bluuebunny/crossref_metadata_2025 huggingface dataset:
P-368 Clinical impact of personalized embryo transfer (pET) guided by endometrial receptivity analysis (ERA) in patients with ≥ 1 failed transfers
Authors: Ruiz-Alonso M , Stankewicz T , Castellón J A , Gómez C , De La Fuente E , Gómez E , Simón C , Valbuena D
Published: June 2023

Study question

Does pET following ERA increase pregnancy (PR), ongoing pregnancy per transfer (OGPR) and live birth rates (LBR) in patients with ≥ 1 previous failed transfer?

Summary answer

In this group of patients, pET guided by ERA obtained a significantly higher PR, OGPR and LBR versus standard embryo transfer.

What is known already

pET consists of synchronizing embryo transfer with the optimal endometrial receptivity status of the patient by the transcriptomics identification of her personalized window of implantation (WOI). Controversial results have been published regarding the clinical usefulness of this precision medicine diagnosis in a range of clinical indications. Here we present data from patients with ≥ 1 previous failed transfer undergoing pET guided by ERA.

Study design, size, duration

Multicenter retrospective study involving 526 patients with at least one previous failed embryo transfer (ET) between 2017 and 2021. These patients were divided into two groups: cases (pET guided by ERA) (n = 385), or controls (standard blind ET) (n = 141). Clinical outcomes compared were PR, OGPR and LBR for each group.

Participants/materials, setting, methods

Age, body mass index (BMI), previous failed attempts, proportion of embryos with PGT-A and transferred embryo quality were compared between the two groups. ERA test was performed in HRT cycles and subsequent embryo transfer was carried out replicating the same conditions and following the recommendation given for pET. Standard ET was also performed in HRT cycles. Wilcoxon rank sum test was applied to quantitative comparations. Chi-square test was done for categorical variables.

Main results and the role of chance

In this retrospective analysis, age and number of previous failed ET was higher in the ERA group (p < 0.05). Clinical results in terms of PR, OGPR and LBR were significantly higher when pET guided by ERA was performed when compared to the non-ERA group.

Limitations, reasons for caution

This is a retrospective study, having limitations of its nature.

Wider implications of the findings

These results show that pET guided by ERA in patients with ≥ 1 failed transfers increased significantly PR, OGPR and LBR versus standard blind ET.

Trial registration number

Hospital Clínico de Valencia Ethic Committee approval nº. 2021/018.
P-717 Segmental aneuploidies are not related to paternal age in young women
Authors: Bronet Campos F , Marta A , Mireia F , Amparo M , Eva M
Published: June 2023

Study question

Is there an impact of paternal age on embryo segmental aneuploidy rate?

Summary answer

Even when segmental aneuploidies are most linked to paternal origin, results do not show a relationship between paternal age and embryo segmental aneuploidies.

What is known already

Most studies consider maternal age as a risk factor for spontaneous abortion, infertility and genetic defects in the offspring. However, attention has only recently turned to the impact of paternal age on reproductive outcome. In Assisted Reproduction Technology male age has been related to a decrease in sperm quality and clinical outcomes and an increase in sperm DNA damage has been identified among elderly males. Studies assessing the type of chromosomal aneuploidy associated with paternal aging have reported mixed relative risk results for chromosomes 13, 18, 21, and X. Segmental aneuploidies are most linked to paternal origin.

Study design, size, duration

Observational, retrospective and multicentric study. The study was approved by the local institutional review board (IRB). All the patients underwent an IVF cycle with oocytes from egg donors, followed by Preimplantation Genetic Testing for Aneuploidy (PGT-A) at IVI-RMA Madrid, IVI-RMA Valencia and IVI-RMA Barcelona from January 2018 to August 2022. A total of 3412 biopsied embryos obtained from 660 cycles were included in the study.

Participants/materials, setting, methods

Exclusion criteria were the following: altered karyotype, single gene disorder and male factor (sperm concentration lower than 5 million/ ml). Embryo biopsies were performed at blastocyst stage (day 5/ 6). After the trophoectoderm biopsy, all embryos were vitrified. Main outcome was segmental aneuploidy rate among different male age groups (<41 y.o./ ≥40 y.o.). Lineal regression analysis was used for continuous parameters and Chi square was used for categorical variables.

Main results and the role of chance

Descriptive parameters showed no differences, particularly in sperm concentration (43.2±15.6 vs. 40.1±14.3) and sperm motility (27.3±13.7 vs. 29.7±14.8). Lineal regression analysis showed no significant differences in segmental aneuploidy rate (p = 0.542). Statistical model showed no significant differences among male age groups (1.28% (0.76-2.01) vs 1.10% (0.69-1.66) p = 0.542).

Limitations, reasons for caution

The study has been conducted in three different clinics, there could be some unknown cofounding factors.

Wider implications of the findings

Male age don’t have an impact on the embryo segmental aneuploidy rate in young/donors’ oocyte

Trial registration number

Not applicable
P-732 High degree of concordance between the genetic results of Noninvasive Preimplantation Genetic Testing for Aneuploidies (NIPGT-A) and those obtained with analysis of the whole embryo
Authors: Franco J G , Petersen C G , Vagnini L , Massaro F C , Petersen B , Izidoro P M , Nicoletti A , Ricci J , Zamara C , Oliani A H , Dieamant F , Oliveira J B A
Published: June 2023

Study question

What is the degree of concordance between Noninvasive Preimplantation Genetic Testing for Aneuploidies (NIPGT-A) versus genetic analysis of the whole embryo?

