bluuebunny/crossref_metadata_2025 huggingface dataset:
P–539 The use of expanded carrier screening of gamete donors
Authors: Payne M , Skytte A B , Harper J
Published: August 2021

Study question

What are the sperm and egg donor rejection rates after expanded carrier screening (ECS)?

Summary answer

Using an ECS panel looking at 46/47 genes, 17.6% of donors were rejected.

What is known already

The use of ECS is becoming commonplace in assisted reproductive technology, including testing of egg and sperm donors. Most national guidelines recommend rejection of donors if they are carriers of a genetic disease. If the use of ECS increases, there will be a decline in the number of donors available.

Study design, size, duration

A review of the current preconception ECS panels available to donors was carried out through an online search. The genetic testing results of donors from Cryos International were analysed to determine how many were rejected on the basis of the ECS.

Participants/materials, setting, methods

Data on gamete donors and their carrier status was provided by Cryos International, who screen donors using their own bespoke ECS panel. The ECS panels identified through the review were compared to the Cryos International panel and data.

Main results and the role of chance

A total of 16 companies and 42 associated ECS panels were reviewed. There were a total of 2673 unique disorders covered by the panels examined, with a mean of 329 disorders screened. None of these disorders were common to all panels. Cryos International screen 46 disorders in males and 47 in females. From 883 candidate donors, 17.6% (155/883) were rejected based on their ECS result. Carriers of alpha-thalassaemia represented the largest proportion of those rejected (19.4%, 30/155), then spinal muscular atrophy (15.5%, 24/155) and cystic fibrosis (14.8%, 23/155).

Limitations, reasons for caution

Panel information was found on company web sites and may not have been accurate.

Wider implications of the findings: This study highlights the need for consistent EU regulations and guidelines which allow genetic matching of gamete donors to recipients, preventing the need to reject donors who are known carriers. A larger ECS panel would be most beneficial, however, this would not be viable without matching of donors and recipients.

Trial registration number

Not applicable
P–559 Proof of principle for Extended Carrier Screening (ECS) in medically assisted reproduction: First 33 cases of genetic matching for donors and recipients
Authors: Shaikly V , Sage K , Callum P
Published: August 2021

Study question

Does implementation of ECS to reduce reproductive risk when using a donor with a known carrier status serves as a wider model for ART patients.

Summary answer

ECS should be routinely offered to ART patients using their own or donor gametes to reduce risk of having a child with a recessive condition.

What is known already

Responsible implementation of ECS in assisted reproduction is required as commercial offerings increase and become more accessible; ESHRE ethical guidelines are shortly to be published after consideration of stakeholder reviews. Increasingly ECS is included in donor screening, rejecting potential donors for a known carrier status will reduce donor gamete availability. Clinics should consider potential match yield in carrier panels to develop tools and specialist support to deliver and guide patients to help make informed decisions for ECS.

Study design, size, duration

Retrospective evaluation of ECS results for the first 33 patients who undertook counter screening in the clinic setting from April 2020 to December 2020 before using a donor with known carrier status. The findings would serve as proof of concept for wider application.

Participants/materials, setting, methods

Patients had opted to undertake ECS after discussion of risk estimates, family history review and personal options.Testing was commissioned between two ECS providers for international donor banks using panels of 283+ genes. Incidence of carrier match, the number of variants reported, and their clinical significance were reviewed. Main results and the role of chance: Of the 33 co-carrier tests, one carrier match for a patient and potential donor was identified. 41%, 26%, 9% and 3% of patients were carriers of 1, 2, 3 and 4 pathogenic variants respectively in 30 different genes. In 21% of patients, no pathogenic variants were reported. Of the variants identified as incidental findings, six were actionable and eligible for cascade screening to the wider family. This included Cystic Fibrosis, Sickle cell and Thalassemia. A variant for Familial hypercholesterolemia had preventative value. An incidental finding of a fragile X pre-mutation allowed for PGT-M as part of planned treatment

Limitations, reasons for caution

Findings from this first cohort of 33 tests may not represent the general population, follow up evaluation as participant numbers increase is required.

Wider implications of the findings: Implementation of guidelines is required to ensure consistency of methodology and availability of transparent information for ECS to ART patients. Incidental findings may be of value to the patient and wider family.

Trial registration number

Not applicable
P–568 Homozygous Pathogenic Variants in ACTL9 Cause Fertilization Failure and Male Infertility in Human and Mouse
Authors: Dai J , Zhang T , Guo J , Zhou Q , Gu Y , Zhang J , Hu L , Zong Y , Song J , Zhang S , Dai C , Gong F , Lu G , Zheng W , Lin G
Published: August 2021

Study question

What are the other male factors that cause total fertilization failure (TFF) excepting for variants in PLCZ1?

Summary answer

Homozygous variants in ACTL9 (actin like 9) cause abnormal localization of PLCζ in a loosened perinuclear theca (PT) structure and leads to TFF.

What is known already

In previous studies, investigators have reported that the female factors in TFF after intracytoplasmic sperm injection (ICSI) include pathogenic variants in WEE2, TLE6, and TUBB8, whereas for male factors, pathogenic variants in PLCZ1 were reported to be the primary cause of TFF, which account for approximately 30% of couples with male factors in TFF excluding globozoospermia. Most recently, it was reported that pathogenic variants in ACTL7A led to reduced expression and abnormal localization of PLCζ, thereby identifying this genetic variant as a potential cause of TFF.

