World Health Organization Reference Values Research Articles

P-023 Gene expression in human sperm as biomarkers and tools for the assessment of male infertility

Abstract Study question Can gene expression as AURKA, HDAC4, and CARHSP1 be used for the diagnosis of sperm quality exploring male infertility? Summary answer The comprehensive outcome of gene expression involving AURKA, HDAC4, and CARHSP1 serves as a key to classifying sperm and predicting their functionality. What is known already Diagnostic male infertility is largely based on semen parameters according to the World Health Organization (WHO) reference values. While these parameters assess sperm quality, they do not provide insights into sperm quality and have a limited predictive value on natural fecundity, fertilization rates, and assisted reproductive technology (ART) outcomes. Study design, size, duration This prospective study investigates the gene expression involved in mitosis, epigenetic regulation, and early embryo development. From February to June 2023, we included all men aged from 20 to 60 years having sperm parameters analysis in our unit center. A total of 277 semen samples were collected, 129 (46.4%) exhibiting three normal sperm parameters according to WHO criteria. Among these, 32 samples showed oligo-astheno-teratozoospermia (OAT), while 116 samples had 1 or 2 abnormal parameters. Participants/materials, setting, methods The mRNA expression levels of three candidate genes (AURKA, HDAC4, and CARHSP1) were quantified in fresh ejaculate semen using real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The thresholds for the spermatozoa function index (SFI) were established by assessing the combined expression of these target genes, considering the morphology and the capability to reach a blastocyst stage. The sperm were ranked according to the concentration (million/ml), motility (%) and morphology (%). Main results and the role of chance We assess the quality of spermatozoa for three biomarkers by analyzing their mRNA expression levels. Receiver operator characteristics curves (ROC) indicate a combined index value expression. This model establishes an index threshold > 320 for an “over-index value,” distinguishing spermatozoa with a normal capacity, an index threshold < 290 for an “under-index value,” and 290 < index < 320 for an “intermediate-index value”. Among the 277, we find 112 (40.4%) have an over-expression index; 161 (58.1%) have an under-expressed index and 4 (1.4%) have an intermediate-index. Interestingly, among the 129 samples with the three normal WHO parameters, we show that 82 (63.5%) have an over-index value, 44 (34.1%) have an under-index value, and 3 (2.3%) display an intermediate-index value. In addition, all the 32 OAT samples have an under-index. These findings suggest that the OAT sperm population implies a potential epigenetic network connected with our three target genes. Furthermore, even in cases with normal sperm parameters, there may be an under-expressed index, indicating lower functionality in terms of fertilization and early embryo development. Limitations, reasons for caution The present method was validated only on ejaculate semen in men free of any chronic disease and any anti-oxidant treatment. This prospective study requires further validation in the largest population. Wider implications of the findings This study’s results could highlight understanding a chaotic early embryo development in ART and used to explore male infertility; particularly in unexplained infertility. Trial registration number not applicable

Growth in height and its association with overweight and obesity in Mexican children: an evaluation based on a nationally representative sample (ENSANUT 2018).

Chronological age and height records (7,097 boys and 6,167 girls) were obtained from the Mexican National Survey of Health and Nutrition database. Height growth curves were fitted using the Preece-Baines 1 (PB1) model and the LMS method. Age at peak height velocity (APHV) was 12.4 and 12.7 years for overweight-obese and normal-weight boys, respectively, and was 9.6 and 10.4 years for overweight-obese and normal-weight girls, respectively. Growth velocity was higher at the age of take-off (TO) in overweight-obese children than in normal-weight children (5.2 cm/year vs. 5 cm/year in boys and 6.1 cm/year vs. 5.6 cm/year in girls); nevertheless, the growth velocity at APHV was higher for normal-weight children than for overweight-obese children (7.4 cm/year vs. 6.6 cm/year in boys and 6.8 cm/year vs. 6.6 cm/year in girls, respectively). Distance curves developed in the present study and by the World Health Organization (WHO) using LMS showed similar values for L and S parameters and a higher M value compared with the WHO reference values. This study concluded that overweight-obese children had earlier APHV and lower PHV than normal-weight children. Furthermore, Mexican children and adolescents were shorter than the WHO growth reference by age and sex.

Association between self-reported mobile phone use and the semen quality of young men

