28-day Cycle Research Articles

Thermal sum accumulated in development stages of tomato crop for industrial processing

Tomato crop for industrial processing is very sensitive to weather variations. Therefore, the objective of this research was to quantify the duration (days and thermal sum) of each developmental stage of different hybrids in two different planting date. For this, 12 commercial hybrids were evaluated: H-1301, BS-P0033, CVR-8161, HM-7885, CVR-6116, HM-7883, H-1536, CVR-2909, TPX-26856, CVR-8126, CTI-35 and N-901, in Abadia de Goiás, Brazil, planted on 03/31/2020 and 05/26/2020. Experimental area with 3,120 m2, 4 blocks with 12 experimental plots each (12 hybrids), and each plot, formed by 3 double planting lines of 10 m, spaced 0.6 m x 1.2 m, with plants every 0.37 m, totaling 27 plants per line and 162 plants per plot. Plant phenology was monitored daily: phase I (planting to set), phase II (set to flowering), phase III (flowering to beginning of maturation) and phase IV (IVa beginning of maturation up to 50% of mature fruits and phase IVb (from 50% to 90% of mature fruits). The results show, on average of all hybrids, thermal sum of 1,394 and 1,364 oC obtained in 124.6 and 116.1 days of cycle, in first and second cycle, respectively. In first cycle, there was a difference in thermal sum between the hybrids in stage IV and in total cycle, which hybrids BS-P0033, CVR-8161, HM-7885, HM-7883, CVR-2909 and TPX-26856 accumulated from 81.29 to 112.88 oC in 6 to 9.3 days to complete maturation, while other hybrids accumulated from 122.85 to 148.11 oC in 10.3 to 13 days. The hybrids BS-P0033, CVR-8161, HM-7885 and HM-7883 had a shorter total cycle duration from 1,334.21 to 1,379.98 oC (119 to 123 days), while other hybrids variated of 1,391.45 to 1,437.05 oC (124.3 to 129 days). The stages of setting, vegetative and beginning of maturation up to 50% of ripe fruits, showed variation in thermal sum and duration of phase, depending on planting date. For the first cycle, the duration of average vegetative stage was 21.7% longer, accumulating 34.1% more oC, compared to the second cycle, providing greater plant height (43.8%) and higher productivity (19.8%). This shows that is need to change irrigation management strategy between transplanting date and crop development stages, making irrigation adjustments by thermal sum and not by number of days for development stage.

Undetected, natural conception pregnancies in luteal phase stimulations-case series and review of literature.

What is the risk of an undetected natural conception pregnancy during luteal phase ovarian stimulation, and how does it impact the pregnancy's course? The risk for an undetected, natural conception pregnancy in luteal phase ovarian stimulation is low and it appears that ovarian stimulation is unlikely to harm the pregnancy. Random start ovarian stimulation appears to be similarly effective as early follicular stimulation start; and it allows ovarian stimulation to be started independent of the cycle day and throughout the cycle, in accordance with the patients' and clinics' schedule as long as there is no intention of a fresh embryo transfer in the same cycle. Starting ovarian stimulation in the luteal phase bears the possibility of an-at the timepoint of stimulation start-undetected, natural conception pregnancy that has already occurred. There is scarce data on the incidence of this event as well as on the possible implications of ovarian stimulation on the course of an existing pregnancy. This retrospective observational study, performed between June 2017 and January 2024, analyzed luteal phase stimulations, in which a natural conception pregnancy was detected during the ovarian stimulation treatment for IVF/ICSI. Luteal phase stimulation was defined as ovarian stimulation started after ovulation and before the next expected menstrual bleeding, with a serum progesterone (P4) level of >1.5 ng/ml on the day of stimulation start or 1 day before. Women who underwent a luteal phase ovarian stimulation in a tertiary referral ART center. A total of 488 luteal phase stimulation cycles were included in the analysis. Luteal phase stimulation was only started after a negative serum hCG measurement on the day or 1 day before commencement of ovarian stimulation. Ten patients (2.1%) had an undetected natural conception pregnancy at the time of luteal phase stimulation start. Eight of these patients underwent an ovarian stimulation in a GnRH-antagonist protocol and two in a progestin-primed stimulation protocol (PPOS). Recombinant FSH was used as stimulation medication for all patients, the patients with a PPOS protocol received additional recombinant LH. One pregnancy (0.2%) was detected after the oocyte retrieval, the other nine pregnancies were detected either due to persistent high serum progesterone levels or due to an increasing progesterone level after an initial decrease before oocyte retrieval. In the cycles with an undetected natural conception pregnancy, the median number of stimulation days was 8 days (range: 6-11 days) and median serum hCG at detection of pregnancy was 59 IU hCG (range: 14.91-183.1). From 10 patients with a pregnancy, three patients delivered a healthy baby, two patients had ongoing pregnancies at the time of summarizing the data, three patients had biochemical pregnancies (patient age: 30, 39, and 42 years), one patient had an ectopic pregnancy which required a salpingectomy, and one patient (age: 34 years) had an early pregnancy loss. The retrospective study design and the small sample size can limit the accuracy of the estimates. Overall, there is a small risk of undetected natural conception pregnancies when luteal phase stimulation is undertaken. It appears that there are no adverse effects through either direct effect on the embryo or indirectly through a detrimental effect on the corpus luteum function on the pregnancy in our cohort. This study did not receive funding. The authors declare that there is no conflict of interest. N/A.

Efficacy, safety, and cost-effectiveness of pegylated PEG-rhg-CSF in pediatric patients receiving high-intensity chemotherapy: results from a phase II study.

High-intensity chemotherapy can cause life-threatening complications in pediatric patients. Therefore, this study investigated safety and efficacy of long-acting pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF; Jinyouli®) in children undergoing high-intensity chemotherapy. Treatment-naive patients received post-chemotherapy PEG-rhG-CSF as primary prophylaxis for two cycles. The primary endpoints were drug-related adverse events (AEs) and bone pain scores. Secondary endpoints included grade 3-4 neutropenia, duration of neutropenia recovery, absolute neutrophil count changes, febrile neutropenia (FN), reduced chemotherapy intensity, antibiotic usage, and AE severity. The cost-effectiveness of PEG-rhG-CSF was compared with that of rhG-CSF (Ruibai®). Here, 307 and 288 patients underwent one and two PEG-rhG-CSF cycles, respectively. Ninety-one patients experienced drug-related AEs, primarily bone pain (12.7%). Moreover, Grade 3-4 neutropenia and FN were observed. Median FN durations were 3.0 days in both cycles. No drug-related delays were observed during chemotherapy. One patient experienced grade 4 neutropenia-induced reduction in chemotherapy intensity during cycle 2. In total, 138 patients received antibiotics. PEG-rhG-CSF exhibited superior cost-effectiveness compared to rhG-CSF. Our findings indicate that PEG-rhG-CSF is safe, efficient, and cost-effective in pediatric patients undergoing high-intensity chemotherapy, providing preliminary evidence warranting further randomized controlled trials.

