Group Of Infertile Patients Research Articles

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 < 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 < 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

Effects of Varicocele Repair on Sperm DNA Fragmentation and Seminal Malondialdehyde Levels in Infertile Men with Clinical Varicocele: A Systematic Review and Meta-Analysis.

Varicoceles can be a source of elevated seminal oxidative stress (OS) and sperm DNA fragmentation (SDF). However, it remains unclear whether varicocele repair (VR) could reduce these parameters. This systematic review and meta-analysis (SRMA) aims to investigate the impact of VR on SDF and seminal malondialdehyde (MDA). A literature search was performed in Scopus, PubMed, Ovid, Embase, and Cochrane databases. This SRMA included randomized controlled trials and observational studies reporting the pre- and postoperative levels of SDF and seminal OS in infertile men with clinical varicocele that underwent VR. Subgroup analyses included techniques of VR and SDF testing. The effect size was expressed as standardized mean difference (SMD). Out of 1,632 abstracts assessed for eligibility, 29 studies with 1,491 infertile men were included. The analysis showed a significant reduction in SDF after VR, compared to preoperative values (SMD -1.125, 95% confidence interval [CI] -1.410, -0.840; p<0.0001) with high inter-study heterogeneity (I²=90.965%). Reduction in SDF was evident with microsurgical technique and non-microsurgical inguinal approaches (SMD -1.014, 95% CI -1.263, -0.765; p<0.0001, and SMD -1.495, 95% CI -2.116, -0.873; p<0.0001), respectively. Reduction in SDF was significant irrespective of testing was done by sperm chromatin dispersion (SMD -2.197, 95% CI -3.187, -1.207; p<0.0001), sperm chromatin structure assay (SMD -0.857, 95% CI -1.156, -0.559; p<0.0001) or TUNEL (SMD -1.599, 95% CI -2.478, -0.719; p<0.0001). A significant decrease in seminal MDA levels was observed following VR (SMD -2.450, 95% CI -3.903 to -0.997, p=0.001) with high inter-study heterogeneity (I²=93.7%). Using pre- and post-intervention data, this SRMA indicates a significant reduction in SDF and seminal MDA levels in infertile men with clinical varicocele treated with VR. These findings may have important implications for the future management of this selected group of infertile patients.

Evaluation of ovarian reserve in unexplained ınfertile cases: a case-controlled study

BackgroundThe aim of this study was to evaluate the effectiveness of current ovarian reserve tests in unexplained infertile cases.Material and methodsThis case–control study was conducted on 70 unexplained infertile women who were included in a tertiary university hospital. Both groups of basal FSH, estradiol, antimullerian hormone (AMH), inhibin B, ovarian volume, total antral follicle count (AFC), ovarian volume, and ovarian stromal blood flow (peak systolic velocity (PSV), S/D (systole and diastole ratio), resistance index (RI), and pulsatility index (PI)) values were compared.ResultsThe mean AMH, inhibin B, PSV, and stromal blood flow values of the control group patients were higher than those in the unexplained infertility group. However, the values of the means of RI and PI of the cases in the control group were lower than those in the infertility group. When PI’s value was ≥ 2.00, its sensitivity was 65.7%, and its specificity was 64.3%. In the case of the RI, its value was ≥ 0.745, its sensitivity was 65.7%, and its specificity was 62.9%. In order to show ovarian reserve in unexplained infertile cases, the sensitivity values can be sorted from high to low as follows: PI > RI > estradiol > FSH > ovarian volume > AFC > inhibin B > stromal blood flow > PSV > S/D.ConclusionIn the unexplained infertile patient group with normal ovarian reserve test results, basal estradiol, decreased PI, and RI values may be used as good ovarian reserve predictors.

P-324 The impact of intrafollicular iron on granulosa cells and follicular development in women with ovarian endometriomas

