bluuebunny/crossref_metadata_2025 huggingface dataset:
P-474 Association between subchorionic hematoma’s size and miscarriage rate in IVF/ICSI patients
Authors: Chen P , Manchao L , Lei J , Cong F
Published: June 2023

Study question

What is the risk factor for miscarriage in patients undergoing IVF/ICSI with subchorionic hematoma(SCH) in the first trimester?

Summary answer

The size of SCH is a risk factor for miscarriage in patients undergoing IVF/ICSI. Miscarriage rate increases as the size of SCH grows.

What is known already

SCH is a frequently observed pathology during routine ultrasound examinations in early pregnancy. Its clinical significance has been unclear. Some studies believed that SCH found in first trimester was not correlated with adverse pregnancy outcome; Other studies believed that SCH in early pregnancy can cause a significant increase in the incidence of late pregnancy complications, such as preterm labor, preeclampsia, and postpartum hemorrhage. Besides, what are the risk factors for miscarriage in pregnant women with SCH? Answers to these questions are urgently needed.

Study design, size, duration

Retrospective cohort study with 646 patients undergoing IVF/ICSI at a tertiary care university hospital, between February 2017 and November 2020.

Participants/materials, setting, methods

All patients who underwent IVF/ICSI from February 2017 to November 2020, achieved pregnancy and underwent transvaginal ultrasound at our center during first trimester were included. Risk factors for miscarriage in patients with SCH were explored. Miscarriage rates in patients with different SCH sizes which was expressed as its' ratio to the area of the gestational sac were compared.

Main results and the role of chance

Patients with SCH who had more embryos transferred (P=0.01), earlier detection of IUH (P=0.003), a smaller GS area (P=0.03) was prone to miscarry. The size of SCH is a risk factor for miscarriage (P = 0.016). Miscarriage rate increased with increasing size of SCH (P for trend: 0.003).

Limitations, reasons for caution

The main limitation of this study is its retrospective nature and relatively small sample size.

Wider implications of the findings

Extra clinical attention needs to be paid to the miscarriage risk of in IVF/ICSI patients with large SCH. There is urgent need for future research on SCH affecting pregnancy outcome and the underlying pathophysiological mechanisms.

Trial registration number

Not applicable
P-475 Effect of transdermal estradiol on endometrial preparation in frozen-thawed embryo transfer: A randomized control study.
Authors: Tran T T T
Published: June 2023

Study question

Is patient usage of transdermal estradiol more effective than oral estradiol on endometrial preparation in frozen-thawed embryo transfer cycles?

Summary answer

This study showed no significant differences in clinical pregnancy rates between the 2 groups. Transdermal gel have advantage of better patient comfort, lesser side effects.

What is known already

Estrogen and progesterone are crucial factors for endometrial preparation in frozen embryo transfer (FET) cycles. Studies assessing different forms of estradiol in FET have already been published. However, literature and studies in Vietnam are still limited to evaluating, research evaluating transdermal estrogen in ART. This study aimed to evaluate the use of transdermal estradiol gel and compare it with oral estradiol for the endometrium preparation in frozen-thawed embryo transfer (FET) cycles.

Study design, size, duration

This randomized clinical trial (RCT) included 380 frozen embryo transfer (FET) cycles from February 2020 to August 2021 at the IVF Department, Hung Vuong Hospital.

Participants/materials, setting, methods

They were randomized into one of the two groups. Group A (n = 190) received oral estradiol and group B (n = 190) received estradiol gel. In both groups, medication was started on day 2 of the menstrual, and endometrial thickness was monitored by ultrasound. Main outcomes were the following: serum estradiol level , endometrial thickness,.... Secondary outcomes were CPR, MR, and side effects in the 2 groups. Statistical testing was performed with Stata 14.

Main results and the role of chance

There was a significant difference in estradiol level on the day of progesterone administration and embryo transfer between the two groups (270.5 pg/ml versus 186.5 pg/ml, p, p. <0.001). According to the comparison, the two groups were not significantly different in the endometrial thickness on the day of progesterone administration (p = 0.85). as the data suggest, the total dose of estradiol used and the total number of days of dosing were similar in the two groups. The biochemical and clinical pregnancy rates were similar between the two groups and did not a significantly differ (56.2% vs. 52.2%, p = 0.474). The rate of miscarriage was higher than in the study group, but it was not statistically significant. Almost 20.3% of patients (n = 37) in group A had mild adverse effects when compared with only 10.1% (n = 18) in group B, and this was clinically significant (P = 0.007).

Limitations, reasons for caution

The limitation of our study was not asses ongoing pregnancy rate and live-birth rate.

Wider implications of the findings

Patients who estradiol valerate is contraindicated such as, high risk for deep vein thrombosis, hyperlipidemia, and clotting disturbance we can use oestrogel to be safe. It is suggested that estradiol transdermal patches be used instead of oral estradiol in FET cycles

Trial registration number

ISRCTN15301227
P-482 Bacterial vaginosis in a subfertile population undergoing fertility treatments: a prospective cohort study
Authors: Van den Tweel M , Van den Munckhof E , Van der Zanden M , Molijn A , Van Lith J , Le Cessie S , Boers K
Published: June 2023

Study question

Does bacterial vaginosis (BV) influences pregnancy rates during fertility treatments?

Summary answer

BV does not significantly impact ongoing pregnancy or live birth rates but could affect miscarriage rates.