Summary answer

Cell free DNA ploidy evaluated by NIPGT-A presents very good concordance that of the DNA from whole embryo cells (Cohen's Kappa concordance coefficient: 0.84).

What is known already

After many years of using PGT-A, there are still many concerns, such as risks of invasive action and difficulties in the correct interpretation of mosaicism, which may lead to errors in the interpretation of false-positive and false-negative results. Recently, a new technology (NIPGT-A) has arisen using cell-free DNA present in the spent culture media of human blastocysts. However, there are still few genetic analyses of concordance between NIPGT-A and the whole embryo (gold standard).

Study design, size, duration

This cohort study included a total of 56 blastocysts vitrified on Day-5 that were previously biopsied for PGT-A. All embryos had a diagnosis of aneuploidy and were donated under informed consent by patients following the Human Medical Authority regulations. Blastocysts were thawed and cultured in 15µl drops of culture medium under oil. After their expansion(4-8 hours), the blastocysts and their corresponding spent media were transferred to PCR tubes and stored at -80 °C until analysis.

Participants/materials, setting, methods

DNA in all samples(spent culture medium and whole embryo) was amplified by MALBAC® technology(Yikon Genomics). The DNA concentration of the amplified product was measured using a Qubit 3.0Fluorometer(Thermo Fisher Scientific). The samples were subjected to next-generation sequencing (NGS) using the Illumina MiSeq® system. The ploidy status results obtained from ChromGoTM software(Yikon Genomics) for spent culture medium and the whole embryo were compared to determine the accuracy of NIPGT-A for screening chromosomal abnormalities in each embryo.

Main results and the role of chance

DNA from all 56 spent medium samples and whole embryos were successfully amplified. Comparing the results of NIPGT-A and whole-embryo sequencing (Table 1), the positive predictive value (PPV) was 93.5%, and the false-positive rate (FPR) was 6.5%. Agreement analysis showed very good coefficient concordance (Cohen's Kappa coefficient: 0.84).
P-752 Cervical cerclage versus vaginal progesterone in the prevention of preterm birth in singleton pregnancies among women with a short cervical length: A retrospective cohort study
Authors: Liu Y , Cao T , Zeng S , Chen R , He L , Liu X
Published: June 2023

Study question

To compare the maternal and neonatal effects of cervical cerclage and vaginal progesterone in preventing singleton preterm births in women with a short cervical length.

Summary answer

Cervical cerclage showed no benefit in preventing preterm birth; however, it prolonged gestation by 39 days compared to vaginal progesterone treatment.

What is known already

Clinically, there may be a bias toward the choice of cervical cerclage if the cervix is short (<10 mm) and, similarly, toward vaginal progesterone use if the cervix is long (>30 mm). However, there are no clear treatment guidelines for the best options for singleton pregnant women with a CL between 10 and 30 mm. Furthermore, there is insufficient evidence to determine whether one treatment is superior to the other in preventing PTB and decreasing adverse neonatal outcomes in singleton pregnancies in such cases.

Study design, size, duration

Asymptomatic pregnant women having singleton pregnancies, with a CL between 10 and 30 mm, measured using transvaginal ultrasound at 12–26 weeks of gestation, who delivered at our hospital between January 2009 and August 2020, were included in our study. Based on the inclusion and exclusion criteria, 267 singleton pregnant women, of whom 116 were treated with cervical cerclage and 151 with vaginal progesterone, were finally included.

Participants/materials, setting, methods

Independent sample t-tests and differential analysis were used to analyze the data based on their distribution. The Cox semi-parametric regression model was used to analyze the gestation weeks at delivery and neonatal outcomes. The decision regarding cesarean delivery was based on a binary logistic regression model.

Main results and the role of chance

In the initial analysis, the number of preterm births was significantly higher in the cerclage group than in the vaginal progesterone group; however, after multivariate adjustment for confounding factors, the latency period from diagnosis to delivery was found to be significantly prolonged in the cerclage group.

Limitations, reasons for caution

There are currently no uniform criteria for determining whether study subjects are eligible for cervical cerclage or vaginal progesterone treatment, which may present some cases of noncompliance.

Wider implications of the findings

In our study, we found that cervical cerclage did not have significant advantages over vaginal progesterone treatment in preventing PTB. However, upon adjustment for confounding factors, it was shown to prolong the gestational age by 39 days compared to vaginal progesterone treatment.

Trial registration number

non-clinical trials
O-112 Jean Purdy - The silent partner
Authors: Kendrew H J
Published: June 2023

The development of a novel technique requires a diverse team whose individuals share the same goal but who each bring a different strength and aspect of their personality to the research/ project.

A “front man” with tenacity drive and vision needs the support of such team. To quote Aristotle “The whole is greater than the sum of it's parts”.