Abstract Study question Whether and how iron overload in ovaries affects follicular development in patients with ovarian endometriosis? Summary answer Iron overload microenvironment that affects the growth and development of granulosa cells and oocytes, leading to fewer oocytes retrieved and decreased ovarian reserve. What is known already The presence of an endometrioma with the high levels of free iron, shows an adverse effect on the surrounding ovarian tissue as reflected by a reduced number of developing follicles and oocytes retrieved in in vitro fertilization cycles. However there is few published data available focusing on the potential risk of free iron in folliculogenesis of patients with endometrioma. This study aimed to identify the impact of intrafollicular iron on granulosa cells (GCs) and follicular development in ovarian endometrioma patients. Study design, size, duration The clinical data of 50 patients with unilateral ovarian endometriosis who underwent in vitro fertilization, intracytoplasmic sperm injection, and embryo transfer in the Reproductive Medicine Center of Sun Yat-sen Memorial Hospital from October 2019 to September 2021 were prospectively collected. Meanwhile, 50 infertile patients without endometriosis were selected as the control group; they were matched by age, duration of infertility, and body mass index. Participants/materials, setting, methods Ffollicular fluid and granulosa cells were collected.The clinical data of the two groups of infertile patients were compared. The iron ion in follicular fluid was detected by colorimetry,transferrin, eatrogen and the ferritin concentration in follicular fluid was detected by enzyme-linked immunosorbent assay. qPCR and Western blotting were used to detect the expression of iron homeostasis-related genes and proteins in luteinized granulosa cells. Oocyte retrieval rates, maturation and fertilization rates were analyzed. Main results and the role of chance There were no significant differences in baseline data, including age, duration of infertility, BMI, between the two groups. The AFC and AMH in the experimental group were significantly lower than that in the control group. The number of oocytes obtained in the experimental group was 8.35 ± 5.80 vs. 13.71 ± 5.62, P &amp;gt; 0.05. P = 0.003; and the average oocyte retrieval rate (68.56 ± 34.97% vs. 88.64 ± 23.11%, p = 0.032) was significantly lower than those in the control group. The concentration of an iron in the follicular fluid of the cystic ovary (63.63 ± 24.69 mg/L) was significantly higher than that of the healthy ovary (51.65 ± 13.80 mg/L) and the control ovary (39.23 ± 16.89 mg/L), P = 0.005. The levels of ferritin light chain and heavy chain were significantly higher but transferrin and estrogen were lower in the cystic ovary than in the healthy ovary and the control ovary. qPCR and Western blot results showed that the mRNA and protein expression of transferrin receptor 1, ferritin heavy chain, and ferritin light chain were significantly higher in the cystic ovary than in the healthy ovary and the control ovary. Limitations, reasons for caution For limitation of sampling, we could not obtain the information from human growing follicles, animal experiments would be involved in our subsequent study. Wider implications of the findings These results provide novel information suggesting that when surgical removal of the endometrioma is not an option, further investigation is needed to clarify whether and how the medical therapy may limit or slow the damage caused by endometrioma. Trial registration number not applicabl

H19 Sperm Methylation in Male Infertility: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis summarize the difference in the methylation of the H19 gene in patients with abnormal versus normal conventional sperm parameters. It also evaluates the effects of age and sperm concentration on H19 methylation in spermatozoa using meta-regression analysis. It was performed according to the MOOSE guidelines for meta-analyses and Systematic Reviews of Observational Studies and the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). The quality of the evidence reported in the studies included was assessed using the Cambridge Quality Checklists. A total of 11 articles met our inclusion criteria. Quantitative analysis showed that H19 methylation levels were significantly lower in the group of infertile patients than in fertile controls. The reduction in methylation was much more pronounced in patients with oligozoospermia (alone or associated with other sperm parameter abnormalities) and in those with recurrent pregnancy loss. Meta-regression analysis showed the results to be independent of both patient age and sperm concentration. Therefore, the H19 methylation pattern should be evaluated among couples accessing assisted reproductive techniques (ART), in order to gain prognostic information on ART outcome and offspring health.

Effects of anti-mullerian hormone, antral follicle count, and follicle stimulating hormone values on pregnancy outcomes in a case with polycystic ovary syndrome