Fixed-Time Artificial Insemination Versus Artificial Insemination at Stalk Detected in Cows And Heifers

Objective: The objective of the present study was to evaluate the pregnancy rate of IACD and IATF in cows and heifers. Theoretical framework: Artificial insemination at a fixed time (IATF) and artificial insemination at detected heat (IACD) are essential tools in livestock farms, improving the production and reproduction of the herd in a short time, considering that differences sometimes occur between the pregnancy rate of cows and heifers with different treatments influencing the production of the herds. Methodology: 194 heifers and 200 Bos taurus x Bos indicus crossbred cows were used. The animals that entered IATF on a random day of the estrous cycle were synchronized with an intravaginal device of Progesterone and Estradiol. The animals that entered IACD were monitored. visual of the characteristic signs of heat twice a day for a period of two hours each, to carry out artificial insemination (AI), the statistical analysis was carried out with the help of the SAS software. Results and discussion: The pregnancy rate among the 215 heifers and cows in the IACD group was 64.00% and 44.00%, respectively, unlike the IATF group with a total of 179 animals, a pregnancy rate of 91.14% for heifers and 78.00% in cows, showing statistically significant differences in follicular size for cows and heifers under treatment with IACD and similar for IATF. Implications of the research: The cyclicity of heifers was efficiently induced in the hormonal protocols with IATF, this group of animals had a higher pregnancy rate and greater follicular diameter unlike the IACD group. Originality/Value: This study contributes to the understanding and effectiveness of using reproductive biotechnologies in livestock herds to increase production and profitability, thus being more sustainable.

Coral spawning patterns on the Luhuitou fringing reef in Hainan Island of the northern South China Sea

Observation of coral spawning times is valuable to detect spawning patterns and identify the potential mechanisms behind coral reproduction. Although large amount of data on global coral spawning records have become available over the past decades, information on coral spawning in the northern South China Sea remains scarce. In this study, we investigated the spawning patterns of scleractinian corals in Luhuitou fringing reef, Hainan Island, China, from 2009 to 2021 in relation to lunar cycles (month and day). The spawning times of 22 coral species from five genera (Acropora, Montipora, Platygyra, Dipsastraea, and Galaxea) within three families (Acroporidae, Merulinidae, and Euphylliidae) were recorded, with spawning occurring from lunar February to May 2009–2021. Recorded spawning events started at a period of increasing seawater temperature. Acropora, the most documented genus, spawned between lunar February and April, but primarily in lunar March. Importantly, the spawning time of Acropora was delayed for one lunar month in 2016 most likely due to a rapid decrease in monthly mean seawater temperature in lunar February. Spawning lunar days before, on or after full moon of corals in the Luhuitou Reef, including those of the Acropora species, were highly variable between years even for the same species. No predictable pattern of spawning times can thus be detected. Nonetheless, our results fill up an information gap on coral spawning patterns in the northern South China Sea that may be useful for further understanding of the reproductive biology of scleractinian corals throughout the Indo–West Pacific.

Phase 2 trial of the farnesyltransferase inhibitor tipifarnib for relapsed/refractory peripheral T-cell lymphoma

AbstractA phase 2, international, open-label, nonrandomized, single-arm trial was conducted to evaluate the efficacy and safety of tipifarnib, a farnesyltransferase inhibitor, as monotherapy for relapsed/refractory peripheral T-cell lymphoma (PTCL) and to evaluate tumor mutation profile as a biomarker of response. Adults with relapsed/refractory PTCL received tipifarnib 300 mg orally twice daily for 21 days in a 28-day cycle. The primary end point was objective response rate (ORR); secondary end points included ORR, progression-free survival (PFS), duration of response (DOR), and adverse events (AEs) in specific subtypes. Sixty-five patients with PTCL were enrolled: n = 38 angioimmunoblastic T-cell lymphoma (AITL), n = 25 PTCL not otherwise specified, and n = 2 other T-cell lymphomas. The ORR was 39.7% (95% confidence interval [CI], 28.1-52.5) in all patients and 56.3% (95% CI, 39.3-71.8) for AITL. Median PFS was 3.5 months overall (954% CI, 2.1-4.4), and 3.6 months (95% CI, 1.9-8.3) for AITL. Median DOR was 3.7 months (95% CI, 2.0-15.3), and greatest in patients with AITL (7.8 months; 95% CI, 2.0-16.3). The median overall survival was 32.8 months (95% CI, 14.4 to not applicable). Tipifarnib-related hematologic AEs were manageable and included neutropenia (43.1%), thrombocytopenia (36.9%), and anemia (30.8%); other tipifarnib-related AEs included nausea (29.2%) and diarrhea (27.7%). One treatment-related death occurred. Mutations in RhoA, DNMT3A, and IDH2 were seen in 60%, 33%, and 27%, respectively, in the AITL tipifarnib responder group vs 36%, 9%, and 9% in the nonresponder group. Tipifarnib monotherapy demonstrated encouraging clinical activity in heavily pretreated relapsed/refractory PTCL, especially in AITL, with a manageable safety profile. This trial was registered at www.ClinicalTrials.gov as #NCT02464228.

Hormonal and cycle phase predictors of within-women shifts in self-perceived attractiveness: Tests of alternative functional models

Prior research has produced mixed findings regarding whether women feel more attractive during the fertile phase of the menstrual cycle. Here, we analyzed cycle phase and hormonal predictors of women's self-perceived attractiveness (SPA) assessed within a daily diary study. Forty-three women indicated their SPA, sexual desire, and interest in their own partners or other potential mates each day across 1–2 menstrual cycles; saliva samples collected on corresponding days were assayed for estradiol, progesterone, and testosterone; and photos of the women taken at weekly intervals were rated for attractiveness. Contrary to some prior studies, we did not find a significant increase in SPA within the estimated fertile window (i.e., cycle days when conception is possible). However, within-cycle fluctuations in progesterone were significantly negatively associated with shifts in SPA, with a visible nadir in SPA in the mid-luteal phase. Women's sexual desire and SPA were positively associated, and the two variables fluctuated in very similar ways across the cycle. Third-party ratings of women's photos provided no evidence that women's SPA simply tracked actual changes in their visible attractiveness. Finally, for partnered women, changes in SPA correlated with shifts in attraction to own partners at least as strongly as it did with shifts in fantasy about extra-pair partners. Our findings provide preliminary evidence for the idea that SPA is a component of women's sexual motivation that may change in ways similar to other hormonally regulated shifts in motivational priorities. Additional large-scale studies are necessary to test replication of these preliminary findings.

Menstrual Irregularity: A Physiological Adaptation to Cope Perceived Stress.