What is known already

BV is known to influence several obstetric outcomes, such as preterm delivery and endometritis. Only few studies investigated the effect of BV in subfertile women, and studies found a negative effect of BV on fecundity especially in the in vitro fertilisation (IVF) population.

Study design, size, duration

Observational prospective study, 76 couples attending a fertility clinic in the Netherlands between July 2019 and June 2022, undergoing a total of 133 attempts of intra uterine insemination (IUI) or IVF.

Participants/materials, setting, methods

Participants undergoing IUI, IVF or intra cytoplasmatic sperm injection (ICSI). Vaginal samples taken at oocyte retrieval or insemination were analysed on qPCR BV and 16S rRNA gene microbiome analysis of V1-V2 region. Logistic regression with a Generalized Estimated Equations (GEE) analysis was used to account for multiple observations per couples. Main study outcome was defined as ongoing pregnancy at 12 weeks. Secondary outcomes were miscarriage rate and live birth rate.

Main results and the role of chance

A total of 26% of the 133 samples tested positive for BV. No significant differences were observed in ongoing pregnancy or live birth rates based on BV-status (OR 0.50 (0.16-1.59), aOR 0.32 (0.09-1.23)) or microbiome community state type (CST). There was a tendency of more miscarriages based on positive BV status (OR 4.22 (1.10-16.21), aOR 4.28 (0.65-28.11)) or microbiome CST group III/IV. Sample outcomes of qPCR BV were in accordance with their microbiome analyses. On baseline groups significantly differed on smoking status and body mass index (BMI). Odds ratios were adjusted for smoking status, BMI and socioeconomic status.

Limitations, reasons for caution

Numbers of the initial sample size calculation were not met. Therefore, numbers may be too small to draw firm conclusions.

Wider implications of the findings

This study describes the influence of BV or an abnormal microbiome in a subfertile population undergoing fertility treatments. A possible effect of lifestyle factors on BV-status is shown. Combining qPCR and microbiome results and analysing both IUI and IVF/ICSI treatments can contribute to better generalisability to the consulting room.

Trial registration number

Z21.031
P-493 Bleeding during early pregnancy after Hormone Replacement Therapy Frozen Embryo Transfer (HRT-FET) – is it more common than we think?
Authors: Nielsen J , Humaidan P , Alsbjerg B , BrixJensen M
Published: June 2023

Study question

How common is bleeding in early pregnancy after HRT-FET? And does bleeding affect the reproductive outcome in this population?

Summary answer

A total of 47% of HRT-FET patients experience bleeding before the 8th week of gestation, however, bleeding does not seem to affect the reproductive outcome.

What is known already

Bleeding occurs in 20% of spontaneously conceived pregnancies. Most pregnancies will proceed to term although episodes of heavy bleeding are associated with an increased risk of miscarriage. The prevalence of bleeding after assisted reproductive technology including in vitro fertilization seems to be higher and, in some reports, up to 36%. However, the knowledge is scanty and in particular the knowledge regarding bleeding during HRT-FET is sparse. As HRT-FET in clinical practice increases, knowledge on the occurrence of early bleeding during pregnancy and the impact on the reproductive outcome in this population is needed.

Study design, size, duration

We performed a cohort study including 489 patients undergoing HRT-FET. The trial was conducted from January 2020 to November 2022 in a public fertility clinic.

Participants/materials, setting, methods

Patients with autologous vitrified blastocyst were treated in a standard HRT-FET protocol. In the event of a positive HCG-test an early pregnancy scan was performed around 8 weeks of gestation. During this visit the women answered a questionnaire covering pregnancy related symptoms, wellbeing, and if bleeding occurred, the type and duration of the bleeding. The information was verified through medical files.

Main results and the role of chance

In this HRT-FET cohort we found that a total of 47% (150/322) of patients with a positive pregnancy test experienced bleeding before 8 weeks of gestation. Mostly the bleeding was described as spotting with a median of 2 days (range 0.5—16 days). Out of 150 patients with one or several bleeding episodes, a total of 107 patients (71 %) had an ongoing pregnancy at 12 weeks of gestation. In comparison, 172 patients reported no bleeding episodes and a total of 115 (67%) of these patients had an ongoing pregnancy at 12 weeks of gestation. This difference was found to be non-significant (p = 0,39).

Limitations, reasons for caution

The patients in our study were treated in a standard HRT-FET protocol. The results may not be transferable to other treatment protocols. Also the data is based on patients self-reported symptoms. Therefore some degree of recall bias may be present.

Wider implications of the findings

Episodes of early bleeding during pregnancy are associated with distress for the pregnant woman – especially in previously infertile patients. Knowledge about the frequent occurrence of bleeding during early pregnancy after HRT-FET and that this does not affect the reproductive outcome will help the clinician reassure and guide the patient.

Trial registration number

2019-001539-29
P-509 Genomic characterization of couples and their embryos/fetuses with idiopathic recurrent pregnancy loss
Authors: Wang W J , Wang L , Sun J , Qing Z , Liu Z
Published: June 2023

Study question

To what extent do genomic variants contribute to idiopathic recurrent pregnancy loss (RPL)?

Summary answer

Pathogenic uniparental disomy, copy number variations, and single nucleotide variants were identified in 18 of 83 couples and their embryos/fetuses with idiopathic RPL.

