bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract
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
O-292 Does ovulation trigger enhance live birth in a natural cycle for frozen embryo transfer: A randomized controlled trial
Authors: Huberlant S , Ranisavljevic N , Bonneau M , Rougier N , Serand C , Anahory T , Hamamah S 
Published: June 2023

Abstract

Study question
Does ovulation trigger enhance pregnancy rate in a natural cycle (NC) for frozen embryo transfer (FET)?

Summary answer
Pregnancy rates after a FET are similar in a natural cycle with detection of a spontaneous LH surge or with a triggered ovulation.

What is known already
Several studies have explored whether one approach might appear to be more beneficial in terms of pregnancy or live birth rates, but with inconsistent results. Thus, the best protocol to identify the time of ovulation in NC and to plan the FET is still undefined.

Study design, size, duration
This was a bicentric, two-arm, randomized, controlled and open-label trial, including 108 patients for 18 months. In the spontaneous-NC group, the LH surge was defined as a rise of the serum LH level at least three times above the basal LH serum value with a serum progesterone level three days after the LH surge above 3 ng/mL.

Participants/materials, setting, methods
Patients included were aged 18- to 39-year-old, had regular cycles and were planned for an autologous frozen day-5 blastocyst transfer in a NC. They did not have endometriosis stage AFSr 3 nor 4 nor adenomyosis. Fifty-four patients per group were included. In the modified-NC group, a spontaneous LH surge was observed in 16 women before the hCG-trigger could be administrated: they were re-allocated to the spontaneous-NC for the per-protocol (PP) analysis.

Main results and the role of chance
Patients characteristics were comparable in both groups. Pregnancy rates were similar in the spontaneous-NC and the modified-NC group in the intention-to-treat (ITT) (41.3 versus 37.8% respectively, p = 0.85) and in the PP analysis (39.3% versus 40% respectively, p = 0.9). Ongoing pregnancy, miscarriage and live birth rates were also similar. Significantly more visits were needed in the spontaneous-NC (3.4 ± 0.81 versus 2.59 ± 1.0, p &lt; 0.0001 in the ITT analysis and 3.18 ± 0.93 versus 2.63 ± 1.03, p = 0.0064 in the PP analysis).

Limitations, reasons for caution
Due to group redistribution (spontaneous LH surge before hCG trigger), the number of subjects in the modified-NC group is low for the PP analysis. This may reduce the power of the trial which may fail to detect a small difference.

Wider implications of the findings
The results reinforce previous data that showed similar efficacy of the s-NC and the m-NC. This allows the patient to choose from several options depending on her preference.

Trial registration number
NCT03428165
O-301 Can advanced sperm selection techniques improve blastocyst euploidy rate of abnormal sperm DNA fragmentation cases to the level of normal ones; prospective randomized controlled trial
Authors: Hasanen E , Hozayen M , Elshimy A , Hazem Y , Alkhader H , Zaki H 
Published: June 2023

Abstract

Study question
To compare PGT-A outcomes of Physiological ICSI (PICSI) and magnetic activated cell sorting (MACS) sperm selection techniques to a control of normal sperm DNA fragmentation.

Summary answer
PGT-A outcomes did not differ between using normal sperm DNA fragmentation semen to the semen processed by PICSI or MACS.

What is known already
Sperm DNA fragmentation can negatively affects pre-implantation embryo development in all stages after ICSI. Advanced sperm selection techniques like PICSI and MACS are thought to be efficient to improve fertilization, cleavage, and blastocyst formation rates in cases with abnormal SDF. It has become evident that a blastocyst's aneuploidy is not only contributed by the oocyte,but can also be caused by the sperm.The relation between sperm selection techniques such as PICSI or MACS and blastocyst euploidy is not investigated yet.

Study design, size, duration
A prospective randomized controlled trial of 351 ICSI cycles in a private fertility center, from October 2019 to December 2022. Cases were included in the study if: female had ≥5 MII oocytes, male had abnormal sperm DNA fragmentation (SDF) index (&gt;20% by TUNEL assay), all blastocysts (≥4BB) had trophoectoderm biopsy.

Participants/materials, setting, methods
Included cases were randomized on the day of ICSI to PICSI or MACS group, along with a control arm of cases with normal SDF needed for comparison. PGT-A was done using Illumina platform (Miseq), and the results were reviewed by artificial intelligence (Cooper Surgical). Cases were categorized according to the female age into 2 subgroups(&lt;35, and &gt; 35 years). Statistical analysis of all pre-implantation embryo development parameters and PGT-A results were done using SPSS.

