Biochemical Pregnancy Rate Research Articles

COVID-19 Vaccines and Assisted Reproductive Techniques: A Systematic Review.

Objective: To review the current knowledge concerning COVID-19 vaccination and assisted reproductive techniques (ART). Methods: A systematic review in Pubmed-Medline, the Cochrane Database, the Web of Science, and the National Guideline was performed. Studies were selected if they were primary studies, included vaccinated (case) and unvaccinated (control) patients, and described fertility treatment response. Results: A total of 24 studies were selected. Outcomes related to the association between COVID-19 vaccination and ART were collected. The vast majority of studies found no statistical differences concerning oocyte stimulation response, embryo quality, implantation rates, or pregnancy outcome (clinical or biochemical pregnancy rates and losses) when comparing cases and controls. Similarly, no differences were found when comparing different types of vaccines or distinct ART (artificial insemination, in vitro fertilization, and embryo transfer of frozen embryos). Conclusions: Patients receiving ART and health care professionals should be encouraged to complete and recommend COVID-19 vaccination, as the available evidence regarding assisted reproductive outcomes is reassuring.

The time interval between laparoscopic tubal ligation and frozen-thawed embryo transfer does not affect the reproductive outcomes

BackgroundHydrosalpinx may decrease implantation and pregnancy rates after embryo transfer. Laparoscopic tubal ligation after embryo freeze and before frozen-thawed embryo transfer (FET) is effective at improving reproductive outcomes for hydrosalpinx patients. This study is to find out the optimal interval between laparoscopic tubal ligation and FET.MethodsWe retrospectively analyzed 259 infertile women who performed laparoscopic tubal ligation for embryo freeze and FET. Participants were divided into three groups, based on the interval between laparoscopic tubal ligation and FET. Group I: <30 days; Group II: 31– 60 days; Group III: >60 days. Outcomes of cleavage-stage and blastocyst-stage embryo FET were analyzed respectively.ResultsThere was no significant difference in clinical pregnancy rate, live birth rate, implantation rate, biochemical pregnancy rate, ectopic pregnancy rate, miscarriage rate and preterm birth rate among the three groups, in both cleavage-stage and blastocyst-stage embryo FET cycles. In cleavage-stage embryo FET cycle, singleton gestational age was significantly younger in group III (38.11 ± 2.28 weeks) compared with group I (39.29 ± 1.06 weeks, P = 0.001) and group II (38.96 ± 1.05, P = 0.026). Singleton birth weight was significantly heavier in group II (3.65 ± 0.32 Kg) compared with group I (3.38 ± 0.29 Kg, P = 0.001) and group III (3.35 ± 0.60 Kg, P = 0.004). Twin birth weight was significantly heavier in group III (2.72 ± 0.43 Kg) compared to group I (2.23 ± 0.67 Kg, P = 0.002). In blastocyst-stage embryo FET cycles, twin gestational age was significantly younger in group II (34.07 ± 3.18 weeks) compared with group I (35.56 ± 2.27 weeks, P = 0.049) and group III (36.50 ± 1.47 weeks, P = 0.005). Twin birth weight was significantly heavier in group III (2.71 ± 0.39 Kg) compared to group II (2.39 ± 0.67 Kg, P = 0.009).ConclusionsThe duration of the interval between laparoscopic tubal ligation and FET does not affect the reproductive outcomes; however, it may affect the neonate outcomes to some extent.

COVID-19 infection after oocyte retrieval did not have detrimental effects on embryo implantation for frozen embryo transfer.

Patients preparing for their renewal fertility treatments with embryos frozen before coronavirus disease 2019 (COVID-19) infection do not need to be concerned about the potential impact of COVID-19 infection on oocyte quality and embryonic development. However, many women are still hesitant to undergo frozen embryo transfer (FET) due to fear of the detrimental effect of COVID-19 infection on endometrial receptivity and embryo implantation. The objective was to explore whether COVID-19 infection after oocyte retrieval is related to an increased risk of adverse pregnancy outcomes in a cohort of Chinese women undergoing FET. A retrospective cohort study was conducted among 300 infertile women undergoing FET with embryos frozen before COVID-19 infection. Women were categorized into noninfection, infection before FET, or infection after FET groups. Multivariable logistic regression was performed to assess the association of COVID-19 infection with clinical pregnancy outcomes, including biochemical pregnancy, clinical pregnancy, and early miscarriage. The implantation rates for patients in the group with infection before FET (29.14%) and the group with infection after FET (30.38%) were not significantly lower than those in the noninfection group (31.03%). The rate of biochemical pregnancy (54.55% vs. 52.27%, p = 0.750; 43.14% vs. 52.27%, p = 0.209) was not significantly different among the three groups. Although the clinical pregnancy rate showed a declining trend from 45.45% in the noninfection group to 38.27% in the group with infection after FET, this result was not statistically significant. The early miscarriage rate was similar in the group with infection before FET and the group with infection after FET compared with that in the noninfection group (3.64% vs. 5.68%, p = 0.496; 6.86% vs. 5.68%, p = 0.739). After adjusting for potential confounders, the biochemical pregnancy rate, clinical pregnancy rate, and early miscarriage rate were not significantly different for patients with infection before or after FET compared with patients without infection. This research indicated that COVID-19 infection after oocyte retrieval with embryos frozen before infection did not cause any detrimental effect on endometrial receptivity for embryo implantation.

Pregnancy outcomes after vaginal probiotic supplementation before frozen embryo transfer: a randomized controlled study

In women receiving assisted reproductive treatment, intrauterine lactobacilli dominance has been associated with higher rates of pregnancy achievement. This randomized controlled trial conducted in the fertility clinic of the university hospital from 7 August 2019 to May 2021, aimed to compare the clinical outcome of embryo transfer in frozen-thaw cycles with Lactobacillus supplementation prior to embryo transfer and the standard treatment. A total of 340 infertile women underwent randomization. The biochemical and clinical pregnancy rates were comparable between the groups (39.9 and 34.2% in the study group vs. 41.8 and 31.7% in the control group); however, the miscarriage rate was significantly decreased in the study group (9.5 vs. 19.1%, respectively, p = 0.02), [OR = 0.44, 95% CI (0.23, 0.86)]. Among 49 women diagnosed with bacterial vaginosis, the live birth rate in the study group was higher than the control group (42.31 vs. 26.09%, p = 0.23), [OR = 2.08, 95% CI (0.62, 6.99)]. In the blastocyst transfer group (n = 206), the live birth rate was significantly higher in the study group than in the control group (35.71 vs. 22.22%, p = 0.03) [OR = 1.9, 95% CI (1.05, 3.59)]. Therefore, intravaginal lactobacilli supplementation before embryo transfer in the frozen-thaw cycle did not improve the biochemical and clinical pregnancy rate in the general population but significantly reduced the miscarriage rate.Trial Registration: TCTR20190429001 (29/04/2019) @ www.thaiclinicaltrials.org.

Dual trigger improves the pregnancy rate in fresh in vitro fertilization (IVF) cycles compared with the human chorionic gonadotropin (hCG) trigger: a systematic review and meta-analysis of randomized trials.