To investigate the association between mobile phone exposure and semen parameters. A nationwide cross-sectional study. Andrology laboratories in close proximity to 6 army recruitment centers. In total, 2886 men from the general Swiss population, 18-22 years old, were recruited between 2005 and 2018 during military conscription. Participants delivered a semen sample and completed a questionnaire on health and lifestyle, including the number of hours they spent using their mobile phones and where they placed them when not in use. Using logistic and multiple linear regression models, adjusted odds ratios and β coefficients were determined, respectively. The association between mobile phone exposure and semen parameters such as volume, sperm concentration, total sperm count (TSC), motility, and morphology was then evaluated. A total of 2759 men answered the question concerning their mobile phone use, and 2764 gave details on the position of their mobile phone when not in use. In the adjusted linear model, a higher frequency of mobile phone use (>20 times per day) was associated with a lower sperm concentration (adjusted β: -0.152; 95% confidence interval: -0.316; 0.011) and a lower TSC (adjusted β: -0.271; 95% confidence interval: -0.515; -0.027). In the adjusted logistic regression model, this translates to a 30% and 21% increased risk for sperm concentration and TSC to be below the World Health Organization reference values for fertile men, respectively. This inverse association was found to be more pronounced in the first study period (2005-2007) and gradually decreased with time (2008-2011 and 2012-2018). No consistent associations were observed between mobile phone use and sperm motility or sperm morphology. Keeping a mobile phone in the pants pocket was not found to be associated with lower semen parameters. This large population-based study suggests that higher mobile phone use is associated with lower sperm concentration and TSC. The observed time trend of decreasing association is in line with the transition to new technologies and the corresponding decrease in mobile phone output power. Prospective studies with improved exposure assessment are needed to confirm whether the observed associations are causal.

Cesarean section rates in Turkey 2018-2023: Overview of national data by using Robson ten group classification system.

Cesarean section (CS) rates continue to rise globally because of various factors. Medically unnecessary cesarean operations have no benefit to the mother or child's health. Since the World Health Organization (WHO) has determined that the acceptable CS rate should not be more than 10-15%, it also stated the use of a classification system to compare different patient groups and facilities. Turkey has the highest CS rates globally and has been rising over the years. This study aims to assess CS rates between 2018 and 2023 using National Health Data and to analyze them according to the Robson classification system and WHO reference values to discuss possible measures against increasing rates. In this study, we assessed the rates of CSs between 2018 and 2023; the CS rate including all 5-years and analysis of CS rates for each Robson group as advocated by WHO. Also, another assessment was done of the facilities where the CSs were applied (Public, private, or university hospitals). The total number of births recorded between 2018 and2023 was 6.161.976. The overall CS rate was 57.55%. The number of total CS operations was 3.546.049. The primary CS rate was 28.83% (N:1.776.503). Significant differences were observed between the public and private centers for each Robson group. The CS rates of Groups 1-4 are obviously higher than expected. The CSs of these groups cumulatively affect the rates of other groups. Nulliparous women have CSs mostly in private hospitals. There is a need for improvements in the health system in this regard for better maternal and child health.

P-247 Total Fertilization Failure after conventional IVF: it is not the end of the story

Abstract Study question Could Rescue IntraCytoplasmatic Sperm Injection (R-ICSI) coupled with frozen transfers be an effective treatment for Total Fertilization Failure (TFF) after conventional InVitro Fertilization (c-IVF) cycles? Summary answer Applying R-ICSI after TFF of c-IVF, a blastulation rate of 28% could be obtained, allowing the cycle rescue in a consistent proportion of couples. What is known already Conventional IVF is to date the most indicated technique in infertile couples in the absence of male factor. However, the incidence of TFF following c-IVF, in presence of normozoospermic samples, ranges from 5 to 20%. TFF leaves experts with limited alternatives, which include cancelling the cycle with subsequent indication to proceed with ICSI in the next cycle or attempting R-ICSI in the current cycle. R-ICSI coupled with frozen embryo transfer may overcome most of the technical and biological issues associated with fresh transfer after R-ICSI, possibly representing an efficient procedure for couples experiencing TFF following c-IVF. Study design, size, duration Our retrospective study included 33 couples who underwent assisted reproduction techniques (ART) at the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico of Milan from October 2021 to December 2022 and that experienced TFF after c-IVF, regardless the number of oocytes retrieved. Overall, TFF was reported in 7% of c-IVF cycles (33/439). An indication for male factor infertility was an exclusion criterium. World Health Organization (WHO) reference values for human semen characteristics have been adopted. Participants/materials, setting, methods Fertilization failure was considered in terms of absence of the two pronuclei and the second polar body. Out of 158 unfertilized oocytes, 128 MII oocytes were microinjected after c-IVF in the same cycle. R-ICSI consists of performing ICSI 22-24 hours after insemination with an unsuccessful c-IVF, using the same semen sample maintained at room temperature overnight. Fertilized oocytes after R-ICSI were cultured to the blastocyst stage according to our standard protocol. Main results and the role of chance The fertilization rate was 42% (95%CI: 34-51%). Fertilization failure was still observed in 9 patients (27%, 95%CI: 13-46%) after R-ICSI, with a median value of 2 [2-5] oocytes available for insemination. In the 24 patients who obtained at least one zygote, the blastulation rate was 28% (95%CI: 16-42%). A total of 15 blastocysts were cryopreserved in 10 patients on day 5 or 6 after R-ICSI. Of these 10 patients, 6 have undergone frozen/thawed single embryo transfer, and the success rate (ongoing pregnancy) was 50% (95%CI: 12-88%). Limitations, reasons for caution One of the limitations is the small sample size, since this is an emergency procedure. However, the study is still ongoing. Women were not subjected to inclusion criteria, thus fertilization failure could be attributed to several factors different from semen quality. Wider implications of the findings This study turns out to be important in light of the interesting implantation rate obtained. With the advantage of reducing both costs and psychological burden of the couple, the technique can be proposed as a rescue strategy in cases of TFF allowing to confidently increase the number of c-IVF procedure. Trial registration number not applicable

