bluuebunny/crossref_metadata_2025_split huggingface dataset:
P–413 The combination of endometrial injury and Freeze-All strategy in women with repeated implantation failures
Authors: Rigos I , Athanasiou V , Vlahos N , Papantoniou N , Siristatidis C 
Published: August 2021

Abstract

Study question
Can the combination of hysteroscopic endometrial injury (EI) and freeze-all strategy improve pregnancy parameters, mainly live birth, in women with repeated implantation failures (RIF)?

Summary answer
The combination of Endometrial Injury and freeze-all strategy has no significant effect on live birth, clinical and miscarriage rates in RIF patients undergoing ART.

What is known already
A variety of strategies and approaches for RIF patients undergoing ART have been used and proposed. Currently there is insufficient evidence in the literature concerning the effect of either EI or freeze-all strategy in IVF cycles and very limited on the combination of these two approaches in RIF patients.

Study design, size, duration
This is a two-center two-arm cohort study conducted at both University and Private Assisted Reproductive Units in Greece, encompassing 60 cycles with vitrification as the cryopreservation method from 60 participants during the last three years.

Participants/materials, setting, methods
The study group comprised of 30 patients with RIF and underwent a hysteroscopic endometrial injury in the menstrual cycle prior that to the embryo transfer. The control group comprised of patients with RIF and underwent a standard cycle with no adjuvant treatment. Our primary analysis was performed to provide a direct comparison between groups. Logistic and Poisson Regression models were further employed to examine possible confounding effects.

Main results and the role of chance
Live birth did not differ between groups (p = 0.0953); similarly, clinical pregnancy and miscarriage rates were comparable among them (p = 0.3472 and p = 0.2542, respectively). The number of retrieved oocytes was the only significant confounder for biochemical pregnancy (p = 0.0481, 95% CI: (0.0014, 0.3223)].

Limitations, reasons for caution
Limitations of the study include the lack of randomization that is linked with known and unknown biases and the small cohort size.
Wider implications of the findings: The combination of both endometrial injury and freeze-all strategy does not appear to improve pregnancy rates, including live birth, in patients with RIF undergoing ART.
The number of retrieved oocytes was the only significant confounder for biochemical pregnancy.

Trial registration number
NCT04597463
P–445 Successful live birth after repeated high-dose radiotherapy to the uterus
Authors: Lu B J , Chi M S , Chen C H 
Published: August 2021

Abstract

Study question
It has been established that radiotherapy can increase the risk of adverse pregnancy outcomes. However, there is currently no consensus on the effective sterilizing dose for adulthood uterine radiotherapy.

Summary answer
Uterine fertility preservation methods should be guided by the age of the patient receiving radiotherapy and the actual dose of radiation exposure to the uterus.

What is known already
Many experts have suggested that a high dose of radiation to the uterus is a reason to counsel patients against future pregnancy. There are major limitations to the current literature regarding off-target radiation damage to the uterus. One study reported a relative risk of 9.1 for stillbirth and neonatal death after 10 Gy doses.

Study design, size, duration
Case report and review of the literature before December 2020

Participants/materials, setting, methods
A case report of a 36-year-old female with three cancers and received repeated high-dose radiotherapy of 66 Gy and 50 Gy to the pelvis. We used a dose-volume histogram, the most widely used tool to calculate the radiation distribution within a volume of interest of the patient during radiotherapy. We determined that her uterus may have received the highest uterine radiation dosage for full-term live birth in current literature.

Main results and the role of chance
Due to iatrogenic ovarian failure, she could only use donor eggs. After endometrium preparation for 18 days, the endometrium reached 8.7 mm with a triple-line appearance. We transferred two cleavage-staged embryos and one of them implanted successfully. The course of the pregnancy was uneventful. Finally, the patient gave birth to a healthy baby via Cesarean section at 38 5/7 weeks of gestation.

Limitations, reasons for caution
It should be noted that the success of our case may not apply to all patients with cancer after they have received RT. We should inform patients about the increased risk of preterm birth, low birth weight infants, uterine rupture, and neonatal death.
Wider implications of the findings: The patient’s age and the dose of RT exposure to the uterus are important factors for the prognosis of a future pregnancy. More well-designed studies will be needed to allow future standard guidelines for uterine fertility preservation.