The purpose of this study was to assess whether the implementation of a "dual trigger" approach, utilizing gonadotropin-releasing hormone agonist (GnRHa) and human chorionic gonadotropin (hCG) in the GnRH antagonist protocol for in vitro fertilization (IVF), leads to improved pregnancy outcomes compared to the conventional hCG trigger alone. Previous meta-analyses have not provided sufficient evidence to support the superiority of the dual trigger over the hCG trigger in fresh or frozen embryo transfer cycles. Thus, a systematic review and meta-analysis of randomized trials were conducted to provide a comprehensive evaluation of the impact of the dual trigger on pregnancy outcomes in fresh or frozen embryo transfer cycles. A systematic review and meta-analysis of randomised controlled trials (RCTs) were conducted. We searched the Medline and Embase databases for articles up to 2023 by using search terms: "dual trigger," "GnRHa," "hCG," "IVF." Eligible RCTs comparing the dual trigger with the hCG trigger were included. The primary outcome was the live birth rate (LBR) per cycle. The secondary outcomes were the number of oocytes retrieved, number of mature oocytes retrieved, implantation rate, biochemical pregnancy rate, CPR, miscarriage rate and ovarian hyperstimulation syndrome (OHSS) rate per started cycle We compared the oocyte maturation and pregnancy outcomes in the dual trigger and hCG trigger groups. In patients undergoing fresh embryo transfer (ET) and frozen-thawed ET, we also conducted a subgroup analysis to evaluate whether dual trigger improves the clinical pregnancy rate (CPR). We included 10 randomised studies, with 825 participants in the dual trigger group and 813 in the hCG trigger group. Compared with the hCG trigger, dual trigger was associated with a significant increase in the LBR per cycle (odds ratio (OR) = 1.61[1.16, 2.25]), number of oocytes retrieved (mean difference [MD] = 1.05 [0.43, 1.68]), number of mature oocytes retrieved (MD = 0.82 [0. 84, 1.16]), and CPR (OR = 1.48 [1.08, 2.01]). Subgroup analyses revealed that dual trigger was associated with a significantly increased CPR in patients who received fresh ET (OR = 1.68 [1.14, 2.48]). By contrast, the dual trigger was not associated with an increased CPR in the patient group with frozen-thawed ET (OR = 1.15 [0.64, 2.08]). The dual trigger was associated with a significantly higher number of retrieved oocytes, number of mature oocytes, CPR, and LBR in IVF than the hCG trigger. The beneficial effect for fresh ET cycles compared with frozen-thawed ET might be associated with increased endometrial receptivity. After dual trigger, delaying ET due to the concern of endometrial receptivity might not be needed.

Clinical pregnancy rate for frozen embryo transfer with HRT: a randomized controlled pilot study comparing 1 week versus 2 weeks of oestradiol priming

Research questionDoes a frozen-embryo transfer in an artificially-prepared endometrium (FET-HRT) cycle yield similar clinical pregnancy rate with 7 days of oestrogen priming compared to 14 days?DesignThis is a single-centre, randomized, controlled, open-label pilot study. All FET-HRT cycles were performed in a tertiary centre between October 2018 and January 2021. Overall, 160 patients were randomized, with a 1:1 allocation, into two groups of 80 patients each: group A (7 days of E2 prior to P4 supplementation) and group B (14 days of E2 prior to P4 supplementation). Both groups received single blastocyst stage embryos on the 6th day of vaginal P4 administration. The primary outcome was the feasibility of such strategy assessed as clinical pregnancy rate, secondary outcomes were biochemical pregnancy rate, miscarriage rate, live birth rate and serum hormone levels on the day of FET. Chemical pregnancy was assessed by an hCG blood test 12 days after FET and clinical pregnancy was confirmed by transvaginal ultrasound at 7 weeks.ResultsThe analysis included 160 patients who were randomly assigned to either group A or group B on the seventh day of their FET-HRT cycle if the measured endometrial thickness was above 6.5 mm. Following screening failures and of drop-outs, 144 patients were finally included both in group A (75 patients) or group B (69 patients). Demographic characteristics for both groups were comparable. The biochemical pregnancy rate was 42.5% and 48.8% for group A and group B, respectively (p 0.526). Regarding the clinical pregnancy rate at 7 weeks, no statistical difference was observed (36.3% vs 46.3% for group A and group B, respectively, p = 0.261). The secondary outcomes of the study (biochemical pregnancy, miscarriage, and live birth rate) were comparable between the two groups for IIT analysis, as well as the P4 values on the day of FET.ConclusionsIn a frozen embryo transfer cycle, performed with artificial preparation of the endometrium, 7 versus 14 days of oestrogen priming are comparable, in terms of clinical pregnancy rate; the advantages of a seven-day protocol include the shorter time to pregnancy, reduced exposure to oestrogens, and more flexibility of scheduling and programming, and less probability to recruit a follicle and have a spontaneous LH surge. It is important to keep in mind that this study was designed as a pilot trial with a limited study population as such it was underpowered to determine the superiority of an intervention over another; larger-scale RCTs are warranted to confirm our preliminary results.Trial registrationClinical trial number: NCT03930706.

Acupuncture benefits to women with recurrent implantation failure: A propensity score-matched cohort study

ObjectivesThe current study aims to assess the effectiveness of acupuncture in improving the live birth rate (LBR), ongoing pregnancy rate (OPR), clinical pregnancy rate (CPR), biochemical pregnancy rate (BPR), and pregnancy loss (early abortion rate, late abortion rate, ectopic pregnancy rate) in patients with recurrent implantation failure (RIF). DesignThis retrospective study compares the outcomes of patients with RIF who underwent frozen embryo transfer (FET) with or without acupuncture. SettingThe medical records of patients diagnosed with RIF and visiting Chengdu Xi'nan Gynecological Hospital between January 2018 and June 2021 were reviewed. The Chengdu Xi'nan Gynecological Hospital Ethics Committee approved this retrospective study (No. 2021–029). ParticipantsA total of 923 patients with RIF who underwent FET were included in this study. The patients were divided into two groups: the Acupuncture (n = 303) and the Non-acupuncture groups (n = 620). ExposureThe Acupuncture group consisted of 303 RIF patients who received acupuncture therapy in addition to standard hormone replacement therapy (HRT)/delayed hormone replacement therapy (d-HRT) for FET. The Non-acupuncture group consisted of 620 RIF patients who received only standard HRT/d-HRT for FET. Primary and secondary outcome measuresThe primary outcome was the LBR. The secondary outcome referred to OPR, CPR, BPR, and pregnancy loss. ResultsThe Acupuncture group had significantly higher BPR (P = 0.08) and CPR (P = 0.049) than the Non-acupuncture group. A potentially higher LBR (P = 0.16) and OPR (P = 0.248) were observed in the Acupuncture group than in the Non-acupuncture group. However, the survival analysis did not show that acupuncture significantly promoted live birth. ConclusionsAcupuncture is an appropriate adjunctive technique in the in vitro fertilization process as it improves biochemical and clinical pregnancies. Therefore, it is necessary to be cautious about the role of acupuncture throughout the whole pregnancy cycle.

Fresh vs. frozen embryo transfer in assisted reproductive techniques: a single center retrospective cohort study and ethical-legal implications.

