Fertile Group Research Articles

Excisional surgery versus ablative surgery for ovarian endometrioma.

Endometrioma are endometriotic deposits within the ovary. Laparoscopic management of endometriomas is associated with shorter hospital stay, faster recovery, and decreased hospital costs compared with laparotomy. The previous version of this systematic review (2008), including randomised controlled trials (RCTs) of surgical interventions for endometrioma, concluded that laparoscopic cystectomy (excision) was preferable to drainage and ablation of endometrioma. We aimed to update the evidence comparing excision with drainage and ablation for improving pain and fertility-related outcomes. To evaluate the safety and efficacy of laparoscopic excision (cystectomy) compared with laparoscopic drainage and ablation of endometrioma in women of reproductive age. We searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycInfo, two trials registries, grey literature sources, and conference proceedings on 19 December 2022. We also checked the reference lists of relevant papers and contacted leaders in the field of endoscopic surgery for any additional trials. Eligible studies were RCTs that compared excision with drainage and ablation of endometriomas. Two review authors independently assessed study eligibility, extracted data, assessed risk of bias, and applied the GRADE approach to rate the certainty of evidence. We identified nine studies (involving 578 women) that investigated laparoscopic excision versus drainage and ablation of endometriomas measuring at least 3 cm in diameter. Participants were women of reproductive age who presented to an outpatient gynaecology clinic with pain, infertility, or both. For most outcomes, we downgraded the certainty of evidence for risk of bias due to lack of blinding and for imprecision due to low participant numbers. At up to two years after surgery, excisional surgery compared with ablative surgery may reduce the risk of dysmenorrhoea recurrence (OR 0.25, 95% CI 0.12 to 0.52; 2 studies, 140 women; low-certainty evidence;). Recurrence of dysmenorrhoea may occur in 49% of women after ablative surgery compared with 10% to 34% after excisional surgery. At up to two years after surgery, excisional surgery compared with ablative surgery may reduce the risk of dyspareunia recurrence (OR 0.09, 95% CI 0.03 to 0.22; 2 studies, 131 women; low-certainty evidence). Recurrence of dyspareunia may occur in 58% of women after ablative surgery compared with 4% to 23% after excisional surgery. At one year after surgery, excisional surgery may reduce the risk of endometrioma recurrence compared with ablative surgery (OR 0.17, 95% CI 0.09 to 0.34; 4 studies, 264 women; low-certainty evidence). Recurrence of endometrioma may occur in 37% of women after ablative surgery compared with 5% to 17% after excisional surgery. At one year after surgery, excisional surgery may reduce the need for further endometrioma surgery compared with ablative surgery (OR 0.16, 95% CI 0.07 to 0.41; 2 studies, 178 women; low-certainty evidence). Our results suggest that 32% of women require further endometrioma surgery after ablative surgery compared with 3% to 16% after excisional surgery. There may be little or no difference between excisional surgery and ablative surgery in terms of their effect on spontaneous pregnancy during the first year after surgery (OR 1.27, 95% CI 0.33 to 4.87; 3 studies, 101 women; low-certainty evidence). Five studies reported that there were no conversions to laparotomy. No studies provided data about any other surgical complications or adverse effects. Surgical management of endometrioma with excision (cystectomy) may be more effective than drainage and ablation for reducing painful menstrual periods, pain during sexual intercourse, endometrioma recurrence, and the need for further endometrioma surgery. However, there may be little or no difference between the techniques in their effect on subsequent pregnancy rates. We found limited evidence on the safety of excisional surgery compared with ablative surgery. Future trials should recruit adequate numbers of women and measure outcomes relating to adverse events and clinical pregnancy.

Testosterone to Estradiol Ratios in Fertile and Subfertile Men: A Large Cohort Analysis

ObjectiveTo validate the established normal testosterone to estradiol ratio and characterize the distribution of testosterone to estradiol ratios in a large cohort of fertile and subfertile men. Materials and MethodsRetrospective review of adult men (≥18 years of age) presenting for fertility evaluation between 2002 and 2021 who underwent evaluation by a reproductive urologist, had two separate semen analyses and had hormonal testing within six months of their index semen analysis. Men were dichotomized into fertile and subfertile groups based on total motile sperm count on two semen analyses. The subfertile cohort included men with a total motile sperm count <20 million on both semen analyses. The main outcome measures were serum testosterone, serum estradiol, and serum testosterone to estradiol ratio. ResultsAmong 816 men, 651 (79.8%) were classified as fertile and 165 (20.2%) as subfertile. Median testosterone (ng/dL) to estradiol (pg/mL) ratios were similar between the groups (14.48 vs 15.00, p=0.5). The 20th percentile testosterone to estradiol ratio for the fertile group was 9.77. ConclusionsThis is the largest study to date characterizing testosterone to estradiol ratios in men presenting for fertility evaluation. We validated the 10/1 ratio that was previously established as the 20th percentile for fertile men. We found no difference in testosterone to estradiol ratios between fertile and subfertile men defined by total motile sperm count, highlighting the need for further investigation to better define the cohort of men with infertility who could benefit from aromatase inhibitor therapy.

Serum pentraxin-3 expression varies according to polycystic ovary syndrome phenotypes.

