Search Results (1,172)

Objective: In this study, we aimed to develop and internally validate a clinically applicable nomogram for predicting live birth following in vitro fertilization (IVF) using routinely available clinical and embryological parameters. Methods: This retrospective study was conducted at a single tertiary IVF center. Women undergoing IVF/ICSI were included if their baseline demographic and clinical data were available, they had undergone at least one fresh or frozen–thawed embryo transfer, and they had a known live birth outcome. Women with cycles without embryo transfer and those missing key outcome data were excluded from the analysis. As a result, a total of 2119 IVF/ICSI treatment cycles resulting in embryo transfer were included in the analysis. To identify independent predictors of live birth, multivariable logistic regression analysis was performed. Results: Among the 2119 treatment cycles analyzed, 541 resulted in live birth (25.5%). Multivariable logistic regression with backward stepwise selection identified female age (OR: 0.959, p < 0.001), high embryo quality (OR: 2.752, p < 0.001), day of embryo transfer (day 5 vs. day 3, OR: 1.427, p = 0.001), and endometrial thickness on the day of transfer as independent predictors of live birth (OR: 1.086, p < 0.001). These variables were incorporated into a nomogram (the Zübeyde Hanim IVF Nomogram) to estimate individualized live birth probability. The model demonstrated acceptable discrimination, with a bootstrap-corrected area under the receiver operating characteristic curve (AUC) of 0.64 (95%CI: 0.61–0.66), and it showed satisfactory calibration across deciles of predicted risk. Conclusions: The Zubeyde Hanim IVF Nomogram provides an individualized and clinically practical tool for predicting live birth following IVF treatment. Based on routinely available parameters, this model may assist clinicians in patient counseling and treatment planning. Full article

Background/Objectives: Hodgkin lymphoma (HL) primarily affects individuals of reproductive age, making gonadal dysfunction after chemotherapy a critical survivorship concern. While fertility preservation options including gamete and gonadal tissue cryopreservation are available before treatment, evidence-based counseling requires regimen-specific risk estimates accounting for patient age and sex. Therefore, a meta-analysis was performed to assess presumed infertility in HL patients, stratified by chemotherapy regimen, age, and sex. Methods: This systematic review and meta-analysis, conducted within the FertiTOX project, included studies published between 2000 and February 2024. Eligible studies reported gonadal function outcomes ≥ 1 year after chemotherapy, excluding patients who received pelvic radiotherapy or stem cell transplantation, or had recurrent disease. Presumed infertility was defined by surrogate markers, including amenorrhea, premature ovarian failure, or abnormal hormonal levels in women, and azoospermia, oligozoospermia, or abnormal hormonal levels in men. Results: Of 2376 screened studies, 50 were included (meta-analysis: 43 studies; 5564 female and 1631 male patients). Overall presumed infertility prevalence was 21% in women (95% CI: 0.14–0.29) and 45% in men (95% CI: 0.29–0.62). The highest prevalence occurred after BEACOPP (women 38%; men 81%), while ABVD was associated with the lowest (6% each in women and men). Childhood/adolescent HL treatment resulted in lower prevalence in women (8%) but remained high in men (67%). Conclusions: Fertility risk depends on regimen, age, and sex, requiring tailored counseling. For female children/adolescents and all patients receiving ABVD, post-treatment fertility evaluation and treatment may suffice. However, pre-treatment fertility preservation is strongly recommended for male adolescents and patients receiving other regimens. Full article

Background: Preserving fertility in young women with cancer is crucial for comprehensive care. Based on GBD 2023 estimates, approximately 1000 women aged 15–39 are diagnosed with haematological malignancies annually in Italy. Guidelines recommend timely fertility preservation (FP) counselling for all at-risk patients, yet real-world access data remain limited. Methods: This multicentre, retrospective observational study analysed FP counselling for women aged 15–39 with haematological malignancies from 2015 to 2023. Counselling data were extracted from the Italian Assisted Reproductive Technology Registry (IARTR). This data collection system, known as PreFerIta, was developed within a project supported by the Italian Ministry of Health to collect data on Fertility Preservation (FP) treatments in oncology patients and/or those at risk of iatrogenic infertility, provided in seven specialised ART centres across Italy. The PreFerIta database includes data on both oocyte cryopreservation and ovarian tissue cryopreservation. Annual visits were related to the estimated regional incidence of new haematological malignancies (GBD 2023). Counselling-to-incidence ratios, absolute/relative gaps, and 95% confidence intervals (CIs) were calculated. Results: From 2015 to 2023, an estimated 4473 new haematological malignancies occurred in the catchment regions. Concurrently, 1200 FP counselling visits were recorded. While incidence modestly declined, counselling activity remained high. The counselling-to-incidence ratio increased from 17.33% in 2015 to 31.92% in 2018, stabilising between 26% and 31% thereafter (30.98% in 2023). The relative counselling gap decreased from 82.67% to 69.02%. These ratios represent lower-bound estimates of access to specialised oncofertility consultations. Conclusions: In this Italian network, approximately one in four to one in three incident haematological malignancies in young women were associated with specialised FP counselling. This reflects a substantial integration of oncofertility services into haematology care, highlighting opportunities to further strengthen referral pathways and achieve full guideline concordance. Full article