What is known already

RPL is defined as the loss of two or more pregnancies before 24 weeks gestation. The etiologies of RPL include antiphospholipid antibody syndrome, and anatomic, endocrinological and chromosomal abnormalities. About 50% of RPL is unexplained and is termed as idiopathic RPL. Chromosomal aberrations and genetic variants have been identified to be associated with idiopathic RPL, demonstrating that genomic factors underlie idiopathic RPL.

Study design, size, duration

We applied genome sequencing to study genomic variations that causing idiopathic RPL. Couples and their embryos/fetuses were collected and sequenced. Genomic variations from women and men experiencing RPL and their embryos/fetuses were analyzed to fully characterize the genomic contribution to idiopathic RPL.

Participants/materials, setting, methods

We recruited 83 Chinese couples with idiopathic RPL and collected 249 samples from their embryos/fetuses and peripheral blood. Genomic DNA of those samples were sequenced, and pathogenic chromosomal abnormalities and genetic variants were identified.

Main results and the role of chance

Generally, pathogenic variants were identified in RPL females, males and embryos/fetuses. One uniparental disomy, 9 copy number variations, and 1 homozygous and 1 de novo single nucleotide variants (SNVs) were identified pathogenic in 12 RPL embryos/fetuses. Five and three pathogenic SNVs were identified in 4 RPL females and 2 RPL males respectively. Many SNVs affect the genes involved in sexual development. In total, 18 of 83 (21.69%) couples with idiopathic RPL could be explained by genomic variation, providing information for clinical treatments.

Limitations, reasons for caution

The sample size is relatively small, and they are from one medical center.

Wider implications of the findings

Genomic variations in females, males and their embryos/fetuses can cause RPL, and identification of genetic causes will facilitate further precision intervention.

Trial registration number

not applicable
P-510 Low neighbourhood socioeconomic status is associated with lower cumulative ongoing pregnancy rate after in vitro fertilization treatment
Authors: Speksnijder J , Marion E , Baart E , Steegers E , Laven J , Bertens L
Published: June 2023

Study question

Is there an association between neighbourhood socioeconomic status (SES) and cumulative ongoing pregnancy after 2.5 years of in vitro fertilization (IVF) treatment?

Summary answer

Low and middle neighbourhood SES is associated with lower odds of an ongoing pregnancy within 2.5 years of IVF treatment than high neighbourhood SES.

What is known already

Low SES is known to have a negative impact on general health and a variety of medical conditions, including perinatal health. However, not much data is available on the impact of SES on IVF treatment outcome.

Study design, size, duration

This is a retrospective observational study of 3720 couples undergoing IVF or IVF-ICSI treatment between 2006 and 2020.

Participants/materials, setting, methods

Neighbourhood SES was assigned to each couple based on the postal code of residence. Subsequently, SES was categorized into low (p80). Multivariable logistic regression analyses were performed with cumulative ongoing pregnancy within 2.5 years as outcome variable, SES category, female age, BMI, smoking status (yes/no), and interaction terms for age*SES and BMI*SES were used as covariates.

Main results and the role of chance

There was no difference in ongoing pregnancy rates between SES groups after the first fresh embryo transfer or in the average number of IVF treatment cycles performed. However, the cumulative ongoing pregnancy rates differ significantly between SES groups (Low; 43.6%, medium; 50.9%, high; 54.1%). Low SES had significantly lower odds for achieving an ongoing pregnancy within 2.5 years (OR = 0.06 (95%CI 0.02-0.22)). The interaction terms age*SES and BMI*SES showed attenuation of this association with increasing age and BMI (OR = 1.07 (95%CI 1.022 – 1.12) and OR = 1.61 (95%CI 1.25 – 2.09), respectively). The associations with medium SES were similar, but less pronounced (OR = 0.16 (95%CI 0.05 – 0.50) with OR = 1.04 (95%Cl 1.00 – 1.09) and OR = 1.41 (1.12 – 1.77) for the interaction terms with female age and BMI respectively.

Limitations, reasons for caution

We were not able to perform additional analysis on individual characteristics like educational level, ethnicity or language proficiency due to lack of data.

Wider implications of the findings

In the Netherlands, health insurance is mandatory. Our study showed that even with equal access to fertility care, patients living in a low SES neighbourhood are disadvantaged. This underlines the importance of taking the whole wellbeing of the patient into account, before starting an IVF treatment.

Trial registration number

not applicable
P-517 Downregulated INHBB in endometrial tissue of recurrent implantation failure patients impeded decidualization through the ADCY1/cAMP signalling pathway
Authors: Zhang H , Zhang X , Wang Z
Published: June 2023

Study question

To identify the mechanism of Inhibin Subunit Beta B (INHBB) in the regulation of human endometrial stromal cells (HESCs) decidualization in recurrent implantation failure (RIF).

Summary answer

INHBB was decreased in endometrial stromal cells of women with RIF, which attenuated decidualization in vitro by suppressing ADCY1-induced cAMP production and cAMP-mediated signalling.

What is known already

INHBB encodes a preprotein subunit of inhibin/ activin, functional cytokines belonging to the transforming growth factor-β (TGF-β) family. INHBB mRNAs were expressed in human decidualized endometrium from the first trimester of pregnancy and increased as the gestation progressed. Furthermore, INHBB expression increases in the mouse uterus in areas undergoing decidualization. These studies indicated that INHBB might play an essential role in endometrial decidualization.