Main results and the role of chance
We found no significant differences between the female age, male age, count, motility, SDF, no. mature oocytes between the studied groups.

Limitations, reasons for caution
The results included all pre-implantation embryo parameters but, subsequent post-implantation events like implantation, pregnancy and miscarriage rates will add more data about the competency of the resulted embryos.

Wider implications of the findings
The usage of advanced sperm selection techniques like PICSI or MACS has showed comparable results to that of normal SDF cases, through eliminating the adverse effects of SDF on ICSI and PGT-A outcomes.

Trial registration number
NCT05494216
P-004 Sperm concentration of less than 1 million/ml in Y microdeletion patients may affect ICSI clinical outcomes: a propensity score matching analysis
Authors: Zhang H 
Published: June 2023

Abstract

Study question
To investigate which semen parameter in AZFc microdeletion patients affect the intracytoplasmic sperm injection (ICSI) clinical outcomes.

Summary answer
AZF-microdeletion caused oligospermia affected the ICSI clinical outcome when the sperm concentration is less than 1x106/ml.

What is known already
To reduce the impact of female factors on clinical outcomes, this study employed a propensity score matching analysis to retrospectively analyze the laboratory and clinical pregnancy results of patients with AZFc deletion who underwent ICSI.

Study design, size, duration
A propensity score matching analysis in a retrospective ICSI cohort of 99 AZFc microdeletion patients and 198 oligospermia patients without AZFc microdeletion.

Participants/materials, setting, methods
Patients/Animals: oligospermia patients with or without AZFc microdeletion undergoing ICSI.
Intervention: ICSI for couples attempting conception.
Main Outcome Measures: Outcomes included normal fertilization rate, high-quality embryo rate on Day 3, clinical pregnancy rate, abortion rate, and live birth rate.

Main results and the role of chance
Patients with AZFc microdeletion had a lower normal fertilization rate (69.55%) and Day-3 high-quality embryo rate (50.73%) than the control group (77.17% and 58.44% respectively, p = 0.000). There was no significant difference between the two groups in the clinical pregnancy rate (67.21% vs. 68.16%, p &gt; 0.05), miscarriage rate (13.41% vs. 12.54%, p &gt; 0.05), and live birth rate (58.20% vs. 59.18%, p &gt; 0.05). Subgroup analysis showed that the fertilization rate, high-quality embryo rate, clinical pregnancy rate, and live birth rate were comparable between the AZFc-microdeletion group and the control groups when the sperm concentration was no less than 106/ml. Interestingly, when the sperm concentration was below 1x106/ml, the fertilization rate (65.60% vs. 73.79%, p = 0.001) and high-quality embryo rate (47.74% vs. 58.48%, p = 0.001) in the AZFc-microdeletion group were significantly lower than those in the control group. Furthermore, the clinical pregnancy rate and live birth rate were lower, while the miscarriage rate was higher in the AZFc-microdeletion group; however, the statistical difference is not significant.

Limitations, reasons for caution
the retrospective study was limited, and the cases of obtaining testicular sperm by microsurgery were not included, so the results may be biased, and prospective studies with larger sample size need to be designed for further confirmation.

Wider implications of the findings
We recommend screening for AZF in Chinese male infertile population when sperm concentration is below 5X106/ml.The male physician should advise the patient to undergo genetic counseling before pregnancy assistance, and choose whether to choose PGT assisted pregnancy according to the patient's wishes.

Trial registration number
not applicable
P-031 Presence of HPV 16 and HPV 18 in spermatozoa and embryos of mice
Authors: Mastora E , Zikopoulos A , Evangelou T , Georgiou I , Zikopoulos K 
Published: June 2023

Abstract

Study question
The clarification of Human Pappiloma Virus (HPV) internalization in spermatozoa and early preimplantation embryos.

Summary answer
Spermatozoa are able to internalize constructs of cloned high risk HPV viruses either as integrated or as episomal DNA.

What is known already
Human Pappiloma Virus (HPV) is a non-enveloped, circular, double stranded DNA virus. Persistent infection with oncogenic HPV genotypes triggers HPV DNA integration into the host genome, eventually leading to chromosomal damage accumulation and genome destabilization in infected cells. Living spermatozoa of almost all species are able to take up spontaneously exogenous DNA and internalize a part of it into their nucleus.

