bluuebunny/crossref_metadata_2025 huggingface dataset:
P–627 Optimal timing of day 6 blastocyst transfer in artificially prepared frozen-thawed embryo transfer cycles
Authors: Kim H K , Ku S.-Y , Kim S H , Suh C S , Kim H
Published: August 2021

Study question

When is the optimal timing of day 6 (D6) blastocyst transfer between the 6thday (P6)and the 7th(P7) day of progesterone administration in artificially prepared frozen-thawed embryo transfer(FET) cycle

Summary answer

When transferring D6 blastocysts in artificially prepared FET cycles, live birth rate tended to be higher in P6 group than in P7 group.

What is known already

Blastocyst transfer in FET cycles has increased due to several reasons including convenience for optimization of endometrial synchronization, improvement of laboratory techniques and preimplantation genetic testing. Meanwhile, D6 blastocyst which cryopreserved on day 6 after being developed to the full blastocyst stage, presented lower pregnancy outcomes in FET cycle than D5 blastocysts. However, there have been few studies on the optimal duration of progesterone administration when transferring D6 blastocysts.

Study design, size, duration

This was a retrospective cohort study including patients who underwent frozen-thawed blastocyst transfer in artificially prepared cycles from January 2000 to May 2020. Patients with D6 blastocyst transfer on the 6th day of progesterone administration were included in D6-P6 group, and patients with D6 blastocyst transfer on the 7th day of progesterone administration were included in D6-P7 group.

Participants/materials, setting, methods

Increasing dose of estradiol valerate was administered from the 3rd day of menstruation: 4 mg/day for the first four days, 6 mg/day for next four days, and then 8 mg/day until the confirmation of pregnancy. Progesterone was administered from the 14th day of menstruation if the endometrial thickness reached ≥7 mm. The independent t-test or Mann-Whitney test, chi-square test, and logistic regression analysis were performed.

Main results and the role of chance

A total of 50 patients were included, and 13 patients underwent FET on P6 and 37 patients underwent FET on P7. Live birth rate was comparable between the P6 group and the P7 group (18.9% vs. 15.4%, p = 0.775). Live birth rate was higher in the D6-P6 group than in the D6-P7 group after adjusting for age, AMH, endometrial thickness on the starting day of progesterone administration and good embryo rate transferred with statistical significance (OR: 6.716, p = 0.005).

Limitations, reasons for caution

Limitations of the present study is the retrospective design and the small sample size. Caution is needed in extrapolating results of this study because only intramural and vaginal progesterone supplementations were included in this study.

Wider implications of the findings: Even if the duration of blastocyst formation was delayed, frozen-thawed D6 blastocyst may need to be considered for on P6 rather than P7. The difference of live birth rate is not statistically significant. This study should be acknowledged for the underestimation of the difference because of the small sample size.

Trial registration number

Not applicable
P–628 Predicting oocyte yield in patients with diminished ovarian reserve using basal antral follicle count
Authors: Balachandren N , Schwab S , Latif S , Foo X , Lukaszewski T , Mavrelos D
Published: August 2021

Study question

Is basal antral follicle count (bAFC) taken on day 1 to 3 of stimulation a useful predictor of oocyte yield in that cycle, in women with diminished ovarian reserve (DOR)?

Summary answer

Basal AFC has moderate correlation with final oocyte yield. A median 75% of the antral follicle count is collected as oocytes.

What is known already

The current theory of folliculogenesis suggests that all follicles available for recruitment are visible on ultrasound in the ovary at the point when ovarian stimulation is applied. This implies a tight correlation between the AFC on day 1–3 of a stimulation cycle (bAFC) and the eventual number of follicles collected. We hypothesise that in women with diminished ovarian reserve who receive maximum stimulation basal AFC would be a useful predictor of final oocyte yield in that cycle.

Study design, size, duration

This was a prospective single centre, observational study in a tertiary referral hospital in London. 125 women with DOR underwent controlled ovarian stimulation between December 2018 and January 2021.

Participants/materials, setting, methods

All study participants were given an antagonist cycle with a starting stimulation dose of 450iu and remained on the same dose throughout their treatment. We assessed the correlation between bAFC taken on day 1–3 of the stimulation cycle and the total number of oocytes collected.

Main results and the role of chance

A total of 150 treatment cycles were included in the analysis. The median age was 37 (IQR 35 – 39). The median AMH was 6.0 (IQR 4.4 – 8.9) and the median FSH was 7.6 (IQR 5.7 – 9.4). The median bAFC at the start was 9 (IQR 6 – 11). The median total stimulation dose was 4050iu (IQR 4050 – 4500). The median oestradiol on day of trigger was 5906 (IQR 4166 – 7397) and median number of oocytes collected was 7 (IQR 5 – 9).

There was a moderate correlation between bAFC and the number of oocytes collected (r = 0.549, p = 0.005). The median ratio of oocytes collected over the number of antral follicles observed at the start was 72.7% (IQR 58.3 – 100).

Limitations, reasons for caution

We have standardised approach to AFC determination and have previously shown that AFC inter and intra-observer variability in our unit is low. Nevertheless, our study involved multiple operators for AFC determination which may introduce variability. Further variability may have been introduced at egg collection by varying technique.

Wider implications of the findings: Studies of antagonist protocol in good prognosis patients suggest poor correlation between basal AFC and oocyte yield. In contrast, our study shows that in a population of women with DOR basal AFC provides useful information which can be used to counsel women around the expected oocyte yield of their cycle.

