bluuebunny/crossref_metadata_2025 huggingface dataset:
P–368 Dynamic metabolomic profiling during early implantation period
Authors: Zhang Y , Zhao Y W , Wang C C , Li T C
Published: August 2021

Study question

To investigate the different metabolomic profiling in serum between pregnant and non-pregnant women during early implantation period.

Summary answer

Metabolomics of progesterone-related hormones enhances from ET day3 for pregnancy women compared with non-pregnancy women.

What is known already

Metabolomics is based on high-throughput analytical methods to identify and quantify metabolites. Compared to other omics study, metabolomics is the closest one to the phenotype, allowing the observation of dynamic changes in phenotype at specific timepoints. So far there is no published work about the metabolomics profile in human early implantation period. Study design, size, duration: Study design: comparative study. Size: 14 pregnancy women and 14 non-pregnancy women. duration: time-course.

Participants/materials, setting, methods

Participants: pregnancy women and unpregnancy women after embryo transfer (ET). Setting: university-based study. Methods: Peripheral blood were collected at ET day0, 3, 6 and 9. metabolomic profiling in serum by platforms of capillary electrophoresis-mass spectrometry (CE-MS) and liquid chromatography–mass spectrometry (LC-MS).

Main results and the role of chance

There were no statistical difference of the age, BMI, basal FSH level, endometrium thickness on the day of embryo transfer, distribution of primary and secondary fertility, embryo transfer cycle as well as the infertile types between the two groups. After deleting those with over 50% missing data, we finally have 310 metabolites into statistical analysis. Among the 310 metabolite, lipid metabolites account the largest percentage, nearly half of all metabolites. The second biggest class of metabolites in our data was organic acids. Combined results in repeated measurement ANOVA (RM-ANOVA) and ANOVA-simultaneous component analysis (ASCA) as well as multivariate empirical Bayes time-series analysis (MEBA), we finally found that progesterone-related hormones were the most important metabolites for the whole time-series data. Those significant metabolites showed a significant down regulation from ET day0 to ET day3 and up regulation from ET day3 to ET day9.

Limitations, reasons for caution

we have limited sample size for this study and further validation is necessary for confirmation.

Wider implications of the findings: The phenomenon of upregulation of progesterone-related hormones from day3 in pregnancy group might be related to the embryo-originated hcg. Because the embryo has entered into endometrium at day3 and produced cytokines, hcg and other interaction with endometrium.

Trial registration number

NA
P–370 RPL-protease A as a potential biomarker for predicting recurrent pregnancy loss
Authors: Pei C Z , Park H B , Choi H S , Choi B , Park H Y , Jung H Y , Baek K H
Published: August 2021

Study question

Could the reduction of RPL-protease A be involved in the dysfunctional trophoblast for resulting in recurrent pregnancy loss (RPL).

Summary answer

Low expression of RPL-protease A may result in RPL and low serum RPL-protease A level may be a potential biomarker for predicting RPL.

What is known already

The RPL-protease A is expressed and secreted by placenta. The RPL-protease A is involved in the pathogenesis of pre-eclampsia, and the serum RPL-protease A level is higher in the patients with pre-eclampsia than that of normal groups. In our previous study, we identified that the RPL-protease A mRNA level was lower in the villi of patients with RPL than that of normal groups.

Study design, size, duration

Using the CRISPR/Cas9 system, the RPL-protease A gene knockout BeWo cell (BeWo KO) line was established, and the wild type (BeWo WT) and BeWo KO cells were applied to investigate the roles of RPL-protease A in trophoblasts. The human serum RPL-protease A levels were investigated by Western blot analysis and ELISA kit.

Participants/materials, setting, methods

The cell-cell fusion, cell counting analysis, invasion and scratch wound assays, cell cycle analysis, and immunocytochemical analysis were used to investigate cellular functions of RPL-protease A in trophoblast. The sera were obtained from 32 normal pregnant women and 60 women with RPL. The Western blot analysis and ELISA were used for detection of serum RPL-protease A levels.

Main results and the role of chance

The β-hCG was detected in fused BeWo WT cells, while the BeWo KO cells cannot fuse and did not express the β-hCG. The ability of invasion was decreased, but the capacity of migration and proliferation was higher in BeWo KO cells than BeWo WT cells. Cell fusion related factor (β-hCG), and cell invasion related factors (MMP–2 and MMP–9) were highly expressed in BeWo WT cells, and cell related factor (FAK), and cell proliferation related factors (ERK, p38, JNK, MKK3, MKK6, Raf, and Ras) were highly expressed in BeWo KO cells. The Western blot analysis and ELISA indicate that the serum RPL-protease A level was decreased in patients with RPL compared to that of normal groups.