This expression could be aptly applied to the pioneers of IVF, Robert Edwards and Patrick Steptoe about whom much has been written. Their drive and determination in the face of societal opposition and competition from across the Atlantic, was supported by a silent group of lesser known individuals.

Jean Purdy (research nurse and laboratory assistant), Muriel Harris (operating theatre superintendent), Lillian Lincoln Howell (philanthropist) and Ruth Fowler (scientist and Robert Edwards wife). Not to mention the 280 unidentified women patients and their partners who played their part. All drawn together in the quest to try and help patients achieve the families they so desired.

In my presentation I am concentrating specifically on the life Jean Purdy and her contribution to the work which sees us all here today in Copenhagen.She had a short but pivotal life, often attributed to being the first embryologist, prematurely dying at the age of 39 from malignant melanoma.

As of March 2021 at least eight million babies worldwide have been born from IVF. I wonder how astounded these pioneers would be to see how far we have come and what they would make of the world wide impact they made in the face of significant criticism, moral outrage and scepticism from their professional peers, the church, media and society?
O-115 Fertility preservation or egg donation for hereditary cancer syndromes?
Authors: Filippi F
Published: June 2023

Individuals with hereditary cancer syndromes are at risk of developing multiple tumours and, therefore, undergo life-long surveillance procedures and risk-reducing and/or therapeutic surgeries. Knowledge and testing for hereditary cancer susceptibility genes is rapidly spreading, often performed at the first cancer diagnosis.

Different physical, psychosocial, ethical and economic considerations need to be taken into account when deciding on reproductive options in individuals with a hereditary cancer syndrome.

The psychosocial impact of genetic predisposition to cancer may be particularly problematic and still represents an ongoing challenge for the professional taking care of these patients. In fact, worries about passing on a genetic risk for cancer to offspring are concerns expressed by the 65% of female young adult cancer survivors when specifically interviewed.

At cancer diagnosis, fertility preservation procedures represent an effort to retain the opportunity to have genetically related children. Unfortunately, oocytes, embryo or ovarian cortex cryopreservation do not guarantee live birth. The success rates of these procedures are highly dependent on age, number of oocytes cryopreserved and may be influenced by other medical, lifestyle and (future) male factors. In addition, carriers of pathogenetic gene variants for cancer predisposition should also be thoroughly counselled about preimplantation genetic testing (PGT), a technique allowing the interruption of passing on the gene associated to cancer risk. However, this option inevitably lowers the efficacy of fertility preservation interventions in terms of future pregnancies.

Egg donation is a spreading procedure with higher success rates than fertility preservation techniques. This approach allows individuals to avoid undergoing oocytes retrieval or ovarian tissue cryopreservation surgery, thus avoiding procedural risks (infection, haemorrhage, ovarian hyperstimulation syndrome) and postponement of oncological treatments. On the other side, offspring will not have a genetic link with recipient and the beneficial psychological role of fertility preservation would be missing. In fact, several recent studies have underlined the message of hope that is indirectly perceived by oncological patients when counselled for fertility preservation. Moreover, counselling on the possibility of egg donation is challenging at the time of cancer diagnosis.

Making the right reproductive choice in carriers of hereditary cancer syndromes is a dilemma which can’t be solved generalizing. Even patients’ attitude could be different according to the time of counselling, whether is at cancer diagnosis or at the genetic predisposition diagnosis in healthy carriers. Egg donation should be considered in the available armamentarium. The complexity of the topic needs a personalized and multidisciplinary counselling.
P-781 Assisted reproductive technology-associated risk factors for retained placenta
Authors: Jwa S C , Tamaru S , Takamura M , Namba A , Kajihara T , Ishihara O , Kamei Y
Published: June 2023

Study question

What are the assisted reproductive technology-associated risk factors for retained products of conception (RPOC) following delivery?

Summary answer

Frozen embryo transfer (FET) with hormone replacement cycles (HRC) constitutes the largest risk factor for RPOC.

What is known already

RPOC is a key cause of secondary postpartum hemorrhage. Previous studies have shown that the use of ART increases the risk of RPOC and subsequent transfusion following delivery. However, the relationships between specific ART-treatment factors and the risk of RPOC have not been elucidated.

Study design, size, duration

We performed a registry-based retrospective cohort study using the Japanese national ART registry, in which all the ART cycles performed in Japan are recorded including the perinatal outcomes.

Participants/materials, setting, methods

Singleton live births between 2007 and 2017 were studied (n = 306,411). Odds ratios (ORs) and 95% confidence intervals (CIs) for the potential risk factors for RPOC associated with fresh and frozen cycles were obtained from multiple logistic regression analysis, incorporating adjustment for maternal age, infertility, and calendar year. Because information regarding assisted hatching (AH) and HRC for endometrial preparation only became available in 2012, these factors were analysed using the data collected between 2012 and 2017.

