Fresh Cycles Research Articles

P-763 Twin births in Belgium: a national cohort analysis of 35 523 double fresh embryo transfers between 2012 and 2021

Abstract Study question Should a national embryo transfer (ET) policy designed in the era of cleavage stage transfers be adapted for blastocyst transfers to avoid twin pregnancies? Summary answer Double embryo transfer policy results in unacceptable high twin rates at all ages and treatment ranks which is significantly more pronounced after double blastocyst transfer. What is known already In 2003, authorities in Belgium implemented a law to reduce multiple pregnancies after ART by tailoring ET policies based on age, embryo quality, and cycle rank. A choice between SET or Double Embryo Transfer (DET) depending on embryo quality is allowed in the second cycle for patients under 36y with SET being mandatory with top quality embryos. DET is allowed as of the first cycle for patients aged 36y or more regardless of embryo quality. Blastocyst transfer results in significantly higher live birth rates, implying an increased risk of multiple pregnancies after multiple blastocyst transfers. Study design, size, duration A analysis of 35,523 double embryo fresh transfer cycles over a period of 10 years from 2012 to 2021 from the Belgian national BELRAP (Belgian Registry on Assisted Procreation) registry was performed. The study included 26,930 double cleavage stage transfers (DET-CL) and 8,593 double blastocyst transfers (DET-BL). Participants/materials, setting, methods The primary outcomes were delivery rate (DR) per transfer and twin delivery rate (TDR). DR includes all deliveries with a least one live birth per transfer; the TDR includes all twin deliveries as a proportion of all deliveries. For analysis, the data were categorized into the following age groups: 18-25 years, 26-29 years, 30-35 years, 36-39 years and 40-45 years. Cycle ranks were categorized as follows: rank 1, rank 2 and cycle 3- ≥ 6. Main results and the role of chance For all age groups and cycle ranks, delivery rate per transfer and twin delivery rate per delivery were significantly higher after DET-Bl compared to DET-Cl (26.0% versus 19.9%; p < 0.0001 and 28.0% versus 20.6%; p < 0.0001, respectively). In the age groups 26-29 years, 30-35 years and 36-39 years, a significantly higher TDR was observed in DET-Bl compared to DET-Cl, respectively (34.4% versus 24.2%, p = 0.0005; 33.5% versus 24.9%, p < 0.0001 and 24.3% versus 17.3%, p = 0.0002). TDR after DET-Bl was significantly lower in women aged 40-45 years compared to all other age groups, 18-25 years, 26-29 years, 30-35 years and 36-39 years, respectively (11.3% versus 32.8%, p < 0.0001; 11.3% versus 34.4%; p < 0.0001; 11.3% versus 33.5%; p < 0.0001 and 11.3% versus 24.3%; p < 0.0001), respectively). DR was significantly lower in cycle rank 1 compared to cycle rank 2 (22.5% versus 25.5%; p < 0.0001) and compared to cycle rank 3 - > 6 rank 1 and (22.5% versus 27.1%; p < 0.0001). After DET-Bl, a significantly lower TDR was observed in cycle rank 1 compared to cycle rank 2 (15.6% versus 30.0%; p < 0.0001) and compared to cycle rank 3 - > 6 (15.6% versus 29.7%; p < 0.0001). Limitations, reasons for caution The retrospective design is a limitation. Outcomes might be influenced by clinical and laboratory improvements over the years. The registry does not collect embryo quality data making it impossible to assess the effect of embryo quality on the ET policy and outcome. Wider implications of the findings This data indicates that a double blastocyst transfer should only be considered from the age of 40 onwards. In the first cycle, regardless of age, we observe a significantly lower twin delivery rate, suggesting that a double ET is performed when only poor-quality blastocysts are available. Trial registration number Not applicable

O-019 Outcomes and correlations between traditional Intracytoplasmic Sperm Injection (ICSI) method and a new AI-enhanced system

Abstract Study question In the context of ICSI, how does the Sperm Tracer Deep Neural Network analysis compare to the embryologist’s sperm selection technique? Summary answer Sperm Tracer AI system significantly improves fertilization rates, offering a standardized, objective approach to sperm selection, but nuanced correlations highlight complexities in sperm parameters. What is known already Traditional sperm selection during ICSI relies on subjective, manual methods, introducing variability and affecting pregnancy success. In response, AI applications, aim to enhance objectivity, potentially improving pregnancy rates. Study design, size, duration Between September and December 2023, the study examined 26 fresh ICSI cycles in a total of 268 sibling oocytes. Men aged 18 years and above with 34.4 mean women’s age. The Sperm Tracer group underwent single embryo culture, while the Embryologists' group underwent group embryo culture. The study analyzes statistical differences in fertilization rates, day 3 and day 5 embryo development. The study duration aligns with the analyzed cycles. Participants/materials, setting, methods The study compared real-time AI-assisted sperm evaluation with the Sperm Tracer system to the traditional ICSI method by embryologists. Correlation analysis was performed for the following kinematic parameters: Amplitude of Lateral Head displacement (ALH), Dance (DNC), Linearity (LIN), Straightness (STR), Wobble (WOB), Curvilinear Velocity (VCL), Linear Velocity (VSL) and Average Path Velocity (VAP). Statistical analysis involved Odds Ratios (OR) with 95% confidence intervals, Mann-Whitney U tests and correlation analyses by Pearson’s coefficient. Main results and the role of chance The Sperm Tracer system exhibited a noteworthy enhancement in fertilization rates (OR: 0.46, 95% Confidence Intervals (CI) [0.23, 0.89], p = 0.0224) but no significant differences in cleavage stages, blastocyst formation, or the production of good-quality embryos compared to conventional methods. For correlation analysis used two groups of sperm population. Group A comprises spermatozoa subjected to ICSI with the Sperm Tracer system, resulting in unsuccessful oocyte fertilization and Group B consists of spermatozoa that achieved successful fertilization. In Group A, correlation analysis identified significant negative associations between DNC and linear parameters (LIN, STR, WOB) (p < 0.001), highlighting the clinical relevance in sperm motility. Group B displayed a distinct negative correlation between DNC and LIN (p = 0.03941), indicating potential effects on sperm linear velocity. LIN in Group A exhibited strong negative correlations with WOB (p = 0.0001), moderate negative correlations with STR (p = 0.0028), and VCL (p = 0.0773). Moreover, ALH analysis in Group A unveiled robust negative correlations with LIN, STR, and WOB, suggesting clinical significance in sperm motility. These intricate findings underscore the Sperm Tracer system's primary advantage in optimizing fertilization rates, offering valuable insights for refining sperm selection strategies in assisted reproduction. Limitations, reasons for caution The study faces limitations due to a small sample, impacting generalizability. Divergence in culture embryo strategies introduces bias, necessitating validation in larger studies. The system includes morphology analysis, but no data analysis has been conducted. Exploring the correlation between morphology, considering embryo culture variations, and motility could provide valuable insights. Wider implications of the findings This study highlights AI applications like Sperm Tracer, showcasing their potential to improve assisted reproduction outcomes. Recognizing AI's impact on IVF success is vital for adoption. Integrating AI into clinic protocols may boost IVF efficiency, requiring training for embryologists to ensure effective utilization. Trial registration number Not applicable

P-393 Operative hysteroscopy versus vacuum aspiration for missed miscarriage in women undergoing in vitro fertilization, a propensity score-matched cohort study