Study design, size, duration

Fifty-four infertile couples with TFF or poor fertilization (fertilization rate of < 20%) at the Reproductive and Genetic Hospital of CITIC-Xiangya during January 2014 to June 2020 were recruited into this study.

Participants/materials, setting, methods

Male factors were identified in (MOAT). WES analysis was used to analyze the genetic factors of individuals with male factors. Sperm morphological study was conducted by H&E staining and TEM. Immunostaining of PLCζ was used to analyze the status of sperm-borne activation factor. A knock-in mouse model was generated by CRISPER-Cas9 technology. Sperm from homozygous Actl9 variant mice were analyzed by TEM and ICSI. ICSI with AOA was performed in couples with ACTL9 variants.

Main results and the role of chance

A total of 54 couples with TFF or poor fertilization were screened, with 21 couples determined to have a male infertility factor by MOAT. Whole-exome sequencing of these 21 male individuals identified three homozygous pathogenic variants in ACTL9 in three individuals. ACTL9 variations led to abnormal ultrastructure of the PT, with PLCζ absent in the head and present in the neck of the mutant sperm, which contributed to failed normal calcium oscillations in oocytes and subsequent TFF. The key roles of ACTL9 in the PT structure and TFF after ICSI were further confirmed in Actl9-mutated mouse model. Furthermore, assisted oocyte activation by calcium ionophore exposure successfully overcame TFF and achieved live births in a couple with an ACTL9 variant.

Limitations, reasons for caution

The mechanism of how ACTL9 regulate PLCζ remains unknown.

Wider implications of the findings: It provided a genetic marker and a therapeutic option for individuals who have undergone ICSI without successful fertilization.

Trial registration number

not applioable
P–599 random antral follicle count, performed at any day of the menstrual cycle, demonstrates the same predictive value for ovarian response in in vitro fertilization cycles
Authors: Razafintsalama M , Bah M , Amand G , Vienet-Lègue L , Pietin-Vialle C , Bry-Gauillard H , Pinto M , Pasquier M , Jung C , Levaillant J M , Massin N
Published: August 2021

Study question

Does antral follicle count (AFC) retains its predictive value for ovarian response to stimulation for in vitro fertilization (IVF) throughout the whole menstrual cycle?

Summary answer

AFC is strongly correlated to anti-mullerian hormone (AMH) and highly predictive of good ovarian response whatever the day of cycle the ultrasound is performed.

What is known already

Usually performed in the early follicular phase (at day 2–3 of the menstrual cycle), AFC and AMH are the most accurate markers of ovarian reserve. They are routinely used to predict ovarian response to ovarian stimulation for IVF and eventually to individualize the gonadotropin starting dose.

Study design, size, duration

Retrospective cohort study performed between January, 2017 and December, 2019.

Participants/materials, setting, methods

410 consecutive women aged 20 to 42 years were included. Random AFC (r-AFC) was performed during the fertility workup whatever the day of their menstrual cycle was: early follicular phase i.e. day 1 to day 6 (eFP-AFC), mid follicular phase i.e. day 7 to 12 (mFP-AFC) and luteal phase i.e. day 13 or after (LP-AFC). A second AFC was performed before the start of the stimulation (SD1-AFC). AMH was measured in the early follicular phase.

Main results and the role of chance

Random AFC (r-AFC) was correlated to AMH (r = 0.692; p < 0.001), SD1-AFC (r = 0.756; p < 0.001) and number of oocytes retrieved (r = 0.491; p < 0.001). When regarding AFC depending on the cycle day group, the correlation with AMH was significantly higher for the LP-AFC, (LP-AFC) (r = 0.853) than for the eFP-AFC (r = 0.657; p < 0.001) and for the mFP-AFC (r = 0.668). The correlation with SD1-AFC was similar regardless of the time of performance of r-AFC (r = 0.739, 0.783, 0.733, respectively for eFP, mFP and LP-AFC). Moreover, the ROC analysis showed the same predictive value for good ovarian response (more than 6 oocytes retrieved) for the eFP-AFC, mFP-AFC and LP-AFC (AUC 0.73, 0.75 and 0.84 respectively) as well as for AMH and SD1-AFC (AUC 0.74 and 0.74, respectively).

Limitations, reasons for caution

This is a retrospective analysis, however data were prospectively collected and the method for ultrasound acquisition of AFC was standardized.

Wider implications of the findings: The absence of significant variation of AFC across the menstrual cycle allows to its random performance. Ultrasound performed besides early follicular phase discloses informations on ovaries, the uterus and the endometrium. It is more comfortable and convenient for women and physicians by limiting targeted appointment during menstruation and reiterated examination.

Trial registration number

Not applicable
P–602 Pregnancy outcomes of progestin primed ovarian stimulation protocol, GnRH antagonist protocol and GnRH agonist protocol for young patients undergoing PGT-M
Authors: Li Y , Zhao W , Liang X
Published: August 2021

Study question

To investigate the pregnancy outcomes of progestin primed ovarian stimulation protocol, GnRH antagonist protocol and GnRH agonist protocol for young patients undergoing preimplantation genetic testing for monogenic gene diseases.

Summary answer

PPOS protocol could reduce the normal chromosome formation and further development potential of embryos, suggesting that the PPOS protocol should be used cautiously.

