bluuebunny/crossref_metadata_2025 huggingface dataset:
O-105 Contribution of ART to fertility rates and family size
Authors: Chambers G , Lazzari E
Published: July 2024

In the last three decades declining fertility has become an increasing global trend. One-half of the global population today lives in countries where the period Total Fertility Rate is below 2.1 births per woman. Many countries in Europe and Asia are experiencing “ultra-low” fertility rates of 1.0-1.4 births per woman. This decline in births creates both social and economic challenges.

In addition, most countries have gone through a long period of increasing average age at birth. The shift in births at older ages has been accompanied by a concomitant decline in completed family size. As the average age at having children has increased over time, the proportion of women experiencing difficulty in achieving a pregnancy has also increased, with assisted reproductive technology (ART) treatments becoming increasingly important in counteracting this decline. However, the demographic impact of ART widely varies across countries, with the proportion of babies born as a result of ART, ranging from almost 10% of birth in in some European countries to < 1% in Latin America and 2% in the USA.

ART is increasingly being raised as a potential policy tool to increase fertility. While ART can broaden the range of possible responses to low fertility rates, there are a number of challenges in quantifying contribution to fertility rates. There are also a number of important unintended consequences that need to be taken into account when trying to estimate their effectiveness as a policy tool to increase fertility.

In this presentation, the evidence for the contribution of ART to total and age-specific fertility rates in different settings will be summarized and compared with other pronatalist policies. The contribution of ART and other forms of fertility treatment to completed family size and childbearing timing will also be described and discussed. Assisted reproduction is making a modest and increasing contribution to the fertility rate of high-income countries, but its potential impact should not be overestimated.
O-110 Adenomyosis : the challenge of classification and diagnosis
Authors: Feki A , Acien M , As Sanie S , De Wilde R L , Gordts S , Guo S -W , Keckstein J , Laganà A S , Leone Roberti Maggiore U , Nisolle M , Saridogan E , Stewart E A , Tellum T , Tomassetti C , Johnson N , Le Clef N , Grimbizis G
Published: July 2024

Study question

What does the collaborative document on adenomyosis terminology, classification, and diagnosis by ESGE, ESHRE, and WES provides?

Summary answer

This good practice recommendations paper offers guidance on the technical aspects, terminology, classification, and diagnosis of adenomyosis in women of reproductive age.

What is known already

The existing literature on adenomyosis terminology is heterogeneous and confusing. Various classification systems based on ultrasound and MRI have been proposed, yet none have gained international acceptance or clinical validation. The contradictory data on the diagnostic accuracy of these modalities further complicate adenomyosis diagnosis in reproductive-age women.

Study design, size, duration

A working group from ESGE, ESHRE, and WES has collaborated to write recommendations concerning the terminology, classification, and diagnosis of adenomyosis.

Participants/materials, setting, methods

Focusing on terminology, classification, and diagnosis, this good practice paper paves the way for further recommendations on the management and surgical treatment of adenomyosis in reproductive-age women.

Main results and the role of chance

The document overviews adenomyosis terminology and reviews proposed classification systems based on histology, ultrasound, and MRI, concluding with diagnostic recommendations.

Limitations, reason for caution

Owing the scarcity of evidence, these recommendations predominantly rely on clinical expertise.

Wider implications of the findings

The recommendations aim to enhance existing adenomyosis guidelines.

Study funding/Competing interests

All costs were covered by ESHRE funds, with no external funding for the development process or manuscript production.
O-119 Architecture and in situ arrangement of the CatSper-channel complex in the sperm flagellum
Authors: Chung J J
Published: July 2024

The sperm calcium channel CatSper plays a central role in successful fertilization as a primary Ca2+ gateway. Here, we applied cryo-electron tomography to visualize the higher-order organization of the native CatSper complex in intact mammalian sperm. The repeating CatSper units form long zigzag-rows along mouse and human sperm flagella. Above each tetrameric channel pore, most of the extracellular domains form a canopy that interconnects to a zigzag-shaped roof. Murine CatSper contains an additional wing-structure connected to the tetrameric channel. The intracellular domains link two neighboring channels to a diagonal array, suggesting a dimer formation. Fitting of an atomic model of isolated monomeric CatSper to the in situ map reveals supramolecular interactions and assembly of the CatSper complex. Loss of EFCAB9-CATSPERζ alters the architecture and interactions of the channels, resulting in fragmentation and misalignment of the zigzag-rows and disruption of flagellar movement in Efcab9−/− sperm. This work offers unique insights into the structural basis for understanding CatSper regulation of sperm motility.
O-125 How to evaluate the tubal function before and during surgery
Authors: Ojha K
Published: July 2024