Abstract Study question Is operative hysteroscopy, compared to vacuum aspiration, associated with increased success rates in the subsequent frozen embryo transfer of women who experienced missed miscarriage? Summary answer Operative hysteroscopy does not show advantages in terms of live birth rate in the subsequent frozen embryo transfer compared to women who underwent vacuum aspiration. What is known already As hysteroscopy to remove retained product of conception is performed under direct visualization control, it may theoretically reduce risks to the uterine cavity and therefore improve future fertility. With the advancements in hysteroscopy technology, an increasing number of women with missed miscarriage are choosing operative hysteroscopy over conventional vacuum aspiration. However, there is currently insufficient research available to determine whether use of operative hysteroscopy to remove retained tissues within the uterus effectively increases the success rate of subsequent frozen embryo transfer. Study design, size, duration This was a propensity score-matched cohort study on women who had experienced an missed miscarriage at 5 to 16 gestational weeks during an IVF cycle in Peking University Third Hospital from 2015 to 2022. Participants/materials, setting, methods We aimed to focus on a specific group of patients who had experienced missed miscarriage during IVF and subsequently underwent frozen embryo transfer. Logistic regression models were used to compare the effect of operative hysteroscopy versus vacuum aspiration, after propensity score matching with a 1:1 ratio. Non-linear interaction was tested on gestational weeks and treatment effect on live birth rate. The primary outcome was the live birth rate in the subsequent frozen embryo transfer. Main results and the role of chance Out of the 3,722 fresh embryo transfer cycles and 5,948 frozen embryo transfer cycles resulting in miscarriage, a total of 2,562 women who underwent vacuum aspiration and 347 women who underwent operative hysteroscopy were included in the analysis. After propensity score matching at a 1:1 ratio, 324 women were included in each group. Compared to women who underwent vacuum aspiration, those who underwent operative hysteroscopy were associated with a lower rate of live birth in the propensity-based matched cohort (29% vs 22%, aOR = 0.67 (0.47, 0.96)). The result was further confirmed by several sensitivity analysis, including using non-imputed data, varying calliper widths for propensity score matching, and matching covariates associated with treatment assignment or pregnancy outcomes. No statistical difference was detected on the biochemical pregnancy rate, clinical pregnancy rate, multiple pregnancy rate, and miscarriage rate. No interaction was detected between the gestational week and the relative treatment effect on live birth (p = 0.75). There was no significant difference in the rate of neonatal outcomes between the vacuum aspiration and operative hysteroscopy groups. 11 women experienced surgery reintervention in the vacuum aspiration group (0.4%), while no one required surgery reintervention in the operative hysteroscopy group. Limitations, reasons for caution The retrospective design and inability to analyze certain confounding factors are notable limitations, despite achieving covariate balance through matching. Our dataset did not capture several important outcomes, including cumulative pregnancies and severe complications after surgery. Future randomised trials are warranted to provide more robust insights into our results. Wider implications of the findings Women may benefit from operative hysteroscopy with a lower rate of reintervention compared to vacuum aspiration. However, this advantage may come at the expense of lower rates of live birth. Our results should be further tested by randomised trials. Trial registration number NA

P-440 Idiopathic infertility does not increase rates of placental abnormalities among singleton pregnancies conceived with either in-vitro fertilization (IVF) or ovulation induction±intrauterine insemination (OI±IUI)

Abstract Study question Is there an adverse impact of idiopathic infertility diagnosis on placental pathology among singleton pregnancies conceived with fertility treatments? Summary answer Idiopathic infertility does not increase rates of placental abnormalities and exhibits distinctive associations within the inflammatory and vascular spectrum of placental pathology. What is known already Pregnancies resulting from fertility treatments are often considered to be at higher risk for placenta-mediated obstetric complications and subsequent adverse perinatal outcomes. Treatment induced hormonal changes altering the endometrial milieu, along with embryo manipulation and culture conditions, may impact the processes of implantation, decidualization, trophoblast invasion, and placental vascularization. Nevertheless, the impact of infertility diagnoses on placental pathology among singleton pregnancies conceived with fertility treatments has not been elucidated, and whether idiopathic infertility alters the risk of placental abnormalities remains unknown. Study design, size, duration Retrospective review of placental pathology data from 1205 singleton livebirths conceived with fertility treatments (899 IVF, and 306 OI±IUI cycles) between 01/2004 and 04/2022. Placenta pathology was reviewed by one expert pathologist and classified as anatomic, inflammatory, infectious, and vascular [including any features of fetal (FVM) or maternal (MVM) vascular malperfusion], using the Amsterdam Workshop Consensus definitions. Placental abnormalities were compared between idiopathic infertility (IdI, n: 269) and all other, non-idiopathic infertility (non-IdI, n:936) diagnoses. Participants/materials, setting, methods Primary outcomes: anatomic, inflammatory, infectious, and vascular placental abnormalities. Parametric, and non-parametric tests were used as appropriately; odds ratios (OR) with 95% confidence intervals (95%CI) were assessed through logistic regression, adjusting for maternal age, body mass index (BMI, kg/m2), race, parity, gestational age, neonatal gender, treatment type, gestational diabetes, and hypertensive disorders. Analyses were further stratified by OI±IUI vs IVF treatments [the latter further stratified into fresh and frozen embryo transfers (FET)]. Main results and the role of chance Mean age, BMI, and AMH did not differ between groups, and neither did placental weight at term. Overall, unadjusted rates of inflammatory, infectious, and vascular abnormalities did not differ between groups (12.6% vs 11.4%, p 0.568; 22.0% vs 19.1%, p 0.256; 54.5% vs 58.6%, p 0.186, respectively). However, a higher rate of anatomic abnormalities was noted among IdI patients (32.8% vs 27.1%, p 0.044, IdI vs. non-IdI, respectively). When adjusting for potential confounders, no differences were noted between groups regarding inflammatory, infectious, and vascular abnormalities, and the observed difference in anatomic abnormalities lost its significance [adjOR(95%CI); inflammatory: 0.98(0.94-1.03), infectious: 1.03(0.98-1.09), vascular: 0.96(0.90-1.02), and anatomic: 1.02(0.96-1.08), non-IdI: ref]. Similarly, when separating OI±IUI from FET and fresh IVF cycles, adjOR(95%CI) revealed no differences in anatomic, infectious, and vascular abnormalities between groups [OI±IUI: 0.97(0.85-1.1), 0.97(0.87-1.08), 0.99(0.87-1.12); FET: 1.08(0.94-1.24), 1.07(0.94-1.23), 1.04(0.98-1.11) and, fresh IVF: 1.06(0.98-1.15), 1.04(0.96-1.13), 0.96(0.87-1.07), for anatomic, infectious, and vascular, respectively]. However, lower odds of inflammatory abnormalities were noted among fresh IVF but not among FET or OI±IUI cycles in IdI [adjOR (95%CI); fresh IVF: 0.95(0.91-0.99), FET: 1.09(0.98-1.21), OI±IUI: 0.97(0.87-1.08), non-IdI: ref]. Interestingly, among vascular abnormalities studied in the programmed FET cycles, MVM showed a difference between the groups [adjOR(95%CI) 0.90(0.85-0.96), non-IdI: ref]. Limitations, reasons for caution This study is limited by its retrospective design. The reported findings are from an infertile population undergoing treatments and thus not easily generalizable to natural conceptions. Other factors, such as environmental, nutritional, and lifestyle, might alter a patient’s individual pregnancy risk for placental abnormalities. Wider implications of the findings Overall, idiopathic infertility does not appear to increase the risk for placental abnormalities. However, it may impact placental pathology in a unique way, within the vascular and inflammatory spectrum, which might differ from that of other infertility diagnoses, and might be further altered by the treatment protocol. Trial registration number Not Applicable

P-760 The effect of assisted hatching on pregnancy outcomes in 1,833,485 single embryo transfer based on Japan Assisted Reproductive Technology Registry System