Background/Objectives: Volatile organic compounds (VOCs) have emerged as promising non-invasive biomarkers for assessing metabolic and reproductive health. In the context of assisted reproductive techniques (ARTs), the volatilomic composition of follicular fluid (FF) may reflect the biochemical environment surrounding the oocyte, influencing fertilization success and embryo development. This study aimed to characterize the volatilomic profile of FF in women undergoing ARTs and to explore associations between specific VOCs and female fertilization-related parameters (FFRPs). Methods: A total of 54 Caucasian women aged 19–39 years, enrolled between October 2015 and July 2019, were recruited at the Assisted Reproduction Laboratory of the Local Health Unit of Cova da Beira, Covilhã. FF samples were analyzed via gas chromatography–mass spectrometry (GC–MS) in scan mode, identifying 136 VOCs, of which 72 were selected based on prevalence. Sixteen FFRPs were evaluated, including age, body mass index (BMI), smoking habits, infertility factor, oocyte yield, embryo quality, β-hCG levels, country of birth, and reproductive history. Associations between VOCs and FFRPs were assessed using the Chi-square (χ²) test. Results: Significant correlations (p ≤ 0.05) were identified between 45 VOCs and 11 FFRPs. The detected compounds comprised alkanes, siloxanes, aromatics, alcohols, ketones, aldehydes, carboxylic acids and esters, fatty acid derivatives, epoxides, acrylates, nitriles, and sterols. Several VOCs were associated with more than one FFRP, indicating overlapping metabolic pathways that may influence reproductive performance. Conclusions: The volatilomic profile of FF demonstrates significant variability linked to individual reproductive and metabolic factors. VOC analysis may provide novel insights into follicular physiology, representing a promising approach for identifying potential biomarkers of infertility and ART outcomes. Full article

An increasing number of young women with hormone receptor-positive (HR+) early breast cancer desire pregnancy after treatment. Prolonged adjuvant endocrine therapy, concerns regarding recurrence risk, and treatment-related fertility decline have historically complicated reproductive decision-making in this population. This narrative review synthesizes current evidence on pregnancy after early HR+ breast cancer, with particular emphasis on prospective data from the POSITIVE trial. We examine the safety of temporary endocrine therapy interruption, the impact of assisted reproductive technologies (ART) in achieving pregnancy, breastfeeding feasibility and impact, hormonal predictors of fertility, pregnancy outcomes and considerations for special populations, including BRCA mutation carriers. Retrospective studies have suggested no adverse survival impact associated with pregnancy after breast cancer. The POSITIVE trial provides prospective evidence that temporary interruption of endocrine therapy to attempt pregnancy does not increase short-term recurrence risk in selected patients. Approximately three-quarters of participants achieved pregnancy. Fertility preservation and ART were commonly used and were not associated with worse short-term oncologic outcomes. Biomarkers such as anti-Müllerian hormone offer supportive but imperfect prediction of fertility potential. Breastfeeding was feasible for many women and did not adversely affect breast cancer outcomes. Available data among BRCA mutation carriers are reassuring but largely observational. Current evidence supports the safety and feasibility of pregnancy after early HR+ breast cancer in carefully selected patients. However, longer follow-up, inclusion of higher-risk populations, and evaluation of newer therapies are needed. Individualized, multidisciplinary counselling remains central to informed decision-making. Full article

