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Background: Polycystic ovarian syndrome (PCOS) occurs in 8% to 13% of all women of reproductive age and 50% of women presenting with infertility (i.e. inability to reach a pregnancy after 12 months or more of regular unprotected sexual intercourse). A proportion of these women ultimately need assisted reproductive technology. In vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) are assisted reproduction techniques used to raise the chances of a pregnancy. In women with PCOS, the supra-physiological doses of gonadotrophins used for controlled ovarian hyperstimulation (COH) often result in an exaggerated ovarian response characterised by the development of a large cohort of follicles of uneven quality, retrieval of immature oocytes, and increased risk of ovarian hyperstimulation syndrome (OHSS). A potentially effective intervention for women with PCOS-related infertility involves earlier retrieval of immature oocytes at the germinal-vesicle stage followed by in vitro maturation (IVM). This is the third update of this Cochrane review on the subject (after the last update on 27 June 2018)., Objectives: To assess the benefits and harms of IVM followed by IVF or ICSI versus conventional IVF or ICSI among women with PCOS., Search Methods: On 27 February 2023, we searched the Cochrane Gynaecology and Fertility Group Specialised Register of Controlled Trials, CENTRAL, MEDLINE, Embase, and the Open Grey database. We further searched the National Institute for Health and Care Excellence (NICE) fertility assessment and treatment guidelines. We also searched reference lists of relevant papers and Google Scholar for any additional trials., Selection Criteria: We included randomised controlled trials (RCTs) comparing IVM before IVF or ICSI with conventional IVF or ICSI for infertile women with PCOS, irrespective of language and country of origin., Data Collection and Analysis: Two review authors independently selected studies, assessed the risk of bias, extracted data from studies, and, where needed, attempted to contact the authors for missing data. Our primary outcomes were live birth per woman randomised and miscarriage. We performed statistical analysis using Review Manager. We assessed the certainty of the evidence using GRADE and the risk of bias using the Cochrane RoB 2 tool., Main Results: We found four published trials suitable for inclusion in this update. The studies involved 810 subfertile women undergoing assisted reproductive technology. Two of four were already included in the previous version of the review, were published as abstracts in international conferences, and were at high risk of bias. The two new studies were at low risk of bias in all domains and in terms of all outcomes. We implemented the random-effects model for the quantitative analyses and restricted the primary analysis to studies at low risk of bias in all domains. We are very uncertain about the effect of IVM or capacitation IVM (a new biphasic IVM system improving the developmental competence of oocytes) on live birth when compared to IVF when a GnRH antagonist protocol was applied (odds ratio (OR) 0.47, 95% confidence interval (CI) 0.17 to 1.32; I 2 = 91%; 2 studies, 739 participants; very low-certainty evidence). This suggests that if the chance of live birth following standard IVF is assumed to be 45.7%, then the chance of IVM would be 12.5% to 52.6%. In contrast, IVM or capacitation IVM increases miscarriage per clinical pregnancy (where clinical pregnancy was defined as evidence of a fetal heart beat on ultrasound at seven gestational weeks) in women with PCOS when compared to IVF (OR 1.66, 95% CI 1.02 to 2.70; I 2 = 0%; 2 studies, 378 clinical pregnancies; high-certainty evidence). This suggests that if the chance of miscarriage following standard IVF is assumed to be 20.1%, then the chance using IVM would be 20.4% to 40.4%. Results remained similar when using the risk ratio (RR) as the measure of effect. We are uncertain about the effect of IVM or capacitation IVM on clinical pregnancy when compared to IVF when a GnRH antagonist protocol was applied (OR 0.49, 95% CI 0.14 to 1.70; I 2 = 94%; 2 studies, 739 participants; very low-certainty evidence). The results were similar after pooling the RRs. IVM or capacitation IVM results in a large reduction in the incidence of moderate or severe OHSS as compared to IVF when a GnRH antagonist protocol was applied (OR 0.08, 95% CI 0.01 to 0.67; I 2 = 0%; 2 studies, 739 participants; high-certainty evidence). This suggests that if the incidence of OHSS following IVF is assumed to be 3.5%, then the incidence with IVM would be 0% to 2.4%. Also, there is probably little to no difference in preterm birth between IVM or capacitation IVM and IVF after the application of a GnRH antagonist protocol (OR 0.69, 95% CI 0.31 to 1.52; I² = 45%; 2 studies, 739 participants; moderate-certainty evidence). As for congenital anomalies, one study reported no events, while another showed an uncertain effect of IVM (OR 0.33, 95% CI 0.01 to 8.24; 1 study, 351 participants; low-certainty evidence). Results remained similar when using the RR as the measure of effect. There were no data from any of the studies for cycle cancellation, oocyte fertilisation, or subgroup analyses., Authors' Conclusions: There is continuous scientific interest in IVM, and promising data have been published. Concerning live birth and clinical pregnancy, we are very uncertain about the effect of the technique when compared to IVF after using a GnRH antagonist protocol. In contrast, high-certainty evidence shows that IVM increases miscarriage per clinical pregnancy and reduces the incidence of moderate or severe OHSS in women with PCOS compared to IVF after a GnRH antagonist protocol. Regarding the rest of the outcomes, low- to moderate-certainty evidence showed little to no difference in preterm birth and risk of congenital anomalies between the two modalities. We eagerly anticipate further evidence from high-quality