Role of assessment of Fallopian tubes in the modern era of highly effective ART remains essential. Both prior to deciding if ART is needed to exclude tubal damage and also in those where ART is needed to exclude hydrosalpinges. The question remains how one should assess tubal function. It is now well established that not all patients needed invasive surgical techniques to assess fallopian tubes. Clinical history of pelvic infection or positive test for STI such as chlamydia and a baseline scan are soft markers indicating the need for an early tubal assessment. Non surgical techniques are the first line approach for tubal assessment such as HyCoSy ( HyFoSy) or HSG. Surgical method such as laparoscopy and dye test are generally recommended when results are inconclusive or pathology has been observed where surgery is indicated. These methods can check tubal patency but not tubal function. Where as tubal function can be assessed either with falloposcopy during laparoscopy or Fertiloscopy through transvaginal route by looking inside the fallopian tube.
O-160 Age at menarche is a marker for increased time to pregnancy
Authors: Warp M , Grindstad T , Magnus M  C , Page C  M , Håberg S  E , Morken N  H , Romundstad L  B , Hanevik H  I
Published: July 2024

Study question

Is age at menarche a marker for increased time to pregnancy later in life?

Summary answer

Very early (<11 years) and very late (>15 years) menarche is associated with decreased fecundability.

What is known already

Several factors such as age, body mass-index and gynecological diseases influence female fecundability. Early or late menarche is associated with increased risk of several negative health outcomes later in life. Previous studies have shown conflicting results regarding if age at menarche is associated with time to pregnancy, a measure of female fecundability.

Study design, size, duration

82 471 pregnant women with complete, self-reported information on age at menarche and time to pregnancy were included in a large retrospective cohort study between 1999 and 2008.

Participants/materials, setting, methods

Among 67 613 women with planned pregnancies participating in the Norwegian Mother, Father and Child Cohort Study we calculated fecundability ratios which indicate the cycle-specific probability of conception, by categories of age at menarche. We adjusted for pre-pregnancy body mass index, highest completed or ongoing education level and age at initiation of trying to conceive.

Main results and the role of chance

We observed a 9% lower probability of conception during any given menstrual cycle up to 12 cycles in women with very early (<11 years) menarche, and a 4% lower probability among those with very late (>15 years) menarche compared to women with onset of menarche in the reference category (12-14 years). Among women with menarche <11 years the adjusted fecundability ratio was 0.91 (95% CI: 0.86-0.96) and among women with menarche >15 years the adjusted fecundability ratio was 0.96 (95% CI: 0.92-0.99).

Limitations, reasons for caution

We didn’t have information about partner characteristics such as sperm quality, nor data on early life exposures such as early nutrition and pre-menarcheal body mass index. Since all participants were pregnant, the results could have limited generalizability to those who never conceive.

Wider implications of the findings

By identifying reduced fecundability as yet another negative health outcome associated with very early or very late menarche, the results from this study further underline the clinical importance of age at menarche as a readily available marker for later reproductive health.

Trial registration number

not applicable
O-163 The effect of ambient exposure to air pollutants on live birth rates in frozen embryo transfer cycles
Authors: Solsona Caba M , Leathersich S , Donno V , Rodriguez I , Polyzos N
Published: July 2024

Study question

Do air pollutants during oocyte retrieval (OPU) and frozen embryo transfer (FET) affect in vitro fertilization (IVF) outcomes?

Summary answer

Environmental exposure to increased concentrations of CO either on oocyte retrieval or embryo transfer day negatively influences clinical outcomes in FET cycles.

What is known already

Exposure to air pollution is linked to adverse perinatal outcomes and reduced fecundity, yet its effect on fertility and IVF cycles is inconclusive. Previous studies explored associations between air pollutant concentrations and IVF outcomes with conflicting results. Nevertheless, few assessed different pollutants’ effects either on oocyte retrieval or embryo transfer days on live birth rates. While Asian and American studies suggest that pollutants affect pregnancy rates, from European studies failed to show meaningful differences in live birth rates. Considering varying pollutant levels globally, we aimed to evaluate their impact on a European population’s fertility outcomes.

Study design, size, duration

A retrospective cohort study analysed 1960 FET cycles conducted by a university affiliated fertility center in Europe between January 2017 to December 2022.

Participants/materials, setting, methods

Daily average ambient concentrations of five air pollutants (PM2.5, NO, SO2, CO, and O3) were obtained from an urban air quality monitoring station on the day of oocyte retrieval and the day of FET. Tertiles (T1, T2, T3) of each pollutant served as cut-off levels. Multiple logistic regression analysis assessed associations between pollutant exposure and pregnancy outcomes, adjusted for confounders.

Main results and the role of chance

Overall pregnancy and live birth rates following FET were 52.55% and 40.71%, respectively. When analysis the results according to air pollutants on the day of FET, ambient exposure to CO was significantly associated with up to 36% lower live birth (T2, OR: 0.64, 95% CI: 0.49—0.84; T3, OR: 0.67, 95% CI: 0.51—0.88; both compared to T1). Higher CO concentrations on the FET day were positively associated with increased miscarriage rates of up to 75% (T2, OR: 1.75, 95% CI: 1.12—2.75; T3, OR: 1.63, 95% CI: 1.04—2.56; both compared to T1).