Pentraxin-3 (PTX-3) is a multibiological protein involved in cumulus cell expansion, fertilization, and implantation. This study was designed to analyze how circulating PTX-3 levels change in women with polycystic ovary syndrome (PCOS). A total of 50 Turkish participants, 35 of whom had PCOS and 15 of whom were fertile, were included in the study. Patients in the PCOS group were divided into 4 different phenotypes according to the NIH criteria (phenotypes A-D). The number of patients in phenotype A was the highest 13 (37.1%). In the calculations made without phenotyping, the serum ptx3 levels of the PCOS group were found to be significantly lower compared to the fertile control group (3.32 ± 0.73 ng/mL vs 4.97 ± 1.29 ng/mL; P < .001). The ptx3 value of phenotypes A and B was significantly lower than phenotype D (P = .008 and P = .009, respectively). When the phenotypes were compared with the fertile control group, the PTX-3 levels of phenotypes A and B were significantly lower than the fertile group. Although the ptx3 levels of phenotypes C and D were lower than the fertile group, the difference did not reach statistical significance. This is the first study to investigate serum ptx3 levels by phenotype in PCOS. While serum PTX-3 levels decreased in phenotypes A and B, ptx3 levels in phenotypes C and D were similar in fertile patients.

Foliar solution hydrophobicity influenced by plant species, product, and concentration

AbstractFoliar application of nutrients and pesticides is a popular practice for plant maintenance and weed control. Understanding how different products and adjuvants interact with the intended plant leaf surface will improve uptake and decrease losses. Various fertilizer, adjuvant, and pesticide solutions were tested to determine solution hydrophobicity on St. Augustinegrass, tall fescue, and white clover. A 1 µL droplet of each solution was placed on the adaxial leaf surface and imaged with a stereomicroscope to determine average solution contact angle. For all solutions groups, plant species had the most consistent effect, with white clover having the highest average contact angle followed by St. Augustinegrass and tall fescue, respectively. All product solutions significantly reduced the average contact angle compared to water. The urea solution resulted in the largest decrease for the fertilizer group at 7.6%. The largest decrease was found with the siloxane nonionic surfactant, which resulted in a decrease of 87.5% compared to water alone. Significant interactions were found between plant species and product solutions, indicating product solutions interact differently dependent upon the leaf surface characteristics. The results suggest that plant leaf surface, product solution and concentration, and their combination should be accounted for to increase wettability of a foliar application and improve product absorption.

High levels of bisphenol A among infertile men can impair spermatogenesis by oxidative stress and elevated levels of microRNA-337

BackgroundStudies have shown that Bisphenol A may interfere with the process of spermatogenesis and result in a decrease in the quality of semen. Nevertheless, the fundamental processes remain unclear. This study was done to investigate the connections between exposure to Bisphenol A, spermatogenesis with microRNA-337, and malondialdehyde in infertile men.MethodsThis study was a case–control study on 73 participants. Infertile group (1a): azoospermia (n = 16), infertile group (1b): oligozoospermia (n = 22), and control group (2): normospermic (n = 35) were enrolled in this study. Full history, local examination, semen analysis, and urine and blood samples were taken from all participants. Urinary Bisphenol A, malondialdehyde, and serum microRNA-337 were measured.ResultsThe mean Bisphenol A level in azoospermia group shows statistically significant increase comparing to fertile control group. The mean microRNA-337 level in oligozoospermia and azoospermia group shows statistically significant increase comparing to fertile controls. The mean malondialdehyde level in infertility groups shows statistically significant increase comparing to fertile control group. No linear correlations were recorded between Bisphenol A levels with semen quality parameters, hormonal profile, and microRNA-337.ConclusionWhile there is no significant change in the levels of Bisphenol A between normal fertile males and infertile males with oligozospermia, a significant elevation in the BPA level was observed in infertile males with azoospermia. A significant upregulation of the miRNA-337 gene expression in infertile males either oligozospermia or azoospermia was also observed. In addition, lipid peroxidation as evident by the significant elevation of MDA levels was marked among infertile patients.

Altered Expression of C4BPA and CXCL1 Genes in the Endometrium of Patients with Recurrent Implantation Failure after In Vitro Fertilization and Thin Endometrium.

Currently, recurrent implantation failure (RIF) after in vitro fertilization is a problem that is commonly faced by reproductive specialists. The phenomenon of a thin endometrium in RIF patients is not yet completely understood or sufficiently treated. This study aimed to reveal the dysregulated expression of selected genes between RIF patients with a thin endometrium and fertile women. Endometrial samples were collected in the implantation window (21-24 days of the natural menstrual cycle) from RIF patients (n = 20) and fertile women (n = 14). Ten genes were chosen as target genes regarding their possible relations with the implantation process. The endometrial gene expression levels showed differences in RIF samples compared to fertile samples. Significant downregulation was observed for the CXCL1 (p = 0.005) and C4BPA (p = 0.03) genes. There was no statistically significant difference between the RIF group and the fertile group in the expression of eight genes: CXCL8, HPRT1, MMP10, INFG, VEGFB, HAND2, IL-15, and TNC (p > 0.05). The use of a combination of two markers (C4BPA + CXCL1) allows for the good discrimination of RIF patients from fertile women (AUC 0.806).