Association Between Dietary Quality, Socioeconomic Level, Body Mass Index, and Age in Adolescents (Eastern Algeria): A Cross-sectional Study

Aim: This article aims to evaluate the quality of adolescents’ diet in Constantine (Eastern Algeria) and investigate factors associated with this quality: Socio-economic Level (SEL), nutritional status (BMI), and age.
 Methods: A cross-sectional survey was conducted in Constantine (Eastern Algeria) in 2019 with 1126 adolescents (aged 11–19 years). The dietary data were collected by a 24-hr recall. The diet quality was assessed by a diet diversity score (DDS) calculated for 9 food groups (DDS above the mean reflects a diversified diet) and a mean adequacy ratio (MAR) calculated for 12 nutrients. MAR’s cut-off value was "one." Weight and height were measured, and BMI was interpreted according to the World Health Organization reference values. The SEL was assessed using a socioeconomic classification score (SECS) according to parents' education level, profession, and other household information.
 Results: The mean DDS was 3.97 ± 1.25. It was shifted to the lowest values compared to the theoretical mean value (4.5). Insufficient scores (DDS ≤4.5) were found in 65.0% of subjects. The mean MAR was 0.59 ± 0.20 and values <1 represented 79.1%. A significant negative correlation was recorded between age and MAR (r = −15%; P < 0.0001), and a positive correlation was found between it and SECS (r = 18%; p < 0.0001). BMI is inversely and significantly associated with MAR (r = −9.9%; P = 0.0009).
 Conclusion: In addition to highlighting a low diversity and a poor adequacy with nutritional recommendations among adolescents in Algeria, this study underlines the significant effect of age, BMI, and socioeconomic level on the quality of diet.
 Keywords: dietary diversity score (DDS), mean adequacy ratio (MAR), BMI, socioeconomic level, adolescents

Impact of a daily legume-based meal on dietary and nutritional intake in a group of omnivorous adults.

Adopting eco-friendly diets will demand the consumption of more plant-based protein food sources such as legumes. However, assessing the impact of such a dietary shift on the dietary and nutritional intake of traditionally omnivorous populations is needed. The objective of this study was to assess the impact of substituting a traditional omnivorous-based lunch for a vegetarian, legume-based meal on the daily dietary and nutritional intake in a group of omnivorous adults in the city of Porto, Portugal. Nineteen, non-vegetarian, healthy young adults consumed a vegetarian, legume-based meal from Monday to Friday, for 8 consecutive weeks. Socio-demographic data, health status, lifestyle-related information and anthropometric parameters were recorded. Three-day food records were used to collect food intake at baseline and week 8. European Food Safety Authority and World Health Organization reference values were used to assess nutritional inadequacies. Variables were described as medians (P25 and P75 ). Wilcoxon signed-rank and Mann-Whitney tests were used for statistical comparisons. A p-value of <0.05 was considered statistically significant. Participants consumed 38.0 (P25 = 35.0; P75 = 40.0) meals, resulting in an intake of 84.5 g (P25 = 74.9; P75 = 98.4) of cooked legumes per meal, meaning 11 subjects (57.9%) met the Portuguese guidelines for legume consumption (≥80 g/day of legumes). The current dietary intervention did not seem to aggravate the prevalence of nutritional inadequacies for the macro- and micronutrients tested, except for the case of vitamin B12 (52.6% [95% CI: 28.9-75.6] vs. 78.9% [95% CI: 54.4-94.0]). This could be linked to the reduction of dietary sources of this vitamin which is an expected consequence of vegetarian meals. Dietary changes towards grain legume-based diets are desirable yet need to be carefully implemented to prevent exacerbating potential nutrient inadequacies, especially of vitamin B12 .

Nutritional Risk and Malnutrition in Paediatrics: From Anthropometric Assessment to Strongkids® Screening Tool.

The prevalence of malnutrition in hospitalized children is high and is associated with negative health impact. The aim of this study was to characterize the nutritional status of hospitalized children as well as comparing nutritional risk stratification using the STRONGkids® tool and anthropometric assessment. A prospective study was conducted between March and June 2019 in a paediatric unit of a district hospital. Children with ages between one month and 17 years were included. Nutritional screening (STRONGkids®) was performed, and demographic and anthropometric variables were assessed by trained doctors and nurses (z-scores for height-for-age, weight-for-age, weight-for-height and body mass index were compared to the World Health Organization reference values) and related to the underlying condition (cause of hospitalization; hospital stay; the presence of chronic disease). A total of 209 children were evaluated, 188 of whom were included. Median age was 4.6 years and median hospital length of stay was four days. Fifty-four per cent were classified with "moderate risk" and 2% with "high risk" of developing malnutrition; 25% were effectively malnourished. Of the 105 children for which it was possible to calculate the z-scores, 6% presented acute malnutrition and nearly 14% presented chronic malnutrition. The STRONGkids® score correlated positively with nutritional status on admission, disease type on admission, and presence of previous underlying disease (p < 0.05). STRONGkids® is a simple, quick nutritional screening tool for hospitalized children that is related to nutritional status on admission. Given that a considerably high percentage of children were identified as being at risk for malnutrition, it is essential to identify this early and provide nutritional intervention during hospitalization.