Objective: In this study, it was aimed to predict pregnancy by anti-mullerian hormone, follicle-stimulating hormone, and antral follicle count values of infertile patients with PCOS. Methods: This retrospective study has been conducted on 555 patients diagnosed with PCOS (polycystic ovary syndrome) according to the Rotterdam Criteria, referred for infertility in the IVF Clinic of Istanbul Training and Research Hospital in the 2010-2019 study. Clinical pregnancy results have been analyzed together with anti-mullerian hormone, antral follicle count, and follicle-stimulating hormone levels. Results: The age of the patients within the group of clinical pregnancy is significantly higher than the group without pregnancy (p ˂ 0.05). Follicle-stimulating hormone (iu/ml) and anti-mullerian hormone (ng/ml) values do not differ significantly (p 0.05) in the group with and without clinical pregnancy. For the group with clinical pregnancy, the antral follicle count value is found to be significantly higher (p ˂ 0.05) than the group without pregnancy. The age of the patients in the group with clinical pregnancy was found to be significantly higher than the group without pregnancy. (p ˂ 0.05). Follicle stimulating hormone (iu/ml) and anti-müllerian hormone (ng/ml) values did not differ significantly in the group with and without clinical pregnancy (p 0.05). Antral follicle count value was found to be significantly higher in the group with clinical pregnancy than in the group with out pregnancy (p ˂ 0.05). Although AFC was found to be significantly higher in the group with clinical pregnancy than in the non-pregnant group, it was examined diagnostically by ROC analysis, but the diagnostic capacity of this variable to distinguish between pregnant and non-pregnant women was not found to be sufficient. (AUC&lt;0.70). Conclusion: We found that anti-mullerian hormone and follicle-stimulating hormone are not related to clinical pregnancy outcomes in the infertile patient group diagnosed with PCOS (polycystic ovary syndrome). Plus, although the AFC value in the group with pregnancy was significantly higher than the group without pregnancy, its diagnostic capacity was not found to be sufficient.

Prevalence of Chlamydia trachomatis, Ureaplasma parvum and Mycoplasma genitalium in Infertile Couples and the Effect on Semen Parameters.

Chlamydia trachomatis, Ureaplasma parvum, and Mycoplasma genitalium are common sexually transmitted microorganisms. Our study aimed to determine the prevalence of C. trachomatis, U. parvum, and M. genitalium in infertile and fertile couples and the effect of these microorganisms on semen parameters. In this case-control study, samples were collected from 50 infertile couples and 50 fertile couples and were subjected to the routine semen analysis and Polymerase chain reaction (PCR). C. trachomatis and U. parvum were detected in 5 (10%) and 6 (12%) of semen samples from infertile men. Also, out of 50 endocervical swabs from the infertile women, C. trachomatis and M. genitalium were detected in 7(14%) and 4 (8%) of swab specimens, respectively. In the control groups, all of the semen samples and endocervical swabs were negative. Also, in the group of infertile patients infected with C. trachomatis and U. parvum, sperm motility was lower than uninfected infertile men. The results of this study showed that C. trachomatis, U. parvum, and M. genitalium are widespread among the infertile couples in Khuzestan Province (Southwest of Iran). Also, our results showed that these infections can decrease the quality of semen. For the prevention of the consequences of these infections, we suggest a screening program for infertile couples.

Diagnostic Accuracy of Salivary aMMP-8 Test in Infertile Women and Blood Finding Analysis.

IntroductionThe literature reviewed in this paper suggests that infertile patients present worse periodontal status, which may be causative to conception complications. This study aimed to validate an aMMP-8 point-of-care mouth rinse test in the population of women with unexplained infertility and compare it to age-matched fertile women with and without periodontitis. Furthermore, blood sampled inflammatory parameters were analyzed and compared between the two groups. It was hypothesized that the infertile women would present worse periodontal status and a greater number of positive aMMP-8 tests than fertile women, and they would have increased inflammatory blood parameters.Material and methodsThe study included 50 healthy norm-ovulatory females aged 25-45 years with strictly defined unexplained (idiopathic) infertility, and 50 healthy norm-ovulatory women of the same age who had conceived and delivered naturally.ResultsThe sensitivity and specificity of the test for detecting periodontitis was 84% and 72% in the group of infertile patients, 88% and 68% in the group of fertile patients and 86% and 70% in the overall patient population. Infertile patients with periodontitis had less advanced periodontitis than the control group although this difference was not statistically significant. Blood inflammatory markers were significantly higher in infertile than in fertile women.ConclusionThis study has shown that infertile patients had better periodontal status and less advanced periodontitis than fertile women of the same age. Therefore, when interpreting the results of aMMP-8 tests for diagnosis of periodontitis, one should keep in mind the periodontal status of the examined population.