The impact of intracytoplasmic sperm injection versus conventional in vitro fertilization on the reproductive outcomes of couples with non-male factor infertility and frozen-thawed embryo transfer cycles

This study was aimed to investigate the impact of intracytoplasmic sperm injection (ICSI) on reproductive outcomes in couples with non-male factor infertility and frozen-thawed embryo transfer (FET) treatment. This retrospective cohort study involved a total of 10,143 cycles from 6206 couples who underwent FET at the Third Affiliated Hospital of Zhengzhou University between January 2016 and September 2022. Patients were categorized into two groups based on the insemination methods of transferred embryos. Clinical and neonatal outcomes were compared between ICSI and conventional in vitro fertilization (cIVF) groups. The results showed that ICSI was not associated with improved clinical outcomes compared to cIVF. However, ICSI was associated with lower birthweight when twins were born. In conclusion, although subgroup analysis showed that ICSI was associated with slightly improved live birth rate for infertile couples with non-male factor infertility compared to cIVF, the regression analysis showed that ICSI did not demonstrate any improvement of the reproductive outcomes. The infertile women with twin pregnancies should be further informed of the lower birthweight and lower birth length when their oocytes were inseminated with ICSI. The findings of this study provide valuable insights for clinicians when discussing the benefits and risks of ICSI in patients with non-male factor infertility.

«Демографический» фактор рождаемости: оценка потенциала территории на примере Нижегородской области

Introduction. Despite the implementation of serious measures in the framework of state family policy to stabilise the demographic situation, it remains difficult in most regions. This is due, firstly, to the new challenges the country is facing, and secondly, to the complexity of the very processes that need to be controlled. Population size, being a complex quantitative indicator of the stability of society, is determined by a number of demographic processes, among which fertility remains the main one. The number of studies attempting to identify the factors determining fertility trends is growing. All of them demonstrate the complexity and multifactorial nature of the process and the changes taking place. More and more often attention is paid to the demographic characteristics (sex-age and marriage structure) of the population as a starting point from which to begin the assessment of the territory and its reproductive potential.Nizhny Novgorod region, being a typical Russian region, has been demonstrating an unfavourable scenario of demographic situation development in recent decades. The article attempts to describe and assess the reproductive potential of the region, to identify the possibilities and limitations of fertility growth in the current conditions, based on the analysis of the ‘demographic’ factor.Materials and methods. The analysis and conclusions are based on the data of the Federal State Statistics Service on demographic processes in Russia and the region for 1990-2023 (population size, birth rate, marriage rate, divorce rate), as well as on the data of regional sociological studies on fertility and family/reproductive behaviour.Results and discussion. The results of the study provide little basis for a favourable forecast in the region. On the one hand, the sex and age structure of the population is not yet characterised by disproportion in fertile ages, except for the oldest groups. However, there is a high probability of its appearance in younger ages under current conditions. In addition, active and potential fertile groups of women are significantly smaller than older groups. The marriage structure is becoming more stable, but with a high probability of divorce, acceptability of cohabitation, and a shift of births to older groups. The studies record a persistent gap between the desired and actual number of children in different socio-demographic groups, which, from the authors' point of view, is important and requires careful research to correctly stimulate fertility.

Depopulation and deep aging: the former Yugoslav and Western Balkans space between the second demographic transition and emigration

The article introduces the tentative concept of deep aging – a label used for a situation when the overall ageing effects of the second demographic transition, due to fertility below replacement level, are topped by the excessive emigration of the fertile contingent (additional loss of active population). Deep ageing thus accelerates population decline. But the loss of fertile contingent may affect the total fertility rates and its apparent rise (TFR). Here, the tempo effect of fertility plays the decisive role. The article first assesses the demographic change in the European macroregions in the period after the fall of the Iron Curtain (1990–2020). It then analyses the changes in the area of former Yugoslavia to assess the extent of population change in the last intercensal period, 2011–2022. Building on the previous research of population loss and migration flows after the break-up of Yugoslavia, the overall population change in the region is being assessed. It is also shown that tempo distortion of fertility rates considerably affects the realistic level of fertility and that approximate completed fertility rates fell less dramatically. Since the migration data are less reliable, the analysis of intercensal change was applied to assess the migration losses across the ex-Yugoslav space. To assess the extent of deep ageing, the intercensal projection of fertile contingent was introduced. The stage of deep ageing is the most pronounced in Croatia and Serbia, especially at the younger fertile group, while the overall loss of fertile population is profound and will certainly affect the further future decrease in population. Similarly difficult demographic situation is in other post-Yugoslav countries, where only Slovenia has not yet slid into the stage of deep ageing.

Reduced Chemical Fertilizer Combined with Vermicompost Application Affects the Growth, Yield, and Quality of Watermelon

