to perform sedation in an out-patient setting only by sedation professionals. It is known dat deep sedation delivered by trained sedation practitioners in an outpatient clinic is feasible in the Netherlands in other fields (gastroenterology etc). Study design, size, duration Prospective cohort study. In September 2021, moderate-to-deep sedation was introduced for oocytes retrievals for 5 days per week. In weekends, light sedation by the fertility nurse remained the standard. This enabled us to study PROs, defined as the view of participating women of their healthcare status, and PREs, defined as the perception of the received care, in both sedation strategies. PROs were assessed with the validated EuroQol-5D-5L questionnaire and PREs with the Iowa-Satisfaction-with Anesthesia-Scale (ISAS). Participants/materials, setting, methods All women who were scheduled for oocyte retrieval were asked to participate in PRO and PRE assessment. We assessed PROs at three time points: (i) day of trigger, (ii) 6-8 hours after discharge, (iii) 24-32 hours after oocyte retrieval. PREs were assessed 24-32 hours after oocyte retrieval. We intended to include 400 consecutive women. We performed mixed-model-analysis for between-group comparison of treatment and time effects (PROs) and a multivariate regression analysis (PRE). Main results and the role of chance A total of 460 women were scheduled for oocyte retrieval. Moderate-to deep sedation was offered 361 women and 352 (98%) received this. Light sedation was offered 83 women and 76 (92%) received this. Women with less than 3 follicles usually received analgesia only; their data were not used. Concerning the PROs, complete baseline questionnaires were available for 404/440 (93%) of women We found a significant time effect on “anxiety/sadness symptoms” which where high at (i) day of trigger in both groups and lowered at (ii) 6-8 hours after discharge; and a significant time effect in “pain” at (ii) 6-8 hours after discharge. We found no treatment effect of moderate-to-deep sedation versus light sedation for the PROs (p = 0.62). Concerning the PREs, the ISAS was scored for 398/440 (90%) of women. The maximum ISAS score is 3 points. The mean ISAS score was significantly higher in the moderate-to-deep sedation group compared to light sedation, indicating a better experience (1.8 ± 0.7 vs 0.9 ± 0.9, p = &amp;lt;0.001). Moderate-to-deep sedation was rewarded higher compared to light sedation because of less pain during the procedure (4 points better), more satisfaction (1 point better) and preference for same sedation in the future (1,5 points better). Limitations, reasons for caution The results are only applicable to the patient population of a tertiary out patient care setting. Wider implications of the findings Measurement of PREs (ISAS) should be standard-of-care to measure experiences of ambulant sedation. Our interpretation is that gynaecologists should abandon light sedation by non-anaesthesiologists and we suggest to provide deep sedation by the sedation professionals only. Trial registration number not applicable

P-619 AMH/AFC ratio as a predictive factor for ovarian responsiveness to gonadotropins during ovarian stimulation

Abstract Study question Does AMH/AFC ratio correlate to the number of follicles on the day of trigger and to the number of oocytes retrieved after ovarian stimulation? Summary answer The AMH/AFC ratio correlates significantly to the number of pre-ovulatory follicles and the number of oocytes collected after ovarian stimulation (OS). What is known already Although AFC is a robust marker of oocyte yield after OS, its combination with Anti-Mullerian hormone (AMH) seems to improve the predictability. Besides, Follicular Output Rate [FORT: (number of pre-ovulatory follicles on day of trigger/AFC at baseline) x 100] and Follicle-to-Oocyte Index [FOI: (number of retrieved oocytes/AFC) × 100] evaluate the ovarian responsiveness to gonadotropins during OS, representing its sensitivity to exogenous FSH. Both parameters take antral follicle count (AFC) only into consideration. AMH and AFC as a ratio might optimize the accuracy of FORT and FOI metrics, helping to predict which patients are at higher risk of suboptimal results. Study design, size, duration This retrospective study analyzed 2,163 ovarian stimulation cycles for IVF/ICSI, performed between May 2015 and October 2023 in a tertiary referral IVF centre. For all the cycles, measurement of AMH using Elecsys (Roche®) no longer than 6 months before starting OS, AFC at baseline, number of pre-ovulatory follicles on the day of trigger, and the treatment outcomes were available. Participants/materials, setting, methods Couples with primary/secondary infertility who underwent OS with antagonist protocol, starting on day 2/3 for IVF/ICSI were included, independent of their age or ovarian reserve parameters. Exclusion criteria were patients with body mass index (BMI) &amp;gt;40 kg/m2, non-vaginal ultrasound measurement for AFC and/or follicles during OS, cycles with previous estradiol priming or oral contraceptives. Ethical approval was obtained from the Research Ethics Committee. Main results and the role of chance 2,163 ovarian stimulation cycles were included in the analysis. The mean age, BMI, AMH, AFC, FOI and FORT of the included women were: 35.6±6.1 years, 27.5±4.7 kg/m2, 2.4±2.1 ng/mL, 12±7 follicles, 1.02±0.66 and 1.38±0.79. The correlation of AMH/AFC ratio (coefficient: 0.62, 95% CI: 0.59 to 0.65, p&amp;lt;0.001) to FOI was stronger than the correlation of AMH (coefficient: 0.31, 95% CI: 0.27 to 0.34, p&amp;lt;0.001) or AFC alone (coefficient: -0.09, 95% CI: -0.14 to -0.05, p&amp;lt;0.001). The correlation of AMH/AFC ratio (coefficient: 0.62, 95% CI: 0.59 to 0.64, p&amp;lt;0.001) to FORT was also stronger than the correlation of AMH (coefficient: 0.21, 95% CI: 0.16 to 0.25, p&amp;lt;0.001) or AFC alone (coefficient: -0.23, 95% CI: -0.27 to -0.19, p&amp;lt;0.001). AMH/AFC ratio was better at predicting stimulation efficiency parameters, FOI and FORT, compared to joint use of AMH and AFC (p&amp;gt;0.001 for both). However, regression analysis showed stand-alone use of the AMH/AFC ratio did not provide a better prediction for collected oocyte count compared to joint use of AMH and AFC. In fact, prediction errors were significantly larger for the AMH/AFC ratio (median: -0.4, range: -11 to 11) compared to the model using AMH and AFC separately (median: -0.2, range: -6 to 7). Limitations, reasons for caution Although clinical assessment was performed in the same centre following the same methodology, inter-observer variability for AFC is a limitation. Additionally, AMH levels used in the study were not obtained in the same cycles, which may adversely affect the performance of the ratio. Wider implications of the findings While AMH/AFC ratio was better at predicting stimulation efficiency compared to FOI and FORT parameters, it was not significantly better at predicting absolute oocyte yield. This may imply AMH/AFC ratio can represent the ovarian sensitivity to exogenous FSH. Trial registration number Not applicable