trials in the field (we found five ongoing trials)., (Copyright © 2025 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Factors contributing to the limited success of in vitro fertilization in horses remain to be studied. In this work, we elucidated the effect of different essential capacitation media components, bicarbonate, and bovine serum albumin or polyvinyl-alcohol, and the incubation microenvironment on sperm parameters associated with capacitation, acrosome reaction, and their ability to activate oocytes via heterologous intracytoplasmic spermatozoa injection in equine cryopreserved spermatozoa., Methods: Frozen-thawed spermatozoa underwent incubation at different time intervals in either Tyrode's albumin lactate pyruvate medium (non-capacitating; NC) or Tyrode's albumin lactate pyruvate supplemented with bicarbonate, bicarbonate and polyvinyl-alcohol, bicarbonate and bovine serum albumin, polyvinyl-alcohol and bovine serum albumin alone. Protein kinase A-phosphorylated substrates and tyrosine phosphorylation levels, sperm motility, and acrosome reaction percentages were evaluated. After determining the best condition media (capacitating; CAP), heterologous intracytoplasmic spermatozoa injection on pig oocytes was performed and the phospholipase C zeta sperm localization pattern was evaluated., Results: Incubation of frozen-thawed equine spermatozoa with bicarbonate and polyvinyl-alcohol in atmospheric air for 45 min induced an increase in protein kinase A-phosphorylated substrates and tyrosine phosphorylation levels compared to NC condition. Sperm incubation in bicarbonate and polyvinyl-alcohol medium showed an increase in total motility and progressive motility with respect to NC (p ≤ 0.05). Interestingly, three parameters associated with sperm hyperactivation were modulated under bicarbonate and polyvinyl-alcohol conditions. The kinematic parameters curvilinear velocity and amplitude of lateral head displacement significantly increased, while straightness significantly diminished (curvilinear velocity: bicarbonate and polyvinyl-alcohol = 120.9 ± 2.9 vs. NC = 76.91 ± 6.9 µm/s) (amplitude of lateral head displacement: bicarbonate and polyvinyl-alcohol = 1.15 ± 0.02 vs. NC = 0.77 ± 0.03 µm) (straightness: bicarbonate and polyvinyl-alcohol = 0.76 ± 0.01 vs. NC = 0.87 ± 0.02) (p ≤ 0.05). Moreover, the spontaneous acrosome reaction significantly increased in spermatozoa incubated in this condition. Finally, bicarbonate and polyvinyl-alcohol medium was established as CAP medium. Although no differences were found in phospholipase C zeta localization pattern in spermatozoa incubated under CAP, equine spermatozoa pre-incubated in CAP condition for 45 min showed higher fertilization rates when injected into matured pig oocytes (NC: 47.6% vs. CAP 76.5%; p ≤ 0.05)., Conclusion: These findings underscore the importance of bicarbonate and polyvinyl-alcohol in supporting critical events associated with in vitro sperm capacitation in the horse, resulting in higher oocyte activation percentages following heterologous intracytoplasmic spermatozoa injection. This protocol could have an impact on reproductive efficiency in the equine breeding industry., (© 2024 American Society of Andrology and European Academy of Andrology.)

Background: Infertility affects millions of individuals worldwide, imposing significant personal and societal burdens. Assisted reproductive technologies (ART), such as IVF and ICSI, provide hope for many, yet clinical pregnancy rate per embryo transfer remains around 35 %. Modifiable lifestyle factors, including sleep, may influence ART outcomes. However, the relationship between specific sleep characteristics and IVF/ICSI success is unclear. This study aims to explore the associations between sleep characteristics and various IVF/ICSI outcomes. Additionally, we investigated if perceived stress mediates these relationships., Methods: This prospective cohort study enrolled 174 women undergoing IVF/ICSI at Zhongnan Hospital of Wuhan University from December 2021 to December 2023. Prior to initial ART treatment, participants completed the Pittsburgh Sleep Quality Index (PSQI) and the Perceived Stress Scale (PSS-10). IVF/ICSI outcomes such as the number of retrieved oocytes, matured oocytes, number of fertilized oocytes, fertilization rate, good-quality embryos, blastocyst formation rate and early pregnancy outcome (implantation and clinical pregnancy) were obtained from medical records. We employed multivariate generalized linear models to assess the associations between sleep characteristics and IVF/ICSI outcomes. Dose-response relationships between napping duration and maturation rate were analyzed using generalized additive models. Mediation analysis was used to assess the role of stress in the relationship between sleep characteristics and IVF/ICSI outcomes., Results: Women reporting poor sleep quality had significantly fewer retrieved oocytes (-22.89 %, 95%CI: 37.82 %, -4.00 %) and matured oocytes (-22.01 %, 95%CI: 37.54 %, -2.62 %). Those sleeping ≥10 h per night had fewer retrieved oocytes (-30.68 %, 95%CI: 48.88 %, -6.00 %), matured oocytes (-27.17 %, 95%CI: 46.57 %, -0.73 %), and good-quality embryos (-45.64 %, 95%CI: 65.43 %, -14.51 %). Women experiencing difficulty falling asleep more than three times a week had a significant reduction in blastocyst rates (-64.40 %, 95 % CI: 85.55 %, -12.30 %). Those reporting difficulty falling asleep less than once a week had fewer retrieved oocytes (-28.89 %, 95%CI: 47.34 %, -3.98 %), and matured oocytes (-27.77 %, 95%CI: 46.90 %, -1.73 %). Napping exceeding 1 h daily was associated with a significantly lower oocyte maturation rate (-73.8 %, 95%CI: 88.91 %, -38.06 %). A significant non-linear dose-response relationship was observed between napping duration and maturation rate (p < 0.001), with maturation rates initially increasing slightly with short naps but declining significantly with longer naps, particularly beyond 1 h. This relationship was significant among women with