Continuous application of chemical fertilizers in plant cultivation can lead to the deterioration of the soil environment, resulting in reduced crop yield and quality. Currently, organic fertilizers, such as vermicompost, can partially replace chemical fertilizers and maximize yields while maintaining soil fertility. However, the effects of chemical fertilizers combined with vermicompost on watermelon (Citrullus lanatus) yield and quality are unclear. A field experiment was carried out on the watermelon cultivar Lihua No. 6. Six treatments were applied: no fertilizer (CK, control, 0N–0P–0K), 100% chemical fertilizer [CF, 5.4N–1P–5.4K (256, 47, and 255 kg·ha−1)], 75% chemical fertilizer + 25% organic fertilizer [A1, 5.4N–1P–5.4K (192, 35, and 191 kg·ha−1) + 2250 kg·ha−1 vermicompost], 50% chemical fertilizer + 50% organic fertilizer [A2, 5.4N–1P–5.4K (128, 24, and 127 kg·ha−1) + 4500 kg·ha−1 vermicompost], 25% chemical fertilizer + 75% organic fertilizer [A3, 5.4N–1P–5.4K (64, 12, and 64 kg·ha−1) + 6750 kg·ha−1 vermicompost], and 100% organic fertilizer (A4, 9000 kg·ha−1 vermicompost). Indices related to the growth, yield, and quality of watermelons were determined. Compared with CK, chemical fertilizer alone or in combination with organic fertilizers significantly increased growth parameters (plant height and leaf area) and chlorophyll content. The five fertilizer treatments enhanced the single fruit weight, yield, and biomass. In addition, the yield of reduced chemical fertilizer plus organic fertilizer was comparable to that of watermelons treated with CF. Compared with CF, the fertilizer treatments, especially the 1:1 mixture of chemical and organic fertilizer (A2) group, had elevated fruit-soluble solids and soluble sugar content, and reduced organic acid levels. Therefore, a combination of 50% chemical fertilizer and 50% organic fertilizer can effectively enhance the yield and quality of watermelons. These findings have important implications for guiding the management of watermelon fertilization and development of sustainable agriculture.

Hypertensive disorders and pregnancy outcomes in oocyte donation pregnancy in comparison with in vitro fertilization group

Hypertensive disorders and pregnancy outcomes in oocyte donation pregnancy in comparison with in vitro fertilization group

No tillage and organic fertilization improved kiwifruit productivity through shifting soil properties and microbiome

AbstractThe preservation of edaphic quality and productivity is critical for the ecological sustainability of vine orchards. The heavy utilization of intensified tillage and singular chemical fertilizers can shift changes in edaphic physicochemical and biological features, thus exerting significant pressure on agroecosystems. In current research, we assessed the shifts in soil physicochemical features and soil microbiome composition over 11 years carrying out no tillage and organic fertilizer substitution in a typical Chinese Guanzhong kiwifruit production area, and explore the fundamental factors that contribute to alterations in the microbial community and the influence on kiwifruit performance. Results showed that long‐term no tillage and organic fertilizer improved the soil condition by significantly increasing the proportion of soil macroaggregates, bulk density, and nutrient content (e.g., organic matter, nitrogen, and ammonia), as compared to conventional tillage with chemical fertilization. Moreover, no tillage significantly increased soil bacterial α‐diversity but had no significant effects on fungal. No tillage also enhanced the abundance of potential beneficial soil bacteria (e.g., Acidobacteria, Actinobacteria, and Nitrospira), while decreasing the abundance of Proteobacteria, Pseudomonas, and Fusarium. In addition, no tillage and mixed fertilized soil microbial network exhibited higher complexity (i.e., node and edge numbers, and positive edge proportion) and connectivity (i.e., average number of neighbors) than conventional tillage and chemical fertilization group. Changes in nitrate, ammonia, available phosphorus, and pH values accounted for the variation in the structure of soil microbial community. Hence, the utilization of both no tillage and organic fertilization practices could serve as a suitable and sustainable approach for managing kiwifruit production in the fragile environmental conditions of the Chinese Guanzhong region, and lead to an improvement in soil nutrient levels and help regulate the soil microbial community.

Transcutaneous electrical nerve stimulation (TENS) for pain control in women with primary dysmenorrhoea.

Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacological treatment that works by delivering electrical currents via electrodes attached to the skin at the site of pain. It can be an alternative to pharmacological treatments. The mechanism of action of TENS for pain relief is related to the inhibition of the transmission of painful stimuli, release of endogenous opioids, and reduced muscle ischaemia of the uterus. Although it has been used for primary dysmenorrhoea ((PD); period pain or menstrual cramps), evidence of the efficacy and safety of high-frequency TENS, low-frequency TENS, or other treatments for PD is limited. To evaluate the effectiveness and safety of transcutaneous electrical nerve stimulation (TENS) in comparison with placebo, no treatment, and other treatments for primary dysmenorrhoea (PD). We searched the Gynaecology and Fertility Group's Specialized Register of controlled trials, CENTRAL, MEDLINE, Embase, PsycINFO, AMED, CINAHL, and the Korean and Chinese language databases up to 9 April 2024. We also searched for ongoing trials in trials registries and the reference lists of relevant studies for additional trials. Language restrictions were not applied. We included randomized controlled trials (RCTs) that included women (aged 12 to 49 years) with PD. Included trials compared low-frequency TENS or high-frequency TENS with other TENS, placebo, or other treatment. Four review authors screened the trials, extracted the data according to the protocol, assessed the risk of bias using RoB 2, and assessed the certainty of evidence for all review comparisons and primary outcomes (i.e. pain relief and adverse effects) using the GRADE approach. This review replaces the current review, published in 2009. We included 20 RCTs involving 585 randomized women with high-frequency TENS, low-frequency TENS, placebo or no treatment, or other treatment. We included five comparisons: high-frequency TENS versus placebo or no treatment, low-frequency TENS versus placebo or no treatment, high-frequency TENS versus low-frequency TENS, high-frequency TENS versus other treatments, and low-frequency TENS versus other treatments. High-frequency TENS versus placebo or no treatment High-frequency TENS may reduce pain compared with placebo or no treatment (mean difference (MD) -1.39, 95% confidence interval (CI) -2.51 to -0.28; 10 RCTs, 345 women; low-certainty evidence; I2 = 88%). Two out of three RCTs reported no adverse effects and hence we were unable to estimate the effect of high-frequency TENS on adverse effects. Low-frequency TENS versus placebo or no treatment Low-frequency TENS may reduce pain compared with placebo or no treatment (MD -2.04, 95% CI -2.95 to -1.14; 3 RCTs, 645 women; low-certainty evidence; I2 = 0%). No trials reported adverse effects for this comparison. High-frequency TENS versus low-frequency TENS It is uncertain whether high-frequency TENS had an effect on pain relief compared with low-frequency TENS (MD 0.89, 95% CI -0.19 to 1.96; 3 RCTs, 54 women; low-certainty evidence; I2 = 0%). One trial contributed data on adverse effects but no adverse events occurred. High-frequency TENS versus other treatments It is uncertain whether high-frequency TENS had an effect on pain relief compared to acupressure (MD -0.66, 95% CI -1.72 to 0.40; 1 RCT, 18 women; very low-certainty evidence), acetaminophen (paracetamol) (MD -0.98, 95% CI -3.30 to 1.34; 1 RCT, 20 women; very low-certainty evidence), and interferential current therapy (MD -0.03, 95% CI -1.04 to 0.98; 2 RCTs, 62 women; low-certainty evidence; I2 = 0%). The occurrence of adverse effects did not differ significantly between high-frequency TENS and NSAIDs (OR 12.06, 95% CI 0.26 to 570.62; 2 RCTs, 88 women; low-certainty evidence; I2 = 78%). Low-frequency TENS versus other treatments It is uncertain whether low-frequency TENS had an effect on pain relief compared with acetaminophen (MD -1.48, 95% CI -3.61 to 0.65; 1 RCT, 20 women; very low-certainty evidence). No trials reported adverse effects for this comparison. High-frequency TENS and low-frequency TENS may reduce pain compared with placebo or no treatment. We downgraded the certainty of the evidence because of the risk of bias. Future RCTs should focus more on secondary outcomes of this review (e.g. requirement for additional analgesics, limitation of daily activities, or health-related quality of life) and should be designed to ensure a low risk of bias.

Male infertility is associated with differential DNA methylation signatures of the imprinted gene GNAS and the non-imprinted gene CEP41.

To investigate whether the DNA methylation profiles of GNAS(20q13.32), MEST(7q32.2), MESTIT1(7q32.2), IGF2(11p15.5), H19 (7q32.2), and CEP41(7q32.2) genes are related to the transcriptomic and epigenomic etiology of male infertility. The DNA methylation levels of spermatozoa were obtained from fertile (n = 30), oligozoospermic (n = 30), and men with normal sperm count (n = 30). The methylation status of each CpG site was categorized as hypermethylated or hypomethylated. Expression levels of target gene transcripts were determined using real-time PCR. The oligozoospermia showed a higher frequency of hypermethylation at GNASAS 1st, 3rd, and 5th CpG dinucleotides (66.7%, 73.3%, 73.3%) compared to the fertile group (33.3%, 33.3%, 40%, respectively). The normal sperm count exhibited a higher frequency of hypermethylation at the 3rd CpG of CEP41 (46.7%) than the fertile group (16.7%). Normal sperm count was predicted by CEP41 hypermethylation (OR = 1.750, 95%CI 1.038-2.950) and hypermethylation of both CEP41 and GNASAS (OR = 2.389, 95%CI 1.137-5.021). Oligozoospermia was predicted solely by GNASAS hypermethylation (OR = 2.460, 95%CI 1.315-4.603). In sperms with decreased IGF2 expression in the fertile group, we observed hypomethylation in the 2nd CpG of IGF2 antisense (IFG2AS), and hypermethylation in the 1st, 2nd, and 4th CpGs of H19. No significant relationship was found between IGF2 expression and methylation status of IGF2AS and H19 in infertile groups. The disappearance of the relationship between IGF2 expression and IGF2AS and H19 methylations in the infertile group provides new information regarding the disruption of epigenetic programming during spermatogenesis. A better understanding of sperm GNASAS and CEP41 hypermethylation could advance innovative diagnostic markers for male infertility.

Quality of Red Clover Forage in Different Organic Production Systems

The aim of this study was to determine the quality of organically grown red clover herbage and silage after being influenced by supplementary mineral fertilization. The experimental treatments were as follows: control treatment without fertilization (group C), treatment where kalimagnesia (Patentkali) was applied (group P), and treatment where potassium sulfate (SOP) was applied (group S). In each year of the experiment, first-cut herbage was harvested at the beginning of flowering and ensiled. The year of the study had a significant (p ≤ 0.05) influence on the analyzed parameters of herbage and silage, excluding the content of calcium (Ca), acetic acid (AA), and ammonia nitrogen (N-NH3). The organic production system exerted a significant (p ≤ 0.05) effect on the concentrations of crude protein (CP), acid detergent lignin (ADL), water-soluble carbohydrates (WSC), minerals (P, K, Ca, Na), lactic acid (LA), ethanol, and N-NH3. The pattern of fermentation was affected by both experimental factors. True protein (TP) content was determined at 70–84% CP in herbage and 53–65% CP in silages. The energy value and the protein value of herbage varied significantly across years of the study and in response to the combined effects of both experimental factors (p ≤ 0.05). Red clover grown in organic production systems supplied high-quality forage.