What is known already

GnRH antagonist protocol (GnRHant) and GnRH agonist protocol (GnRHa) have been used in clinic for many years as routine regimens, and their ovarian stimulation effects and pregnancy outcomes have been confirmed by a large number of literatures. As a new protocol in recent years, the reports of pregnancy outcomes of progestin primed ovarian stimulation protocol (PPOS) are inconsistent.

Study design, size, duration

This retrospective cohort study was performed in a reproduction center from a tertiary hospital between September 2018 and November 2020 which included 147 young patients (<35 year old) undergoing preimplantation genetic testing for monogenic gene diseases (PGT-M) after stimulated by progestin primed ovarian stimulation protocol (n = 44), GnRH antagonist protocol (n = 60) or GnRH agonist protocol (n = 43).

Participants/materials, setting, methods

This study included 147 young patients (<35 year old) undergoing preimplantation genetic testing for monogenic gene diseases (PGT-M) after stimulated by progestin primed ovarian stimulation protocol (PPOS, n = 44), GnRH antagonist protocol (GnRHant, n = 60) or GnRH agonist protocol (GnRHa, n = 43). The primary outcomes were normal karyotype embryo rate and live birth rate. The embryological and clinical outcomes were measured.

Main results and the role of chance

Basic characteristics such as infertility duration, age, and body mass index (BMI) were comparable in study groups. No significant difference was found in the number oocytes retrieved or viable embryos between the groups.

Normal karyotype embryo rate of PPOS protocol was significantly lower than GnRHant and GnRHa protocol (57.6% for PPOS vs 76.0% for GnRHant vs 67.3% for GnRHa).

No significant difference were found in chemical pregnancy rate (77.3% for PPOS vs 73.3% for GnRHant vs 74.4% for GnRHa) or clinical pregnancy rate (69.8% for PPOS vs 71.7% for GnRHant vs 72.5% for GnRHa). While live birth rate of PPOS protocol was significantly lower than GnRHant and GnRHa protocol ( 45.5% for PPOS vs 58.3% for GnRHant vs 72.2% for GnRHa).

Limitations, reasons for caution

This is a preliminary study which needs to be further confirmed by large-scale clinical studies.

Wider implications of the findings: Although this is a preliminary study which needs to be further confirmed by large-scale clinical studies, the current results suggest that the application of PPOS should be cautious.

Trial registration number

-
P–604 Effectiveness comparison of antral follicular count (AFC), follicular-output-rate (FORT), follicle-to-oocyte-index (FOI), oocyte-sensitivity-index (OSI), and follicular-sensitivity-idex (FSI) for predicting clinical pregnancy rates in IVF
Authors: Bayu P , Syam H H
Published: August 2021

Study question

Which is better for predicting clinical pregnancy rate : AFC, FORT, FOI, FSI, or OSI?

Summary answer

Both AFC and OSI can be used to predict clinical pregnancy better than FORT, FOI or FSI.

What is known already

AFC, FORT, FOI, OSI, FSI can be used to predict clinical pregnancy, but no study compared which one is better

Study design, size, duration

Retrospective study using data from medical record (2016–2018) Subjects were patients underwent IVF cycle at Aster Clinic in Hasan Sadikin Hospital Bandung. Subjects divided into 2 groups: clinically pregnant that is visible gestational sac on ultrasound (n = 83) and not pregnant (n = 148). Inclusion criteria : antagonist protocols, <45 years, basal follicle stimulating hormone (FSH) ≤ 12 IU/L, ICSI fertilization method, and fresh transfer cycle.

Participants/materials, setting, methods

AFC categorized < 5 and ≥ 5 (poseidon) FORT=pre-ovulatory follicles(16–20 mm) x 100 divided by AFC(2–10 mm). FOI=oocytes obtained x 100 divided by AFC. OSI=oocytes obtained x 1000 divided by total FSH dose. FSI=pre-ovulatory follicles x 100,000 divided by (AFC x total FSH dose). FORT and FSI divided using percentil 33 and 67. OSI divided into 3 groups by cut-off 1.697/IU for poor-response and 10.07/IU for hyperresponse. FOI divided into 2 groups, ≤ 50% or > 50%

Main results and the role of chance

Group of AFC ≥ 5 had a significantly higher clinical pregnancy rate than the AFC < 5 group (39.49% vs. 16.67% ; p = 0.009). High and moderate OSI had higher clinical pregnancy rate than low OSI (66.37% vs. 37.72% vs. 25.45% ; p = 0.038). There is a significant negative correlation between OSI and age (–0.454) or total FSH dose (–0.594). There is a significant positive correlation between OSI and AFC (0.625), the number of follicles at trigger (0.792), and oocytes (0.923). There were no significant differences in clinical pregnancy rates between the FORT, FOI, and FSI groups.

Limitations, reasons for caution Limitation

Retrospective study using medical record data Ultrasound measurement was done by many reproductive gynecology specialist (not 1 person) --- observer bias.

Wider implications of the findings: This study found no association between FORT, FOI, FSI on clinical pregnancy. Why?

FORT, FSI, FOI use measurement number of follicles at trigger and antral follicle. Differences among observers in interpreting antral follicles and number of follicles at trigger, or inaccurate measurement. No FORT, FOI, and FSI cut off values from previous study.