Limitations, reasons for caution

The retrospective nature of the study and the omission of various potential covariates including environmental and patient factors that could affect IVF outcomes, limit our findings. Exposure assessment exclusively considered specific IVF days, and reliance on data from one air quality station reduces accuracy. Caution advised when interpreting the results.

Wider implications of the findings

This study highlights the potential impact of air quality on IVF cycle outcomes. Further investigations are needed to determine vulnerable IVF cycle phases and clarify mechanisms underlying fertility impairment.

Trial registration number

not applicable
O-171 Apicobasal RNA asymmetries regulate cell fate in the early mouse embryo
Authors: Hawdon A , Geoghegan N  D , Mohenska M , Elsenhans A , Ferguson C , Polo J  M , Parton R  G , Zenker J
Published: July 2024

Assessing the morphological appearance of an embryo as it progresses from zygote to blastocyst is the primary method used by embryologists to evaluate embryo viability and developmental potential. Standard embryo grading techniques, using time-lapse microscopy, analyse morphological characteristics such as size, shape, number, and appearance of blastomeres. The aim of this study was to determine how individual cells of the embryo function on a subcellular level to build a healthy embryo.

RNA localisation plays indispensable roles in establishing asymmetries and coordinating cell fate decisions during early embryogenesis across various non-mammalian species. To direct the spatiotemporal distribution of RNA within the cells of an embryo, the microtubule cytoskeleton provides highly sophisticated trafficking pathways. Yet, it remains unknown whether subcellular heterogeneities exist during mammalian preimplantation development and how they contribute to cell fate determination.

Using advanced live imaging, we visualised global RNA transcripts at high spatiotemporal resolution from fertilisation to the blastocyst stage in living preimplantation mouse embryos. We discovered apicobasal RNA asymmetries specific to outer cells of the 16-cell stage mouse embryo, coinciding with cell fate decisions and the emergence of the pluripotent inner cell mass. Highly clustered RNAs accumulated proximal to the basal membrane, while more dispersed RNA foci were identified apically as the embryo reaches the late 16-cell stage. The targeted distribution of membrane-less RNA molecules was facilitated by the microtubule cytoskeleton, associated with lysosomes which serve as RNA transport vehicles.

We discovered that apically located RNA foci were more dynamic and accompanied an enrichment of translation components. Furthermore, we uncovered that the established RNA asymmetries enhanced translation capacity in apical regions compared to basal regions. These spatiotemporal RNA heterogeneities were unevenly inherited by outer and inner daughter cells during subsequent cell divisions. Notably, embryos that were unable to establish RNA asymmetries failed to allocate cells to the trophectoderm and inner cell mass.

Our study provides insights into a subcellular mechanism driving asymmetric RNA localisation and compartmentalised translational regulation in outer cells of the 16-cell stage embryo, which may contribute to cell fate decisions during mammalian preimplantation embryogenesis. We envision that when paired with classical morphological assessment criteria of the embryo, these findings may assist with selecting the embryo with the highest developmental potential.
O-176 Hoping for the best, expecting the worst: pregnancy after loss
Authors: Bailey S
Published: July 2024

Recurrent pregnancy loss (RPL) is an extremely distressing condition and can be both physically and emotionally traumatising. The condition is compounded by the fact that even after diagnostic procedures, the majority of cases, remain unexplained.

The early waiting period of a new pregnancy, when confirmation by ultrasound scan of an ongoing and viable pregnancy is awaited, represent a particularly challenging time for those affected by this condition. This waiting period is associated with high levels of distress due to the anxiety of possibly experiencing a further miscarriage. However, there is a lack of understanding amongst some health professionals of the emotional burden of this difficult waiting period, furthermore, limited support and counselling is available, and many women are left to manage their distressing emotions without coping support. While some seek frequent confirmation of viability by ultrasound scans, this approach is not feasible in most clinical settings and, in any case, appears to be of limited efficacy in reducing anxiety. An alternative approach was to provide the woman with tools that could bolster their ability to cope with this challenging period.

Our programme of research has investigated the use of the Positive Reappraisal Coping Intervention (PRCI), a self- administered coping technique, based on the principles of positive reappraisal, as a method of providing much needed emotional support. Qualitative research findings have provided deep insight into the lived experience of RPL during the early waiting stages of a new pregnancy, establishing that for those with a history of RPL, this is a traumatic time of great uncertainty, emotional turmoil and immense personal significance, where those affected ‘hope for the best, but expect the worst.’

Whilst our programme of research is still ongoing, studies to date, have demonstrated that study participants were receptive to the use of the PRCI and that it appeared to convey benefits, with no apparent downside. It was a ‘go to’ resource in times of strong emotional need and one that stimulated positive coping, providing respite from the stressor of uncertainty.

