Polycystic Ovary Syndrome (PCOS) is a multifaceted endocrine disorder with diverse phenotypic presentations. This study aimed to evaluate the prevalence of PCOS phenotypes among Iranian infertile women and compare their clinical, hormonal, and metabolic parameters across these groups. This cross-sectional study included 534 infertile women with PCOS (diagnosed via Rotterdam criteria) attending the Milad Infertility Center in Mashhad, Iran. Patients were classified into four phenotypes (A, B, C, and D). Data on height, weight, hormonal profiles, and metabolic parameters were extracted and analyzed using SPSS version 26. A total of 534 infertile women with PCOS were included (mean age = 28.3 ± 5.4 years). The most prevalent phenotype was phenotype A (57.3
Cumulus–oocyte complex (COC) manipulation is an essential procedure in assisted reproductive technology (ART) laboratories. Conventional plastic pipettes are widely used for oocyte handling; however, material properties and surface characteristics of these devices may influence handling performance and biological compatibility. This study aimed to develop a medical-grade silicone pipette for COC manipulation and to perform preliminary biological evaluation of the fabricated device. A silicone-based pipette was designed and fabricated for aspiration, washing, and transfer of COCs. The developed device was evaluated using Human Sperm Assay (HSA) and Mouse Embryo Assay (MEA) as biological compatibility assessments. Sperm motility changes following exposure to the device were assessed using the Sperm Motility Index (SMI). Embryo developmental outcomes, including cleavage to the 2-cell stage and blastocyst formation, were compared between the silicone pipette and conventional pipette groups. Exposure to the developed silicone pipette did not demonstrate a detectable adverse effect on sperm progressive motility. The SMI values remained above the predefined acceptance threshold throughout the evaluated exposure periods. In the MEA, cleavage rates were comparable between the silicone pipette and control groups (92
Abstract Background Anti-Müllerian hormone (AMH) and antral follicle count (AFC) are routinely used to stratify women undergoing in vitro fertilization (IVF), but virtually all widely cited cut-offs were derived in European or East-Asian cohorts. Women of Arabian Peninsula ancestry have AMH and AFC values 20–30% lower than these reference populations, raising concern that imported thresholds may systematically misclassify Saudi patients. We quantified this misclassification, derived locally calibrated cut-offs, and assessed clinical utility using decision-curve analysis (DCA). Methods Single-center retrospective cohort of 186 consecutive women undergoing fresh-transfer IVF on a uniform gonadotropin-releasing hormone (GnRH)-antagonist protocol at a private fertility center in Jeddah, Saudi Arabia (June–December 2024). The primary outcome was clinical pregnancy. We applied published European and European Society of Human Reproduction and Embryology (ESHRE)/Bologna thresholds to our cohort to quantify misclassification, derived locally optimal cut-offs by Youden index, and evaluated clinical utility by DCA across a range of threshold probabilities. Results The clinical pregnancy rate was 38.2% (71/186). Applying the European “good-prognosis” AMH threshold (> 3.5 ng/mL) to our cohort would have excluded approximately 53.5% of women who actually achieved clinical pregnancy from a favorable counseling category; a comparable AFC threshold (> 14) would have excluded 50.7%. Conversely, ESHRE/Bologna “poor-responder” thresholds (AMH < 1.1 ng/mL; AFC < 7) had specificity above 93% but sensitivity below 30%, providing little discrimination of poor outcomes in this population. Locally optimal cut-offs were AMH > 2.8 ng/mL (sensitivity 74.6%, specificity 73.0%) and AFC > 11 follicles (73.2%, 79.1%). On DCA, an AMH-based decision rule produced positive net benefit across plausible threshold probabilities (10–60%) while a treat-all strategy became harmful above a threshold probability (pₜ) of approximately 0.40. Conclusion Western-derived AMH and AFC thresholds materially misclassify Saudi women undergoing IVF, with up to half of women who go on to achieve clinical pregnancy falling below European “good-prognosis” cut-offs. Locally calibrated thresholds (AMH > 2.8 ng/mL; AFC > 11) better reflect this population and add net clinical benefit over default-treatment strategies on DCA. These findings should be interpreted as derivation-cohort estimates requiring multicenter external validation before clinical implementation. Because clinical pregnancy is a surrogate for live birth, these thresholds should be confirmed against cumulative live-birth rates in future work.