An insight into the vaginal microbiome of infertile women in Bangladesh using metagenomic approach.

The dysbiosis of vaginal microbiota is recognized as a potential underlying factor contributing to infertility in women. This study aimed to compare the vaginal microbiomes of infertile and fertile women to investigate their relationship with infertility. Metagenomic analysis was conducted on samples from 5 infertile and 5 fertile individuals using both amplicon 16S and metagenomics shotgun sequencing methods. In the infertile group, the bacterial community was primarily represented by three major bacterial genera: Lactobacillus (79.42%), Gardnerella (12.56%) and Prevotella (3.33%), whereas, the fertile group exhibited a more diverse composition with over 8 major bacterial genera, accompanied by significantly reduced abundance of Lactobacillus (48.79%) and Gardnerella (6.98%). At the species level, higher abundances of L. iners, L. gasseri and G. vaginalis were observed in the infertile group. Regarding the microbiome composition, only one fertile and two infertile subjects exhibited the healthiest Community State Types, CST-1, while CST-3 was observed among two infertile and one fertile subject, and CST-4 in three other fertile and one infertile subject. Overall, alpha diversity metrics indicated greater diversity and lower species richness in the control (fertile) group, while the infertile group displayed the opposite trend. However, beta-diversity analysis did not show distinct clustering of samples associated with any specific group; instead, it demonstrated CST-type specific clustering. Shotgun metagenomics further confirmed the dominance of Firmicutes, with a greater abundance of Lactobacillus species in the infertile group. Specifically, L. iners and G. vaginalis were identified as the most dominant and highly abundant in the infertile group. Fungi were only identified in the control group, dominated by Penicillium citrinum (62.5%). Metagenome-assembled genomes (MAGs) corroborated read-based taxonomic profiling, with the taxon L. johnsonii identified exclusively in disease samples. MAG identities shared by both groups include Shamonda orthobunyavirus, L. crispatus, Human endogenous retrovirus K113, L. iners, and G. vaginalis. Interestingly, the healthy microbiomes sequenced in this study contained two clusters, Penicillium and Staphylococcus haemolyticus, not found in the public dataset. In conclusion, this study suggests that lower species diversity with a higher abundance of L. iners, L. gasseri and G. vaginalis, may contribute to female infertility in our study datasets. However, larger sample sizes are necessary to further evaluate such association.

Comparative analysis of the testicular and uretral microbiota in azoospermia patients using next generation sequencing (NGS)

Aim. To determine the role of taxonomic bacterial diversity of the urethral and testicular microbiota in the development of male infertility using high-throughput next-generation sequencing (NGS).Material and methods. In the period between 2018 and 2022 we examined 53 patients. Three study groups were formed: Infertile patients with nonobstructive azoospermia and concomitant varicocele (n = 13) – group 1; Infertile patients with obstructive azoospermia (n = 29) – group 2; Fertile patients with confirmed paternity and testicular pathology requiring histological verification to exclude testicular oncopathology (n = 11) – group 3. Each patient underwent TESE with testicular both and urethral tissue sampling in order to compare the bacterial landscape and control the purity of the method. The obtained material was sequenced using a high-throughput method (NGS).Results.According to our findings, the testicular tissue of obstructive azoospermia patients had significantly depleted bacterial diversity in comparison to nonobstructive azoospermia and concomitant varicocele ones. Also, the fertile group turned out to be the most diverse in its taxonomic community. These results may suggest the bacterial microbiome’s influence on men’s reproductive health.Discussion.Our urogenital bacterial diversity analysis showed that human testicular tissue is not a microbiologically sterile environment and also presented new data associated with testicular tissue and its possible relations with male infertility.Conclusion. A focus on the qualitative and quantitative composition of the testicular microbial community may form the new basis in the diagnosis and treatment of male infertility associated with various types of azoospermia

P-336 Efficacy of Gonadotrophin (GnRH) antagonists for endometriosis-associated pelvic pain - A systematic review and meta-analysis