There is a compelling need to provide those experiencing RPL with increased emotional support to help them manage the stressful early waiting period of a new pregnancy. Findings suggest that PRCI could provide a useful adjunct to care pathways and has the potential to be made more widely available as an effective, safe, convenient, and low-cost intervention to provide emotional support in RPL clinics.
O-245 Is AMH testing relevant for fertility preservation in young oncology patients?
Authors: Stern K
Published: July 2024

As the prevalence of cancer in young people rises, and with improved survival rates such that over 80% of young cancer patients can expect to recover, future fertility and having their own family has become an important consideration which needs to be addressed. Best-practice oncofertility management includes initial discussion, assessment of fertility risk and medical risk, and consideration of preservation strategies prior to commencement of potentially gonadotoxic therapy, where possible, as well as post cancer-treatment fertility care. The window of opportunity for oocyte cryopreservation and/or ovarian tissue cryopreservation may be very limited. Therefore it is of paramount importance that a patient’s medical condition, gonadotoxicity risk, and current reproductive health and potential are considered when planning fertility preservation. Antimullerian hormone (AMH) is one of a group of tests performed which can assist with planning treatment and with counselling regarding the likely yield of a cycle. Knowledge regarding pre-treatment AMH, along with a patient’s age and the type of cancer treatment, may also assist with counselling regarding the likelihood of recovery of fertility after completion of this treatment. However, there are many factors which affect AMH levels, and it is well-known that the results of stimulation can be very variable, as can be the long-term impact of the potentially gonadotoxic treatment. Hence an AMH test, while useful, needs to be contextualized as being only one of many factors to be considered when planning optimal (in terms of yield and safety) fertility preservation treatment and advising re future fertility.
P-466 The effect of Virtual Reality technology (VR) during oocyte pick up (OPU) in 100 IVF/ICSI patients - A randomised controlled trial (RCT)
Authors: Brock Spanggaard K , Byrum S , Jensen M  B , Jensen H  K , Sørensen L , Kyndi M , Lysdal A  M , Mailund S , Elbaek H  O , Humaidan P
Published: July 2024

Study question

Does VR technology improve patient experience in terms of nervousness, nausea, pain, and total experience as well as consumption of painkillers during the OPU procedure?

Summary answer

The use of VR technology seems to have a positive influence on patient experience during OPU. No effect was seen regarding consumption of painkillers.

What is known already

In recent years, the VR technology has received increasing attention for its suggested calming and pain-relieving effect during medical procedures. Thus, a previous study using VR technology in women undergoing hysteroscopy showed a significant difference in anxiety compared to women not using VR. We previously performed a small pilot study in patients undergoing OPU. That study suggested that VR technology had a positive effect on patients before OPU in terms of level of relaxation and stress. Importantly, in the pilot project patients solely used the VR technology before the OPU procedure.

Study design, size, duration

This RCT included a cohort of 100 IVF/ICSI patients undergoing OPU. Patients were computer randomized into two groups: an intervention group (VR) and a control group (no VR) during OPU. Randomization was performed on the day of ovulation induction. The study was conducted from April 2023 to December 2023 in a public university affiliated fertility clinic.

Participants/materials, setting, methods

10 minutes before the OPU procedure the VR headset was placed and remained in place during OPU in the intervention group. The control group was treated according to the standard procedure of the unit. Both groups answered a questionnaire, including 14 questions using VAS (Visual Analog Scale) before and after OPU regarding nervousness, nausea, pain and total experience. Moreover, blood pressure, heart rate, saturation, and consumption of medication was recorded.

Main results and the role of chance

The study showed that the use of VR technology in women undergoing OPU significantly (P = 0.01) lowered the patient’s systolic blood pressure before the procedure. Moreover, the study showed a trend towards a reduction in nervousness and consumption of painkillers. The comments of the patients regarding their total experience of the effect of VR were in favour of VR usage and several patients would choose VR technology for a possible future OPU.

Limitations, reasons for caution

The patient experience might have differed if the same nurse participated during all the OPUs. To find a possible significant effect of VR usage as regards nervousness and consumption of painkillers a future larger sample size is required.

Wider implications of the findings

The use of VR technology during OPU might be considered as a supplement for patients during OPU.

Trial registration number

NCT05826938
P-080 Unveiling the molecular determinants of sperm endpiece stabilization
Authors: Jonkers S
Published: July 2024

Study question

How are microtubules at the endpiece of the mammalian sperm tail stabilized?

Summary answer

SAX01 and SPACA9 are microtubule inner proteins that binds at the endpieces. In addition, singlet microtubules are capped by a complex of proteins.

What is known already

At the core of the sperm flagellum is the axoneme, a supramolecular assembly of nine doublet microtubules around a central pair of singlet microtubules. At the endpiece, axoneme structure is lost and only singlet microtubules remain. Using cryo-electron microscopy (cryo-EM) our group showed that the singlet microtubules contain species-specific microtubule inner proteins in a helical arrangement. Furthermore, we observed a protein density capping the microtubules plus-ends in pig, horse, and mouse sperm.

Study design, size, duration

To elucidate the function of the sperm endpiece plug and its associated proteins, we apply single-particle analysis cryo-EM.