Unexplained infertility (UI) and recurrent pregnancy loss (RPL) pose substantial challenges in reproductive medicine, often arising from impaired endometrial receptivity during the critical implantation window. This narrative review synthesizes current evidence on the role of genetic polymorphisms in key regulatory genes interleukin-2 (IL-2), thrombin-activatable fibrinolysis inhibitor (TAFI), progestagen-associated endometrial protein (PAEP), and vascular endothelial growth factor (VEGF) in modulating immune responses, fibrinolytic balance, uterine remodeling, and angiogenesis. We explore how single nucleotide polymorphisms (SNPs) in these genes influence molecular and cellular mechanisms essential for successful embryo implantation and pregnancy maintenance. The review highlights associations of specific SNPs such as IL-2 -330 T/G, TAFI Thr325Ile, VEGF − 1154 G/A, and VEGF − 2578 C/A with altered gene expression and protein function, contributing to implantation failure, pregnancy loss, and infertility. Understanding these genetic factors enhances insights into the pathogenic pathways of UI and RPL and may guide the development of diagnostic markers and personalized therapeutic strategies to improve reproductive outcomes.
Selecting an appropriate gonadotropin starting dose in GnRH antagonist protocols remains challenging due to substantial inter-individual variability in ovarian response and the need to balance treatment efficacy with safety. In this retrospective cohort study, women undergoing IVF/ICSI with GnRH antagonist protocols were included. Machine learning models, including XGBoost and Random Forest, were developed to predict oocyte yield and moderate-to-severe ovarian hyperstimulation syndrome (OHSS) using baseline clinical and hormonal variables. A multi-objective optimization framework incorporating a composite score (oocyte yield − 5.0 × OHSS probability) was applied to derive individualized starting doses, balancing efficacy against safety. A total of 770 cycles were included in the final analysis. The model demonstrated predictive performance for oocyte yield (R² = 0.523, RMSE = 4.75) and moderate discrimination for moderate-to-severe OHSS (AUC = 0.597). Feature importance analysis identified AMH, AFC, and age as the most influential predictors. Dose-response simulations revealed substantial inter-individual variability in optimal dosing, with higher ovarian reserve patients requiring lower starting doses to achieve favorable outcomes while minimizing OHSS risk. This study presents a machine learning-based multi-objective optimization framework for individualized gonadotropin dosing, offering clinically actionable decision support and advancing precision medicine in assisted reproduction.
Abstract Background The short LH surge induced by a GnRH agonist (GnRHa) trigger minimizes the risk of ovarian hyperstimulation syndrome (OHSS), but its sufficiency to support optimal outcomes remains uncertain. This prospective cohort study evaluated the impact of pre- and post-trigger LH levels on the stimulation outcomes of GnRHa-triggered ICSI cycles. Methods Ninety-four women (≤ 40 years) undergoing GnRHa-triggered ICSI with a freeze-all approach were included. Ovulation was triggered using 0.3 mg triptorelin followed by 0.2 mg after 12 h. LH was measured on the trigger day and 12 h post-trigger. The primary outcome was oocyte maturation rate; secondary outcomes included fertilization and blastulation rates. Data were analyzed using Mann–Whitney, Pearson correlation and ROC curve analysis. Results Pre-trigger LH levels correlated with blastulation rates with modest predictive ability (AUC = 0.67). While post-trigger LH levels correlated significantly with oocyte maturation with modest predictive ability (AUC = 0.70). No significant associations were found with fertilization outcomes. Pre- and post-trigger LH levels were positively correlated ( r = 0.36, p = 0.01). Conclusions In GnRHa-triggered ICSI cycles, post-trigger LH levels were associated with oocyte maturation, while pre-trigger LH levels were associated with blastulation rate. However, discriminative performance was modest, and post-trigger LH data were available only in a subset of patients. These findings should be considered exploratory and require validation in larger prospective cohorts before clinical application.