Study design, size, duration

The Medical Ethics Committee of Nanjing Drum Tower Hospital approved this study (No. 2013-081-01). Written informed consent was obtained from each participant. Between January 2020 and November 2021, 28 infertile and 18 fertile control women aged 20-40 years with normal and regular menstrual cycles (25-35 days) and no history of steroid hormone medication in the last 3 months were included in the study.

Participants/materials, setting, methods

RNA-seq was conducted to identify the differentially expressed genes in the endometria from control and RIF patients. RT-qPCR, WB, and immunohistochemistry were performed to analyse the expression levels of INHBB in decidualised HESCs. RT-qPCR and immunofluorescence were used to detect changes in decidualization after knockdown INHBB. Then, RNA-seq was used to dig out the mechanism of INHBB regulating decidualisation.

Main results and the role of chance

Our results showed significantly reduced expression of INHBB in endometrial stromal cells of women with RIF. In addition, INHBB was increased in the endometrium of the secretory phase and significantly induced in in-vitro decidualization of HESCs. Notably, with RNA-seq and siRNA-mediated knockdown approaches, we demonstrated that the INHBB-ADCY1-mediated cAMP signalling pathway regulates the reduction of decidualization. We found a positive association between the expression of INHBB and ADCY1 in endometria with RIF (R2= 0.3785, P = 0.0005).

Limitations, reasons for caution

Our results indicated that INHBB regulates cAMP level by inducing the expression of ADCY1, while the regulation mechanism between INHBB and ADCY1 in endometrial decidualization requires further exploration.

Wider implications of the findings

The decline of INHBB in HESCs suppressed ADCY1-induced cAMP production and cAMP-mediated signalling, which attenuated decidualization in RIF patients, indicating that INHBB is an essential component in the decidualization process.

Trial registration number

not applicable
P-526 Modified Applebaum uterine scoring system to predict uterine receptivity in frozen embryo transfer(FET) cycles
Authors: Sapkota A , Sharma S
Published: June 2023

Study question

To evaluate modified Applebaum uterine scoring system in predicting the uterine receptivity and clinical pregnancy rate?

Summary answer

The modified version of Applebaum uterine scoring system has sensitivity of 0.9411 and specificity of 0.5869 in predicting the uterine receptivity in embryo transfer cycle.

What is known already

The endometrial receptivity have been accepted to be major limiting factors in the establishment of pregnancy. Different techniques have been developed to evaluate endometrial receptivity, such as endometrial receptivity array or histological dating. The advantage of Ultrasound is it’s non-invasiveness, repeatability, real time monitoring and predictability.

Study design, size, duration

It is a prospective observational study. Study group comprises of 200 female with primary infertility over a period of 6 month.

Participants/materials, setting, methods

Exclusion criteria was patients associated with male sub-fertility or having uterine anomalies. The study was conducted at D.Y.Patil fertility centre, unit of Bloom IVF. All the patients were given uterine scoring before FET based on Endometrial thickness, morphology, vascularisation, myometrial echogenicity, uterine artery PI and EDF, myometrial blood flow.

Main results and the role of chance

The overall pregnancy rate was 54%. A perfect score of 20 was associated with 97.4% pregnancy rate. Scores of 17 to 19 was associated with the pregnancy rate of 85.4% and scores of 14 to 16 was associated with the pregnancy rate of 28.6%. Score less than 13 is not associated with any pregnancy. The Modified Applebaum scoring system showed the sensitivity of 0.9411 and specificity of 0.5869 in predicting the outcome of the cycle.

On an individual basis, endometrial morphology, end diastolic blood flow(EDF) and Pulsatility index(PI) of uterine artery and myometrial blood flow were found to be significant for a pregnancy on the basis of Z score and p value of < 0.01

Limitations, reasons for caution

As there were no case of secondary infertility, Grade III/IV endometriosis, endocrine disorder and uterine anomalies. The scoring system might not replicate the same results.

Wider implications of the findings

As the sensitivity and specificity of this uterine scoring system is quite good. It could be a good tool in assessing endometrium before embryo transfer.

Trial registration number

Not applicable
P-585 Iron intake in relation to ovarian reserve among women seeking infertility treatment
Authors: Chavarro J , Jimenez-Cardozo N , Mitsunami M , Minguez-Alarcon L , Ortiz-Panozo E , Wang S , Hauser R , Souter I
Published: June 2023

Study question

Is there an association between iron intake and ovarian reserve among women seeking fertility care?

Summary answer

Supplemental iron intake above 45mg/d is associated with lower ovarian reserve among women seeking fertility care.

What is known already

Although the literature regarding iron intake in relation to ovarian reserve is scant and inconsistent, some evidence suggest that iron may have gonadotoxic effects.

Study design, size, duration

Observational study including 582 female participants attending the Massachusetts General Hospital Fertility Center (2007–2019) enrolled in the Environment and Reproductive Health (EARTH) Study

Participants/materials, setting, methods

Iron intake was estimated using a validated food frequency questionnaire (FFQ). Markers of ovarian reserve included antral follicle count (AFC) (assessed via transvaginal ultrasound) and day 3 FSH, both obtained during the course of infertility evaluation. The association between iron intake and ovarian reserve was evaluated using Poisson regression models for AFC and quantile regression models for day 3 FSH adjusted for age, menstrual cycle characteristics, physical activity, carbohydrate intake and total energy intake.

