RESEARCH QUESTION: Does the use of embryo warming with an ultrafast protocol influence clinical and perinatal health outcomes when compared with conventional warming protocols? DESIGN: A retrospective cohort study was co...RESEARCH QUESTION: Does the use of embryo warming with an ultrafast protocol influence clinical and perinatal health outcomes when compared with conventional warming protocols? DESIGN: A retrospective cohort study was conducted at a single IVF centre evaluating frozen embryo transfer cycles performed between November 2023 and December 2024. Traditionally vitrified embryos were subsequently warmed using either traditional or ultrafast protocols. Live birth rate and perinatal outcomes including gestational age, neonatal birthweight and twin rates were calculated. RESULTS: A total of 4061 blastocyst warming events in 3657 embryo transfer cycles were analysed, of which 2761 involved warming using an ultrafast protocol and 1300 warming using a traditional protocol. Embryo survival was 99% following both methods. Live birth rates were comparable (37% versus 35.4%). No significant differences were observed in perinatal health outcomes. CONCLUSIONS: Warming with an ultrafast protocol provides excellent embryological and clinical outcomes equivalent to those achieved with traditional warming, without evident adverse effects on perinatal health outcomes. These findings support the efficiency of the ultrafast protocol as a routine approach in assisted reproduction and its potential to maintain optimal patient outcomes.
RESEARCH QUESTION: In women undergoing fertility-sparing surgery for unilateral ovarian endometriomas, how do recurrence rates and postoperative ovarian reserve compare between plasma energy ablation (PEA) and laparoscop...RESEARCH QUESTION: In women undergoing fertility-sparing surgery for unilateral ovarian endometriomas, how do recurrence rates and postoperative ovarian reserve compare between plasma energy ablation (PEA) and laparoscopic cystectomy? DESIGN: Retrospective cohort study including 176 women aged 18-40 years with unilateral ovarian endometriomas treated at a single tertiary referral centre between 2011 and 2024. Patients underwent laparoscopic management with either PEA (n = 87) or cystectomy (n = 89). The primary outcome was the ipsilateral endometrioma recurrence rate over 48 months. Secondary outcomes were postoperative changes in serum anti-Müllerian hormone (AMH) and antral follicle count (AFC). RESULTS: No significant differences were observed in ipsilateral recurrence-free survival between PEA and cystectomy (recurrence rate at 48 months: 23.7% versus 26.6%, respectively; log-rank P = 0.866). The recurrence rate in the contralateral ovary was also comparable between groups. Cox regression, adjusted for confounders, confirmed that surgical technique was not independently associated with risk of recurrence. Postoperative ovarian reserve was preserved more effectively in the PEA group. Mean reduction in serum AMH was -0.3 ± 0.5 ng/ml for the PEA group and -0.9 ± 0.7 ng/ml for the cystectomy group (P < 0.001). AFC in the operated ovary improved after PEA (2.0 ± 3.3), but declined after cystectomy (-1.0 ± 2.8) (P < 0.001). Complete absence of antral follicles (AFC = 0) in the operated ovary occurred in 1.1% of patients in the PEA group and 33.7% of patients in the cystectomy group (P < 0.001). CONCLUSIONS: PEA and cystectomy demonstrated comparable recurrence rates for unilateral endometriomas over a 48-month follow-up period. However, PEA was associated with significantly better preservation of ovarian reserve.
RESEARCH QUESTION: What is the biological effectiveness and source of antioxidant activity in commercial IVF media? DESIGN: Antioxidant activity, defined by the ability of individual culture media to scavenge hydrogen pe...RESEARCH QUESTION: What is the biological effectiveness and source of antioxidant activity in commercial IVF media? DESIGN: Antioxidant activity, defined by the ability of individual culture media to scavenge hydrogen peroxide, free radicals and lipid hydroperoxide, was assessed over 24 h in the presence and absence of spermatozoa. Motility, DNA integrity and mitochondrial reactive oxygen species (ROS) generation were investigated. Protein concentration, identification and activity were studied using the DC protein assay, sodium dodecyl sulphate polyacrylamide gel electrophoresis and thiol quantification, respectively. Molecular filtration was employed to determine the role of albumin in supporting sperm function. RESULTS: The results revealed highly significant differences between media in their capacity to support sperm motility and DNA integrity. Media that optimally supported sperm function generally possessed high levels of antioxidant activity. Moreover, spermatozoa were shown to consume antioxidant equivalents from these media, particularly with respect to their hydrogen peroxide scavenging activity. The major antioxidant present in these commercial preparations was found to be albumin. When albumin was selectively removed, the abilities of these media to support sperm motility, control mitochondrial ROS generation and suppress DNA damage were lost. However, if the albumin content of these media was subsequently restored, all these supportive properties were recovered. Thiol oxidation and the binding of cytotoxic metabolites were central to albumin's protective action. CONCLUSIONS: These studies emphasize the importance of antioxidant activity in supporting sperm function in vitro. As albumin is the only antioxidant available to these cells in current media formulations, an opportunity exists to optimize how such protection is delivered in the future.