Limitations, reasons for caution

The results of this study have the limitation of RPL-protease A functions in vitro.

Wider implications of the findings: The cellular functions of RPL-protease A in trophoblasts were investigated to explain the pathogenesis of RPL, and low serum RPL-protease A level can be used for a potential biomarker predicting RPL.

Trial registration number

Not applicable
P–392 Clinical outcomes of endometrium receptivity analysis(ERA) testing in patients with repeated IVF failures
Authors: Yang W J , Lu F , Che. yu L , Hsuan Y. Y , Chin. Hung C , Jac. Yujen H
Published: August 2021

Study question

Is ERA testing different between RIF patients with control group?

Summary answer

In RIF patients, there were more chances of non-receptive endometrium. ERA testing may be helpful for the patients with repeated IVF failure. What is known already: The endometrium receptivity analysis testing might have the ability to detect the implantation window. In repeat implantation failure patients, detecting of precisely implantation window may have some benefits.

Study design, size, duration

This was a single-center retrospective observational study. Two hundred and forty-nine patients who underwent ERA testing following frozen-thawed embryo transfer in our center were including in this study between January 2019 and May 2020.

Participants/materials, setting, methods

181 patients having unexplained repeated IVF failure (RIF group, at least tow implantation failure) and 68 patients having no experience with embryo transfer (Control group) who underwent ERA testing were including in this study. Both of Patients having a receptive (R) ERA and having a non-receptive (NR) ERA underwent a personalized embryo transfer (pET) on ERA. ERA results and clinical outcomes compared between RIF group and control group were analyzed by Chi-square test.

Main results and the role of chance

The proportion of R/NR results were 33:35 for the RIF group and 118:63 for the Control group, demonstrating the displacement of the window of implantation in patients with RIF. Our results revealed an endometrial factor in 51% RIF patients, which was significantly greater than the Control group 34.8% (P = 0.02). Among the patients with NR ERA result, there are not significantly difference in clinical pregnancy rate in the RIF group compared with control group (57.1%. vs. 61.9%). The clinical pregnancy rate of the patients with receptive ERA result also is comparable in both group (70.3% vs. 66.7%).

Limitations, reasons for caution

This is a retrospective, single center study with limited case number. There were may some bias with ERA testing errors.

Wider implications of the findings: In RIF patients, there were more chances of non-receptive endometrium. ERA testing may be helpful for the patients with repeated IVF failure. Larger randomized studies are required to validate these results.

Trial registration number

18MMHISO70e
P–394 Intralipid infusion at time of embryo transfer in women with history of recurrent implantation failure: a systematic review and meta-analysis
Authors: Rimmer M P , Black N , Keay S , Quenby S , Wattar B. H.A
Published: August 2021

Study question

What is the effectiveness of IV Intralipid (IVI) in improving pregnancy rates in women undergoing IVF with history of Recurrent implantation failure (RIF) to improve reproductive outcomes.

Summary answer

The evidence to support the use of IVI at the time of embryo transfer in women with RIF is limited. More RCTs are needed. What is known already: Optimising the implantation process following embryo transfer remains a clinical challenge with 10% of couples undergoing IVF affected by (RIF). Immunotherapy could help to optimise endometrial receptivity and increase the chances for successful conception in women with history of RIF. Intra-venous Intralipid (IVI), a fat-based emulsion of soybean oil, glycerine, phospholipids, egg, and polyunsaturated fatty acids, has been evaluated in several trials as a potential intervention to downregulate the uNK cells and macrophages as well as inhibit the pro-inflammatory mediators including T1 helper cells. Evidence synthesis is needed to evaluate the effectiveness of this intervention.

Study design, size, duration

We performed this systematic review using a prospectively registered protocol (CRD42019148517) and reported in accordance with the PRISMA guidelines. Participants/materials, setting, methods: We searched MEDLINE, EMBASE and CENTRAL for any randomised trials evaluating the use of IVI at the time of embryo transfer in women undergoing assisted conception until September 2020. We extracted data in duplicate and assessed risk of bias using the Cochrane Risk of Bias tools. We meta-analysed data using a random effect model and reported on dichotomous outcomes using risk ratio (RR) and 95% confidence interval (CI).