Participants/materials, setting, methods

-

Main results and the role of chance

We revealed that the microtubule inner proteins in the singlets are SAX01 and SPACA9. Our high-resolution structure shows that SPACA9 forms a discontinuously intraluminal spiral. It consists of a bundle of alpha helices that binds across the intradimer α/β-tubulin interface as well as between adjacent protofilaments. Specifically, SPACA9 interacts with both α- and β-tubulin within a dimer while also interacting with the M-loop of α-tubulin from the neighbouring protofilament. Our structure further shows that SAX01 binds longitudinally along individual protofilaments with its Mn motif, a 5- to 6-residue helix flanked by a Tyr/Phe residue on one end and by a Ser/Thr on the other that binds the shoulder of the α -tubulin S9/S10 loop. We further observed that microtubule termini are capped with yet to be identified protein complexes. Taken together, we show that microtubule inner proteins longitudinally and laterally reinforce the microtubule lattice, while capped in their termini.

Limitations, reasons for caution

Limitations include species-specific variations as we previously observed between mouse sperm endpieces and porcine or horse. Cryo-EM structures represent averages across singlet microtubules, so individual variation within particles may be lost.

Wider implications of the findings

Investigating the mechanism behind stabilization of the endpiece singlet microtubules using cryo-EM provides better understanding of sperm tail stabilization that holds potential for progress in understanding male infertility and can be utilized for a development of male contraception.

Trial registration number

not applicable
P-018 Study of sperm DNA fragmentation in the infertile population before, during and after the SARS-CoV-2 pandemic: a nationwide retrospective cohort study
Authors: Lara-Cerrillo S , Lacruz-Ruiz T , Rosado-Iglesias C , Serrano-Berenguer L , Garcia-Peiro A
Published: July 2024

Study question

Did the values of single- and double-strand sperm DNA breaks (SSB and DSB) increase during the SARS-CoV-2 pandemic?

Summary answer

During the SARS-CoV-2 pandemic (2020), the mean values of SSB and DSB in infertile patients were statistically higher compared to the periods 2018-2019 and 2021-2022.

What is known already

Some studies have found lower sperm concentration and motility in patients during and after SARS-CoV-2 infection (COVID-19). These effects appear to be reversible, with significant improvements being observed after three months post-infection (complete spermatogenesis cycle). On the contrary, vaccination against this virus does not seem to affect semen parameters. The objective of the study was to compare the values of SSB and DSB sperm DNA fragmentation in the periods before the pandemic (2018-2019), during (2020, highest number of infections and social confinement), and after (2021-2022, lower infection rate, end of social confinement and vaccination period).

Study design, size, duration

The average SSB and DSB sperm DNA fragmentation values of 11,215 patients referred from 74 fertility centres throughout Spain from January 2018 to December 2022 were retrospectively compared.

Participants/materials, setting, methods

Semen samples from infertile patients were analysed using the Comet assay in alkaline or neutral pH conditions to evaluate SSB or DSB, respectively. Three periods were compared (two years before, during 2020, and two years after). Mean SSB and DSB values were statistically compared among these periods using the Kruskal-Wallis and Mann-Whitney tests. Differences were established at the 99% confidence interval.

Main results and the role of chance

The average SSB values obtained were: 41.67%±15.33 in 2018-2019; 43.92%±17.84 in 2020, and 41.68%±18.58 in 2021-2022. The average DSB values obtained were: 65.64%±14.27 in 2018-2019; 67.77%±13.90 in 2020, and 65.23%±15.18 in 2021-2022. The SSB and DSB values were statistically higher in 2020 compared to the periods 2018-2019 and 2021-2022 (p < 0.001 in both cases). No differences were detected between the previous period (2018-2019) and the following period (2021-2022) (p = 0.101 and p = 0.235, respectively).

Limitations, reasons for caution

The observed increase in SSB and DSB values during 2020 cannot be directly attributed to the SARS-CoV-2 infection (COVID-19). It is possible that it is associated with other concurrent factors. The studied samples were only from infertile patients, not from the general male population.

Wider implications of the findings

Given that the SARS-CoV-2 virus still exists in 2021-2022 but the social situation has normalized, the increase in fragmentation observed during 2020 could be more related to other aspects of the pandemic, such as social confinement, stress, among others.

Trial registration number

Not applicable
P-040 The characteristic of human seminal plasma extracellular vesicle (SPEVs) profiles with different sperm features in a large cohort of 309 Taiwanese men
Authors: Cheng Y , Lin Y  C , Chen H  Y , Hou H  C , Lin T  Y , Lin S  C
Published: July 2024

Study question

To investigate human seminal plasma extracellular vesicle profiles in different sperm characteristics and their potential clinical application.

Summary answer

Normozoospermic semen has significantly higher SPEV concentration than asthenozoospermic or oligozoospermic samples. Moreover, SPEV concentration was highly correlated with total motile sperm count.

What is known already

Seminal plasma extracellular vesicles (SPEVs) are cell-derived membrane structures that carry proteins, nucleic acid, and lipids, which can modify the constitution and biological function of sperm. However, the characteristics of SPEVs in different sperm features remained unclear.

Study design, size, duration

From January 2021 to September 2023, 309 men who visited the NCKUH andrology clinic agreed to collect semen samples for this study, which the Institutional Review Board has approved.