Trial registration number

Not applicable
P–652 Higher live birth rates with controlled ovarian stimulation vs. natural cycles in donor sperm IUI
Authors: Lubamba C
Published: August 2021

Study question

Are pregnancy rates after intra uterine insemination-donor sperm (IUI-D) in good prognosis patients with controlled ovarian stimulation (COS) different from those in natural cycles?

Summary answer

In good prognosis patients, IUI-D cycles with COS provided higher pregnancy outcomes compared to IUI-D in natural cycles.

What is known already

There is no consensus about the systematic use of COS for IUI-D in good prognosis patients, considering efficacy, safety, and efficiency. The objective of this study is to compare the clinical pregnancy rate in good prognosis patients undergoing an IUI-D cycle with COS versus natural cycle (NC).

Study design, size, duration

Retrospective cohort study of 5,369 first IUI-D performed between January 2012 and September 2019 in one fertility center. IUI-D with COS (n = 4,417) versus natural cycles (n = 952) were compared. Differences in pregnancy outcomes between study groups were evaluated using a Pearson’s Chi2 test. A p < 0.05 was considered statistically significant.

Participants/materials, setting, methods

Good prognosis patients were defined as women aged ≤38 years old, with a BMI ≤35 Kg/m2, and having regular menses. The indications for IUI-D were an absence of male partner or a sever partner male factor. COS consisted in a standard protocol of r-FSH or hMG-HP, in a dose between 25 IU to 75 IU, depending on the patient’s age and the acceptance of multiple pregnancy, to obtain between 1 to 2 follicles at ovulation.

Main results and the role of chance

Average age was slightly higher in COS patients (33.0±3.8 versus 31.6±4.1 years old in NC), as was BMI (23.7±3.6 in COS vs 23.08±4.1 in NC). Further, in the last follicular control, estradiol was higher (321±180 vs 244±108 pg/ml), LH was lower in (14 vs 28 UI/L), and the number of follicles > 16mm was higher (1.06±0.5 vs 0.96±0.4) in COS vs NC, respectively. Progesterone levels did not differ between groups. Stimulated cycles provided significantly better results for all pregnancy outcomes (p < 0.001): biochemical pregnancy rate was 27.8% in COS versus 23.0% in NC; clinical pregnancy rate was 20.5% versus 14.8%; ongoing pregnancy rate was 18.5% versus 13.3%; and live birth rate was 16.8% versus 12.3%. While the analysis was not adjusted for potential confounding factors, baseline characteristics between groups were very similar, so we could expect that the improved reproductive results were due to COS.

Limitations, reasons for caution

The main limitation of the study is its retrospective nature and the collection of data from one clinic. Differences found between study groups should be confirmed in a prospective controlled trial.

Wider implications of the findings: In good prognosis patients undergoing their first IUI-D, controlled ovarian stimulation provides better reproductive outcomes; further analysis of cumulative pregnancy rate after 3 cycles would provide information for recommendations on the complete treatment cycle.

Trial registration number

non applicable
P–657 Prostaglandin D2 is correlated with follicles development and a reliable marker of ovarian reserve of poor ovarian responder patients
Authors: Choi K H , Kim Y J , Kang K Y , Park E A , Kim Y S , Kim M J , Kim H O , Koong M K , Kim Y S , Yoon T K , Ko J J , Lee J H
Published: August 2021

Study question

Is the prostaglandin D2 (PGD2) associated with growing follicles and ovarian reserve of poor ovarian responders?

Summary answer

PGD2 is correlated with ovarian stimulation activity and follicle growth. Especially, poor ovarian responders show a significant decrease in the level of follicular fluid.

What is known already

Prostaglandins (PGs) are involved in the female reproductive process, mainly ovulation, fertilization, and implantation.

Study design, size, duration

We investigated the PGD2 level in the follicular fluid of poor ovarian responders. The collection of human follicular fluid was approved by the Institutional Research and Ethical Committees of CHA University (approval number: 1044308–201611-BR–027–04) from January to December 2019. Follicular fluid was collected from patients with normal ovarian response and patients with POR.

Participants/materials, setting, methods

We studied whether prostaglandin has related to POR in the clinical key factor by measuring human follicular fluid. Follicular fluid was collected from patients with normal ovarian response and patients with POR. The concentration of PGD2 in follicular fluid was determined with ELISA kits following the manufacturer’s protocol.

Main results and the role of chance

We analyzed the level of PGD2 in the follicular fluid of patients with normal ovarian response and patients with POR using an ELISA. The PGD2 concentration was significantly lower in the follicular fluid of patients with POR than in the follicular fluid of young and old patients with normal ovarian response.

Limitations, reasons for caution

This study has an identification of biomarker of the clinical samples as POR criteria patients. Therefore, further investigations aimed at specific recovery of low PGD2 metabolic activity in the CCs during control ovarian stimulation.

Wider implications of the findings: Until now there is no specific biomarker of POR. AMH is just an ovary reserve marker for an indication of ovary function. PGD2 is one of the metabolites in steroid metabolism in the ovary. Therefore, we can find some cure through further study for improved PGD2 production to POR patients.

Trial registration number

none
P–665 Influence of premature progesterone elevation on embryo development
Authors: Lefebvre T , Duval G , Loubersac S , Lammers J , Barriere P , Freour T , Reignier A
Published: August 2021

Study question

Does a serum progesterone level higher than 1.3 ng/mL on the day of ovulation trigger have an impact on blastocyst development?

Summary answer

Elevated progesterone level has no significant impact on top blastocyst rate, usable blastocyst rate and on morphokinetics.

