bluuebunny/crossref_metadata_2025_split huggingface dataset:
O-238 Preterm birth after recurrent pregnancy loss: A systematic review and meta-analysis
Authors: Wu C , Nichols K , Carwana M , Nicholas C , Maratta C 
Published: August 2021

Abstract

Study question
What is the impact of recurrent pregnancy loss on the risk of preterm birth?

Summary answer
Women with RPL were found to be at increased odds of having preterm deliveries (&lt;37 weeks gestation) in their subsequent live pregnancies.

What is known already
Recurrent pregnancy loss (RPL) occurs in up to 5% of all women with miscarriages. The emotional, physical, and financial burden associated with RPL is unequivocal, and over the years, much research has gone into the management of RPL. However, relatively little is known about the perinatal outcomes following RPL. Past research in the area reports conflicting data on the association between RPL and preterm birth (PTB) in a subsequent pregnancy.

Study design, size, duration
A systematic search was performed across thePubMed, EMBASE and Google Scholar databases for relevant studies published up until October 2020. Observational cohort and case-control studies comparing the risk of preterm birth (PTB) among women with and without a history of RPL were included. Effect estimates were pooled using a DerSimonian and Laird random-effects meta-analysis model. Study appraisal was performed using the Newcastle-Ottawa scale.

Participants/materials, setting, methods
We included studies where the study population consisted of women with a history of RPL (defined as 2 or more pregnancy losses), where the comparator group consisted of women without a history of RPL, and where the outcomes assessed included PTB (defined as birth prior to 37 completed weeks gestation). Two reviewers independently extracted data in duplicate. Publication date, population, exposure and outcome data were extracted.

Main results and the role of chance
A total of 12 retrospective observational studies met inclusion criteria, and were included in the systematic review and meta-analysis (N = 37,046 women with a history of RPL). Incidence of PTB among the RPL groups ranged from 5.8% to 19.6%, and from 1.5-14.0% in the non-RPL groups. A pooled OR of 1.59 with 95% CI 1.40-1.80 was observed in our random-effects meta-analysis with an I2 of 84%. Subgroup analyses were completed for the pooled risk of only 2 RPL (pooled odds ratio [OR] 1.35; 95% CI 1.08-1.69; I2=84.7%); ≥2 RPL (pooled OR 1.42; 95% CI 0.91-2.22; I2=68.9%); and ≥3 RPL (pooled OR 1.86; 95% CI 1.51-2.29; I2=79.5%).

Limitations, reasons for caution
Inconsistent adjustment for confounders and significant between-study heterogeneity were noted in this study.

Wider implications of the findings
Despite significant heterogeneity among studies, we found that women with a history of RPL had significantly higher odds of delivering preterm infants in their subsequent pregnancies.

Trial registration number
CRD 224763
P–003 Transposon insertion profiling by sequencing (TIPseq) identifies novel LINE–1 insertions in human sperm
Authors: Berteli T , Wang F , McKerrow W , Navarro P , Fenyo D , Boeke J , Kohlrausch F , Keefe D 
Published: August 2021

Abstract

Study question
Do human sperm contain novel LINE–1 insertions and are they affected by paternal age?

Summary answer
Human sperm contain novel LINE–1 insertions. Their location or number are not affected by paternal age.

What is known already
LINE–1 comprises 17% of the human genome and some LINE–1s are the only autonomous retrotransposons in humans. Retrotransposons influence genomic instability and/or regulation if new retrotransposition events disrupt coding or regulatory regions in the host genome. Demethylation during germ cell development de-represses retrotransposons. Advanced paternal age is associated with genomic instability. Previously we showed that sperm LINE–1 copy number decreases with paternal age. We hypothesize that human sperm exhibit de novo retrotransposition and that sperm from older men contain increased novel LINE–1 insertions.

Study design, size, duration
Cross-sectional case–control study with semen samples collected between February to July 2020.