Participants/materials, setting, methods

Semen parameters were measured by the X1 CASA system (Bonraybio, Taiwan). SPEVs were isolated by size exclusion chromatography column and ExoQuick™. Next, the SPEVs’ concentration and size distribution were performed with nanoparticle tracking analysis. The Kruskal-Wallis test calculated comparison in multiple groups, and Dunn’s multiple comparison tests accessed group-group comparison. The Pearson correlation coefficient r of exosome concentration with individual sperm parameters was calculated. A p-value less than 0.05 was set as statistical significance.

Main results and the role of chance

Among them, 59 semen samples were presented with normozoospermia, 36 were oligozoospermia, 73 were asthenozoospermia, and 141 samples had no sperm in semen. Among these 141 azoospermic men, 89 men are characterized by non-obstructive azoospermia (NOA), while the other 52 men had a vasectomy. Our data showed that normozoospermic semen has significantly higher SPEV concentration than asthenozoospermic or oligozoospermic semen samples (26 x109 [IQR 17.25 x109-56.25 x109] versus 12 x109 [IQR 5.6 x109-19.5 x109] versus 15.5 x109 [IQR 8.575 x109-26.75 x109], p = 0.0001). Nevertheless, azoospermic semen has the lowest SPEV concentrations. The concentration of SPEVs from infertile men diagnosed with NOA is slightly lower than vasectomized men (3.9 x109 [IQR 1.875 x109-7.675 x109] versus 5.4 x109 [IQR 2.9 x109-8 x109], p = 0.0001). The Pearson r coefficient of SPEV concentration with sperm concentration, progressive motility, and total motile sperm count was 0.238, 0.303, and 0.451, respectively. (P < 0.0001)

Limitations, reasons for caution

Because our data were collected from Taiwanese men, it is not yet known whether SPEV profiles differ among races.

Wider implications of the findings

Human SPEV concentration and its bio-content may be a potential non-invasive biomarker to predict the male reproductive outcome.

Trial registration number

not applicable
P-064 Adolescent varicocele: clinical profile and impact of treatment
Authors: Majzoub A , Fadol N , Elbardisi H , ElSaid S , AlMalki A , Khalafalla K , Ata Y , AlKubaisi K , Al Saeedi A , Arafa M
Published: July 2024

Study question

What is the clinical presentation of adolescent varicocele and the impact of its repair on semen quality?

Summary answer

Adolescent varicocele usually presents as testicular pain and does not influence semen quality. Varicocele ligation does not impact postoperative semen results in this patient population.

What is known already

Varicocele is a common condition characterized by the abnormal dilation of the pampiniform plexus of veins resulting in testicular dysfunction and impaired semen quality. While the effect of varicocelectomy on the fertility potential of adult men has been commonly explored, its impact on semen parameters of adolescents is less commonly investigated.

Study design, size, duration

The charts of 2171 patients who underwent microsurgical subinguinal varicocelectomy for clinically palpable disease between 2011-2023 were retrospectively reviewed. Patients <19 years of age were included in the analysis.

Participants/materials, setting, methods

The patients’ medical charts were reviewed to include demographic and clinical characteristics; indication of surgery, body mass index, testis size, grade of clinical disease, vein diameter (assessed with scrotal ultrasound) and semen analysis results (WHO 2010). Data were analyzed using Wilcoxon Signed Ranked. Mean ± SD and median (IQR) were used to report normally and non-normally distributed data, respectively. A p value <0.05 was considered significant.

Main results and the role of chance

A total of 94 adolescent patients were included in the study. Their mean BMI was 22.14±5 Kg/m2, mean left testis size was 12.26 ± 3.05 cm3 and right testis size 13.26±3.94 cm3. The maximum vein diameter 4.7±1.04 mm and right vein diameter 2.21±0.83 mm. 83 patients underwent unilateral Microsurgical Varicocelectomy while 5 patients underwent bilateral Microsurgical Varicocelectomy. Left varicocele was of grades 3, 2 and 1 in 65, 18 and 11 patients, respectively. Surgery was indicated for testis size discrepancy in 36.2% of cases and on elective basis (prior to army recruitment) in 63.8% of cases. Table 1 presents the pre- and post-operative semen parameter results. Patients had normal pre-operative medians of sperm count, total motility and normal morphology. No significant post-operative changes were observed in the semen quality of adolescents.

Limitations, reasons for caution

Results were obtained from a relatively small sample size. However, varicocele is less commonly performed on adolescents necessitating further studies on this patient population.

Wider implications of the findings

Results of this study shed the light on the characteristics of adolescents presenting with varicocele.

Trial registration number

NA
P-115 GATAD2B is required for pre-implantation embryo development by delaying zygotic genome activation
Authors: Cao G
Published: July 2024

Study question

Major zygotic genome activation (ZGA) involving the activation of thousands of genes occurs at the late-2cell stage, but the regulatory mechanisms governing ZGA remain unclear.

Summary answer

Our results demonstrate that GATAD2B is essential for early embryonic development, in part through facilitating zygotic genome activation (ZGA).