Among the different causes of infertility, uterine cavity malformations are one of the chief causes with a prevalence of 10–15
Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine-metabolic disorder in which oxidative stress is closely implicated in pathophysiology. The integration of dynamic thiol/disulfide homeostasis, advanced oxidation protein products (AOPP), total antioxidant capacity (TAC), and metabolic markers (serum citrate and lactate dehydrogenase) has not been explored in a single PCOS cohort. To evaluate systemic redox status and associated metabolic markers in women with PCOS by measuring thiol/disulfide homeostasis, AOPP, malondialdehyde (MDA), TAC, serum citrate, and lactate dehydrogenase (LDH). We conducted a case-control study that enrolled 100 women: 50 with Rotterdam-defined PCOS and 50 age-matched healthy controls (the two groups were not matched for body mass index; see below). Spectrophotometric assays quantified serum native thiol, total thiol, disulfide, AOPP, MDA, TAC, citrate, and LDH activity. Diagnostic accuracy was assessed using receiver operating characteristic (ROC) analysis, and group differences were re-examined after adjustment for BMI using analysis of covariance. PCOS patients exhibited significantly depleted native and total thiols, along with elevated disulfide, AOPP, and MDA levels, and reduced TAC and serum citrate (p < 0.001). LDH activity was markedly higher in the PCOS group (p < 0.001). All between-group differences remained significant after adjustment for BMI. ROC analysis highlighted native thiol (AUC = 0.865) and LDH (AUC = 0.850) as the strongest single markers. A multivariable logistic model combining these biomarkers discriminated PCOS with high accuracy (apparent AUC = 0.99; 10-fold cross-validated AUC = 0.99; bootstrap optimism-corrected AUC = 0.98). PCOS is characterized by a coordinated redox imbalance accompanied by a metabolic shift toward anaerobic glycolysis consistent with mitochondrial inefficiency. Integrating these biomarkers into evaluation may refine diagnostic precision and support hypothesis-generating work on antioxidant-targeted strategies.
Abstract Background Declining fertility rates and limited awareness of fertility risk factors pose major reproductive health challenges. FertiSTAT is a self-assessment tool for fertility risk awareness but has not been culturally adapted suitable for Indonesian population. Objective To perform transcultural adaptation and evaluate the validity and reliability of the Indonesian version of FertiSTAT as a screening tool for fertility risk awareness for Indonesian population. Methods This methodological study was conducted involving 7 expert panel members, 4 certified translators, and 92 subjects, through a 6 stages transcultural adaptation process which included expert content validation, forward–backward translation, face validation, cognitive debriefing, and test–retest reliability assessment. Content validity was measured using the Content Validity Index, while reliability was assessed using Cohen’s kappa and Spearman correlation. Results All items retained conceptual equivalence and cultural relevance. Content validity showed CVI > 0.80 for all items and face validity demonstrated mean Likert scores > 3. Test–retest reliability showed variable agreement; several items achieved strong consistency, while lower values were mainly due to sensitive, subjective, fluctiative or strong homogenity of test-retest responses. Stability was sufficient for screening purposes. One additional item, tuberculosis was included on expert panel recommendations due to its prevalence and relevance to infertility in Indonesia. Conclusion The Indonesian version of FertiSTAT demonstrated good content and face validity following transcultural adaptation, with preliminary test-retest reliability findings showed variation across individual items, likely reflecting differences in item sensitivity, subjectivity, and or low-variability nature of some questions. Nevertheless, these items were retained based on expert panel judgment regarding their conceptual and clinical relevance, and future refinement may include brief explanatory notes to support more consistent interpretation by respondents. Further studies with larger, more diverse populations may be needed to strengthen psychometric evaluation and confirm broader clinical and public health applicability. Beyond its clinical relevance, the Indonesian version of FertiSTAT may also support policy development, public health promotion, and fertility awareness campaigns by providing a structured means of improving fertility-related knowledge. It also has potential for integration into digital health applications, which may improve access to fertility awareness information and support earlier decision making and health-seeking behavior.