Abstract Study question Does assisted hatching (AH) affect pregnancy outcomes especially when it was performed selectively on specified group? Summary answer No clinically significant effect of AH on pregnancy outcomes was demonstrated for the entire single embryo transfer (SET) cycle after adjusting for covariates. What is known already AH is a technique used in assisted reproduction by artificially thinning or making a small hole in the zona pellucida in order to facilitate the hatching process. It is suggested that AH may improve the chance of embryo implantation and success of pregnancy. However, there is insufficient evidence to conclude that AH improves pregnancy outcomes, despite its widespread and longtime use. In 2014, the Practice Committee of ASRM recommended that AH should not be conducted routinely for all patients. On the other hands, it has been suggested that AH could be effective for patients with poor prognosis. Study design, size, duration A retrospective observational study based on the national ART registry maintained by the Japan Society of Obstetrics and Gynecology (JSOG) was performed. The study included 1,833,485 single embryo transfer (SET) for in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) from January 2010 to December 2019. This study was approved by the Registration and Research Subcommittee of the JSOG and Tokyo University Ethics Committee. Participants/materials, setting, methods To determine the effect of AH, the rate of clinical pregnancy and live birth were compared in SET with and without AH as primary outcome measures. In addition, the prevalence of miscarriage, multiple pregnancy, ectopic pregnancy, placental malposition, and placenta accreta were analyzed as secondary outcomes. We performed inverse probability of treatment weighting and outcome regression analyses. Main results and the role of chance Out of 1,833,485 SET cycles, AH was conducted in 983,242 cycles (53.6%). In all SET cycles, clinical pregnancy rate (CRP) and live birth rate (LBR) were 31.0% vs. 26.2%, and 21.6% vs. 18.7% in AH vs. without AH group, respectively. AH was more frequently performed in patients with advanced maternal age, frozen-thawed ET cycles (88% vs. 47%, AH vs. without AH), blastocyst transfer cycles (70% vs. 42%), patients with tubal factor (17% vs 14.3%), and hormonal replacement cycles (66% vs. 43%). After adjusting for these covariates, the propensity-weighted CPR (28.4% vs. 29.1%, AH vs. without AH) and LBR (20.1% vs. 20.6%) were slightly yet significantly lower in AH group. As secondary outcomes, AH may lead to increased risk of multiple pregnancy (0.21% increase), ectopic pregnancy (0.02%), and placenta accreta (0.03%), and 0.24% decreased risk of miscarriage. On the other hands, subgroup analysis suggested that AH could be effective in the following cycles: frozen-thawed cycles with either blast or cleavage with maternal age under 35 years, and fresh blastocyst transfer cycles with maternal age over 40 years. Limitations, reasons for caution The limitation of this study is that the information regarding the history of repeated implantation failure and methods of AH were not included in this registry system. Another limitation is that duplicate data from same patients who underwent multiple embryo transfers exists in this retrospective study for 10 years. Wider implications of the findings Despite of frequent use of AH in Japan, AH in SET cycles for all patients is not recommended because of increased risk of adverse events without improvement of pregnancy outcomes. On the other hands, AH may improve pregnancy outcomes for some groups associated with maternal age and duration of culture. Trial registration number not applicable’

P-615 Can the use of progestin in egg donation cycles influence morphokinetic parameters of embryos when compared with GnRH antagonist during ovarian stimulation? A case-control study

Abstract Study question Are there differences in clinical and morphokinetic parameters of embryos obtained from fresh egg donation cycles using GnRH antagonist versus PPOS on same donor? Summary answer Lower number of oocytes retrieved and faster early morphokinetics parameters were observed in PPOS protocol. What is known already Controlled ovarian hyperstimulation (COH) is a crucial step in assisted reproduction treatments and the ideal protocol should be chosen according to the patient’s profile, based on literature results, intending to achieve high effectiveness. The use of PPOS in ovarian stimulation protocols is getting attention because of its safety, efficacy and proved to be patient friendly and an economical alternative to avoid premature LH surge. In the last years, morphokinetics parameters started to be considered in embryo classification and selection, as they correlate to embryo implantation potential. Here, morphokinetics parameters were compared from two different COH in donated oocyte cycles. Study design, size, duration Case-control study including cycles from 10 oocyte donors and 20 recipient patients, whose embryos formed with fresh oocytes were cultured in a time-lapse system (Embryoscope® Plus), in a single private IVF center between Jun/2020 and Oct/2022. Each donor were submitted to two cycles: first stimulation with standard GnRH antagonist (ant) short protocol (group A) and in a posterior cycle: a second stimulation with progesterone (PPOS protocol with dydrogesterone, group B). Participants/materials, setting, methods All donors used menotropin for COH (doses adjusted according to patient’s profile). Group A started GnRh ant with follicle above 14 mm. On group B, dydrogesterone 10 mg was started on the first day of COH and maintained until the day of ovulation trigger, which was performed with GnRH agonist. Clinical and morphokinetics parameters were compared. Paired t-test, t-test or Mann-Whitney were used properly, values of p < 0.05 were considered significant. Main results and the role of chance A total of 70 blastocysts were analyzed, 39 from group A and 31 from group B. The following morphokinetics parameters were annotated: time of PN fading (tPNf), time to two cells (t2), three cells (t3), four cells (t4), five cells (t5), eight cells (t8), time to morula (tM), time to blastulation (tB) and KIDScoreTM. Statistically significant differences were observed for tPNf: group a) 24,01 ± 3,28h versus b) 22,59 ± 2,48h, p = 0,0484, t2: a) 26,30 ± 3,24h versus b) 24,76 ± 2,27h, p = 0,0211; t3: a) 37,04 ± 4,44h versus b) 35,53 ± 2,93, p = 0,0347 and t4: a) 38,38 ± 5,15h versus b) 36,05 ± 3,32h, p = 0,0152. Clinical characteristics of the donors were also analyzed: age, body mass index (BMI), total gonadotropin dose, antral follicular count (AFC), follicle stimulating hormone (FSH), basal hormone levels, follicle count, oocyte pick-up (OPU), altered oocytes, number of germinal vesicles, metaphase I (MI) and metaphase II (MII) oocytes. Differences were observed only between two clinical aspects: patients’ age: a) 24,2 ± 3,6 versus b) 25,0 ± 3,3, p = 0,0031 and OPU: a) 23,3 ± 9,1 versus b) 18,6 ± 8,3, p = 0,004, however both variables does not seem to affect embryo formation potential. Limitations, reasons for caution The results should be interpreted with caution due to the limitations of evaluate a small dataset of donors, resulting in low number of embryos in each group of protocols for analysis. Wider implications of the findings In this case-control study, a lower number of oocytes retrieved and faster early morphokinetics times were observed in PPOS compared to antagonist protocol. The implications of these differences still need further data analyses to compare if these findings can change clinical outcomes. Trial registration number Not applicable.

P-429 Measuring serum progesterone levels on the day of a fresh blastocyst transfer is debatable as there is no evidence for correlation with ongoing pregnancy results