Among the many symbols that appear in the medical literature, few have received as much attention as the letter 'P'. It is printed in almost every table, discussed in every result section and often treated as the final w...Among the many symbols that appear in the medical literature, few have received as much attention as the letter 'P'. It is printed in almost every table, discussed in every result section and often treated as the final word in the interpretation of scientific findings. In reality, the P-value is neither over-rated nor under-rated. It is simply misunderstood. It is an important tool, but it is not the main factor that determines the value of a study. What matters is not the number itself, but how we think about it and what it truly represents. This manuscript revisits the 'value' of the P-value in reproductive medicine.
Recent advances in cancer diagnosis and therapy have increased the 5-year survival rate. However, anticancer treatments are gonadotoxic; therefore, fertility preservation is recommended prior to the initiation of therapy...Recent advances in cancer diagnosis and therapy have increased the 5-year survival rate. However, anticancer treatments are gonadotoxic; therefore, fertility preservation is recommended prior to the initiation of therapy to optimize future chances of conceiving. The only method for preserving fertility in prepubescent girls, also suitable for women, is ovarian tissue cryopreservation (OTC). Although approximately 250-300 births have been reported with this approach, significant variability in cryopreservation protocols is observed across fertility preservation centres. Importantly, the presence of residual disease in cryopreserved ovarian fragments will prevent the restoration of fertility. The primary aim of this review is to offer an overview of the impact of cancer and its treatment on female fertility, including the latest updates on novel therapies. This will help to refine fertility preservation indications - a growing concern in the oncofertility field. This review will also provide a comprehensive summary of the different procedures used for OTC, with the aim of standardizing protocols in clinical practice, and offer an updated overview of alternative, albeit experimental, approaches that are being developed to restore fertility and overcome the limitations of transplantation. This will highlight next-generation solutions for restoring the fertility of young female patients.
RESEARCH QUESTION: Do platelets exert a protective effect against oxidative stress in human endometrial stromal cells (HESC) in vitro? DESIGN: An in-vitro oxidative stress model was developed in HESC by exposing them to...RESEARCH QUESTION: Do platelets exert a protective effect against oxidative stress in human endometrial stromal cells (HESC) in vitro? DESIGN: An in-vitro oxidative stress model was developed in HESC by exposing them to varying concentrations (0, 100, 200, 300, 400 and 500 μM) of hydrogen peroxide (HO). Rat platelets were collected and co-cultured with oxidatively damaged HESC, and changes in viability, apoptosis rate, reactive oxygen species (ROS) concentrations, apoptosis-related proteins, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signalling pathway activation, and inflammatory cytokine profiles were measured systematically using a Cell Counting Kit-8 assay, flow cytometry, quantitative reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blot analyses. RESULTS: Platelet treatment reduced the apoptosis rate and intracellular ROS accumulation significantly compared with the HO group (ROS: P ≤ 0.0003; apoptosis rate: P < 0.0001), and decreased the concentration of malondialdehyde and pro-inflammatory cytokine secretion (P ≤ 0.0129). Similarly, platelets enhanced superoxide dismutase activity and restored viability (P ≤ 0.0459). Furthermore, exposure to platelets reversed the HO-induced increase in Bcl-2-associated X protein (Bax)/B-cell lymphoma 2(Bcl-2) protein ratio (P = 0.0029), and upregulated the phosphorylation levels of PI3K and AKT in the PI3K/AKT signalling pathway (P ≤ 0.0457). CONCLUSION: These results showed that platelets can mitigate oxidative stress and enhance endometrial resilience, suggesting that they have high potential for clinical management of thin endometrium.