Endometriosis, defined by the abnormal growth of endometrial-like tissue outside the uterus, impacts 6–10
Abstract Introduction Hemorrhage represents a significant complication during laparoscopic myomectomy, with transfusion requirements occurring in 5–40% of procedures. Vasopressin, a potent vasoconstrictor, has been employed for hemostasis in gynecologic surgery but evidence regarding its efficacy and safety for laparoscopic myomectomy has not been systematically synthesized. This systematic review and meta-analysis comprehensively evaluates vasopressin efficacy and safety for hemostasis during laparoscopic fibroid removal. Evidence acquisition Systematic search of PubMed/MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science, and Scopus databases conducted until November 28, 2025, identified studies comparing vasopressin to control interventions during laparoscopic myomectomy. Randomized controlled trials and observational comparative studies reporting blood transfusion requirement, blood loss, or adverse events were included. Two reviewers independently screened studies, extracted data, and assessed risk of bias using Cochrane RoB 2 and ROBINS-I tools. Random-effects meta-analysis calculated pooled odds ratios (OR) for transfusion and mean differences (MD) for blood loss. GRADE methodology assessed evidence certainty. Subgroup analyses evaluated effect modification by fibroid characteristics, study quality, and surgical approach. Evidence synthesis After removal of protocol-only, non-laparoscopic/open, hysteroscopic-only, and unverifiable records from the quantitative synthesis, eight verified comparative studies were retained for qualitative synthesis. Five studies contributed to the revised primary transfusion analysis, demonstrating lower transfusion requirement with vasopressin versus control (OR 0.18, 95% CI: 0.09–0.34, P < 0.001; approximate NNT = 8). Sensitivity analysis excluding the high-risk observational study Thiek [1] showed a similar but attenuated effect (OR 0.21, 95% CI: 0.11–0.41). Six laparoscopic/robot-assisted datasets showed reduced intraoperative blood loss (MD -100.6 mL, 95% CI: -134.3 to -66.9; I²=38%). Cohen [2] was the only included study that incorporated surgeon-estimated blood loss; excluding this study yielded MD -109.2 mL (95% CI: -136.5 to -81.9; I²=0%). Blood-loss findings should therefore be interpreted as hypothesis-generating because ascertainment methods were not fully uniform across studies. Hemoglobin preservation was directionally consistent but should be interpreted with caution because of differences in study design and measurement timing. Reported adverse events were mainly transient hemodynamic changes, especially mild hypertension, with no permanent vasopressin-attributable cardiovascular injury documented in the verified evidence base. Conclusions Current evidence suggests that intramyometrial vasopressin may reduce transfusion requirement and estimated blood loss during laparoscopic or robot-assisted laparoscopic myomectomy when diluted preparations and careful hemodynamic monitoring are used. However, the certainty of the evidence is limited by small study numbers, observational data, publication-bias signals, and residual methodological heterogeneity. Vasopressin should therefore be considered a useful hemostatic adjunct in selected higher-risk cases rather than an unequivocal universal standard. Larger, prospectively registered randomized trials are needed to define optimal dosing, dilution, safety monitoring, and long-term reproductive outcomes. Prospero registration CRD420261340513; registered 14 March 2026 after completion of the literature search on 28 November 2025, and therefore retrospectively registered.