good sleep quality (PSQI ≤5) (p < 0.001) and those with normal BMI (p = 0.0005). Perceived stress did not significantly mediate these associations., Conclusion: Our findings suggest that sleep characteristics, particularly poor quality, difficulty falling asleep, long sleep durations, negatively impact various IVF/ICSI outcomes. Longer daytime napping is inversely associated with oocyte maturation rates, especially among women with good sleep quality and normal BMI. Perceived stress did not appear to influence the relationship between sleep and IVF outcome. While optimizing sleep patterns may hold promise for improving IVF/ICSI success rates, it is essential to approach lifestyle guidance with caution, given the current limitations in confirming causative roles. Further studies are needed to clarify the extent and nature of the relationship between sleep characteristics and IVF/ICSI outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The question of whether patients are more likely to succeed with testicular sperm intracytoplasmic sperm injection (T-ICSI) after unsuccessful ICSI with ejaculated sperm (Ej-ICSI) remains unknown., Objective: The study aimed to identify potential predictors of successful T-ICSI in men with idiopathic infertility and oligozoospermia (sperm concentration < 15 × 10 6 /mL, non-azoospermic) who had previously experienced unsuccessful Ej-ICSI., Materials and Methods: In total, 154 couples with male partners who had oligozoospermic conditions after two unsuccessful cycles of Ej-ICSI switched to T-ICSI. Before initiating T-ICSI, the sperm DNA fragmentation index (DFI) was assessed in ejaculated specimens. Participants were divided into two groups: group A (live birth (+), n = 60) and group B (live birth (-), n = 94)., Results: Fertilization, clinical pregnancy, live births, and miscarriages had rates of 72.7%, 44.2%, 39%, and 5.2%, respectively. The total motile sperm (TMS) count in group A was significantly higher (3.8 ± 1.5 million) than in group B (3 ± 1.6 million; p = 0.002). DFI was significantly higher in group A (24.2 ± 12.3) than in group B (18.1 ± 11; p = 0.001). Hormone levels and oocyte counts showed no statistically significant differences between groups. Multivariate regression analysis revealed that TMS (odds ratio [OR]: 1.46; 95% CI, 1.14-1.87, p = 0.003) and DFI (OR: 1.04; 95% CI, 1.01-1.08, p = 0.009) were found to be significant predictors of live birth outcomes. At a cutoff point of 2.55 (area under the curve [AUC] = 0.65), the optimal sensitivity and specificity values for TMS were 78% and 48%, respectively. At a cutoff point of 25.8 (AUC = 0.65), DFI had a maximum sensitivity of 51.7% and a specificity of 78.7%., Conclusions: TMS and DFI were found to be significant predictors of live birth outcomes in couples with oligozoospermic male partners undergoing T-ICSI. These findings may help clinicians tailor treatment strategies for this specific patient population., (© 2024 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

In this study, we aimed to apply preimplantation genetic testing for monogenic disorders (PGT-M) based on mutated allele revealed by sequencing with aneuploidy and linkage analyses (MARSALA) to block the transmission of inborn errors of metabolism (IEMs). After the disease-causing variants were identified through genetic testing, four carrier couples having children affected with IEMs, including methylmalonic aciduria, glutaric acidemia type 1, beta-ketothiolase deficiency, and ornithine transcarbamylase deficiency, sought PGT-M. A series of PGT procedures involving intracytoplasmic sperm injection, blastocyst culture, biopsy of trophectoderm cells, and next-generation sequencing (NGS)-based MARSALA, was performed to provide comprehensive chromosome screening and variant gene analysis. Finally, embryos were selected for transfer, and prenatal diagnosis was conducted to confirm the PGT-M results. All four carrier couples obtained transferrable embryos after PGT. The results of the prenatal diagnosis were consistent with the PGT results, and all couples gave birth to healthy babies free of IEMs. The results of this study confirm that NGS-based MARSALA is an effective approach for families with IEMs to prevent the subsequent transmission of pathological genetic variants to the next generation., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval: The protocols for this study were evaluated and approved by the Ethics Committee of Fuzhou General Hospital (Ethics approval no. 2013027)., (© 2024. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)

Objective: To study the correlation between anti-Müllerian hormone levels and pregnancy outcomes after in vitro fertilization/intracytoplasmic sperm injection in women with polycystic ovary syndrome, which remains controversial., Methods: This retrospective cohort study recruited 4,719 women with infertility and polycystic ovary syndrome aged 20-40 years who underwent treatment at the Reproductive Center of Peking University Third Hospital between February 2017 and June 2023. We divided the participants into three groups according to the 25th and 75th percentile cutoffs of serum anti-Müllerian hormone: low (≤ 4.98 ng/mL, n = 1,198), average (4.98 - 10.65 ng/mL, n = 2,346), and high (≥ 10.65 ng/mL, n = 1,175). Pregnancy outcomes included live birth rate, miscarriage rate, clinical pregnancy rate, and cumulative live birth rate., Results: The live birth rate for fresh embryo transfer was 39.8%, 35.9%, and 30.4% in the low, average, and high anti-Müllerian hormone groups, respectively. The miscarriage rate was 11.3%, 17.1%, and 21.8% in the low, average, and high anti-Müllerian hormone groups, respectively. Significant intergroup differences were observed in the live birth rate (P = 0.017) and miscarriage rate (P = 0.018). No significant intergroup difference was observed in the clinical pregnancy rate (P = 0.204) or cumulative live birth rate (P = 0.423). After adjusting the confounders by multivariable logistic regression