Main results and the role of chance

RPOC was diagnosed for 132 deliveries (0.04%), of which 122 (92.4%) followed FET cycles and only 10 (0.01%) followed fresh embryo transfer (ET). No significant risk factors for RPOC were identified using the fresh ET data. For FET cycles, the use of HRC as an endometrial preparation method represented the largest risk factor (adjusted OR, 4.9; 95% CI, 2.0 to 12.3), with RPOC occurring in 0.05% of deliveries following HRC (51/97, 958 deliveries) but in only 0.01% following natural cycles (5/47, 79 deliveries). AH was also associated with a significantly higher risk of RPOC (adjusted OR, 1.9; 95% CI, 1.2 to 3.1), although the risk was lower than that associated with HRC). Subgroup analysis showed that these significant associations of HRC and AH with RPOC were present for transvaginal deliveries, but not deliveries by caesarean section.

Limitations, reasons for caution

The registry lacks important information regarding risk factors for RPOC, such as parity, body mass index, and history of previous uterine surgery. Furthermore, the lower prevalence of RPOC in the present study (0.04%) than in other studies (approximately 1%) suggests the possibility of non-differential misclassification for the outcomes of RPOC.

Wider implications of the findings

Although the possibility of residual confounding factors remains, the present findings suggest that additional care should be taken in the management of patients undergoing vaginal deliveries following FET who have HRC or AH.

Trial registration number

Not applicable
O-156 Embryo-like models: Using 3D gastruloids to understand human development
Authors: Moris N
Published: June 2023

The mammalian embryo develops through coordinated cell fate decisions that enable emerging spatiotemporal and morphogenetic complexity. While much insight into this process has been gained through studying model organisms, including mouse embryos, equivalent experiments are technically and ethically challenging in the human embryonic context. Instead, we use gastruloids: 3-dimensional aggregates of pluripotent stem cells that undergo multilineage differentiation to all three germ layers, polarise their gene expression and exhibit axial organisation that recapitulates many of the features of gastrulation and early organogenesis. By closely examining the dynamics and coordination of cell fate decisions and spatial gene expression organisation, we hope to better understand the regulatory logic behind early developmental events, particularly those that are human-specific. Likewise, by carefully manipulating the environment in which these gastruloids are grown, we can bias the structures towards particular lineages and morphological structures of interest. Doing so allows us to explore many of the principles of early development, and provides an opportunity to probe the mechanisms of biomedically-relevant conditions, such as congenital abnormalities.
O-157 Modelling human early development
Authors: David L
Published: June 2023

Understanding human peri-implantation development is necessary to improve in vitro fertilisation. Technical progress, such as scRNAseq and integrated stem cell models have dramatically improved our ability to understand human peri-implantation development. However, in-depth analysis and systematic validation in human embryos remains necessary to build a reliable reference. Here, we started by integrating pre- and post-implantation scRNAseq embryo datasets to generate a peri-implantation reference, highlighting progression of fates during early human development. Second, we identified the dynamics of genes modules, groups of genes with similar expression pattern. In particular, this highlighted the hierarchy of transcription factor potentially driving cell fate progression. Importantly, we performed prolonged embryo culture to validate by immunofluorescence progression of EPI and TE fates. Moreover, we compared the expression profile of the identified markers in stem cell models. Finally, we used the combination of gene modules to benchmark blastoid models. Altogether, our study paves the way for modelling human peri-implantation development with stem cell models.

Trial registration number

NA

Study funding:

Funding source:
O-166 Distinct molecular signatures of successful sperm in situ
Authors: Chung J J
Published: June 2023

Out of millions of ejaculated sperm, a few reach the fertilization site in mammals. Flagellar Ca2+ signaling nanodomains, organized by multi-subunit CatSper calcium channel complexes, are pivotal for sperm migration in the female tract, implicating CatSper-dependent mechanisms in sperm selection. Here using biochemical and pharmacological studies, we demonstrate that CatSper1 is an O-linked glycosylated protein, undergoing capacitation-induced processing dependent on Ca2+ and phosphorylation cascades. CatSper1 processing correlates with protein tyrosine phosphorylation (pY) development in sperm cells capacitated in vitro and in vivo. Using 3D in situ molecular imaging and ANN-based automatic detection of sperm distributed along the cleared female tract, we demonstrate that spermatozoa past the utero-tubal junction possess the intact CatSper1 signals. Together, we reveal that fertilizing mouse spermatozoa in situ are characterized by intact CatSper channel, lack of pY, and reacted acrosomes. These findings provide molecular insight into sperm selection for successful fertilization in the female reproductive tract.
O-172  Room and directions for improvement in oocyte cryopreservation
Authors: De Los Santos M J
Published: June 2023

Cryopreservation and more specifically oocyte vitrification has become a before and after in the field of Assisted Reproduction Techniques. Despite great efforts to improve slow oocyte freezing protocols, the levels of reproducibility, survival rates and clinical outcomes achieved by oocyte vitrification have never been reached by any of these old approaches.

However, once this barrier was overcome, new challenges emerged. We must reassert ourselves on issues such as the efficacy, efficiency and safety of a technique that is now fully implemented in IVF laboratories around the world.

Continuos monitoring and improvement as part of the quality management system is mandatory, to keep the the standards of qualilty, identify factors that may affect survival rates and look for room for improvemnt and finetune the protocols.

But also it is important to provide answers to women who wish to preserve their fertility for medical or non-medical reasons. They have key questions such as how many oocytes to store, what the survival rate will be after warming, will the cryopreserved oocytes be able to fertilize and develop as good as the fresh counterparts, how does the number of oocytes used affect the cumulative live birth rate?