Menstrual cycle characteristics are regulated hormonally and are integrated at the level of the hypothalamus. Stress can affect the hypothalamic-pituitary gonadal axis. The objective of the study was to analyse the stress levels of women and compare their autonomic tone and menstrual characteristics. A group of 100 apparently healthy, young, female volunteers were included in this pilot cohort study. Subjects were assessed for perceived stress using the Perceived Stress Scale 14 Item (PSS-14) questionnaire, underwent a heart rate variability (HRV) test on the second, 10th, and 21st days of their menstrual cycle, and their menstrual history was recorded.The statistical analysis was done using Statistical Product and Service Solutions (SPSS, version 21.0; IBM SPSS Statistics for Windows, Armonk, NY) software. Metric data were expressed in terms of numerical value and analysed as mean ± SD. Paired Student's T-test was used to compare the HRV data of all three days of the menstrual cycle separately, and p value<0.05 was considered significant. Menstrual irregularity was complained of by 13 subjects (Group A), and the rest (87 subjects) reported regular menses (Group B). The perceived stress scores of Group A were significantly higher than Group B (32.53±5.062 vs 28.057±7.618; p=0.044). On second day, Group A had higher median R-R interval (714.38±106 vs 656.84±73.50 ms; p=0.015) and lower average heart rate (85.85±12.07 vs 92.39±9.98 bpm; p=0.034) than Group B, suggesting parasympathetic dominance. On the 10th day, Group A had a higher standard deviation of heart rate (7.09±1.88 vs 5.97±1.71 bpm; p=0.032) and a very low-frequency band (1105.94±984.12 vs 730.49±557.41 μs2; p=0.046) than Group B, indicating parasympathetic dominance in Group A. On the 21st day, Group A had a higher standard deviation of R-R interval (58.19±20.46 vs 44.85±14.55 ms; p=0.004), root mean square standard deviation (55.71±29.84 vs 31.89±15.99 ms; p<0.001), percentage of R-R differing by 50 ms (19.20±19.58 vs 10.87±10.31%; p=0.020), total power (3,440.23±2722.29 vs 2,068.28±1,322.49 μs2; p=0.004), high-frequency band (1,247.57±1173.54 vs 539.06±HPO438.92 μs2; p<0.001), standard deviation ratio of the Poincaré plot (0.53±0.19 vs 0.39±0.16; p=0.003), normalised HF (44.0±12.9 vs 35.4±10.6; p=0.009), and a lower LF/HF ratio (1.43±0.80 vs 2.11±1.16; p=0.043) and normalised LF (53.9±14.4 vs 64.1±11.9; p=0.006) than Group B, suggesting higher parasympathetic tone of Group A than Group B. Analysing these results, it can be concluded that, in apparently healthy young women, menstrual irregularity is a physiological adaptation to combat perceived stress and maintain parasympathetic dominance.

Regorafenib plus FOLFIRINOX as first-line treatment for patients with RAS-mutant metastatic colorectal cancer (FOLFIRINOX-R trial): a dose-escalation study.

The combination of bevacizumab and FOLFIRINOX is used in patients with RAS-mutant metastatic colorectal cancer (RASm-mCRC). Regorafenib, an oral multi-tyrosine kinase inhibitor, has antiangiogenic properties, cytostatic effects and also true cytotoxic effects, unlike bevacizumab. The aim of this study was to determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of the regorafenib-FOLFIRINOX combination in patients with RASm-mCRC. The FOLFIRINOX-R trial was a phase 1/2 study where the dose-escalation part (3 + 3 design with three dose levels, DLs) was completed before its early termination. FOLFIRINOX (14-day cycle) included oxaliplatin (standard dose), folinic acid, fluorouracil and irinotecan (150 or 180mg/m²). Regorafenib (120 or 160mg daily) was given from day 4 to day 10 of each cycle. Dose-limiting toxicity (DLT) was studied in the first three cycles. Eligibility criteria included ECOG performance status ≤ 1 and not previously treated RASm-mCRC. Thirteen patients (median age: 65 years; min-max: 40-76) were enrolled. DLT could not be evaluated in one patient (DL3) due to poor observance. The median treatment duration and median follow-up were 6.2 (min-max: 2.3-10) and 13.4 (min-max: 3.8-18.0) months, respectively. Dose was modified in 12/13 (92%) patients. One grade 3 hypokalemia occurred at DL2. MTD was not reached at DL3. Grade 3 diarrhea was recorded in 7/13 patients (13 events) equally distributed in all DLs. The RP2D for this regorafenib-FFX combination could not be determined due to a high prevalence of grade 3 diarrhea related to treatment as advised by our Independent Data Monitoring Committee. ClinicalTrials.gov : NCT03828799.

Ruxolitinib in treatment-naive or corticosteroid-refractory paediatric patients with chronic graft-versus-host disease (REACH5): interim analysis of a single-arm, multicentre, phase 2 study

Chronic graft-versus-host disease (GVHD) is a debilitating, and sometimes life threatening, complication of allogeneic haematopoietic stem-cell transplantation (HSCT). We aimed to investigate the activity, pharmacokinetics, and safety of ruxolitinib added to corticosteroids in paediatric patients (ie, <18 years) with moderate-to-severe chronic GVHD. In this single-arm, phase 2 study, patients were recruited at 21 hospitals or clinics across 14 countries in Asia, Europe, and Canada. Eligible patients were aged 28 days to younger than 18 years, had undergone allogenic HSCT, and had been diagnosed with treatment-naive or corticosteroid-refractory moderate-to-severe chronic GVHD, per 2014 National Institutes of Health consensus criteria. Patients received oral ruxolitinib dosing on the basis of their age at the start of treatment: those aged 12 years to younger than 18 years received 10 mg twice daily (age ≥12 to <18 years group), those aged 6 years to younger than 12 years (age ≥6 to <12 years group) received 5 mg twice daily, and those aged 2 years to younger than 6 years received 4 mg/m2 twice daily (age ≥2 to <6 years group). Treatment was to be administered in 28-day cycles for approximately 36 months, alongside supportive treatment per institutional guidelines. The primary activity endpoint was overall response rate at cycle 7 day 1. Activity and safety analyses are reported in the full analysis set, which included all patients who received at least one dose of ruxolitinib. Here we report the prespecified interim analysis, scheduled to occur after all patients had completed 1 year of treatment or discontinued treatment, and the results for the primary endpoint evaluation reported here is to be considered final. This study is registered with ClinicalTrials.gov, NCT03774082, enrolment is complete, and the study is ongoing. Between May 20, 2020, and Sept 17, 2021, 48 patients were screened, of whom 45 were enrolled and received at least one dose of study drug (median age was 11·0 years [IQR 7·2-14·3], 16 [36%] were female, 29 [64%] were male, 21 [47%] were White, one [2%] was Black or African American, 23 [51%] were Asian, 17 [38%] were treatment-naive, 28 [62%] were corticosteroid-refractory). As of data cutoff (Oct 19, 2022), after a median ruxolitinib exposure of 55·1 weeks (IQR 13·1-75·3), the overall response rate at cycle 7 day 1 was 40·0% (18 of 45; 90% CI 27·7-53·3), with responses seen in seven (41%) of 17 treatment-naive patients and 11 (39%) of 28 corticosteroid-refractory patients. The most common treatment-related adverse events of grade 3 or worse were neutropenia (eight [18%] of 45) and thrombocytopenia (six [13%]). Seven (16%) patients had grade 3 or worse serious treatment-related adverse events; the most common was hyponatraemia (two [4%] of 45). Three (7%) patients died while on-treatment (within 30 days of treatment discontinuation), one due to Aspergillus infection, one due to septic shock, and one due to acute respiratory distress syndrome; none were considered to be related to study drug. Pending final analysis, this study suggests that ruxolitinib is active and well tolerated in both treatment-naive and corticosteroid-refractory patients aged 2 years to younger than 18 years with chronic GVHD, thereby supporting its use in this patient population. The safety profile of ruxolitinib in this patient population is consistent with that of adults. Final analysis of this study will provide further information on the long-term benefits of ruxolitinib in children with chronic GVHD. Novartis.