RESEARCH QUESTION: Does changing frozen embryo transfer (FET) protocols after initial unsuccessful, autologous, single euploid FET improve pregnancy outcomes in the second cycle? DESIGN: Retrospective cohort study (n = 2...RESEARCH QUESTION: Does changing frozen embryo transfer (FET) protocols after initial unsuccessful, autologous, single euploid FET improve pregnancy outcomes in the second cycle? DESIGN: Retrospective cohort study (n = 2199) including patients without ongoing pregnancy (fetal cardiac activity at 8‒9 weeks' gestation) after first, single, euploid FET using programmed (exogenous hormones) or modified natural (MNC) with trigger protocols between January 2017 to December 2024 and changed protocols in the second FET. Primary outcome was ongoing pregnancy. Secondary outcomes were implantation (beta-HCG >5 mIU/ml), clinical pregnancy (intrauterine pregnancy with cardiac activity), pregnancy loss and live birth (liveborn infant >24 weeks). RESULTS: Of the 2199 included patients, 1619 remained on same protocol and 580 changed protocols in the second FET. Changed patients had a higher oocyte age and maternal age at time of second FET and lower anti-Müllerian hormone. Parity, primary diagnosis, paternal age, endometrial thickness, blastulation day and SART embryo grade were comparable. Implantation was similar (adjusted RR [aRR] 1.03, 95% CI 0.98 to 1.08, P = 0.30), but patients who changed protocols had higher chances of clinical (aRR 1.09, 95% CI 1.02 to 1.16, P = 0.008) and ongoing pregnancy (aRR 1.14, 95% CI 1.06 to 1.22, P = 0.001), live birth (aRR 1.14, 95% CI 1.06 to 1.24, P = 0.001) and lower risk of loss (aRR 0.73, 95% CI 0.59 to 0.90, P = 0.003). Sensitivity analyses restricting nulliparous patients and patients with a negative beta-HCG after their first FET yielded similar results. No differences were found among parous patients. Subgroup analyses found improved probability of ongoing pregnancy changing from programmed to MNC (aRR 1.16, 95% CI 1.07 to 1.25) but not from MNC to programmed (aRR 1.01, 95% CI 0.84 to 1.21). CONCLUSION: Changing protocols in a second FET, particularly from programmed to MNC, may improve the probability of ongoing pregnancy and live birth.
Ovarian hyperstimulation syndrome (OHSS) is a potentially serious complication associated with ovarian stimulation for assisted reproductive technology. While measures to prevent and reduce the incidence of OHSS are part...Ovarian hyperstimulation syndrome (OHSS) is a potentially serious complication associated with ovarian stimulation for assisted reproductive technology. While measures to prevent and reduce the incidence of OHSS are part of good clinical practice, OHSS still occurs, and patients may present to clinicians with varying familiarity with the condition. Diagnosis is largely clinical, although radiological and laboratory testing helps determine the severity of the syndrome. Management of moderate and severe OHSS is primarily supportive as either an outpatient or an inpatient and may include paracentesis. Critical OHSS needs hospitalization and multidisciplinary care. This clinical practice guideline assesses the published evidence regarding the diagnosis and management of patients presenting with moderate and severe OHSS.
The 2025 World Health Organization (WHO) Guideline for the Prevention, Diagnosis, and Treatment of Infertility represents the first comprehensive global framework integrating male and female contributors to infertility w...The 2025 World Health Organization (WHO) Guideline for the Prevention, Diagnosis, and Treatment of Infertility represents the first comprehensive global framework integrating male and female contributors to infertility within a unified public health strategy. This commentary examines the male-relevant components of the guideline from the perspective of reproductive biology and translational andrology. The WHO guideline mandates a parallel evaluation of both partners and structures male assessment around the medical history, a focused physical examination and semen analysis as a triage tool. While pragmatic and globally applicable, semen analysis remains a descriptive rather than a mechanistic test, underscoring the need for a deeper investigation into sperm chromatin integrity, epigenetics and molecular function. The guideline's conservative treatment recommendations - limited to clinical varicocele repair and antioxidant therapy - reflect Population, Intervention, Comparison, Outcome prioritization, the GRADE methodology and an emphasis on pregnancy and live-birth outcomes, as well as considerations of equity and feasibility across diverse health systems. By embedding male reproductive health within a global infertility approach, the guideline promotes structured evaluation, early specialist referral and reproductive equity, while highlighting critical gaps in mechanistic understanding that must inform future research and clinical innovation.