Trial registration number
TMU-JIRB N20204149
P–465 Effect of letrozole over Ki–67 expression in breast cancer during controlled ovarian stimulation (COS) for fertility preservation (FP): case report
Authors: Vanni V S , Cioffi R , Bergamini A , Sarais V , Signorelli S , Corti L , Papaleo E , Candiani M , Mangili G 
Published: August 2021

Abstract

Study question
Does concomitant letrozole administration during COS alter Ki–67 expression in women undergoing FP procedures before breast cancer surgery?

Summary answer
Concomitant letrozole administration during COS, even for a short period, can reduce Ki–67 expression in breast cancer.

What is known already
The biggest concern with COS in breast cancer patients is the increase in serum estradiol levels, caused by the development of multiple follicles simultaneously. This has always been a major hindrance to the use of traditional ovarian stimulation regimens in these patients, due to the large amount of evidence on the pathogenetic role of estrogen in breast cancer propagation. To limit the rise of estradiol during COS, most centers have adopted concomitant letrozole administration. Recently, some studies have reported changes in tumor pathology after letrozole administration, such as a significant fall in Ki–67 expression.

Study design, size, duration
Case report including 2 patients undergoing COS with concomitant letrozole administration for 12 days before breast cancer surgery.

Participants/materials, setting, methods
The first patient was a 28-year-old Caucasian woman with a breast biopsy showing an infiltrating ductal carcinoma in the upper external quadrant of the right breast. The second patient was a 33-year-old Caucasian woman with a diagnosis of infiltrating ductal carcinoma of the upper external quadrant of the left breast. Both patients underwent COS with concomitant letrozole administration 5 mg daily for 12 days. Ovarian stimulation was performed using a GnRH-antagonist random-start protocol.

Main results and the role of chance
In the first patient, Ki–67 expression in the initial biopsy was 55%. After completion of FP procedures, she underwent quadrantectomy with sentinel-lymphnode biopsy. In the final histopathological report Ki–67 expression fell to 25%. In the second patient, the first biopsy showed a Ki–67 expression of 30%, while after mastectomy it fell to 10%.

Limitations, reasons for caution
Only 2 patients were included in the study.
Wider implications of the findings: COS is feasible before breast cancer surgery, as long as an adequate cancer biopsy with immunohistochemical evaluation has been collected. Cytological diagnosis is not enough to start FP procedures. Evaluation of biological parameters after letrozole administration could lead to underestimation of cancer proliferation rate and to inappropriate treatment strategies.

Trial registration number
NA
P–517 The relationship between mitochondrial gene CYB (MT-CYB) single nucleotide polymorphisms and male infertility
Authors: Jawish M , Dahadhah F W , Ei. Hammadeh M , Amor H 
Published: August 2021

Abstract

Study question
Do single nucleotide polymorphisms of the mitochondrial gene CYB (MT-CYB) affect male fertility?

Summary answer
there was a significant association between male fertility and rs527236194, rs28357373, and rs41504845 single nucleotide polymorphisms of the mitochondrial gene CYB (MT-CYB).

What is known already
Male infertility can be occurred as a result of various factors. However, genetic factors are detected in 15% of male infertility cases and can be classified into two groups: chromosomal abnormalities and single gene mutations. Sperm mitochondrial DNA alterations may have serious effects on spermatogenesis, sperm motility and the ability of sperm to fertilize the oocyte. Mutations of the MT-CYB gene might lead to various disorders and deficiencies specially in complex III which might interrupt in the ATP production process. Study design, size, duration: 111 semen samples were included in this prospectively designed study which carried out between 2017 and August 2019. Participants/materials, setting, methods: This study carried out at the Department of Obstetrics and Gynecology at Saarland University, Germany. Samples were divided into 67 subfertile “cases” and 44 fertile “control” groups.
After preparation of semen samples by density gradient centrifugation, nuclear and mitochondrial DNA (MT-DNA) was extracted using QIAamp DNA Mini Kit from QIAGEN. Thereafter, the MT-DNA was amplified using REPLI-g Mitochondrial DNA Kit from QIAGEN, followed by PCR and Sanger sequencing steps.

