Flexible Protocol Research Articles

Challenges and Lessons Learned for Conducting Usability Evaluations in Applied Military Research Environments

Conducting usability evaluations in applied military environments is notably different from traditional usability testing, as such environments pose restrictions on when, where, and how testing is conducted. In addition, specialized experience needed from military personnel pose challenges to recruitment and obtaining sufficient time with representative end users. This paper will discuss some challenges and lessons learned for consideration before, during, and after usability assessment data collection. Main recommendations include: recruiting experts qualified to provide feedback that aligns with the purpose of the evaluation; developing a flexible research protocol to allow for the maximum participation possible from any and all involved; and conducting domain research to supplement the researchers’ own knowledge base to minimize reliance on SMEs. Finally, it is important to carefully document not only results, but knowledge and experience gained from specific efforts in order to assist future researchers in conducting work with similar systems.

Assessment of Binding Site and Development of Small Molecule Inhibitors Targeting Epidermal Growth Factor Receptor Mutations in Non-Small Cell Lung Cancer (NSCLC)

Background:Mutations occurring in the epidermal growth factor receptor of the tyrosine kinase family concerned with non-small cell lung cancer have been specifically targeted.Objectives:The library design and R-group enhancement technique have been carried out on the preexisting marketed drugs to increase the binding affinity of the designed novel compounds. The screening of compounds was done using a flexible docking protocol.Methods:Molecular docking studies provided information about binding pockets and interactions of molecules with the mutant (PDB: 4I1Z) as well as wild-type (PDB: 4I23) EGFR enzymes. The flexible docking was well supported by ADMET and molecular dynamic simulation studies.Results:On the basis of docking score and protein-ligand interactions, the highest-scoring molecule was selected for molecular dynamics simulation, providing a complete insight into the ligand interaction and saturationConclusion:The screened molecules can act as potential EGFR inhibitors in the management of drug resistance.

Teasing out elevational trends in infraspecific Prunus taxa: A vein analysis approach.

Using 33 specimens collected from across their range in Turkey, we demonstrate that the subspecies of Prunus microcarpa C.A.Mey react very differently to altitude. We first outline a simplified, flexible protocol for sectioning and removing the epidermis of small, difficult-to-image leaves for leaf vein studies. We then used venation analysis software to evaluate the two subspecies of this wild cherry in relation to altitude. We also found key differences in venation features between short-shoot and long-shoot leaves for each taxon. Differences include statistically significant negative correlation between vein density, and positive correlation between areole area and altitude in long-shoot leaves of Prunus microcarpa subsp. microcarpa, while its short-shoot leaves had a positive relationship between maximum areole area, and negative relationship between vein density, numbers of veins and endpoints. Meanwhile, P. microcarpa subsp. tortuosa (Boiss. & Hausskn.) Browicz recorded trends that were largely opposite of this, but beside vein thickness and areole area, were not statistically significant. This difference may be part of each taxon's overarching syndrome of anatomical and morphological adaptations to its external environment. RESEARCH HIGHLIGHTS: Features of vein density and thickness fell, while areole area and vein length rose with altitude in P. microcarpa. P. microcarpa subsp. tortuosa showed opposite trends, but reacted less strongly to altitude. Short-shoot and long-shoot have significantly different venation parameters. Using sections proportionate to leaf size is useful to compare venation of leaves that vary due to dimorphism. We discuss protocol strategies for imaging of difficult leaves for venation analyses.

Oral Contraceptive Pill Pretreatment in Polycystic Ovary Syndrome Patients Undergoing IVF/ICSI Using the Gonadotrophin Releasing Hormone Antagonist Protocol (A Randomized Controlled Trial)

Abstract 700 women with PCOS undergoing IVF/ICSI using flexible GnRH antagonist protocol, were included in the study, and randomized to either OCP pretreatment (n = 350), or no pretreatment (n = 350). The latter group received OCP pretreatment in the form of 30µg ethinyl estradiol / 3mg drospirenone (Yasmin®, Bayer AG, Berlin, Germany) pills for an interval of 21 to 28 days; after which COH was started following a 5-day pill wash-out period. OCP-pretreated PCOS women had more retrieved oocytes, albeit, on the expense of increased gonadotropin consumption. However, this increased oocyte yield did not translate to a significant effect on conception rates among intended-to-treat PCOS woman receiving OCP pretreatment. Conversely, it shifted among OCP-pretreated women who actually started COH cycle, to a significant 18% reduction in the probability of successful pregnancy.