Several studies have shown higher pregnancy rates and better perinatal outcomes with frozen embryo transfers than with fresh techniques, with better results in patients with polycystic ovary syndrome (PCOS) but with a higher rate of pregnancy complications such as preeclampsia. This retrospective cohort study aims to compare the cumulative live birth rates, maternal and neonatal complications of fresh embryo transfers (ET) and frozen-embryo transfers (FET) in infertile women who underwent assisted reproduction techniques (ART) at the Azienda Ospedaliera Ospedali Riuniti(AOOR) Villa Sofia Cervello, Palermo, Italy. In addition, the authors have focused on the legislative and ethical complexities which such a procedure entails. Out of 475 women undergoing in vitro fertilization programs from January 2017 to January 2021, 128 were enrolled; 70 patients underwent ET, and 58 patients FET. The main outcome measure was live birth rates. Secondary outcomes were clinical pregnancy, ongoing pregnancy, pregnancy loss, low birth weight (LBW), ectopic pregnancy, and obstetrical and perinatal complications. The cumulative live birth rates were similar between the fresh transfer (95.7%) and frozen transfer (93.1%). Biochemical pregnancy rates, clinical pregnancy, ongoing pregnancy, and pregnancy loss were similar between the groups. Obstetrical outcomes were not statistically different between the two groups; a higher preterm delivery rate was reported in the FET group. ET birth weights were notably lower for singletons compared to the freeze-all strategy. ET patients also had higher LBW rates, with a 2.5-fold higher rate compared to FET. No significant differences were found in cumulative live birth rates between ET and FET, which is consistent with earlier studies. FET protocols are linked to higher neonatal birth weight and lower risk of LBW than fresh ET. The ethical and legal quandaries inherent in such techniques, as technology moves on and outpaces current legislative frameworks, cannot be discounted.

P-537 Intentional endometrial injury significantly improves ongoing pregnancy rates of an oocyte donation program in patients without recurrent implantation failure (RIF): a randomized controlled trial.

Abstract Study question Is endometrial scratching a useful add-on to be applied in assisted reproduction patients without recurrent implantation failure (RIF)? Summary answer Endometrial scratching results in significantly higher clinical and ongoing pregnancy rates per intention to treat (ITT) among women undergoing oocyte donation without RIF. What is known already The effect of endometrial injury or endometrial scratch (ES) on reproductive outcomes has been widely studied by randomized controlled trials but from the information obtained regarding its benefit on improving endometrial receptivity remains controversial. Oocyte donation programs (OD) provides with the ideal setting for this research, as the recipient's endometrial priming guarantees the homogeneity of the endometrium avoiding a deleterious differential effect of the stimulation on endometrial receptivity and makes comparable the quality of the oocytes and transferred embryos, then limiting the confounding factors involved in studies with autologous oocytes and their frozen surplus embryos, better addressing the research question. Study design, size, duration A multicentric, open-label, randomized controlled trial has been conducted in a private setting from Oct 2013-Nov 2022. Eligible recipients were randomly assigned in a 1:1 ratio to either ES (by pipelle biopsy in the luteal phase of the menstrual cycle prior to the embryo transfer, n = 303) or no intervention (NES, n = 310), through a computer-generated randomization list, and embryo transfers (ET) performed in the cycle following the intervention. Participants/materials, setting, methods 18-44 years aged ovum recipients with preserved ovarian function, 19-29.9 kg/m2, first/ second OD fresh embryo transfer, endometrial thickness &amp;gt; 6 mms, and 1-2 optimal quality blastocysts transferred. Exclusion: any adverse condition, RIF with OD, ET not performed in the cycle following the intervention. Outcomes included ongoing implantation rate (ongoing sacs/ embryo transferred), biochemical, clinical and ongoing pregnancy rates analyzed per ITT basis and per protocol strictly completed (PP, treatment correctly received, embryo transfer achieved). Main results and the role of chance A total number of 458 recipients underwent OD-embryo transfer, 226 in scratching arm and 232 in the NES group. No differences existed in mean age and BMI of recipients and oocyte donors, oocytes retrieved and microinjected, fertilization rates, blastocysts transferred, endometrial thickness and estradiol /progesterone levels after their endometrial priming, nor other clinically relevant parameters. The biochemical pregnancy rate was 62.6%95%CI(56.6-68.3) and 55.6%95%CI(49.7-61.3) in the ES arm and in NES arm on the ITT analysis (OR 1.073 95%CI(0.990-1.163), p = 0.088); and 75.3%95%CI(69.0-80.7) vs. 70.7%95%CI(64.3-76.4), respectively PP (OR1.048 95%CI(0.965-1.137), p = 0.266. The clinical pregnancy rate was 57.1%95%CI(51.0-63.1) and 47.5% 95%CI(41.7-53.3) in the ES arm and in NES arm on the ITT analysis (OR = 1.102 95%CI(1.015-1.196); p = 0.021), and in the per protocol analysis, 68.6% 95%CI(62.0-74.6) vs 60.3%95%CI(53.7-66.6) respectively, OR = 1.086 95%CI(0.995-1.186), p = 0.066. The ongoing pregnancy rate was 45.1%95%CI(39.1-51.2) and 36.3% 95%CI(30.8-42.1) in the ES arm and in NES arm on the ITT analysis (OR = 1.092 95%CI(1.007-1.183); p = 0.033), and in the per protocol analysis, 53.8%95%CI(47.0-60.5) vs 46.1%95%CI(39.6-52.8) respectively, OR = 1.080 95%CI(0.985-1.184), p = 0.101. The ongoing implantation rate was in the PP analysis, 61.4%95%CI(55.1-67.8) in ES, and 56.5%95%CI(50.1-68.2) in NES respectively, p = 0.276, while in the ITT analysis, 51.3% 95%CI(45.4-57.2) vs 44.4% 95%CI(38.7-50.1), p = 0.098 in the ES arm and in NES arm. Limitations, reasons for caution The number of patients not fulfilling the complete procedure probably avoided to find significant differences on the PP analysis, and during the study, there may be some clinical and/or laboratory changes through the years, that should have been affecting outcomes on both groups. Wider implications of the findings This RCT shows that ES in the luteal phase of the cycle preceding the OD embryo transfer in recipients without RIF would pose a significant benefit thus its consideration for all IVF patients can be advised at this point. Trial registration number NCT01955356

P-161 Impact of physical activity (PA) on oocyte quality: a prospective study among IVF/ICSI patients