Main results and the role of chance
A total of 13 single nucleotide polymorphisms (SNPs) in the MT-CYB gene in each of the case and control groups were detected. Eight SNPs were non-synonymous variants including: rs2853508, rs28357685, rs41518645, rs2853507, rs28357376, rs35070048, rs2853506, and rs28660155 and five SNPs were synonymous variants: rs527236194, rs28357373, rs28357369, rs41504845, and rs2854124.Among these SNPs, three of them showed a significant difference in the genotype’s frequency test between sub-fertile and fertile groups: rs527236194 (T15784C; P = 0.0005), rs28357373 (T15629C; P = 0.0439), and rs41504845 (C15833T; P = 0.0038). For the allele’s frequency test, two SNPs were significant: rs527236194 (T15784C; P = 0.0014) and rs41504845 (C15833T; P = 0.0147).

Limitations, reasons for caution
The study population size
Wider implications of the findings: A larger prospective study will be required to confirm the associations between these mitochondrial gene polymorphisms in MT-CYB (rs527236194, rs28357373, rs41504845) and male infertility and to clarify the definite effect of the mitochondrial genetic variations on male infertility.

Trial registration number
Not applicable
P–522 Cervical secretion methylation profile is associated with the success of frozen-thawed embryo transfer - a proof-of-concept study
Authors: Lee Y X , Tzeng C R , Hu Y M , Chen C H , Chen C W , Liao C C , Chen L Y , Weng Y C , Wang H C , Huang R L , Lai H C 
Published: August 2021

Abstract

Study question
Is cervical secretion gene methylation profile different between receptive and non-receptive endometrium and associated with implantation outcome in frozen-embryo transfer (FET) cycle?

Summary answer
The combination of candidate genes methylation profiles obtained from cervical secretion showed significant associations with pregnancy outcomes.

What is known already
Implantation failure remains a black box in reproductive medicine, and the exact mechanism of how endometrial receptivity is regulated is still unknown. Epigenetic modifications play a role in the gene expression pattern and may alter the endometrial receptivity in the human endometrium. Cervical secretion containing various implantation-related cytokines, and the gene methylation change can be used as a non-invasive molecular source that reflects the endometrium condition.

Study design, size, duration
In this retrospective case-control study, sixty-two women who entered the FET cycle (30 pregnant and 32 non-pregnant women) were enrolled.

Participants/materials, setting, methods
Cervical secretion was collected before embryo transfer from women enrolled in multicenter university-affiliated reproductive units. The DNA methylation status of six candidate genes was measured using quantitative methylation-specific PCR (qMSP). The correlation between methylation change and the pregnancy outcome was analyzed.

Main results and the role of chance
The candidate genes were selected from that associated with implantation with literature review and the original genome-wide DNA methylation data from NCBI GEO DataSets (GSE90060) which processed using bioinformatics analysis. Six candidate genes whose CpG-level methylation analysis with β-value statistically higher in receptive endometrium than in a pre-receptive endometrium were selected. All six candidate genes showed different degrees of correlation with the pregnancy outcomes. Among them, PRKAG2 methylation changes showed the highest correlation with the pregnancy outcome. A logistic regression model was used to evaluate the performance of a single gene or a combination of genes for implantation prediction. The results showed a statistically significant association between the methylation status of a combination of genes (PRKAG2, KRS1, HAND2) and the pregnancy outcome (p = 0.008), resulting in an optimal AUC of 0.7 (95% CI: 0.57 - 0.81) for implantation prediction.

Limitations, reasons for caution
The results obtained from a relatively small cohort size. A larger study and further comprehensive methylome investigations are warranted.
Wider implications of the findings: This study is the first proof-of-concept study that cervical secretion methylation profile is associated with implantation outcome in a FET cycle, and showed potential as a non-invasive method for implantation prediction.