Ayurvedic Management of Endometriosis – A Case Study

Introduction: Endometriosis is a benign gynaecological disorder defined by presence of endometrial glands and stroma outside the lining of uterine cavity. This ectopic endometrial tissue behaves as normal endometrial tissue and bleeds every month. This blood may become encysted and form endometrioma. The exact prevalence is not known but estimates range from 10-15% within the woman reproductive age group. Materials and methods: A 26-year-old married patient came to the OPD of Prasutitantra evam Streeroga on 10 September 2023 with the complains of failure to conceive since four and half years along with early and scanty menses since 3 years. A chocolate cyst of size 18*21*13mm in right ovary and a haemorrhagic cyst of size 42*36*41mm in left ovary was detected by USG. She was given Virechana Karma in first cycle, followed by Matra Basti with Dashamoola Trivruta Taila for 7 days in next consecutive cycle and orally Saptasara Kashayam along with Purana Guggulu Choorna as Prakshepa and Goghruta as Anupana. Result: After treatment her USG on 31/11/2023 relieved complete resolution of the chocolate cyst. The follow-up was done for 1 month which showed no recurrence of the cyst. Discussion: Virechana eliminates the Doshas and normalizes the ovarian functions. Dashamoola Trivruta Taila Matra Basti helps in Vaatanulomana and does Tridosha Shamana, in Saptasara Kashayam most of the ingredients are having digestive, carminative, analgesic, anti-inflammatory, Stroto Shodhana, Vatakaphashamana, laxative, and blood purifier properties. Guggulu when given with Saptasar Kashayam will increase the efficiency of the formulation by its Yogavahi property thus helping in breaking the pathogenesis.

O-151 Endometrial preparation using CONCEIVF algorithm with intrauterine and sub-endometrial endosera administration for enhanced pregnancy rates in women with thin endometrium

Abstract Study question Could personalized regenerative medicine based strategies promote endometrial growth and receptivity in women with refractory thin endometrium resulting in successful implantation and live births? Summary answer Personalized regenerative medicine based strategies remarkably promote endometrial growth and receptivity in women with refractory thin endometrium resulting in successful implantation and live births What is known already Thin endometrium (&amp;lt;7mm) is considered sub-optimal for embryo transfer and associated with reduced pregnancy chances. Regenerative medicine based strategies utilizing stem cells, growth factors alone or in combination for endometrial regeneration have been proposed as futuristic clinical therapies. Data-intensive biomedical technologies in research studies reveals that humans vary widely at genetic, biochemical, physiological, exposure and behavioral levels, especially with respect to disease processes and treatment responsiveness. Hence there is a need to deeply ‘personalize,’ interventional strategies at clinical and dosage level for individual patients. Study design, size, duration In this self- controlled study, 60 women with history of more than 3 failed IVF cycles due to persistent refractory thin endometrium (&amp;lt;7mm) were enrolled between July 21-December 23. 42 women were treated with intrauterine administration of Endosera and 18 patients were treated with sub-endometrial administration of Endosera as suggested by CONCEIVF - Proprietary Algorithm from Seragen.. Endosera is Autologous platelet derived implantation friendly anti-inflammatory cytokines and concentrated growth factors and progenitor cells. Participants/materials, setting, methods CONCEIVF-Algorithm classifies patients (High, Moderate, Poor responders) based on age, BMI, clinical history, guiding standardized dosage routines for proliferative, secretory, implantation phases including CD 33/CD34 cells minimal threshold, are specified. Intrauterine Endosera administration, 2 or 3 times from menstrual cycle day 5 during FET, precedes embryo transfer. Sub-endometrial administration involves Endosera with endothelial progenitor cell support on cycle days 5-7, followed by embryo transfer two days after the final Endosera infusion in the subsequent cycle. Main results and the role of chance Clinical pregnancy rate was 77%(46/60), no pregnancy in 10 patients accounting for 17%. 50% (30/60) delivered healthy babies and 17%(10/60) of uneventful pregnancies are progressing. 3 patients (5%) had miscarriage between 6-8 weeks. Improvement in endometrium thickness (EMT) was 90% with mean difference of 1.9mm improvement in 54 patients. No adverse effects reported. 33 patients out of 42 conceived and 6 out of 42 patients did not conceive and 3 out of 42 patients are yet to undergo embryo transfer in the intra-uterine group. 13 patients out of 18 conceived and 4 out of 18 patients did not conceive and 1 out of 18 patient is yet to undergo embryo transfer in the sub-endometrial group. Live birth rate and on-going pregnancies are indicators of overall endometrial quality (thickness and receptivity) improvement and validates that personalization helps to achieve maximum success rate. 15 out of 60 patients who were referred to surrogacy have conceived. In women with a history of cycle cancellations due to thin endometrium, CONCEIVF algorithm recommended personalized Endosera dosages resulted in improved endometrial thickness, clinical pregnancy and live birth. Personalization holds the key for precision because now two patients are alike! Limitations, reasons for caution This prospective self-control study, contains small sample size and lacks randomized controlgroup. Our results are encouraging but large cohort of patients is needed to establish efficacy. of protocols and positive patient predictors score to strengthen Conceivf personalized recommendations. Wider implications of the findings Despite global rise in FET for diverse indications, ongoing efforts to find the optimal endometrial preparation protocol persist. Our personalized approach achieved cumulative 74% pregnancy rate (40/54 ETs done), inspiring planned randomized trials to validate results and help women with resistant thin endometrium to conceive without surrogacy. Trial registration number Not applicable

P-421 Enhancing the success of frozen embryo transfer by human chorionic gonadotropin injection on the day of progesterone supplementation onset - a machine learning study