analysis, anti-Müllerian hormone was associated with decreased live birth rate in the high anti-Müllerian hormone group compared with that in the low anti-Müllerian hormone group (odds ratio: 0.629, 95% confidence interval: 0.460-0.860). Anti-Müllerian hormone was associated with increased miscarriage rate in the average and high anti-Müllerian hormone groups compared with that in the low anti-Müllerian hormone group (average vs. low: odds ratio: 1.592, 95% confidence interval: 1.017-2.490); high vs. low: odds ratio: 2.045, 95% confidence interval: 1.152-3.633)., Conclusion: High anti-Müllerian hormone is a prognostic factor for reduced live birth rate after fresh embryo transfer in women with polycystic ovary syndrome aged 20-40 years undergoing in vitro fertilization/intracytoplasmic sperm injection, and is associated with increased miscarriage rate in these patients., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Medical Science Research Ethics Committee of Peking University Third Hospital (Reference Number M3032464) and was conducted according to the Declaration of Helsinki for Medical Research involving Human Subjects. All participants provided written informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Purpose: To investigate the association of sleep quality during pregnancy on in vitro fertilization/intra-cytoplasmic sperm injection (IVF/ICSI) and natural conceiving (NC), as well as anxiety, depression, and perceived stress., Methods: This prospective cohort study includes 500 infertile pregnant women undergoing IVF/ICSI and 678 NC women in a Sichuan birth cohort. Data on sleep, anxiety, depression, and stress was collected in the first trimester (T1), second trimester (T2), and third trimester (T3) using integrated questionnaires. Sleep quality is quantified by the Pittsburgh Sleep Quality Index (PSQI) with a cut-point of 5 indicating poor sleep. The Self-rating Anxiety Scale (SAS), the Center for Epidemiologic Study of Depression scale (CES-D), and the Perceived Stress scale (PSS) were used for assessing anxiety, depression, and perceived stress symptoms. Additionally, the matched husbands are surveyed. Multivariable logistic regression models with adjustments for influencing factors were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations of sleep quality., Results: In the IVF/ICSI group, 61.1%, 55.5%, and 66.5% of participants in T1, T2, and T3 reported poorer sleep quality compared to the NC group, which had 43.2%, 37.4%, and 46.4% throughout the same trimesters. Additionally, the IVF/ICSI group exhibited higher levels of negative psychological factors as measured by the CES-D and PSS during T1 and T2, showing statistical significance in T1 (P = 0.008, P < 0.001) and T2 (P = 0.038, P < 0.001), except at T3 (P = 0.107, P = 0.253). In addition to psychological factors and IVF/ICSI treatment, poor sleep quality was also associated with advanced age. However, there was no significant difference in sleep quality between the husbands of the IVF/ICSI and NC groups., Conclusion: The study reveals that women receiving IVF/ICSI treatment are at a higher risk of experiencing sleep disturbances throughout their pregnancy compared with women with natural conception. While partners typically do not report major sleep problems, they do exhibit increased anxiety levels. These findings underscore the necessity for screening and addressing sleep issues in women pregnant through assisted IVF/ICSI treatment, to promote their well-being during this critical period., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Xie, Peng, Xiao, Li and Li.)

Background: The success of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) in endometriosis patients varies widely, and predicting the likelihood of achieving a live birth remains a clinical challenge. This study aims to develop a predictive nomogram for assessing the cumulative live birth (CLB) rate following IVF/ICSI cycles among patients with endometriosis., Method: A retrospective cohort study was conducted to analyze the clinical data of 1457 patients with endometriosis after IVF/ICSI treatment from January 2017 to August 2022. The patients were divided into a training set (70%) and a validation set (30%) using a random number table. Univariate analysis and multifactorial logistic regression analysis were employed to identify relevant predictive factors affecting CLB rate. A predictive model was then established based on the identified factors., Results: Univariate analysis and multifactorial logistic regression analysis revealed that patients with concurrent adenomyosis had a decreased CLB rate (OR = 0.51, 95% CI: 0.31-0.82). As the duration of infertility increased, the CLB rate decreased (OR = 0.93, 95% CI: 0.88-0.99). Higher numbers of fertilized oocytes and high-quality embryos were associated with an increased likelihood of CLB. A nomogram predictive model for CLB rate, based on age, concurrent adenomyosis, duration of infertility, number of fertilization, and number of high-quality embryos, was developed. The area under the curve (AUC) for the training set and validation set was 0.823 (95% CI: 0.798-0.849) and 0.773 (95% CI: 0.729-0.818), respectively. The stratified analysis demonstrated the applicability of the model in the validation cohort., Conclusion: This predictive nomogram for CLB rate in patients with endometriosis provides valuable and precise information for personalized decision-making, which could be a visual and easily applied tool for IVF/ICSI counselling., Competing Interests: Declarations. Ethics approval and consent to participate: This study adhered to the principles outlined in the Declaration of Helsinki and received approval from the Medical Research Ethics Committee of Women's Hospital, Zhejiang University School of Medicine (Ethics approval number: IRB-20230258-R). The requirement for informed consent was waived, due to the retrospective nature of the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Recent advances in embryology have shown that the