Main results and the role of chance

Participants had a median age of 35 years and median total iron intake of 29 mg/d. Total iron intake was inversely related to AFC and this association was driven by intake of supplemental iron. Compared to women with a supplemental iron intake ≤20mg/day, women consuming 45-64mg/d of supplemental iron had a 17% (-35%, 0.3%) lower AFC and women consuming ≥65mg/d of supplemental iron had a 32% (-54%, -11%) lower AFC after adjusting for potential confounders (p, linear trend=0.003). Similarly, in multivariable-adjusted analysis, day 3 FSH levels were 0.9 (0.5, 1.3) IU/mL higher among women with a supplemental iron intake ≥65mg/d when compared to women with a supplemental iron intake ≤20mg/d (p, linear trend=0.02).

Limitations, reasons for caution

Iron intake was estimated using a method that relies on self-report and we had no biomarkers of iron status in our participants. Also, only 36 women consumed ≥45mg/d of supplemental iron.

Wider implications of the findings

Since all study participants were seeking fertility treatment, our findings may not apply to women in the general population. Although our findings are consistent with studies of women with iron overload, given the paucity of literature on this topic it is essential that this question is revisited in future studies.

Trial registration number

Not applicable, not a randomized trial
P-591 Follicular fluid-derived exosomes rejuvenate ovarian aging through miR-320a-3p-mediated FOXQ1 inhibition
Authors: Liu Y , Yan L , Xixiang M , Wenpei X
Published: June 2023

Study question

Dose the follicular fluid-derived exosomes rejuvenate ovarian aging?

Summary answer

Follicular fluid-derived exosomes efficiently rescued ovarian function in aged mice, which was achieved via transfer of miR-320-3p to granulosa cells and subsequent Foxq1 inhibition.

What is known already

The ovary enters the malfunctional aging phase earlier and faster than other organs and systems. Ovarian aging is mainly characterized by a progressive decline in oocyte quantity and quality, which ultimately leads to female infertility. Various therapies have been established to cope with age-related ovarian dysfunction, among which exosome-based therapy has been considered a promising strategy that can benefit ovarian functions via multiple pathways.

Study design, size, duration

Ovarian granulosa cells of young C57BL/6J mice (6-8 w) and old C57BL/6J mice (40 w) were cultured in vitro. The follicular fluid exosomes of young mice and the same amount of PBS were respectively injected into the ovarian sac of old mice.

Participants/materials, setting, methods

Cell proliferation and apoptosis were detected by CCK8, flow cytometry and Western Blot. Mitochondrial function was assessed by measuring mitochondrial membrane potential, ATP levels, mtDNA copy numbers. The number of ovarian follicles were observed by HE staining. Senescence and telomere related gene expression levels were detected by RT-qPCR. 2-cell rates and blastocyst formation rates were observed after in vitro fertilization. The model mice were directly cooped up to observe the pregnat and litter sizes.

Main results and the role of chance

The follicular fluid exosomes from young mice can promote the proliferation of ovarian granulosa cells from old mice and improve mitochondrial function. When the follicular fluid exosomes from young mice were injected into the ovarian sac of old mice, the number of primordial and growing follicles in the ovaries of old mice were increased and the developmental ability of oocytes was improved.

Limitations, reasons for caution

Findings in mouse.

Wider implications of the findings

This study suggests that young follicular fluid exosomes may be involved in ovarian senescence by transferring miR-320a-3p targeting FOXQ1 into ovarian granulosa cells of aged mice.

Trial registration number

no
P-613 Deletion of the CLPP gene in oocytes exacerbates chemotherapy-induced ovarian damage
Authors: Gu J , Guo C , Xiao Y , Hua R , Hai Z , Zhao P , Su J , Wang T
Published: June 2023

Study question

We attempted to investigate the role of the Clpp in chemotherapy-induced ovarian damage and the decline of oocyte function

Summary answer

We clarified that the deletion of Clpp gene in oocytes will aggravate the ovarian damage and the decline of oocyte function caused by chemotherapeutic drugs.

What is known already

Chemotherapy is extensively used to treat cancers and is often associated with ovarian damage which leads to premature ovarian insufficiency and infertility. Mitochondria have the critical role of producing energy and maintaining normal cellular activities for oocyte maturation and folliculogenesis.

Study design, size, duration

This study used a mouse model with oocyte-specific deletion of mitochondrial stress response gene Caseinolytic peptidase P (Clpp) to investigate mitochondrial homeostasis in oocytes from mice receiving a chemotherapeutic drug cyclophosphamide (CTX).

Participants/materials, setting, methods

First, analyze the reproductive phenotype and fertility test of mice, observe the ovarian development, the proportion of follicles at all levels, the spindle of oocytes and the aneuploidy rate of chromosomes at the MII stage, and using multiple mitochondrial function indicator kit to detect mitochondrial function. Then, we modeled 8-week-old mice with a single injection of 100ul 75uM cyclophosphamide. After 14 days, check the above indicators again. the impact of cyclophosphamide modeling will be analyzed.

Main results and the role of chance

We found the specific deletion of Clpp in oocytes reduced fecundity of the mice at advanced age. The Clpp deletion led to meiotic defects and impaired mitochondrial distribution and function in the MII oocytes. CTX induction further affected oocyte competence in Clpp cKO mice and lead to an exhaustive disruption of blastocytes formation due to the severe effects on mitochondrial distributions and functions.

Limitations, reasons for caution

We only clarified that the deletion of Clpp gene in oocytes will through affecting the mitochondrial function aggravate the ovarian damage and the decline of oocyte function caused by chemotherapeutic drugs.But the underlying mechanism has not been able to explore further.