Abstract Study question To determine if various levels of PA have an influence on oocyte quality, ovarian response to controlled stimulation and IVF/ICSI success rate. Summary answer Globally, PA has no influence on ovarian response in IVF cycles. However, in certain subgroups (endometriosis, disovulation, normal-BMI) high PA is associated with higher response. What is known already Lifestyle is considered a key factor concerning health. According to WHO, moderate PA is an effective way to lower the risk of many pathologic conditions, although the impact of PA on female fertility is still unknown. There is scientific evidence that vigorous exercise can be detrimental for female fertility Studies evaluating the effect of PA on oocyte quality are lacking. However, murine models show that PA may have a positive impact on it. Study design, size, duration Prospective observational study. PA was evaluated before the IVF cycle, using the International PA Questionnaire (IPAQ) (n = 617), assessing frequency and duration of PA in the previous week, and using accelerometer (n = 102). Mean age of women was 35. Patients were classified into three levels of PA: low, moderate, high. The following outcome measures were analysed: number of collected oocytes, mature oocytes, ovarian response, biochemical pregnancy rate. Size: 617 infertile women undergoing IVF/ICSI cycles January 2019 - October 2020 Participants/materials, setting, methods 617 participants voluntarily fulfilled the IPAQ prior to IVF/ICSI cycle. Ethical approval was obtained from the Clinical Research Ethics Committee (CEIC E19/06). IPAQ’s results were measured in metabolic equivalent of task (METs-min/week) (Walking = 3.3 METs; Moderate PA = 4 METs; Vigorous PA = 8 METs). 1 MET = resting metabolic rate. In 102 participants PA was objectively measured for 7 consecutive days, prior to IVF cycle, using triaxial accelerometry. Setting: Human Reproduction Unit of a Universitary Hospital (Spain) Main results and the role of chance The number of collected oocytes was similar in all three groups according IPAQ (9.23 ± 7.72; 8.35 ± 5.57; 8.82 ± 6.38). Something similar happened with the number of mature oocytes (MII) (6.97 ± 5.99; 6.84 ± 4.85; 7.05 ± 5.61) and fertilized oocytes (3.72 ± 3.84; 4.16 ± 3.35; 3.98 ± 3.88). Biochemical pregnancy rate was slightly superior in high PA vs moderate vs low (38% vs 34.8% vs 29%), but without statistical significance. In the subgroup of patients having endometriosis the number of MII oocytes was significantly superior in high and moderate vs low PA (p = 0.024). In the group of disovulating women there were also more MII oocytes in high vs moderate vs low PA (p = 0.038). When performing the analysis according to accelerometer, even though the number of total collected oocytes (9.93 ± 9.1; 7.93 ± 5.38), MII oocytes (8.36 ± 7.64; 6.79 ± 4.63) and fertilized oocytes (5.25 ± 6.41; 3.91 ± 2.82), tended to be slightly superior in high vs moderate PA, there were no significant differences. In women with normal BMI, high PA was associated with a greater number of collected oocytes (p = 0.005), MII oocytes (p = 0.004) and fertilized oocytes (p = 0.007). Limitations, reasons for caution This study was performed in infertile women undergoing IVF/ICSI cycles. Hence, it is not possible to determine if PA has an impact on natural fertility. The self-administration of IPAQ has some disadvantages as subjectivity, memory bias or overestimation of PA. Subgroups’ sample size was small. Wider implications of the findings In general it does not seem that modifying short-term PA in women undergoing IVF could improve oocyte quality. However in some subgroups of patients (endometriosis, disovulation, normal-weight women), perhaps changes in PA could improve oocyte quality and ART success rates. More prospective clinical studies are needed. Trial registration number Not applicable

O-024 Exploring the optimal transfer day of day 6 (D6) vitrified blastocysts in Hormone Replacement Therapy Frozen Embryo Transfer (HRT-FET) cycles - a cohort study

Abstract Study question Should blastocysts cryopreserved D6 be transferred on the 5th or 6th day of progesterone administration in HRT-FET cycles? Summary answer No significant differences in outcome parameters were found when D6 vitrified blastocysts were transferred on either day 5 or day 6 of progesterone in HRT-FET. What is known already Several studies have shown that D6 blastocyst transfer should be avoided in fresh transfer IVF cycles; consequently, these more slowly developing embryos are transferred in a HRT-FET cycle on the 6th day of progesterone administration in line with day 5 (D5) blastocysts. For successful implantation, a receptive endometrium and optimal synchronization between the endometrium and embryo are important. However, no definitive evidence exists regarding the optimal timing of transferring D6 blastocysts. Interestingly, a few studies have reported better reproductive outcomes if D6 blastocysts are transferred on the 5th day of progesterone administration instead of the 6th day of progesterone administration. Study design, size, duration This cohort study included a total of 718 vitrified D6 single blastocyst HRT-FET cycles performed between 2013 and 2022. 576 blastocysts were transferred on the 6th day of progesterone administration (2013-2021), and 142 blastocysts transferred on the 5th day of progesterone administration (2021-2022). Main outcomes were biochemical pregnancy rate (PR), implantation rate (IR), clinical pregnancy rate (CPR), and early pregnancy loss rate (EPLR). Participants/materials, setting, methods Patients undergoing HRT-FET in a public Fertility Clinic. Endometrial preparation included oral oestradiol (6mg/24hours), followed by vaginal micronized progesterone. As mentioned above, single blastocyst transfer was performed on either the 5th or 6th day of progesterone administration. Serum β-hCG level was measured 9-11 days after embryo transfer and biochemical pregnancy was defined as an hCG level &amp;gt;10 IU/L. Clinical pregnancy was defined as visualization of a gestational sac and fetal heartbeat in gestational week 7. Main results and the role of chance In this cohort of a total of 718 HRT-FET cycles transferred on either the 5th or 6th day of progesterone administration the mean age of the patients at embryo transfer was 34.5±4.5 years vs. 33.0±4.9 years, respectively, p = 0.30. There was no significant difference between numbers of top-quality blastocyst transfers within the two groups 63% (89/142) vs. 64% (369/576), p = 0.76. The overall, biochemical pregnancy rate (PR), implantation rate (IR), clinical pregnancy rate (CPR) and early pregnancy loss (EPLR) in the group of patients transferred on the 5th day of progesterone administration were 38% (54/142), 29% (41/142), 25% (36/142) and 33% (18/54). In the group of patients transferred on the 6th day of progesterone administration 41% (235/576), 33% (191/576), 30% (170/576) and 28% (65/235). There were no significant differences between PR, IR, CPR and EPLR when transferring D6 vitrified blastocysts on either the 5th or the 6th day of progesterone administration (38% vs. 41%, p = 0.53, 29% vs. 33%, p = 0.33, 25% vs. 30%, p = 0.33 and 33% vs. 28%, p = 0.41). Limitations, reasons for caution Limitations of the study are the retrospective design and the limited number of D6 vitrified blastocysts transferred on the 5th day of progesterone administration. Furthermore, the two groups represented two different time periods. Wider implications of the findings Growing evidence shows that D5 vitrified blastocysts have better reproductive outcomes than slower developing embryos which are vitrified on day 6. Whether this is caused by intrinsic embryonic factors or poor timing of transfer in a subsequent FET cycle still needs to be unraveled. Trial registration number not applicable

P-097 Embryological and Clinical Outcomes of Microdissection testicular sperm extraction combined with Intracytoplasmic sperm injection (microTESE-ICSI) in patients with and without Klinefelter syndrome