Abstract Study question Are Gonadotropin-releasing hormone (GnRH) antagonists effective and safe in managing pain associated with endometriosis? Summary answer GnRH antagonists seem effective and safe in managing endometriosis-associated pain for at least 12 weeks of use. There is uncertainty with the evidence. What is known already GnRH agonists are commonly used as effective second-line treatment for endometriosis-associated pain. However, these agonists have drawbacks and are not well-tolerated by many women. GnRH antagonists, offer potential advantages over the agonists while providing similar efficacy. They lack the initial stimulatory effects thereby avoiding the initial flare-up of symptoms, which is common with agonists. Furthermore, unlike agonists, which are mainly available as injections, the antagonist are also available as oral preparations, which allow titration of doses. In-vitro and animal studies have shown antagonists to induce regression of endometriotic lesions by apoptosis. However, their efficacy in relieving endometriosis-related pains remains uncertain. Study design, size, duration Extensive electronic search was conducted by the Cochrane Gynaecology and Fertility group, up to October 2023 to identify randomised controlled trials (RCTs) evaluating efficacy of GnRH antagonists in managing endometriosis-related pains compared with placebo and/or GnRH agonists. The main searched databases included CENTRAL, MEDLINE and EMBASE. Screening and selection of suitable studies were undertaken. Study eligibility criteria included treatment for ≥12 weeks, laparoscopically confirmed endometriosis and assessment of pelvic pain scores as the primary endpoint. Participants/materials, setting, methods Primary end-point was a change in endometriosis-related pain score after 12-week treatment with GnRH antagonists compared with placebo and/or GnRH agonists. Changes in pain and quality of life (QoL) scores and adverse-events of GnRH-antagonists were compared between the antagonist versus the agonist/placebo groups. Data were analysed using RevMan software (V5.4) to calculate the standard mean difference (SMD) for continuous data, and the risk ratios (RRs) with 95% confident intervals (95% CI) for categorical data. Main results and the role of chance Seven eligible RCTs (n = 3043) were included, all of which compared GnRH-antagonist versus placebo, and only three also compared versus GnRH-agonist (leuprorelin). The GnRH-antagonists included ASP1707, Elagolix, Linzagolix and Relugolix. Meta-analysis of overall pelvic pain data from seven RCTs (n = 1684) showed significantly greater reduction in pain scores after 12 weeks of GnRH-antagonist versus placebo at low (SMD -0.29 95%CI -0.39 to -0.19; I2=0) and high doses (SMD-0.53 95%CI -0.63 to -0.43, I2=38%). Similarly, meta-analysis of other pains (dysmenorrhoea, non-menstrual pain, and dyspareunia) showed significantly greater pain score reduction with GnRH-antagonists versus placebo. Meta-analysis of overall pelvic pain from two RCTs (n = 263) comparing GnRH-antagonist versus leuprorelin showed comparable reduction in pain scores after 12 weeks at low (SMD 0.33 95%CI 0.09 to 0.58, I2=44%) and high doses (SMD 0.06 95%CI -0.19 to 0.30, I2=0%). Similarly, meta-analysis of other forms of pain revealed comparable reductions of pain scores between both drugs. Meta-analysis of QoL data (2RCTs, n = 259) revealed significantly greater improvements in scores with leuprorelin versus antagonists at low (SMD 0.74 95% CI 0.46 to 1.01; I2=98%) and high doses (SMD 0.35, 95%CI, 0.09 to 0.60, I2=97%). The most frequently reported treatment-related side-effects were hot-flushes, headaches and nasopharyngitis. No life-threatening side-effects were reported. Limitations, reasons for caution There was high heterogeneity between studies (e.g. differences in antagonists and pain scoring systems). No information was provided on prior endometriosis surgery, which is a confounding factor. Additionally, declared COI by authors of all trials could introduce high risk of bias. Evidence certainty was therefore deemed low to very low. Wider implications of the findings GnRH-antagonists seem to offer a promising treatment for endometriosis-related pain, with comparable efficacy to the agonists, but with several potential advantages. However, given the low quality and uncertainty of the evidence in this meta-analysis, high quality RCTs with robust designs are needed before making any firm recommendations for clinical practice. Trial registration number not applicable

O-016 To be or not to be capacitated after sperm preparation: tyrosine phosphorylation as predictive indicator for capacitation status and male fertility potential

Abstract Study question Can post-capacitation tyrosine phosphorylation (TP) levels distinguish “capacitated” from “non-capacitated” molecular profiles, and are these similarly distributed among infertile and fertile men? Summary answer TP levels after 3 hours of incubation post-capacitation robustly predicted “capacitated” and “non-capacitated” molecular profiles, with the latter being more common in the infertile group. What is known already TP is considered one of the most relevant intracellular signalling events in the capacitation process and in the regulation of sperm function. Despite the recognized general trend of increased TP post-capacitation, interindividual variability can be observed, with some samples showing phosphorylation levels like those before capacitation. Currently, no test is conducted on capacitated samples to verify whether they have indeed acquired a molecular pattern consistent with capacitation. Therefore, the objective of this study was to evaluate the predictive ability of post-capacitation TP levels measured at various time points in distinguishing molecularly “capacitated” patterns from “non-capacitated” ones. Study design, size, duration Prospective experimental study conducted from June 2021 to September 2023 with the aim of assessing TP levels in different populations before (B-cap) and after (A-cap) in vitro capacitation and after different incubation times (1h and 3h) under capacitating conditions. A total of 335 samples, including infertile patients (n = 111), tests for the inclusion in the sperm donation program (n = 57) and sperm donors (n = 167) were included. Participants/materials, setting, methods Semen samples were examined following WHO guidelines and in vitro capacitation was performed using density gradient centrifugation. Flow cytometry was used to assess global TP (%) (B-cap, A-cap, 1h and 3h). Receiver operating characteristic (ROC) curve analyses were performed to evaluate the discriminatory potential of post-capacitation TP levels (A-cap, 1h and 3h) against B-cap, aiming to distinguish between “capacitated” and “non-capacitated” molecular profiles. Chi-square test was used to compare proportions. P &amp;lt; 0.05 was considered statistically significant. Main results and the role of chance The dataset was randomly split into two subsets, one for model development and the other for subsequent performance evaluation. The areas under the curve (AUC) for A-cap, 1h and 3h were 73.8% (95% CI = 69.3%-78.3%), 84.5% (81.0%-88.0%), and 92.7% (90.4%-95.0%), respectively. Sensitivity and specificity values were calculated for the curve with the highest AUC, constructed with TP values from non-capacitated (B-cap) and 3-hours incubated (3h) samples. The selected cut-off point was 4.35% (sensitivity: 85.0%, specificity: 85.7%). The model exhibited robust overall performance in identifying molecularly “capacitated” and “non-capacitated” samples, with a sensitivity, specificity, false positive rate and false negative rate of 85.2%, 89.7%, 9.4% and 12.9%, respectively. Accuracy, positive predictive value and negative predictive value were 87.3%, 90.2%, and 84.5%, respectively. In infertile patients, using TP values at the third hour of incubation and the selected cut-off, the model identified 73.9% (82/111) of samples as molecularly “capacitated” and 26.1% (29/111) as “non-capacitated,” despite laboratory capacitation. In contrast, in the control group, the model identified 93.4% (156/167) of samples as “capacitated” and 6.6% (11/167) as “non-capacitated”. A significantly higher number of seminal samples were identified as “non-capacitated” in the infertile patient group compared to the proven fertile donor group (p &amp;lt; 0.001). Limitations, reasons for caution The model's performance demonstrates its utility and reliability in identifying samples with a molecular “non-capacitated” profile, even after in vitro capacitation. However, further refinement is possible by incorporating additional data. External validation is essential to confirm generalizability of the results. Wider implications of the findings The assumption that a molecular capacitation profile is acquired following in vitro sperm processing may be questioned. Our results suggest a potential link between the selected threshold and fertility, offering insights into male infertility aetiology and paving the way for personalized intervention strategies. Trial registration number NCT04962100