Participants/materials, setting, methods
Normospermic sperm samples (n = 10; 5 &lt;35 years old and 5 ≥45 years old) obtained from consenting men undergoing IVF at NYU Fertility Center were submitted to a novel method, single cell Transposon Insertion Profiling by Sequencing (scTIPseq) to identify and map LINE–1 insertions in human sperm. TIPseqHunter, a custom bioinformatics pipeline, compared the architecture of sperm LINE–1 to known LINE–1 insertions from the European database of human specific LINE–1 (L1Hs) retrotransposon insertions in humans (euL1db).

Main results and the role of chance
TIPseq identified 17 novel insertions in sperm, 8 from older (≥ 45 years) and 9 in younger men (&lt;35 years). New insertions were mainly intergenic or intronic, including AC007402 (2/10), TMEM163 (2/7), CTTNBP2NL (3/5), AC107023 (3/3), TMC2 (2/19), MacroD2 (2/6), RAB3C (3/4), LINC02664 (1/1), AC079052 (2/3) and AC017091 (4/4). One novel insertion (&lt;35 years old) hits a known regulatory element. Only one sample (≥ 45 years old) did not exhibit any new insertion. The location or number of novel insertions did not differ by paternal age.

Limitations, reasons for caution
The small sample-size and use of normospermic specimens limit interpretation of paternal age effect on LINE–1. Besides, the novel insertions could be polymorphic sites that have low allele frequency and thus have not yet been described.
Wider implications of the findings: This study for the first time reports novel LINE–1 insertions in human sperm, demonstrating that scTIPseq method is a feasible technique, and identifying new contributions to genetic diversity in the human germ line. Further studies are needed to evaluate the impact of these insertions on sperm function.

Trial registration number
Not applicable
P–007 Effect of swim-up on sperm morphology
Authors: Ganeva R , Parvanov D , Handzhiyska M , Stamenov G 
Published: August 2021

Abstract

Study question
To evaluate the effect of swim-up on the percentage of certain morphological defects in the semen population

Summary answer
Swim-up preparation led to significantly lower percentage of spermatozoa with cytoplasmic droplets, thick neck and also multiple defects.

What is known already
Swim-up is routinely used sperm preparation technique in ART practice. It is widely known that swim-up enhances sperm quality in terms of motility and sperm morphology. However, the effect of swim-up on the frequency of occurrence of the specific sperm morphological abnormalities is still missing.

Study design, size, duration
This observational study involved 30 teratozoospermic patients of Nadezhda Women’s Health hospital between December 2020 and January 2021. Sperm morphology was evaluated before and after swim-up preparation.

Participants/materials, setting, methods
Native semen was liquefied and was subjected to swim up. Semen analysis performed according to WHO 2010. Native semen and swim up samples from the same men were subjected to Kruger strict morphological evaluation.
The analyzed sperm morphological defects included: head defects (large, small, tapered, pyriform, round, amorphous and double heads); midpiece defects (bent, asymmetrical, thin, thick, presence of cytoplasmic droplet); tail defects (short, hairpin, bent, coiled tail and terminal droplet) and multiple defects.

Main results and the role of chance
Wilcoxon paired test showed that the percentage of morphologically normal spermatozoa was significantly higher in the swim-up samples in comparison to the native semen (8.5±4.2% vs 4.9±3.2%, p &lt; 0.05). In addition, the percentage of spermatozoa bearing multiple defects was found to be significantly lower in the swim-up samples than in the native semen (25.8±11.6% vs 37.0±15.0%, p &lt; 0.05). Two specific sperm morphological defects were found to be significantly lower after swim-up preparation: the presence of cytoplasmic droplets (6.0±1.0% vs 8.6±1.5%, p &lt; 0.05) and the thick neck (9.7±5.5% vs 12.8±5.8%, p &lt; 0.05). No significant different were observed in the other morphological defects between swim up samples and native semen (p &gt; 0.05).

Limitations, reasons for caution
Results obtained from this study need to be confirmed by larger group of samples.
Wider implications of the findings: Our study showed a significant reduction of certain midpiece defects after swim-up. The observed selection of spermatozoa without thick necks and cytoplasmic droplets explains the effectiveness of swim-up on ART. In addition, the obtained results can serve as a guide for future validation of new sperm preparation techniques.