A social relationship-based energy efficient routing scheme for Opportunistic Internet of Things

Opportunistic Internet of Things (OppIoT) combines Opportunistic Networks and the Internet of Things to provide opportunistic communication between IoT devices and human-created communities in order to improve network connectivity, reliability, and longevity. This is significant because it introduces a new approach to connect and communicate smart devices in situations where there is no end-to-end connectivity. Due to the non-stable existence of connectivity between nodes, building a scalable, flexible, interoperable, and energy efficient routing protocol is a difficult issue. This study presents a new routing protocol for the Opportunistic Internet of Things called Social relationship based Energy Efficient Routing (SEER), which bases routing decisions on the forwarding feasibility degree, residual energy, and buffer capacity of nodes. SEER surpasses EBR and EDR in terms of delivery probability, hop count, and overhead ratio, according to simulation results utilizing the Opportunistic Network Environment (The ONE) simulator.

Effectiveness of oestrogen pretreatment in patients with expected poor ovarian response (POSEIDON groups 3 and 4) undergoing GnRH antagonist protocol: study protocol for a randomised controlled trial

IntroductionWomen characterised by diminished ovarian reserve are considered to have poor ovarian response (POR) according to Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) criteria. Patients in this population often have...

Aliphatic Alcohol Hydroxyl‐Directed One‐Pot Stepwise Synthesis: A Concise Synthesis of 1H‐pyrrolo[3,4‐b]quinoline‐1,3(2H)‐diones

AbstractA concise and flexible protocol to assemble structurally diverse 1H‐pyrrolo[3,4‐b]quinoline‐1,3(2H)‐diones (29 examples, 70–87% yields) has been developed via one‐pot stepwise synthesis. The potentially valuable quinine‐fused heterocycles were synthetized by utilizing aliphatic alcohol hydroxyl as directing group which promoted a sequential transformation to form functionalized aminomaleimides, and then underwent an I2‐oxidized tandem annulations. This route involved the formation of multiple new chemical bonds (C=N, 2C−N, C−C) in a one‐pot fashion under mild conditions.

A Double machine learning trend model for citizen science data

Abstract Citizen and community science datasets are typically collected using flexible protocols. These protocols enable large volumes of data to be collected globally every year; however, the consequence is that these protocols typically lack the structure necessary to maintain consistent sampling across years. This can result in complex and pronounced interannual changes in the observation process, which can complicate the estimation of population trends because population changes over time are confounded with changes in the observation process. Here we describe a novel modelling approach designed to estimate spatially explicit species population trends while controlling for the interannual confounding common in citizen science data. The approach is based on Double machine learning, a statistical framework that uses machine learning (ML) methods to estimate population change and the propensity scores used to adjust for confounding discovered in the data. ML makes it possible to use large sets of features to control for confounding and to model spatial heterogeneity in trends. Additionally, we present a simulation method to identify and adjust for residual confounding missed by the propensity scores. To illustrate the approach, we estimated species trends using data from the citizen science project eBird. We used a simulation study to assess the ability of the method to estimate spatially varying trends when faced with realistic confounding and temporal correlation. Results demonstrated the ability to distinguish between spatially constant and spatially varying trends. There were low error rates on the estimated direction of population change (increasing/decreasing) at each location and high correlations on the estimated magnitude of population change. The ability to estimate spatially explicit trends while accounting for confounding inherent in citizen science data has the potential to fill important information gaps, helping to estimate population trends for species and/or regions lacking rigorous monitoring data.

Improved TDD operation on Software-Defined Radio platforms towards future wireless standards

Software-Defined Radio (SDR) platforms are valuable for research and development activities or high-end systems that demand flexible wireless protocols. While low-latency digital baseband processing can be achieved using a dedicated processing unit, like an FPGA or hardware accelerator, its multi-purpose Radio Frequency (RF) front-end often poses a limitation. Zero Intermediate Frequency (ZIF) transceivers are favorable for SDR, however, even for Time Division Duplex (TDD) systems, these transceivers suffer from self-interference when the transmitting and receiving Local Oscillator (LO) is set to the same frequency. To achieve low self-interference, switching from receiving to transmitting mode is needed. However, the time this takes (turnaround time, TT) for configurable RF front-ends often violates the strict timing requirements of protocols like Wi-Fi and 5G, which require response times in the order of microseconds. In this work, we first evaluate the advantages and disadvantages of several methods to suppress self-interference of a ZIF transceiver. Next, a novel approach is proposed, which can reduce the TT to as low as 640ns using the widely used AD9361 configurable ZIF RF front-end, while the noise floor is at the same level as achieved by the conventional way of switching between transmit and receive mode. We have realized and validated this approach using openwifi — an open-source Wi-Fi implementation on SDR. As a result, the receiver sensitivity is improved by up to 17dB in the 2.4GHz band and 9.5dB in the 5GHz band, for over-the-air transmissions.