Abstract Study question Does serum progesterone (P4) level on the day of a fresh blastocyst transfer relate to ongoing pregnancy rate (OPR)? Summary answer OPR after a fresh single blastocyst transfer seems not to be associated with serum P4 level on the day of transfer. What is known already Several studies have suggested an optimal serum P4 threshold for embryo transfers in frozen embryo transfer cycles. However, for fresh embryo transfers, data are scarce and conflicting. Study design, size, duration A retrospective single-center cohort study was performed on 598 complete data cycles, retained out of 631 consecutive fresh single blastocyst transfer cycles. Data were collected from patients undergoing a fresh IVF/ICSI cycle with autologous oocytes at a tertiary fertility center between June 2022 and August 2023. Participants/materials, setting, methods A total of 482 unique patients underwent one or more single fresh blastocyst transfers using micronized vaginal progesterone (MVP) 800mg BID for luteal phase support starting day after oocyte retrieval. Serum P4 levels were determined on day of transfer. The primary endpoint was OPR, positive hCG-test and early pregnancy loss (EPL) were secondary endpoints. Unadjusted and adjusted generalized estimating equations (GEE) assessed P4 level association with the endpoints, using an exchangeable working correlation matrix. Main results and the role of chance No association was identified between P4 levels on day of transfer and OPR after accounting for maternal age, blastocyst quality, P4 and estradiol level at last ultrasound, BMI and endometrial thickness. Data were grouped according to 10/50/90 and 25/50/75 percentiles, resulting in groups < = or > 27ng/ml and < = or > 40ng/ml, with omission of 90th and 75th percentile groups due to right-skewed distribution. With serum P4 levels higher than 40ng/ml, the probability of a positive hCG-test significantly increased (OR 1.79, CI 1.11-2.91; p = 0.018). No significant difference was observed in patients with serum P4 < = or > 27ng/ml (OR 1.23, CI 0.66-2.30; p = 0.506). Regarding OPR, no significant differences were observed when comparing patients with serum P4 < = or > 27/ng/ml or < = or > 40ng/ml (OR 0.88, CI 0.42-18.85; p = 0.736 and OR 1.41, CI 0.83-2.37; p = 0.203, respectively). Moreover, EPL did not significantly differ between serum P4 level groups (OR 1.93, CI 0.61-6.13; p = 0.265 and OR 1.2, CI 0.51-2.84; p = 0.674). Age (p < 0.001) and embryo quality (p < 0.001) are significantly related with OPR. Additionally, late follicular progesterone levels and OPR are significantly associated (OR 2.39, CI 1.16-4.95 in patients with P4 < = or > 27/ng/ml and OR 2.21, CI 1.07-4.55 in patients with < =40ng/ml and >40ng/ml). Limitations, reasons for caution Limitations include the retrospective design and the lack of live birth outcome data. Progesterone levels exceeding 60 ng/ml were not further analyzed to their precise value but grouped as 60 plus which did not allow to identify potential detrimental effects of very high P4 levels on treatment outcome. Wider implications of the findings Our data suggest that measuring P4 on the day of a single blastocyst transfer with MVP luteal phase support may not be indicative of OPR or the risk of EPL. This raises questions regarding the necessity for routine P4 measurements as well as the development of rescue strategies. Trial registration number ONZ-2023-0628

P-639 Are GnRH-agonists (GnRH-a) safer and more effective ovulation triggers than human chorionic gonadotrophin (hCG)? A retrospective analysis of frozen embryo replacement cycle (FERC) outcomes

Abstract Study question Are GnRH-agonists (GnRH-a) safer and more effective ovulation triggers than human chorionic gonadotrophin (hCG)? A retrospective analysis of frozen embryo replacement cycle (FERC) outcomes Summary answer GnRH-a trigger reduces the incidence and severity of ovarian hyperstimulation syndrome (OHSS) leading to significantly improved clinical outcomes when compared to hCG trigger for FERCs. What is known already Ovulation induction plays a crucial role in the success and safety of ART cycles. hCG is extensively used as an alternative to LH to trigger ovulation. However, high levels of sustained hCG exposure increases the risk of OHSS, a potentially life-threatening complication of ART. To eliminate the risk and incidence of OHSS, GnRH-a can be used to trigger ovulation. Although there are concerns regarding clinical outcomes with fresh transfers following GnRH-a trigger, it elicits a more physiological response compared to hCG. This may lead to improved embryo quality, utilisation, and better clinical outcomes following a freeze-all strategy, reducing patients’ time-to-pregnancy. Study design, size, duration This was a retrospective data analysis of FERC outcomes following fresh IVF or ICSI cycles, involving ovulation induction using either hCG or GnRH-a as a final trigger. The evaluation included results from cycles spanning an eight-year period, from January 2012 to December 2019 at Hammersmith Hospital London. A total of 160 cycles were included in the study, with 76 in the hCG trigger group and 84 in the GnRH-a trigger group. Participants/materials, setting, methods Strict inclusion criteria were employed to render the study groups as comparable as possible and to minimise the effect of independent variables, such as oocyte and sperm factors, on oocyte or embryo developmental competence. Inclusion criteria: women ≤37 years old at the start of treatment, GnRH antagonist stimulation, blastocyst vitrification-warming and transfers only. Statistical significance was calculated using independent t-test and Fisher’s Chi-square exact test. Main results and the role of chance The mean age (±SD) of patients at the time of oocyte retrieval was comparable across groups. The average number of oocytes collected were significantly higher in the GnRH-a group compared to hCG (28.31 vs. 18.07, respectively, P < 0.001). Embryological data (maturation, fertilisation, blastocyst formation, blastocyst utilisation and good quality blastocyst formation rates) were comparable across both groups. OHSS rate was significantly lower in the GnRH-a group (17% vs. 50%. P < 0.0001). The following clinical data were significantly higher (P < 0.05) in the GnRH-a group compared to hCG: implantation rate (56% vs. 36%), clinical pregnancy rate (56% vs. 36%) and live birth rate (42% vs. 27%). Limitations, reasons for caution The biggest limitation of this study is its retrospective nature and the application of various inclusion-exclusion criteria that have resulted in relatively small sample sizes. Additionally, numerous other confounders, e.g. patient body mass index, cause/duration of infertility and stimulation duration, have not been considered in this study. Wider implications of the findings The findings of this study are promising and demonstrate a great potential for benefit in the use of GnRH-a trigger with a freeze-all strategy to minimise the risk of OHSS, diminishing the associated patient morbidity and mortality, reducing healthcare costs, improving clinical outcomes, and reducing the overall time-to-pregnancy for patients. Trial registration number not applicable

P-536 Preimplantation Genetic Testing for hereditary breast and ovarian cancer syndrome due to BRCA pathogenic variant : the parisian center experience

Abstract Study question What are the outcomes of Preimplantation genetic testing for monogenic disease (PGT-M) for BRCA pathogenic variants? Summary answer Among couples entering a PGT-M program for BRCA pathogenic variants, 23.5% achieved a live-birth. What is known already BRCA pathogenic variants are associated with an oncologic predisposition with variable penetrance and are accessible to screening and preventive procedures to avoid or early detect the development of cancer. Transmission of BRCAmutations to offspring poses a significant reproductive concern for BRCA mutation carriers. PGT-M offers a solution to prevent this mutation transmission. Despite reproductive challenges related to BRCA status, there are no existing international guidelines for applying PGT-M in these situations. In France, authorization for BRCA related PGT-M is case-specific, considering the personal and familial severity of the disease and submitted to a multidisciplinary prenatal diagnosis center (CPDPN). Study design, size, duration This retrospective observational study, is a single-center analysis of 46 requests for PGT-M related to BRCA pathogenic variants at our PGT center from January 2015 to December 2022. Participants/materials, setting, methods Forty-six couples asked for PGT-M for BRCA pathogenic variant carried by one of the partner. The present study involves the examination of data encompassing referrals, decisions as well as clinical outcomes associated with PGT-M. Main results and the role of chance Forty-six requests for PGT-M due to the risk of hereditary predisposition to breast and ovarian cancer have been received: 36 for a pathogenic variant in the BRCA1 gene and 10 for BRCA2. Nine couples ultimately did not proceed and dropped out. Eight requests were declined, either due to the refusal of the multidisciplinary prenatal diagnosis center (CPDPN) based on family history (n = 4) or alteration of ovarian reserve (n = 4), the 2 latter requests are still under investigation. In total, requests from 27 couples (55%) were considered eligible and feasible. Among them, 17 (63%) underwent at least one PGT-M cycles (5 dropped out before the beginning and 5 are still pending). Overall, 33 ovarian stimulation cycles for in vitro fertilization were initiated, resulting in the retrieval of 192 mature oocytes and the formation of 145 embryos. Of these, 97 were biopsied, and 38 did not carried the BRCA pathogenic variant. A total of 21 fresh or frozen embryo transfers were performed and 8 pregnancies were achieved, leading to 4 deliveries and 5 live births (23.5% of couples who started a PGT-M cycle). Limitations, reasons for caution In the absence of established guidelines, there is variability in information regarding PGT-M among oncogeneticists. Thus, only selected carriers of BRCA pathogenic variants are addressed to our PGT centers. Additionally, women participating in a fresh PGT cycle were selected on several criteria including ovarian reserve parameters. Wider implications of the findings PGT-M provides a viable alternative for couples seeking to prevent the transmission of BRCA mutations. To increase the PGT-M cumulative live birth rate, the transfer of male embryos carrying the variant, assumed to have lower tumor risks, should be considered and discussed with patients. Trial registration number Not applicable