Trial registration number
Not applicable
P–011 Automated sperm morphology assessment using artificial intelligence technology
Authors: Agarwal A , Panne. Selvam M K 
Published: August 2021

Abstract

Study question
Can LensHooke X1 PRO semen analyzer be used to evaluate sperm morphology in men with infertility?

Summary answer
Morphology results generated by X1 PRO are highly reliable when normal sperm forms are ≥4% and therefore they can be reported in such cases .

What is known already
Most laboratories rely on manual evaluation of sperm morphology smears, which is a time-consuming procedure and its results are subjected to a relatively high variability. However, in recent years the computer-assisted semen analyzers are being increasingly used to evaluate sperm morphology. The X1 PRO semen quality analyzer was designed for in vitro diagnostic use to analyze sperm concentration, total, progressive and non-progressive motility as well as sperm morphology based on WHO 5th edition criteria. Evaluation of sperm morphology using X1 PRO based on AIOM (Artificial Intelligence Optical Microscopic)-based technology requires no fixation steps or staining unlike the manual method.

Study design, size, duration
This cross-sectional study used 31 semen samples from 8 normozoospermic healthy volunteers and 5 infertile men with a minimum abstinence period between 2 - 3 days. While the 8 healthy semen donors produced a total of 26 ejaculates, which were split into 88 aliquots, the 5 infertile patients produced 5 ejaculates that were split into 13 aliquots.

Participants/materials, setting, methods
A total of 101 aliquots were prepared from the native semen samples either by dilution or concentration using seminal plasma of the respective donors. Automated semen analysis was performed by the X1 PRO semen analyzer and the results of sperm morphology were compared with manual morphology results using Diff-Quik staining. Statistical analysis was carried out to calculate the positive predictive value (PPV) and negative predictive value (NPV) of X1 PRO semen analyzer.

Main results and the role of chance
The X1 PRO sperm morphology results show a weak non-significant (P = 0.2441) correlation (r = 0.119) with the manual results. However, X1 PRO demonstrated a high PPV (97.7%) and a low NPV (9.1%) for correct assessment of sperm morphology (≥4%) when compared to manual results. Due to its high PPV, laboratories can report the morphology results generated by X1 PRO in all such cases when normal sperm forms are ≥4%. However, a manual evaluation is necessary in patients with abnormal morphology (&lt;4%).

Limitations, reasons for caution
One of the limitation of this study is that X1 PRO morphology values did not correlate with manual results. The low NPV seen in our study is due to the inclusion of very few samples with abnormal sperm forms (&lt;4%) in the analysis.
Wider implications of the findings: The X1 PRO’s combination of speed, ease of use, accuracy and portability makes it a good choice of device for small medical offices to large IVF centers. High PPV of X1 PRO allows it to correctly identify normal sperm forms for diagnostic use.

Trial registration number
18–771
P–027 Does air pollution impact on semen parameters? Findings from a real-life cross-sectional study in white-European infertile men
Authors: Belladelli F , Pozzi E , Boeri L , Fallara G , Capogrosso P , Cignoli D , Candela L , Schifano N , Raffo M , Colandrea A , Montorsi F , Salonia A 
Published: August 2021

Abstract

Study question
We aimed to investigate the association between air pollutants levels and semen parameters in a cohort of white-European men seeking medical attention for couple’s infertility.

Summary answer
We found that Pm10, Pm 2.5, and NO2 levels were negatively associated with sperm morphology.

What is known already
Air pollutants levels have been monitored closely for environmental and research issues in industrialized countries.

Study design, size, duration
Data from 156 infertile men consecutively assessed between 01/2019 and 12/2020 were analysed.

Participants/materials, setting, methods
Semen analyses were based on 2010 WHO reference criteria. We analysed the annual average level of the main markers of air pollution (Pm10, Pm2.5, and NO2) between 2014–2018 (Legambiente, 2020, Annual dossier series on air quality in Italy) relative to patients’ addresses of the last 5 years. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI). Descriptive statistics and linear regression analyses were used to test the association between air pollutants and semen parameters.