Second look hysteroscopy following hysteroscopic septum resection improves reproductive outcomes in patients undergoing ICSI

The aim of this study was to compare the reproductive outcomes between infertile women who underwent hysteroscopic uterine septum resection and those who required a second look hysteroscopy due to residual septum prior to intracytoplasmic sperm injection (ICSI) cycles with selective single ‘Grade A’ embryo transfer (ET). All second look hysteroscopies were performed due to partial remnant septum in a control three dimensional transvaginal ultrasonography (3D TVUSG) after the first hysteroscopic resection. Miscarriage and biochemical pregnancy rates were not different between the groups while clinical pregnancy and live birth rates were significantly higher in Group 2 than in Group 1. Second look hysteroscopic metroplasty performed to restore remnant septum significantly improves live birth rate as well as clinical pregnancy rates while it appears not to alleviate abortion and biochemical pregnancy rates in women undergoing ICSI-ET. IMPACT STATEMENT What is already known on this subject? The effect of hysteroscopic septum resection on reproductive outcomes in IVF treatment in infertile patients with uterine septum is not clearly known. What do the results of this study add? With the selective single ET strategy, complete or partial hysteroscopic correction of the uterine septum before ICSI and subsequent resection of the residual septum with control hysteroscopy significantly increases the live birth rates in the infertile population. What are the implications of these findings for clinical practice and/or further research? In the group of infertile patients with uterine septum, second control hysteroscopy should be performed 1 month later for residual septum or adhesions after hysteroscopic septum resection performed once.

Comparing the ICSI outcome between different causes of subfertility and estimate the role of IL-1β in predicting ICSI outcome.

Background : The physiological regulation of the ovary is a complicated process ; the growth factor, steroid hormones, gonadotropins, and cytokines all take part. Inflammatory cytokines are found in many compartments of the ovary, such as the follicles. The ovarian tissue produces them in addition to the macrophages. In this study, we aimed to compare the level of serum and follicular fluid IL-1Beta (IL-1β) for different groups of infertile patients, comparing the ICSI outcome between sub-fertile couples due to different causes. The results of this study IL-1β was significantly higher in the patients with unexplained subfertility (p-value < 0.05), no significant difference was found in the ICSI outcome between patients with different causes of subfertility. The lowest pregnancy rate was found in patients with unexplained subfertility, but the difference is insignificant. In conclusion, immunity plays a role in unexplained subfertility as patients with unexplained subfertility have a significantly higher serum level IL-1β than the other causes of subfertility. However, IL-1β does not affect ICSI outcome. Therefore, the ICSI outcome is not affected by the cause of subfertility. J. Med. Invest. 69 : 180-184, August, 2022.

The Significance of Planned Fertility Preservation for Women With Endometrioma Before an Expected Ovarian Cystectomy

Endometrioma is known to reduce the ovarian reserve and the extent of the decrease is more severe when ovarian surgery is performed. Therefore, to prevent this decline in fertility, patients with endometrioma are considered candidates for preoperative fertility preservation (FP). In this study, we evaluate the efficacy of FP in women with endometrioma before planned ovarian surgery. A total of 95 cycles in 62 patients with endometrioma, undergoing controlled ovarian stimulation (COS) for FP using a gonadotropin-releasing hormone (GnRH) antagonist protocol before an expected ovarian surgery, were enrolled retrospectively. COS outcomes were compared according to endometrioma laterality. Additionally, first COS cycle outcomes in patients with endometrioma were compared with those in infertile patients, or in patients with a benign ovarian cyst using propensity score matching. When multiple COS cycles were performed, the results of cumulative cycles were analyzed. Embryo quality was worse in the bilateral endometrioma group. Compared with the infertile patient group, the patients with endometrioma had significantly lower Anti-Müllerian Hormone (AMH) and fewer numbers of oocytes retrieved (median, 3.3 vs. 1.2, p<0.001; 7.0 vs. 4.0, p=0.009, respectively). Compared with mature oocytes in infertile patients or patients with a benign cyst, mature oocytes were fewer in patients with endometrioma, but this was not statistically significant (median, 4.0 vs. 3.0, p=0.085; 5.5 vs. 3.0, p=0.052, respectively). The median value of the cumulative number of cryopreserved oocytes or embryos was 14.5 up to the fourth cycle compared to 3 up to the first cycle, with cumulative effect. Women with endometrioma should be counseled for FP before planned ovarian cystectomy. The number of cryopreserved oocytes or embryos can be increased by repeated cycles.

Whole-exome sequencing of a cohort of infertile men reveals novel causative genes in teratozoospermia that are chiefly related to sperm head defects.