Trial registration number

Not applicable
P–644 Effect of a reduced dose of long-acting gonadotropin releasing hormone (GnRH) agonist versus short-acting GnRH agonist on pregnancy outcome in patients undergoing ICSI/ET cycles
Authors: Kabodmehri R , Mehrafza M
Published: August 2021

Study question

Are pregnancy outcome different between reduced dose of long-acting GnRH agonist and short-acting GnRH agonist in patients undergoing ICSI/ET cycles?

Summary answer

Clinical outcomes were not significantly different between the two group.

What is known already

There is no consensus on which of two GnRH agonist protocol is the most effective form and it has been challenging which one improves the clinical pregnancy rate.

Study design, size, duration

This is randomized clinical trial that 394 patients, who were candidates for ICSI/ET, were included in this study between April 2019 and January 2020.

Participants/materials, setting, methods

Patients were randomly divided into two groups using blocks of 8; hereby every 8 subjects were randomized, four were allocated to the long-acting GnRH agonist, and four were allocated to the short-acting GnRH agonist randomly.

Main results and the role of chance

No significant difference was noted between the two groups in progesterone and estradiol levels at hCG administration day. Despite no significant difference between the two groups in ART outcomes, interestingly rate of ovarian hyperstimulation syndrome (OHSS) occurrence was significantly higher in the short-acting group (P = 0.005).

Limitations, reasons for caution

We couldn’t evaluate the long-term consequence of pregnancy including live birth rate and effect of GnRH analogue on fetus.

Wider implications of the findings: A lower rate of OHSS occurrence in the long-acting group, and similar ART outcomes in both groups.

Trial registration number

IRCT20190609043845N1
P–649 Should women receive luteal support following natural cycle frozen embryo transfer? A systematic review and meta-analysis
Authors: Mizrachi Y , Horowitz E , Gane. Herman H , Farhi J , Raziel A , Weissman A
Published: August 2021

Study question

Should women receive luteal phase support (LPS) following natural cycle frozen embryo transfer (NC-FET)?

Summary answer

Progesterone LPS following NC-FET increases the live birth rate. There is no evidence to support the administration of hCG for LPS in these cases.

What is known already

Whether or not women should receive LPS following NC-FET is highly controversial. Previous studies have shown conflicting results.

Study design, size, duration

We conducted a systematic search of the literature published in Medline/PubMed, Embase and the Cochrane Library, from January 2000 until December 2020. We included all original English, peer-reviewed articles, irrespective of study-design. The search strategy included keywords related to natural cycle frozen embryo transfer and luteal phase support. Studies reporting the results of artificial or stimulated FET cycles were excluded.

Participants/materials, setting, methods

Our systematic search generated 395 records. After screening, eight studies were included in the review and seven studies were included in the meta-analysis. Two studies (n = 858) used hCG, and 6 studies (n = 1507) used progesterone for luteal support. Four studies were randomized controlled trials (RCTs), whereas the other four were historic cohort studies.

Main results and the role of chance

In a meta-analysis using random effects model, hCG administration for LPS did not increase the clinical pregnancy rate (two studies, OR 0.85, 95% CI 0.64–1.14). On the other hand, progesterone LPS was associated with a higher clinical pregnancy rate (five studies, OR 1.48, 95% CI 1.14–1.94), and a higher live birth rate (three studies, OR 1.67, 95% CI 1.19–2.36).

Limitations, reasons for caution

There was large heterogeneity in progesterone dose and route of administration, as well as the methods used for ovulation detection and triggering. Moreover, only four studies were randomized. Finally, both studies examining the use of hCG for LPS were performed by the same group of researchers in a single center.

Wider implications of the findings: The available evidence indicates that progesterone administration for LPS is beneficial following natural cycle frozen embryo transfer. There is no evidence to support the administration of hCG for LPS in these cases. Additional Large RCTs are necessary in order to improve the quality of evidence and validate our findings.

Trial registration number

PROSPERO ID: CRD42020199045
P–664 Bone morphogenetic protein–7 (BMP–7) reduces E2 and P4 production of human luteinized granulosa cells by down-regulating the expression of the steroidogenic enzymes StAR and 3B-HSD
Authors: Yildiz C S , Oktem O
Published: August 2021

Study question

What is the biological role of BMP–7 on the granulosa cells after luteinization?

Summary answer

BMP–7 down regulates the steroidogenic enzymes and reduces E2 and P4 output of luteinized granulosa cells.

What is known already

BMP–7 is a member of TGF-B super family that is mainly produced by theca cells in the ovary. It promotes the transition of primordials into primary follicles, and the growth and preantral and antral follicles, and inhibits progesterone (P4) production during FSH-induced growth phase of Graafian follicles (luteinization inhibitor). However, limited data is available regarding the role of this hormone on the molecular luteal characteristics of granulosa cells after ovulation and luteinization processes. We therefore aimed to address this issue in the current study.

Study design, size, duration

A basic science study on the corpus luteum biology

Participants/materials, setting, methods

Human luteal granulosa cells were obtained from 10 normo-responder IVF patients undergoing ovarian stimulation with rec-FSH and GnRH antagonist protocol and cultured with recombinant forms of BMP–7, hCG and activin-A for 24h. The presence of cognate receptors for these hormones were validated using RT-PCR. The expression of the steroidogenic enzymes were analyzed with quantitative immunoblotting, real-time RT-PCR and confocal microscopy. E2 and P4 production of the cells were measured using ECLIA method.