O-152 Pre-implantation genetic testing for aneuploidies (PGT-A) improves reproductive outcomes in advanced maternal age patients undergoing IVF/ICSI: a multicentre retrospective cohort study with propensity score matching

Abstract Study question In patients > 37 years undergoing IVF/ICSI, does PGT-A improve live birth rates (LBR) and cumulative live birth rates (CLBR)? Summary answer In advanced maternal age women with ≥1 embryo to transfer, PGT-A improves the live birth and cumulative live birth rates. What is known already The age-related rate of aneuploidy remains a major cause of IVF failure. Therefore, PGT-A has been proposed as a method to select embryos with the highest implantation potential. Previous studies have shown that women younger than 37 years old do not benefit from PGT-A given the comparable outcomes in terms of implantation, clinical pregnancy, and live-birth rates. Moreover, PGT-A may also be inherently ineffective given the risk of mitotic mosaicism, sampling errors and misinterpretation of results. However, we are currently lacking solid scientific evidence to support whether this approach benefits advanced maternal age women. Study design, size, duration A multicenter retrospective cohort study was conducted including 9328 patients >37y undergoing their first IVF/ICSI cycle with an oocyte retrieval performed between 1/01/2013-31/07/2021 in a multinational private fertility clinic. The study group (n = 4664) included patients who performed PGT-A. The control group included patients without PGT-A (n = 4664) and was selected by propensity score matching adjusted for age at oocyte retrieval, number of oocytes retrieved and year of oocyte retrieval. Participants/materials, setting, methods The primary outcome was CLBR (delivery of at least one live birth per started cycle, including the fresh and subsequent frozen embryo transfer cycles). The secondary outcomes were LBR and time to pregnancy. The analysis was conducted including all patients with an initiated cycle of ovarian stimulation and also per embryo transfer. Comparisons are presented as adjusted odd-ratios (adjOR) and 95% confidence intervals (95%CI) following multivariable logistic regression (LBR) or cox regression (CLBR) analysis. Main results and the role of chance Patients in the PGT-A group had more oocytes retrieved (11.03±6.82 vs 9.24±6.15, p < 0.001), and a higher number of available blastocysts (2.82±2.21 vs 1.22±2.00, p < 0.001). In the PGT-A group, 13.153 embryos were analysed, with an euploidy rate of 29.30% (n = 3854). In total, 49.83% (n = 2324) patients did not undergo embryo transfer due to unavailable euploid embryos. Considering all patients that initiated ovarian stimulation, the PGT-A group presented a higher unadjusted CLBR per started cycle (27.38% vs 21.81%, p < 0.001). Considering only patients who underwent embryo transfer, a total of 5934 embryo transfers were analysed (n = 3166 in the control group and n = 2768 in the PGT-A group). Following multivariable logistic regression analysis, LBR and CLBR were significantly higher in the PGT-A group (respectively, adjOR 1.56 [95% CI 1.38-1.77], adjOR 1.53 [95% CI 1.39-1.68]). Following the transfer of 5 embryos, the CLBR was approximately 100% in the PGT-A group and 74.51% in the control group. Survival analysis was also perfomed to assess the impact of PGT-A on time to pregnancy. Despite the fact that from 6 months onwards the CLBR was higher in the PGT-A group, the median time to pregnancy was higher in the PGT-A group (3.27 (95%CI 3.16-3.40) vs 2.74 months (95%CI 2.57-3.03). Limitations, reasons for caution This study is limited by its retrospective design and low number of women with more than 3 embryos transferred. Also, the fact that only the first IVF/ICSI cycle was analysed provides a proper patient counselling in this specific context but does not provide data on repeated cycle outcomes. Wider implications of the findings Our findings suggest that, in women older than 37 years with at least one available embryo to biopsy, performing PGT-A may improve the reproductive outcomes in terms of LBR and CLBR, providing a useful clinical tool for embryo selection. Trial registration number not applicable

P-001 Comparing two monomorphic teratozoospermia syndromes in terms of ICSI outcomes - Round vs. pin-head

Abstract Study question Whether ART clinical outcomes are affected at extremes of morphological presentations, in samples where typical forms are unavailable for ICSI. Summary answer The study found no correlation between the severity of sperm defect and ICSI results. What is known already One of the challenging topics in the field of Andrology is the predictive role of monomorphic teratozoospermia, specifically head defects, in assisted reproductive technology (ART) outcomes. The definitive requirement of conducting intracytoplasmic sperm injection (ICSI) is the presence of at least one motile spermatozoon. Two schools of thought provide contradicting views; some believe that sperm morphology can significantly predict fertilization, clinical pregnancy, and live birth rates in fresh ICSI cycles and others support that the degree or nature of sperm morphological dysfunction lacks a significant impact on the outcome of ICSI outcomes. Study design, size, duration This retrospective cohort study was included 7,881 couples with male factor infertility who underwent 11,536 IVF/ICSI cycles at a tertiary referral fertility center over a 13-year period. Participants/materials, setting, methods From this cohort, 10 cases were identified with >90% acephalic sperm syndrome and 11 patients had >90% globozoospermic sperm. The implantation rate, pregnancy, and live birth rates per initiated cycle (iC) and per patient were compared between the two groups. The rates were also compared between each group with the general ICSI population. Main results and the role of chance The data analysis suggests no statistically significant differences between the two patient groups. Implantation was 20% versus 15.1% (95% CI, 0.33 to 5.97; OR, 1.4) for round and pin-head groups. The pregnancy per iC and patient were 25% vs 23.1% (95% CI, 0.25 to 9.5; OR, 1.55) and 27.3% vs 30% (95% CI, 0.13 to 5.8; OR, 0.87) for round-head and pin-head groups, respectively. The live birth rates matched the pregnancy rates. For the general ICSI population the rates were as follows: implantation rate was 17.3%; pregnancy rate (per iC and per patient) was 27.2% and 44.7%; and live birth rate (per iC and per patient) was 23.2% and 38.2%. The study found no significant differences between the outcomes for the general ICSI population and the two groups. Limitations, reasons for caution It is uncertain whether this lack of association is genuine or whether it is affected by the limited number of cases with extreme monomorphic abnormalities. The absence of evidence should not be taken as evidence of absence. Wider implications of the findings Conducting such studies should be encouraged to provide insight by informing systematic reviews. A significant portion of existing literature on teratozoospermia comprises of case reports, which are rationally excluded from systematic reviews and meta-analyses. Additional research is warranted to definitively establish the investigated relationships. Trial registration number not applicable