Also for women undergoing ART, oocyte vitrification may represent a successful strategy. For example, patients with low response or women at risk of ovarian hyperstimulation, the two sides of the coin, may benefit from oocyte cryopreservation. The former, by storing and accumulating oocytes that allow them to obtain success rates comparable to those of normal responders while avoiding the adverse effects of a low response; the latter, by postponing insemination over time, investing in safety.

Yet embryo vitrification can offer good alternatives to oocyte vitrification so both options can be explored and compared

Trial registration number

XXXX
O-174 The transition from fertility to maternity care services - a Royal College of Nursing publication
Authors: Steyn F
Published: June 2023

Study question

Is there a need for guidance for nurses and midwives involved in the delivery of care for patients transitioning from fertility service to maternity services.

Summary answer

There is a potential knowledge gap that exists in the transition of care from fertility to maternity services.

What is known already

Once a patient becomes pregnant through fertility treatment in the UK, they are usually discharged out into NHS maternity care services via their general practitioner. This means that the maternity service staff are often unaware of the time it has taken to conceive, fertility treatments and procedures, fertility medications and emotional trauma that the patient has been through already and may not be aware of some of the complexities surrounding the fertility treatment journey.

Study design, size, duration

A project group of 14 key contributors was invited to be part of the publication that included fertility nurses, midwives, early pregnancy specialist nurses and patient representative members. An initial literature review took place and each person contributed from their specialist area. The project to produce the guidance took 9 months of planning, reviewing and meeting to discuss content with a final publication in September 2022.

Participants/materials, setting, methods

An initial literature review of the project subject did not highlight any existing research or publications in this area. A forum governance bid was submitted to produce a 45 page online resource aimed at fertility nursing staff, early pregnancy care staff and maternity services staff. The key project team contributed from their specialist areas and was reviewed by stakeholder groups.

Main results and the role of chance

Pregnancy following fertility treatment can be an exciting, challenging and anxious time for expectant parents. This projects aim was to primarily raise awareness of possible pathways of care for women and others (their partners/support networks) as they travel through fertility treatment and pregnancy, and how they can best be supported by the health care professionals they encounter along their journey. A 45 page online resource was produced and disseminated to fertility, early pregnancy and maternity staff via stakeholder groups and a webinar to launch the publication.

Limitations, reasons for caution

No limitations identified. The publication is available for all staff working in all three areas and provided guidance for all patient pathways including those from the LGBTQIA community.

Wider implications of the findings

No wider implications.

Trial registration number

Not applicable
P-560 Stigma related to male infertility in China: a scale development and validation study
Authors: Zou F , Lin Y , Hang S , An G , Cao M , Liu J
Published: June 2023

Study question

Is it possible to develop a trustworthy instrument to evaluate the infertile men's stigma and to document fully all methodological steps, including validation?

Summary answer

The Male Infertility Stigma Scale (MISS) has been developed to evaluate the stigma status of infertile men with a good reliability and validity.

What is known already

Infertile men regard childless as a hidden stigma, which influence all the dimensions of their lives and well-being. Most instruments focus exclusively on women and no questionnaires have been directed at infertile men.

Study design, size, duration

A cross-sectional study was conducted to analyse the validity and reliability of MISS. This was a one-centre study in the Center of Reproductive Medicine of the Third Affiliated Hospital of Guangzhou Medical University between January 2019 to May 2019.

Participants/materials, setting, methods

This study was carried out on men (n = 432) with a diagnosis and treatment for male-factor infertility. Item generation and reduction of MISS was formed by combining literature review, interviews of experts and patients, and related scale. Exploratory factor analysis (n = 216) and confirmatory factor analysis (n = 216) were performed to indicate the scale constructs. In addition, reliability analyses including internal consistency and test–retest analysis (n = 18)were carried out. Validity was analyzed by convergent validity and content validity.

Main results and the role of chance

This study developed a 18-item MISS with three dimensions (social marginalization, self-devaluation, psychological insecurity). Exploratory factor analysis indicated that these three dimensions explained 60.14% of total variances.The confirmatory factor analysis showed that the construct of the MISS fitted well with the hypothetical model. The Cronbach's α,split-half coefficient and test–retest correlation coefficient for the whole scale was 0.951, 0.884,and 0.945, respectively. The associations of the MISS with other measure suggested good convergent validity. The Content Validity Index (CVI) was 0.988.

Limitations, reasons for caution

The reliability and validity of the MISS developed in this study were verified only among the infertility men in Guangzhou and the discriminant validity of dimension 3(psychological insecurity) in this survey was a little poor. The convenience sampling method precluded the validity and generalization of the conclusions.

Wider implications of the findings

This study may create an effective evaluation measurement to understand the stigma status of infertile men. Future studies should focus on using the MISS in larger samples with different characterizations, such as different areas, and then taking some measures to help them .