The impact of different WHO reference criteria for semen analysis in clinical practice: Who will benefit from the new 2021 thresholds for normal semen parameters?

BackgroundIn 2021, the World Health Organization (WHO) has provided the latest update on processing and evaluating semen analysis.ObjectivesTo assess (i) the rate of discordance in semen parameters categorization across three different WHO reference values (namely WHO21, 2010 and 1999) and (ii) the clinical differences among discordant semen analyses from a cohort of primary infertile men.Materials and methodsData from 788 infertile men were analyzed. Semen parameters were interpreted based on WHO21, WHO10, and WHO99 reference criteria. Pregnancy outcomes with assisted reproductive techniques (ART) were available for 110 (14%) patients. Descriptive statistics was applied to describe potential differences among the three consecutive WHO references criteria.ResultsSemen parameters categorizations were highly different across the three groups (p < 0.001). Of all, 271 (42.2%) patients had normal semen parameters according to WHO10 but were pathologic when considered with WHO21 reference criteria (namely, men with increased semen abnormalities). Infertile men with increased semen abnormalities had lower testicular volume (p < 0.001) but higher FSH (p < 0.01) and LH (p < 0.001) values than those who had no change in terms of semen parameters categorization. Negative ART outcomes were more frequently reported in men with worsening semen parameters compared with those with confirmed semen parameters at WHO21 versus WHO10 (26.8% vs. 49%, p = 0.03). Conversely, infertile men with worsening semen parameters at WHO21 versus WHO99 were similar in terms of clinical and hormonal characteristics compared with those with the same rate of semen abnormalities.ConclusionsOne out of three infertile men showed worsened semen categorization according to WHO21 versus WHO10. Infertile men with worsening of semen parameters had worse clinical and hormonal characteristics than those with confirmed numbers of semen abnormalities. Moreover, live birth rates were lower in men with worsening semen abnormalities as for WHO21.

MANTA and MANTA-RAy: Rationale and Design of Trials Evaluating Effects of Filgotinib on Semen Parameters in Patients with Inflammatory Diseases.

IntroductionThe phase 2 MANTA and MANTA-RAy studies were developed in consultation with global regulatory authorities to investigate potential impacts of filgotinib, a Janus kinase 1 preferential inhibitor, on semen parameters in men with active inflammatory diseases. Here we describe the methods and rationale for these studies.Methods and RationaleThe MANTA and MANTA-RAy studies included men (aged 21–65 years) with active inflammatory bowel disease (IBD) and rheumatic diseases, respectively. Participants had no history of reproductive health issues, and the following semen parameter values (≥ 5th percentile of World Health Organization reference values) at baseline: semen volume ≥ 1.5 mL, total sperm/ejaculate ≥ 39 million, sperm concentration ≥ 15 million/mL, sperm total motility ≥ 40% and normal sperm morphology ≥ 30%. Each trial included a 13-week, randomized, double-blind, placebo-controlled period (filgotinib 200 mg vs placebo, up to N = 125 per arm), for pooled analysis of the week-13 primary endpoint (proportion of participants with ≥ 50% decrease from baseline in sperm concentration). All semen assessments were based on two samples (≤ 14 days apart) to minimize effects of physiological variation; stringent standardization processes were applied across assessment sites. From week 13, MANTA and MANTA-RAy study designs deviated owing to disease-specific considerations. All subjects with a ≥ 50% decrease in sperm parameters continued the study in the monitoring phase until reversibility, or up to a maximum of 52 weeks, with standard of care as treatment. Overall conclusions from MANTA and MANTA-RAy will be based on the totality of the data, including secondary/exploratory measures (e.g. sperm motility/morphology, sex hormones, reversibility of any effects on semen parameters).ConclusionsDespite the complexities, the MANTA and MANTA-RAy studies form a robust trial programme that is the first large-scale, placebo-controlled evaluation of potential impacts of an advanced IBD and rheumatic disease therapy on semen parameters.Trial RegistrationEudraCT numbers 2017-000402-38 and 2018-003933-14; ClinicalTrials.gov identifiers NCT03201445 and NCT03926195.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-022-02168-4.