Study design, size, duration
Taking into account the capability of sperm cells to integrate exogenous DNA into their genome, we sought to clarify HPV internalization into sperm genome. A total of 26 sperm samples were studied. The control group included 97 embryos. As for the HPV 16 and HPV 18 group, a total of 89 embryos were studied.

Participants/materials, setting, methods
Sperm was incubated with plasmid vectors containing the complete genome of human HPV 16 and HPV 18 tagged with the green fluorescent protein (GFP) gene, to investigate HPV 16 and HPV 18 integration in mouse spermatozoa. Oocytes were in vitro fertilized with preincubated spermatozoa to investigate HPV 16 and HPV 18 potential transfer to mouse embryos.

Main results and the role of chance
Spermatozoa were able to internalize constructs of cloned high-risk HPV either as integrated or as episomal DNA. Constructs of cloned HPV can also be transferred to mouse embryos, through in vitro fertilization of the oocytes by mouse spermatozoa.

Limitations, reasons for caution
Viral DNA integration into the sperm nucleus could not be directly demonstrated, but nevertheless integration is evident by GFP gene expression.

Wider implications of the findings
This study highlights the possibility of viral DNA transmission to the early embryo via sperm, opening new perspectives on the effect of HPV in reproductive cells. HPV persistence may impair sperm parameters, suggesting caution in the use of these cells for assisted reproduction techniques or sperm banking.

Trial registration number
Not applicable
P-076 Sperm selection by thermotaxis: a novel technique to enhance assisted reproductive technologies’ outcomes
Authors: Guleresi K , Santos Ribeiro S , Reis Soares S , Nunes Gouveia S , Gómez Alves S 
Published: June 2023

Abstract

Study question
Does sperm selection by thermotaxis increase competent spermatozoa count?

Summary answer
When compared to capacitation alone, our findings suggest an improvement in the availability of high quality spermatozoa after thermotaxis in terms of motility and morphology.

What is known already
Thermotaxis is a natural mechanism that guides competent spermatozoa through the female genital tract. It has been previously shown that, in the mice model, thermotaxis may improve pregnancy rates following in vitro fertilization (IVF). However, thus far, there is little information to support these findings with human spermatozoa.

Study design, size, duration
A prospective single-center paired pilot analysis was performed between April 2021 and April 2022 including 21 male individuals, 12 of whom were sperm donors and 9 who were patients with asthenozoospermia (defined as &lt; 32% progressive sperm motility).

Participants/materials, setting, methods
Only otherwise healthy men between 18 and 45 years old were included. All subjects performed a sperm collection at the clinic after a maximum of 3 days following the last ejaculation. Sperm concentration, motility, morphology (all using the WHO 2010 criteria) and DNA fragmentation (TUNEL) were assessed within the same sample at three time-points: fresh sample, after capacitation and following the extra thermotaxis procedure.

Main results and the role of chance
The average age of the participants was 34.9 ± 6.6 years old. The mean sperm concentration was 66.9 ± 39.1 million/mL (91.4 ± 26.1 in the donor subset (group A) versus 34.2 ± 28.0 in the asthenozoospermia patient (group B) subgroup). The median sperm motility was 62.0% (66.5% in group A versus 24.0% in group B). The mean sperm morphology was 7.2% (7.7% in the group A versus 6.7% in the group B). When compared to the sample in which only capacitation was performed, a statistically significant increase in spermatozoa motility (52.10% vs 82.14%, p &lt; 0.05) and normal morphology (11% vs 16%, p &lt; 0.05) was observed following capacitation plus thermotaxis. Conversely, DNA fragmentation did not vary significantly within the capacitated samples before and after thermotaxis (13% vs 14%).

Limitations, reasons for caution
The present pilot study is based on a limited number of participants and should be extended further.

Wider implications of the findings
The combination improvement in terms of morphology and progressive motility following thermotaxis may optimize selection of sperm cells and ultimately increase pregnancy rates after IVF. In the light of our experience, it is possible that this technique, which does not require high-end equipment, may increase the usable competent spermatozoa count.

Trial registration number
NCT04849156
P-083 Associations of sperm epigenetic aging with semen parameters among men from the U.S. general population
Authors: Pilsner R , Sawant S , Houle E , Oladele O 
Published: June 2023

Abstract

Study question
Is sperm epigenetic aging (SEA) associated with semen parameters among men in the general population?

Summary answer
While SEA was not associated with general semen parameters, advanced SEA was positively associated with sperm head defects such as length, perimeter, and pyriforms.