Abstract Objective To compare embryo development and pregnancy outcomes associated with the use of light versus heavy paraffin oil for embryo culture in patients undergoing in vitro fertilization (IVF). Methods This single-center, prospective, non-randomized cohort study screened 718 IVF cycles between May 2023 and December 2023, of whom 578 were included in the final analysis. Embryological outcomes were assessed for these cycles, frozen embryo transfer and pregnancy outcomes were subsequently followed through January 2025. Embryos were cultured under either light paraffin oil or heavy paraffin oil, with group allocation based on routine laboratory workflow rather than formal randomization. Embryological outcomes included fertilization rate, cleavage rate, proportion of good-quality embryos, blastocyst formation rate, and proportion of good-quality blastocysts. Pregnancy outcomes included positive human chorionic gonadotropin rate, implantation rate, clinical pregnancy rate, ongoing pregnancy rate, live birth rate, and miscarriage rate. Results Among 204 patients in the light paraffin oil group and 374 patients in the heavy paraffin oil group, embryos cultured under heavy paraffin oil showed significantly higher cleavage rate (98.71% vs. 97.57%, p = 0.011) and blastocyst formation rate (63.10% vs. 57.28%, p = 0.007). However, no significant differences were observed in pregnancy outcomes between the two groups. Conclusions Heavy paraffin oil was associated with improved embryo development. However, these laboratory advantages did not translate into improved pregnancy outcomes. Further randomized controlled and multicenter studies are warranted to confirm these findings.
Abstract Background Microdissection testicular sperm extraction (micro-TESE) is an important treatment option for men with non-obstructive azoospermia (NOA) because it can provide sperm for intracytoplasmic sperm injection when other routes to biological fatherhood are unavailable. Counseling, however, should include not only the probability of sperm retrieval but also postoperative structural, endocrine, symptomatic, and repeat-procedure outcomes. Main body This narrative review used structured searches of PubMed/MEDLINE, Scopus, and Web of Science from database inception to May 2026, supplemented by Google Scholar and reference-list screening. Human micro-TESE studies were prioritized; mixed surgical retrieval studies, mechanistic studies, and guidelines were used when direct evidence was limited. Micro-TESE appears less damaging than conventional testicular sperm extraction, but focal ultrasonographic abnormalities, testicular volume change, testosterone decline, gonadotropin change, and occasional clinically relevant atrophy have been reported. Most changes appear transient or asymptomatic, whereas men with small testes, borderline testosterone, elevated luteinizing hormone, Klinefelter syndrome, previous cryptorchidism or orchidopexy, adverse histology, relevant comorbidities, or failed previous retrieval may require closer counseling and follow-up. Proposed mechanisms, including inflammation, blood–testis barrier disturbance, oxidative stress, and local microcirculatory stress, should be distinguished from direct post-micro-TESE evidence. Repeat surgery should be counseled differently after prior successful retrieval and after initial failed retrieval. Conclusions Micro-TESE should not be discouraged when clinically indicated. A practical counseling approach should balance the chance of sperm retrieval and cryopreservation against testicular reserve, possible structural injury, endocrine risk, symptoms, genetics, comorbidities, and patient preferences. Men with small testes or persistent symptomatic hypogonadism require endocrine-andrology reassessment. Testosterone therapy should be reserved for confirmed symptomatic testosterone deficiency after fertility goals and any further sperm-retrieval plans have been addressed.