Main results and the role of chance

BMP–7 significantly down-regulated the expression of StAR and 3b-HSD in immunoblotting and confocal images and caused a substantial decrease in P4 production in the luteal GCs in a dose dependent manner. It did not cause any notable change in aromatase expression, however E2 output declined in parallel with P4 due to the reduced expression of StAR, which is the rate limiting enzyme in steroidogenesis. hCG significantly up-regulated StAR and 3b-HSD expression and enhanced P4 output whereas activin-A did the opposite effect. Viability assay with Yo-PRO–1 uptake assay did not reveal any significant differences in the viability of the cells before and after treatment with these hormones.

Limitations, reasons for caution

In-vitro findings requires validation using in-vivo models.

Wider implications of the findings: Reversal of luteinization and down-regulation of steroidogenesis with BMP–7 and other hormones with similar actions warrant further investigation to test their in-vivo effects in order to develop new strategies against ovarian hyperstimulation syndrome (OHSS).

Trial registration number

Not applicable
P–670 Urine estrone–3-glucuronide (E3G) assay: is there any place during ovarian stimulation for IVF cycles?
Authors: Vladimirov I , Martin V , Desislava T
Published: August 2021

Study question

Could the urine estrone–3-glucuronide (E3G) assay be used efficiently to monitor a controlled ovarian hyperstimulation (COH) cycle, in comparison to a serum estradiol (E2) assay?

Summary answer

E3G testing provides an alternative to serum E2 assessment and a new “patient friendly” approach for COH monitoring.

What is known already

In many IVF clinics basic monitoring tools for controlled ovarian stimulation during IVF procedure are ultrasound measurements of follicle growth and hormone assessment of serum E2 levels. The monitoring can occur 4–6 times during stimulation, but repeated blood sampling causes patient stress. In contrast, E3G sampling, one of principal metabolites of estradiol in urine, is non-invasive and can be performed by the patients themselves and measured by fluorescent immunoassay. A correlation has been shown between concentrations of E2 present in plasma and concentrations of E3G in different phases of menstruation cycle.

Study design, size, duration

This is a pilot, prospective study, in a single IVF clinic. Twenty female participants were recruited November 2020 -January 2021, aged 25–43 years and BMI: 18–28kg/m2. Dynamic change of serum E2 and urine E3G at ovarian stimulation monitoring are being analyzed.

Participants/materials, setting, methods

Concurrent urine E3G and serum E2 values were collected from patients who provided between 2 and 4 samples on different days of their COH IVF cycle. Serum E2 values were assessed routinely, while E3G values were measured and validated using a fluorescent immunoassay Mira Fertility Plus® analyzer.Main results and the role of chance: The urine E3G of assay was validated for intra- and inter-assay variability with a coefficient of variation of < 20%. It was also validated for analytical and functional sensitivity and sample stability. Linear regression of serum E2 and E3G values of 56 early morning urine samples who had evaluated between Days 4 and 13 of menstruation cycle provided an R = 0,81. Urine E3G values also correlated to follicle growth. Patient survey results showed that urine sampling was the preferred method of analysis.

Limitations, reasons for caution

We have provided proof of principle that urine E3G measurement can be accurately carried out using fluorescent immunoassay technology during routine COH for IVF cycles. The patients’ study group has to be expanded in order to enable us to find the appropriate place of urine E3G assay in COH protocol.

Wider implications of the findings: Urine E3G testing correlates well to serum E2 assessment in COH. Urine E3G assay provides an alternative to serum-based assessment. The ease of urine sampling allows a reduction in patient discomfort during venopuncture, costs, time, and infection risks in epidemics/pandemics, like COViD–19, and offers a patient-friendly approach to ovarian stimulation.

Trial registration number

NA
P–673 A visualized clinical model predicting cumulative pregnancy rate after IVF-ET: a real-world study
Authors: Zhang M
Published: August 2021

Study question

How is the cumulative pregnancy probability of individual patients after IVF-ET,could we develop a visualized clinical model to predict it based on patient’s characteristics?

Summary answer

The visualized clinical mode incorporates five items of female age, number of oocytes, antral follicle count, endometrium thickness and basal FSH level.

What is known already

Many factors can result in infertility, prognosis prediction is clinically relevant for making the right therapeutic strategy while avoiding overtreatment. It is also helpful in counselling, making the patient aware of possible treatment duration and estimated expense and managing patient’s expectation. Visualized clinical mode and accurate prediction would also be helpful in designing clinical trials to evaluate new treatments.

Study design, size, duration

We conducted a retrospective analysis of a single-center database using prospectively collected data from women who underwent IVF/ICSI treatment from January 2013 to December 2015, All the participants were followed up for at least 2 years, 3538 IVF-ET cycles were included in the study.A total of 3538 IVF/ICSI cycles were included in the study.