What is known already

Acetylation modifications of histone tails promote transcriptional activation, and the maternal deletion of H4K16ac leads to failure in ZGA. GATAD2B is one of the core subunits of the Nucleosome remodeling and histone deacetylation complex(NuRD).

Study design, size, duration

Using mouse embryos as the research model, the study was conducted over a period of approximately two years to ensure a relatively small-scale investigation.

Participants/materials, setting, methods

We examined the dynamic expression of NURD complex components, including GATAD2B, during pre-implantation embryonic stages. GATAD2B expression was specifically reduced via microinjection of GATAD2B-siRNA during the zygote stage, revealing its impact on early embryonic development in mice. Zygotic genome activation (ZGA), morula compaction, and blastocyst lineage differentiation were investigated using immunofluorescence, western blot, and other techniques. Additionally, we employed RNA-seq, protein immunoprecipitation, and mass spectrometry to uncover underlying molecular mechanisms.

Main results and the role of chance

Our research has shown that GATAD2B exhibits specific nucleus localization and high protein expression from the late-2-cell to 8-cell. This intriguing phenomenon prompted us to investigate the relationship between GATAD2B and the ZGA. We discovered a distinctive pattern of GATAD2B, starting from the late 2-cell stage with nuclear localization. GATAD2B depletion resulted in defective embryonic development, including increased DNA damage at morula, decreased blastocyst formation rate and abnormal differentiation of ICM/TE lineages. Consistent with the delay during the cleavage stage, the transcriptome analysis of the 2-cell revealed inhibition of the cell cycle G2/M phase transition pathway. Furthermore, the GATAD2B proteomics data provided clear evidence of a certain association between GATAD2B and molecules involved in the cell cycle pathway. As hypothesized, GATAD2B-deficient 2-cell embryos exhibited abnormalities in ZGA during the maternal-to-embryonic transition, with lower expression of the major ZGA mark MERVL.

Limitations, reasons for caution

Given the limitations of antibody effectiveness and specificity required for the experiments, the exploration of molecular mechanisms is still ongoing.

Wider implications of the findings

Our findings have elucidated the impact of GATAD2B on early embryonic development through the regulation of zygotic genome activation (ZGA), providing a novel genetic explanation for clinical defects in early embryonic development.

Trial registration number

not applicable
P-127 The RNA m6A landscape of mouse oocytes and preimplantation embryos
Authors: Li Y
Published: July 2024

Study question

Despite the significance of N6-methyladenosine (m6A) in gene regulation, the requirement for large amounts of RNA has hindered m6A profiling in mammalian early embryos.

Summary answer

We apply picoMeRIP-seq to map m6A in mouse oocytes and preimplantation embryos. We define the landscape of m6A during the maternal-to-zygotic transition.

What is known already

N6-methyladenosine (m6A), the most prevalent internal modification in eukaryotic messenger RNA (mRNA), plays key regulatory roles in many biological processes (for example, RNA stability, splicing, transport and translation) and is involved in a variety of physiological processes (for example, cell differentiation and reprogramming, embryonic development and stress responses).

Study design, size, duration

We recently developed an m6A mapping assay for low RNA input, low-input methyl RNA immunoprecipitation and sequencing (picoMeRIP-seq), which enables mapping of the m6A methylome using a low number of cells. In this article, we applied picoMeRIP-seq to multiple developmental stages of mouse oocytes and early embryos to profile their m6A landscapes.

Participants/materials, setting, methods

We use mouse as study materials.Using picoMeRIP-seq, we generated transcriptome-wide m6A maps for six stages (GV, MII, zygote, two-cell, eight-cell and blastocyst), with two biological replicates per stage and 49–110 oocytes/embryos per replicate.

Main results and the role of chance

We define the landscape of m6A during the maternal-to-zygotic transition, including stage-specifically expressed transcription factors essential for cell fate determination. Both the maternally inherited transcripts to be degraded post fertilization and the zygotically activated genes during zygotic genome activation are widely marked by m6A. In contrast to m6A-marked zygotic ally-activated genes, m6A-marked maternally inherited transcripts have a higher tendency to be targeted by microRNAs. Moreover, RNAs derived from retrotransposons, such as MTA that is maternally expressed and MERVL that is transcriptionally activated at the two-cell stage, are largely marked by m6A. Our results provide a foundation for future studies exploring the regulatory roles of m6A in mammalian early embryonic development.

Limitations, reasons for caution

The effect of m6A on the turnover of retrotransposon-derived transcripts abundant in oocytes and early embryos needs to be further addressed in future studies.

Wider implications of the findings

Our results provide a foundation for future studies exploring the regulatory roles of m6A in mammalian early embryonic development.

Trial registration number

not applicable
P-137 A deep learning model using time-lapse imaging data to predict successful clinical pregnancy and embryo euploidy
Authors: Maekawa R , Tanaka A , Kuramoto T , Sugino N
Published: July 2024

Study question

Are the deep learning models helpful in selecting embryos with a high probability of clinical pregnancy and euploidy from time-lapse imaging during embryo growth?