Is There an Association Between Sperm Parameters and Sexual Orientation? A Cross Sectional Study

ObjectiveTo evaluate whether sexual orientation affects sperm parameters. MethodsThis was a cross-sectional study using existing data from an academic reproductive centre for the period of April 01, 2009, to March 31, 2021. We compared the results of sperm analysis from male patients who were in same-sex relationships (study group) with those of men in heterosexual relationships who did not have male-factor infertility (control group). A subsequently comparison of both groups with World Health Organization (WHO) reference values was also performed. ResultsThirty-nine samples from the study group were compared with 494 samples from the control group. All parameters, apart from morphology, were comparable. The median sperm concentrations were 64 (interquartile range [IQR] 32.1–102.9) million/mL and 50.1 (IQR 25.3–92.5) million/mL in the study and control groups, respectively (P = 0.252), whereas the median percentage of progressive motile sperm was 50% (IQR 34–65) in the study group and 52% (IQR 33–65) in the control group (P = 0.198). The median percentage of morphologically normal sperm was higher in the control group than in the study group (6% vs. 5%; P = 0.019). However, no significant difference was found when sperm morphology was dichotomized with the cut-off of ≥4% (74.1% and 74.4%, respectively; P = 0.966). When compared with the WHO reference group, the percentage of men with total motile sperm counts ≥10 million and the percentage of men with normal morphology were significantly lower in both groups. ConclusionOur study suggests that there is no relationship between sexual orientation and sperm parameters.

Prevalence of overweight, obesity, and early adiposity rebound in nursery school children in southeastern France

BackgroundThe aim of the present study was to assess the prevalence of overweight, obesity, and early adiposity rebound in nursery school children aged 3.5–4.5 years and to evaluate associations with deprivation. MethodsA cross-sectional study was conducted in the Bouches-du-Rhône department in southeastern France. Data for all nursery school children aged 3.5–4.5 years were collected during systematic medical examinations. The prevalence of overweight and obesity was determined using French, International Obesity Task Force (IOTF), and World Health Organization reference values. A French ecological deprivation index was used to assess associations with deprivation. ResultsAmong 19,295 children included in the study, the prevalence of overweight (IOTF-25 < BMI < IOTF-30) was 9.1% and the prevalence of obesity (BMI > IOTF-30) was 2.6%. Children attending nursery schools in the most disadvantaged areas were 4.3 times more likely to be affected by obesity than those from schools in the most advantaged areas (OR: 4.32; 95% CI: 2.98–6.25, p < 0.001), after adjusting for gender, age group, and school status. Early adiposity rebound was observed in 2131 of 9872 children (21.6%). ConclusionPrograms to prevent childhood overweight and obesity in France should be intensified and take account of major persistent social inequalities. Medical practitioners should learn to systematically assess BMI curve dynamics and early adiposity rebound.

WHO 2021 and 2030 reference values for semen assessment: three challenges for andrology in the journey ahead

Whilst formulating the World Health Organization reference values for semen assessment for 2021, three key challenges were identified, namely the quality of semen assessments, the transparency and reporting of data and, lastly, the paucity of studies with primary data. There is an urgent need to address these issues and we present suggested solutions that will have a real-world influence on the next iteration of the reference values for semen assessments and andrology in general.

O-040 The evolution of WHO Manual. Where are we now?

Abstract text Male factor infertility is associated with impaired overall health, decreased life expectancy, lower quality of life and may affect reproductive outcomes even under assisted reproductive technology (ART) settings. Male factors, alone or combined with female factors, contribute to at least 50% of reported infertility cases. Despite this, the male partner is often overlooked in the evaluation and treatment of infertility. A routine semen analysis is frequently the only test carried out to assess a man’s fertility potential. The state-of-art on how the human semen should be assessed is provided by the World Health Organization (WHO), which periodically releases manuals that include specific protocols and reference standards. These manuals include detailed laboratory methods for semen examination, protocols for sperm preparation and cryopreservation, quality assurance and quality control, results’ interpretation, and reference ranges. Unlike the previous four versions, the latest 2010 WHO reference values relied on clinical chemistry principles to generate 95% intervals for sperm volume, count, motility, vitality, and morphology from recent fathers. The fifth centile was deemed suitable for representing semen characteristics at lower limits. The reference values ultimately obtained were markedly lower than those previously reported, raising concerns about its clinical utility and generalizability. Criticisms included the limited geographical area of patients analyzed, the methods used for semen evaluation, and the potential impact of the new reference range on patient referral, diagnosis, and treatment guidance. An updated new WHO manual (6th edition) is about to be released with much expectation. Although semen analysis remains one of the cornerstones of the infertility evaluation, a male infertility workup primarily based on routine semen analysis does not provide men with an optimal fertility pathway for many reasons. First, reference intervals do not reliably distinguish fertile from subfertile subjects. Second, an individual patient’s results have limited prognostic value for both natural and assisted conception unless at extreme lower limits. Third, there is a wide variation in how laboratories perform a semen analysis. Lastly, routine semen analysis does not detect sperm DNA defects that might adversely impact embryo development, implantation, and offspring’s health. Guidelines issued by professional societies recommend that a full andrological assessment be performed in all men with couple infertility. Well-trained reproductive urologists or clinical andrologists should perform the male evaluation, including a detailed history, physical examination, semen analysis, endocrine assessment, and other tests as needed. Therefore, the importance of WHO manuals remains critical. However, the goals of a comprehensive male infertility workup go beyond the laboratory assessment of human semen. It comprises i. Diagnosis, i.e., detection of any underlying relevant medical or lifestyle conditions potentially impairing the (reproductive) health of the male or his offspring; ii. Counselling, particularly regarding the impact of infertility, genetic factors, age, and lifestyle on pregnancy prospects, reproductive and overall health, and offspring’s well-being; and iii. Management Guidance, i.e., identifying optimal treatment options to improve the likelihood of achieving natural pregnancy or ART success. The prevention and management of male infertility are integral components of comprehensive sexual and reproductive health services needed to attain a sustainable development goal.