Background/Objectives: Endocrine therapy (ET) is a common treatment for hormone-dependent breast cancer and is associated with a significant reduction in recurrence and mortality rates. However, the decision to initiate endocrine therapy is a critical and often distressing juncture for patients. The need to weigh its survival benefits against the potential burden of side effects, including mood changes, pain, muscle stiffness, and fatigue, can render this decision-making phase a source of significant distress. The present systematic review aimed to identify and synthesize the sociodemographic and psychosocial predictors of the decision-making process related to ET adherence among women with breast cancer. Methods: A systematic literature search was conducted in three electronic databases—PubMed Central, ProQuest, and Scopus—to identify studies examining the association between sociodemographic and psychosocial factors and the decision-making process regarding ET among women with breast cancer. Inclusion criteria encompassed cross-sectional studies published between 2000 and 2025. Data were extracted and analyzed to identify recurring predictors across studies. The findings were synthesized through a narrative synthesis. Results: Twelve cross-sectional studies met the inclusion criteria, comprising a total of 8510 women diagnosed with breast cancer and undergoing ET. Ten studies (83%) identified sociodemographic variables—such as age, marital status, educational level, and ethnicity—as significant predictors of decision-making. Moreover, nine studies (75%) reported psychosocial factors, including quality of life (QoL), fear of progression, infertility concerns, and social support, as influential in the decision to initiate or continue ET. Specifically, the decision to adhere to ET is generally supported by younger age, higher education, better perceived quality of life, and greater social support. Conversely, it is hindered by lower income, lower education, fertility concerns related to marital status, and diminished quality of life. Conclusions: The findings of this review indicate that both sociodemographic and psychosocial factors play key roles in shaping women’s decisions regarding adherence to ET. Understanding these predictors can facilitate decision-making and inform the development of targeted interventions aimed at improving treatment adherence and supporting patient-centered care in breast cancer treatment. The focus on decision-making processes, rather than on adherence rates, is what distinguishes this review from other systematic reviews. Full article

The functional deterioration of granulosa cells (GCs), essential for follicular growth, steroidogenesis, and oocyte competence, indicates ovarian aging and reduced fertility. An expanding corpus of research indicates that oxidative stress is a primary molecular contributor to granulosa cell dysfunction, culminating in mitochondrial impairment, reduced metabolic support for oocytes, and the activation of regulated apoptotic pathways that end in follicular atresia. Ferroptosis, an emergent type of iron-dependent lipid peroxidation, has been identified as a crucial mechanism contributing to chemotherapy-induced ovarian insufficiency, polycystic ovary syndrome (PCOS), and granulosa cell death in aging ovaries, in addition to conventional apoptosis. The SIRT1-Nrf2 axis acts as a crucial anti-oxidative and anti-ferroptotic system that protects GC viability, maintains mitochondrial homeostasis, and upholds redox equilibrium. SIRT1 promotes mitochondrial biogenesis and metabolic resilience by deacetylating downstream proteins, including FOXO3 and PGC-1α. Nrf2 simultaneously controls the transcriptional activation of detoxifying and antioxidant enzymes, including HO-1, SOD2, NQO1, and GPX4, which are critical inhibitors of ferroptosis. Disruption of SIRT1-Nrf2 signalling accelerates GC senescence, follicular depletion, and reproductive aging. In contrast, pharmaceutical and nutraceutical therapies, including metformin, melatonin, resveratrol, and agents that increase NAD⁺ levels, may reverse ovarian deterioration and reactivate SIRT1-Nrf2 activity. This narrative review highlights innovative treatment prospects for ovarian aging, fertility preservation, and assisted reproduction by synthesising current evidence on ferroptotic pathways, SIRT1-Nrf2 interactions, and oxidative stress in granulosa cells. An understanding of these interrelated biological networks enables the development of tailored therapies that postpone ovarian ageing and enhance reproductive outcomes for women receiving fertility therapy. Full article