Main results and the role of chance
Overall, median (IQR) age and BMI were 37 (33–41) years and 25.1 (23.4–27.3) kg/m2, respectively. A CCI≥1 was found in 12 (7.7%) men, and 47 (30.1%) participants were smokers. As for sperm parameters, semen volume, sperm concentration, sperm progressive motility and normal sperm morphology were 3 (2–4) ml, 18 (5–45.5) x106/ml, 32 (22–45)% and 2 (1–3)%, respectively. Pm10 was negatively associated with sperm morphology (ß: –0.580, p = 0.001). Furthermore, Pm10 was found to be an independent predictor for sperm morphology worsening (ß: –0.729, p = 0.006) (Fig.1A), after adjusting for age, BMI, CCI and smoking status. Similarly, Pm2.5 levels were negatively associated with sperm morphology (ß: –0.595, p = 0.009) (Fig.1B). After adjusting for the same variables, the association between Pm2 and sperm morphology remained significant (ß: –0.724, p = 0.015) (Fig.1C). NO2 levels were found to be associated with sperm morphology worsening after adjusting for age, BMI, CCI, and smoking status (ß: –0.471, p = 0.006).

Limitations, reasons for caution
It is a retrospective analysis at a single, tertiary-referral academic centre, thus raising the possibility of selection biases. Moreover, markers of air pollutions divided by residence may not completely evaluated the single patient exposure.
Wider implications of the findings: In this cross-sectional study we found that Pm10, Pm 2.5, and NO2 levels were negatively associated with sperm morphology, while they were not consistently associated with an increased risk of other abnormal sperm parameters in infertile men. Further studies are needed to characterize air pollution effects on sperm parameters.

Trial registration number
Not applicable
P–044 A non-classical splice site variant in ANOS1 gene leading to Kallmann syndrome
Authors: Guo H , Xia Y , Cui C 
Published: August 2021

Abstract

Study question
Genetic risk of the non-classical splice site variant in ANOS1 gene

Summary answer
A non-classical ANOS1 splice site variant, c.1062 + 4T&gt;C, causes Kallmann syndrome.

What is known already
Genetic abnormalities play a key role in the development of Kallmann syndrome. Although an overwhelming majority of missense and nonsense mutations occur in the exons of a gene, intron mutations can also be pathogenic.

Study design, size, duration
The research object is a family. Eight patients of the family were recruited in this study, three of them were diagnosed with Kallmann syndrome.

Participants/materials, setting, methods
Genomic DNA was extracted from peripheral blood and whole-exome sequencing (WES) was performed to identify the genetic abnormalities. PCR was performed to verify the WES results. The functional splicing reporter mini gene assay was performed to assess the impact of sequence variants on splicing.

Main results and the role of chance
The proband and other two patients exhibited the typical clinical features of KS. A non-classical splice site variant, c.1062 + 4T&gt;C in ANOS1 gene was identified, whereas the other unaffected family members did not have this mutation. This mutation caused the disappearance of the splicing site of intron 7 and the splicing position became the 156th base of exon 7, which caused a frame-shift mutation, leading to a premature termination of translation.

Limitations, reasons for caution
Since the ANOS1 gene is almost not expressed in the blood, in order to uncover the effect of this splice site variant of ANOS1, we carried out a functional splicing reporter mini gene assay in the mini gene vector pEGFP-N1.
Wider implications of the findings: This study shows that mutations in non-classical splicing regions are also pathogenic. Therefore, it is recommended that the detection and analysis of this gene should pay attention to the non-classical splice site variant.

Trial registration number
Not applicable
P–069 microfluidic sperm sorting vs density gradient to yield sperm with reduced DFI for patients undergoing IVF-ICSI
Authors: Makwana D P , Makwana S , Sen T 
Published: August 2021

Abstract

Study question
To compare the effect of sperm preparation methods on the DFI of semen sample for patients undergoing ICSI.

Summary answer
On comparing the results, microfluidic sperm sorting yielded sperms with significantly less DFI as compared to density gradient method of sperm preparation.

What is known already
The DNA integrity of the sperm plays an important role to ensure formation of good quality embryos with increased potential of fertilization, growth and ultimately implantation.. Centrifugation has shown to add stress to the sperm and leading to DNA damage, therefore there is a need to develop techniques of sperm preparation which help in retrieving as many sperms with intact DNA from the unprocessed sample as possible. Microfludic is fluid dynamic based technique of sperm preparation. in this study, we evaluated if microfluidic sperm sorter can recover motile sperm with better DNA integrity compared to density gradient preparation method.