Quantum based flexible secure authentication protocol (SAP) for device to device (D2D) communication

Quantum based flexible secure authentication protocol (SAP) for device to device (D2D) communication

A premature luteinizing hormone surge without elevated progesterone levels has no adverse effect on cumulative live birth rate in patient undergoing a flexible GnRH antagonist protocol: a retrospective study

BackgroundA premature luteinizing hormone (LH) surge refers to an endogenous LH peak that occurs before follicle maturation or human chorionic gonadotropin injection in the process of controlled ovarian hyperstimulation. The effect of premature LH surge on pregnancy outcomes in fresh embryo transfer cycles is still controversial. The aim of this study was to explore the effect of a premature LH surge without elevated progesterone levels on the cumulative pregnancy rate (CPR) and cumulative live birth rate (CLBR) of patients during a flexible GnRH antagonist protocol.MethodsA total of 730 infertile women undergoing IVF/ICSI were recruited for this retrospective study. Only women who either delivered a live infant or had no remaining frozen embryos after a single stimulation cycle were included in the analysis. During the study period, each patient underwent a flexible GnRH antagonist protocol. Women were divided into two groups according to the presence or absence of a premature LH surge. The primary outcome measures were the CPR and CLBR per ovarian stimulation cycle. The secondary outcome measures were the number of oocytes retrieved, fertilization rate, good-quality embryo rate, and clinical pregnancy rate.ResultsNinety-one women (12.47%) experienced a premature LH surge without elevated progesterone levels, and the other 639 (87.53%) women were assigned to the control group. The numbers of oocytes retrieved and fertilization rate were significantly greater in the premature LH surge group than in the control group. There was no significant difference between groups in the good-quality embryo rate, clinical pregnancy rate or live birth rate in the fresh embryo transfer cycle. The primary outcome measures, the CPR and CLBR per ovarian stimulation cycle, were not significantly different between the premature LH surge group and the control group. According to the analysis stratified by ovarian response (normal or high), there were no significant differences in pregnancy outcomes between the groups with and without a premature LH surge.ConclusionsThe retrospective study demonstrated that the patients experiencing a transient premature LH surge without progesterone elevation had equivalent pregnancy outcomes with those without a premature LH surge on a flexible GnRH antagonist protocol. The present conclusions need to be further validated in a prospective well-designed large-scale study.

Computational study of the binding orientation and affinity of noncovalent inhibitors of the papain-like protease (PLpro) from SARS-CoV-1 considering the protein flexibility by using molecular dynamics and cross-docking.

The papain-like protease (PLpro) from zoonotic coronaviruses (CoVs) has been identified as a target with an essential role in viral respiratory diseases caused by Severe Acute Respiratory Syndrome-associated coronaviruses (SARS-CoVs). The design of PLpro inhibitors has been proposed as an alternative to developing potential drugs against this disease. In this work, 67 naphthalene-derived compounds as noncovalent PLpro inhibitors were studied using molecular modeling methods. Structural characteristics of the bioactive conformations of these inhibitors and their interactions at the SARS-CoV-1 PLpro binding site were reported here in detail, taking into account the flexibility of the protein residues. Firstly, a molecular docking protocol was used to obtain the orientations of the inhibitors. After this, the orientations were compared, and the recurrent interactions between the PLpro residues and ligand chemical groups were described (with LigRMSD and interaction fingerprints methods). In addition, efforts were made to find correlations between docking energy values and experimentally determined binding affinities. For this, the PLpro was sampled by using Gaussian Accelerated Molecular Dynamics (GaMD), generating multiple conformations of the binding site. Diverse protein conformations were selected and a cross-docking experiment was performed, yielding models of the 67 naphthalene-derived compounds adopting different binding modes. Representative complexes for each ligand were selected to obtain the highest correlation between docking energies and activities. A good correlation (R 2 = 0.948) was found when this flexible docking protocol was performed.