P-498 Multicentre two-arm randomised controlled trial of Beyond Fertility: A brief face-to-face psychosocial intervention to promote patients’ healthy adjustment when ending unsuccessful fertility treatment

Abstract Study question Is Beyond Fertility effective in ameliorating the negative impact of ending unsuccessful fertility treatment (EoT) on patients’ quality of life? Summary answer Patients allocated to Beyond Fertility (intervention group) reported higher quality of life six months after EoT than patients allocated to care as usual (control group). What is known already Around four in every ten patients end all IVF/ICSI treatment cycles without achieving a live birth (referred as EoT). Recent mixed-methods research indicates 93.3% of patients want to be prepared for and supported through EoT. Two interventions have been proven to improve the wellbeing of people with an unfulfilled wish for children after they proactively started trying to conceive, but, to our knowledge, no intervention focused on preparing and supporting fertility patients through this experience. Following the Medical Research Council guidelines, we developed Beyond Fertility, a face-to-face psychosocial intervention integrating preventive with early-interventive care to ease patients’ adjustment during EoT. Study design, size, duration Multicentre two-arm parallel-group open-label RCT with 1:1 allocation to intervention (Beyond Fertility) or control (usual mental-healthcare at participating clinics, CaU). Beyond Fertility includes seven therapeutic sessions: one (individual/couple) within one month the last IVF/ICSI cycle (preventive care) and six (individual/couple and group) sessions after EoT (early-interventive care). Participants self-reported on quality-of-life one month before their last reimbursed IVF/ICSI cycle (T1, pre-session 1), two weeks (T2, post-session 1) and six months (T4, post-intervention) after cycle ended. Participants/materials, setting, methods Women patients were consecutively screened and invited to participate with their partners at four public fertility centres in Portugal (Dez 2021-Mar 2023). Inclusion criteria were being adults scheduled to initiate their last reimbursed IVF/ICSI cycle within one month. Primary outcome was quality-of-life, self-reported online with FertiQoL (Melo et al., 2012). Linear-mixed-effect models compared changes in quality-of-life from T1 to T2 and T4 in intervention and control groups. Outcome data were reported for modified intention-to-treat (mITT). Main results and the role of chance From 143 eligible women(90.51% eligibility rate), 74(51.75% consent rate) and 41 partners completed T1 assessment(N=115) and were allocated to Beyond Fertility(n=60) or CaU(n=55). Average age was 38 years. Sixty-four percent were women, 62% had university education, 92% were employed, all were in a heterosexual relationship, and 30% had children. Participants were undergoing treatment for around three years. Fourteen(14.14%) achieved a pregnancy in their last reimbursed IVF/ICSI cycle, 34(34.34%) did not achieve a pregnancy and ended treatment (i.e. faced EoT), and 51(51.52%) did not achieve a pregnancy and continued treatment. Among participants who were allocated to Beyond Fertility and faced EoT, eight(44.44%) withdrew from its early-interventive care mainly due to not accepting the group format, and only four(22.22%) received the full intervention due to practicality issues. Among participants who faced EoT, participation rates for Beyond Fertility and CaU groups were 88.89%(n=16) and 100%(n=16) at T2, and 77.78%(n=14) and 93.75%(n=15) at T4, respectively. Among these participants, those allocated to Beyond Fertility had an estimated mean quality-of-life score around 6 points higher than participants allocated to CaU at T2 (β=6.17, p=0.113) and around 9 points higher (almost one standard deviation above the baseline mean of the total sample) at T4 (β=8.95, p=0.035). Limitations, reasons for caution The trial was not blind, and therefore, response bias cannot be ignored. Attrition was slightly higher in the Beyond Fertility than the CaU group, suggesting that mITT may marginally overestimate the effect of Beyond Fertility. Wider implications of the findings Structured psychosocial care that starts during treatment and continues in its aftermath to support patients who end treatment without achieving pregnancy is effective in ameliorating declines in quality-of-life, suggesting it can ease adjustment during this difficult life transition. Benefits may be maximised by tailoring it to patients’ preferred delivery format. Trial registration number ISRCTN Registry ISRCTN85897617