Can whole-exome sequencing (WES) and in vitro validation studies identify new causative genes associated with teratozoospermia, particularly for sperm head defect? We investigated a core group of infertile patients, including 82 cases with unexplained abnormal sperm head and 67 individuals with multiple morphological abnormalities of the sperm flagella (MMAF), and revealed rare and novel deleterious gene variants correlated with morphological abnormalities of the sperm head or tail defects. Teratozoospermia is one of the most common factors causing male infertility. Owing to high phenotypic variability, currently known genetic causes of teratozoospermia can only explain a rather minor component for patients with anomalous sperm-head shapes, and the agents responsible for atypical sperm head shapes remain largely unknown. We executed WES analysis of a Chinese cohort of patients (N = 149) with teratozoospermia to identify novel genetic causes particularly for defective sperm head. We also sought to reveal the influence of different abnormalities of sperm morphology on ICSI outcome. In this study, a cohort of 149 infertile men (82 with abnormal sperm head and 67 with MMAF) were recruited. We implemented WES on infertile patients and analyzed the negative effects of the mutations of candidate genes on their protein conformations and/or expression. We also investigated the candidate genes' spatiotemporal expression/localization during spermatogenesis in both humans and mice, and explored their interactions with proteins that are known to be involved in sperm development. We also compared the ICSI outcomes of the affected individuals with various aberrations in sperm morphology. We identified rare and deleterious variants of piwi like RNA-mediated gene silencing 4 (PIWIL4: 1/82 patients, 1.21%), coiled-coil and C2 domain containing 1B (CC2D1B: 1/82 patients, 1.21%), cyclin B3 (CCNB3: 1/82 patients, 1.21%), KIAA1210 (KIAA1210: 2/82 patients, 2.43%) and choline phosphotransferase 1 (CHPT1: 1/82 patients, 1.21%), which are novel correlates of morphological abnormalities of the sperm head; functional evidence supports roles for all of these genes in sperm head formation. The mutations of septin 12 (SEPTIN12: 2/82 patients, 2.43%) are suggested to be associated with acrosome defects. We additionally observed novel causative mutations of dynein axonemal heavy chain 2 (DNAH2: 1/67 patients, 1.49%), dynein axonemal heavy chain 10 (DNAH10: 1/67 patients, 1.49%) and dynein axonemal heavy chain 12 (DNAH12: 1/67 patients, 1.49%) in patients with MMAF, and revealed a significantly lower fertilization rate of the abnormal sperm-head group compared to the MMAF group following ICSI. Consequently, our study also suggests that the mutations of PIWIL4 and CC2D1B might be circumvented by ICSI to a degree, and that CHPT1 and KIAA1210 loss-of-function variants might be associated with failed ICSI treatment. In this study, we discovered the relationship between the genotype and phenotype of the novel causative genes of sperm head deformities in humans. However, the molecular mechanism of the relevant genes involved in sperm head development needs to be further illuminated in future research. Furthermore, evidence should be provided using knockout/knock-in mouse models for additional confirmation of the roles of these novel genes in spermatogenesis. This cohort study of 149 Chinese infertile men documents novel genetic factors involved in teratozoospermia, particularly in anomalous sperm head formation. For the first time, we suggest that SEPTIN12 is related to human acrosomal hypoplasia, and that CCNB3 is a novel causative gene for globozoospermia in humans. We also uncovered variants in two genes-KIAA1210 and CHPT1associated with acrosomal biogenesis in patients with small or absent acrosomes. Additionally, it is postulated that loss-of-function mutations of PIWIL4 and CC2D1B have a contribution to the abnormal sperm-head formation. Furthermore, we are first to demonstrate the influence of different sperm morphologies on ICSI outcomes and indicates that the abnormal sperm head may play a significant role in fertilization failure. Our findings therefore provide valuable information for the diagnosis of teratozoospermia, particularly with respect to abnormalities of the sperm head. This will allow clinicians to adopt the optimal treatment strategy and to develop personalized medicine directly targeting these effects. This work was financed by the West China Second University Hospital of Sichuan University (KS369 and KL042). The authors declare that they do not have any conflicts of interests. N/A.

Levels of anxiety sensitivity, somatosensory amplification and alexithymia in patients with unexplained infertility.