Abstract Study question Does subcutaneous injection of human chorionic gonadotropin (hCG) at the onset of progesterone supplementation affect clinical pregnancy rate in frozen embryo transfer cycles? Summary answer Clinical pregnancy rates are higher when hCG injection is administered at the onset of 300 mg/day progesterone in patients undergoing frozen embryo transfer. What is known already HCG and progesterone play crucial roles in embryo transfer and implantation during in vitro fertilization. Exisitng studies have demonstrated that pre-administration of hCG at the onset of progesterone supplementation for frozen embryo transfer increases clinical pregnancy rates in patients with endometriosis. However, the synergistic effects of hCG and progesterone co-supplementation in a broader range of patients remain unexplored and require further investigation. A multifactorial analysis of hormone replacement therapy, covering various patient-specific aspects, is necessary to understand the implications of this approach. Study design, size, duration This retrospective cohort study analyzed data from 2,251 single frozen embryo transfers performed between Jan 2019-Aug 2023 at the INVICTA Fertility Centre, Poland. The dataset was selected by the practitioner and included age, AMH, BMI, embryo morphology grade, total number of transfers, medical and embryological procedures, recurrent implantation failure, preimplantation genetic testing, endometrial thickness before transfer (≥ 7 mm), and the menstrual cycle day on which progesterone was started. Participants/materials, setting, methods Patients (21-47 years) receiving 300 or 600 mg/day progesterone for five days were divided into the control and hCG (6,500 IU hCG injection on progesterone onset) groups. A machine learning model was trained using a gradient boosting technique (100 decision trees, four leaves, maximum depth of two nodes, learning rate of 0.05) to identify factors affecting the clinical pregnancy rate. Statistical analysis was performed to compare clinical pregnancy rates between the groups. Main results and the role of chance Our machine-learning model revealed that hCG injection (512 processes vs. 1739 processes without it) at the onset of progesterone administration is an important feature for the clinical pregnancy rate. The performance accuracy of the model was approximately 70%. Of the 1,294 protocols where patients received 300 mg/day progesterone, 311 included hCG injection while 983 did not. The clinical pregnancy rate was significantly higher in the hCG group than that in the control group (54% vs. 46%, P &amp;lt; 0.05), with 167 clinical pregnancies observed in patients receiving hCG injections against 452 pregnancies without it. In contrast, among the 957 protocols where 600 mg/day progesterone was administered, the previously observed effect was not significant (P &amp;gt; 0.05). Comparing 201 processes with hCG injection to 756 processes without it, the incidence of clinical pregnancies was 46.8% and 47.2% (with 94 and 357 confirmed pregnancies), respectively. Other factors such as the morphology grade of the embryo used for transfer, patient’s age, AMH, BMI, total number of transfers performed on the patient, menstrual cycle day on which progesterone was started, occurrence of recurrent implantation failure, and the use of preimplantation genetic testing were not significantly different between the groups. Limitations, reasons for caution This study focused on frozen embryo transfers and validation across other protocols using fresh embryo transfers, and different doses or routes of hCG and progesterone administration are needed. The impact of hCG administration on patients with various causes of infertility should also be explored. Wider implications of the findings Pre-administration of hCG injection along with a daily dose of 300 mg/day progesterone enhanced clinical pregnancy rates for frozen embryo transfer. This holds the potential for the optimization of hormon supplementation protocols to increase overall success rates in assisted reproductive technologies. Trial registration number not applicable

P-775 What is the potential of cervicovaginal mucus as a biomarker for identifying the fertile window and the effectiveness of AI-enhanced prediction for scalability and accessibility?

Abstract Study question What is the potential of cervicovaginal mucus as a biomarker for identifying the fertile window and the effectiveness of AI-enhanced prediction for scalability and accessibility? Summary answer Cervicovaginal mucus is a reliable biomarker for the fertile window. AI Foundation models show promise in enhancing this method’s scalability and predictability. What is known already The timing of ovulation corrosponds to the fertile window. Although modern methods of ovulation detections yield high accuracies, they often require the purchase of sensors/equipment which creates a barrier to those in low-resource settings. Natural fertility awareness based methods, such as CVM monitoring, eliminate this problem, but there are limited recent large-scale studies validating cyclical CVM changes. Digitising CVM monitoring could remove the subjectivity of the interpretation of symptoms. Despite the advances of AI in other FABM areas, limited work has been done on computer vision models for CVM evaluation, which could revolutionise accessibility and scalability, particularly in low-resource settings. Study design, size, duration The study involved analysis of self-reported CVM characteristics data from over 57,000 individuals; largest sample size used in any study investigating the use of CVM as a biomarker. Furthermore, a dataset of CVM images were collected from the public survey and labeled manually (n = 13). The study included retrospective and pilot components, employing statistical analyses like ANOVA, chi-squared, and Spearman correlation, and AI techniques like zero-shot learning for binary segmentation of CVM from smartphone-captured images Participants/materials, setting, methods Self-reported CVM data was obtained from a fertility tracking app and analysed using ANOVA and chi-squared tests to identify and validate findings of cyclical variations, and correlation with lifestyle data. Zero-shot learning was employed using foundation models. An ethically-reviewed survey was generated to collect images for subsequent model training Images from the survey were segmented using the Grounding DINO and the SAM. The surface area and elasticity extracted are used to determine the fertility score. Main results and the role of chance In individuals with 28-day cycles, CVM showed significantly higher quality during the ovulatory phase, marked by increased elasticity (p = 0.00001), amount (p = 0.00001)), and lubricative texture (p &amp;lt; 0.0001), when compared to both the follicular and luteal phases. However, variations in individuals with longer, irregular cycles of over 35 days length, were less pronounced. Age was found to significant positive correlation with overall CVM quality (r = 0.06, p &amp;lt; 0.0001), while no significant correlations were observed with smoking (r = 0.11, p = 0.23), alcohol consumption (r = 0.13, p = 0.17), or BMI (r = 0.006, p = 0.41)). Zero-shot learning for segmentation showed improved accuracy in detecting and extracting CVM from images, with precision of 0.867 and F1 score of 0.929, highlighting the model’s ability to correctly distinguish between CVM patterns corresponding to fertile and infertile status. The intersection over union score suggested consistent model performance. Overall, CVM emerged as a scalable fertility biomarker in typical menstrual cycles, with AI models showing potential for enhancing prediction accuracy and scalability. Limitations, reasons for caution The study’s limitations include its reliance on self-reported CVM data and the potential bias in the foundation models as there was no fine-tuning, due to a small dataset (n = 13). Additionally, the effectiveness of CVM as a biomarker in irregular menstrual cycles and subfertility requires further exploration. Wider implications of the findings Automated analysis of CVM can be a low-cost, scalable (potentially to millions, via mobile application), non-invasive method for fertility awareness. Our findings highlight the potential of AI in empowering fertility awareness, especially in low-resource settings with little access to reproductive healthcare, thus contributing to global health equity. Trial registration number n/a

O-012 Three Injections Protocol for IVF; a proof of concept study into elaborating the outmost patient friendly protocol in IVF

Abstract Study question To examine if 3 injections in follicular phase, with long-acting FSH, long-acting antagonist and HCG/Agonist triggering can result in efficient egg retrieval and blastocyst formation. Summary answer In this proof-of-concept study, all patients retrieved mature oocytes and ended having adequate blastocysts by receiving only 3 injections in the follicular phase. What is known already The old-fashioned way with multiple injections (majority minimum 15 injections) is still the golden IVF standard. Twenty years ago, a long-acting FSH gonadotropin brought into market (corifollitropin alpha) which represented a huge step in simplifying the follicular phase Recently, a new long-acting GnRH-antagonist emerged (degarelix) which can downregulate the hypophysis for 30 days. We have published that titrating this long-acting antagonist to 0,1mg single dose we can downregulate hypophysis without LH surge. Study design, size, duration A prospective proof of concept study included in total 15 patients 30-39 years old who followed IVF treatment with homologous oocytes during 2020-2022 in Assisting Nature IVF Clinic, Thessaloniki, Greece. In this study, we test if by delaying one day the long-FSH and also delaying the long-antagonist, still patients can produce mature eggs without needed extra FSH doses. Institutional review board approved the protocol. Participants/materials, setting, methods Patients were enrolled if AMH was 1,5-3,0 ng/ml and antagonist protocol applied. 150IU fixed corifollitropin-a (Elonva) for ovarian stimulation administered either on evening cycle Day-3 or morning day-4. Fixed 0,1 mg of long-acting GnRH-antagonist (Degarelix) administered on cycle Day 8. Fixed 250mcg recombinant-hCG (Ovitrelle) or 0,3 mg of Triptorelin (Arvekap) for ovulation triggering administered as soon as 3 follicles of 18mm were present. Produced blastocysts were all cryopreserved and transferred in subsequent thawed cycles. Main results and the role of chance All 15 patients reached ovum pick-up with mature eggs retrieved (mean 13,5 oocytes). None experienced any LH surge, however, 3/15 (20%) required an extra dose of 300IU FSH (Puregon) to enhance follicular development. The majority 12/15 reached OPU without any FSH adjuvant. All 15 patients had blastocysts formed (mean 3,3) and in their subsequent thawed cycles the cumulative live birth rate was 53,3% (8/15). Patient satisfaction was excellent though closer monitoring was applied due to novelty of the protocol. Limitations, reasons for caution Limited number of patients as it is a complete novel protocol with unknown outcome. Protocol was focused in normo-ovarian-reservers to secure follicular production. Some patients might need an extra dose of gonadotropin. Long-acting antagonist still not registered for IVF use. Wider implications of the findings Current study promising results indicate that a 3-injection follicular stimulation can efficiently produce mature eggs, viable blastocysts and pregnancies. Although, few patients required an extra fourth injection of FSH, if such approach will be tested in larger studies will re-establish our way for stimulation at least for normo-reservers. Trial registration number NCT03877185