What is known already

Premature elevation of progesterone level on the day of ovulation trigger prior to IVF is common and causes a decrease in endometrial receptivity. A freeze all strategy is then recommended. However, cumulative live birth rates have also been described as lower in cases of high progesterone levels.

Study design, size, duration

This was a retrospective bicentric cohort follow-up study, including 1150 IVF/ICSI cycles performed between 2016 and 2018 with at least 1 day–5 blastocyst available for transfer or freezing. Among these cycles, 524 were performed with use of a time-lapse system (Embryoscope). Serum Progesterone level was measured on the day of ovulation trigger, and a value >1.3 ng/ml was used to identify premature progesterone elevation.

Participants/materials, setting, methods

The cycles were divided into 2 groups according to serum progesterone level: 1335 cycles were allocated in the normal progesterone group (P < 1,3) and 215 in the progesterone premature elevation group (P > 1.3). Patient’s characteristics, ovarian stimulation characteristics, IVF cycles characteristics and embryology parameters were anonymously recorded and compared between the 2 groups.

Main results and the role of chance

Female age, smoking status, AFC and AMH levels were comparable between the 2 groups. Female BMI was significantly higher in the P < 1,3 than in the P > 1.3 group (26.1 versus 24.7 kg/m² respectively). Total FSH dose, estradiol level, number of follicles >11mm and number of retrieved oocytes were significantly higher in the P > 1.3 group than in P < 1.3 group No difference was observed between the 2 groups in terms of top blastocyst rate per mature oocyte and usable blastocyst rate per mature oocyte. When morphokinetic analysis was available, time to blastulation was the only significantly different parameter between the 2 groups (110.4 hours in P < 1.3 versus 107.9 hours in P > 1.3, p = 0.04). Cumulative live birth rate per cycle was not statistically different between the two groups (23.1% for P < 1.3 versus 28.7% for P > 1.3) (p > 0.05).

Limitations, reasons for caution

The retrospective design of the study should lead to careful analysis of the results. The progesterone threshold refers to a specific assay, and should not be generalized to other assays.

Wider implications of the findings: Premature elevation of serum progesterone level on the day of ovulation trigger does not seem to affect embryo developmental competence. This further supports the relevance of freeze all strategy in this situation.

Trial registration number

Not applicable
P–704 Does the type of ovarian stimulation scheme and dose matter when calculating the amount of gonadotropins used to obtain an egg?
Authors: Lorenzo F , Youn. Obejero E , De. Camp. Echegoyen M J , Garcia J , Felici M
Published: August 2021

Study question

Is the controlled ovarian stimulation protocol important to determine the ovarian sensitivity index (number of oocytes retrieved / total gonadotropin dose)?

Summary answer

OSI in an interesting tool in estimating the ovarian sensitivity to exogenous gonadotropins and can be adjusted when different kinds of COS procotols are used.

What is known already

In our country, Argentina, as the fertility treatments are financed by different health care insurance companies, COS protocols may vary depending on the drugs provided. The objective of our study is to assess the oocyte retrieval number in patients undergoing COS, for IVF or fertility preservation (egg freezing), on the basis of the kind of protocol and the average gonadotropin dose.

Study design, size, duration

This is a retrospective and descriptive study in which 684 cycles, performed between November 2018 and March 2020, were evaluated. Patients underwent COS for IVF or fertility preservation purposes.

Participants/materials, setting, methods

COS protocols were analysed including different parameters such as: number of mature follicles (17mm or more) the trigger day, number of oocytes retrieved, number of M2 retrieved, follicle to oocyte index (FOI), and the kind of protocol.Each of these groups were divided into four groups depending on the protocol used. Group A: FSHr; Group B: FSHr/LHr; Group C: FSHr + HMG; Group D: Clomiphene citrate + HMG. Oocyte donors and incomplete medical records were excluded

Main results and the role of chance

The total number of cycles analysed was 684. There were 135(19.7%) cycles in the under 35 age group; 340(42%) in the 35 to 39 group; 209(38%) in the older than 40 group. They were subdivided in Group A: 54(6.67%) cycles; Group B 93(11.11%) cycles; Group C 465(71.72%); Group D 72(10.5%). A total number of 11351 oocytes were retrieved, with a mean average of 4.6 +- 2.5 SD per patient. Assessment of dose of gonadotropin per oocyte retrieved in each different group: GROUP A 360IU+–38 SD; GROUP B 390IU+–43 SD; GROUP C 375IU +–44 SD; GROUP D 479+–36 SD.

Limitations, reasons for caution

This is a retrospective study. Further prospective studies and a higher sample size are needed to confirm whether the OSI is a useful tool to adjust gonadotropins doses related to an specific COS protocol and improve the oocyte pick up.

Wider implications of the findings: The main conclusion obtained was that the average dose of gonadotropin needed to obtain one mature oocyte was 360 to 390 IU. The HMG and clomiphene citrate protocol needed the highest dose of gonadotropin (479 IU) but no significant stadistical differences were observed.

Trial registration number

NA
P–710 The possible relation between kisspeptin and apoptosis on granulosa cells of PCOS patients
Authors: Erener E , Kocaman A , Ayas B
Published: August 2021

Study question

Does kisspeptin administration affect the apoptotic factors of granulosa cells of Polycystic Ovary Syndrome (PCOS) patients?

Summary answer

Kisspeptin administration significantly increased apoptosis related factors.

What is known already

Kisspeptin plays a critical role in central gonadotropin secretion by acting on GnRH neurons in the hypothalamus. Kisspeptin receptors are also expressed on the ovaries. Kisspeptin–54 has recently been known as a prominent agent in oocyte maturation. Although there are many studies on the possible roles of kisspeptin administration in vivo on hypothalamic gonadotropin secretion and ovarian function and the possible roles of these effects in the pathogenesis of PCOS, there is not enough information about the effect of in vitro application of kisspeptin on ovarian function and conditions that lead to the development of PCOS.