Wider implications of the findings

This is first study specifically on the impact of oocyte specific deletion of Clpp on oocyte competence and early embryo development. At the same time, the role of Clpp gene in the ovary damaged by chemotherapy drugs was further clarified.

Trial registration number

not applicable
P-614 Endometrial preparation: effect of estrogen levels before the embryo transfer on the live birth rate from 14825 freezing-all cycles
Authors: Li Y , Xiaojuan W , Ge L , Fei G
Published: June 2023

Study question

Is there a difference in live birth rate during discrepant estrogen levels before the embryo transfer following either hormone replacement therapy (HRT) or natural cycle(NC)?

Summary answer

The higher estrogen level on the day before embryo transfer may reduce the live birth rate in either HRT or NC.

What is known already

The endometrial preparation of frozen embryo transfer cycle is to synchronize of endometrium and embryo under the condition of exogenous estrogen and progesterone drugs in HRT or follicle monitoring in NC. Estrogen is crucial and different estrogen levels could imply variations on endometrial preparation. Information on the effect of discrepant estrogen levels before the embryo transfer on reproductive outcomes of women undergoing freezing-all cycles is scarce.

Study design, size, duration

Retrospective cohort study including 14825 first frozen embryo transfers following IVF/ICSI undergoing freezing-all cycles from January 2016 to December 2020. A total of 12305 (83.0%) patients received NC while 2520 (17.0%) received HRT.

Participants/materials, setting, methods

Effect of estrogen levels on live birth rates, stratifified by deciles and ROC to determine the cutoff values for estrogen level on the day before embryo transfer.Multivariable logistic regression analysis was performed to adjust for confounders.

Main results and the role of chance

The live birth rate was 44.7% and 52.4% in HRT and NC respectively. The live birth rate of HRT began to decline when the estrogen level was P60 in the deciles which the cut-off values of ROC was closed with the estrogen level was 891.6 pg/ml. The lower level of estrogen on the day before embryo transfer in HRT corresponds to a higher live birth rate（51.4% vs 32.9%）.The cut-off values of ROC in NC was statistically different with the estrogen level was 194.4 pg/ml. The lower level of estrogen on the day before embryo transfer in NC corresponds to a higher live rate（53.0% vs 48.6%）.After adjusting the possible confounding factors by multivariate logistic regression, it was found that the estrogen level on the day before embryo transfer in HRT and NC was the independent influencing factor of live birth rate with the OR of 0.57 (0.47,0.68) and 0.82 (0.74,0.90), respectively.

Limitations, reasons for caution

The greatest limitation of this study is its retrospective study. On the other hand, this study was performed using non-PGT cycle, although this is unlikely to affect the results,we cannot exclude the possibility that euploid embryo responds differently to endometrial state in comparison to aneuploid embryo.

Wider implications of the findings

In freezing-all cycles, the higher estrogen level on the day before embryo transfer may reduce the live birth rate in either HRT or NC. Clinicians should pay attention to the control of estrogen level in luteal phase.

Trial registration number

Nona
P-615 Ovarian rejuvenation with human placenta hydrolyzate
Authors: Rybina A , Askar E , Abshekenova A , Karibayeva S , Valiev R , Lokshin V
Published: June 2023

Study question

Is it possible to rejuvenate the ovaries with human placenta hydrolyzate?

Summary answer

Injecting human placenta hydrolyzate into the ovaries can activate dormant follicles and produce mature oocytes in patients with ovarian insufficiency.

What is known already

Patients with low ovarian reserve and/or ovarian failure are a difficult category for reproductive specialists. Attempts to rejuvenate the ovaries have been made for several years. The use of adjuvant therapy such as PRP can activate dormant follicles. Human placenta hydrolyzate contains growth factors, hormones, trace elements, vitamins. Administration of human placenta hydrolyzate directly to the ovaries can also activate folliculogenesis and oogenesis.

Study design, size, duration

A cohort study was conducted, which involved 20 women with low ovarian reserve who underwent IVF / ICSI at the Person ICCR in 2022. AMH, FSH, the number of antral follicles, the number of received oocytes were determined before the injection of the human placenta hydrolyzate (JAPAN BIO PRODUCTS Co, LTD, Japan) into the ovaries and 1-3 months after procedures.

Participants/materials, setting, methods

All patients had previously undergone IVF/ICSI. 20 women with infertility, mean age was 39±6 years. In September-October 2022, we received a human placenta hydrolyzate intraovarially. The human placenta hydrolyzate was injected into the ovaries as in a transvaginal puncture with a 20 G needle, 1 ml into each ovary. All participants gave their voluntary informed consent to the procedure.

Main results and the role of chance

On the 2-3rd day of the cycle before the procedure, the average level of AMH was 0.11±0.09 ng/ml, FSH 38.11±10.86 mIU/ml, the number of antral follicles 1.18±0, 38, the number of mature oocytes obtained on TVP, 0.68±0.19. After the introduction of the human placenta hydrolyzate into the ovaries, measurements were repeated 1-3 months later: AMH was 0.46±0.18 ng/ml, p = 0.09; FSH was 13.54±7.86 mIU/ml, p = 0.074; CAF 1.96±0.17, p = 0.068; oocytes M2 1.51±0.38, p = 0.058. Due to small cohort size and short follow-up time, we believe that ovarian activation by placental hydrolyzate takes place, this is especially noticeable in the number of obtained mature oocytes that went for freezing or fertilization: 4 patients received embryos suitable for PGT-A, one the embryo (mosaic) was transferred into the uterine cavity and pregnancy occurred. There was no any side effect after the injection.