P-396 Modified Flare/GnRH antagonist protocol versus GnRH antagonist protocol in oocyte cryopreservation cycles

Abstract Study question Is there an advantage for modified flare/ GnRH antagonist protocol in comparison to antagonist protocol in oocyte cryopreservation cycles? Summary answer Modified flare/ GnRH antagonist protocol is at least as good as antagonist protocol in oocyte cryopreservation cycles, potentially improving maturity rate in subgroup of patients. What is known already Ultrashort flare GnRH agonist (GnRHa)/GnRH -antagonist protocol offer benefits of stimulatory effect of repeated microdose flare on endogenous FSH and the advantages of GnRH antagonist suppression, including the option to use GnRHa ovulation trigger to avoid ovarian hyperstimulation syndrome. GnRHa ovulation trigger has been associated with suboptimal response that refers to lesser than expected oocyte yield. Our research group previously demonstrated the value of GnRHa follicular challenge test (FACT) in prediction of suboptimal response assessed by post ovulation trigger LH levels and as a dynamic ovarian reserve test (not published yet). Study design, size, duration A retrospective, age- matched, cohort study that included all non-medical oocyte cryopreservation cycles from October 2020 to December 2021. The study group included 110 women that received modified flare/ GnRH antagonist protocol and were matched with 110 women that received antagonist protocol. Participants/materials, setting, methods Women in the modified flare/ GnRH antagonist protocol were administered GnRHa (Decapeptyl 0.2 mg) on day 2 to menstrual cycle followed by flexible antagonist protocol. They were compared to age matched women that received flexible antagonist protocol. In both study groups GnRHa final ovulation trigger was administered. Main results and the role of chance Among 110 women that underwent non-medical fertility preservation with modified Flare/GnRH antagonist protocol, in comparison to 110 women that received antagonist protocol, a reduced dosage of gonadotropins was consumed with more oocytes retrieved (14.63 vs. 13.86) and more mature oocytes cryopreserved (11.32 vs. 10.14), but differences were not significantly different. In a subgroup with more than 6 oocytes retrieved significantly more mature oocytes were cryopreserved in women that received modified flare/antagonist protocol (14.03± 0.90 vs. 11.63± 0.71, p = 0.03) in comparison to women that received antagonist protocol. Limitations, reasons for caution Limitations of our study are its retrospective nature and lack of information on the oocyte’s fertilization competence and pregnancy outcomes. Wider implications of the findings Future studies will further explore the advantages of this protocol in terms of higher oocytes maturity rate, intra cycle prediction of ovarian response and suboptimal response to GnRHa triggering. Trial registration number not applicable

P-671 Comparing clomiphene citrate/ flexible GnRH antagonist vs ultrashort flare GnRH agonist protocols for controlled ovarian stimulation in poor ovarian reserve patients

Abstract Study question How do Clomiphene citrate (CC)/ flexible GnRH antagonist and ultrashort flare GnRH agonist protocols compare in poor ovarian reserve patients (POSEIDON groups 3 & 4)? Summary answer In poor ovarian reserve patients, irrespective of age, use of CC / flexible antagonist vs ultrashort flare protocol significantly reduces gonadotrophin consumption and stimulation duration. What is known already Poor responders constitute 47% of ART patients and up to 65% of these have diminished ovarian reserve. Despite the various treatment options available, lack of good quality evidence to enable recommendation of a particular protocol or adjuvant continues to pose a challenge to their effective management. The need for multiple stimulations for pooling up embryos also makes effective cost of treatment an added concern in them. Study design, size, duration An open label, multi centric, randomized controlled study was conducted over a period of 1 year recruiting 116 women having AMH <1.2ng/dl and antral follicle count (AFC) <5 who were further analysed in POSEIDON 3 and 4 subgroups. Patients were randomized to 1 of 2 groups for controlled ovarian stimulation. Those with severe endometriosis, adenomyosis, autoimmune or metabolic disorders, sustained hyperprolactinaemia, congenital uterine malformations and with male partners having severe oligoasthenoteratozoospermia were excluded. Participants/materials, setting, methods Group A (55 women) received CC 100mg from D1-D5 with 300 IU human menopausal gonadotrophin (hMG) in a flexible GnRH antagonist protocol. Group B (61 women) underwent ultrashort flare protocol. 1mg leuprolide was administered from D1-D4 and 300 IU hMG given D2 onwards followed by flexible GnRH antagonist administration. Dual trigger with triptorelin and recombinant hCG was administered 35-36 hours before oocyte retrieval. Embryos cultured till D5 were vitrified for transfer at a later stage. Main results and the role of chance The two groups were well matched for baseline characteristics like age, BMI, AMH, duration of infertility, D2 AFC, estradiol and FSH levels. The mean total gonadotrophin consumption (3387.29 + 1082.5 vs 4407 + 1224.2, p value <0.01) and the duration of stimulation (10.71 + 2.52 vs 11.95 + 2.43, p value <0.01) were significantly lower in group A vs group B. The primary outcomes of median number of oocytes retrieved (4 vs 4, p value- 0.71) , M2 rate (3 vs 3, p value-0.91), fertilisation rate were similar in the two groups. The secondary outcomes of oocyte retrieval rate (103.05 + 42.97 vs 97.14 + 42.96, p value- 0.63), FORT (0.81 +0.68 vs 0.96 + 0.48, p value- 0.37) FOI (0.91 + 0.55 vs 0.92+ 0.54, p value 0.92), top quality embryo rate (0.53 + 1.1 vs 0.41 + 0.84, p value 0.61), cycle cancellation rate (26.22% vs 29.09%), implantation rate (23.63% vs 24.59%) and clinical pregnancy rate (21.31% vs 20%) were also similar in group A vs B respectively. A subgroup analysis of POSEIDON 3 versus POSEIDON 4 patients revealed similar outcomes with both the protocols in the two groups. Limitations, reasons for caution Small sample size of the cases limits the current statistical power of the study. Wider implications of the findings CC /flexible GnRH antagonist protocol is an effective alternative to ultrashort flare protocol in patients with poor ovarian reserve irrespective of their age. The lower gonadotrophin dosage required and shorter duration of stimulation observed make it a viable option in patients who might need multiple stimulations for pooling up embryos. Trial registration number Not applicable