Summary answer

Our deep learning models using time-lapse imaging data predicted the probabilities of successful clinical pregnancy and euploidy of embryos with high accuracy.

What is known already

Recent studies have attempted to select the most viable embryo using deep learning of time-lapse imaging during incubation. However, most studies included embryos that were not transferred due to low evaluation by the embryologist as embryos with unsuccessful pregnancies, or they mixed single and multiple embryo transfer cases in the analyses. Some studies’ algorithms rely on humans’ subjective interpretation of morphological and morphokinetic features, leading to embryologist-to-embryologist and within-embryologist variabilities. Some reports, including the study predicting embryo aneuploidy, used a snapshot image for prediction. These approaches have restricted the potential of deep learning in embryo selections.

Study design, size, duration

Retrospective analyses of time-lapse videos of 2,192 embryos with clinical pregnancy outcomes, defined as confirmed gestational sacs in utero, and 1,467 embryos with karyotype outcomes examined by preimplantation genetic testing for aneuploidy (PGT-A). The data were obtained from two different in-vitro fertilization clinics between November 2017 and December 2021. All transfers were performed as a single embryo transfer.

Participants/materials, setting, methods

The deep learning model was trained using time-lapse videos with known clinical pregnancy outcomes for predicting the probability of clinical pregnancy with given time-lapse video sequences and patient ages (CP model). Another deep learning model was trained using time-lapse videos with known karyotype outcomes by PGT-A for predicting the probability of euploidy (AP model). The models’ predictive powers were measured using the average area under the curve (AUC) of the receiver operating characteristic curve.

Main results and the role of chance

The CP model predicted clinical pregnancy with an AUC of 0.693. The AP model predicted embryo aneuploidy with an AUC of 0.702.

Limitations, reasons for caution

The CP model is based on the embryos that were transferred because the embryologist judged them as having a high probability of pregnancy. Clinical pregnancy may be associated with maternal factors besides embryo factors.

Wider implications of the findings

Our two deep learning models, the CP and AP models, will be helpful for selecting the embryos to be transferred. The CP model may increase pregnancy rates in patients undergoing assisted reproductive technology. The AP model may reduce the miscarriage caused by embryo aneuploidy.

Trial registration number

not applicable
P-280 Influences of CD8(+) tissue resident memory T cells on eutopic endometrial immune microenvironment and endometrial receptivity of minimal/mild endometriosis
Authors: Huang X , Wei H
Published: July 2024

Study question

Our study aimed to focused on the influence of CD8+ tissue resident memory T cells (CD8+ TRM) on endometrial immune microenvironment and endometrial receptivity.

Summary answer

CD8+TRM participated in inflammatory endometrial immune microenvironment, influenced expression of endometrial receptivity and decidualization markers of stromal cells of eutopic endometrium of minimal/mild endometriosis.

What is known already

CD8+ tissue resident memory T cells (CD8+ TRM) are abundant in endometrium,CD8+ TRM have important physiological functions and of pathological significance in endometrium.

Study design, size, duration

Endometrial samples were collected using Pipelle sampling from women with or without endometriosis (minimal/mild) during hysteroscopy-laparoscopy. Tissue for immunofluorescence was fixed in 4% paraformaldehyde, for cell analysis was isolated into single cell immediately.

Participants/materials, setting, methods

We analyzed number variation, tissue location, cytotoxicity, degranulation and cytokine secretion of CD8+TRM in endometriosis and control during menstrual cycle through flow cytometry and polychromatic tissue immunofluorescence. We cocultured CD8+TRM and endometrial stromal cell to know the influence of CD8+TRM to endometrial receptivity and decidualization. The concentration of TNF-α, IFN-γ, IGFBP-1 and PRL were analyzed via ELISA and q-PCR. Western blot and q-PCR were used to test the expression level of HOXA10 and FOXO1.

Main results and the role of chance

Flow cytometry founded that the number of CD8+TRM in proliferative phase were more than secretory phase in both endometriosis and control. CD8+TRM were not only scattered in stroma of endometria, and also gathered in lymphoid aggregates. During secretory phase, the cytotoxicity, degranulation, and inflammatory cytokine expression resourced from CD8+ TRM were higher in endometriosis than control. CD8+TRM inhibited the expression of endometrial receptivity markers (HOXA10 and FOXO1) and decidualization markers (IGFBP-1 and PRL) of endometrial stromal cells in coculture system. When blocking the IFN-γ in coculture system, the expression of endometrial receptivity markers and decidualization markers were improved.

Limitations, reasons for caution

The mechanism of CD8+TRM influence on endometrial receptivity and decidualization of endometriosis is needed to further investigation.

Wider implications of the findings

CD8+TRM participated in inflammatory endometrial immune microenvironment, influenced expression of endometrial receptivity and decidualization markers of stromal cells of eutopic endometrium of minimal/mild endometriosis. CD8+TRM and its secretion of IFN-γ could be immunotherapeutic target for defective endometrial receptivity of endometriosis.

Trial registration number

NA