P-592 Comparison of the cumulative live birth rate of different doses of rFSH in poor ovarian reserve women undergoing GnRH antagonist ART treatment: a Randomized Controlled Trail

Abstract Study question Does an increased FSH dosage result in higher cumulative live birth rates in advanced age women with poor ovarian reserve treated with IVF or ICSI? Summary answer In poor ovarian reserve women, FSH dose of 300 IU/day does not improve cumulative live birth rates as compared to 150 IU/day. What is known already Natural fecundity and pregnancy rate following ART decrease dramatically in women aged 35 years and above. An open-label multicenter RCT described no difference in the cumulative live birth rate between the increased FSH dose (225/450 IU/day) and standard dose (150 IU/day) in women with a predicted poor ovarian response. Nevertheless, it is still unclear whether advanced age women with poor ovarian reserve who are undergoing IVF/ICSI benefit from a higher gonadotrophin dose. Therefore, we aimed to assess whether rFSH 300 IU/day compared to 150 IU/day in advanced age women with poor ovarian reserve resulted in higher cumulative live birth rates. Study design, size, duration A single center prospective randomized controlled trail that included first in vitro fertilization cycle with a GnRH-ant protocol and subsequent fresh and frozen-thawed cycles from April 2019 to December 2022. The study group included 104 women that received rFSH 150 IU/day and 99 women received rFSH 300 IU/day in antagonist protocol. Participants/materials, setting, methods Women for their first stimulation cycle, aged 35 to 42 years with antral follicle count（AFC）≤ 5 or anti-mullerian hormone （AMH） ≤ 1.2 ng/ml were randomized. Study group and control group respectively received 300 IU and 150 IU rFSH from menstrual cycle day 2 or 3 till the day of trigger. The primary outcome was cumulative live birth rate per woman per stimulation over a 2-year period to account for the first live birth. Main results and the role of chance This study included 203 women with the GnRH antagonist protocol. Of them, 99 patients were in 300 IU/day rFSH group, and 104 patients were in 150 IU/day rFSH group, respectively. The two groups were comparable for all baseline characteristics. The cumulative live birth rate for increased rFSH dosing (300 IU) versus standard dosing (150 IU) was 13.13% (13/99) versus 25% (26/104) per stimulation cycle. (P = 0.049). There were no differences in cumulative pregnancy rates 27.27% (27/99) vs 35.58% (37/104) per stimulation cycle. (P = 0.262). The cumulative live birth rate and cumulative pregnancy rates per transfer cycle in 300 IU/day rFSH group vs 150 IU/day rFSH group presented no statistical difference. No significant difference was found in secondary outcomes including time to live birth, number of MII oocytes, number of transferable embryos, implantation rate, multiple pregnancy rate, ectopic pregnancy rate and miscarriage rate between the two groups. Limitations, reasons for caution As this study is open-label, potential selective cancelling of cycles in women could have influenced the cumulative results. Also, this study practiced in a single-center and specific patient population, the results may not be generalizable to a broader population. Wider implications of the findings In women 35 years or older with poor ovarian reserve, improving rFSH dosage to 300IU in GnRH-ant protocol did not improve cumulative live birth rate. rFSH 150IU/day may be recommended at the start of COS to achieve live birth outcomes while decrease costs. Trial registration number ’not applicable

O-208 The Programmed Ovulatory Frozen-Thawed Embryo Transfer Cycle (PO-FET): a suggested FET protocol integrating aspects of embryo transfer scheduling, efficacy optimization and maternal/fetal safety

Abstract Study question What is the effect of 30mg oral dydrogesterone (DYD), given to induce endometrial receptivity in natural-proliferative-phase-FET-cycles (NPP-FET), on ovulation, progesterone and DYD/DHD-levels, respectively, and outcomes? Summary answer Oral DYD 30mg allows scheduling endometrial receptivity in natural cycles while not interfering with ovulation in the vast majority of patients. What is known already Globally, approximately 60% of all ETs are performed after cryopreservation. Hormone Replacement Treatment (HRT)-FET cycle-regimens have come under scrutiny, because of i) risk of insufficient progesterone exposure with conventional dosing-schemes and ii) maternal/fetal risks stemming from the iatrogenic lack of a corpus luteum. Oral DYD 10mg (tid) supposedly does not interfere with ovulation/corpus luteum formation, and does not cross-react with progesterone in ELISA. It could thus be used for inducing endometrial receptivity (scheduling, in a natural cycle, the time point of ET) and luteal phase support, while allowing ovulation dissociated from the window-of-implantation and monitoring of endogenous progesterone serum levels. Study design, size, duration Within a multi-centric, prospective, clinical cohort study (NCT03507673), 559 normally cycling women from the routine care population who underwent FET after IVF/ICSI in a natural cycle (2/2021 – 8/2023) had serum/plasma samples prospectively collected/stored on day of FET for measurement of E2, progesterone and DYD/DHD in Roche Elecsys®-Immunoassay and liquid chromatography/tandem mass spectroscopy (LC-MS/MS), respectively. FET was performed on day 2/3 (cleavage-stage) or day 4/5 (morula/blastocyst) in 17.4% and 82.6% of FETs, respectively. Participants/materials, setting, methods From cycle day 10, women underwent endocrine (E2, LH and P) and sonographic monitoring until E2 &amp;gt;180pg/ml, leading follicle &amp;gt;16mm and endometrial thickness was &amp;gt;6mm. Physicians could then initiate oral DYD10mg (tid) or–in absence of LH rise–postpone initiation, under 2-daily monitoring, to meet the organizational preferences of the patient and/or center (for example, avoiding weekends). FET was performed for day 2 (cleavage), 3, 4 or 5 (blastocyst) on day 3-6 of DYD-intake, respectively. Main results and the role of chance Previously reported PK of 10mg DYD (tid) are confirmed/extended. While log-levels of DYD and DHD were highly correlated (0.95), P-levels were not (0.02, 0.02). In 94.4% of patients, ovulation could be confirmed by serum-P levels on the day of FET or in late luteal phase. Medians (IQR) of DYD and P on day 3 and days 5, respectively, were 0.93ng/ml (0.93ng/ml) and 2.96ng/ml (3.19ng/ml), and 1.13ng/ml (1.09ng/ml) and 8.50ng/ml (4.40ng/ml). Serum-P levels increased with the FET day (medians 2.0, 3.0, 6.6, and 8.5 ng/ml on days 2, 3, 4, and 5) and only very weakly correlated with LH, E2 levels, and follicular diameter at last monitoring. 42.5% and 34.8% of patients had positive hCG and ongoing clinical pregnancy, respectively. Ongoing pregnancy was independent from plasma-DYD levels (&amp;lt; 25th percentile [&amp;lt;0.66 ng/ml] 37.9% vs. ≥25thperc. [≥0.66 ng/ml] 34.3%, RD 1.5%, 95%CI: -16.5% to 17.4%, p = 0.334), yet dependent from serum-P levels (&amp;lt; 25thperc [&amp;lt;4.85 ng/ml] 25.9% vs. ≥25thperc [≥4.85 ng/ml] 35.3%, RD 9.4%, 95% CI 0.4% to 17.6%, p = 0.0161).However, neither of the two serum hormone values is predictive of a dichotomous outcome in isolation, nor do they demonstrate predictive interaction when considered together in logistic regression modelling. Limitations, reasons for caution DYD, like hCG or any other progestin given for LPS, may negatively interfere with LH surge, ovulation and luteal phase characteristics. Controlled studies on different progestin types and doses are necessary to better understand how to optimize luteal phase and thereby optimally support embryo nidation, pregnancy maintenance and maternal/fetal health. Wider implications of the findings The PO-FET protocol induces the implantation window, thus offers (some) flexibility in FET timing, shows little interference with ovulation/corpus luteum formation, provides double gestagenic support with no need for monitoring P or DYD levels, however allows corpus luteum activity monitoring in luteal phase and early pregnancy, is injection-free, and low-cost. Trial registration number NCT03507673