P-662 Embryo ploidy rates following PPOS or GnRH antagonist protocol. A prospective study with repeated ovarian stimulation

Abstract Study question Is there any difference in embryo ploidy rates following progesterone primed ovarian stimulation (PPOS) using micronized progesterone or GnRH antagonist protocol? Summary answer Pituitary downregulation with a PPOS protocol with micronized progesterone results in a comparable number of euploid blastocysts with a GnRH antagonist protocol. What is known already Although the GnRH antagonist is consider by most the gold standard protocol for controlling the LH surge during ovarian stimulation for IVF/ICSI, progesterone-primed ovarian stimulation protocols (PPOS) are being increasing used in freeze-all protocols. Still, despite the promising results of PPOS protocols, an early randomized trial reported potentially lower live births in recipients of oocytes resulting following downregulation with medroxyprogesterone acetate as compared with a GnRH antagonist protocol. The scope of the current prospective study was to investigate whether PPOS with micronized progesterone results in equivalent blastocyst euploidy rates as compared with a GnRH antagonist protocol. Study design, size, duration In this prospective study, performed between September 2019 to January 2022, 44 women underwent two consecutive ovarian stimulation (OS) protocols within a period of 6 months in a GnRH antagonist protocol or in a PPOS protocol with oral micronized progesterone. Participants/materials, setting, methods Overall, 44 women underwent two OS cycles with identical fixed dose of rFSH (225 or 300 IU) in both cycles. Downregulation in the 1st cycles was performed with the use of a flexible GnRH antagonist protocol and consecutively, after a washout period of one month, control of LH surge was performed with oral micronized progesterone from stimulation day 1. After the completion of both cycles, all generated blastocysts underwent genetic analysis for aneuploidy screening (PGT-A). Main results and the role of chance Comparisons between cycles did not reveal differences between the duration of OS neither in the gonadotrophins dose. Hormonal profile on the day of trigger revealed statistically significant differences between cycles in all the tested hormones except for FSH: with significantly higher serum E2 levels, more elevated LH levels and higher Progesterone levels in PPOS cycles as compared with antagonist cycles, respectively. PPOS protocol resulted in a significantly higher number of oocytes (10.27± 5.84 versus 12.68± 8.09), (DBM -2.4 [95% CI -4.1; -0.73]), MIIs (7.34±4.15 versus 9.09± 6.12), (DBM -1.8 [95% CI -3.1; -0.43]), and 2PNs (5.66±3.35 versus 7.14± 4.99), (DBM -1.5 [95% CI -2.6.1; -0.32]) as compared with the GnRH antagonist protocol. Nevertheless, no differences were observed regarding the mean number of blastocysts (2.84±2.12 versus 2.91±2.11), (DBM -0.07 [95% CI -0.67; 0.53]) and the mean number of biopsied blastocysts (2.86±2.15 versus 2.93±2.16), (DBM -0.07 [95% CI -0.70; 0.56]). Finally, no difference was observed for the primary outcome, with a mean number of euploid embryos of 0.86 ± 0.90 vs. 1.00 ± 1.12 for the comparison of PPOS vs. GnRh antagonist. Limitations, reasons for caution The study was powered to detect differences in the mean number of euploid embryos and not in terms of pregnancy outcomes. Additionally, per protocol there was no randomisation, the first cycle was always a GnRH antagonist cycle and the 2nd a PPOS with one month of washout period in between. Wider implications of the findings The current study provides evidence that the PPOS may result in equivalent blastocyst euploidy rates compared with antagonist protocol. This may imply that in case of a freeze-all protocol, clinicians may safely consider PPOS to control the LH surge and patients could benefit from the advantages (cost and oral administration). Trial registration number NCT04108039