Trial registration number

None
O-227 Viral, bacterial and fungal infections in patients with recurrent miscarriage
Authors: Laven J
Published: June 2023

Miscarriages occur in 15% of clinically recognized pregnancies in the general population. Miscarriage has several physical and psychological consequences and might be a risk marker of severe obstetrical complications during the following pregnancies and various long-term pathological conditions, such as venous thromboembolism and cardiovascular diseases. Up to 80% of reproductive losses occur in the first trimester. Miscarriage may be caused by chromosomal abnormalities, antiphospholipid syndrome and other thrombophilia’s, immune and endocrine disorders as well as inflammation. However, in up to 50% of cases, the cause of the miscarriage remains unknown.

The microbiome consists of microbes that are both helpful and potentially harmful. Most are symbiotic and some, in smaller numbers, are pathogenic. In a healthy body, pathogenic and symbiotic microbiota coexist without problems. But if there is a disturbance in that balance brought on by infectious illnesses, certain diets, or the prolonged use of antibiotics or other bacteria-destroying medications dysbiosis occurs, stopping these normal interactions. In this presentation the role of the microbiome as well as the virome in recurrent miscarriage will be discussed. Possible mechanism of action will be reviewed and, if available, treatment of a perturbed microbiome will be presented.

Trial registration number

XXXX
O-228 Dysbiosis and reproduction
Authors: Svarre Nielsen H
Published: June 2023

Bacteria, viruses, and fungi are collectively known as our microbiome and constitute approximately 1-2% of our body weight. The microbiome is closely associated with our health. Dysbiosis refer to a suboptimal microbiome composition and while gut dysbiosis has been extensively investigated there is far less studies on how the reproductive microbiome is associated with reproductive health. This presentation will cover definitions, methods, and give an overview of the studies that have investigated the association between gut, vaginal and endometrial microbial dysbiosis and the association with implantation and early pregnancy. Possible mechanisms and treatment options will also be adressed.
O-234 Constant antioxidant supplementation increases blastocyst formation from oocyte donors
Authors: González Martínez J , Ramirez-Dominguez L B , Jimenez Medina I , Matamoros-Volante A , Villar-Muñoz L G , Rambhatla A , Agarwal A , Maldonado I
Published: June 2023

Study question

Does constant supplementation of antioxidants to the culture media increase blastocyst formation from oocyte donors?

Summary answer

The constant supplementation of antioxidants to the culture media increases blastocyst formation from oocyte donors

What is known already

The use of a combination of various antioxidants in embryo culture media has recently been investigated to explore the potential benefit for embryo development and clinical outcomes. However, the concentration of antioxidants added to the culture has only been determined by its effect. In this study, we performed a repeated antioxidants supplementation to resemble a physiological oxidation reduction environment. Therefore, we investigated the effect of antioxidants added every 12 hours to the culture media on blastocyst formation and expansion in oocyte donors.

Study design, size, duration

This prospective study was conducted at CITMER, Mexico from April 2020 to November 2022.We included a total of 258 recipients from oocyte donors undergoing IVF/ICSI.

Participants/materials, setting, methods

A total of 2403 zygotes were divided into 4 groups and cultured in the following conditions until blastocyst stage: Group 1A: 563 zygotes 20% O2 with antioxidants every 12 hours, Group 1B: 1109 zygotes 20% O2 with antioxidants at the beginning, Group 2A: 339 zygotes 5% O2 with antioxidants every 12 hours, Group 2B: 392 zygotes 5% O2 with antioxidants at the beginning. Embryo development was assessed. Odds ratio and Fisher test were performed. p < 0.05=significant

Main results and the role of chance

For both oxygen tensions, we found a significant increase in the total blastocyst formation rate (day 5+day 6) when antioxidants were added repeatedly (1A: 54.7% vs 1B: 45.9%, p = 0.0007*; 2A: 58.7% vs 2A: 46.9%, p = 0.001*). In addition, the rate of expansion at days 5 + 6 was also significantly higher than in the groups where the antioxidants were added only at the beginning of the culture (1A: 35.9% vs 1B: 29.9%, p = 0.01*; 2A: 41.3% vs 2A: 31.6%, p = 0.006*).

Limitations, reasons for caution

Given this is a sibling zygotes study, patients are their own controls.

Wider implications of the findings

Constant supplementation of antioxidants to the culture media increases blastocyst formation from oocyte donors as well as the expansion rate, which may significantly improve clinical outcomes.

Trial registration number

06162020-aox04
P-465 Effect of male age on the outcome of frozen embryo trnasfer cycle in women over 40 years
Authors: Shin S Y , Koo H S , Kim J H , Kim J H , Kwon H , Park C , Choi D H , Shin J E
Published: June 2023

Study question

Does male age affect the outcome of in vitro fertilization in women over 40?

Summary answer

Advanced male partner's age is associated with decreased pregnancy rate, implantation rate and ongoing pregnancy/live birth rate.

What is known already

Fertility is known to have the greatest correlation with female age. Older women have a relatively lower pregnancy rate and higher miscarriage rate. It is also widely known that male partner's age is associated to pregnancy rate with increased sperm DNA fragmentation and decreased sperm motility. Age of marriage is delayed both male and female partners, assisted reproductive techniques are often conducted in women over 40 years. The effect of male age on IVF/ICSI outcomes on women over 40 is poorly explored.

