bluuebunny/crossref_metadata_2025_split huggingface dataset:
O-057 Newly identified female mutations causing failed fertilization
Authors: Cardona Barberán A 
Published: July 2024

Abstract
Over the past decade, advancements in next-generation sequencing technology, alongside reduced costs, and the rising demand for infertility medical care, have resulted in the discovery of new genes and genetic variants linked to infertility conditions. Phenotypes of ICSI failure, such as oocyte maturation arrest (OMA), fertilization failure (FF) and embryo developmental arrest (EDA), can now be attributed to male or female genetic causes. This represents a transformative shift in patient treatment, allowing the identification of some cases previously classified as unexplained infertility, thereby reducing patient stress. Moreover, it facilitates personalized treatment recommendations, as well as paves the way for the exploration of novel treatment options, thus expanding research opportunities.
This talk will review the genetic causes of FF following ICSI, with the main focus on the newly identified female causes, as well as give an update on current diagnostic tests and treatment options for this infertility condition. FF after ICSI still occurs in 1-3% of ICSI cycles, primarily due to oocyte activation deficiency (OAD). Defects in the male PLCζ protein, responsible of inducing calcium oscillations during oocyte activation, have long been known as the leading cause of OAD. Recent discoveries have identified genetic variants in the male genes ACTL7A, ACTL9 and IQCN, which also reduce PLCζ protein content in sperm cells and thus, contribute to FF after ICSI. Additionally, for the first time in 2018, mutations in a female gene (WEE2) crucial for oocyte activation were identified. WEE2 is an oocyte kinase that acts downstream the calcium release during fertilization. Interestingly, genetic variants in other female genes, such as PATL2, TUBB8 and CDC20 associated mainly to OMA and TLE6 and NLRP5 associated mainly to EDA, have also been described to cause failed fertilization in some patients.
Determining whether the deficiency lies in sperm- or oocyte-related genes is crucial for tailoring the most effective treatment for FF after ICSI. For sperm-related factors, assisted oocyte activation (AOA), which consists in the artificial induction of calcium oscillations using calcium ionophores, has proven highly beneficial. However, most patients with oocyte-factors do not benefit from AOA (e.g. patients with WEE2 variants). In this regard, wild-type cRNA injection of the defected protein has been shown to rescue fertilization. A more generalist approach, such as maternal spindle transfer, which consists in replacing poor-quality oocyte cytoplasm with healthy cytoplasm from a donor oocyte, represents a potential treatment for these patients, as recently demonstrated in infertile females with repeated IVF failures. Nevertheless, further research into the safety of these procedures is needed before clinical application, and for now, gamete donation should be considered when facing female-related FF.
P-699 High levels of total FSH during COS is detrimental to oocyte development in good responders: results from a three-year retrospective, multicenter study
Authors: Karimova H , Pylypenko N , Hudkova D , Kotlyarova O , Vozniuk V , Barbakadze L , Aydin B , Dorofeyeva U 
Published: July 2024

Abstract

Study question
Are elevated doses of follicle stimulating hormone (FSH) detrimental to oocyte maturation and the efficacy of ovarian stimulation in good responders?

Summary answer
Elevated FSH levels reduce the number of oocytes collected from good responders. Patients receiving lower total FSH doses had optimal and higher maturation rates.

What is known already
There is an inverse relationship between the dose of exogeneous follicle stimulating hormone (FSH) and the number of oocytes retrieved. This relationship is independent of patient age or health and implies that excessive FSH doses administered during artificial reproductive technologies (ART) may be detrimental to oocyte maturation.

Study design, size, duration
This three-year retrospective, multicenter study included 1,075 oocyte donor cycles performed in three IVF clinics between January 2020 and December 2023 with at least a six-month interval between each cycle. Donors were all considered good responders and divided according to the total dose of FSH received per cycle (n = 289 cycles with &lt;1,700 IU FSH; 400 cycles with 1,700 to 2,900 IU FSH; and 386 cycles with &gt;2,900 IU FSH).

Participants/materials, setting, methods
The mean oocyte donor age was between 26.13 and 27.45 years old. The mean BMI for all three groups was 21. The association between the total FSH dose and serum anti-Müllerian hormone (AMH) level, follicle-to-oocyte index (FOI), number of oocytes retrieved, and oocyte maturation was assessed using the Student’s t-test (parametric) or Mann-Whitney-U test (non-parametric).