Trial registration number
non applicable
P–523 Whole-chromosome aneuploidies revealed by transcriptome of trophectoderm biopsied from human pre-implantation blastocyst
Authors: Song L , Yanwen X , Bing C , Yan X , Xiu Y , Canquan Z 
Published: August 2021

Abstract

Study question
Whether mRNA transcriptome of biopsied trophectoderm (TE) in human pre-implantation blastocyst can predict embryo karyotype?

Summary answer
mRNA transcriptome of biopsied TE can precisely predict whole-chromosome aneuploidies but not mosaicism or segmental aneuploidies.

What is known already
Karyotype of human pre-implantation blastocyst is well recognized by PGT-A. However, genome can’t demonstrate gene expression level which might infer the development potential of euploidy. Transcriptome of blastocyst by singe-cell RNA-seq has revealed the lineage segregation of human pre-implantation blastocyst. It is not known whether transcriptome of biopsied TE used in PGT-A can infer the karyotype of human pre-implantation blastocyst.

Study design, size, duration
A total of 74 TE samples were biopsied from 26 blastocysts which were donated from patients who underwent PGT at our Reproductive Medicine Center. All of these embryos have been previously diagnosed as aneuploidies (n = 19) or euploidies (n = 7) with monogenic disorder.

Participants/materials, setting, methods
The DNA and mRNA of all biopsied TEs were separated independently using a modified oligo-dT bead capture, followed by PGT-A of DNA and smart2-sequencing of mRNA (G&T-seq). Karyotype of biopsied TEs were confirmed with PGT-A performed in MiSeq system (Illumina) in our PGT laboratory with the use of next-generation sequencing. Data of transcriptome was analyzed using Rstudio and R package InferCNV to predict aneuploidies by referring to euploidies which were inferred with corresponding PGT-A results.

Main results and the role of chance
In human pre-implantation blastocyst, all whole-chromosome aneuploidies could be inferred by transcriptome of biopsied TE, which were consistent with PGT-A result. But chromosomal mosaicism or segmental aneuploidies were hard to be predicted precisely by transcriptome of TE.

Limitations, reasons for caution
The main limitation of this study lies in the inability to retrieve the exact copy number variations from mRNA transcription. Gene expression is in a great imbalance in such an early development of human pre-implantation blastocyst.
Wider implications of the findings: Our data suggest that mRNA transcriptome is enough for prediction of whole-chromosome aneuploidies. The method and value for predicting mosaicism and segmental aneuploidies by transcriptome should be further investigated.

Trial registration number
Not applicable
P–524 Is polycystic ovary syndrome really a risk factor for embryonic chromosomal aberrations? A multicenter retrospective cohort study
Authors: Luo L , Zhang L , Wang Q 
Published: August 2021

Abstract

Study question
Does the rate of embryonic chromosomal aberrations increase in the setting of PCOS independent of maternal age and BMI?

Summary answer
Controlling for maternal age and BMI, embryonic chromosomal aberration rate was not significantly different with controlled women undergoing preimplantation genetic testing for monogenic defects (PGT-M).

What is known already
It has been reported that women with PCOS have higher risk of early spontaneous pregnancy loss, and it is well known that embryonic chromosomal abnormalities play an important role as a direct factor. However, whether PCOS women have increased risk of embryonic chromosomal aberrations remains inconclusive.

Study design, size, duration
A multicenter retrospective cohort study was undertaken examining the incidence of chromosomal abnormalities in blastocysts using next-generation sequencing (NGS) for women undergoing PGT-M with and without PCOS (1398 PGT cycles, 5577 blastocysts) from 3 university-affiliated IVF centers between 2015 and 2019. Participants/materials, setting, methods: The blastocyst formation rate and the incidence of chromosomal abnormalities were compared between 163 PCOS women and 1235 non-PCOS women. Main results and the role of chance: Stratification analysis by maternal age with matched BMI showed no differences with regard to blastocyst formation rates for women with and without PCOS aged 20–29y (55.0% vs. 58.5%), 30–34y (54.7% vs. 58.9%) and &gt;35y (56.7% vs. 52.4%), P &gt; 0.05. The total embryonic chromosomal aberration rates for women aged 20–29y, 30–34y and &gt;35y with and without PCOS were were also comparable, which were respectively 121/331 (36.4%) vs. 496/1209 (41.0%); 89/251 (35.5%) vs. 903/2175 (41.5%) and 72/130 (55.4%) vs. 789/1481 (53.3%), P &gt; 0.05. Multivariate regression showed that controlling for maternal age and BMI, PCOS were not an independent risk factor for embryonic chromosomal abnormalities (OR = 0.89, 95% CI = 0.62 ∼ 1.35, P = 0.73).