Regulatory T cells (Tregs), particularly their phenotypically distinct subpopulations, are critical for the establishment of maternal immune tolerance during embryo implantation. Despite advances in assisted reproductive technologies, implantation failure remains a frequent and often unexplained clinical challenge. Variations in Treg frequency and phenotype have been proposed to influence implantation success, particularly under differing hormonal conditions. This study aimed to investigate peripheral blood Treg levels and their subpopulations on the day of blastocyst transfer in both stimulated in vitro fertilization (IVF/ICSI) cycles involving controlled ovarian hyperstimulation (COH) and true natural cycles with frozen embryo transfer (FET), and to examine their associations with systemic hormone levels and anti-Müllerian hormone (AMH). A prospective observational study was conducted including women undergoing IVF/ICSI with fresh embryo transfer (ET) and women undergoing natural cycle FET. Peripheral blood samples were collected on the day of ET and analyzed using 13-colour flow cytometry, enabling detailed subdivision of Tregs into multiple subpopulations based on the expression of differentiation and chemokine markers, including CXCR5. In addition, because common $\gamma$-chain cytokines may influence pregnancy success by modulating the balance between suppressive Treg and non-Treg subsets, intracellular STAT5 signaling was assessed using phospho-specific flow cytometry. Serum estradiol, progesterone, FSH, LH, and AMH levels were measured in parallel. Significant differences were observed in Treg subpopulation distributions between women who conceived and those who did not. Higher frequencies of naïve CXCR5⁻ Tregs were associated with clinical pregnancy, independent of age, and correlated with serum progesterone levels. Moreover, both naïve Treg frequency and enhanced IL-7-dependent STAT5 signaling in naïve Tregs from women undergoing COH were associated with AMH levels, suggesting a link between ovarian reserve and Treg homeostasis mediated by signal transducer and activator of transcription 5 (STAT5) signaling. In conclusion, Treg subpopulations, particularly CXCR5⁻ naïve Tregs, appear to play a central role in implantation success following ET. Their distribution differs between stimulated and natural cycles and is influenced by systemic progesterone levels and STAT5 signaling. These findings suggest that peripheral Treg profiling may represent a potential biomarker of implantation competence and could inform personalized approaches in assisted reproduction. Full article

Background and Objectives: Obesity is a major contributor to female reproductive dysfunction, frequently resulting in menstrual irregularity, anovulation, and subfertility. Bariatric surgery improves metabolic health; however, its effect on reproductive outcomes—particularly the shift from assisted to spontaneous conception—remains incompletely defined. This study aimed to evaluate the impact of laparoscopic sleeve gastrectomy (LSG) on menstrual cycle regularity and spontaneous pregnancy rates in women of reproductive age. Materials and Methods: This retrospective observational study included 52 women aged 18–40 years who underwent LSG between January 2013 and October 2017. Self-reported menstrual history, as documented during routine preoperative assessment in the electronic medical records, and reproductive outcomes (including spontaneous and assisted conception) were compared between the preoperative and postoperative periods. The median follow-up duration was 38 months. Results: A significant improvement in menstrual regularity was observed (46.2% to 94.2%, p < 0.001). Among women attempting conception, 10/15 (66.7%) achieved spontaneous pregnancy; one conceived via ART. Notably, 57.1% of all pregnancies occurred within the first 12 months post-surgery, including three unintended conceptions. Additionally, among women who conceived spontaneously, four had a history of requiring assisted reproductive technologies (ART), including two who had previously failed to conceive despite ART treatment. Conclusions: LSG is associated with significant normalization of menstrual cycles and a qualitative shift toward spontaneous conception in morbidly obese women. The rapid return of fertility, which may exceed patient awareness, underscores the importance of comprehensive perioperative counseling regarding effective contraception to prevent unintended pregnancies during the active weight-loss phase. Full article

Cervical cancer remains a significant global health burden, disproportionately affecting women in low- and middle-income countries despite being preventable. Since 2018, rapid advances in molecular profiling, immunotherapy, refinement of minimally invasive surgery, and targeted therapeutics have transformed diagnostic and therapeutic paradigms. This narrative review synthesizes clinical and translational progress across the continuum of care from 2018 to 2025. We summarize the evolving landscape of precision screening—including HPV genotyping, DNA methylation assays, liquid biopsy, and AI-assisted cytology—and discuss their implications for global elimination goals. Surgical management has shifted toward evidence-based de-escalation with data from SHAPE, ConCerv, and ongoing RACC informing fertility preservation and minimally invasive approaches. For locally advanced disease, KEYNOTE-A18 establishes pembrolizumab plus chemoradiation as a new curative standard, while INTERLACE underscores the benefit of induction chemotherapy. In the metastatic setting, survival outcomes have improved with the integration of checkpoint inhibitors (KEYNOTE-826, BEATcc, EMPOWER-Cervical 1), vascular-targeted therapies, and antibody–drug conjugates, including tisotumab vedotin and emerging HER2 and TROP-2–directed agents. We further highlight emerging biomarkers—PD-L1, TMB, MSI status, HPV integration patterns, APOBEC signatures, methylation classifiers, ctHPV-DNA—and their evolving role in treatment selection and surveillance. Future directions include neoadjuvant checkpoint inhibition, PARP-IO combinations, HER3-directed ADCs, DDR-targeted radiosensitizers, HPV-specific cellular therapies, and AI-integrated precision medicine. Collectively, these advances are reshaping cervical cancer care toward biologically individualized, globally implementable strategies capable of accelerating WHO elimination targets. Full article