In this study, we aimed to focus on the psychological aspect of unexplained infertility by comparing their psychological features to those of infertile patients with a known causes and fertile patients. Sixty unexplained infertility patients, 50 infertile patients with a known cause and 56 fertile patients were included in the study. Patients were evaluated using socio-demographic data form, Toronto Alexithymia Scale (TAS-20), Somatosensory Amplification Scale (SAS) and Anxiety Sensitivity Index (ASI-3). No significant differences in the levels of alexithymia, somatosensory amplification and anxiety sensitivity were detected between the groups (P>.05). When the correlation of clinical scale scores with each other was analysed in the whole group of infertile patients regardless of the cause, a weak positive correlation was found between anxiety sensitivity and difficulty in identifying feelings. In our study, it has been found out that; regardless of the knowledge of the aetiology of infertility, the levels of alexithymia, somatosensory amplification and anxiety sensitivity of infertile cases did not differ from those of fertile women. However, it has been shown that as the difficulty in identifying emotions increases in infertile cases, anxiety sensitivity, which may cause psychological infertility, also increases.

COMPARISON OF DISPOSITION DECISIONS OF ELECTIVE FERTILITY PRESERVATION VERSUS FERTILITY TREATMENT PATIENT POPULATIONS UTILIZING ASSISTED REPRODUCTIVE TECHNOLOGIES

The objective of this study is to compare surplus oocyte or embryo disposition decisions in the elective fertility preservation (FP) and fertility treatment (FT) populations. Retrospective cohort study conducted at a single academic medical center. Patients who underwent ART cycles between January and December 2019 were included. Demographic, occupational and insurance data were collected from medical records and disposition decisions at age 50 and at death were gathered from consent forms completed prior to cycle initiation. Disposition options include disposal, donation to research, transfer to a storage facility, or reassignment of ownership. Descriptive statistics were reported as mean ± (SEM) for continuous variables and percentages for categorical variables. All continuous variables were compared using Mann-Whitney test, and categorical variables were compared using Fisher’s exact test or Chi-square test. A p-value<0.05 was considered statistically significant. All statistical analyses were done using GraphPad Prism software. When investigating disposition decisions at age 50, the elective FP population predominantly elected to donate oocytes to research while the FT population elected to discard supernumerary embryos (OR 0.5667 [0.3905-0.8315], p=0.0032). As such, the elective FP population predominantly chose non-disposal disposition decisions compared to the FT population (OR 0.2914 [0.2060-0.4131], p<0.0001). An analysis of disposition decisions at death showed that there was no difference in the proportion of each population that discarded versus donated to research. When comparing disposal to any other decision, FT patients were more likely to discard while elective FP patients elected non-disposal decisions (OR 0.3540 [0.2520-0.4996], p<0.0001). Both populations had a majority that elected other options than donation to research, however a significantly higher proportion did so within the elective FP population (OR 0.6721 [0.4879-0.9416], p=0.0236). The FT population represents a group of infertility patients, in contrast to the elective FP population who are mostly unaware of their fertility status at the time of cycle start. The odds that elective FP patients donate to research compared to FT patients reflects a differential value placed on oocytes compared to embryos in these two populations. This phenomenon touches on the perceived “moral status” held by an embryo that oocytes do not, that in turn influences patients’ desire for these to be a substrate for research. Furthermore, the increased odds of the FT population to dispose embryos than the elective FP population to dispose oocytes implies that in the case of oocytes, FP patients are more comfortable with gamete use in research or reassignment of ownership while FT patients want to retain full control of embryo fate.

Reproductive senescence impairs the energy metabolism of human luteinized granulosa cells

Research questionFemale age is the single greatest factor influencing reproductive performance and granulosa cells are considered as potential biomarkers of oocyte quality. Is there an age effect on the energy metabolism of human mural granulosa cells? DesignObservational prospective cohort and experimental study including 127 women who had undergone IVF cycles. Women were allocated to two groups: a group of infertile patients aged over 38 years and a control group comprising oocyte donors aged less than 35 years. Individuals with pathologies that could impair fertility were excluded from both groups. Following oocyte retrieval, cumulus and granulosa cells were isolated and their bioenergetic properties (oxidative phosphorylation parameters, rate of aerobic glycolysis and adenine nucleotide concentrations) were analysed and compared. ResultsHuman mural luteinized granulosa and cumulus cells present high rates of aerobic glycolysis that cannot be increased further when mitochondrial ATP synthesis is inhibited. Addition of follicular fluid to the experimental media is necessary to reach the full respiratory capacity of the cells. Granulosa cells from aged women present lower mitochondrial respiration (12.8 ± 1.6 versus 11.2 ± 1.6 pmol O2/min/mg; P = 0.046), although mitochondrial mass is not decreased, and lower aerobic glycolysis, than those from young donors (12.9 ± 1.3 versus 10.9 ± 0.5 mpH/min/mg; P = 0.009). The concurrent decrease in the two energy supply pathways leads to a decrease in the cellular energy charge (0.87 ± 0.01 versus 0.83 ± 0.02; P < 0.001). ConclusionsHuman mural luteinized granulosa cells exhibit a reduction in their energy metabolism as women age that is likely to influence female reproductive potential.