P-799 Augmenting endometrial thickness and implantation rates: investigating the efficacy of autologous blood cell derivative - endosera in women struggling with thin endometrium and infertility

Abstract Study question Could autologous platelet derived growth factor based strategies promote endometrial growth in women with refractory thin endometrium resulting in sustained implantation and live births? Summary answer Autologous platelet derived growth factor based strategies remarkably promote endometrial thickness and receptivity in women with refractory thin endometrium and pregnancy outcomes What is known already Repeated implantation failure (RIF) attributed to thin endometrium poses significant challenge in reproductive medicine. In cases where conventional treatments prove ineffective, couples often contemplate stressful option of surrogacy. Regenerative strategies, such as platelet-rich plasma (PRP), exhibit promise by capitalizing on anti-inflammatory and pro-regenerative attributes of platelet-derived growth factors. Recognizing the imperative for anti-inflammatory microenvironment conducive to successful implantation, Endosera, a cell-free growth factors concentrate tailored for implantation has been formulated. This study seeks to evaluate the effectiveness of Endosera in augmenting endometrial thickness and implantation rates, offering potential remedies for RIF and thin endometrium. Study design, size, duration In this prospective self-controlled study 62 women (24-47 years) were enrolled spanning May 2021 to December 2023. Women experienced &amp;gt;2 failed IVF cycles and multiple cycle cancellations due to refractory thin endometrium with poor endometrial receptivity defined as endometrial thickness of &amp;lt; 7mm despite standard medical therapy, abnormal endometrial pattern and suboptimal endometrialvascularity, negative hysteroscopic screening for endometrial pathology, and negative bacteriologicscreening and despite multiple failed conventional therapies were selected to undergo Endosera treatment. Participants/materials, setting, methods After obtaining informed consent, patients underwent three intrauterine infusions of Endosera on menstrual cycle Day 7, Day 12, and 2 days before frozen embryo transfer (FET). Alongside standard hormone replacement therapy (HRT), 0.8 ml of Endosera was introduced into the uterine cavity. Pregnancy confirmation relied on a positive serum β-HCG test two weeks post-ET, while clinical pregnancy was established by detecting fetal heartbeat through transvaginal ultrasound four weeks post-ET. Main results and the role of chance In this study involving 62 patients facing multiple cancelled IVF cycles due to refractory thin endometrium, the administration of three doses of Endosera demonstrated significant positive outcomes. Average endometrial thickness notably increased from 6.2 ± 1.2 mm to 8.4 ± 1.2 mm (P &amp;lt; 0.0001) after the 2nd Endosera dose, reaching an optimal thickness of ≥ 8mm. Among the participants, 43 achieved positive pregnancy result (69.4%), with 26 (41.9%) delivering healthy babies and 7 (11.3%) uneventful ongoing pregnancies. Poor outcomes included for 2 (3.2%) patients cycle was cancelled due to no endometrial improvement 5(8.1%) miscarriages before 10 weeks, while 12 (19.4%) women didn’t conceive and for 4.8%(3) patients results awaited post ET. No adverse effects were reported, indicating safety of Endosera.Cumulative positive pregnancy outcomes recorded to be 53.2% (33). The formulation, standardized to contain 6-9 times higher growth factor levels than peripheral blood, emphasizes implantation-friendly and anti-inflammatory cytokines. This optimized composition aligns with cyclical requirements of the endometrial phases (proliferation, secretion, and implantation), creating an angiogenic and anti-inflammatory environment crucial for successful implantation. Endosera’s safety, reproducibility, and efficacy in mimicking natural tissue repair and regeneration processes position it as promising solution for refractory thin endometrium-related challenges. Limitations, reasons for caution This study, though demonstrating improved outcomes in refractory thin endometrium cases with Endosera treatment, acknowledges limitations such as a small sample size and absence of a randomized control group. To establish Endosera as a routine adjuvant in IVF, larger study with stringent inclusion criteria for refractory thin endometrium is recommended. Wider implications of the findings Endosera demonstrated notable success with significant improvement in implantation, pregnancy, and live birth rates for refractory thin endometrium patients prompts rigorous randomized controlled studies. These will include diverse populations, validating results and offering patients hope to reduce financial and psychological stress and challenges associated with cycle cancellations and surrogacy. Trial registration number Not Applicable

P-683 Progestins vs flexible GnRH antagonist for LH suppression during controlled ovarian stimulation in POSEIDON groups 3 and 4 patients: Analysis of effectiveness and cycle outcomes