China has experienced a population decline since 2022, and its total fertility rate has dropped to about 1.0 in 2025. This is despite the lifting of the one-child policy in 2015 and the pivot to the two-child policy and three-child policy in, respectively, 2016 and 2021. Based on a review of recent research, this paper provides an interpretation that the continued fertility decline reflects a perfect storm of socioeconomic and demographic processes, long-term effects of the one-child policy, and unprecedented social changes in Chinese society. Socioeconomic and demographic changes since the 1950s prepared the ground for the “late, sparse, few” policy, resulting in a sharp fertility decline in the 1970s. While the one-child policy that followed did not result in a fertility decline in the 1980s, its effects appear to be long-lasting, including concentrated investment by the “inverted family” in the only child that drives up society-wide childrearing costs. Significant improvement in women’s educational attainment, individualistic orientation that prioritizes personal goals, increased diversity in family structure, such as one-person households, and changing views about getting married and having children have all contributed to continued downward pressure on fertility. These findings hint at the relevance of the concept of the second demographic transition for China and suggest that policy is only effective if it is aligned with what people want. Full article

With increasing life expectancy driven by rapid biomedical science advancement, reproductive longevity has become a key concept in women’s health. Preventing reproductive senescence is important not only to extend fertility potential but also to preserve endocrine health, enhance quality of life, and promote healthy aging. The end of ovarian function and fertility is symbolized by menopause, as the most eminent index of reproductive aging. Hormone replacement therapy (HRT) remains the mainstay for managing menopausal symptoms. However, as the use of HRT is often limited, there is a need for safe and effective alternatives. This narrative review summarizes current and emerging approaches targeting different stages of reproductive aging. Both hormonal and non-hormonal therapies for vasomotor and genitourinary symptoms are discussed alongside developing fertility preservation techniques, including oocyte vitrification, ovarian tissue cryopreservation, in vitro follicle maturation, and artificial ovary engineering. Furthermore, evolving and experimental ovarian regenerative strategies, such as stem cell transplantation, intraovarian platelet-rich plasma (PRP) injections, antioxidants, metabolic modulators, telomerase activators, and stem cell-derived extracellular vesicles, offer new prospects for delaying or reversing ovarian aging. Overall, personalized regenerative strategies and innovative solutions may reshape the future of women’s reproductive health and longevity. Full article

Women of reproductive age, especially those with polycystic ovarian syndrome (PCOS), often use glucagon-like peptide-1 receptor agonists (GLP-1RAs) to improve their metabolic functions. A growing body of evidence suggests that GLP-1R signaling may directly affect ovarian physiology, influencing granulosa cell proliferation, survival pathways, and steroidogenic production, in addition to its systemic metabolic effects. Nonetheless, there is a limited comprehension of the molecular mechanisms that regulate these activities and their correlation with menstrual function, reproductive potential, and assisted reproduction. This comprehensive review focuses on ovarian biology, granulosa cell signaling networks, steroidogenesis, and translational fertility outcomes, integrating clinical, in vivo, and in vitro information to elucidate the effects of GLP-1 receptor agonists on reproductive health. We conducted a thorough search of PubMed, Scopus, and Web of Science for randomized trials, prospective studies, animal models, and cellular experiments evaluating the effects of GLP-1RA on reproductive or ovarian outcomes, in accordance with PRISMA criteria. The retrieved data included metabolic changes, androgen levels, monthly regularity, ovarian structure, granulosa cell growth and death, FOXO1 signaling, FSH-cAMP-BMP pathway activity, and fertility or IVF results. Clinical trials shown that GLP-1 receptor agonists improve menstrual regularity, decrease body weight and central adiposity, increase sex hormone-binding globulin levels, and lower free testosterone in overweight and obese women with PCOS. Liraglutide, when combined with metformin, significantly improved IVF pregnancy rates, whereas exenatide increased natural conception rates. Mechanistic studies demonstrate that GLP-1R activation affects FOXO1 phosphorylation, hence promoting granulosa cell proliferation and anti-apoptotic processes. Incretin signaling altered steroidogenesis by reducing the levels of StAR, P450scc, and 3β-HSD, so inhibiting FSH-induced progesterone synthesis, while simultaneously enhancing BMP-Smad signaling. Animal studies demonstrated both beneficial (enhanced follicular growth, anti-apoptotic effects) and detrimental results (oxidative stress, granulosa cell death, uterine inflammation), indicating a context- and dose-dependent response. GLP-1 receptor agonists influence female reproductive biology by altering overall physiological processes and specifically impacting the ovaries via FOXO1 regulation, steroidogenic enzyme expression, and BMP-mediated FSH signaling. Preliminary clinical data indicate improved reproductive function in PCOS, as seen by increased pregnancy rates in both natural and IVF cycles; nevertheless, animal studies reveal a potential risk of ovarian and endometrial damage. These results highlight the need for controlled human research to clarify reproductive safety, molecular pathways, and optimum therapy timing, particularly in non-PCOS patients and IVF settings. Full article