Main results and the role of chance
There were no significant differences in the mean serum AMH levels (5.31 vs. 5.27 vs. 5.13 ng/mL, respectively) and FOI (81.1 vs. 80.2 vs. 81.5, respectively) of patients who received different total doses of FSH. However, the number of oocytes retrieved from each group was inversely related to the total dose of FSH received (24.4 vs. 22.9 vs. 21.01 oocytes, respectively; p &lt; 0.05)

Limitations, reasons for caution
Full characterization of the oocytes and their developmental potential was outside the scope of this retrospective study.

Wider implications of the findings
Gaining a better understanding of the complex interplay of gonadotropins throughout folliculogenesis can help optimize ovarian stimulation protocols to maximize the number of mature and developmentally competent oocytes recovered for clinical use.

Trial registration number
non applicable
P-724 Long-term health outcomes of 19 years follow-up of mothers conceived after oocyte donation based on the registry of a large healthcare organization
Authors: Shalev H , Wiser A , Rahav-Koren R , Roi S , Haikin-Herzberger E , Levi M , Miller N 
Published: July 2024

Abstract

Study question
Short term outcomes of oocyte donation (OD) pregnancies are known. Yet, long term effect of OD pregnancies on mother’s health are lacking.

Summary answer
Comparing women after OD pregnancies to spontaneous pregnancies or nulliparous women, a higher risk of thyroid diseases was found (1.41, p &lt; 0.0001 and 2.13, p &lt; 0.0001, respectively)

What is known already
Short term outcomes of oocyte donation pregnancies show increased risk of placental disease and pregnancy-related hypertensive disorders.

Study design, size, duration
This retrospective cohort study, conducted from 2000 to 2018, utilized the computerized records of a major healthcare provider. It compared the demographic data and long-term health outcomes of mothers who had undergone OD pregnancies with three groups: In Vitro Fertilization using autologous oocytes, spontaneously pregnancies, and nulliparous women.

Participants/materials, setting, methods
The study tracked the onset of chronic diseases from the date of delivery to the diagnosis of any chronic disease. The risk of various diseases and mortality among these groups was assessed using a Cox proportional hazards model. This model adjusted for variables such as age at the index date, number of children, body mass index (BMI), and smoking habits. Statistical significance was determined using two-sided p-values, with a threshold of P &lt; 0.05.

Main results and the role of chance
Regarding long-term outcomes, no difference was found between mothers after oocyte donation comparted to mothers after IVF (See table 1).. When comparing oocyte donation pregnancies to mothers after spontaneous conception, mothers after oocyte donation had less lower prevalence of rheumatology diseases (6% vs 8.9%) and more higher prevalence of thyroid diseases (21.9% vs. 17.6%). However, in cox regression, taking into account smoking, number of birth and mom’s age, we only found a higher risk of thyroid diseases (OD 1.41, p &lt; 0.0001). Lastly, oocyte donation pregnancies compared to nulliparous had more thyroid diseases (21.9% vs. 6.7%, p &lt; 0.001), also in cox regression (OD 2.13, p &lt; 0.0001)

Limitations, reasons for caution
The temporal aspect of chronic disease diagnosis; a diagnosis made at a specific point does not preclude the presence of the disease at an earlier time. Also, the infrequency of some conditions within our study population could have reduced the statistical power to detect differences or associations.

Wider implications of the findings
The longer-term health outcome for women conceiving after OD is reassuring, and is very similar to that of IVF children and naturally conceived children, exempt for higher risk of thyroid disease. The main recommendation should be a yearly surveillance of thyroid function.