Study design, size, duration

This basic research study was an in vitro experimental approach involving the use of granulosa cell from a PCOS and normal cases between July to December in 2020. 32 women were included in both control and PCOS groups.

Participants/materials, setting, methods

Women with (n = 16) and without (n = 16) PCOS were included in the study. Granulosa cells, follicular fluids and blood samples were collected on oocyte pick-up day. Cells were isolated from follicular fluids. Kisspeptin–54 levels were determined by ELISA in serum and follicle fluids. Also, FSH and LH levels were determined in serum. Kisspeptin–54 administrated in vitro to the half of the samples. Fluorescence spectrophotometer and laser scanning confocal microscope were used to evaluate calcium concentrations

Main results and the role of chance

The serum kisspeptin level was found significantly higher in PCOS patients compared to the control group (p < 0.05). Also, the level of kisspeptin in follicular fluid was statistically significantly higher in PCOS patients compared to the control group (p < 0.05). The mean serum FSH level of PCOS patients was found to be significantly lower than the control group (p < 0.05). Furthermore, the mean serum LH level of PCOS patients was significantly higher than control groups (p < 0.05). The intracellular calcium concentration in granulosa cells obtained from PCOS patients was significantly lower than the control group (p < 0.05).

Limitations, reasons for caution

The KISS1, KISS1R, BCL–2, CASPASE–3, FSHR, LHCGR, STAR, ESR1, ESR2, INHBA gene expression levels of apoptotic process is still under analyses. The protein expression analyses of these genes may strength the results.

Wider implications of the findings: Using kisspeptin antagonists may be supposed as an additional treatment for patients with PCOS.

Trial registration number

OMU KAEK 2019 /724
P–717 Where do cryopreserved embryos end up after a positive pregnancy test?
Authors: Young E , Argibay S Garci , Isa L , Zappacost. Villarroel M P , Inza R , Valcarcel A
Published: August 2021

Study question

What is the destination of supernumerary embryos after a positive pregnancy test?

Summary answer

Half of the surplus cryopreserved embryos in assisted reproduction treatments are not transferred.

What is known already

Many of the surpernumerary cryopreserved embryos in assisted reproductive technologies are not transferred. This is a constant issue in many fertility centers around the world. Our objective was to report what happens with vitried surplus embryos after IVF in patients with a positive pregnancy test, carrying out an analysis according to age and final evolution of the pregnancy.

Study design, size, duration

This is a retrospective descriptive study. We analyzed 245 embryo transfer cycles, performed between January 2013 to December 2017, in 235 patients with a positive pregnancy test and who vitrified surplus embryos.

Participants/materials, setting, methods

All the patients underwent treatment with their own oocytes. The variables studied were: age, miscarriage rate (MR) and live birth rate (LBR). We compared the destination of the cryopreserved embryos according to the patient’s age and pregnancy evolution. Statistical analysis was performed with Fisher’s exact test.

Main results and the role of chance

20% of the IVF cycles (n = 49) were performed in women older than 40 years, 42% between 35 and 39 (n = 103) and 38% in women younger than 35 (n = 94). Average age was 35.8 ± 4.1 years. 859 embryos were cryopreserved (3.5 ± 1.9 cryopreserved embryos/patient). Average search time for surplus embryos was 20.5 ± 17.9 months, rising to 36.9 ± 14.9 months after delivery and decreasing to 8.7 ± 7.8 months after miscarriage (P < 0.0001). Up to date there are 118 (48.2%) patients whose cryopreserved embryos have not been transferred yet. Signficant differences were found in the three groups in using the cryopreserved embryos according to whether or not they had delivery. Almost half of the surplus cryopreserved embryos are not transferred. Regardless of the age of the patient, all groups showed the same behavior regarding the utilization of the cryopreserved embryos after delivery. It is essential to advise couples who perform assisted reproductive technologies, with a good probability of success (regardless of the patient’s age), about the responsibility that embryonic cryopreservation entails. Argentine legislation has limitations regarding the availability of cryopreserved surplus embryos.

Limitations, reasons for caution

This is a retrospective study.

Wider implications of the findings: We believe that Public Health policies related to this issue should be re evaluated based on these results.

Trial registration number

Not applicable
P–718 Paternal smoking in the preconception period is associated with an increased risk of spontaneous miscarriage in a dose-dependent manner: a systematic review and meta-analysis
Authors: Fossé N. D , Va. de. Hoorn M L , Buisman N , Va. Lith J , Cessie S L , Lashley L
Published: August 2021

Study question

What is the association between paternal lifestyle factors in the preconception period and the risk of spontaneous miscarriage? Summary answer: Preconception paternal cigarette smoking is associated with an increased risk of spontaneous miscarriage, while no associations were found with paternal alcohol consumption and obesity.

What is known already

Although maternal lifestyle risk factors for miscarriage are well-established, studies on potentially contributing paternal factors remain sparse. Recently, a significant association was found between advanced paternal age and spontaneous miscarriage. Biological evidence indicates that smoking, excessive alcohol consumption and obesity may lead to sperm oxidative DNA damage, being a known risk factor for miscarriage. Study design, size, duration: Systematic review and meta-analysis.