What is known already
We have previously shown that advanced SEA was strongly associated with longer time-to-pregnancy among couples in the general population.

Study design, size, duration
A population-based prospective cohort study of couples discontinuing contraception to become pregnant recruited from 16 US counties from 2005 to 2009.

Participants/materials, setting, methods
Sperm DNA methylation from 379 semen samples were assessed via Illumina EPIC Array and SEA was estimated using Super Learner, an ensemble machine learning algorithm. Linear regression models were employed to examine the associations between semen parameters and SEA adjusting for male age and current smoking.

Main results and the role of chance
None of the general semen characteristics such as count, concentration, motility or morphology were associated with SEA. However, several sperm head parameters were positively associated with SEA including length (β = 3.6, 95% confidence internal (CI): 1.01 - 6.23; p = 0.007); perimeter (β = 4.04, 95% CI: 0.1 – 0.05; p = 0.045) and pyriforms (β = 0.29, 95% CI: 0.1-0.49; p = 0.003). SEA was also inversely related to sperm elongation factor (β = -2.9, 95% CI: -4.8 - -1.1; p = 0.002).

Limitations, reasons for caution
This prospective cohort study consisted primarily of Caucasian men and women and thus large diverse cohorts are necessary to confirm the associations between SEA and sperm head defects in other races/ethnicities.

Wider implications of the findings
These data suggest that advanced sperm epigenetic aging may be related to improper sperm head condensation during spermatogenesis.

Trial registration number
N/A
P-232 Beyond 12 months, blastocyst cryostorage duration in close system affects live birth rate: a monocentric retrospective study
Authors: Yahyaoui A , Barry F , Anav M , Loup V , Mullet T , Anahory T , Brouillet S , Hamamah S 
Published: June 2023

Abstract

Study question
In order to evaluate the effect of blastocyst cryopreservation duration on live birth rate (LBR).

Summary answer
Blastocyst cryopreservation duration negatively affects live birth rate when blastocysts are vitrified in complete close system for more than 12 months.

What is known already
With the development of embryo vitrification, frozen-thawed program embryo transfer has been widely used in the past decade. However, the association between cryopreservation duration and frozen blastocyst transfer outcomes are limited. So far, very few studies have provided evidence on the relationship between blastocyst storage duration and LBR.

Study design, size, duration
This monocentric retrospective study included 1267 women (n = 1462 cycles) who underwent single frozen blastocyst transfer. Duration of vitrification in close system was categorized into five groups included 2144 frozen blastocysts (Day 5/6) : &lt;3 months (n = 417; mean female age = 32.6 ± 4.74y), 3-6 months (n = 596; mean female age = 33.2 ± 4.96y), 6-12 months (n = 440; mean female age = 33.4 ± 4.83y), 12-36 months (n = 512; mean female age = 32.6 ± 4.75y), and &gt;36 months (n = 179; mean female age = 31.1 ± 3.90y).

Participants/materials, setting, methods
Clinical pregnancy and live birth outcomes were compared between the cohorts stratified according to blastocyst cryostorage duration. A binary multivariate logistic regression was performed, adjusting for confounders: female age at vitrification, male age, ART technique (IVF or ICSI) and endometrial preparation protocol (spontaneous, substituted and stimulated FET cycle).
Multivariable analysis was used to assess the association between crystorage duration of vitrified blastocyst and LBR. All frozen blastocyst transfers were realized in spontaneous, substituted or stimulated cycles.

Main results and the role of chance
After multivariable analysis, live birth rate was significantly different depending on blastocyst cryostorage duration (all groups combined) (p = 0.033): live birth rate was significantly lower when blastocyst cryostorage duration was between 12-36 months (OR 0.740 IC95%[0.558; 0.981] p = 0.036) and beyond 36 months (OR 0.674 IC95%[0.456; 0.986] p = 0.044) compared to less than 3 months of blastocyst cryostorage duration. However, no significant impact of blastocyst cryostorage duration was observed on clinical pregnancy rate (p = 0.52).

Limitations, reasons for caution
Our study was limited by its retrospective design with restricted samples.

Wider implications of the findings
This study provides new findings on the effect of blastocyst cryostorage duration with a significant impact on LBR beyond 12 months of vitrification in close system. However, it’s crucial to confirm that cryostorage duration doesn’t lead to adverse obstetric and perinatal outcomes after vitrified blastocyst transfer.

Trial registration number
not applicable