RESEARCH QUESTION: Is there a relationship between the location of adenomyosis lesions and obstetric and neonatal outcomes? DESIGN: A total of 466 women diagnosed with adenomyosis via transvaginal ultrasound between Janu...RESEARCH QUESTION: Is there a relationship between the location of adenomyosis lesions and obstetric and neonatal outcomes? DESIGN: A total of 466 women diagnosed with adenomyosis via transvaginal ultrasound between January 2019 and December 2021 were included. Inclusion criterion was a clinical pregnancy (natural conception or ART) achieved within 2 years after diagnosis; patients were followed up until a definitive pregnancy outcome. Women were divided into internal and non-internal adenomyosis groups based on the location of the adenomyosis lesion. Obstetric and neonatal outcomes were compared. Adjusted ratio ratios (aORs) and 95% confidence intervals were calculated by multivariate analysis. Outcomes were adjusted for age, gravidity, mode of conception, history of hysteroscopy and presence of ovarian endometriosis. RESULTS: A total of 251 women (53.9%) presented with internal adenomyosis compared with women with non-internal adenomyosis (n = 215). The internal adenomyosis group were older (35.0 ± 4.3 versus 34.2 ± 4.3 years, P = 0.029) and had more pregnancies. After adjusting for confounders, the internal adenomyosis group had a lower likelihood of live birth (aOR 0.43, 95% CI 0.29 to 0.64, P < 0.001) and a higher risk of early spontaneous miscarriage (aOR 2.27, 95% CI 1.29 to 4.10, P = 0.005). Among women who had live births, women in the internal adenomyosis group had a higher risk of preterm premature rupture of membranes (aOR 3.06, 95% CI 1.37 to 7.27, P = 0.008) and a small for gestational age infant (aOR 2.73, 95% CI 1.24 to 6.32, P = 0.015). CONCLUSION: Women with internal adenomyosis face a higher risk of adverse obstetric and neonatal outcomes; affected patients should be referred early to a high-risk clinic for intensified surveillance and individualized management to improve maternal and infant outcomes.
RESEARCH QUESTION: Do certain killer-cell immunoglobulin-like receptor (KIR) polymorphisms of uterine natural killer (uNK) cells contribute to early pregnancy losses, and if so, how? DESIGN: This prospective, cohort stud...RESEARCH QUESTION: Do certain killer-cell immunoglobulin-like receptor (KIR) polymorphisms of uterine natural killer (uNK) cells contribute to early pregnancy losses, and if so, how? DESIGN: This prospective, cohort study included 23 European ancestry women under 43 years old with a normal body mass index (19-25 kg/m²) who experienced idiopathic early pregnancy loss (<12 gestational weeks) after a single euploid embryo transfer following intracytoplasmic sperm injection/preimplantation genetic testing for aneuploidies between June 2022 and December 2024. Participants were categorized based on KIR haplotypes and the presence or absence of the activating genes KIR2DS1 and KIR3DS1. Endometrial biopsies were collected and used for transcriptomic analysis and to establish co-cultures of patient-derived primary uNK cells with trophoblast-derived JEG-3 spheroids. RESULTS: Participants lacking the KIR2DS1 and KIR3DS1 genes exhibited higher luteal progesterone concentrations (P = 0.0059, P = 0.0151). Transcriptomic analysis revealed that patients with inhibitory KIR profiles showed a down-regulation of cell signalling and molecular transduction coupled with an upregulation of immune response. Functional assays demonstrated that uNK cells derived from individuals with activator KIR profiles exhibited higher cytokine production (AgRP, IFN-γ, IL-8, IL-17A, IP-10, TNF-β; P ≤ 0.0482), with a lower production of IL-12p40 (P = 0.0492), than in patients carrying the inhibitory KIR haplotype. Additionally, intracellular reactive oxygen species production positively correlated with progesterone concentrations (P < 0.05), especially in KIR3DS1 participants. Further correlations were observed between cytokine secretion, progesterone concentrations and ROS, with key molecules like FGF-4, TGF-β1 and follistatin. CONCLUSIONS: KIR polymorphisms influence endometrial gene expression, progesterone concentrations, cytokine secretion and oxidative stress in women with unexplained early miscarriage in the current cohort, highlighting FGF-4, TGF-β1 and follistatin as candidate mediators of early maternal-fetal cross-talk. However, as this study is limited to a single patient ethnicity, larger cohorts are necessary to validate the results.