UTERINE MICROBIOME IN HEALTHY FERTILE WOMEN AND IN CASE OF ENDOMETRIUM PATHOLOGY IN MULTIPLE FAILURES OF IN-VITRO-FERTILIZATION PROGRAMS

Background: Thanks to new diagnostic technologies, it is of no doubt that the uterus is no longer considered to be sterile. A disturbed microbiome of endometrium can be a significant reason for preterm birth, infertility, the recurrence of pregnancy loss, and repeated implantation failures in in-vitro-fertilization programs. Aim: Study the endometrial microbiome features in healthy fertile women and in women with multiple in-vitro-fertilization failures. Methods: To assess the differences in the endometrial microbiota of 20 women with infertility and experiencing multiple unsuccessful attempts of in-vitro-fertilization and 15 fertile, healthy women, endometrial microbiome was studied using an NGS of 16S rRNA. Results and Discussion: Lactobacillus (29.4%), Comamonas (16.8%), and Mesorhizobium (6.0%) were the most abundant genera in group of healthy fertile patients, and Lactobacillus (33.3%), Ralstonia (7.9%) and Pediococcus (4.8%) were most abundant in the group of infertile patients. The mean relative abundance of Lactobacillus did not significantly differ between groups and comprised 33.3% in the group of infertile women and 29.4% in healthy fertile women. A considerably higher mean relative abundance of bacteria of the genus Brevundimonas and Ralstonia was recorded in the group of infertile women. The fertile women had a statistically significantly higher mean relative abundance of Acidovorax, Brevibacillus, Caulobacter, Comamonas, Delftia, Distigma, Pseudomonas, Schlegelella, and Thermus. Conclusions: The presented data confirm that endometrium is not a sterile tissue despite long-standing concepts concerning its sterility. Lactobacillus are dominant genera; however, there is no absolute dominance of Lactobacillus over 90%. The mean relative abundance of Lactobacillus in the uterine microbiome in fertile patients and patients with multiple in-vitro-fertilization failures did not differ.

Detection of intracavitary lesions in 436 infertile women by office hysteroscopy and comparison with histopathology results

Aim: To examine the importance of office hysteroscopy in detecting and treating endometrial pathologies of infertile patient groups.Materials and Methods: For this retrospective observational study, first, electronic hospital records were examined in order to identify patients who underwent office hysterescopy at our clinic, between 2003 and 2020, for infertility. The office hysteroscopy findings of 436 patients were included in the study, and examined and compared with the histopathological results.Results: The age distribution of the patients included in the study was homogeneous in terms of group variances. Thehysteroscopy findings of the patients were as follows: normal cavityin 137 patients(31.4%), endometrial polyps in 199 patients(45.6%), synechia in 14 patients(3.2%), subseptum or arcuate uterus in 32 patients (7.3%), t-shaped uterus in 28 patients (6.4%), cervical polyps in 6 patients (1.4%), Asherman’s syndrome in 6 patients (1.4%), and submucous myoma in 14 patients (3.2%). The most frequently detected lesion with office hysteroscopy was polyps,at a rate of 47% with 205 patients. In the pathology results, of the 137 patients who were diagnosed with normal endometrium via office hysteroscopy and underwent biopsy, 119were reported as normal (89.6%), while 6 were diagnosed with polyps (4.4%). The sensitivity and specificity of office hysteroscopy in detecting endometrial polyps were 94% and 56%, respectively.Conclusion: Office hysteroscopy may be one of the first alternative methods that can be used for safe and practical outpatient diagnosis and treatment in infertile patient groups.