Abstract Study question This retrospective study aims to identify the embryo development and clinical outcomes in non-mosaic Klinefelter syndrome patients treated with microTESE-ICSI Summary answer Non-mosaic Klinefelter patients can retrieve their sperm using microTESE and can have their biological offsprings by combining microTESE with ICSI What is known already Klinefelter syndrome patients are classified into two main groups, namely non-mosaic Klinefelter (47, XXY) and mosaic Klinefelter (46, XY/47, XXY). To retrieve sperm from non-mosaic Klinefelter, microTESE is a crucial treatment that yields a successful rate of approximately 50%. Recent research reports that microTESE-ICSI is a treatment regime that brings a higher in-vitro fertilization (IVF) success rate for those with non-mosaic Klinefelter syndrome. However, most of the previous studies on this group focuses on sperm retrieval rate and male factors. Few studies have reported embryo development and clinical outcomes, especially, under the adjustment for female partner’s age and oocyte quantity Study design, size, duration This retrospective study was conducted to evaluate spermatozoa retrieval, embryo development, and clinical outcomes in 931 patients with microTESE treatment at Andrology and Fertility Hospital of Hanoi from 6/2019 to 9/2022. Patients were divided into two groups including 118 patients with non-mosaic Klinefelter syndrome (KS) and 813 patients without Klinefelter syndrome (non-KS). Participants/materials, setting, methods In 931 patients, 63 KS and 417 non-KS had spermatozoa retrieved from microTESE were carried out ICSI. In ICSI group, 59 KS and 319 non-KS patients whose partners were under 35 years old were selected to compare embryological and clinical outcomes. Outcomes included fertilization rate, day 3 usable embryo rate, usable blastocyst rate, pregnancy rate (positive beta-hCG test), biochemical pregnancy rate, ongoing pregnancy, and live-birth rate (calculated on the total number of IVF cycles). Main results and the role of chance Spermatozoa retrieval rate by microTESE in the KS group was 53.4% (63/118), while this rate in the non-KS group was 51.2% (417/813) (p &amp;gt; 0.05). The mean age of female partners was significantly lower in the KS group than in non-KS group (26.6 ± 4.0 vs. 28.0 ± 3.5; p = 0.006). The mean of mature oocytes between these two groups was similar (15.7 ± 8.1 vs 14.5 ± 7.2; p &amp;gt; 0.05). Fertilization rates in KS and non-KS groups were 62.7% and 65.3%, respectively. Day 3 usable embryo rate (embryo with over 6 blastomeres at day 3) in two groups was not significantly different (69% vs 69.5%, p &amp;gt; 0.05). Usable blastocyst rate (embryo quality is over 2BB, Gardner grading system) in the KS group (19.9%, n = 54) was significantly lower than in non-KS group (41.1%, n = 281) (p &amp;lt; 0.001). Pregnancy rate and biochemical pregnancy rate were 75.9% and 6.9% in KS group (n = 58), respectively. Those rates were 81.5% and 3.2% in non-KS group (n = 313), respectively. There was no significant difference in ongoing pregnancy rate between these two groups (61.1% vs 74.5%; p &amp;gt; 0.05). Live-birth rate in the KS group was 43.2% (16/37), while this rate in the non-KS group was 46.5% (67/145). Limitations, reasons for caution This research had limitations of a retrospective study. Male hormonal factors and baby health could not be thoroughly measured because of difficulties in contact with patients at the time of the study. Besides, day 3 top-quality embryos were directed to freeze, so usable blastocyst rate was low in this study. Wider implications of the findings These data confirmed that microTESE provides opportunities for non-mosaic Klinefelter syndrome patients to retrieve their own sperm. Combination of microTESE and ICSI is an effective treatment regimen that helps these patients to have their own usable embryos and babies. Trial registration number not applicable

P-700 preimplantation genetic testing for aneuploidy failed to improve cumulative live birth rate in patients with limited good-quality embryos

Abstract Study question To evaluate whether preimplantation genetic testing for aneuploidy (PGT-A) can improve pregnancy and neonatal outcomes for patients with limited good-quality embryos. Summary answer PGT-A failed to improve cumulative live birth rate or shorten time to pregnancy, but optimized pregnancy outcomes per transfer for patients with limited good-quality embryos. What is known already PGT-A is currently widely used to screen for aneuploidy with the goal of improving live birth rates. Remarkably, previous studies have focused on the effect of PGT-A on cumulative clinical outcomes in women with good pregnancy prognosis. However, it is still unclear whether PGT-A can improve the cumulative pregnancy outcomes in patients with limited good-quality embryos. Study design, size, duration A retrospective cohort study was performed among 1553 women who intended PGT-A for the first time but obtained only two or less good-quality embryos on day 3 after oocyte retrieval from March 2017 to June 2021. Participants/materials, setting, methods A total of 1553 patients were divided into two groups: 997 in the PGT-A group and 556 in the drop-out group of withdrawing PGT-A due to poor embryological outcome. Multivariable logistic regression was performed to adjust for potential confounders when comparing the clinical outcomes between two groups. Main results and the role of chance After adjusting for potential confounding factors, PGT-A group exhibited significantly lower cumulative rates of biochemical pregnancy (19.96% vs. 30.22%, P-adj &amp;lt; 0.001), clinical pregnancy (17.55% vs. 23.38%, P-adj &amp;lt; 0.001) and live birth (14.14% vs. 16.19%, P-adj = 0.005) per oocyte retrieval and longer median time to pregnancy and live birth compared with drop-out group. However, significant increases in rates of biochemical pregnancy (72.16% vs. 35.50%, P-adj &amp;lt; 0.001), clinical pregnancy (61.86% vs. 26.98%, P-adj &amp;lt; 0.001), and live birth (48.45 vs. 18.26%, P-adj &amp;lt; 0.001) per transfer were found in the PGT-A group. No significant differences were observed in cumulative miscarriage and ectopic pregnancy rates, number of ETs needed per live birth and neonatal outcomes. Limitations, reasons for caution This study was limited by the inherent potential bias of retrospective studies and small sample size. Thus, additional studies with larger sample sizes are needed to confirm our findings. Wider implications of the findings PGT-A failed to improve cumulative live birth rate or shorten time to pregnancy, but optimized pregnancy outcomes per transfer for patients with limited good-quality embryos. Trial registration number Not applicable

P-301 Assessment of ongoing clinical outcomes prediction of an AI system on retrospective SET data

Abstract Study question Would patients with fresh and frozen embryo transfer had achieved pregnancy before if the embryo was chosen by AI? Summary answer CHLOE (AI) can predict pregnancy, ongoing clinical pregnancy, and miscarriage following a single embryo transfer (SET). What is known already The use of time-lapse incubators has provided embryologists with more information to evaluate embryo development, resulting in varying clinical practices among clinics in prioritizing this information. However, manual annotation of time-lapse videos is time-consuming and prone to interoperator inconsistencies. To overcome these challenges, AI tools like CHLOE (Fairtility) can be utilized. CHLOE uses AI-based predictors to predict implantation and provides clarity on the biological factors driving these predictions. However, before incorporating AI tools into clinical practice, it is important to validate their effectiveness. Study design, size, duration Single study center that took place between July of 2021 and December 2022 at a private clinic in Spain. This was a retrospective cohort analysis that reviewed 118 time-lapse videos from single fresh embryo transfers and 92 time-lapse videos from single frozen embryo transfers with known ongoing clinical pregnancy outcome. CHLOE EQ score and CHLOE Rank efficacy of prediction of clinical outcomes and miscarriage was quantified using the metric AUC. Participants/materials, setting, methods Time-lapse videos were evaluated using CHLOE (Fairtility), an AI tool, to determine CHLOE EQ score and rank related to clinical outcomes (biochemical pregnancy, clinical pregnancy, and miscarriage) following fresh and frozen SET. CHLOE rank and embryology were compared with chi-square and AUC was calculated with logistic regression to measure prediction accuracy. T-test was used to check differences in CHLOE EQ score in different outcomes. Main results and the role of chance Embryologist vs CHLOE Ranking weren’t significant (p &amp;gt; 0.05). In fresh SET the mean EQ score was 7.76, and in frozen SET was 7.07. Following fresh SET, CHLOE EQ score was not-significantly predictive of biochemical pregnancy (AUC = 0.53, n = 104, p = 0.462), clinical pregnancy (AUC = 0.51, n = 79, p = 0.949), and miscarriage rate (AUC = 0.50, n = 68, p = 0.949); CHLOE Ranking was more predictive than embryologist rank for biochemical pregnancy (embryologist vs CHLOE rank: AUC = 0.51, p &amp;gt; 0.05 vs AUC = 0.61, p &amp;gt; 0.05), clinical pregnancy (embryologist vs CHLOE rank: AUC = 0.51, p &amp;gt; 0.05 vs AUC = 0.70, p &amp;gt; 0.05) and miscarriage rate (embryologist vs CHLOE rank: AUC = 0.51, p &amp;gt; 0.05 vs AUC = 0.75, p &amp;gt; 0.025). Following frozen SET, only top 1 embryos ranked by embryologists were transferred, and CHLOE EQ score was predictive of biochemical pregnancy (AUC = 0.60, n = 85, p = 0.213), clinical pregnancy (AUC = 0.64, n = 60, p = 0.919), and miscarriage rate (AUC = 0.87, n = 52, p = 0.437); CHLOE Ranking was predictive of biochemical pregnancy (AUC = 0.59, p &amp;gt; 0.05), clinical pregnancy (AUC = 0.64, p &amp;gt; 0.05) and miscarriage rate (AUC = 0.90, p &amp;gt; 0.05). Limitations, reasons for caution This study is a single-center retrospective analysis where embryos were chosen for transfer by human embryologists and is part of a broader effort to validate the responsible integration of AI into clinical practice. Wider implications of the findings The use of AI-based tools has the possibility to enhance the consistency, efficiency, and effectiveness of embryo selection. The information from quantitative and qualitative morphokinetics provided by AI tools like CHLOE brings greater clarity to predictions, enabling more personalized care for each individual embryo. Trial registration number Not Applicable