Participants/materials, setting, methods

PubMed and Embase databases were searched in August 2020. Paternal factors examined were: cigarette smoking, alcohol consumption and Body Mass Index (BMI). A qualitative risk of bias assessment was performed for all included studies. Meta-analysis was performed if sufficient data was available from studies that controlled for maternal factors. PRISMA guidelines for systematic reviews were followed.

Main results and the role of chance

The systematic search included 3386 articles of which 11 articles met the inclusion criteria. In a meta-analysis of eight studies, paternal smoking of > 10 cigarettes per day in the preconception period was found to be associated with an increased risk of spontaneous miscarriage, after adjustment for maternal smoking status (1–10 cigarettes per day: 1.01, 95% CI 0.97–1.06; 11–20 cigarettes per day: 1.12, 95% CI 1.08–1.16; >20 cigarettes per day: 1.23, 95% CI 1.17–1.29). Based on five available studies, no clear association was found between paternal alcohol consumption and spontaneous miscarriage. No studies were retrieved that evaluated the association between paternal BMI and spontaneous miscarriage.

Limitations, reasons for caution

Investigating the relation between paternal lifestyle factors and spontaneous miscarriage is challenging and prone to different forms of bias, especially in retrospective studies.

Wider implications of the findings: Awareness of the association between heavy paternal smoking in the preconception period and the risk of spontaneous miscarriage should be raised. More well-designed studies are needed to further investigate the effects of other paternal lifestyle factors on the risk of spontaneous miscarriage.

Trial registration number

Not applicable
P–745 The efficacy of Buscopan® in reducing pain during ultrasound-guided manual vacuum aspiration (USG-MVA): A double-blind randomised placebo-controlled trial
Authors: Chung J P W , Law T , Sahota D , Mak J , Li T C
Published: August 2021

Study question

Does Buscopan® reduce abdominal pain experienced by women undergoing ultrasound-guided manual vacuum aspiration (USG-MVA)?

Summary answer

The addition of 20mg Buscopan® intravenous injection was not associated with a statistical reduction in pain score but leads to a higher patient satisfaction score.

What is known already

Ultrasound-guided Manual Vacuum aspiration is a feasible and effective out-patient treatment option for treating early pregnancy loss. However, it is associated with a moderate amount of pain due to uterine contraction.

Study design, size, duration

This randomised, double-blinded, placebo-controlled trial was conducted in a university-affiliated tertiary hospital. The study assessed whether 1 ml of 20mg Buscopan® intravenous injection 5 minutes before the USG-MVA will reduce the abdominal pain experienced by the women immediately and 2 hours after the procedure. Participants were randomised between June 2018 to January 2020 using a computer-generated number series in a 1:1 ratio.

Participants/materials, setting, methods

Women aged 18 years or older with first-trimester miscarriage undergoing the USG-MVA procedure were eligible. In total, 122 participants out of 128 eligible were included. Of whom, 111 underwent the USG-MVA procedure, 60 randomised to the Buscopan® group, and 62 to the placebo group.

Main results and the role of chance

The median abdominal pain scores in the Buscopan® group were 16.0% and 21.2% lower than the placebo group immediately post-procedure and 2 hours after the procedure in the Buscopan® group. Repeated measures ANOVA indicated that the both vaginal and abdominal pain scores improved significantly with the time (Vaginal F(1,108)=180.1,p<0.0001; Abdominal: F(1,108)=83.41,p<0.001) but not with group. No difference was noted in the complications and side effects profile. The physiological stress measured by Log10 sAA levels reduced significantly with time (F(2.8,286.1)= 6.3, p < 0.001) but not with group (F = 0.1, p = 0.96). Women randomised to Buscopan® had a significantly higher (p = 0.032) mean VAS satisfaction scores compared to those receiving placebo (79.0±17.3 vs 73.4±24.1).

Limitations, reasons for caution

This study was a single-centre study, thus one should be cautious in the overall generalisability of the results.

Wider implications of the findings: Few studies have evaluated the use of anti-spasmodic agents to minimise uterine contraction pain in women undergoing outpatient uterine evacuation. We consider Buscopan® a useful adjunct in the pain control of USG-MVA to specifically reduce uterine cramps. Further larger studies are required to evaluate its efficacy.

Trial registration number

ChiCTR1800014590
P–784 Neonatal follow-up of babies born derived from mono-pronuclear zygotes
Authors: Tsuji H , Kitasaka H , Fukunaga N , Asada Y
Published: August 2021

Study question

Are the neonatal outcomes normal of babies derived from the transfer of blastocysts derived from mono-pronuclear(1PN) zygotes?

Summary answer

There was no effect on growth or increase in congenital anomalies up to 18-months in babies of 1PN-derived births.

What is known already

1PN zygotes are observed in ART, albeit at a low rate. We have previously reported that 80.7% of 1PN zygotes derived from IVF or ICSI had a biparental chromosome using Live Cell imaging techniques, and some of these developed to the blastocyst stage (Tokoro et al. ASRM 2013). Furthermore, we have reported that these blastocysts can result in a viable pregnancy and healthy live birth (Tsuji et al. ASRM2020). However, there is some uncertainty about the developmental mechanism of 1PN zygotes, and there is no clear consensus on their clinical utility.

Study design, size, duration

This was a retrospective study which included 55 cases where there was a live birth after single embryo transfer of a blastocyst derived from 1PN zygote. The incidence of birth defects, birth weight was recorded as well as a physical development survey of 25 children who responded to the 18-months follow-up survey. The time period was 72 months (January 2013 to December 2018).

Participants/materials, setting, methods

Patients seeking fertility treatment at an established private IVF clinic. We compared the birth weight, birth after18-months height and weight of children born to 1PN zygotes with data from a control, 2PN group. Statistical significance was determined using the t-test (level of P < 0.05).