Limitations, reasons for caution

Limitations relate to study design. More patients and longer follow-up are also needed.

Wider implications of the findings

Ovarian rejuvenation is currently an adjuvant therapy, high-level evidence is not yet available. However, for women with POI and POR, any opportunity to improve the chances of obtaining their own oocytes is valuable.

Trial registration number

NO APPLICABLE
P-627 Effects of ntraovarian Injection of Autologous Platelet-Rich Plasma on Ovarian Reserve in Poor Responders undergoing IVF Treatment
Authors: Gao F , Min F , Yanbin W
Published: June 2023

Study question

Does intracortical injections of autologous platelet-rich plasma (PRP) improve the outcomes in patients with poor ovarian response (POR) undergoing the IVF treatment?

Summary answer

PRP injections could improve the markers of low ovarian reserve, especially the first month after the injection.

What is known already

Poor ovarian responders (PORs) with poor reproductive outcomes during the IVF treatment is considered the main challenges of reproductive science. PORs are presented by low ovarian reserve, poor oocyte quality and low response to ovarian stimulation protocols. Despite several approaches that have been investigated to improve the ovulation outcome in PORs, the pregnancy rate remains low.

Study design, size, duration

The pilot study was designed as prospective observational studies. 39 PORs based on Bologna criteria were included and followed by 3 months. Couples presenting with any other infertility etiology other than POR were excluded. All participants provided written informed consent prior to treatment.

Participants/materials, setting, methods

The patients in the study were received at least two previous failed Intracytoplasmic Sperm Injection (ICSI)-Embryo Transfer (ET) fresh cycle. PRP intraovarian infusion treatment was performed following the last failed ICSI-ET cycle. The patients were followed 3 months after the injection. Primary outcome measures were levels of anti-müllerian hormone (AMH), antral follicle count (AFC), follicle stimulating hormone (FSH), and oocyte yield after the PRP treatment.

Main results and the role of chance

The level of AMH was significantly elevated from 0.52±0.43ng/ml before the PRP treatment to 0.82±0.61ng/ml after the treatment. The AFC showed the same trend from 2.52±1.50 to 5.83±4.25 and the FSH level was decreased by 31.98%. But the number of retrieved oocytes and embryo available were not significantly increased.

Limitations, reasons for caution

The design of the observational studies and the small sample size.

Wider implications of the findings

PRP injection may be a potiental treatment for PORs in IVF.

Trial registration number

not applicable
Generalized Chromatic Functions
Authors: Aliniaeifard Farid , Li Shu Xiao , van Willigenburg Stephanie
Published: June 2023

We define vertex-colourings for edge-partitioned digraphs, which unify the theory of $P$-partitions and proper vertex-colourings of graphs. We use our vertex-colourings to define generalized chromatic functions, which merge the chromatic symmetric and quasisymmetric functions of graphs and generating functions of $P$-partitions. Moreover, numerous classical bases of symmetric and quasisymmetric functions, both in commuting and noncommuting variables, can be realized as special cases of our generalized chromatic functions. We also establish product and coproduct formulas for our functions. Additionally, we construct the new Hopf algebra of $r$-quasisymmetric functions in noncommuting variables, and apply our functions to confirm its Hopf structure, and establish natural bases for it.
Lessons (Machine) Learned From COVID-19
Authors: Sullivan Timothy
Published: June 2023

Since coronavirus disease 2019 (COVID-19) first emerged more than 3 years ago, more than 1200 articles have been written describing “lessons learned” from the pandemic. While these articles may contain valuable insights, reading them all would be impossible. A machine learning clustering analysis was therefore performed to obtain an overview of these publications and to highlight the benefits of using machine learning to analyze the vast and ever-growing COVID-19 literature.
RNA Editing as a General Trait of Ebolaviruses
Authors: Mehedi Masfique , Ricklefs Stacy , Takada Ayato , Sturdevant Dan , Porcella Stephen F , Marzi Andrea , Feldmann Heinz
Published: June 2023

RNA editing has been discovered as an essential mechanism for the transcription of the glycoprotein (GP) gene of Ebola virus but not Marburg virus. We developed a rapid transcript quantification assay (RTQA) to analyze RNA transcripts generated through RNA editing and used immunoblotting with a pan-ebolavirus monoclonal antibody to confirm different GP gene–derived products. RTQA successfully quantified GP gene transcripts during infection with representative members of 5 ebolavirus species. Immunoblotting verified expression of the soluble GP and the transmembrane GP. Our results defined RNA editing as a general trait of ebolaviruses. The degree of editing, however, varies among ebolaviruses with Reston virus showing the lowest and Bundibugyo virus the highest degree of editing.
Limited evidence for extensive genetic differentiation between X and Y chromosomes in Hybognathus amarus (Cypriniformes: Leuciscidae)
Authors: Caeiro-Dias Guilherme , Osborne Megan J , Waterman Hannah M , Krabbenhoft Trevor J , Turner Thomas F
Published: June 2023