Abstract Background Infertility is a common yet underrecognized public health issue in the Middle East and North Africa, affecting up to 30% of couples in some countries. Although advances in assisted reproductive technologies have improved treatment outcomes globally, access to infertility care across the region remains uneven and limited. Understanding the barriers that prevent timely and equitable access to care is essential to improving reproductive health outcomes. This structured narrative review synthesizes evidence from published literature identified through a systematic search of major electronic databases (PubMed, MEDLINE, Scopus, and Google Scholar), and integrates expert-informed perspectives from fertility specialists across the region on financial, sociocultural, healthcare system, and policy-related barriers to infertility care. The systematic search identified 81 records, of which 76 remained after duplicate removal and underwent title and abstract screening. Following full-text assessment of 24 articles, 7 studies met eligibility criteria and were included in the final synthesis. Financial constraints emerged as the most significant obstacle, driven by high out-of-pocket costs and limited or absent insurance coverage for fertility treatments. Sociocultural factors, including stigma, gendered blame, and misconceptions surrounding infertility, further discourage care-seeking, particularly among women. Limited awareness of infertility and its treatments, combined with educational gaps among patients and healthcare providers, contributes to delayed presentation, poor treatment adherence, and unrealistic expectations. The psychological burden of infertility is substantial, with many individuals experiencing anxiety, depression, and marital strain, often compounded by the lack of structured counseling and psychosocial support within fertility services. Expert perspectives consistently highlighted the need for systemic reforms to address these interconnected financial, social, and healthcare system challenges. Conclusion These findings demonstrate that barriers to infertility care in the Middle East and North Africa are multifactorial and interrelated, encompassing financial, sociocultural, healthcare system, and regulatory dimensions. These factors contribute to substantial inequities in access to infertility services across the region. Graphical Abstract Barriers to infertility care in the MENA region
Abstract Objective Endometrial receptivity is a critical determinant of embryo implantation and successful pregnancy in in vitro fertilization–embryo transfer (IVF-ET). Although ultrasound-based scoring systems have been proposed to improve its assessment, their predictive performance remains unclear. This study aimed to evaluate the diagnostic value of the Applebaum scoring system and its modified version in predicting clinical pregnancy outcomes. Methods This retrospective study included 341 patients undergoing IVF-ET. Transvaginal ultrasound was performed on the day of embryo transfer, and endometrial receptivity was assessed using the Applebaum scoring system (A) and a modified version (B). Clinical pregnancy, defined as the presence of a gestational sac with fetal cardiac activity, was evaluated 35 days after embryo transfer. Receiver operating characteristic (ROC) curve analysis was used to assess predictive performance. Results No statistically significant differences were observed in scores between the pregnancy and non-pregnancy groups for either scoring system (P > 0.05). ROC analysis demonstrated poor discriminatory performance, with area under the curve (AUC) values of 0.54 (95% CI: 0.47–0.60) for system A and 0.56 (95% CI: 0.50–0.63) for system B. Conclusions Both scoring systems showed poor predictive performance, with AUC values close to 0.5. These findings suggest limited clinical utility, and ultrasound-based scoring systems should not be used as standalone predictors of IVF outcomes.
Abstract Background Endometriosis is a biologically heterogeneous disorder frequently encountered in women undergoing assisted reproductive technology (ART). Reported effects on in vitro fertilization and intracytoplasmic sperm injection (IVF/ICSI) outcomes remain inconsistent across studies, partly due to variations in disease phenotype, prior surgical treatment, ovarian reserve, and concomitant uterine pathology. Objective To critically evaluate contemporary evidence regarding IVF/ICSI outcomes in women with endometriosis, with emphasis on phenotype-related reproductive variability, sources of evidence heterogeneity, and implications for individualized reproductive management. Methods A structured narrative review was performed using PubMed/MEDLINE, Embase, and Scopus databases. Literature published between January 2015 and March 2026 was screened, with particular focus on contemporary studies evaluating ovarian response, embryological parameters, implantation, live birth, cumulative reproductive outcomes, and the potential confounding role of adenomyosis. Results Current evidence suggests that the reproductive impact of endometriosis is not uniform across patient populations. Ovarian endometrioma and previous ovarian surgery are most consistently associated with reduced ovarian reserve and lower oocyte yield, whereas superficial peritoneal disease appears to exert less pronounced effects on ovarian responsiveness. Embryological outcomes are frequently preserved despite impaired ovarian response, although substantial heterogeneity exists among studies. Implantation and live birth outcomes may additionally be influenced by uterine factors, particularly adenomyosis, which may independently impair reproductive efficiency. Differences in study design, patient selection, disease classification, and outcome reporting contribute significantly to variability in the available literature. Conclusions IVF/ICSI prognosis in women with endometriosis should be interpreted within a phenotype-specific and multifactorial clinical context rather than through a single generalized disease model. Contemporary evidence supports individualized reproductive assessment integrating ovarian reserve, surgical history, adenomyosis evaluation, and cumulative treatment trajectory when counselling and managing women with endometriosis undergoing ART.