sister blastomeres of two-cell mouse and human embryos differ reciprocally in potency. An open question is whether the blastomeres became different as opposed to originating as different. Here we wanted to test two relevant but conflicting models: one proposing that each blastomere contains both animal and vegetal materials in balanced proportions because the plane of first cleavage runs close to the animal-vegetal axis of the fertilized oocyte (meridional cleavage); and the other model proposing that each blastomere contains variable proportions of animal and vegetal materials because the plane of the first cleavage can vary - up to an equatorial orientation - depending on the topology of fertilization. Therefore, we imposed the fertilization site in three distinct regions of mouse oocytes (animal pole, vegetal pole, equator) via ICSI. After the first zygotic cleavage, the sister blastomeres were dissociated and subjected to single-cell transcriptome analysis, keeping track of the original pair associations. Non-supervised hierarchical clustering revealed that the frequency of correct pair matches varied with the fertilization site (vegetal pole > animal pole > equator), thereby, challenging the first model of balanced partitioning. However, the inter-blastomere differences had similar signatures of gene ontology across the three groups, thereby, also challenging the competing model of variable partitioning. These conflicting observations could be reconciled if animal and vegetal materials were partitioned at the first cleavage: an event considered improbable and possibly deleterious in mammals. We tested this occurrence by keeping the fertilized oocytes immobilized from the time of ICSI until the first cleavage. Image analysis revealed that cleavage took place preferentially along the short (i.e. equatorial) diameter of the oocyte, thereby partitioning the animal and vegetal materials into the two-cell blastomeres. Our results point to a simple mechanism by which the two sister blastomeres start out as different, rather than becoming different., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Background: Gonadotropin-releasing hormone agonists (GnRHa) are commonly used in assisted reproduction technology (ART) cycles to prevent a luteinising hormone (LH) surge during controlled ovarian hyperstimulation (COH) prior to planned oocyte retrieval, thus optimising the chances of live birth. We compared the benefits and risks of the different GnRHa protocols used., Objectives: To evaluate the effectiveness and safety of different GnRHa protocols used as adjuncts to COH in women undergoing ART., Search Methods: We searched the following databases in December 2022: the Cochrane Gynaecology and Fertility Group's Specialised Register, CENTRAL, MEDLINE, Embase, and registries of ongoing trials. We also searched the reference lists of relevant articles and contacted experts in the field for any additional trials., Selection Criteria: We included randomised controlled trials (RCTs) comparing any two protocols of GnRHa, or variations of the protocol in terms of different doses or duration, used in in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycles in subfertile women., Data Collection and Analysis: We used standard methodological procedures recommended by Cochrane. Our primary outcome measures were number of live births or ongoing pregnancies and incidence of ovarian hyperstimulation syndrome (OHSS) per woman/couple randomised. Our secondary outcome measures included number of clinical pregnancies, pregnancy losses, number of oocytes retrieved, amount of gonadotropins used, and cost and acceptability of the treatment protocols., Main Results: We included 40 RCTs (4148 women). The trials evaluated 10 different comparisons between protocols. The evidence is current to December 2022. Only half of the studies reported the primary outcome of live birth or ongoing pregnancy rates. We restricted the primary analysis of live birth and ongoing pregnancy to trials with low risk of selection and reporting bias. Nineteen studies compared long and short protocols. The primary analysis restricted to trials with low risk of bias included five studies reporting on live birth or ongoing pregnancy rates. Results showed little or no difference when the long protocol was compared with a short protocol (odds ratio (OR) 1.45, 95% confidence interval (CI) 0.83 to 2.52; I² = 0%; 5 studies, 381 women; low-certainty evidence). For the same comparison, there was evidence that the long protocol may improve clinical pregnancy rates when compared to the short protocol (OR 1.56, 95% CI 1.01 to 2.40; I² = 23%; 8 studies, 552 women; low-certainty evidence). No study in this comparison reported on OHSS. We are uncertain if there is a difference between groups in terms of live birth and ongoing pregnancy rates when the following GnRHa protocols were compared: long versus ultrashort (OR 1.78, 95% CI 0.72 to 4.36; 1 study, 150 women; very low-certainty evidence); long luteal versus long follicular phase (OR 1.89, 95% CI 0.87 to 4.10; 1 study, 223 women; very low-certainty evidence); GnRHa reduced-dose versus GnRHa same-dose continued in the long protocol (OR 1.59, 95% CI 0.66 to 3.87; 1 study, 96 women; very low-certainty evidence); GnRHa administration for two versus three weeks before stimulation (OR 0.88, 95% CI 0.37 to 2.05; 1 study, 85 women; very low-certainty evidence); GnRHa continued versus discontinued after human chorionic gonadotropin (HCG) administration in the long protocol (OR 0.89, 95% CI 0.49 to 1.64; 1 study, 181 women; very low-certainty evidence); and 500 µg dose versus 80 µg dose in the short protocol (OR 0.31, 95% CI 0.10 to 0.98; 1 study, 200 women; very low-certainty evidence). Clinical pregnancy rates may improve with a 100 µg dose compared to a 25 µg dose in the short protocol (OR 2.30, 95% CI 1.06 to 5.00; 2 studies, 133 women; low-certainty evidence). Only four of the 40 included studies reported adverse events. We are uncertain of any difference