Single Nucleotide Polymorphism of Follicle Stimulating Hormone Receptor Gene in Iraqi Infertile Men

The study was directed to determine Single Nucleotide Polymorphism (rs6166 A&gt;G) of follicle stimulating hormone receptor gene and their association as a risk factor with male infertility in Iraqi sterile patient. In the present study after seminal and serum analysis 50 patient (25 Azoospermia and 25 oligozoospermia) and 50 healthy fertile control were joined. The samples were collected from the Biotechnology Department/college of science/Baghdad university and Kamal Al-Samarie IVF Hospital, Baghdad, Iraq. through the period of two months from November 2018 to January 2019. The SNP (rs 6166) determination was carried out by using real-time polymerase chain reaction (qPCR) of blood samples. The difference in the mean of genotype showed a significantly different (p&lt;0.05) in infertile patients group likened to corresponding means infertile control group. Survey of follicle stimulating hormone receptor gene SNP genotypes and allele frequencies in Azoospermia and oligozoospermia patient groups with the control group, showed that there was a significant variation in the heterozygous (AG) and homozygous mutant (GG) genotype frequencies in (rs 6166). It concluded that this SNP may have a role in an Azoospermia and oligozoospermia Iraqi patients complaining from idiopathic infertility.

Resistin in Human Seminal Plasma: Relationship with Lipid Peroxidation, CAT Activity, GSH/GSSG Ratio, and Semen Parameters.

Resistin is an adipokine involved in inflammation and able to induce the expression of other proinflammatory cytokines. It is known that, in human semen, resistin is correlated with inflammatory cytokines and sperm quality. The aim of this prospective study was to explore the potential relationship between resistin, lipid peroxidation (LPO), catalase (CAT) activity, and reduced and oxidized glutathione (GSH/GSSG) ratio in semen samples of infertile patients with leukocytospermia (no. 19), infertile patients with varicocele (no. 17), and fertile men (no. 17). Semen analysis was performed following the WHO guidelines, and sperm apoptosis and necrosis were evaluated with annexin V/propidium iodide assay. Seminal plasma samples were used to determine resistin levels by an immunological method, MDA concentration by a HPLC analysis with UV detection, GSH/GSSG ratio by an enzymatic method, CAT activity by a spectrophotometric method. The results showed that, in both groups of infertile patients, semen parameters were significantly reduced (P < 0.001) and sperm apoptosis and necrosis percentages were increased. Resistin levels were significantly higher in leukocytospermia and varicocele groups (P < 0.001 and P < 0.01, respectively) as well as MDA concentration (P < 0.001) compared to controls. The MDA level was also significantly increased in the leukocytospermia group versus the varicocele group (P < 0.05). The GSH/GSSG ratio was higher in fertile controls than the leukocytospermia group (P < 0.05) and the varicocele group (P < 0.001) and in the leukocytospermia group versus the varicocele group (P < 0.05). Both the leukocytospermia and varicocele groups showed increased values of CAT activities (P < 0.001) than controls. Briefly, the correlation between variables, calculated in the whole patient population, showed that resistin levels positively correlated with MDA levels, CAT activity, sperm apoptosis, and necrosis and negatively with sperm parameters and GSH/GSSG ratio. These results support an active role of resistin in an inflammatory process causing LPO, increase of CAT activity, and decrease of GSH/GSSG ratio in seminal plasma of infertile men vs. fertile controls.

Piezo-assisted ICSI improves fertilization and blastocyst development rates compared with conventional ICSI in women aged more than 35years.

PurposePiezo‐assisted intracytoplasmic sperm injection (Piezo‐ICSI) is reported to be an effective method for inseminating fragile oocytes compared with conventional ICSI (c‐ICSI). However, infertile patient groups suitable for Piezo‐ICSI have not been elucidated. This study was conducted to determine age groups suitable for Piezo‐ICSI using sibling egg controls inseminated by a well‐trained embryologist to reduce technical inequalities.MethodsA total of 947 matured oocytes were inseminated either by Piezo‐ICSI or by c‐ICSI in sibling oocytes as controls. Fertilization (2 pronuclei, PN), survival, and blastocyst development rates on day (D) 5 and D6 after insemination were compared between the Piezo‐ICSI and c‐ICSI groups. Further analyses were applied to groups of women >35 or ≤35 years of age.ResultsThere were no significant differences in fertilization, survival, or blastocyst development rates between the two insemination treatment groups. However, for women >35 years of age, the fertilization (P = .008) and blastocyst development (P = .016) rates with Piezo‐ICSI on D5 and D6 were significantly higher than in those subjected to c‐ICSI.ConclusionsPiezo‐ICSI was useful for inseminating oocytes from women >35 years of age.