Trial registration number
0046-18-BBL
O-168 The therapeutic potential of stem cells for ovarian rejuvenation
Authors: Seli E 
Published: July 2024

Abstract
Stem cells and induced pluripotent stem cells (iPSCs), hold immense promise in regenerative medicine due to their ability to differentiate into various cell types. However, in the context of ovarian rejuvenation, controversies surround the concept of post-natal oogenesis in mammals, challenging the established belief that female mammals are born with a finite pool of oocytes. Recent studies refute the presence of ovarian stem cells, sparking debates in the scientific community. The proposed use of ovarian stem cell-derived mitochondria for oocyte rejuvenation, known as AUGMENT, aimed to enhance fertility but fell short of expectations in clinical trials. Conversely, autologous stem cell ovarian transplantation (ASCOT) seems to offer a promising avenue to increase reproductive potential by replenishing ovarian function. While still under investigation, initial results show encouraging outcomes. Furthermore, recent advancements in in vitro generation of oocytes from stem cells present a groundbreaking approach to overcome infertility associated with ovarian failure. By mimicking the natural process of oogenesis, researchers aim to provide new opportunities for fertility preservation and treatment. These developments underscore the dynamic landscape of stem cell research in reproductive medicine, offering hope for addressing infertility and expanding our understanding of reproductive biology.
P-044 Increased CYP1A1 expression enhances sperm apoptosis in idiopathic infertile men
Authors: Bakhtiari M , Hemati Harsini M , Asgari R 
Published: July 2024

Abstract

Study question
How are the CYP1A1 and Caspase-9 genes expression and the relationship among the expression of these genes with sperm parameters in idiopathic infertile men?

Summary answer
The CYP1A1 and Caspase-9 gene expression showed a significant increase in patients in comparison with the healthy group.

What is known already
CYP1A1 (Cytochrome P450 Family 1 Subfamily A Member 1) plays a crucial role in xenobiotic metabolism induced by aryl hydrocarbon receptor (AHR). AHR, as a ligand-activated transcription factor is involved in exogenous ligand activation. CYP1A1 is one of the most essential enzymes in phase 1 of detoxification, metabolism, and bio-activation of carcinogens and is the most well-known target gene for AHR. Monooxygenase activity of CYP1A1 may lead to oxidative stress and the formation of reactive intermediates with destructive effects such as apoptosis in testicular germ cells. CYP1A1 may lead to apoptosis via Caspase-9 activation.

Study design, size, duration
In this study, we aimed to determine the CYP1A1 and Caspase-9 gene expression.

Participants/materials, setting, methods
The infertile idiopathic and healthy fertile men were selected and evaluated for sperm analysis and gene expression. The expression levels of CYP1A1 and Caspase-9 were also determined by real time PCR.

Main results and the role of chance
The sperm count, morphology and motility were significantly lower in patients compared to the control group (p &lt; 0.05). The CYP1A1 and Caspase-9 gene expression showed a significant increase in patients in comparison with the healthy group (p &lt; 0.05).

Limitations, reasons for caution
Further investigations of the effect of CYP1A1 and Caspase-9 expressions on infertility by using more infertile patients and also studying the effect of other important genes such as AHR can show us more accurate results.

Wider implications of the findings
Our results suggest that increased CYP1A1 and Caspase-9 expression could increase the rate of male infertility. In addition, the increase in Caspase-9 expression could lead to a reduced number of sperms and an increased infertility rate by increased apoptosis in the spermatogenic lineage.

Trial registration number
not applicable
P-084 Exome sequencing reveals the novel genetic mutations associated with teratospermia
Authors: Long S 
Published: July 2024

Abstract

Study question
This research aims to explore the molecular mechanisms of genetic variations in the small acrosome sperm subtype within teratospermia and its correlation with male infertility.

Summary answer
Novel gene mutations associated with teratospermia were identified, providing important insights into the genetic mechanisms underlying this condition.

What is known already
Male infertility is a substantial challenge in reproductive medicine, impacting a significant proportion of couples globally. Teratospermia, marked by abnormal sperm morphology, is a major factor in male reproductive disorders. Unraveling the genetic foundation of teratospermia is essential for comprehending the intricate molecular mechanisms governing male fertility.

Study design, size, duration
This study uses exome sequencing to investigate the genetic landscape of male infertility, particularly focusing on teratospermia. Through a comprehensive examination of the exome, our goal is to uncover novel gene mutations and understand the molecular mechanisms connecting genetic changes to abnormal sperm morphology and, consequently, male infertility.

Participants/materials, setting, methods
Sperm DNA was extracted from 55 patients with a confirmed diagnosis of teratospermia for this study. Subsequently, comprehensive exome sequencing was performed on the extracted sperm DNA to investigate potential genetic variations associated with teratospermia.Further functional studies were conducted to unveil the potential roles of mutated genes in the development of the reproductive system and spermogenesis.