Obstructive sleep apnea (OSA) is a highly prevalent disorder with far-reaching systemic consequences. While its cardiometabolic and neurocognitive impacts are well established, growing evidence highlights OSA as a contributor to infertility in both men and women. The pathophysiological mechanisms include intermittent hypoxia, oxidative stress, systemic inflammation, and endocrine disruption, all of which can impair spermatogenesis, reduce semen quality, alter gonadal hormone secretion, and compromise ovarian function. Clinical studies consistently demonstrate associations between OSA and impaired semen parameters, reduced testosterone, and erectile dysfunction in men. In women, OSA is frequently observed in those with polycystic ovary syndrome, is associated with ovulatory dysfunction, and negatively affects in vitro fertilization outcomes, pregnancy rates, and miscarriage risk. Despite these findings, infertility is not systematically included in global burden estimates of OSA, leading to the underestimation of its true health and socioeconomic impact. Therapeutic strategies such as weight loss, continuous positive airway pressure, and integrative approaches show promise, though robust evidence from randomized trials is still lacking. Integrating sleep health into reproductive medicine may provide a cost-effective and equitable pathway to improve fertility outcomes worldwide. Full article

Background and Objectives: Klotho (KL) is a multifunctional protein involved in reproductive physiology; however, its precise role in ovarian reserve and in vitro fertilization (IVF) outcomes remains unclear. This study aimed to evaluate the relationship between follicular fluid KL levels, ovarian reserve markers, and key IVF success parameters. Materials and Methods: This prospective study included a total of 150 women undergoing IVF, of whom 82 had diminished ovarian reserve (DOR) and 68 had normal ovarian reserve (NOR). All participants underwent controlled ovarian stimulation using a standard antagonist protocol. During oocyte pick-up (OPU), the first aspirated follicular fluid sample was collected, processed, and analyzed for KL concentrations using a Human Klotho ELISA kit. Hormonal profiles, ovarian reserve markers, and IVF outcomes were compared between groups. Results: Follicular fluid KL levels were significantly lower in the DOR group compared with the NOR group (117.07 ± 28.88 pg/mL vs. 266.13 ± 58.29 pg/mL; p < 0.001). Anti-Müllerian hormone (AMH) levels were reduced, whereas follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels were significantly higher in the DOR group (all p < 0.001). Implantation and clinical pregnancy rates were also significantly lower in the DOR group compared with the NOR group (p < 0.001 and p = 0.003, respectively). KL levels showed a strong positive correlation with the number of fertilized oocytes in both groups (DOR: r = 0.690; NOR: r = 0.552). Each one-unit increase in KL was associated with a 3.7% increase in implantation probability and a 3.2% increase in clinical pregnancy probability in the DOR group, and with corresponding increases of 4.4% and 1.2% in the NOR group (all p < 0.05). Conclusions: This study demonstrates significant associations between follicular fluid KL levels and fertilization, implantation, and clinical pregnancy outcomes. These associations appear to be more pronounced than those observed with traditional ovarian reserve markers such as AMH and antral follicle count. Reduced KL levels are associated with fewer fertilized oocytes, whereas higher KL concentrations correspond to increased implantation and clinical pregnancy probabilities. Nevertheless, similar to other non-invasive biomarkers, current evidence is insufficient to support routine clinical use of KL. Large-scale, well-designed, multicenter studies are therefore required to validate its clinical relevance and to determine whether KL can serve as a reliable and practical predictor of IVF success. Full article