RESEARCH QUESTION: In letrozole-stimulated frozen embryo transfer (FET) cycles, is oestradiol concentration on the day of ovulatory trigger associated with live birth? DESIGN: Retrospective cohort study of all patients i...RESEARCH QUESTION: In letrozole-stimulated frozen embryo transfer (FET) cycles, is oestradiol concentration on the day of ovulatory trigger associated with live birth? DESIGN: Retrospective cohort study of all patients in a private fertility network who underwent autologous single blastocyst letrozole-stimulated FET cycles from January 2017 to November 2023. Patients with recurrent pregnancy loss, unmitigated uterine factor, use of gestational carriers or donor gametes, and use of gonadotrophins or oestradiol supplementation to increase endometrial thickness were excluded. RESULTS: In total, 968 FET cycles were performed in 883 patients. The mean ± SD maternal age was 35.2 ± 3.9 years, median peak oestradiol concentration on trigger day was 184.9 pg/ml (IQR 126.0-249.1), and median endometrial thickness was 8.9 mm (IQR 8.1-10.1). Oestradiol concentration was not significantly associated with live birth when evaluated either continuously or categorically (adjusted for age, body mass index, and use of preimplantation genetic testing for aneuploidy). The point estimate for live birth was 8% lower at 60 pg/ml [risk ratio (RR) 0.92, 95% CI 0.71-1.19] and 15% higher at 200 pg/ml (RR 1.15, 95% CI 0.92-1.45) relative to 100 pg/ml, with rates plateauing thereafter up to 400 pg/ml. CONCLUSION: In this cohort, no significant association was found between oestradiol concentration on trigger day in letrozole-stimulated FET and live birth. Although a reduction in live birth was observed as the oestradiol concentration decreased below 100 pg/ml on trigger day, this finding did not reach significance. Importantly, even among cycles with lower oestradiol concentrations, the probability of live birth remained >40%.
The clinical utility and validity of preimplantation genetic testing for aneuploidies (PGT-A) in IVF practice is often questioned. Some major societies (Practice Committees of the American Society for Reproductive Medici...The clinical utility and validity of preimplantation genetic testing for aneuploidies (PGT-A) in IVF practice is often questioned. Some major societies (Practice Committees of the American Society for Reproductive Medicine and the Society for Assisted Reproductive Technology 2024) have released ambiguous statements about PGT-A, leaving the potential and benefits of embryo selection, enhanced by chromosome profile assessments, indeterminant. The Preimplantation Genetic Diagnosis International Society (PGDIS) Task Group has gathered the scientific information and critically evaluated the evidence about the clinical value of PGT-A. We considered technical aspects, genetic principles and clinical outcome studies, and conclude that the proper implementation of PGT-A results in increased benefits for IVF embryo selection. It is envisioned that this report will remove some of the confusion surrounding PGT-A, lead to informed choices about the use of PGT-A and ultimately result in improved transfer outcomes.
RESEARCH QUESTION: Do FSH types (recombinant FSH [rFSH] versus highly purified human menopausal gonadotrophin (HP-HMG) versus corifollitropin alfa (CFA) differ in the efficiency of ovarian response, as assessed by follic...RESEARCH QUESTION: Do FSH types (recombinant FSH [rFSH] versus highly purified human menopausal gonadotrophin (HP-HMG) versus corifollitropin alfa (CFA) differ in the efficiency of ovarian response, as assessed by follicular output rate (FORT) and follicle-to oocyte index (FOI)? DESIGN: Retrospective cohort study analysing 4525 antagonist IVF and intracytoplasmic sperm injection cycles using CFA (n = 728), rFSH (n = 1848) or HP-HMG (n = 1949). The FORT and FOI indices were calculated as ratios of follicle or oocyte yield to antral follicle count (AFC). Generalized estimating equations were used to account for clustering by patient with covariates for age, anti-Müllerian hormone (AMH), weight, stimulation duration, gonadotrophin dose and elective freeze. RESULTS: The CFA yielded the highest ovarian response indices (FORT 16-22 [61.6%], FOI-COC [106.4%], FOI-MII [81.1%]), compared with rFSH (49.3%, 98.0%, 74.6%) and HP-HMG (39.6%, 71.5%, 46.5%). Stratified analyses confirmed this ranking across AMH strata. In low AMH (<1.1 ng/ml), FOI-MII was 81.4% with CFA, 64.5% with rFSH and 49.2% with HP-HMG. In normal/high AMH (1.1-3 ng/ml) FOI-MII was 86.3%, 64.5% and 53.1%. Generalized additive model analyses demonstrated a modest non-linear AMH effect only for CFA, peaking at about 1.5-2.0 ng/ml before declining, whereas rFSH rose gradually and HP-HMG remained quite flat. Age-stratified analyses showed a uniform decline across FSH types. The risk of OHSS (>18 follicles ≥11 mm) was lowest with CFA (6.5%), compared with 19.8% for HP-HMG and 39.2% for rFSH. CONCLUSION: After adjusting for AFC, CFA achieved the highest FORT and FOI across most AMH strata, consistently outperforming HP-HMG and matching or exceeding rFSH, while maintaining the lowest follicle-count-based OHSS risk.