O-123 Trends and challenges in the practice of ART in China

Abstract China is a large country with a population of over 1.4 billion. In 1988, the first in-vitro fertilization-embryo transfer (IVF-ET) baby was born in Peking University Third Hospital. In the following 3 decades, assisted reproductive technology (ART) has developed rapidly in China, and the availability and accessibility of the ART service have improved markedly. In 2004 totally, only 37 institutions had passed the administrative licensing procedure to carry out ART. While in 2020, 536 institutions obtained the ART license. Since 2016, the total number of ART service cycles(Artificial insemination included)has exceeded 1 million, and the number of babies born has exceeded 300,000, accounting for about 2% of the total live births in China in 2016. At present, assisted reproductive technology has become one of the important medical interventions for the treatment of infertility in China, which has brought good news to infertile couples and their families, and has made great contributions to social harmony and family happiness. Cycles per million population (C/M) in 2009 was 120. In 2020, it has increased to 668, with more and more infertile couples having access to this technique in China. The success rate of assisted reproductive technology remained stable. In 2020, the clinical pregnancy rates (CPR)of conventional IVF and ICSI fresh embryo transfer cycles reached 52.4% and 49.4%, respectively, and the live birth rates were 43.0% and 40.6%, respectively. The clinical pregnancy rate and live birth rate of frozen-thawed embryo cycle were 51.3% and 40.5% per transfer. With the widespread application of embryo freezing technology, the cumulative live birth rate was estimated to reach 49.5% (CLBR estimate) in 2020. The safety monitoring indicators of assisted reproductive technology showed that since 2015, the multiple pregnancy rates of conventional IVF, ICSI and FET have decreased year by year, and have dropped to 22.4%, 21.4% and 17.6% in 2020, respectively. The incidence of moderate-severe ovarian hyper-stimulation syndrome (OHSS) and severe bleeding were also under control, within a reasonable range. Assisted reproductive technology, which involves many medical, social, ethical and legal issues, is a special clinical technology with limit application for medical indication. The Chinese government attaches great importance to the quality and safety management of assisted reproductive technology. A series of management documents such as the Administrative Measures for Human Assisted Reproductive Technology, the Regulations for Human Assisted Reproductive Technology and so forth, have been issued since 2001. Further improvement of key performance indicators (KPIs) correlated with ART quality and safety control is of the top priority and also challenging. In addition, the ART surveillance data in China is still aggregated data, which does not include important indicators such as age stratification, infertile factors or indications and delivery gestational age, maternal and infant outcomes, with some limitations for surveillance. Continuous improvement of data quality, and initiation of cycle-based data collection and security measures of case information are also challenging for the next step.

Comparison of pregnancy outcomes between 4th day morula and 5th day blastocyst after embryo transfer: a retrospective cohort study

BackgroundThis study was designed to evaluate pregnancy outcomes between morulae transferred on day 4 (D4) and blastocysts transferred on day 5 (D5).MethodsFrom September 2017 to September 2020, 1963 fresh transfer cycles underwent early follicular phase extra-long protocol for assisted conception in our fertility center were divided into D4 (324 cases) and D5 (1639 cases) groups, and the general situation and other differences of patients in both groups were compared. To compare the differences in pregnancy outcomes, the D4 and D5 groups were further divided into groups A and B based on single and double embryo transfers. Furthermore, the cohort was divided into two groups: those with live births (1116 cases) and those without (847 cases), enabling a deeper evaluation of the effects of D4 or D5 transplantation on assisted reproductive outcomes.ResultsIn single embryo transfer, there was no significant difference between groups D4A and D5A (P > 0.05). In double embryo transfer, group D4B had a lower newborn birthweight and a larger proportion of low birthweight infants (P < 0.05). The preterm delivery rate, twin delivery rate, cesarean delivery rate, and percentage of low birthweight infants were lower in the D5A group than in the D5B group (P < 0.05). Analysis of factors influencing live birth outcomes further confirmed the absence of a significant difference between D4 and D5 transplantation in achieving live birth (P > 0.05).ConclusionWhen factors such as working life and hospital holidays are being considered, D4 morula transfer may be a good alternative to D5 blastocyst transfer. Given the in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) success rate and risk of twin pregnancy, D4 morula transfer requires an adapted decision between single and double embryo transfer, although a single blastocyst transfer is recommended for the D5 transfer in order to decrease the twin pregnancy rate. In addition, age, endometrial thickness and other factors need to be taken into account to personalize the IVF program and optimize pregnancy outcomes.

P-245 Evaluating the impact of embryos undergoing multiple freeze-thaw cycles in preimplantation genetic testing for aneuploidy (PGT-A) on treatment outcomes in IVF

Abstract Study question Do cryopreserved embryos subjected to thaw, biopsy, re-freeze (TBR) exhibit inferior pregnancy outcomes compared to embryos undergoing standard PGT-A with a single vitrification-warming cycle? Summary answer Transfer of twice-thawed euploid embryos demonstrated comparable clinical pregnancy outcomes, yet elevated miscarriage rates following a repeated vitrification-warming cycle warrants further scientific inquiry. What is known already There is often hesitancy to test cryopreserved embryos that were not initially PGT-A tested due to concerns about embryo survival during the additional freeze-thaw cycle those embryos will endure. However, the TBR technique has shown efficacy, particularly for IVF patients with recurrent failed attempts using fresh, untested embryos. Previous studies on TBR consistently report comparable embryo survival rates to fresh cycles. Nevertheless, there is no consensus on whether transferring euploid TBR embryos adversely affects pregnancy outcomes compared to euploid fresh biopsy embryos, potentially due to the relatively low number of transferred TBR embryos in such studies. Study design, size, duration This study retrospectively analysed euploid freeze-thaw single embryo transfer (SET) data from embryos that underwent PGT-A at a large fertility clinic in London, between January 2019 and June 2022. Pregnancy outcomes were compared between freshly biopsied embryos (control group, n = 349) and cryopreserved embryos that underwent thaw and biopsy before freeze-thaw SET (twice-thawed group, n = 35). Embryos previously biopsied with PGT-A, subsequently cryopreserved, and then subjected to thaw and re-biopsy were classified in the twice-thawed group. Participants/materials, setting, methods Blastocysts cultured from fresh embryos (control group) or derived from frozen-thawed blastocysts (twice-thawed group) underwent PGT-A using standard protocols before freeze-thaw SET. The study assessed biopsy rates, post first thaw and survival rates post second thaw in the twice-thawed group, comparing to the control group. The clinical outcomes evaluated were Implantation rate (IR), Live Birth Rate (LBR), and Miscarriage Rate (MR). Statistical analysis included one-way ANOVA for continuous and Pearson’s chi-squared test for categorical variables Main results and the role of chance Blastocyst characteristics, including morphological quality (characterised into ‘GOOD’, ‘FAIR’ and ‘POOR’) and day of biopsy (5 or 6), did not significantly differ between blastocyst transfers of the twice-thawed and control group. Furthermore, maternal factors including age, number of previous PGT-A attempts and endometrial thickness did not significantly differ between groups. However, compared with the control group, the number of eggs collected was significantly higher in the twice-thawed group (15.8±8.20 vs. 25.8±18.7, p = &amp;lt;0.001). The biopsy rate of previously cryopreserved embryos that underwent TBR was 79%. However, there was no significant difference between the survival rate after the second thaw and before SET between the twice-thawed and control groups. There was no difference in IRs (71.1% vs. 74.3%, p = 0.687) and LBRs (56.4% vs. 40.0%, p = 0.062) between groups. Although, compared to the control, MRs were significantly higher in the twice-thawed group (20.6% vs. 46.2% p = 0.003). Limitations, reasons for caution The twice-thawed group includes patients with diminished ovarian reserve, previously undergoing single freeze-thaw SET resulting in recurrent miscarriages. Thus, further research is essential to clarify whether elevated miscarriage rates result from repeated freeze-thaw cycles. Additionally, as single freeze-thaw SET is preferred, small sample size in the twice-thawed group limits conclusions. Wider implications of the findings This study suggests employing TBR on previously frozen blastocysts yields non-inferior IRs and LBRs, with an additional freeze-thaw cycle not adversely affecting embryo survival before SET. Therefore, such techniques should be considered in previously frozen IVF embryos to reduce wastage, mitigate unforeseen fertility complications, and concurrently achieve favourable pregnancy outcomes. Trial registration number Not applicable