Water quality assessment and geochemical processes in the unconfined coastal Boa Viagem Aquifer, Recife, NE Brazil

A hydrochemical study was conducted on the Quaternary Aquifer, in Recife, Brazil. Groundwater samples were collected in March–April 2015, at the beginning of the rainy season. Conventional graphics, ionic ratios, saturation indices, GIS mapping, and geostatistical and multivariate statistical analyses were used to water quality assessment and to characterize the main hydrochemical processes controlling groundwater’s chemistry. Q-mode hierarchical cluster analysis separated the samples into three clusters and five sub-clusters according to their hydrochemical similarities and facies. Principal Component Analysis (PCA) was employed to the studied groundwater samples where a three-factor model explains 80% of the total variation within the dataset. The PCA results revealed the influence of seawater intrusion, water-rock interaction, and nitrate contamination. The physico-chemical parameters of ~30% groundwaters exceed the World Health Organization (WHO) guidelines for drinking water quality. Nitrate was found at a concentration &gt;10 mg NO3−/L in ~21% of the wells and exceeded WHO reference values in one. The integrated approach indicates the occurrence of the main major hydrogeochemical processes occurring in the shallow marine to alluvial aquifer as follow: 1) progressive freshening of remaining paleo-seawater accompanying cation exchange on fine sediments, 2) water-rock interaction (i.e., dissolution of silicates), and 3) point and diffuse wastewater contamination, and sulfate dissolution. This study successfully highlights the use of classical geochemical methods, GIS techniques, and multivariate statistical analyses (hierarchical cluster and principal component analyses) as complementary tools to understand hydrogeochemical processes and their influence on groundwater quality status to management actions, which could be used in similar alluvial coastal aquifers.

Semen parameter thresholds and time-to-conception in subfertile couples: how high is high enough?

AbstractSTUDY QUESTIONWhat thresholds for total sperm count, sperm concentration, progressive motility, and total progressive motile sperm count (TPMC) are associated with earlier time-to-conception in couples undergoing fertility evaluation?SUMMARY ANSWERValues well above the World Health Organization (WHO) references for total sperm count, concentration, and progressive motility, and values up to 100 million for TPMC were consistently associated with earlier time-to-conception and higher conception rates.WHAT IS KNOWN ALREADYAlthough individual semen parameters are generally not able to distinguish between fertile and infertile men, they can provide clinically useful information on time-to-pregnancy for counseling patients seeking fertility treatment. Compared to the conventional semen parameters, TPMC might be a better index for evaluating the severity of male infertility.STUDY DESIGN, SIZE, DURATIONWe used data from a longitudinal cohort study on subfertile men from 2002 to 2017 and included 6061 men with initial semen analysis (SA) in the study.PARTICIPANTS/MATERIALS, SETTING, METHODSMen from subfertile couples who underwent a SA within the study period were included, and 5-year follow-up data were collected to capture conception data. Couples were further categorized into two subgroups: natural conception (n = 5126), after separating those who achieved conception using ART or IUI; natural conception without major female factor (n = 3753), after separating those with severe female factor infertility diagnoses. TPMC was calculated by multiplying the semen volume (ml) by sperm concentration (million/ml) and the percentage of progressively motile sperm (%). Cox proportional hazard models were used to report hazard ratios (HRs) with 95% CIs before and after adjusting for male age, the number of previous children before the first SA, and income. Using the regression tree method, we calculated thresholds for total sperm count, sperm concentration, progressive motility, and TPMC to best differentiate those who were more likely to conceive within 5 years after first SA from those less likely to conceive. We also plotted continuous values of semen parameters in predicting 5-year conception rates and time-to-conception.MAIN RESULTS AND THE ROLE OF CHANCEOverall, the median time to conception was 22 months (95% CI: 21–23). A total of 3957 (65%) couples were known to have achieved conception within 5 years of the first SA. These patients were younger and had higher values of sperm concentration, progressive motility, and TPMC. In the overall cohort, a TPMC of 50 million best differentiated men who were more likely to father a child within 5 years. Partners of men with TPMC ≥50 million had a 45% greater chance of conception within 5 years in the adjusted model (HR: 1.45; 95% CI: 1.34–1.58) and achieved pregnancy earlier compared to those men with TPMC &amp;lt; 50 million (median 19 months (95% CI: 18–20) versus 36 months (95% CI: 32–41)). Similar results were observed in the natural conception cohort. For the natural conception cohort without major female factor, the TPMC cut-off was 20 million. In the visual assessment of the graphs for the continuous semen parameter values, 5-year conception rates and time-to-conception consistently plateaued at higher values of sperm concentration, total sperm count, progressive motility, and TPMC compared to the WHO reference levels and our calculated thresholds. For TPMC, values up to 100–150 million were still associated with a better conception rate and time-to-conception in the visual assessment of the curves.LIMITATIONS, REASONS FOR CAUTIONThere was limited information on female partners and potential for inaccuracies in capturing less severe female infertility diagnoses. Also we lacked details on assisted pregnancies achieved outside of our healthcare network (with possible miscoding as ‘natural conception’ in our cohort). We only used the initial SA and sperm morphology, another potentially important parameter, was not included in the analyses. We had no information on continuity of pregnancy attempts/intention, which could affect the time-to-conception data. Finally, most couples had been attempting conception for &amp;gt;12 months prior to initiating fertility treatment, so it is likely that we are underestimating time to conception. Importantly, our data might lack the generalizability to other populations.WIDER IMPLICATIONS OF THE FINDINGSOur results suggest that a TPMC threshold of 50 million sperm provided the best predictive power to estimate earlier time-to-conception in couples evaluated for male factor infertility. Higher values of sperm count, concentration and progressive motility beyond the WHO references were still associated with better conception rates and time-to-conception. This provides an opportunity to optimize semen parameters in those with semen values that are low but not abnormal according to the WHO reference values. These data can be used to better inform patients regarding their chances of conception per year when SA results are used for patient counseling.STUDY FUNDING/COMPETING INTEREST(S)None.TRIAL REGISTRATION NUMBERN/A.