Abstract Background Assisted reproductive technologies (ART), particularly intracytoplasmic sperm injection (ICSI), have transformed infertility treatment. Growing evidence suggests that ART-conceived offspring may exhibit altered cardiovascular development. Sensitive echocardiographic parameters including mitral annular plane systolic excursion (MAPSE), tricuspid annular plane systolic excursion (TAPSE), and the myocardial performance index (MPI) may detect early subclinical myocardial dysfunction. Objective To evaluate fetal cardiac function using MAPSE, TAPSE, and MPI in ICSI-conceived versus spontaneously conceived pregnancies, with adjustment for maternal confounders, and secondarily to compare fresh versus frozen embryo transfer subgroups. Methods This prospective case–control study included 200 singleton pregnancies at 20–27 weeks’ gestation: 100 conceived via ICSI and 100 spontaneously conceived controls frequency-matched for gestational age. Fetal cardiac function was assessed using M-mode and pulsed-wave Doppler to measure TAPSE, MAPSE, and left ventricular modified MPI. Analyses included multivariable linear regression, Bonferroni and Benjamini–Hochberg corrections for multiple comparisons and prespecified sensitivity analyses. Intra-observer reproducibility was evaluated in a 50-fetus subsample. Results Groups were comparable on all baseline characteristics except maternal age, which was higher in the ICSI group (p < 0.001) and included as a covariate. MAPSE was lower in the ICSI group than in controls in the unadjusted (0.483 ± 0.087 versus 0.517 ± 0.110 cm; p = 0.018) and matched-pair (paired p = 0.007) analyses but was attenuated and non-significant after multivariable adjustment for maternal age and other covariates (adjusted p = 0.056) and was borderline under Bonferroni correction (adjusted p = 0.053); the MAPSE result is therefore interpreted as borderline rather than robust. MPI was higher in ICSI-conceived fetuses than in controls (0.716 ± 0.057 versus 0.690 ± 0.072; p = 0.006) and remained significant under all multiple-comparison corrections, multivariable adjustment, and matched-pair analysis. TAPSE did not differ between groups in any analysis (p = 0.408). Intra-observer reproducibility was excellent (intraclass correlation coefficients ≥ 0.980). The observed MPI difference fell below the minimum detectable change for an individual fetus. Fresh and frozen embryo transfer subgroups did not differ on any cardiac parameter. Conclusion ICSI-conceived fetuses at mid-gestation demonstrate a modest elevation in the modified myocardial performance index, while longitudinal systolic function parameters show borderline or absent differences. These preliminary findings suggest subtle subclinical alteration in global myocardial performance; further longitudinal studies are warranted to determine their clinical significance.
Abstract Objective To evaluate whether hereditary thrombophilias and thromboprophylaxis are associated with live birth outcomes in patients with recurrent pregnancy loss (RPL). Methods This was a retrospective cohort study. We compared the odds of achieving a live birth in two groups of patients with RPL, those with hereditary thrombophilias and those without. Participants were seen at a tertiary referral centre specializing in the management of RPL. Hereditary thrombophilias were diagnosed by identifying Factor V Leiden (R506Q) or prothrombin mutation, or by detecting deficiencies in antithrombin, protein C, or protein S. We also evaluated the effect of thromboprophylaxis on live birth outcomes in patients with hereditary thrombophilias who conceived. Treatment options included aspirin, dalteparin (a low molecular weight heparin), hydroxychloroquine, and/or prednisone. Results Of the 458 patients with RPL included, 13.3% had hereditary thrombophilias, while 86.7% did not. There was no significant association between hereditary thrombophilias and live birth odds (adjusted odds ratio: 0.91; 95% confidence interval: 0.50–1.65). Of the 16 patients who received thromboprophylaxis, 56.2% achieved a live birth, compared to 39.1% in the untreated group, with no statistically significant difference (P = 0.342). Conclusions Hereditary thrombophilias and their thromboprophylaxis were not clearly associated with achieving live birth in the RPL population. However, these findings should be interpreted with caution. Larger studies are needed to verify these findings.