O-039 Con - the faster the better

Abstract Late o’clock: Are slow growing embryos clinically usable? Con - the faster the better Reproductive medicine and, within it, embryology, have experienced milestones in the understanding of pre-implantation embryonic development over the last quarter of a century. The development of blastocyst culture media for embryo culture even after embryonic genome activation and the possibility of continuous monitoring of embryonic morphokinetics throughout the pre-implantation period have been major contributors. The development of molecular genetic techniques has also played an important role. The introduction of new cryopreservation techniques has also improved the success rate of the clinical use of surplus embryos, including slow-growing embryos not otherwise selected for fresh cycle transfer. Two questions are most frequently encountered in clinical embryology today: which embryo in a cohort has the best chance of resulting in a live-born child, and how slow and morphologically suboptimal can an embryo be to still be considered clinically useful? In particular, the latter question does not have an easy answer, as embryos demonstrate varying pace of development. A further problem arises if there are no optimal embryos available in the cohort and this answer has to be given on day 2, 3 or 5, as this is when the embryo transfer is scheduled to take place. Some studies suggest that longer timing of any stage of embryonic development from pronuclear fading onwards means that the embryo is late in development due to certain abnormalities and is likely to be energetically depleted by the activation of its repair mechanisms. Such embryos not only have a lower implantation potential compared to fast embryos, but also diverge in time from the optimal receptivity of the endometrium. Additional testing and/or storage of slow-growing embryos brings the question of their clinical usability to the time of frozen embryo replacement cycles and quiets the couple's expectation of a “successful” completion of the stimulated cycle. Whether embryos are to be selected for fresh ET or FER, the “the faster - the better” principle is likely to be applied. In daily clinical practice, decisions on the use of slow-growing and/or morphologically sub-optimal embryos and the timing of embryo transfer are made on an individual basis, taking into account various medical as well as non-medical (e.g. economic, logistical) factors. These may also include portraying a positive image of the centre's performance. However, patients expect infertility specialists to make realistic assessments not only of the viability of slow growing embryos, but also of the outcome of the transfer of them. The assessment must be based not only on medical and ethical but also on rational grounds.

International Committee for Monitoring Assisted Reproductive Technology world report: assisted reproductive technology, 2015 and 2016

ObjectiveTo report utilization, effectiveness, and safety of assisted reproductive technologies in 2015 and 2016. DesignRetrospective, cross-sectional survey of 3103 assisted reproductive technology clinics in 74 countries in 2015 and 3249 clinics in 79 countries in 2016 that submitted cycle and pregnancy outcome data through national and regional registries. SubjectsPatients undergoing assisted reproductive technology procedures. ExposureAssisted reproductive technology. Main Outcome MeasuresOutcomes on country, regional, and global levels. ResultsReported for 2015: 2,358,239 cycles with 548,652 babies born; for 2016: 2,807,963 cycles with 647,188 babies born. Estimated in 2015, ≥2,683,677 cycles resulted in >675,134 babies; in 2016, ≥3,100,448 cycles resulted in ≥723,026 babies. Reported cycles represent approximately 80% of global utilization. In 2015 and 2016, 27.6% and 27.8%, respectively, of women undergoing fresh autologous cycles were age ≥40 years. Frozen-thawed embryo transfer cycles accounted for 47.0% and 51.9%, respectively, of all embryo transfers in 2015 and 2016. Oocyte donation cycles accounted for 6.7% and 7.1% of all embryo transfers in 2015 and 2016. Intracytoplasmic sperm injection was performed in 57.7% and 56.4% of autologous aspiration cycles in 2015 and 2016, respectively. The cumulative delivery rate per aspiration cycle for fresh and frozen-thawed embryo transfer was 32.4% in 2015 and 33.1% in 2016, respectively. The average number of transferred embryos was 1.70 in 2015 and 1.69 in 2016. The proportion of single embryo transfers in fresh autologous cycles increased from 42.1% in 2015 to 44.0% in 2016. The twin delivery rate decreased from 16.0% in 2015 to 14.7% in 2016, and the triplet rate decreased from 0.6% in 2015 to 0.4% in 2016. The proportion of single embryo transfers in frozen-thawed embryo transfer autologous cycles was 62.2% in 2015 and 64.2% in 2016, with twin and triplet rates of 10.1% and 0.3% in 2015 and 10.0% and 0.2% in 2016, respectively. ConclusionUtilization of assisted reproductive technology and births per cycle increased from 2015 to 2016 while multiple births were reduced . Increasing proportion of frozen-thawed embryo transfer cycles, continuing wide variation in use of intracytoplasmic sperm injection, and increase in single embryo transfer rates are reported.

Trends and outcomes of fresh and frozen donor oocyte cycles in the United States

ObjectiveTo examine trends, characteristics, and outcomes of donor oocyte embryo transfer cycles by original oocyte and resultant embryo state and determine whether oocyte state (fresh or frozen) is differentially associated with clinical pregnancy, live birth, and term, normal birthweight neonates among singleton live births. DesignRetrospective cohort study SubjectsPatients undergoing donor oocyte embryo transfer cycles in the United States reporting to National Assisted Reproductive Technology Surveillance System (NASS) from 2013–2020 ExposureOriginal donor oocyte and resultant embryo state (fresh or frozen) Main Outcome MeasuresAnnual numbers and proportions of total donor oocyte embryo transfer cycles stratified by oocyte and embryo state and single embryo transfer cycles resulting in live birth of term (≥37 weeks gestation), normal birthweight (≥2500g) singletons during 2013–2020. Rates of live birth and term, normal birthweight neonates among singleton live births for 2018–2020 are also reported. Relative risks (RR) examine associations between donor oocyte state and live birth and term, normal birthweight neonates among singleton live births resulting from donor oocyte embryo transfer cycles. ResultsFrom 2013-2020, there were 135,085 donor oocyte embryo transfer cycles, of which the proportions increased for frozen embryos (42.3% to 76.6%), fresh embryos using frozen donor oocytes (19.9% to 68.3%) and single embryo transfer (SET) (36.4% to 85.5%). During 2018–2020, there were 48,679 donor oocyte embryo transfer cycles. Rates of live birth were lower with frozen compared to fresh donor oocytes for both fresh (46.2%, 55.9%; aRR 0.83 [95% CI 0.79–0.87]) and frozen (41.3%, 45.8%; aRR 0.94 [95% CI 0.91–0.98]) embryo transfer cycles. Among singleton live births, rates of delivering a term, normal birthweight neonate were similar for frozen compared to fresh donor oocyte transfer cycles among fresh (77.3, 77.2%; aRR 1.01 [95% CI 0.98–1.03]) and frozen (75.6, 75.1%; aRR 1.02 [95% CI 0.99–1.04]) embryos. ConclusionIn this national study of donor oocyte embryo transfer cycles, frozen embryo transfers, fresh embryo transfers using frozen oocytes, and SET increased. Although frozen compared to fresh oocytes were associated with a slightly reduced rate of live birth, rates of term, normal birthweight neonates among singleton live births were comparable between donor oocyte states.

A modified flexible GnRH antagonist protocol using antagonist early cessation and a gonadotropin step-down approach improves live birth rates in fresh cycles: a randomized controlled trial.