P-692 Effect of intra-ovarian instillation of autologous platelet rich plasma on live birth rate in POSEIDON 3 versus POSEIDON 4 group: A prospective follow-up study

Abstract Study question What is the effect of intra-ovarian platelet rich plasma(PRP) on live birth rate(LBR) in POSEIDON-3 versus POSEIDON-4 group? Summary answer Intra-ovarian PRP improves the live birth rate in low prognosis patients irrespective of age, this giving them hope of their own biological child. What is known already With the emerging regenerative medicine promising various treatment modalities, PRP is considered a novel therapeutic option. Various anecdotal cases have been reported, demonstrating successful pregnancy outcomes after the PRP treatment. But the data still remains elusive, especially for women of Asian ethnicity, who have a rapid decline in ovarian reserve when compared to the Caucasian population. Consequently, we attempt to compare the effects of autologous PRP on LBR in POSEIDON-3 versus POSEIDON-4 groups. Study design, size, duration After ethical approval, a prospective interventional study was conducted at ART Centre, Department of Obstetrics and Gynaecology of a tertiary care institute during a period from July 2020 to April 2022. 72 women between the ages of 20 and 40 years with idiopathic poor ovarian reserve (AMH 1.2&amp;lt;ng/ml; AFC&amp;lt;5) and a normal adequate uterine cavity were enrolled, and those with a history of radiotherapy, chemotherapy, endometriosis, or ovarian/tubal surgery were excluded. Participants/materials, setting, methods Women between 20-40 years of age with low ovarian reserve received 1.5 ml-PRP prepared from 30 ml venous-blood, was instilled in each ovarian stroma between day 6-10 of menses. Patients were followed up for 3-consecutive months to assess ovarian-reserve parameters (FSH, AMH, AFC). Patients showing significant improvement (AFC&amp;gt;5) were enrolled in antagonist-IVF cycles and categorised into two groups: POSEIDON-3 vs 4 groups. Paired/signrank test and Independent/ranksum test compared clinical parameters between the two groups. Main results and the role of chance The mean age and BMI of the recruited women were 31.7 + 4.2 years and 24.89 + 3.73 kg/m2. Out of 72 participants, 16.67% responded in 1st month of follow-up(AFC: 5 vs 3,p&amp;lt;0.001), 43% in 2nd month(AFC: 6 vs 3,p&amp;lt;0.001)(AMH: 1.02 vs 0.99,p=0.02) and 12.5% in 3rd month(AFC:4 vs 3,p&amp;lt;0.001)(AMH:0.89 vs 0.85,p=0.01). 20 participants showed no improvement in AFC, AMH, or FSH. Excluding one, 43 underwent antagonist cycle. Despite the evident age-difference between the POSEIDON-3 and 4 groups(29.6 vs 36.6 years), the POSEIDON-4 group women were more obese (27.4 + 1.30 vs 23.3 + 0.49,p=0.0007). Although the number of oocytes retrieved was similar (6.35 + 1.83 vs 5.75 + 1.35,p=0.21), the E2 levels on the day of trigger were significantly low in POSEIDON-4 patients (1082.33 + 273.03 vs 1727.16 + 867.79,p=0.01). Also, the dose of HMG requirement was higher in POSEIDON-4 (1450 + 96.53 vs 1190.3 + 66.49,p=0.04) thus depicting the effect of advanced age. Otherwise, there was no significant difference in dose of rFSH requirement (2705.6 + 48.93 vs 2737 + 54.74,p=0.71), fertilisation rate (60.86% vs 57.86%,p=0.66), biochemical pregnancy rate (30.7% vs 29.03%,p=0.78), CPR (25% vs 25.8%,p=0.95) and LBR (22.6% vs 16.66%,p=0.66) between the two-groups. No adverse events reported. Limitations, reasons for caution Our study was a non-randomized study with no control/sham, arm as doing so would be unethical and impose a financial burden on the patients with no guaranteed clinical success. Wider implications of the findings With the impetus to provide a biological child to the women with poor ovarian reserve, ovarian-rejuvenation with PRP seems to be a promising treatment. It can be concluded that PRP improves the ovarian reserve which translates into better reproductive outcomes in women who were planned and counselled for donor-oocyte IVF. Trial registration number Not applicable

O-023 ‘The PiNC Trial’: Progesterone in Natural Cycles for the treatment of unexplained infertility

Abstract Study question Does exogenous progesterone for luteal phase support in natural cycles affect the biochemical, clinical pregnancy, livebirth or miscarriage rates in women with unexplained infertility (UI)? Summary answer Progesterone luteal support lead to an increase in livebirth rate from 7% to 15.3% and a decrease in miscarriage rates from 40% to 20%. What is known already Unexplained infertility is a diagnosis likely to encompass a population with varying underlying subtle pathologies. The only treatments currently recommended for treating UI are intrauterine insemination (IUI) and IVF/ICSI which are both expensive and invasive. The evidence for IUI with and without controlled ovarian hyperstimulation (COH) is inconclusive. A recent systematic review and meta-analysis reported a progesterone-mediated reduction in endometrial receptivity as a possible mechanism in the pathogenesis of UI. No trial has been published investigating the effectiveness of exogenous progesterone for luteal support in otherwise natural, unmedicated cycles to improve reproductive outcomes in couples with UI. Study design, size, duration We conducted an open-label, parallel arm, single centre, randomised controlled trial of an investigational medicinal product (cTIMP) from February 2020 to November 2022. We randomised 143 couples with UI to either luteal phase progesterone support or no luteal phase support and analysed the results on an intention-to-treat basis. Each couple participated for 3 menstrual cycles and they were followed up until either the end of a 3rd non-conceptual cycle or any resulting pregnancy. Participants/materials, setting, methods Couples with normal semen analysis (WHO 2020), regular ovulation, bilateral patent tubes, female partner aged ≤42yrs and BMI ≤30 were recruited and randomised following screening and informed consent. Participants timed their luteinising hormone (LH) surge using digital ovulation kits and had timed intercourse for 3 cycles. The treatment group took progesterone suppositories 400mg bd for 14 days after the LH surge. All pregnancies were scanned at 6-7/40 and ongoing pregnancies followed up to delivery. Main results and the role of chance 143 couples were recruited and randomised. Livebirth rates were 11/72 (15.3%) in the treatment group vs. 5/71 (7.0%) in the control group (Odds Ratio (OR) 2.38, 95%CI 0.78-7.24). Biochemical pregnancy rates (defined by a positive urinary pregnancy test) were 15/72 (20.8%) (treatment) vs 10/71 (14.1%) (control) (OR 1.61, 95%CI 0.67-3.86). Clinical pregnancy rates (defined by a gestation sac seen on ultrasound at a minimum of 6/40 gestation) were 14/72 (19.4%) (treatment) vs 9/71 (12.7%) (control) (OR 1.66, 95% CI 0.67-4.13). The miscarriage rate including biochemical losses was 3/15 (20%) of all pregnancies (treatment) vs. 4/10 (40%) (control). One pregnancy in the control group was terminated due to fetal anomalies. There was one ectopic pregnancy in the treatment group. Logistic regression demonstrated that none of the pregnancy outcomes were affected by participant age, BMI, ovarian reserve markers, previous parity or semen analysis parameters. The two participants in the treatment group who experienced miscarriages were both off-protocol. Although the results did not reach statistical significance, the 15.3% livebirth rate and OR of 2.37 for livebirths are clinically significant (equivalent to the success rates of stimulated intrauterine insemination treatment) as is the miscarriage rate of 0/11 clinical intra-uterine pregnancies for women taking progesterone as per protocol.Limitations, reasons for caution Despite the lack of statistical significance, differences in livebirth and miscarriage rates are clinically significant compared with alternative treatments. The trial was unblinded but the objective outcomes are unlikely to be affected by this. A larger trial using the effect size from this study to guide sample size is planned. Wider implications of the findings The treatment investigated here represents a simple, non-invasive and inexpensive option that is acceptable to couples with UI and may increase their chance of pregnancy and livebirth. If this treatment offers similar success rates to stimulated IUI it is likely to become a first-line option for many couple worldwide. Trial registration number 2019-003468-27