Participants/materials, setting, methods

Data from a total of 2312 IVF/ICSI cycles from January 2013 to December 2014 were randomly split into training dataset (1550, 67%) and internal validation dataset (762, 33%). A total of 1226 IVF/ICSI cycles in 2015 was applied to external validation dataset (temporal validation)

Main results and the role of chance

Multivariable logistic regression model combined with restricted cubic splines function was used to test independent prognostic factors and estimate their effects on treatment outcome for patients treated with IVF/ICSI. Female age, number of oocytes retrieved, AFC, endometrium thickness and basal FSH were included the final model. The above model was used to calculate prediction scores for all women in the training and validation datasets. The C-index was 0.693 (95% CI: 0.692∼0.695) in training sets, 0.689 in internal validation sets and 0.710 in external validation sets, which denotes a good performance. Calibration curves suggest excellent model calibration, with an ideal agreement between the prediction and actual observation . The DCA showed that if the threshold probability is between 0 and 0.7, using the nomogram derived in the present study to predict cumulative pregnancy provided a greater benefit than either thetreat-all or the treat-none strategy.

Limitations, reasons for caution

it was a retrospective, single-center study.In the future, prospective, randomized controlled, multicenter clinical studies will be designed.

Wider implications of the findings: The visualized nomogram model provides great predictive value for infertility patients in their first IVF/ICSI cycle, and predicts the pregnancy probability of individuals ,and could help clinicians improving clinical counselling.

Trial registration number

Not applicable
P–700 Increased progesterone to mature oocyte index is associated with lower top-quality embryo rate in GnRH antagonist protocols
Authors: Şükür Y E , Pouya K , Özmen B , Sönmezer M , Berker B , Atabekoğlu C S , Aytaç R
Published: August 2021

Study question

Do progesterone elevation (PE) on trigger day and progesterone to mature oocyte index (PMOI) affect embryo quality and the chance of live birth?

Summary answer

The top-quality embryo rate is decreased by increasing PMOI, but it has no association with absolute serum progesterone levels.

What is known already

Progesterone elevation have been reported to significantly decrease pregnancy and implantation rates. The main mechanism of this adverse effect is mainly related to an asynchrony between the endometrium and the embryo. Many of the previous studies have failed to show a significant impact of PE on embryo quality and the success of subsequent frozen-thawed embryo transfer (FET) cycle. However, PMOI was suggested to be more predictive than PE of ART outcome and might be associated with embryo quality.

Study design, size, duration

A single-centre retrospective cohort study was conducted. All FET cycles performed in a university hospital infertility centre between January 2016 and December 2019 were reviewed. A total of 44 patients who had PE (>1.5 ng/ml) on trigger day and 134 patients who did not have PE were assessed.

Participants/materials, setting, methods

The study group consisted of patients who had PE (>1.5 ng/mL) during fresh COS cycle and the control group consisted of patients who did not have PE. In addition to effect of PE on subsequent FET cycle outcome, an association between PMOI and embryo quality was assessed. The threshold level to define increased PMOI (>0.12 ng/ml) was calculated as the median level of the whole study cohort.

Main results and the role of chance

The mean ages of the study and control groups were 30.4±5.4 years and 31.1±5.6 years, respectively (P = 0.413). Although the number of oocytes collected and MII oocytes were significantly higher in patients with PE, the total number of frozen embryos were similar between the groups. There were no significant differences concerning the outcome measures including live birth rate in the subsequent FET cycle between participants with and without PE (27.3% vs. 23.9%, respectively; P = 0.652). The rate of top-quality embryos was similar between participants with and without PE (43% vs. 52%, respectively; P = 0.370). However, the rate of top-quality embryos was significantly lower in cycles with PMOI>0.12 ng/ml than in cycles PMOI<0.12 ng/ml (42% vs. 56%, respectively; P = 0.027).

Limitations, reasons for caution

The retrospective design and the small sample size derived from a single institution.

Wider implications of the findings: Increased PMOI, which is associated to lower top-quality embryo rate, may in turn result in diminished cumulative live birth rate.

Trial registration number

Not applicable
P–709 Dual stimulation in-vitro-maturation (Duostim IVM) for overcoming oocyte maturation arrest, resulting in embryo transfer and livebirth
Authors: Hatirnaz S , Hatirnaz E , Dahan M , Ata B , Basbug A , Hatirnaz K , Tan S
Published: August 2021

Study question

Does luteal phase followed by follicular phase letrozole priming and dual oocyte retrieval for in-vitro maturation (IVM) overcome oocyte maturation arrest (OMA)?

Summary answer

Oocyte maturation, fertilization,embryo cryopreservation and livebirth can be achieved with letrozole priming IVM in rare cases of OMA.

What is known already

OMA is an intractable problem resulting in only immature oocytes being collected and to date no succesful treatment exists. Attempts to mature oocytes collected in stimulated IVF cycles with OMA have so far failed. Cases with OMA can be due to intrinsic oocyte defects, intrafollicular factors or resistance to stimulation.

Study design, size, duration

Six women with OMA in ≥ 2 prior stimulated IVF cycles were treated between March 2019 and December 2020.

Participants/materials, setting, methods

Participants had total of 18 (range 2 - 6) prior IVF cycles yielding only 166 immature oocytes. Letrozole 5mg was given days 15–18 of ovulatory cycle; SC decapeptyl 0.1mg trigger given at follicles 12 mm, 38 hours<OPU. After menstruation, letrozole 5mg days 3–7; SChCG 250ug when follicles=12 mm 38 hours<OPU. After in-vitro-maturation oocytes reaching MII were fertilized. Embryos from luteal collection were frozen and fresh embryo transfer was attempted after follicular phase collection.