Can pregnancy outcomes following fresh elective single embryo transfer (eSET) in gonadotropin-releasing hormone (GnRH) antagonist protocols increase using a gonadotropin (Gn) step-down approach with cessation of GnRH antagonist on the day of hCG administration (hCG day) in patients with normal ovarian response? The modified GnRH antagonist protocol using the Gn step-down approach and cessation of GnRH antagonist on the hCG day is effective in improving live birth rates (LBRs) per fresh eSET cycle. Currently, there is no consensus on optimal GnRH antagonist regimens. Studies have shown that fresh GnRH antagonist cycles result in poorer pregnancy outcomes than the long GnRH agonist (GnRHa) protocol. Endometrial receptivity is a key factor that contributes to this phenomenon. An open label randomized controlled trial (RCT) was performed between November 2021 and August 2022. There were 546 patients allocated to either the modified GnRH antagonist or the conventional antagonist protocol at a 1:1 ratio. Both IVF and ICSI cycles were included, and the sperm samples used were either fresh or frozen from the partner, or from frozen donor ejaculates. The primary outcome was the LBRs per fresh SET cycle. Secondary outcomes included rates of implantation, clinical and ongoing pregnancy, miscarriage, and ovarian hyperstimulation syndrome (OHSS), as well as clinical outcomes of ovarian stimulation. Baseline demographic features were not significantly different between the two ovarian stimulation groups. However, in the intention-to-treat (ITT) population, the LBRs in the modified antagonist group were significantly higher than in the conventional group (38.1% [104/273] vs. 27.5% [75/273], relative risk 1.39 [95% CI, 1.09-1.77], P = 0.008). Using a per-protocol (PP) analysis which included all the patients who received an embryo transfer, the LBRs in the modified antagonist group were also significantly higher than in the conventional group (48.6% [103/212] vs. 36.8% [74/201], relative risk 1.32 [95% CI, 1.05-1.66], P = 0.016). The modified antagonist group achieved significantly higher implantation rates, and clinical and ongoing pregnancy rates than the conventional group in both the ITT and PP analyses (P < 0.05). The two groups did not show significant differences between the number of oocytes retrieved or mature oocytes, two-pronuclear zygote (2PN) rates, the number of embryos obtained, blastocyst progression and good-quality embryo rates, early miscarriage rates, or OHSS incidence rates (P > 0.05). A limitation of our study was that the subjects were not blinded to the treatment allocation in the RCT trial. Only women under 40 years of age who had a good prognosis were included in the analysis. Therefore, use of the modified antagonist protocol in older patients with a low ovarian reserve remains to be investigated. In addition, the sample size for Day 5 elective SET was small, so larger trials will be required to strengthen these findings. The modified GnRH antagonist protocol using the Gn step-down approach and cessation of GnRH antagonist on hCG day improved the LBRs per fresh eSET cycle in normal responders. This project was funded by grant 2022YFC2702503 from the National Key Research & Development Program of China and grant 2021140 from the Beijing Health Promotion Association. The authors declare no conflicts of interest. The RCT was registered in the Chinese Clinical Trial Registry; Study Number: ChiCTR2100053453. 21 November 2021. 23 November 2021.

Nomogram to predict the probability of clinical pregnancy in women with poor ovarian response undergoing in vitro fertilization/ intracytoplasmic sperm injection cycles.

Poor ovarian response (POR) is associated with decreased clinical pregnancy rates, emphasizing the need for developing clinical prediction models. Such models can improve prognostic accuracy, personalize medical interventions, and ultimately enhance live birth rates among patients with POR. This study aims to develop and validate a prognostic model for predicting clinical pregnancy outcomes in individuals with POR undergoing in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI) cycles. A retrospective cohort of 969 patients with POR undergoing fresh embryo transfer cycles at the Reproductive Center of Fujian Maternal and Child Health Center from January 2018 to January 2022 was included. The cohort was randomly divided into model (n = 678) and validation (n = 291) groups in a 7:3 ratio. A single-factor analysis was performed on the model group to identify variables influencing clinical pregnancy. Optimal variables were selected using LASSO regression, and a clinical prediction model was constructed using multivariate logistic regression analysis. The model's calibration and discrimination were assessed using receiver operating characteristic (ROC) and calibration curves, while the clinical utility was evaluated using decision curve analysis. Multivariate logistic regression analysis revealed that the age of the women (odds ratio [OR] 0.936, 95% confidence interval [CI] 0.898-0.976, P = 0.002), body mass index (BMI) ≤ 24 (OR 2.748, 95% CI 1.724-4.492, P < 0.001), antral follicle count (AFC) (OR 1.232, 95% CI 1.073-1.416, P = 0.003), anti-Müllerian hormone (AMH) (OR 1.67, 95% CI 1.178-2.376, P = 0.004), number of mature oocytes (OR 1.227, 95% CI 1.075-1.403, P = 0.003), number of embryos transferred (OR 1.692, 95% CI 1.132-2.545, P = 0.011), and transfer of high-quality embryos (OR 3.452, 95% CI 1.548-8.842, P = 0.005) were independent predictors of clinical pregnancy in patients with POR. According to the receiver operating characteristic (ROC) analysis, the prediction model exhibited an area under the curve (AUC) of 0.752 (0.714, 0.789) in the model group and 0.765 (0.708, 0.821) in the validation group. The clinical decision curve demonstrated that the model held maximum clinical utility in both cohorts when the threshold probability of clinical pregnancy ranged from 6-81% to 12-82%, respectively. Clinical pregnancy outcomes in patients with POR who underwent IVF/ICSI treatment were influenced by several independent factors, including the age of the women, BMI, AFC, AMH, number of mature oocytes, number of embryos transferred, and transfer of high-quality embryos. A clinical prediction model based on these factors exhibited favorable clinical predictive and applicative value. Therefore, this model can serve as a valuable tool for clinical prognosis, intervention, and facilitating personalized medical treatment.

Comparison of luteal support protocols in fresh IVF/ICSI cycles: a network meta-analysis

Despite the proven superiority of various luteal phase support protocols (LPS) over placebo in view of improved pregnancy rates in fresh cycles of IVF (in vitro fertilization) and ICSI (intracytoplasmic sperm injection) cycles, there is ongoing controversy over specific LPS protocol selection, dosage, and duration. The aim of the present study was to identify the optimal LPS under six core aspects of ART success, clinical pregnancy, live birth as primary outcomes and biochemical pregnancy, miscarriage, multiple pregnancy, ovarian hyperstimulation syndrome (OHSS) events as secondary outcomes. Twelve databases, namely Embase (OVID), MEDLINE (R) (OVID), GlobalHealth (Archive), GlobalHealth, Health and Psychosocial Instruments, Maternity & Infant Care Database (MIDIRS), APA PsycTests, ClinicalTrials.gov, HMIC Health Management Information Consortium, CENTRAL, Web of Science, Scopus and two prospective registers, MedRxiv, Research Square were searched from inception to Aug.1st, 2023, (PROSPERO Registration: CRD42022358986). Only Randomised Controlled Trials (RCTs) were included. Bayesian network meta-analysis (NMA) model was employed for outcome analysis, presenting fixed effects, odds ratios (ORs) with 95% credibility intervals (CrIs). Vaginal Progesterone (VP) was considered the reference LPS given its’ clinical relevance. Seventy-six RCTs, comparing 22 interventions, and including 26,536 participants were included in the present NMA. Overall CiNeMa risk of bias was deemed moderate, and network inconsistency per outcome was deemed low (Multiple pregnancy χ2: 0.11, OHSS χ2: 0.26), moderate (Clinical Pregnancy: χ2: 7.02, Live birth χ2: 10.95, Biochemical pregnancy: χ2: 6.60, Miscarriage: χ2: 11.305). Combinatorial regimens, with subcutaneous GnRH-a (SCGnRH-a) on a vaginal progesterone base and oral oestrogen (OE) appeared to overall improve clinical pregnancy events; VP + OE + SCGnRH-a [OR 1.57 (95% CrI 1.11 to 2.22)], VP + SCGnRH-a [OR 1.28 (95% CrI 1.05 to 1.55)] as well as live pregnancy events, VP + OE + SCGnRH-a [OR 8.81 (95% CrI 2.35 to 39.1)], VP + SCGnRH-a [OR 1.76 (95% CrI 1.45 to 2.15)]. Equally, the progesterone free LPS, intramuscular human chorionic gonadotrophin, [OR 9.67 (95% CrI 2.34, 73.2)] was also found to increase live birth events, however was also associated with an increased probability of ovarian hyperstimulation, [OR 1.64 (95% CrI 0.75, 3.71)]. The combination of intramuscular and vaginal progesterone was associated with higher multiple pregnancy events, [OR 7.09 (95% CrI 2.49, 31.)]. Of all LPS protocols, VP + SC GnRH-a was found to significantly reduce miscarriage events, OR 0.54 (95% CrI 0.37 to 0.80). Subgroup analysis according to ovarian stimulation (OS) protocol revealed that the optimal LPS across both long and short OS, taking into account increase in live birth and reduction in miscarriage as well as OHSS events, was VP + SCGnRH-a, with an OR 2.89 [95% CrI 1.08, 2.96] and OR 2.84 [95% CrI 1.35, 6.26] respectively. Overall, NMA data suggest that combinatorial treatments, with the addition of SCGnRH-a on a VP base result in improved clinical pregnancy and live birth events in both GnRH-agonist and antagonist ovarian stimulation protocols.