P-341 Endometrial compaction and its impact on reproductive outcome

Abstract Study question Is there a relationship between endometrial compaction and clinical pregnancy rate in frozen embryo transfer (FET) cycles? Summary answer Clinical pregnancy rate (CPR) were similar in both patients that demonstrated endometrial compaction or no compaction in FETs cycles. What is known already There has been increasing interest in the correlation between endometrial compaction and clinical outcomes but there has been conflicting evidence from prior investigations. Study design, size, duration Retrospective Observational data Analysis of (n-350) patients undergoing Embryo Transfer during January 2022 to December 2022 at our clinic. Participants/materials, setting, methods This study was performed at a single, academically affiliated fertility center in which patients who had an FET using programmed/modified natural cycle protocol were included. Endometrial thickness at time start of progesterone(T1)(TVS) &amp; at time of Embryo transfer (T2)(TAS)was measured, and percentage on ET compaction in both HRT cycle and modified natural cycle was studied. The primary outcome (CPR) was based on proportion of compaction (percentage difference in EMT between T1 and T2). Main results and the role of chance Of the 350 participants included, 64%, 38% and10%, of women exhibited &amp;gt;0%, &amp;gt;5% and &amp;gt;10% endometrial compaction, respectively. Endometrial compaction was not predictive of Clinical Pregnancy Rate (CPR) at any of the defined cutoffs .Primary outcomes included CPR (defined as the presence of at least one gestational sac with a fetal pole with cardiac activity on transvaginal ultrasound between 6 and 9 weeks gestation), biochemical pregnancy rate and spontaneous abortion rate. Patients were discharged to their obstetrician when a clinical pregnancy was confirmed between 6 and 9 weeks gestation. Limitations, reasons for caution There was the potential for measurement error in the recorded EMTs. The T2 measurement was performed transabdominally, which may cause potential measurement error, as it is generally accepted that transvaginal measurements of EMT are more accurate, though, any bias is expected to be non-differential Wider implications of the findings Assessing endometrial compaction may lead to unnecessary cycle cancellation. However, further studies are needed to determine if routine screening for endometrial compaction would improve clinical outcomes. Trial registration number not applicable

P-683 Live birth rate following medicated frozen-thawed embryo transfer with or without GnRH-antagonist (Cetrotide) pituitary suppression. A randomised, controlled pilot trial

Abstract Study question Does the administration of GnRH-antagonist (Cetrotide) in medicated frozen-thawed embryo transfer (FET) cycles improve live birth (LBR) or cycle cancellation rate? Summary answer Live birth and cycle cancellation were similar with or without Cetrotide. However, cancellation for threatened ovulation was statistically significantly lower when Cetrotide was administered. What is known already During medicated FET, embryo and endometrial development must be synchronized, with endometrial window of implantation dependent on duration of progesterone. Suppression of spontaneous ovulation is key to maintaining synchrony. There are insufficient data regarding the use of supplementary pituitary suppression in medicated FET. A recent Cochrane review identified one small RCT comparing live birth rate between medicated FET with or without GnRH-agonist pretreatment. The study suggested benefit to GnRH-agonist, but cycles were not monitored for ovulation. One RCT compared GnRH-antagonist with agonist showing better clinical pregnancy rate with GnRH-antagonist. No published RCT has compared medicated FET with versus without GnRH-antagonist. Study design, size, duration We conducted an open, two-arm, single-centre, randomised, controlled trial comparing medicated FET with or without Cetrotide. Target recruitment was 300. However, the study was stopped due to the Covid-19 pandemic. Recruitment occurred between 23rd January 2019 and 11th March 2020 and ended at 161 participants. Analysis was undertaken on an intention-to-treat basis, with live birth rate (LBR) as the primary outcome. Participants/materials, setting, methods Patients were given oestradiol 2mg orally TDS. Once the endometrium was ≥7mm, vaginal progesterone was commenced, with FET on the sixth day of progesterone. The Cetrotide group were given Cetrotide 0.25mg SC OD from days 1-7. Urine pregnancy test was done 11 days following FET, with oestradiol and progestogen continued to 10 weeks gestation. Cycles were cancelled for “threatened ovulation” if daily urinary LH-surge testing was positive or an ovarian follicle (≥12mm) was growing. Main results and the role of chance 161 patients were randomised (Cetrotide: 76, no Cetrotide: 85). Six were withdrawn after randomisation (three withdrew consent, two did not start, one natural pregnancy). 155 participants started treatment (Cetrotide: 73, no Cetrotide: 82) and 140 had embryo transfer (Cetrotide: 68, no Cetrotide: 72). The LBR was similar between groups (Cetrotide: 39% (30/76), no Cetrotide (29/85): 34%; OR 0.79, 95% CI 0.42 - 1.51), as were pregnancy rate (42% versus 38%; OR 0.87; 95% CI 0.47-1.63), clinical pregnancy rate (52% versus 49%; OR 0.83; 95% CI 0.44 – 1.56), biochemical pregnancy rate (20% versus 24%; OR 1.25; 95% CI 0.44 - 3.58) and miscarriage rate (7% versus 10%; OR 1.55; 95% CI 0.24 – 9.97). In the Cetrotide group, 7% of cycles were cancelled, compared to 12% in the no Cetrotide group (NS). However, cancellation due to threatened ovulation was statistically significantly lower in the Cetrotide group, with 0% of cycles cancelled compared to 5% in the no Cetrotide group (OR 1.05; 95% CI 1.001 – 1.105). Baseline characteristics (age at oocyte retrieval, age at FET, parity, subfertility diagnosis, number of oocytes retrieved, number of viable blastocysts, proportion of IVF/ICSI, endometrial thickness, number of embryos transferred, embryo quality) were similar between groups. Limitations, reasons for caution The study is limited by the fact it was unblinded, undertaken at a single site and was underpowered for live birth due to early trial cessation. Wider implications of the findings Results suggest no effect of Cetrotide on LBR in medicated FET. There was a significantly higher risk of cycle cancellation due to risk of ovulation in patients not taking Cetrotide. This is clinically significant and requires further study, as cancelled cycles increase costs and duration to birth. Trial registration number EudraCT Number: 2018-001915-63