in OHSS rate in the GnRHa reduced-dose versus GnRHa same-dose regimen in the long protocol (OR 0.47, 95% CI 0.04 to 5.35; 1 study, 96 women; very low-certainty evidence) or when administration of GnRHa lasted for two versus three weeks before stimulation (OR 0.93, 95% CI 0.06 to 15.37; 1 study, 85 women; very low-certainty evidence). Regarding miscarriage rates, we are uncertain of any difference when the GnRHa long protocol was administered for two versus three weeks before stimulation (OR 0.93, 95% CI 0.18 to 4.87; 1 study, 85 women; very low-certainty evidence) and when a 500 µg dose was compared with an 80 µg dose in the short protocol (OR 3.15, 95% CI 0.32 to 31.05; 1 study, 131 women; very low-certainty evidence). No studies reported on cost-effectiveness or acceptability of the different treatment protocols. The certainty of the evidence ranged from low to very low. The main limitations were failure to report live birth or ongoing pregnancy rates, poor reporting of methods in the primary studies, imprecise findings due to lack of data, and insufficient data regarding adverse events. Only eight of the 40 included studies were conducted within the last 10 years., Authors' Conclusions: When comparing long and short GnRHa protocols, we found little or no difference in live birth and ongoing pregnancy rates, but there was evidence that the long protocol may improve clinical pregnancy rates overall. We were uncertain of any difference in OHSS and miscarriage rates for all comparisons, which were reported by only two studies each. There was insufficient evidence to draw any conclusions regarding other adverse effects or the cost-effectiveness and acceptability of the different treatment protocols., (Copyright © 2025 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: The incidence rate of ectopic pregnancy (EP) with assisted reproductive technology (ART) has been reported to be higher than that of spontaneous pregnancy. Endometrial thickness (EMT) is considered an independent risk factor., Objectives: Evaluation of endometrial thickness as a predictor of ectopic pregnancy in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles., Design: Case-control study., Setting: Women's Health Specialist Hospital, formerly known as King Abdulaziz Medical City, National Guard Health Affairs, Riyadh, Saudi Arabia., Patients and Methods: This study was a 1:2 matched case-control study that enrolled 24 ectopic pregnancy patients and 50 matched intrauterine pregnancy patients. They were matched on maternal age, the presence of tubal factor, and parity. The estimated sample size for patients with ectopic pregnancy was 25-30, whereas that for controls was estimated to be 60 patients. The sampling technique was a purposive (nonprobability)., Main Outcome Measures: Endometrial thickness after IVF/ICSI is a predictor of ectopic pregnancy., Sample: 79 patients., Results: Multivariate logistic regression analysis was performed to analyze EP predictors, and a receiver operating characteristic (ROC) curve was used to evaluate the predictors of EP. After adjustment for other factors in the logistic regression model, we found that the tubular factor increased the risk of EP by 7.6 times, whereas the ovarian factor significantly decreased EP by 85%. Other factors, including EMT, did not significantly affect the probability of developing ectopic pregnancy., Conclusions: EMT was not predictive nor protective of EP in women who underwent ART cycles. Nevertheless, the presence of tubular factors has strong predictive value, whereas ovarian factors have significant protective value against EP., Limitations: The study design affects the generalizability and level of evidence provided. The small sample size and single-center inclusion had an impact on the results and statistical tests used., Competing Interests: CONFLICT OF INTEREST: None.

Aim: This study aims to assess the impacts of various trigger day progesterone (P 4 ) and luteinizing hormone (LH) levels on live birth rates (LBRs) in fresh in vitro fertilization (IVF) cycles, considering their elevation from stimulation and premature luteinization., Methods: This retrospective cohort study included the first ovarian stimulation cycles with GnRH antagonist protocol of 1253 patients who underwent intracytoplasmic sperm injection and fresh embryo transfer at a tertiary clinic's IVF center between 2010 and 2016. Participants were divided into four groups based on trigger day serum P 4 and LH levels, using the 90th percentile thresholds for P 4 (1.7 ng/mL) and LH (5.2 IU/L). The primary outcome measure was LBR., Results: The LBRs observed in the respective groups were as follows: P 4  < 1.7 ng/mL and LH <5.2 IU/L (21.3%, 214/1005); P 4  < 1.7 ng/mL and LH ≥5.2 IU/L (19.1%, 22/115); P 4  ≥ 1.7 ng/mL and LH <5.2 IU/L (19.3%, 23/119); and P 4  ≥ 1.7 ng/mL and LH ≥5.2 IU/L (28.6%, 4/14). There were no statistically significant differences between the groups (p = 0.782). Additionally, a multivariate generalized additive model, adjusted for female age, body mass index, infertility duration, number of embryos transferred, and embryo transfer day, found that the interaction between LH and P 4 levels did not significantly predict LBRs (p = 0.533). However, univariate analysis identified an optimal trigger day P 4 range between 0.58 and 1.69 ng/mL for achieving higher LBRs, demonstrating a non-linear relationship. Furthermore, total FSH and LH dosages during stimulation had a statistically significant combined effect on trigger day P 4 levels (p = <0.001), with the addition of LH leading to lower P 4 levels compared to cycles stimulated with recombinant FSH alone., Conclusions: The relationship and interaction between trigger day LH and P 4 levels do not significantly influence LBRs, as variations in LH do not alter the effect of P 4 , suggesting that the impact of P 4 elevation on LBRs is independent of its cause, whether from ovarian stimulation or premature luteinization., (© 2025 Japan Society of Obstetrics and Gynecology.)