Limitations, reasons for caution
The study is mainly limited by its retrospective design and relatively smaller sample size for PCOS group which carries inherent potential for bias (i.e. misclassifification and errors due to inadequate clinical notes).
Wider implications of the findings: Our results indicated that chromosomal abnormalities might not be the most important causal factor for the increased risk of early pregnancy loss for women with PCOS. By contrary, the non-chromosomal embryonic aberrations and/or maternal intrauterine factors could play more important role and needs to be clarifified

Trial registration number
not applicable’
P–542 Relationship between the single nucleotides polymorphisms in Mitochondrial Nicotinamide Adenine Dinucleotide Hydride dehydrogenase (NADH) Subunit 4 gene (MT-ND4) and male infertility
Authors: Dahadhah F , Jaweesh M. Sale , Zoubi M. Sali. A , Issa. Ab. Alarjah M , Hammadeh M Ei , Amor H 
Published: August 2021

Abstract

Study question
Is there any association between male infertility and the polymorphic variants of Mitochondrial Nicotinamide Adenine Dinucleotide Hydride dehydrogenase (NADH) Subunit 4 (MT-ND4)?

Summary answer
Our findings suggested that male infertility was correlated to rs2853495 and rs869096886 SNPs in MTND4.

What is known already
The rate of mutations in the mtDNA, the powerhouse of the cell, is high due to the lack of histones and DNA repair mechanisms. Therefore, mutations that occur in the mitochondrial genome, play a major role in some human genetic disorders. 15 - 30% of male infertility are related to genetic predisposition. Sperm containing defective mitochondria cannot effectively produce ATP and more likely to produce reactive oxygen species (ROS) and free radicals, thereby causing a defect in mtDNA, make trouble energy, and deteriorate motility and fertility. Study design, size, duration: A prospective study carried out between 2018 and 2019. 112 semen samples were collected in this study.

Participants/materials, setting, methods
The present study was carried out at the department of Obstetrics and Gynecology, University of Saarland, Germany. Samples were divided into 68 subfertile and 44 fertile men. Mitochondrial DNA was extracted using a QIAamp DNA Mini Kit, after that the mtDNA was amplified by using REPLI-g Mitochondrial DNA Kit. Polymerase chain reaction (PCR) was used to amplify MT-ND4 gene. Then, samples were purified and sequenced using the Sanger method in the Microsynth Seq lab, Germany.

Main results and the role of chance
The genotypes frequencies of the study population showed a statistically significant association between rs2853495 G&gt;A (Gly320Gly) and male infertility (P = 0.0351). Similarly, the allele frequency test showed that rs2853495 G&gt;A (Gly320Gly) and rs869096886 A&gt;G (Leu164Leu) were significantly associated with male infertility (adjusted OR = 2.616, 95% CI = 1.374 - 4.983, P = 0.0028; adjusted OR = 2.237, 95% CI = 1.245 - 4.017, P = 0.0073, respectively). On the other hand, no statistically significant difference was observed between the asthenozoospermia, oligozoospermia, teratozoospermia, asthenoteratozoospermia, oligoasthenoteratozoospermia, oligoteratozoospermia subgroups of subfertile males and the fertile ones.

Limitations, reasons for caution
The size number of the study samples.
Wider implications of the findings: A larger prospective study will be required to confirm these associations of mitochondrial gene polymorphisms rs2853495 and rs869096886 in MT-ND4 and male infertility and to clarify the definite effect of the mitochondrial genetic variations on male infertility.

Trial registration number
Not applicable