Main results and the role of chance

Six women underwent DuoStim IVM, median (quartiles) 3.5 (0 - 9) GV and 0.5 (0 - 2) MI oocytes were collected from luteal phase OC and 0 (0 - 0) GV and 2(0 – 4.5) MI oocytes were collected from follicular phase OC. They had a total of 166 immature oocytes collected in prior IVF cycles. There were no MII oocytes at the time of collection in any cycles.0 (0 – 3.5) oocytes matured from luteal phase OC and 1 (0 – 4) from follicular phase OC. 0 (0 – 1.5) embryos were available from luteal phase and 0 (0 - 2) from follicular phase OC.Two subjects (29 and 33 years old) underwent fresh DET and the 29 year old with 2 previous failed IVF cycles achieved a livebirth (50% per ET and 16.7% per started cycle). None of the women who did not have an embryo for fresh transfer from the follicular phase collection had an embryo from the luteal phase collection. The same 29 year old has 2 luteal phase and 2 more follicular phase embryos vitrified.

Limitations, reasons for caution

OMA is a rare condition with a variety of etiologies. Different etiologies can require different managements.

Wider implications of the findings: It may be possible to overcome OMA with letrozole IVM in rare cases. This case is the first recorded live birth. The value of dual stimulation overcoming OMA remains uncertain.

Trial registration number

This study is approved by the local ethical commitee of Medicana Samsun International Hospital by a Grant number of 02/05.02.2020: registration is not required due to retrospective status
P–778 Repeated cryopreservation process impairs embryo implantation potential but does not affect neonatal outcomes
Authors: Wang M , Zhu L , Jin L
Published: August 2021

Study question

Does repeated cryopreservation process effect embryo implantation potential and neonatal outcomes of human embryos?

Summary answer

Repeated cryopreservation impaired embryo implantation potential, resulting in a lower live birth rate and higher miscarriage rate, despite a comparable neonatal complication rate.

What is known already

With significant advances in the field of ART, the number of available embryos for transfer per cycle has also increased, resulting in a slew of surplus embryo cryopreservation. However, limited researches have focused on the embryonic development potential, clinical outcomes, pregnancy complications as well as the neonatal complications of embryos experiencing repeated cryopreservation.

Study design, size, duration

This was a retrospective, single-center cohort study. All ART cycles from January 2014 to December 2018. Age, body mass index, and number of oocytes retrieved were preferentially matched within a required range, with a total of 709 couples included in the study.

Participants/materials, setting, methods

The study was conducted in the Reproductive Medicine Centre affiliated to a university. Preferentially matched participants were divided into three groups according to the times of embryo cryopreservation: the fresh group (n = 249), the cryopreservation group (n = 244) and the re-cryopreservation group (n = 216). Embryo implantation rate, live birth rate, miscarriage rate, and neonatal complication rate were compared among these three groups.

Main results and the role of chance

The embryo implantation rate, clinical pregnancy rate and live birth rate in the re-cryopreservation group were significantly lower, and there was also a slight increase in the miscarriage rate. Logistic regression analysis indicated that embryos with repeated cryopreservation and lower TE scores were at higher risk of embryo implantation failure in single embryo transfer cycles (OR = 1.79 and 1.56 respectively). No significant differences were observed in gender, gestational age, birthweight, neonatal abnormality, and neonatal complications among the groups.

Limitations, reasons for caution

This was a retrospective cohort study conducted in single center. A multi-center prospective study with a larger sample size in well-matched participants is needed to reinforce our findings.

Wider implications of the findings: Our findings demonstrated the adverse effect of repeated cryopreservation on embryo implantation potential. To avoid embryo waste, or in some special circumstances such as re-biopsy in PGT cycles, an additional cryopreservation on embryos was considered to be available to achieve clinical pregnancy and live birth.

Trial registration number

Not applicable
On the Shape Fields Finiteness Principle
Authors: Jiang Fushuai , Luli Garving K , O’Neill Kevin
Published: August 2021

In this paper, we improve the finiteness constant for the finiteness principles for $C^m({\mathbb{R}}^n,{\mathbb{R}}^D)$ and $C^{m-1,1}({\mathbb{R}}^n,{\mathbb{R}}^D)$ selection proven in [ 19] and extend the more general shape fields finiteness principle to the vector-valued case.
A fast, resource efficient, and reliable rule-based system for COVID-19 symptom identification
Authors: Sahoo Himanshu S , Silverman Greg M , Ingraham Nicholas E , Lupei Monica I , Puskarich Michael A , Finzel Raymond L , Sartori John , Zhang Rui , Knoll Benjamin C , Liu Sijia , Liu Hongfang , Melton Genevieve B , Tignanelli Christopher J , Pakhomov Serguei V S
Published: August 2021

Objective

With COVID-19, there was a need for a rapidly scalable annotation system that facilitated real-time integration with clinical decision support systems (CDS). Current annotation systems suffer from a high-resource utilization and poor scalability limiting real-world integration with CDS. A potential solution to mitigate these issues is to use the rule-based gazetteer developed at our institution.

Materials and Methods

Performance, resource utilization, and runtime of the rule-based gazetteer were compared with five annotation systems: BioMedICUS, cTAKES, MetaMap, CLAMP, and MedTagger.

Results

This rule-based gazetteer was the fastest, had a low resource footprint, and similar performance for weighted microaverage and macroaverage measures of precision, recall, and f1-score compared to other annotation systems.