Background: It has been shown that antinuclear antibodies (ANAs) are associated with adverse reproductive events. The presence of ANAs may reduce the pregnancy rate in women undergoing assisted reproductive technology (ART) treatment., Methods: This study aimed to investigate the potential effect of ANAs on the outcomes of infertile women undergoing in-vitro fertilization and embryo transfer (IVF-ET) or intracytoplasmic sperm injection (ICSI) for the first time. In total, 907 women were enrolled, with 192 (21.14 %) cases in the ANA+ group and 715 (78.86 %) cases in the ANA- group. Baseline data were collected, and associations between ANAs and oocyte maturation rate, high-quality embryo rate, clinical pregnancy rate, live birth rate and miscarriage rate were analysed., Results: Compared with the ANA- group, the ANA+ group had a considerably lower oocyte maturation rate (0.69 ± 0.31 vs 0.77 ± 0.26; P = 0.003) and a lower high-quality embryo rate (0.53 ± 0.30 vs 0.78 ± 0.92; P < 0.01). ANAs had no effect on clinical pregnancy rate, live birth rate and miscarriage rate in infertile women receiving ART for the first time., Conclusions: These findings suggest that ANAs reduce oocyte maturation rate and high-quality embryo rate in infertile women undergoing IVF-ET/ICSI for the first time, but do not have a significant effect on clinical pregnancy rate, live birth rate and miscarriage rate. When testing for ANAs is part of the planned treatment protocol, this should be undertaken in advance of starting IVF-ET/ICSI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Research Question: What is the level of understanding, and what are the attitudes and considerations regarding preconception carrier screening (PCS) among couples seeking IVF or intracytoplasmic sperm injection (ICSI)?, Design: A mixed-methods design was used. Nine interviews were conducted with couples or individual partners (n = 16) who had an initial consultation for IVF/ICSI in the 2 years preceding this study. A questionnaire was completed by 115 participants. No actual PCS was offered., Results: All interviewed couples expressed a positive attitude towards PCS, and over half of the respondents stated that they would pursue or seriously consider pursuing PCS if possible. Some couples falsely believed that PCS could identify a cause for their fertility problems and increase their chance of conceiving. The desire to make an informed reproductive decision was the most important argument in favour of PCS. The primary argument against PCS was the apprehension of being confronted with reproductive dilemmas. The longer the delay to IVF/ICSI treatment required to perform PCS, the more couples would be inclined to decline screening. Participants indicated that they would prefer to receive information about PCS from a medical specialist at an early stage in their IVF/ICSI treatment., Conclusion: Although attitudes towards PCS were generally positive, some concerns were raised about treatment delays and potential reproductive dilemmas, and some couples had misconceptions about the purpose of screening within the context of their IVF/ICSI treatment. These findings highlight the importance of tailoring information and counselling to the specific needs of couples seeking IVF/ICSI., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Round spermatid injection (ROSI) into oocytes offers men with nonobstructive azoospermia (NOA) the opportunity to have biological offspring in cases where mature spermatozoa are not detected. However, the clinical outcomes of ROSI remain poor. This study compared the outcomes of ROSI with intracytoplasmic sperm injection (ICSI) and investigated the effect of hormonal pretreatment., Methods: This retrospective cohort study enrolled infertile couples undergoing either ROSI or ICSI at the reproductive center in Taipei Veterans General Hospital. The administration of selective estrogen receptor modulators, gonadotropins, and aromatase inhibitors in male patients were recorded. Relevant hormonal markers and biochemical parameters were determined. The outcomes of ROSI and ICSI were assessed based on fertilization rate, implantation rate, and live birth rate., Results: A total of 36 couples were recruited in the ROSI group, whereas 39 couples were recruited in the ICSI group for the analysis. Patients in each group demonstrated similar characteristics, except for a higher proportion of male patients in the ROSI group who were pretreated with anastrozole. The fertilization rate and implantation rate were similar between ROSI and ICSI groups after adjusting for confounding variables. The live birth rate was significantly lower in the ROSI group (8.3%) than in the ICSI group (30.8%) before and after adjusting for confounding variables., Conclusion: ROSI demonstrated fertilization and implantation rates comparable to those of ICSI for male patient with NOA undergoing testicular sperm extraction surgery. Anastrozole may improve the outcomes of ROSI into oocytes. Further studies evaluating the effect of anastrozole administration on ROSI outcomes are warranted., Competing Interests: Conflicts of interest: Dr. William J. Huang Dr. Yi-Jen Chen, editorial board members at Journal of the Chinese Medical Association , had no role in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)

Abstract: Primary ciliary dyskinesia (PCD) is a clinically rare, genetically and phenotypically heterogeneous condition characterized by chronic respiratory tract infections, male infertility, tympanitis, and laterality abnormalities. PCD is typically resulted from variants in genes encoding assembly or structural proteins that are indispensable for the movement of motile cilia. Here, we identified a novel nonsense mutation, c.466G>T, in cilia- and flagella-associated protein 300 ( CFAP300 ) resulting in a stop codon (p.Glu156*) through whole-exome sequencing (WES). The proband had a PCD phenotype with laterality defects and immotile sperm flagella displaying a combined loss of the inner dynein arm (IDA) and outer dynein arm (ODA). Bioinformatic programs predicted that the mutation is deleterious. Successful pregnancy was achieved through intracytoplasmic sperm injection (ICSI). Our results expand the spectrum of CFAP300 variants in PCD and provide reproductive guidance for infertile couples suffering from PCD caused by them., (Copyright ©The Author(s)(2024).)