Main results and the role of chance

We included five randomised trials reporting on 843 women with an overall moderate risk of bias. All trials used 20% IVI solution at the time of embryo transfer compared to normal saline infusion or no intervention (routine care). The IVI group had a higher chance of clinical pregnancy (172 vs 119, RR 1.55, 95%CI 1.16–2.07, I2 44.2%) and live birth (132 vs 73, RR 1.83, 95%CI 1.42–2.35, I2 0%) post treatment compared to no intervention.

Limitations, reasons for caution

Our findings are limited by the small sample size and the variations in treatment protocols and population characteristics.

Wider implications of the findings: Our meta-analysis offers an overview on the value of IVI to help women affected by RIF. Given the limitations and the quality of included trials, adopting the use of IVI a-la-carte to couples undergoing IVF remains immature. IVI should not be offered until larger RCTs demonstrate a persistent benefit.

Trial registration number

CRD42019148517
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

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

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

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

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

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

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

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 >35y (56.7% vs. 52.4%), P > 0.05. The total embryonic chromosomal aberration rates for women aged 20–29y, 30–34y and >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 > 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

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>A (Gly320Gly) and male infertility (P = 0.0351). Similarly, the allele frequency test showed that rs2853495 G>A (Gly320Gly) and rs869096886 A>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
P–544 The results of embryo transfer cycles with low mosaic embryos: A case report
Authors: Göktolga U , Rama A , Mesic A , Göktaşılarla C , Fetahovic M
Published: August 2021

Study question

What are the results of embryo transfer cycles with low mosaic embryos?

Summary answer

The clinical and ongoing pregnancy rates were 50%. The results of Amniocentesis were reported as normal karyotype for all the pregnant women.

What is known already

Many current studies, quote the rates of mosaicism in blastocyst biopsies to be higher at 20–30%. Embryonic mosaicism was found to result from mitotic errors occurring after fertilization, occasionally in the first cleavage but more commonly in the second or third cleavage. The increased reporting of mosaicism in embryos has given rise to new challenges in PGS results interpretation and patient counseling. Previously, embryos were diagnosed as either euploid or aneuploid, and in most cases only euploid embryos were considered for transfer. Now, if mosaic embryos are considered to represent a third category of results.

Study design, size, duration

Case Report for The results of 10 embryo Transfer Cycles with Low Mosaic Embryos Participants/materials, setting, methods: We are presenting the results of ten embryo transfer cycles with low mosaic embryos at Bahceci BIH IVF Center, Sarajevo BIH, between January 2019 – October 2020. All the patients have been informed by a written informed consent form, and had genetic counseling before embryo transfer. Amniocentesis has been performed for all the pregnant women between 14–18 weeks of the pregnancy as prenatal testing.

Main results and the role of chance

Out of the total ten patients, 5 had pregnancy, and the 5 other were not pregnant. The average age of the whole group was; 34.0 ± 5.49 years. The average age of the pregnant women was ; 30.6 ± 5.54 years, and 37.40 ± 2.88 years who were not pregnant

Limitations, reasons for caution

There are limited number of papers in literature about transferring of the low mosaic embryos. The strength of our presentation is, amniocentesis have been performed as prenatal testing for all the pregnancies.

Wider implications of the findings: There were no correlation between the type of low mosaicism and pregnancy. Since all the pregnant women were 35 years of age or less, It was the only factor which is influencing the pregnancy.We hope that, the results of our cases will improve the management protocols for these cases.

Trial registration number

Not applicable
P–570 Embryos originating from oocytes with smooth endoplasmic reticulum clusters have a lower euploidy rate via PGT-A testing using next-generation sequencing
Authors: Li C J , Chang C L , Huang H Y , Soong Y K , Wu H M
Published: August 2021

Study question

Does the presence of smooth endoplasmic reticulum clusters (sERCs) in oocytes affect the human embryo ploidy?

Summary answer

The euploidy rate of embryos originating from sERCs + oocytes is lower

What is known already

While an expert panel strongly recommended that sERCs+ oocytes should not be inseminated, some normal healthy babies derived from sERCs+ oocytes have been reported. In previous studies have shown that declined fertilization rate and lower proportions of good quality embryos are found in oocytes showing sERCs. The updating findings of the molecular status of sERC+ oocytes elucidated the sERCs+ oocytes may have impaired chromosomal segregation ability. However, no study reveals the relation between sERCs and embryo ploidy.