Discussion

Opportunities to increase its performance include fine-tuning lexical rules for symptom identification. Additionally, it could run on multiple compute nodes for faster runtime.

Conclusion

This rule-based gazetteer overcame key technical limitations facilitating real-time symptomatology identification for COVID-19 and integration of unstructured data elements into our CDS. It is ideal for large-scale deployment across a wide variety of healthcare settings for surveillance of acute COVID-19 symptoms for integration into prognostic modeling. Such a system is currently being leveraged for monitoring of postacute sequelae of COVID-19 (PASC) progression in COVID-19 survivors. This study conducted the first in-depth analysis and developed a rule-based gazetteer for COVID-19 symptom extraction with the following key features: low processor and memory utilization, faster runtime, and similar weighted microaverage and macroaverage measures for precision, recall, and f1-score compared to industry-standard annotation systems.
Comparison of beaver density and foraging preferences between urban and rural riparian forests along the South Saskatchewan River, Canada
Authors: England Kirby , Westbrook Cherie J
Published: August 2021

Beavers have recolonized much of their historic range throughout the northern hemisphere and numerous studies have documented their habitat preferences and foraging behavior in rural riparian areas. Beavers, however, are also recolonizing waterways in cities, yet there has been little study of habitat use and foraging practices in these managed, urban systems. We studied beaver lodge distribution and riparian foraging preferences along the South Saskatchewan River, Canada, comparing a reach (24 km) passing through the City of Saskatoon where beavers and trees are managed with an upstream reach (29 km) passing through a conservation area where neither beavers nor trees are managed. In a canoe-based census at low flow, we found that beaver density in the conservation area was twice that in the city. Lodges were dispersed in the city with longer water-based distances between them. We found both differences and similarities in beaver foraging behavior. Riparian tree sampling along transects revealed that while diversity in the city and conservation area is markedly different, beavers preferentially cut green ash, Manitoba maple, paper birch and three poplars in both places. Beavers also cut six other tree species in the city, including three that are introduced, but the diversity was higher. A least-squares general linear model showed greater probability of cutting of trees further from the river in the city than conservation area, but of smaller diameter. Study results will be useful to urban planners in managing urban riparian forests and in developing beaver management plans.
A retrospective analysis of bull:cow ratio effects on pregnancy rates of beef cows previously enrolled in fixed-time artificial insemination protocols
Authors: Timlin Claire L , Dias Nicholas W , Hungerford Laura , Redifer Tracey , Currin John F , Mercadante Vitor R G
Published: August 2021

This retrospective study aimed to determine if the number of cows exposed per bull affects pregnancy rates of cows returning to estrus after fixed-time artificial insemination (FTAI). Data were compiled over the course of 13 breeding seasons (six fall and seven spring seasons) between 2010 and 2017 from the Virginia Department of Corrections herd. Available records contained data from 17 farms and 324 groups of cows (average 47 cows/group). Multiparous cows and heifers (average age per group: 5.11 ± 0.14 yr; n = 14,868) were exposed to FTAI. After FTAI, animals were placed on pasture with bulls diagnosed as fertile by a breeding soundness exam for natural service of cows who did not become pregnant to FTAI (n = 7,248; average 22 cows/group). Animals were classified as pregnant to FTAI, to natural service on first return to estrus, or to natural service on second or subsequent estrus determined by fetal aging at pregnancy diagnosis. The bull:cow ratio for the total number of cows exposed ranged from 1:9 to 1:73 with an average of 1:31. The bull:cow ratio considering only open cows exposed after FTAI ranged from 1:2 to 1:44 with an average of 1:14. There was significant negative, small correlation between the bull:cow ratio for total number of cows exposed and return to estrus pregnancy rate in fall breeding seasons (P = 0.01, r2 = 0.04) but not in spring (P = 0.90). There was a significant negative, small correlation between bull:cow ratio of open cows exposed and pregnancy rates to first return to estrus in fall herds with a single sire (P < 0.001, r2 = 0.11). There was no correlation in fall herds using multiple sires or spring herds (P ≥ 0.12). Bull:cow ratio accounted for only 1–11% of variation in the pregnancy rates, thus we conclude that a decreased bull:cow ratio (up to 1:73) did not affect natural service return to estrus pregnancy rate. Cattlemen may consider a reduced number of bulls needed for natural service breeding after FTAI, which can decrease bull related costs and increase the economic feasibility of adopting FTAI protocols.
Motivation and Engagement of Nursing Students in 2 Gamified Courses
Authors: Killam Laura A. , Timmermans Katherine E. , Shapiro Sidney J.
Published: August 2021

Background

Evidence suggests that gamification increases student engagement in course activities. However, student feedback about gamification in nursing contexts is needed.

Purpose

The aim of this study was to describe nursing student perceptions of how gamification impacts student motivation and engagement.

Methods

A convergent mixed-methods study was conducted. Surveys were completed by 58 first-year nursing students. Survey comments and data extracted from the learning management system were also collected.

Results

Students generally found gamification valuable, interesting, and enjoyable. Gamification took effort and was perceived as important. Students felt that they had some choice in participation in the gamified activities.

Conclusions

Gamification is a viable strategy for promoting motivation and engagement among first year nursing students. More qualitative research is needed to enable game design refinement through investigation of contextualized student experiences. Refined game design may impact the development of learner skills through a moderating effect on engagement in course activities.