Abstract Study question How do cycle outcomes differ between controlled ovarian stimulations using progestins vs flexible GnRH antagonists for LH suppression in women with diminished ovarian reserve (DOR)? Summary answer While progestin use is associated with significantly higher blastocyst rate than GnRH antagonists in POSEIDON group 4, the latter gives better results in group 3. What is known already Controlled ovarian stimulation (COS) in patients with DOR carries the additional risk of premature luteinizing hormone (LH) surge and ovulation.GnRH antagonists are popular for LH suppression in COS because of their convenient, quicker onset of action, flexibility to use GnRH agonist as a trigger and continue as double stimulation, allowing rapid pooling of embryos. Ease of oral administration, combined with cost-effectiveness and retention of all the benefits of GnRH antagonists makes progestins an attractive alternative to GnRH antagonists for COS in patients with DOR who often need multiple stimulation cycles to enable the pooling of embryos. Study design, size, duration An open-label, multicentric, randomized controlled study was conducted over 1 year from January 2023 to December 2023. 140 women aged 21- 42 years and with AMH &amp;lt;1.2 ng/dl were randomized into 2 groups in a 1:1 ratio, using either oral progestins or GnRH antagonists for LH suppression. The two groups were further comparative analyzed under POSEIDON 3 and 4 subgroups. Those with BMI &amp;gt;40kg/m2 and with partners having severely compromised semen parameters were excluded. Participants/materials, setting, methods In Group A (PPOS): Medroxyprogesterone acetate 10 mg orally was given daily with gonadotropins (hMG 300- 375 IU) from cycle day 2 until trigger. In Group B (Antagonist), patients had daily GnRH antagonist, cetrotide 0.25 mg, subcutaneous administration started when the dominant follicles reached 12-14 mm size during controlled ovarian stimulation. This was continued until the trigger. Following oocyte retrieval and ICSI, embryos were cultured until D5 and vitrified fortransfer in subsequent HRT cycles. Main results and the role of chance Patients in Group A, using PPOS, were noted to have significantly better fertilization rates than those in Group B, using flexible GnRH antagonists (0.82 + 0.2 vs 0.66 + 0.4, p-value &amp;lt;0.01). Though the number of top-quality embryos (TQE) frozen was not significantly different between groups A and B (p-value = 0.44), a significant difference in the outcome was noted when comparatively analyzed under the subgroups of POSEIDON groups 3 and 4. While patients in POSEIDON group 4 got significantly more top-quality embryos (TQE) when progestins were used for LH suppression (1 + 0.11 vs 0.77 + 0.41, p-value &amp;lt;0.01), those in POSEIDON group 3 got significantly more top-quality embryos when GnRH antagonist was used (0.94 vs 2, p-value &amp;lt;0.01). Patients in Group A and B were found to have no significant difference in the following outcomes: incidence of premature LH surge (4.3% vs 7.1%, p value= 0.71), number of days of stimulation (10.26 + 2.18 vs 10.26 +2.94, p value= 0.99), total gonadotropin dosage used (3448.64+ 1007.98 vs 3087.41 + 1260.56, p value=0.06), total number of oocytes retrieved (5.84 + 3.3 vs 4.9 + 3.4, p value=0.09) and total cycle cancellation rate (30.1% vs 35.7%, p value= 0.11). Limitations, reasons for caution The small sample size of the cases limits the current statistical power of the study. The results being encouraging need to be confirmed in a larger patient population and followed for a longer duration to enable calculation of implantation and clinical pregnancy rates for all patients. Wider implications of the findings Oral progestins are an effective and cheaper, patient-friendly alternative to injectable GnRH antagonists during COS in women with DOR. Considering the significantly higher TQEs formed, PPOS can be preferred in older, POSEIDON group 4 patients, whereas flexible GnRH antagonist protocol can be our choice in the younger, POSEIDON group 3. Trial registration number Not applicable

P-664 Insulin-like peptide 3 as a potential biomarker in predicting IVF success and ovarian reserve in women with unexplained infertility and diminishing ovarian reserve

Abstract Study question Could insulin-like peptide 3 (INSL3) predict ovarian reserve and in vitro fertilization (IVF) success in women with unexplained infertility (UI) and diminishing ovarian reserve (DOR)? Summary answer In women with DOR, reduced intrafollicular and serum INSL3 levels correspond with low AMH and high FSH levels, similar to established ovarian reserve markers. What is known already INSL3, belonging to the insulin-like peptide family, is produced by theca interna cells within antral follicles and the corpora lutea. It is hypothesized that INSL3 is integral to the initial development and function of antral follicles, specifically through its regulatory effect on androgen biosynthesis in the thecal cells of these follicles. Moreover, INSL3 is implicated in the modulation of the ovarian microenvironment, which is essential for facilitating the maturation of oocytes. Study design, size, duration This research was carried out at the IVF centers of two tertiary university hospitals, assessing 49 infertile women with either UI (n = 24) or DOR (n = 25) during IVF treatment. A control group (n = 26) comprised women with normal ovarian reserve undergoing IVF due to male or tubal factors. Outcome parameters are ovarian reserve markers (serum FSH, estradiol, AMH, INSL3 concentration and antral follicle count [AFC]), positive pregnancy rate and live birth rate (LBR) (gestational age ≥28 weeks). Participants/materials, setting, methods Women aged between 20-40 with a body mass index (BMI)&amp;lt;30 kg/m² were included. Serum FSH, estradiol, AMH, INSL3 levels and AFC were evaluated on menstrual cycle days 2 or 3, and INSL3 in follicular fluid from dominant follicles (&amp;gt;14 mm) were evaluated during oocyte retrieval. Exclusions included endocrine abnormalities (e.g., polycystic ovary syndrome, hyperprolactinemia, hypo and hyperthyroidism) cycle cancellation due to lack of a viable embryo, uncorrected Mullerian anomalies, recurrent miscarriage history and hydrosalpinx presence. Main results and the role of chance The mean age in the study groups was 28.41±3.5 (UI), 32.40±4.21 (DOR), and 29.65±3.91 (control). In the DOR group, female age (p = 0.001), BMI (p = 0.049), duration of infertility (p = 0.006), previous IVF attempts (p &amp;lt; 0.001), basal FSH (p &amp;lt; 0.001), and basal estradiol (p &amp;lt; 0.001) were higher, while AMH (p &amp;lt; 0.001), AFC (p &amp;lt; 0.001), and follicular fluid INSL3 (p &amp;lt; 0.001) were lower. Serum INSL3 in DOR was lower but not statistically significant. No correlation was found between serum INLS, follicular fluid INSL3, ovarian reserve markers, positive pregnancy rates, miscarriage, and LBR. DOR group had longer stimulation durations (p = 0.017), but lower max estradiol (p &amp;lt; 0.001), fewer oocytes (p &amp;lt; 0.001), mature follicles (p &amp;lt; 0.001), and PN (p &amp;lt; 0.001). Pregnancy rates were 54.1% (UI), 24% (DOR), and 53.84% (control); LBRs were 54.1% (UI), 20% (DOR), and 42.3% (control), with significant differences in pregnancy tests (p = 0.04) and LBR (p = 0.03), both lower in DOR. Univariate analysis identified duration of infertility (p = 0.019) and basal FSH (p = 0.009) as significant LBR predictors. Multivariable analysis confirmed basal FSH (p = 0.033) as significant, with increased duration of infertility and basal FSH level reducing LBR probability. Limitations, reasons for caution The limited sample size of our study potentially undermines the robustness of circulating INSL3 as a predictive biomarker for DOR, evidenced by the non-significant decrease in serum INSL3 levels in the DOR group. Moreover, the lack of INSL3 level assessment during oocyte retrieval further constrains our findings. Wider implications of the findings Our research explored INSL3 as a viable biomarker for predicting ovarian reserve and IVF success in UI and DOR cases. Reduced INSL3 levels in circulation and follicular fluid in DOR patients could be beneficial in clinical practice. Trial registration number not applicable