P-592 Follicular GnRH agonist challenge test (FACT) to predict suboptimal response to GnRH agonist trigger in oocyte cryopreservation cycles

Abstract Study question Can follicular GnRH agonist administration predict suboptimal response to GnRH agonist trigger assessed by LH levels post ovulation trigger in non-medical oocyte cryopreservation program? Summary answer Follicular agonist challenge test (FACT) can serve as an adjunct pre-trigger, intracycle tool to predict adequate response to agonist trigger. What is known already Suboptimal response to GnRH agonist ovulation trigger refers to failure to retrieve the expected number of oocytes. It was demonstrated in up to 5.5% of cycles based on relatively low number of studies with heterogenous suboptimal response definitions and prevalence, no clear cut-offs and mainly post - stimulation tools to predict unsuccessful cycle. The most studied variable associated with suboptimal response was LH levels 10-12 hours after ovulation trigger below 12-15IU. Study design, size, duration We prospectively recruited all women that underwent non-medical fertility preservation in our tertiary university affiliated medical center between October 2020 and February 2022 and agreed to participate in the study. The study included 91 women. Participants/materials, setting, methods On day 2 to menstrual cycle, blood tests were drawn (basal Estradiol/E2, basal FSH/FSH2, basal LH/LH2, Progesterone/P2) and ultrasound (US) was performed. On that evening, the women were instructed to inject 0.2 mg GnRH agonist and arrive for repeated blood workup 10-12 hours later at the next morning, followed by a flexible antagonist protocol. On the morning after ovulation trigger blood tests were again taken and LH levels were compared to FACT LH levels. Main results and the role of chance LH levels following agonist ovulation trigger below 15IU occurred in 1.09 % of cycles and were predicted by FACT, r = 0.57, p < 0.001. ROC analysis demonstrated that FACT LH > 42.70 IU would predict LH post trigger of more than 30 IU with 75% sensitivity and 70% specificity, AUC= 0.81. LH levels post trigger also displayed significant positive correlation to basal FSH (r = 0.35, p = 0.002) and basal LH (r = 0.54, p < 0.001). LH levels post ovulation trigger were not associated with total oocytes number or maturity rate. The strongest correlation to the total number of retrieved oocytes and mature oocytes was progesterone level post ovulation trigger (r = 0.74, p < 0.001). Limitations, reasons for caution Limitation of our study include the relatively small sample size designed to detect 5% suboptimal proportion and might have been insufficient to allow identification of very rare suboptimal responses Wider implications of the findings Suboptimal response to agonist trigger, as assessed with post trigger LH levels is a rare event. FACT could serve as an adjunct pre-trigger, intracycle tool to predict adequate response to agonist ovulation trigger. Future studies should focus on optimization of agonist trigger efficacy assessment and prediction, especially in high responders. Trial registration number 0304-20-ASF

P-660 No association between BMI, oocyte yield and maturation following different trigger strategies: a large observational study including 5000 cycles.