Despite growing evidence, the contribution of paternal factors to embryo morphokinetics and clinical outcomes in assisted reproductive technology (ART) has been largely overlooked. This systematic review and meta-analysi...Despite growing evidence, the contribution of paternal factors to embryo morphokinetics and clinical outcomes in assisted reproductive technology (ART) has been largely overlooked. This systematic review and meta-analysis was conducted to evaluate associations between sperm parameters and embryo morphokinetic events, and to assess their impact on ART outcomes. Studies published between January 2015 and December 2024 were screened in accordance with the PRISMA guidelines. Morphokinetic variables and clinical outcomes were extracted, and random-effects meta-regression was performed to examine the influence of sperm quality on embryo development and clinical endpoints. Nine studies with heterogeneous case-control definitions and 26,111 embryos (8144 cases versus 17,967 controls) met the inclusion criteria. In study-level meta-analysis and meta-regression, early cleavage events were not significantly associated with sperm quality, whereas lower sperm concentration and motility were associated with delays in later developmental stages. The meta-regression showed that sperm motility was positively associated with implantation (β = 0.035, 95% CI 0.014-0.056; P = 0.0012) and live birth (β = 0.041, 95% CI 0.004-0.080; P = 0.031), while sperm concentration was associated with implantation alone (β = 0.025, 95% CI 0.016-0.034; P < 0.001). No significant associations were observed for fertilization, clinical pregnancy or miscarriage. These findings provide meta-analytic evidence linking paternal sperm quality to embryo morphokinetics, and underscore the importance of considering paternal factors in ART outcomes.
RESEARCH QUESTION: What does the Australian public know about mitochondrial donation and think about its potential clinical implementation? DESIGN: 1042 people aged ≥18 years living in Australia completed an online anony...RESEARCH QUESTION: What does the Australian public know about mitochondrial donation and think about its potential clinical implementation? DESIGN: 1042 people aged ≥18 years living in Australia completed an online anonymous survey between October and December 2022. Participants were recruited through a market research company. The survey included multiple choice and Likert-scale questions gauging respondents' knowledge and attitudes. Bivariate analysis investigated differences in support for mitochondrial donation based on different sociodemographic groups. RESULTS: Just 19% of respondents had ever heard of mitochondrial donation prior to participation (n = 202). The average level of agreement with the statement 'If the clinical trial proves mitochondrial donation is safe, I support it becoming available in Australia' was 3.36 out of a possible 4, indicating agreement. Significant differences in the average agreement level were reported across the different 'prior use of assisted reproductive technology', 'sexual orientation', 'genetic condition' and 'mitochondrial disease' groups; however, the average level of agreement in each group was consistently >3. CONCLUSIONS: The findings indicate broad public support for the clinical implementation of mitochondrial donation in Australia, provided that clinical trials demonstrate its safety. Although these results may not extrapolate directly to other contexts, they may guide other jurisdictions in considering their position towards mitochondrial donation.