P-630 Comparison of follitropin delta versus follitropin alfa in progestin-primed ovarian stimulation in IVF

Abstract Study question Is there a difference in a clinical outcome between using follitropin delta and follitropin alfa undergoing a progestin primed ovarian stimulation (PPOS) protocol? Summary answer There was no difference between follitropin delta and follitropin alfa in terms of pregnancy rates. What is known already Follitropin delta (REKOVELLE, Ferring Pharmaceuticals, Switzerland) is the first recombinant human follicle-stimulating hormone (FSH) using the algorithm-based individualized dosing regimen while reducing the risk of ovarian hyperstimulation syndrome (OHSS) as compared with conventional dosing strategies. The efficacy and safety of follitropin delta has been demonstrated in randomized controlled trials (RCTs). Study design, size, duration We performed a retrospective analysis of 645 patients who underwent ovarian stimulation by a PPOS protocol using follitropin delta or follitropin alfa between April 2022 and August 2022. (325 patients using follitropin delta and 320 patients using follitropin alfa, respectively.) Participants/materials, setting, methods 325 cycles of women who used follitropin delta were compared to 320 cycles of women who used follitropin alfa. The following outcomes were analysed; fertilized rate, 2 pronuclear embryo rate, good quality embryo rate, blastocyst rate, good quality blastocyst rate. A total of 499 women who underwent embryo transfer in cryo cycles using natural cycle or hormone replacement cycle were analysed about biochemical pregnancy rate, clinical pregnancy rate. Main results and the role of chance Baseline demographics for 325 women in follitropin delta group and 320 women in follitropin alfa were: age, 35.1±4.3 years and 35.2±4.3 years; number of previous IVF cycles, 1.6±1.6 and 1.7±1.7, respectively. The laboratory data were: fertilization rate, 81.4% and 80.1%, 2 pronuclear embryo rate, 73.9% and 71.5%, good quality cleavage stage embryo rate, 59.4% and 55.9%, blastocyst rate, 58.9% and 55.7%, good quality blastocyst rate, 41.3% and 38.7%, respectively. Only good quality cleavage stage embryo rate and good quality blastocyst rate were significantly higher (P &amp;lt; 0.05) in follitropin delta group. A vitrified-warmed embryo transfer was performed for 257/325 women (79.1%) and 242/320 women (75.6%) and subsequent positive β-human chorionic gonadotropin (βhCG) reported for 218/621 cycles (35.1%) and 194/570 cycles (34.0%), respectively. Ongoing pregnancy rate after embryo transfer were 19.2% (n = 119) and 19.6% (n = 112) and cumulative ongoing pregnancy rate were both 46.3%. Mild OHSS was reported for 131 women (40.3%) and 170 women (53.1%), respectively (P = 0.07). Limitations, reasons for caution This is a non-controlled, retrospective study. Wider implications of the findings The present study shows that in addition to reducing the OHSS risk, follitropin delta in its individualised fixed-dose regimen has the potential to improve the quality of embryos although there was no significant difference in clinical outcomes. Trial registration number not applicable

P-521 A gene expression risk signature of endometrial failure for prognosis in In Vitro Fertilization (IVF) patients

Abstract Study question It is possible to identify a characteristic pattern of endometrial gene expression indicative of implantation failure, which is independent of implantation window displacements? Summary answer An endometrial transcriptomic signature was able to identify patients with a &amp;gt; 3-fold increased risk of implantation/pregnancy failure with 95% accuracy. What is known already Implantation failure of endometrial origin is a complex and multifactorial symptom with diverse causes, diagnosed in IVF patients after repeated failures with good quality embryos. A generation of gene expression tools have assumed that Window of implantation (WOI) displacement is the principal cause of this condition, but strategies seeking to counteract this problem by adjusting the day of embryo transfer have not yielded convincing improvements in outcomes. However, it is conceivable that other forms of endometrial disruptions, relevant to embryo implantation, could exist. New endometrial diagnostic strategies are needed to understand, diagnose and potentially treat patients affected with such problems. Study design, size, duration A prospective multicenter study between January 2018 and December 2021 recruited 281 Caucasian IVF patients (mean age of 39.4±4.8 years and BMI of 22.9±3.5 kg/m2) undergoing hormone replacement therapy and encompassing 114.5±7.2 h of progesterone administration at time of endometrial biopsy. Following experimental quality controls and clinical follow up, 186 patients who had a good quality embryo transferred in the cycle after endometrial biopsy collection were included for gene discovery and prediction performance. Participants/materials, setting, methods The expression of 404 genes selected for their potential to distinguish endometrial timing and/or endometrial disruption was measured. Transcriptomic variation related to progression of the menstrual cycle was removed using transcriptomic endometrial dating (TED) and linear models. Study groups were established according to clinical and gene expression parameters through a semi-supervised artificial intelligence procedure. Gene signature discovery and a cross-validation processes were undertaken to define predictive expression patterns. Reproductive outcomes were compared between prognosis profiles. Main results and the role of chance We developed a procedure called Clinically Acute Transcriptomic Stratification (CATranS), combining clinical parameters and deep transcriptomic molecular characterisation to stratify patients according to endometrial prognosis: ‘poor’ (n = 137) or ‘good’ (n = 49). These two transcriptomic profiles were associated with differing reproductive outcomes in the single embryo transfer following biopsy: pregnancy rate (45.1% vs 79.6%, poor vs good prognosis, respectively, p = 3.8E-5); live birth rate (56.4% vs 97.5%, p = 3.0E-06); clinical miscarriage rate (27.9% vs 2.6%, p = 0.0020); biochemical pregnancy rate (20.4% vs 0%, p = 0.0023). Patients with a poor prognosis profile had 3.3-times higher relative risk of a transferred embryo failing to implant or a pregnancy not being sustained to term, compared with good prognosis patients. Initially, a reference dataset was used to build a prototype for diagnosing endometrial failure, revealing that a gene expression signature consisting of 135 genes was the most predictive. Prediction performance was estimated using a 5-fold 100-times cross-validation process, resulting in a median accuracy of 0.92, median sensitivity of 0.96, and median specificity of 0.84. From these 135 predictive genes, 122 were differentially expressed (FDR&amp;lt;0.05) in endometrial poor prognosis, 59 up- and 63 down-regulated, most involved in functional processes such as regulation (17%), metabolism (8.4%), immune response and inflammation (7.8%). Limitations, reasons for caution We describe a potential new strategy for evaluating endometrial competence. However, to confirm predictive value, validation using additional samples from patients independent of signature discovery set is required. Further research to identify potential treatments for patients classified as poor prognosis is needed, providing a tailored clinical pathway for these patients. Wider implications of the findings The prototype described is a novel concept, potentially leading to development of a new generation of tools for diagnosis of fertility problems related to endometrial factors. The ‘poor’ prognosis profile is not caused by asynchronies in menstrual cycle progression, opening the possibility of finding new treatment pathways for these patients. Trial registration number NA