Abstract Study question Is patients’ BMI associated with oocyte yield and maturation following different trigger strategies with r-hCG, GnRH agonist (GnRHa) or dual trigger? Summary answer Patients’ BMI is not associated with oocyte yield and oocyte maturation following triggering with rhCG, GnRHa or dual trigger. What is known already Triggering final oocyte maturation is a key step of ovarian stimulation for IVF/ICSI treatment. Although hCG has traditionally been the gold standard for final oocyte maturation, GnRHa is increasingly used as optimal trigger in “freeze-all” era. Recent evidence has demonstrated excellent results with dual-trigger, a combination of hCG and GnRHa. Despite this swift in clinical practice, early studies demonstrated that hCG plasma levels depend on hCG trigger dose and BMI. Furthermore, although dose-finding studies following for GnRHa trigger demonstrated equal efficacy of triptorelin doses ranging from 0.1-0.4mg, these studies pertained only to low BMI patients. Study design, size, duration This is a retrospective observational study including 5190 consecutive cycles ovarian stimulation cycles (OS) performed between January 2019 -September 2022 in a tertiary Fertility Unit within a University Affiliated Hospital. Overall 5190 ovarian stimulation cycles were analyzed: 2691 cycles triggered with subcutaneous administration of 0.2 mg of GnRHa (triptorelin), 1110 with 250 mcg of r-hCG and 1389 with a dual trigger (combination of both 0.2 mg triptorelin+ 250 mcg of r-hCG). Participants/materials, setting, methods Ovarian stimulation was performed with recombinant FSH or HMG at a starting dose 150-300IU depending on patients’ ovarian reserve and BMI. Control of LH surge was accomplished by a flexible GnRH antagonist or PPOS protocol. The primary outcome measures were oocyte maturation rate (MII/oocytes) and FOI (oocytes/AFC); secondary outcomes were oocyte and MII yield. Multivariable regression models were performed to evaluate the interaction between BMI and type of trigger in relation to study’s outcomes. Main results and the role of chance Overall, oocyte and MII yield was significantly different between different types of trigger mainly due the fact that GnRHa was primary used in freeze-all cases, with excellent ovarian reserve. This resulted in a higher number of oocytes (15.95 ± 8.88) and MIIs (12.31 ± 7.27) as compared with cycles triggered with in rhCG (7.83 ± 5.42 and 5.86 ± 4.22 respectively) or dual trigger (8.51 ± 5.70 and 6.44 ± 4.54 respectively) was utilized. Nonetheless, when oocyte maturation rate was comparable between trigger groups (% [95% CI]): GnRHa 77.2 [76.6; 77.8] vs rhCG 74.9 [73.3; 76] vs dual 75.6 [74.5; 76.7]. Multivariable regression analysis, adjusting for confounding factors, demonstrated that BMI was not associated with oocyte maturation rate (OR:1.00 [95% CI: 0.99;1.01]) and FOI (Beta 0.52 [95% CI: -0.49;1.54]). Similarly BMI was not associated number oocytes (Beta 0.02 [95% CI: -0.08; 0.13]) or on the number of MIIs (Beta 0.01 [95% CI: -0.08; 0.10]) retrieved. Interactions between BMI and trigger groups were considered in each model. All analyses were conducted considering patients’ weight, but no association was revealed. Limitations, reasons for caution This is a retrospective study, and we cannot exclude the presence of residual bias despite the large series, the multiple regression models and the indexes like maturation rate and FOI we adopted to account for confounding factors. Wider implications of the findings Although previous small observational studies supported an association between BMI and hCG levels, our large analysis of > 5000 cycles clearly shows that the efficiency of r-hCG, triptorelin or dual trigger is not associated with the patient's BMI and weight, as no significant differences were found in maturation rate and FOI. Trial registration number Not applicable

Results of a Flexible Patient-Centered Approach to the Timing of Thoracic Outlet Decompression in Paget Schroetter Syndrome