Main results and the role of chance
Within the known genes associated with spermatogenic dysfunction, we identified one pathogenic/likely pathogenic variant and four variants of unknown significance, all of which have not been previously reported.Cell phenotype experiments revealed that mutations in CCDC62 and KCNU1 have specific effects on the proliferation and apoptosis of GC-2 cells.

Limitations, reasons for caution
Further molecular experiments and pathway mechanism studies are required to enhance our understanding of the observed effects and provide a more comprehensive interpretation of the findings.

Wider implications of the findings
This study unveils novel genes and pathways in teratospermia, informing diagnosis, prognosis, and potential treatments for male infertility. Exploring the genetic landscape enhances our comprehension of the complex interplay between genetics and male fertility, guiding personalized approaches in reproductive medicine.

Trial registration number
not applicable
P-101 Mitochondria-mediated apoptosis induced testicular dysfunction in bisphenol F treated rats: ameliorative effect of baicalin
Authors: Hamed M , Odetayo A 
Published: July 2024

Abstract

Study question
Will baicalin treatment ameliorate bisphenol F (BPF)-induced testicular dysfunction?

Summary answer
Baicalin ameliorates BPF-induced mitochondrial dysfunction-associated apoptosis

What is known already
BPF is a chemical presently considered a major replacement for bisphenol A and has been widely used in the canning and other food processing industries. However, a major limitation of this chemical is its gonadotoxic effect. Studies have shown that BPF disrupts testicular function via apoptotic signaling, although, its mechanism of action has not been fully explored. On the other hand, baicalin is an anti-apoptotic agent. Yet, none of these studies has reported the effect of baicalin on BPF-induced testicular injury

Study design, size, duration
This is a prospective experimental study using an animal model. Twenty-four sexually matured male Wistar rats of comparable weight were used for this study. All treatments were via oral gavage and lasted for 8 weeks

Participants/materials, setting, methods
Animals were acclimatized for two weeks, then randomized into 4 groups (n = 6); control: animals received 0.5 mL of corn oil as vehicle, BPF: animals received 30 mg/kg of BPF, baicalin: animals treated with 100 mg/kg of baicalin, BPF+ baicalin: animals treated with 30 mg/kg BPF and 100 mg/kg baicalin

Main results and the role of chance
: Baicalin ameliorated BPF-induced decrease in spermatogenic indices and sperm quality, circulatory levels of follicle-stimulating hormone, luteinizing hormone, and testosterone, and testicular concentrations of 3β-HSD and 17β-HSD. Also, baicalin ameliorated BPF-induced decline in testicular superoxide dismutase, catalase, total thiol, glutathione, glutathione S-transferase, and glutathione peroxidase activities and nuclear factor erythroid 2-related factor 2 concentrations. Furthermore, baicalin alleviated BPF-induced increase in testicular malondialdehyde, myeloperoxidase, TNF-α, IL-6, and NF-kB levels. These events were associated with the dampening of BPF-induced decline in NAD+/NADH and Bcl-2 activities and BPF-induced increase in Bax and caspase 3 activities by baicalin.

Limitations, reasons for caution
This study was conducted in a rat model; therefore the results of the present study should be extrapolated to humans with caution

Wider implications of the findings
The present study described the ameliorative effect of baicalin treatment on BPF-induced testicular toxicity.

Trial registration number
N/A
P-142 The developmental time to reach the blastocyst stage in the human is an indicator of diploid mono-pronuclear embryos
Authors: Tsuji H , Tokoro M , Fukunaga N , Asada Y 
Published: July 2024

Abstract

Study question
Is it possible to determine diploid mono-pronuclear (1PN) human embryos by the speed of development to blastocyst formation?

Summary answer
The developmental time to reach the blastocyst stage is a discrimination indicator for diploid 1PN embryos.

What is known already
We have previously reported that 80.7% of 1PN zygotes had a biparental chromosome using a Live-Cell imaging technique, and some of these developed to the blastocyst stage (Tokoro et al. ASRM 2013). Furthermore, we have reported that these blastocysts can result in a healthy live birth (Tsuji et al. ASRM 2020), and there was no effect on growth up to 5 years of age (Tsuji et al. ASRM 2023). On the other hand, it was also shown that a few of the 1PN embryos that developed into blastocysts were haploid embryos.