Study design, size, duration

A retrospective study enrolled 129 preimplantation genetic testing (PGT) cycles from January 2017 to March 2020 at Chang Gung Memorial Hospital, Lonkou.

Participants/materials, setting, methods

ICSI fertilization rate, Day5 usable blastocyst rate (D5UBR), total usable blastocyst rate (TUBR), euploidy rate, mosaic rate, and aneuploidy rate are investigated between embryo originating from sERCs+ and sERCs- oocytes.

Main results and the role of chance

Although higher TBUR in blastocyst derived from sERCs+ oocytes than sERCs- group (73.7% vs. 62.5%) but accompanied lower euploidy rate (7% vs. 29%) and higher aneuploid rate (79% vs. 54%).

Limitations, reasons for caution

Limited sample size, need a large-scale study to confirm the conclusion. The live-birth rate per embryo transfer cycle was not included for analysis. As we did not perform polar body analysis, we cannot state for sure that embryonic aneuploidy was related to the oocyte.

Wider implications of the findings: This study demonstrates that embryos originating from sERCs+ oocytes have a lower euploidy rate.

Trial registration number

CMRPG3H0751
P–585 The influence of omega–3 fatty acids on female fertility in assisted reproductive technology
Authors: Buch S
Published: August 2021

Study question

Is there evidence that the intake of omega–3 fatty acids has a positive effect on probability of clinical pregnancy in women undergoing IVF/ICSI treatment?

Summary answer

No significant correlation was found between omega- 3 fatty acid intake (neither supplemental or as fish intake) and clinical pregnancy. What is known already: Omega–3 fatty acids are important substrates in metabolism and the supplement of omega–3 fatty acids have been thought to have a positive effect on semen quality in infertile men. Studies have shown that the intake of omega–3 fatty acids might also have a direct effect on oocytes, the quality of the embryos, and implantation of the embryo in the uterus at conception. However, the role of omega–3 fatty acids in female fertility still remains unclear as the relationship between omega–3 fatty acids and successful IVF treatment in women has shown conflicting results.

Study design, size, duration

Systematic review. Systematic literature research (PRISMA) on PubMed, Embase, and Cochrane identifying clinical studies focusing on omega–3 fatty acid intake amongst women receiving IVF treatment, using good scientific practice for literature search and management. 5 articles meeting inclusion criteria were found, with a total of 1.100 women undergoing IVF/ICSI treatment. Participants/materials, setting, methods: Population: women in fertility treatment Intervention: omega–3 fatty acid and/or fish intake Comparison: No/low intake of omega–3 fatty acid and/or fish intake Outcome: Primary: clinical pregnancy rate, Secondary: number of follicles, embryo quality, live birth rate

Main results and the role of chance

Number of follicles was found to be inversely associated to omega–3 intake in a single study. Higher levels of total omega–3 intake were found to be positively associated to embryo morphology scores, and thus quality, independent on energy intake. None of the four studies considering clinical pregnancy found any statistical significance in the association between fish intake and clinical pregnancy. Regarding live birth as an endpoint, fish intake, but not fish oil supplements, was seen to significantly increase the probability in one study with a dose-response relationship. A similar association was not found by the only other study also examining live birth. Limitations, reasons for caution: Only five studies were found to meet inclusion criteria. None of the included studies were randomized controlled trials. No meta-analysis was carried out due to the heterogeneity of the studies.

Wider implications of the findings: The need for further studies, including randomized controlled trials of high quality with larger population sizes, is critical in order to thoroughly investigate and conclude any possible association of the beneficial effect of omega–3 fatty acids on female fertility in regard to IVF treatment.

Trial registration number

Not applicable
P–596 Association of oleic acid production in cumulus-granulosa cells with glutathione of in vitro matured oocytes
Authors: Fayezi S , Ghaffar. Novin M , Norouzian M , Nouri M , Farzadi L
Published: August 2021

Study question

Does oleic acid production in cumulus-granulosa cells affect glutathione levels of in vitro matured oocytes?

Summary answer

Oleic acid availability in cumulus-granulosa cells is associated with a higher glutathione level in in vitro matured oocytes.

What is known already

The monounsaturated fatty acid oleic acid is de novo synthesized by desaturation of stearic acid and can promote steroidogenesis and oocyte development in vitro. The endogenous antioxidant glutathione content in metaphase II oocyte is significantly higher than immature stages and is related to the normal oocyte maturation.