Anaemia Among Children Who Attended the Children's Teaching Hospital in Karbala, Iraq.

IntroductionThe World Health Organization (WHO) reported a moderate incidence of anaemia among pregnant and nonpregnant women and among children younger than 59 months in 2011.PurposeThe aim of this study was to investigate anaemia among children younger than 14 years submitted to haematological exams at the Children’s Teaching Hospital in Karbala, Iraq.Patients and MethodsThis was a cross-sectional study carried out in the Children’s Teaching Hospital Laboratory Department in Karbala, Iraq, from 1 July 2019 until 1 September 2019.ResultsThe prevalence of anaemia among children aged 0–14 years in Karbala was 9.9%. There was no significant relationship between the type of anaemia diagnosed and age or sex. However, there was a significantly positive relationship between the type of anaemia diagnosed and each ferritin level, mean corpuscular volume, and mean corpuscular haemoglobin (p<0.0001). The study participant skull diameter and length in relation to sex were compared to the WHO reference values for child growth standards, and the study values were less than the normal range for children below 5 years of age.ConclusionA high prevalence of anaemia among children was reported with its apparent consequence on their health. This study highlights the prevalence of anaemia among children up to 14 years of age in Karbala, and future research is encouraged.

Evaluation of the impact of marijuana use on semen quality: a prospective analysis.

Aims:To assess if marijuana consumption – prevalent among men of reproductive age and becoming widespread due to decriminalization – is associated with changes in semen parameters. Marijuana’s active metabolite, tetrahydrocannabinol, can alter signaling pathways within spermatozoa, affecting spermatogenesis and fertility.Methods:We prospectively evaluated semen analyses (SA) from men presenting for infertility evaluation at one institution from July 2017 to April 2018. Participants completed a reproductive health questionnaire including items regarding marijuana consumption. SA was performed in accordance with World Health Organization (WHO) 5th Edition criteria. SA parameters included volume (ml), concentration (million/ml), motility (%), progressive motility (%), and Tygerberg strict morphology (%).Results:A total of 409 patients completed the questionnaire; 174 (43%) men reported marijuana use (ever-users). Current and past users comprised 71 (17%) and 103 (25%), respectively. Compared with never-users, current and past users had a significantly higher likelihood of abnormal sperm strict morphology (33.1% versus 50.7% and 53.4%, respectively; p < 0.001). However, sperm motility was more likely to be less than WHO reference values in never-users than current and past-users (38.3% versus 21.1% and 27.2%, respectively; p = 0.01). In multivariate logistic regression analyses, current use was associated with increased odds of abnormal strict morphology [odds ratio (OR) 2.15, 95% confidence interval (CI): 1.21–3.79] and semen volume less than WHO reference value (OR 2.76, 95%CI: 1.19–6.42), while odds of less than WHO reference value sperm motility were reduced (OR 0.47, 95%CI: 0.25–0.91).Conclusion:Marijuana use is common among men presenting for fertility evaluation, and may have a detrimental effect on semen quality, particularly morphology and volume, but may be protective against abnormal sperm motility. Large, prospective studies of both semen quality and fertility in this growing, at-risk population are warranted.

Residential radon - Comparative analysis of exposure models in Switzerland.