Study design, size, duration
This was a retrospective study that included 28 blastocysts derived from a 1PN zygote. The time period was 72 months (January 2017 to December 2022). These embryos are used for research following obtaining informed consent.

Participants/materials, setting, methods
The frequency rate of diploid embryos was compared from time of PN fading to blastocyst formation (Gardner’s classification: ≥ expansion grade 3). Two development time range groups were examined and designated: fast-developing embryos (65.7-78.7h) and slow-developing embryos (116.8-139.7h). Ploidy status was determined using whole blastocyst cells and NGS-based SNP analysis. Statistical significance was determined using Fisher’s exact test (level of P&lt;0.05).

Main results and the role of chance
There was no significant difference in the average age (years) of the two development time groups (fast-developing embryos group; 35.5 +/- 5.5, slow-developing embryos group; 34.1 +/- 2.8).
The frequency of diploid status in 1PN embryos with fast developing embryos was 100% (14/14), and in 1PN embryos designated as having slow development, the frequency of diploid embryos was only 14.3% (2/14), haploid embryos 71.4% (10/14), and other was 14.3% (2/14). As a result, the diploid embryo rate was significantly higher in fast-developing embryos than in slow-developing embryos (P&lt;0.001).

Limitations, reasons for caution
This study was limited to extremely fast or slow-developing embryos to see trends. It is important to study the threshold time between diploidy and haploidy in 1PN embryos.

Wider implications of the findings
These results confirmed that fast developing 1PN embryos have a high diploid rate and can be used as transferable embryos in addition to 2PN embryos. Conversely, slow developing 1PN embryos should be considered to have a lower priority for transfer because of the high rate of haploid embryos.

Trial registration number
not applicable
P-163 Does severe endometriosis (SE) have an effect on embryo morphokinetic parameters?
Authors: Ozkara G , Sezer F , Yelke H , Ozer G , Kahraman S 
Published: July 2024

Abstract

Study question
Does severe endometriosis (SE) have an effect on embryo morphokinetic parameters?

Summary answer
Severe endometriosis may have an effect on embryonic cell divisions and could change morphokinetic parameters of in vitro developing embryos.

What is known already
Endometriosis is one of the leading causes of infertility that affects approximately one third of women who apply for in vitro fertilization (IVF) treatment. Controversial results were reported regarding the effect of endometriosis on both morphological and dynamic characteristics of embryos so far.

Study design, size, duration
This was a retrospective comparative analysis including a total of 1280 embryos (SE: 729, Tubal factor (control): 551) of 241 patients (SE: 134, control: 107) that were incubated at Time-Lapse Monitoring System (TLM) in Memorial Sisli Hospital, ART and Reproductive Genetics Center between October 2011 and July 2023. Patients with ≥ 38 years, BMI ≥ 30 and partners having severe male factor (sperm concentration: &lt;5 mil/ml) were excluded from the study.

Participants/materials, setting, methods
Severe endometriosis was defined as Grade III and IV according to ASRM classification. IMSI (Intracytoplasmic Morphologically Selected Sperm Injection) was performed to all oocytes. Embryos were evaluated according to Gardner’s classification. Fertilization rates were assessed using Chi-square test. Morphokinetic parameters of embryos were compared by Student’s t-test using SPSS 28.0.

Main results and the role of chance
There was a homogenous distribution in terms of female age, BMI, basal FSH, AMH levels, total and mature (MII) oocyte count between study groups. Abnormal fertilization rate was higher in SE group than controls ( 4.3% vs 2.4%, p = 0.035). All morphokinetic parameters were found significantly delayed in the SE group than in the control group (p &lt; 0.05), however, no statistical significance was obtained in terms of tSC and tEB (p &gt; 0.05). Duration of first, second and third embryo cell cycles (ECC1, ECC2, and ECC3), synchronization of cell divisions (S2: t4-t3) and cleavage patterns (S3: t8-t5) were also found statistically significant between SE and control groups (p &lt; 0.05).

Limitations, reasons for caution
The major limitation of this small-sized, retrospective study is that clinical outcomes of the embryos were not assessed.

Wider implications of the findings
Delayed development was observed in the embryos of SE patients. Prospective studies with larger cohorts are needed to have a better understanding between severe endometriosis and embryo morphokinetics.

Trial registration number
Not applicable