RESEARCH QUESTION: Can a non-invasive artificial intelligence (AI) model based on time-lapse imaging (TLI) data accurately predict embryo ploidy and support embryo selection in IVF? DESIGN: This retrospective multicentre...RESEARCH QUESTION: Can a non-invasive artificial intelligence (AI) model based on time-lapse imaging (TLI) data accurately predict embryo ploidy and support embryo selection in IVF? DESIGN: This retrospective multicentre study involved 4822 blastocyst-stage embryos with known ploidy from three IVF clinics for training and internal validation, and 706 embryos from an independent patient cohort used for external testing. The AI model was trained using spatio-temporal features from TLI videos, producing a continuous score (0-100) reflecting the likelihood of euploidy. Associations with morphology, fetal heartbeat and ploidy subtypes were evaluated. RESULTS: In a blind test set (n = 705), higher AI ploidy scores were significantly associated with euploidy (odds ratio [OR] = 1.39, P < 0.001) and presence of a fetal heartbeat (FH+; OR = 1.26, P = 0.043). Euploid embryos had higher mean scores than aneuploid embryos (51.3 versus 43.44, P < 0.001); FH+ embryos scored higher than FH- embryos (53.63 versus 48.42, P = 0.013). AI ploidy scores decreased with increasing aneuploid complexity (P < 0.001), and within-patient differences were significant (P = 0.0098). External validation (n = 706) confirmed the model's ability to outperform an existing AI pregnancy predictor in ploidy discrimination (area under the curve [AUC] = 0.64 versus 0.61). Combined with morphology, predictive performance improved (AUC = 0.65). Top-quartile AI ploidy scores were associated with euploidy rates of over 90%. CONCLUSIONS: This validated, non-invasive AI model predicts embryo ploidy from TLI data and adds value to morphology in embryo selection. It demonstrates generalizable performance across clinics and may be especially useful when preimplantation genetic testing for aneuploidies is not feasible.
This guideline provides evidence-based recommendations, drawn exclusively from recent randomized control trials, for the clinical management of frozen embryo transfers (FET). In Canada, the incidence of freeze-all cycles...This guideline provides evidence-based recommendations, drawn exclusively from recent randomized control trials, for the clinical management of frozen embryo transfers (FET). In Canada, the incidence of freeze-all cycles has increased from 24.0% to 78.4% over the last decade. While a freeze-all strategy can be a pivotal tool for preventing ovarian hyperstimulation syndrome, the available data do not support its routine use for improving live birth rates, reducing pregnancy loss or enhancing obstetric outcomes in the general IVF population. Similarly, ovulatory FET cycles do not offer advantages over artificial FET cycles for live birth or pregnancy loss, and current evidence remains conflicting for obstetric and perinatal outcomes. The route of progesterone administration in artificial FET cycles does not significantly affect live birth or pregnancy loss rates. FET approaches should be individualized based on patient characteristics and clinical context, and further research is necessary to optimize outcomes and inform best practices.
RESEARCH QUESTION: Can metabolomic profiling of blastocyst spent culture medium (SCM) serve as a non-invasive tool to predict live birth? DESIGN: This pilot study investigated the association between metabolite profiles...RESEARCH QUESTION: Can metabolomic profiling of blastocyst spent culture medium (SCM) serve as a non-invasive tool to predict live birth? DESIGN: This pilot study investigated the association between metabolite profiles in SCM and clinical outcomes following single blastocyst transfer. Seventy SCM samples were analysed using untargeted liquid chromatography-mass spectrometry. Metabolites were identified via Human Metabolome Database and Compound Discoverer 3.3. Statistical analyses were performed using SPSS. RESULTS: In total, 173 metabolites were detected in SCM samples. Six metabolites exhibited significant differences between the pregnancy and non-pregnancy groups, while 10 metabolites varied between the live birth and non-live birth groups. Notably, eicosapentaenoic acid, a polyunsaturated fatty acid, decreased in pregnancy cases. In contrast, 1-(4-methoxyphenyl)-3-pentanone and (2S)-2-(6-methoxynaphthalen-2-yl) propanoic acid were consistently elevated in both the pregnancy and live birth groups. Additional differential metabolites included L-glutamine, pyroglutamylglycine, alanylproline and 15,16-dihydroxyoctadecanoic acid, potentially reflecting implantation-related metabolic activity. Logistic regression and receiver operating characteristic curve analyses demonstrated acceptable predictive performance, with area under the curve values of 0.788 for pregnancy and 0.834 for live birth. CONCLUSIONS: Metabolomic profiling of SCM may offer a promising non-invasive adjunct to embryo selection strategies. While these findings suggest biological relevance of several metabolites, particularly lipids and amino acid derivatives, larger studies are needed to validate predictive value and clinical applicability.