Treatment algorithms for subclavian vein (SCV) effort thrombosis (Paget-Schroetter syndrome- PSS) are multiple, ranging from thrombolysis (TL) with immediate or delayed thoracic outlet decompression (TOD) to conservative treatment with anticoagulation alone. We follow a regimen of TL / pharmacomechanical thrombectomy (PMT) followed by TOD with first rib resection, scalenectomy, venolysis and selective venoplasty (open or endovascular) performed electively at a time convenient for the patient. Oral anticoagulants are prescribed for 3 months or longer based upon response. The aim of this study was to evaluate outcomes of this flexible protocol. Clinical and procedural details of consecutive patients treated for PSS from Jan 2001 to August 2016 were retrospectively reviewed. Endpoints included success of TL and eventual clinical outcome. Patients were divided into two groups-Group I: TL/PMT + TOD; Group II: medical management / anticoagulation + TOD. PSS was diagnosed in 114 patients; 104 (62 female, mean age 31 years) who underwent TOD were included in the study. Group I: 53 patients underwent TOD after initial TL / PMT (23 at our institution and 30 elsewhere) with success (acute thrombus resolution) in 80% (n=20) and 72% (n=24) respectively. Adjunctive balloon-catheter venoplasty was performed in 67%. TL failed to recanalize the occluded SCV in 11% (n=6). Complete thrombus resolution was seen in 9% (n=5). Residual chronic thrombus in 79% (n=42) resulted in median SCV stenosis of 50% (range 10 to 80%). With continued anticoagulation, further thrombus retraction was noted with median 40% improvement in stenosis including in veins with unsuccessful TL. TOD was performed at a median of 1.5 months (range 2 - 8months). Re-thrombosis of the SCV occurred in 3 patients 1-3 days postoperatively and was managed with MT / SCV stenting/balloon angioplasty and anticoagulation. Symptomatic relief was achieved in 49/53 (92%) patients at a median follow up of 14 months. 51 patients underwent TOD following medical treatment elsewhere with anticoagulation alone for an average 6 months (range 2-18 months) with recurrent SCV thrombosis in 5 (11%). Thirty-nine patients (76%) had persistent symptoms; the remaining had asymptomatic compression of the SCV with maneuvers. SCV occlusion persisted in 4 patients (7%); the indication for TOD being residual symptoms from compression of collateral veins, the median residual stenosis was 70% (range 30-90%). TOD was performed at a median of 6 months after diagnosis of PSS. Open venous reconstruction with endovenectomy and patch was performed in 4 patients and stenting in 2. Symptomatic relief was achieved in 46/51 (90%) at a median follow up of 24 months. For Paget Schroetter syndrome a management protocol encompassing elective thoracic outlet decompression at a convenient time following thrombolysis is safe and effective, with low risk of re-thrombosis. Continued anticoagulation in the interim results in further recanalization of the subclavian vein and may reduce the need for open venous reconstruction.

Improving Racial and Ethnic Equity in Clinical Trials Enrolling Pregnant and Lactating Individuals.

Racial and ethnic marginalized populations have historically been poorly represented, underrecruited, and underprioritized across clinical trials enrolling pregnant and lactating individuals. The objectives of this review are to describe the current state of racial and ethnic representation in clinical trials enrolling pregnant and lactating individuals and to propose evidence-based tangible solutions to achieving equity in these clinical trials. Despite efforts from federal and local organizations, only marginal progress has been made toward achieving equity in clinical research. This continued limited inclusion and transparency in pregnancy trials exacerbates health disparities, limits the generalizability of research findings, and may heighten the maternal child health crisis in the United States. Racial and ethnic underrepresented communities are willing to participate in research; however, they face unique barriers to access and participation. Multifaceted approaches are required to facilitate the participation of marginalized individuals in clinical trials including partnering with the local community to understand their priorities, needs, and assets; establishing accessible recruitment strategies; creating flexible protocols; supporting participants for their time; and increasing culturally congruent and/or culturally sensitive research staff. This article also highlights exemplars in pregnancy research.

Comparison of fixed and flexible progestin-primed ovarian stimulation protocols to prevent premature luteinization in patients with diminished ovarian reserve.

Flexible progestin-primed ovarian stimulation (PPOS) protocol is demonstrated to be effective in suppressing premature luteinization in few studies. We aimed to compare fixed and flexible PPOS protocols in preventing premature luteinization in patients with diminished ovarian reserve. This retrospective cohort study included patients with a diminished ovarian reserve who were administered PPOS protocols for pituitary suppression during ovarian stimulation in a tertiary center in between January 2019 and June 2022. At fixed protocol, 20mg/day dydrogesterone was started in cycle day two or three along with gonadotropins and continued until trigger day. In contrast, at flexible protocol, 20mg/day dydrogesterone was commenced when the leading follicle reached 12mm or serum estradiol (E2) level was > 200pg/mL. A total of 125 patients, of whom 83 were administered fixed PPOS protocol and 42 were administered flexible PPOS protocol, were included in the analysis. Both groups had similar baseline characteristics and cycle parameters, including total days of gonadotropin administration and total gonadotropin dose (p > 0.05). Premature luteinization occurred at 7.2% and 11.9% of patients in fixed and flexible PPOS protocols, respectively (p = 0.505). Retrieved oocytes numbers, metaphase II oocyte numbers, and 2PN numbers were also similar (p > 0.05). Clinical pregnancy rates per transfer were 52.5% in fixed and 36.4% in flexible protocols (p = 0.499). Both fixed and flexible PPOS protocols had statistically similar outcomes in preventing premature luteinization and other cycle parameters. The flexible PPOS protocol seems to be as effective as the fixed PPOS protocol for patients with diminished ovarian reserve; however, further prospective studies should be conducted to validate the results of our research.