Study design, size, duration

This is a retrospective cohort study analysed 1046 cycles of couples with an age of 40 or more of female partners and their male partners, performed at a single IVF center of university hospital between 2019 and 2022. The primary outcome was ongoing live birth and secondary outcomes were clinical pregnancy and miscarriage.

Participants/materials, setting, methods

Couples of primary/secondary infertility with female partner age over 40 years who underwent frozen-embryo transfer cycles were selected. couples who collected their sperm from TESE/TESA were excluded.

Main results and the role of chance

We decided the male partner's age in three groups, age less than 40, 41-45, and age over 45. There was a negative effect of male age on ongoing live birth and clinical pregnancy rate.(20.0%, 10.3%, 10.9%, p < 0.001, 33.7%, 28.4%, 19.9%, p = 0.017). And we sub-analyzed ongoing live birth rate and clinical pregnancy rate into female age group(female age of 40, 41-42, and over 43). The ongoing pregnancy/live birth rate and clinical pregnancy rate were negatively associated with male partner's age especially in female age group of over 43 years.

Limitations, reasons for caution

This study is limited to the information on confounding factors. The study may also be limited due to its selection criteria.

Wider implications of the findings

This study provides information regarding IVF/ICSI outcomes on women over 40 years of age

Trial registration number

not applicable
O-245 Monitoring oxytocin release in vivo during female sexual behavior using a genetically encoded sensor
Authors: Wang P
Published: June 2023

Study question

To investigate if the release of oxytocin (OT) in the medial prefrontal cortex (mPFC) fluctuates during discrete phases of female sexual behavior.

Summary answer

Using a highly sensitive OT-specific genetically encoded sensor, we have recorded behavioral phase-specific OT release in mPFC in freely moving mice.

What is known already

OT has been reported to participate in the regulation of sexual behavior of both male and female mice. OT activated mPFC neurons by increasing their firing activity. Loss of function studies indicated that pharmacological or genetic ablation of OT signaling in mPFC largely disrupts female sociosexual interest in male mice. OT action is indispensable in female sociosexual behavior, however, its release dynamics have never been recorded before due to technical difficulties. We have developed a highly sensitive OT-specific G-protein-coupled receptor activation-based sensor (OT1.0), and recorded intracellular OT release in behaving mice on the millisecond time-scale.

Study design, size, duration

Eight C57BJ/6N mice were divided into two groups (n = 4 per group). Intracellular viral transduction with OT1.0 or OT1.0mut vectors was administrated to each group. After viral transduction, 3 weeks were waited to allow sufficient viral expression.

Participants/materials, setting, methods

After anesthetization, AAVs encoding hSyn-OT1.0 or hSyn-OT1.0mut were injected into the left mPFC of adult female wild-type C57BJ/6N mice; Optical fibers were implanted into the mPFC 3 weeks after AAV injection. The animal’s sexual behaviors were recorded and annotated, while a fiber photometry system was used to record fluorescence signals in the mPFC, using a 470-nm laser at 50 μW for OT1.0 or OTmut.

Main results and the role of chance

To investigate the dynamics of OT release in mPFC during female sexual behavior, we recorded OT1.0 fluorescence in behaving female mice using fiber photometry. In mPFC of female mice, increases in OT1.0 fluorescence were first observed during the sniffing stage (with rise and decay time constants (T1/2) of 0.4 s and 1.4 s, respectively ). After ejaculation of male mice, mPFC OT1.0 signals of the female mice increased significantly with rise and decay time constants (T1/2) of 0.5 s and 1.5 s, respectively. As a negative control, fluctuation of fluorescence was not observed during any phase of sexual behavior in mice expressing OT1.0mut, suggesting the specificity of the signals measured in mice expressing OT1.0.

Limitations, reasons for caution

The OT dynamics in mPCF during female sexual behaviors are only recorded in mice. Clinical trials and imaging studies are required to substantiate the therapeutic role of OT in human subjects.

Wider implications of the findings

This study is likely to deepen our understanding of the role of OT in modulating female sociosexual behavior, which provides more evidence suggesting OT’s potential therapeutic potential in treating sexual dysfunctions.

Trial registration number

not applicable
O-263 Effect of clindamycin and a live biotherapeutic containing lactobacilli on the reproductive outcomes of IVF patients with abnormal vaginal microbiota: a double-blind, placebo-controlled multicentre trial
Authors: Haahr T , Jensen J S , Alsbjerg B , Elbaek H O , Laursen R , Brix M , Mikkelsen A , Pedersen T , Praetorius L , Pinborg A , Freiesleben N , Humaidan P
Published: June 2023

Study question

Does treatment of abnormal vaginal microbiota improve the reproductive outcomes of IVF patients?

Summary answer

Data is being analysed and will be presented at ESHRE 2023.

What is known already

An increasing number of studies reported an association between abnormal genital tract microbiota and adverse reproductive outcomes in IVF patients. One hypothesis could be that vaginal microbiota ascend to the endometrium where the microbiota hampers implantation. To the best of our knowledge, this is the first study powered to investigate causality between abnormal genital tract microbiota - in this study defined by a bacterial vaginosis like vaginal microbiota - and clinical pregnancy rate in IVF patients.