Main results and the role of chance

The incidence of birth defects in 1PN embryo-derived infants was 1.8% (1/55). The average birth weight of boys in the 1PN group was 3105.6+/–360.3g, which was not significantly different from 3041.0+/–443.3 g in the 2PN group. In girls, the average birth weight was 3085.7+/–454.9 g in the 1PN group, which was not significantly different from the 2PN group (2938.9+/–311.5 g). The average height at 18-months, was 81.6+/–2.5 cm vs 80.5+/–3.4 cm for boys; 79.0+/–1.8 cm vs 79.0+/–3.4 cm for girls in the 1PN and 2PN groups, respectively. The average body weights of the 1PN and 2PN groups were 11.1+/–1.1 kg vs 10.7+/–1.1 kg for boys; 9.7+/–0.9 kg vs 10.1+/–1.0 kg for girls, respectively. There was no significant difference in average height and weight up-to the 18-months follow-up survey.

Limitations, reasons for caution

The incidence of 1PN derived births is low and the study was limited to cases of single blastocyst embryo transfer.

Wider implications of the findings: The incidence of congenital anomalies in Japan was around 1.7 to 2%, and the incidence was similar in the 1PN. There was no difference in the birth weight and 18-months follow-up survey of the 1PN compared with the 2PN. We have demonstrated that there is clinical utility of 1PN embryo.

Trial registration number

Not applicable
P–789 Obstetric and perinatal outcomes in poor ovarian responders and normal responders flowing fresh embryo transfer: a prospective, monocentric, observational study
Authors: Deng J
Published: August 2021

Study question

Whether women pregnant after a poor response in IVF have obstetric and perinatal complications more frequently than women with pregnancies after a normal response in IVF?

Summary answer

There were no statistically significant differences in obstetric and perinatal complications rate between poor responders and normal responders in Chinese women.

What is known already

Poor ovarian response usually indicates a reduction in follicular response, resulting in a reduced number of retrieved oocytes. Patients are less likely to conceive and have a higher risk of cycle cancellation and low clinical pregnancy rate. Whether poor ovarian response is associated with obstetric and perinatal complications is however debated.

Study design, size, duration

Design: Prospective, monocentric, observational study.

Size: 1664 women with poor ovarian response and 1061 women with normal ovarian response

duration : July 1, 2017 to Aug 15, 2019.Participants/materials, setting, methods: 1664 women with poor ovarian response and 1061 women with normal ovarian response undergoing IVF or ICSI were enrolled in this study. The primary outcome was obstetric and perinatal complications rate.

Main results and the role of chance

1664 women with POR and 1061 women with NOR were enrolled in this study.Poor and normal responders did not have significantly different incidences in obstetric and perinatal complications(25.42% vs 25.45%), nor were there a significant difference in preeclampsia, gestational diabetes mellitus, postpartum hemorrhage or abruptio placentae. But POR group have a lower frequency of twin pregnancies(8.47% vs 28.66%,P<0.01),low birth weight(5.08% vs 14.23%,P<0.01)and prematurity (9.32% vs 17.03%,P<0.01).

Limitations, reasons for caution

Despite its size, an observational study such as this has a number of inherent limitations, and the best way to confirm its findings will be to compare obstetric and perinatal outcomes in different subgroup of pregnancies following ART in an adequately powered randomized, controlled trial.

Wider implications of the findings: This prospective, monocentric, observational study suggests that women with poor ovarian response did not have higher perinatal complication rate than women with normal ovarian response. Oocyte quality and quantity may not affect the rate of perinatal complications.

Trial registration number

Not applicable
The Bernstein Projector Determined by a Weak Associate Class of Good Cosets
Authors: Kim Yeansu , Spice Loren , Varma Sandeep
Published: August 2021

Let ${\text G}$ be a reductive group over a $p$-adic field $F$ of characteristic zero, with $p \gg 0$, and let $G={\text G}(F)$. In [ 15], J.-L. Kim studied an equivalence relation called weak associativity on the set of unrefined minimal $K$-types for ${\text G}$ in the sense of A. Moy and G. Prasad. Following [ 15], we attach to the set $\overline{\mathfrak{s}}$ of good $K$-types in a weak associate class of positive-depth unrefined minimal $K$-types a ${G}$-invariant open and closed subset $\mathfrak{g}_{\overline{\mathfrak{s}}}$ of the Lie algebra $\mathfrak{g} = {\operatorname{Lie}}({\text G})(F)$, and a subset $\tilde{{G}}_{\overline{\mathfrak{s}}}$ of the admissible dual $\tilde{{G}}$ of ${G}$ consisting of those representations containing an unrefined minimal $K$-type that belongs to $\overline{\mathfrak{s}}$. Then $\tilde{{G}}_{\overline{\mathfrak{s}}}$ is the union of finitely many Bernstein components of ${G}$, so that we can consider the Bernstein projector $E_{\overline{\mathfrak{s}}}$ that it determines. We show that $E_{\overline{\mathfrak{s}}}$ vanishes outside the Moy–Prasad ${G}$-domain ${G}_r \subset{G}$, and reformulate a result of Kim as saying that the restriction of $E_{\overline{\mathfrak{s}}}$ to ${G}_r\,$, pushed forward via the logarithm to the Moy–Prasad ${G}$-domain $\mathfrak{g}_r \subset \mathfrak{g}$, agrees on $\mathfrak{g}_r$ with the inverse Fourier transform of the characteristic function of $\mathfrak{g}_{\overline{\mathfrak{s}}}$. This is a variant of one of the descriptions given by R. Bezrukavnikov, D. Kazhdan, and Y. Varshavsky in [8] for the depth-$r$ Bernstein projector.
Evaluating the Efficacy, Safety, and Tolerance of Silver Sulfadiazine Dressings Once Daily Versus Twice Daily in the Treatment of Burn Wounds
Authors: Lagziel Tomer , Asif Mohammed , Born Louis , Quiroga Luis H , Duraes Eliana , Slavin Benjamin , Shetty Pragna , Caffrey Julie , Hultman C Scott
Published: August 2021