Study design, size, duration
Prospective randomized study conducted in 80 patients undergoing IVF-ICSI with normal semen parameters (based WHO criteria 2010). DFI was done using Sperm Chromatin Dispersion (SCD) test in split semen samples prepared by microfluidic sperm sorter and density gradient method. Sperm morphology and motility were also recorded and evaluated based on the WHO 2010 criteria.

Participants/materials, setting, methods
Semen parameters of the sample were assessed by microscopic examination. DFI of each unprocessed sample was carried out using SCD test, following that the sample was split and sperm preparation was done using microfluidic sperm sorter and density gradient. the recovered sperm were tested for DFI and the results were compared.

Main results and the role of chance
Mean DFI in unprocessed semen samples was 23%. the analysis of split semen samples post preparation showed that the DFI was significantly reduced with the use of microfluidic sperm sorter (mean DFI 0.6%) as compared to density gradient (mean DFI 9%).

Limitations, reasons for caution
A major limitation of the microfluidic sperm sorter is the use sperm concentration and motility of the semen sample. In oligospermic and asthenospermic samples, density gradient is the preferred method of preparation. Lack of data showing improvement in clinical outcomes with reduced DFI is also a major limitation.
Wider implications of the findings: Microfluidics has shown to significantly reduce the DFI of the semen sample, it requires no extra equipment and cost and is relatively easy to pick up. Density gradient method of sperm preparation continues to be the preferred method due to its versatility and recovery of good quality sperm.

Trial registration number
Not applicable
P–070 Evaluation of SARS-CoV–2 in human semen and effect on total sperm number: A prospective observational study
Authors: Best J , Kuchakulla M , Khodamoradi K , Lima T , Frech F , Achua J , Rosete O , Mora B , Arora H , Ibrahim E , Ramasamy R 
Published: August 2021

Abstract

Study question
Is the SARS-CoV–2 virus present in human semen and what is the impact on semen parameters following an infection?

Summary answer
SARS-CoV–2 infection, though not detected in semen of recovered men, can affect TSN in ejaculate in the acute setting.

What is known already
Early epidemiological data has suggested that the primary mode of transmission is through respiratory droplets, but the presence of SARS-CoV–2 has been identified in other bodily fluids such as feces, urine, and semen.

Study design, size, duration
We prospectively recruited thirty men diagnosed with acute SARS-CoV–2 infection using real-time reverse transcriptase-polymerase chain reaction (RT-PCR) of pharyngeal swab specimens. Thirty semen samples from recovered men were obtained 11–64 days after testing positive for SAR-CoV–2 infection. The median duration between positive SAR-CoV–2 test and semen collection was 37 days (IQR=23).

Participants/materials, setting, methods
Semen samples were collected from each individual using mailed kits. Follow-up semen samples were done with mailed kits or in-person in office setting. Semen analysis and PCR was performed after samples were received.

Main results and the role of chance
The median total sperm number (TSN) in ejaculate was 12.5 million (IQR=53.1). When compared with age-matched SARS-CoV–2(-) men, TSN was lower among SARS-CoV–2(+) men (p = 0.0024). Five men completed a follow-up sperm analysis (median 3 months) and had a median TSN of 18 million (IQR=21.6). No RNA was detected by means of RT-PCR in the semen in 16 samples tested.

Limitations, reasons for caution
First, most of the semen samples came from non-severe men of whom were in the recovery stage and lacked symptoms. Additionally, our sample size was relatively small and overnight mail-in semen analysis kits were used during the acute phase of infection to minimize contact with positive subjects.
Wider implications of the findings: Our findings suggest extremely low risk of viral transmission during sexual contact and assisted reproductive techniques, although further data need to be obtained. The impact on TSC in recovered men from SARS-CoV–2 infection is concerning, nevertheless long-term follow-up of these men is critical to determine the nadir of TSC.

Trial registration number
20200401