Abstract Background The microbiota of the reproductive system is a vital factor in fertility, pregnancy and neonatal health. Microbiota composition may control implantation, gestational preservation and neonatal colonization. The vaginal, cervical and uterine/endometrial niches exhibit varying levels of consistency with evidence based on sampling techniques and analysis. Methods We searched PubMed, Google Scholar, Scopus and Web of Science for articles published between January 2015 and September 2025. The inclusion criteria were human studies that have assessed microbiota of the reproductive tract in the vaginal, cervical, endometrial, placental or amniotic compartments against fertility, pregnancy or neonatal outcome. We excluded male-only, non-reproductive microbiomes or outcomes not aligned to fertility, pregnancy complications or neonatal health. Screening was done independently by two reviewers while a third reviewer assisted with conflict resolution. Due to heterogeneity, a structured meta-analysis was not possible. We synthesized evidence narratively following screening for eligibility. Results The most consistent evidence links vaginal dysbiosis particularly depletion of stable Lactobacillus-dominant communities and enrichment of anaerobic taxa with inflammatory disruption of cervicovaginal barrier function and increased risk of preterm birth related outcomes. By contrast, associations involving cervical especially endometrial microbiota with implantation failure, recurrent pregnancy loss and IVF outcomes remain suggestive but less consistent across studies. Evidence for a resident placental microbiota remains controversial with several recent low-biomass analysis favoring contamination interpretations over proof of viable colonization. Across sites, Lactobacillus dominance was not uniformly protective because species and strain level differences especially between Lactobacillus crispatus and Lactobacillus iners appeared clinically relevant. Maternal dysbiosis occurring pre-conception or early in pregnancy seem to have the greatest impact on adverse outcomes such as preterm birth. Modulation of local immune responses, inflammatory signaling and cervicovaginal barrier integrity were major highlighted mechanistic pathways. Emerging translational strategies include strain targeted probiotics/live biotherapeutics and vaginal microbiota transplantation although safety and standardized endpoints remain key constraint. Interventional and translational studies suggests that microbiome modulation can shift cervicovaginal community structure toward Lactobacillus enrichment. Conclusion There are significant relations between the reproductive tract microbial conditions, anatomical/immune health and reproductive outcomes but they are species/strain and context specific. There is a need to make early risk stratification, mechanistic validation and carefully controlled intervention studies priorities in future work before broad clinical implementation.
Abstract Hypertensive disorders of pregnancy (HPD) remain a leading cause of maternal and perinatal morbidity and mortality worldwide. Increasing evidence indicates that dysregulation of angiogenic factors contributes to the pathophysiology of maternal hypertension and pregnancy-related complications, particularly preeclampsia. This review synthesizes current evidence on the prognostic value of key angiogenic biomarkers, including placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and vascular endothelial growth factor (VEGF), in predicting maternal blood pressure changes and adverse pregnancy outcomes. A narrative literature review was conducted using PubMed, Scopus, and Google Scholar. Evidence suggests that an imbalance between pro-angiogenic and anti-angiogenic factors contributes to abnormal placentation and endothelial dysfunction. Reduced circulating PlGF and elevated sFlt-1 levels are consistently associated with an increased risk of preeclampsia. The sFlt-1/PlGF ratio has emerged as a clinically useful tool for risk stratification and short-term prediction of disease progression. However, challenges remain regarding the standardization of diagnostic thresholds and population variability. Integration of these biomarkers into routine antenatal care may improve diagnostic accuracy, early detection, guide clinical decision-making, and reduce adverse maternal and neonatal outcomes. Further large-scale prospective studies are required to establish clinical protocols.