Residential radon exposure is a major public health issue in Switzerland due to the known association between inhaled radon progeny and lung cancer. To confirm recent findings of an association with skin cancer mortality, an updated national radon model is needed. The aim of this study was to derive the best possible residential radon prediction model for subsequent epidemiological analyses. Two different radon prediction models were developed (linear regression model vs. random forest) using ca. 80,000 measurements in the Swiss Radon Database (1994-2017). A range of geographic predictors and building specific predictors were considered in the 3-D models (x,y, floor of dwelling). A five-fold modelling strategy was used to evaluate the robustness of each approach, with models developed (80% measurement locations) and validated (20%) using standard diagnostics. Random forest consistently outperformed the linear regression model, with higher Spearman's rank correlation (51% vs. 36%), validation coefficient of determination (R2 31% vs. 15%), lower root mean square error (RMSE) and lower fractional bias. Applied to the population of 5.4 million adults in 2000, the random forest resulted in an arithmetic mean (standard deviation) of 75.5 (31.7) Bq/m3, and indicated a respective 16.1% and 0.1% adults with predicted radon concentrations exceeding the World Health Organization (100 Bq/m3) and Swiss (300 Bq/m3) reference values.

Chromosomal abnormalities after ICSI in relation to semen parameters: results in 1114 fetuses and 1391 neonates from a single center.

Is there a relationship between karyotype abnormalities in fetuses and children conceived by ICSI and their father's semen parameters? The de novo chromosomal abnormality rate in pre- and postnatal karyotypes of ICSI offspring was higher than in the general population and related to fathers' sperm parameters. Several studies have reported a higher rate of de novo chromosomal anomalies in ICSI fetuses but recent data from large cohorts are limited. Overall, reported prevalences of non-inherited karyotype aberrations are increased in fetuses conceived after ICSI and vary between 1.6% and 4.2%. Only a few studies focus on the relation between karyotype anomalies in ICSI offspring and semen parameters of their fathers. Furthermore, an increased incidence of abnormal karyotypes in ICSI neonates has been described, but the rates vary widely across studies. We report on karyotype results from prenatal testing by means of chorionic villus sampling and amniocentesis and results from postnatal blood sampling in offspring conceived by ICSI in a single center. Ongoing pregnancies resulting from an oocyte retrieval between January 2004 and December 2012 and after transfer of fresh ICSI embryos obtained using ejaculated or non-ejaculated sperm (fresh or frozen-thawed) were considered. Pregnancies following frozen embryo transfer, oocyte or sperm donation, IVF, preimplantation genetic testing and IVM were excluded. All abnormal prenatal results after sampling are reported irrespective of the outcome of the pregnancy. From the 4816 ongoing ICSI pregnancies, information on pregnancy outcome was available for 4267 pregnancies. Prenatal testing was performed in 22.3% of the pregnancies, resulting in a diagnosis in 1114 fetuses. A postnatal karyotype was obtained in 29.4% of the pregnancies in which no invasive prenatal diagnosis was performed, resulting in a total of 1391 neonates sampled. The prevalence of chromosomal anomalies according to maternal age and semen quality was analyzed with logistic regression. For definitions of normal semen quality, the World Health Organization reference values for human semen characteristics were adopted. An abnormal fetal karyotype was found in 29 singletons and 12 multiples (41/1114; 3.7%; 95% CI 2.7-4.9%): 36 anomalies were de novo (3.2%; 95% CI 2.3-4.4), either numerical (n = 25), sex (n = 6) or structural (n = 5), and five were inherited. Logistic regression analysis did not show a significant association between maternal age and a de novo chromosomal fetal abnormality (odds ratio (OR) 1.05; 95% CI 0.96-1.15; P = 0.24). In all but one case, fetuses with an abnormal karyotype were conceived by ICSI using ejaculated sperm.Abnormal karyotypes were found in 14 (1.0%; 95% CI 0.6-1.7) out of 1391 postnatal samples of children born after ICSI who were not tested prenatally: 12 were de novo anomalies and two were inherited balanced karyotypes. The 14 abnormal karyotypes were all found in children born after ICSI using ejaculated sperm.The odds of a de novo karyotype aberration increased with maternal age when combining pre- and postnatal data (OR 1.11; 95% CI 1.04-1.19). A higher rate of de novo chromosomal abnormalities was found in fetuses and children of couples with men having a sperm concentration <15 million/ml (adjusted OR (AOR) 2.10; 95% CI 1.14-3.78), sperm concentration <5 million/ml (AOR 1.9; 95% CI 1.05-3.45) and total sperm count <10 million (AOR 1.97; 95% CI 1.04-3.74). We cannot exclude that the observation of a higher prevalence of karyotype anomalies in ICSI offspring compared to literature data in the general population is due to enhanced surveillance after ART given the lack of a control group. Although we did not find more chromosomal anomalies after ICSI with non-ejaculated sperm, the small numbers do not allow firm conclusions. The observed increased risk of a de novo karyotype anomaly after ICSI conception in couples with poor sperm warrants continued counseling toward prenatal testing.The current and widespread use of innovative non-invasive prenatal testing will result in larger datasets, adding to a balanced estimation of the prevalence of karyotype anomalies in ICSI offspring. This study was supported by the Methusalem grants issued by the Vrije Universiteit Brussel. All authors declared no conflict of interest related to this study. N/A.