Topical silver sulfadiazine (SSD) is an effective antimicrobial therapy used to prevent burn wound infection and promote healing, but the frequency of application has not been previously examined. This study compares once versus twice daily dressing changes with SSD, focusing on development of wound infections, incidence of hospital acquired complications, patient pain scores, and length of stay. The objective of this study was to evaluate whether a once-daily or twice-daily application of SSD impacts burn wound healing outcomes. Our institution maintained a twice-daily dressing change standard of care until January 1, 2019. Patients admitted after that date had their dressing changed once daily. We performed a noninferiority analysis which indicated that a sample size of 75 per group would be sufficient to detect a significant difference with a power of 0.80. Our goal is to review outcomes for 75 patients before the change-of-practice and 75 patients after. Our main outcomes recorded are wound infection, average pain scores, average daily narcotic requirements, and length-of-stay. Results from 75 pre-change-of-practice and 75 post-change-of-practice patients showed slightly better outcomes in the post-change-of-practice group. The wound-infection rates were the same for both groups (pre = 5.33%, post = 5.33%), average daily pain levels for the pre-change group were slightly higher but the difference was negligible and not statistically significant (pre = 5.27, post = 5.25), hospital-related complication rates (unrelated to wound care) were higher pre-change (pre = 10.67%, post = 6.67%), and length-of-stay, was longer in the pre-change group (pre = 11.97, post = 10.31). The amount average amount of SSD (g/day) used per patient per hospital stay was higher as well (pre = 320.14, post = 202.12). Further statistical analysis of the results, particularly in the distribution of burn type, age, and burn depth showed no discrepancy and a generalized decreased length-of-stay with once-daily SSD dressing change. Our results show that once-daily dressing changes of SSD in burn wounds have no negative impact on wound outcomes. However, it is associated with a decreased length-of-stay, decreased pain levels, and less hospital-acquired complications. A decreased length-of-stay means reduced medical expenses for the patient and the hospital. In addition, less hospital-acquired complications result in better patient recovery. Since the difference in wound outcomes is negligible and statistically insignificant, changing the standard-of-care to once daily could prove beneficial.
Remembrances of Gurus Past: Reading the Smṛti Sthāna in the Sarangpur BAPS Swaminarayan Temple Complex
Authors: Kim Hanna H.
Published: August 2021

In the Bochasanwasi Shri Akshar Purushottam Swaminarayan Sanstha (BAPS) tradition, the guru is satpuruṣa and Aksharbrahman, an already perfect devotee and the existential form in whom God, who is Parabrahman, is resident on earth. At death, the guru’s mortal body undergoes cremation but the eternal ontological category of Aksharbrahman is manifested in a successor in whom Bhagwan Swaminarayan (Parabrahman) is fully present. This article explores BAPS’s understanding of guru’s corporeality and divinity and the built forms that arise at the place of cremation, samādhi sthaḷa, to memorialise the Aksharbrahman guru. The memorial places, smṛti sthāna, are active material and devotional agents, tied to the theological foundations of BAPS Swaminarayan bhakti. As agentive devotional structures, these memorial sites act upon, visually define, and invite engagement with those who visit them. These dimensions of the material are inseparable from the guru’s role in the conceptualisation, location, and construction of BAPS smṛti sthāna. This article examines the material and devotional significances of two memorial places in the Sarangpur BAPS Swaminarayan temple complex in Gujarat, India. The argument is that smṛti sthāna are sites whose construction is materially tied to BAPS bhakti: these memorial places uphold the centrality of past gurus’ and the present guru’s ontological position and materialise the vital singularity of the Aksharbrahman category through whom devotees can experience the continuing presence of the guru lineage and Bhagwan Swaminarayan.1
The Neuropathology of 1p36 Deletion Syndrome: An Autopsy Case Series
Authors: Conway Kyle S , Ghafoor Fozia , Gottschalk Amy C , Laakman Joseph , Eigsti Renee L , Nashelsky Marcus , Blau John , Hefti Marco M
Published: August 2021

1p36 deletion syndrome is the most common terminal deletion syndrome, manifesting clinically as abnormal facies and developmental delay with frequent cardiac, skeletal, urogenital, and renal abnormalities. Limited autopsy case reports describe the neuropathology of 1p36 deletion syndrome. The most extensive single case report described a spectrum of abnormalities, mostly related to abnormal neuronal migration. We report the largest published series of 1p36 autopsy cases, with an emphasis on neuropathologic findings. Our series consists of 3 patients: 2 infants (5-hours old and 23-days old) and 1 older child (11 years). Our patients showed abnormal cortical gyration together with a spectrum of neuronal migration abnormalities, including heterotopias and hippocampal abnormalities, as well as cerebellar hypoplasia. Our findings thus support the role of neuronal migration defects in the pathogenesis of cognitive defects in 1p36 deletion syndrome and broaden the reported neuropathologic spectrum of this common syndrome.
Polymorphous Low-Grade Neuroepithelial Tumor of the Young (PLNTY): Molecular Profiling Confirms Frequent MAPK Pathway Activation
Authors: Ida Cristiane M , Johnson Derek R , Nair Asha A , Davila Jaime , Kollmeyer Thomas M , Minn Kay , Fadra Numrah M , Balcom Jessica R , Fung Kar-Ming A , Kim Dong Kun , Kaufmann Timothy J , Kipp Benjamin R , Halling Kevin C , Jenkins Robert B , Giannini Caterina
Published: August 2021

Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a recently described epileptogenic tumor characterized by oligodendroglioma-like components, aberrant CD34 expression, and frequent mitogen-activated protein kinase (MAPK) pathway activation. We molecularly profiled 13 cases with diagnostic histopathological features of PLNTY (10 female; median age, 16 years; range, 5–52). Patients frequently presented with seizures (9 of 12 with available history) and temporal lobe tumors (9 of 13). MAPK pathway activating alterations were identified in all 13 cases. Fusions were present in the 7 youngest patients: FGFR2-CTNNA3 (n = 2), FGFR2-KIAA1598 (FGFR2-SHTN1) (n = 1), FGFR2-INA (n = 1), FGFR2-MPRIP (n = 1), QKI-NTRK2 (n = 1), and KIAA1549-BRAF (n = 1). BRAF V600E mutation was present in 6 patients (17 years or older). Two fusion-positive cases additionally harbored TP53/RB1 abnormalities suggesting biallelic inactivation. Copy number changes predominantly involving whole chromosomes were observed in all 10 evaluated cases, with losses of chromosome 10q occurring with FGFR2-KIAA1598 (SHTN1)/CTNNA3 fusions. The KIAA1549-BRAF and QKI-NTRK2 fusions were associated respectively with a 7q34 deletion and 9q21 duplication. This study shows that despite its name, PLNTY also occurs in older adults, who frequently show BRAF V600E mutation. It also expands the spectrum of the MAPK pathway activating alterations associated with PLNTY and demonstrates recurrent chromosomal copy number changes consistent with chromosomal instability.
Delaying or delivering: identification of novel NAM-1 alleles that delay senescence to extend wheat grain fill duration
Authors: Chapman Elizabeth A , Orford Simon , Lage Jacob , Griffiths Simon
Published: August 2021

Senescence is a complex trait under genetic and environmental control, in which resources are remobilized from vegetative tissue into grain. Delayed senescence, or ‘staygreen’ traits, can confer stress tolerance, with extended photosynthetic activity hypothetically sustaining grain filling. The genetics of senescence regulation are largely unknown, with senescence variation often correlated with phenological traits. Here, we confirm staygreen phenotypes of two Triticum aestivum cv. Paragon ethyl methane sulfonate mutants previously identified during a forward genetic screen and selected for their agronomic performance, similar phenology, and differential senescence phenotypes. Grain filling experiments confirmed a positive relationship between onset of senescence and grain fill duration, reporting an associated ~14% increase in final dry grain weight for one mutant (P<0.05). Recombinant inbred line (RIL) populations segregating for the timing of senescence were developed for trait mapping purposes and phenotyped over multiple years under field conditions. Quantification and comparison of senescence metrics aided RIL selection, facilitating exome capture-enabled bulk segregant analysis (BSA). Using BSA we mapped our two staygreen traits to two independent, dominant, loci of 4.8 and 16.7 Mb in size encompassing 56 and 142 genes, respectively. Combining association analysis with variant effect prediction, we identified single nucleotide polymorphisms encoding self-validating mutations located in NAM-1 homoeologues, which we propose as gene candidates.
Two ubiquitin-associated ER proteins interact with COPT copper transporters and modulate their accumulation
Authors: Li Xifeng , Wang Zhe , Fu Yunting , Cheng Xi , Zhang Yan , Fan Baofang , Zhu Cheng , Chen Zhixiang
Published: August 2021

The endoplasmic reticulum (ER) contains an elaborate protein quality control network that promotes protein folding and prevents accumulation of misfolded proteins. Evolutionarily conserved UBIQUITIN-ASSOCIATED DOMAIN-CONTAINING PROTEIN 2 (UBAC2) is involved in ER-associated protein degradation in metazoans. We have previously reported that two close UBAC2 homologs from Arabidopsis (Arabidopsis thaliana) not only participate in selective autophagy of ER components but also interact with plant-specific PATHOGEN-ASSOCIATED MOLECULAR PATTERN (PAMP)-INDUCED COILED COIL (PICC) protein to increase the accumulation of POWDERY MILDEW-RESISTANT 4 callose synthase. Here, we report that UBAC2s also interacted with COPPER (Cu) TRANSPORTER 1 (COPT1) and plasma membrane-targeted members of the Cu transporter family. The ubac2 mutants were significantly reduced in both the accumulation of COPT proteins and Cu content, and also displayed increased sensitivity to a Cu chelator. Therefore, UBAC2s positively regulate the accumulation of COPT transporters, thereby increasing Cu uptake by plant cells. Unlike with POWDERY MILDEW RESISTANCE 4, however, the positive role of UBAC2s in the accumulation of COPT1 is not dependent on PICC or the UBA domain of UBAC2s. When COPT1 was overexpressed under the CaMV 35S promoter, the increased accumulation of COPT1 was strongly UBAC2-dependent, particularly when a signal peptide was added to the N-terminus of COPT1. Further analysis using inhibitors of protein synthesis and degradation strongly suggested that UBAC2s stabilize newly synthesized COPT proteins against degradation by the proteasome system. These results indicate that plant UBAC2s are multifunctional proteins that regulate the degradation and accumulation of specific ER-synthesized proteins.