Sex determination systems and genetic sex differentiation across fishes are highly diverse but are unknown for most Cypriniformes, including Rio Grande silvery minnow (Hybognathus amarus). In this study, we aimed to detect and validate sex-linked markers to infer sex determination system and to demonstrate the utility of combining several methods for sex-linked marker detection in nonmodel organisms. To identify potential sex-linked markers, Nextera-tagmented reductively amplified DNA (nextRAD) libraries were generated from 66 females, 64 males, and 60 larvae of unknown sex. These data were combined with female and male de novo genomes from Nanopore long-read sequences. We identified five potential unique male nextRAD-tags and one potential unique male contig, suggesting an XY sex determination system. We also identified two single-nucleotide polymorphisms (SNPs) in the same contig with values of FST, allele frequencies, and heterozygosity conforming with expectations of an XY system. Through PCR we validated the marker containing the sex-linked SNPs and a single nextRAD-tag sex-associated marker but it was not male specific. Instead, more copies of this locus in the male genome were suggested by enhanced amplification in males. Results are consistent with an XY system with low differentiation between sex-determining regions. Further research is needed to confirm the level of differentiation between the sex chromosomes. Nonetheless, this study highlighted the power of combining reduced representation and whole-genome sequencing for identifying sex-linked markers, especially when reduced representation sequencing does not include extensive variation between sexes, either because such variation is not present or not captured.
Chlorophyll fluorescence-based high-throughput phenotyping facilitates the genetic dissection of photosynthetic heat tolerance in African (Oryza glaberrima) and Asian (Oryza sativa) rice
Authors: Robson Jordan K , Ferguson John N , McAusland Lorna , Atkinson Jonathan A , Tranchant-Dubreuil Christine , Cubry Phillipe , Sabot François , Wells Darren M , Price Adam H , Wilson Zoe A , Murchie Erik H
Published: June 2023

Rising temperatures and extreme heat events threaten rice production. Half of the global population relies on rice for basic nutrition, and therefore developing heat-tolerant rice is essential. During vegetative development, reduced photosynthetic rates can limit growth and the capacity to store soluble carbohydrates. The photosystem II (PSII) complex is a particularly heat-labile component of photosynthesis. We have developed a high-throughput chlorophyll fluorescence-based screen for photosynthetic heat tolerance capable of screening hundreds of plants daily. Through measuring the response of maximum PSII efficiency to increasing temperature, this platform generates data for modelling the PSII–temperature relationship in large populations in a small amount of time. Coefficients from these models (photosynthetic heat tolerance traits) demonstrated high heritabilities across African (Oryza glaberrima) and Asian (Oryza sativa, Bengal Assam Aus Panel) rice diversity sets, highlighting valuable genetic variation accessible for breeding. Genome-wide association studies were performed across both species for these traits, representing the first documented attempt to characterize the genetic basis of photosynthetic heat tolerance in any species to date. A total of 133 candidate genes were highlighted. These were significantly enriched with genes whose predicted roles suggested influence on PSII activity and the response to stress. We discuss the most promising candidates for improving photosynthetic heat tolerance in rice.
Developing an Integrated Petrogenetic Model for Understanding REE Deportment of the Ampasibitika Intrusion and Associated Ion Adsorption Deposits
Authors: Marquis E , Goodenough K M , Smith M P , Estrade G , Rasolonirina F , Rakotoson R L
Published: June 2023

Alkaline–peralkaline igneous systems are promising sources of rare earth elements (REEs). Preservation bias has resulted in a gap in the geological record for alkaline–peralkaline magmatic systems, with the hypabyssal plumbing system linking magma chambers to extrusive volcanic rocks poorly represented. Large plutonic varieties of these systems are often proposed to have fed (now eroded) volcanoes, and current peralkaline volcanic systems obscure the plutonic system at depth. The alkaline to peralkaline Ampasibitika Intrusion in Madagascar is a rare example where the magmatic–volcanic interface between a deeper level magma reservoir and its genetically related caldera volcano is exposed. This c. 24 Ma sub-volcanic intrusive system comprises silica-undersaturated to silica-oversaturated units, of peralkaline to metaluminous and peraluminous characters, with varying styles of REE mineralisation, including supergene ion adsorption-style REE occurrences in the overlying weather profiles. There are two main intrusive suites: (1) the concentric Marginal Dyke Swarm (MDS) formed of quartz–microsyenite and peralkaline granite dykes (PGDs), and (2) the Ampasibitika Ring Dyke (ARD) comprising alkali feldspar syenites and subordinate nepheline syenites, trachytes and phonolites. We present new field observations and geochemical data to indicate that the MDS was emplaced as a series of low-viscosity, volatile-rich melt batches, which coalesced in the magma reservoir roof zone and intruded prior to caldera collapse, whereas the ARD was emplaced into the ring fault as a heterogeneous mix of variably evolved syenitic crystal mushes and phonolitic to trachytic-melt batches. As such, we suggest the MDS represents the residual melt fraction of the magma reservoir, whereas the ARD contains portions of the fractionating, silica-neutral to silica-undersaturated syenite, cumulate assemblage. In this revised framework, we assess the major and trace element geochemistry of amphibole- and clinopyroxene-group minerals to gain insight into the magmatic evolution of the Ampasibitika Intrusion and partitioning of REE between early cumulate and residual melt phases. Ultimately, the most REE-enriched units, the PGDs of the MDS, are identified as the product of the most volatile-rich, highly evolved melts from the roof zone of the magma reservoir. However, although REE enriched, the mineralogy does not always enable efficient release of REE for ion adsorption-style mineralisation; instead, lower REE-content protoliths with REE-host phases more amenable to decomposition release a greater proportion of REE.