Study design, size, duration

Double-blind, placebo-controlled multicentre trial in IVF patients diagnosed with abnormal vaginal microbiota and subsequently randomised into three parallel groups 1:1:1. The first group received clindamycin 300 mg ×2 daily for 7 days followed by vaginal Lactobacillus crispatus until the clinical pregnancy scan. The second group received clindamycin and placebo, whereas the third group received placebo/placebo. A total of 1518 patients were screened, and 338 patients were randomised. The study duration was from 2017 to 2023.

Participants/materials, setting, methods

IVF patients with any cause of infertility embarking on their first, second or third IVF stimulation cycle or embryo transfer were approached for inclusion. At a minimum 12 days prior to embryo transfer, patients were screened for abnormal vaginal microbiota defined by a qPCR assay, targeting high quantitative loads of Fannyhessea vaginae and Gardnerella spp. Patients were excluded if they had intrauterine malformations like polyps, septum, and fibroma.

Main results and the role of chance

Data and safety monitoring board has decided not to open the randomization code yet. The final dataset is being completed. Data is being analysed and will be presented at ESHRE 2023.

Limitations, reasons for caution

Data is being analysed and will be presented at ESHRE 2023.

Wider implications of the findings

The present drug intervention study used clindamycin and a live biotherapeutic containing Lactobacillus crispatus. The results of the study could have a worldwide important clinical impact on daily IVF practice as currently there is no evidence that screening and treating IVF patients with abnormal vaginal microbiota improves the reproductive outcome.

Trial registration number

EudraCT 2016-002385-31
O-264 Vaginal Microbiota Transplantation (VMT) for treatment of vaginal dysbiosis without the use of antibiotics – A Randomized Controlled Trial in healthy women with vaginal dysbiosis
Authors: Wrønding T , Mortensen B , Vomstein K , Westh H , Munk Petersen A , Ingdam Halkjær S , Svarre Nielsen H
Published: June 2023

Study question

Can vaginal microbiota transplantation with shotgun-verified eubiotic vaginal microbiome over three menstrual cycles, convert vaginal dysbiosis to eubiosis in healthy women?

Summary answer

The RCT is ongoing until it is by March 2023. Results will be ready for presentation at EHSRE conference.

What is known already

Vaginal dysbiosis covers imbalances in the vaginal flora, caused by the composition of bacteria, viruses, and vaginal fungi. A large proportion of women who have vaginal dysbiosis do not experience any symptoms. Dysbiosis occurs in about 16-20% of all women. Vaginal dysbiosis is associated with infertility, euploid pregnancy loss, preterm labour or bacterial vaginosis. Treatment of vaginal dysbiosis consists of antibiotic treatment, and/or probiotics. Vaginal transplantation with eubiotic vaginal bacterial flora in combination with antibiotics has successfully been performed in four out of five recipients in an earlier study, but no study has been performed without use of antibiotic pretreatment.

Study design, size, duration

Randomized, controlled, double-blinded trial with a randomization ratio 3:1 to receive either a eubiotic microbiome transplant or placebo. 320 healthy women between 18 and 40 years, was enrolled for screening of vaginal dysbiosis. 30 donors with a eubiotic vaginal microbiome and 48 recipients with a dysbiotic microbiome were identified. The trial began in June 2021 and will end in March 2023

Participants/materials, setting, methods

Vaginal microbiome composition was assed by next-generation ShotGun sequencing. To qualify as donor bacterial DNA from a vaginal swab had to show a bacterial composition of at least 80% lactobacilli and less than 5% pathogenic bacteria. To qualify as recipient vaginal microbiome composition should be with at least 20% pathogenic bacteria and no more than 10% lactobacilli. The recipient could have up to three attempts of VMT treatments with a follow-up period of 6 months.

Main results and the role of chance

We expect the RCT to end in March 2023, and the results of this trial will be presented at the ESHRE annual meeting . If we can show engraftment of a eubiotic microbiome transplant without the use of pre-treatment with antibiotics it could be a potential treatment of vaginal dysbiosis.

Limitations, reasons for caution

As this is the first VMT without antibiotic pretreatment we did not have reliable data for our power calculation and a negative result may be due to lack of statistical power.

Wider implications of the findings

Effective treatments for vaginal dysbiosis are urgently needed and VMT may be one such treatment strategy.

Trial registration number

NCT04855006
O-283 Impact of metabolic syndrome and effect of treatment on male and female reproductive capacity
Authors: Legro R
Published: June 2023

Obesity is associated with sub fertility and multiple adverse pregnancy outcomes including miscarriage and later pregnancy complications such as pre-eclampsia and gestational diabetes. Weight loss preconception is recommended for women with obesity and infertility. The etiology of infertility may affect the response to weight loss with WHO type 2 patients more likely to ovulate spontaneously or with oral medications after modest weight loss. The evidence for weight loss improving fertility outcomes is weak for women with unexplained infertility. There may also be unrecognized harms to weight loss including increased risks of miscarriage and weight rebounding excessively during pregnancy. Unique hurdles to weight loss interventions including the types, duration and best comparators will be discussed. Blanket recommendations that weight loss improves fertility and pregnancy outcomes should be avoided. Other factors such as age and ovarian reserve should be factored into any preconception weight loss strategies