Study design, size, duration

Mouse germinal vesicles were co-cultured for 24 hours, during in vitro maturation, with granulosa cells treated with a specific inhibitor of oleic acid synthesis alone or in combination with oleic acid.

Participants/materials, setting, methods

Fluorescence staining was used to assess the glutathione content of mouse metaphase II oocytes following in vitro maturation as an indicator of cytoplasmic maturation. Glutathione was stained using Cell Tracker Blue –CMAC for 30 min at 37 °C. After being washed in fresh media, stained oocytes were photographed by a fluorescence microscope. Cell area and associated fluorescence were quantified in 20 metaphase II mouse oocytes randomly chosen from in vitro matured oocytes for each condition.

Main results and the role of chance

The intracellular glutathione content was profoundly lower in metaphase II oocytes obtained from co-cultures with inhibitor-treated cumulus-granulosa cells than with the control cumulus cells (–50%, p < 0.01). Oleic acid effectively recovered the negative effect of inhibitor on glutathione level nearly up to the level of the mock-treated cells.

Limitations, reasons for caution

The findings are limited to metaphase II. Measurement at more advanced stages of oocyte development is of interest. Inhibition of cellular fatty acid synthesis was performed solely with a specific chemical.

Wider implications of the findings: Involvement of the oleic acid availability for cumulus-granulosa cells in normal oocyte maturation may be of relevance in reproductive disorders, particularly in the pathological mechanism of impaired oogenesis.

Trial registration number

400/3226
P–611 Innovative controlled ovarian stimulation (COS) for polycystic ovary syndrome (PCOS) produces high-quality oocytes and no ovarian hyper stimulation syndrome (OHSS)
Authors: Yanagihara Y , Tanaka A , Nagayoshi M , Yamaguchi T , Tanaka I , Ohno M , Itakura A
Published: August 2021

Study question

How can we find an ovarian stimulation method that does not cause hyper stimulation syndrome but can produce a high pregnancy rate at one cycle?

Summary answer

This newly developed method for PCOS has a higher accumulative clinical outcome for one trial and no OHSS.

What is known already

Almost all conventional treatments for PCOS have managed to avoid OHSS by reducing the number of growing follicles, which are associated with high Estradiol levels and stimulate the production of vessel endothelial growth hormone (VEGF), leading to increased vessel permeability. Low dose FSH administration, In vitro maturation (IVM), Ovarian Drilling and Coasting have been performed to achieve this. However, their actual clinical outcome is still unsatisfactory.

Study design, size, duration

Evaluation of the efficiency of this method was conducted retrospectively at St. Mother Clinic. The embryonic development and the clinical outcome were studied for 34 PCOS patients during the period between November 2018 and December 2019.

Participants/materials, setting, methods

We started injections of FSH (150iu/ml), then we did ultrasound follicle monitoring. GnRH antagonist shots were started when the leading follicle reached 18mm and continued until the largest follicle was 22–24mm and the E2 value was over 4000pg/ml. Letrozole (2.5mg) and leuprorelin acetate (1.88mg) was injected as trigger. Two tablets each of Letrozole, Cabergoline and GnRH antagonist were given for 5 consecutive days after the oocyte retrieval. All embryos were cryopreserved.

Main results and the role of chance

Number of patients and cycles were 34 and 59. Average number of cryopreserved blastocysts was 6.12 (1–16). The frequencies of OHSS (mild, moderate, severe) were 29.4% (10/34), 0% (0/34), 0% (0/34). Average days between oocyte collection and withdrawal hemorrhage was 5.44(5–7). Cryopreservation rate was 100.0% (34/34). Clinical pregnancy rate and miscarriage rate was 42.3% (25/59) and 16.0% (4/25). The cumulative pregnancy rate was 73.7% (25/34). The four remaining unsuccessful cases still have 10,6,3 and 7 frozen embryos. So, there is a high possibility that they become successful, that would bring the cumulative pregnancy rate up to 82.3% (28/34).

Limitations, reasons for caution

This COS for PCOS seems promising, however it is premature to conclude that this method is established. This method requires caution monitoring for hormone level, follicle size and number and coagulant function. It also accompanied with the risk of ovarian hemorrhage on aspiration of a great number of oocytes.

Wider implications of the findings: This COS seems viable for PCOS cases. It could control the cohort of antral follicles with different doses of Letrozole to find the optimal COH method and it could become the first option for COS of PCOS.

Trial registration number

N/A