Purpose: Previous studies have suggested a link between serum progesterone levels on the day of the HCG trigger in IVF cycles and oocyte and embryo quality. This study aims to explore this relationship more thoroughly., Methods: This study included 496 infertility patients at Moloud Infertility Treatment Center, Zahedan, Iran. Statistical methods were used to assess factors such as oocyte maturation and embryo quality, fertilization rate, BMI, and gonadotropin dosage., Results: While an initial progesterone cutoff of 1.2 ng/ml was used to perform fundamental analysis, a more accurate cutoff of 1.54 ng/ml was identified, beyond which the average number of M1 oocytes significantly declined. A strong relationship was found between higher progesterone levels and a greater number of retrieved oocytes (p = 0.004), with M1 oocytes showing a similar relation. Also, BMI was significantly related to the quality of eight-cell grade B embryos (p = 0.006). However, no significant correlations were found between progesterone levels and other factors, including patient age (p = 0.327), fertilization rate (p = 0.603), or embryo quality at other stages., Conclusions: The findings demonstrate that elevated progesterone level, particularly beyond the identified cutoff of 1.54 ng/ml, is a valuable clinical indicator of suboptimal IVF outcomes due to its negative impact on oocyte maturation., Competing Interests: Declarations. Ethical approval: The studies involving human participants were reviewed and approved by the Zahedan University of Medical Sciences Ethics Committee and were conducted according to the guidelines on human experimentation of the 1975 Declaration of Helsinki. The patients/participants provided their written informed consent to participate in this study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Although meiosis plays an essential role for the survival of species in natural selection, the genetic diversity resulting from sexual reproduction impedes human-driven strategies to transmit the most suitable genomes for genetic improvement, forcing breeders to select diploid genomes generated after fertilization, that is, after the encounter of sperm and oocytes carrying unknown genomes. To determine whether genomic assessment could be used before fertilization, some androgenetic haploid morula-stage bovine embryos derived from individual sperm were biopsied for genomic evaluation and others used to reconstruct "semi-cloned" (SC) diploid zygotes by the intracytoplasmic injection into parthenogenetically activated oocytes, and the resulting embryos were transferred to surrogate females to obtain gestations. Compared to controls, in vitro development to the blastocyst stage was lower and fewer surrogates became pregnant from the transfer of SC embryos. However, fetometric measurements of organs and placental membranes of all SC conceptuses were similar to controls, suggesting a normal post-implantation development. Moreover, transcript amounts of imprinted genes IGF2, IGF2R, PHLDA2, SNRPN, and KCNQ1OT1 and methylation pattern of the KCNQ1 DMR were unaltered in SC conceptuses. Overall, this study shows that sperm can be replaced by genotyped haploid embryonic-derived cells to produce bovine embryos carrying a predetermined paternal genome and viable first trimester fetuses after transfer to female recipients., Summary Sentence: Haploid morula-stage embryonic cells derived from a single sperm can be genotyped and injected into activated oocytes to reconstruct diploid zygotes that develop both in vitro into blastocysts and in vivo into viable post-implantation bovine conceptuses with predetermined paternal genomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Follicular fluid (FF) oxidation-reduction potential (ORP) has shown promise as a predictor for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes has been demonstrated. This study aimed to determine the association between the ORP in FF and IVF/ICSI outcomes., Methods: This cross-sectional study involved data collection from 341 couples undergoing IVF/ICSI treatment. The FF sample was taken from the first follicle to exceed 18 mm during oocyte retrieval and was analyzed for ORP using the MiOXSYS system (Caerus Biotechnologies)., Results: ORP in FF exhibited a statistically significant negative correlation with the fertilization rate (correlation coefficient, -0.126; p=0.019). The ORP levels in the FF from the group with a lower fertilization rate (<80%) were significantly higher than those in the group with a higher fertilization rate (≥80%) (89.90 mV vs. 78.98 mV, p=0.030). No significant correlations were found between ORP in FF and other outcomes., Conclusion: Our findings suggested that the ORP in FF may be correlated with the fertilization rate and could be evaluated as a predictor of fertilization in ICSI.

This article reports a case of Massilia timonae, an understudied Gram-negative rod, in the culture media of an embryo produced by intracytoplasmic sperm injection into the oocyte cytoplasm. Cultivation was monitored with a time-lapse technology. Microbial contamination can cause embryo developmental arrest.

Objective: To investigate whether anti-centromere antibody (ACA) is associated with embryonic development and clinical outcomes in patients undergoing IVF/ICSI treatment., Materials and Methods: Women who underwent fresh or frozen embryo transfer cycles at a reproductive center between January 1, 2017 and January 1, 2023, were retrospectively studied. Women were divided into ACA- group and ACA+ group according to ACA levels. After controlling the bias between groups using the propensity score-matching (PSM) method, the impact of ACA on embryonic development and clinical outcomes was compared between the two groups. Propensity score regression adjustment and inverse probability treatment weighting were used for sensitivity analysis., Results: A total of 18 578 patients with ACA screening information were included in the analytical sample, with 164 patients (0.88%) diagnosing ACA positive. After 1:3 PSM, 656 patients (492 in the ACA- group, 164 in the ACA+ group) were finally included. There were significant differences in the rates of cleavage, available embryo, blastocyst formation, and high-quality blastocyst formation between the ACA- group and the ACA+ group. Linear regression analysis indicated that ACA was negatively associated with the rates of available embryos on Day 3, blastocyst formation, and high-quality blastocyst formation after adjusting potential confounding factors. Binary logistic regression analysis suggests that ACA positivity does not affect clinical outcomes after IVF/ICSI treatment., Conclusions: In this cohort study of patients undergoing IVF/ICSI treatment, ACA positivity significantly interfered with embryonic development. These findings suggest that ACA evaluation before IVF/ICSI treatment might be a promising biomarker for predicting embryonic development but not for clinical outcomes., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: This study compared the outcomes of conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in patients with polycystic ovarian syndrome (PCOS), tubal factor (TF) infertility, and unexplained infertility whose partners had normal semen parameters., Methods: This retrospective study included 360 couples diagnosed with infertility involving PCOS (n=157), unexplained infertility (n=140), and TF infertility (n=63). Sibling oocytes were randomly assigned to undergo ICSI or conventional IVF insemination. The fertilization rate and embryo morphology were evaluated as outcomes., Results: Retrieved cumulus-oocyte complexes from patients with PCOS (2,974), unexplained infertility (1,843), and TF infertility (844) were split and inseminated by conventional IVF and ICSI respectively. In comparison to the ICSI method, the conventional IVF approach was linked to a significantly higher fertilization rate in groups with PCOS (68.81% vs. 77.49%), unexplained infertility (67.62% vs. 78.84%), and TF issues (69.23% vs. 78.63%) (p<0.05). The proportion of embryos with grade A produced by the conventional IVF method was significantly higher than that produced using the ICSI method in the PCOS and unexplained infertility groups (p<0.05). Additionally, the percentage of grade B embryos produced with the ICSI method was significantly higher than that produced with the conventional IVF method in PCOS patients (p=0.002)., Conclusion: Our results indicated that the conventional IVF method was associated with higher zygote production and a higher proportion of grade A embryos when all infertile groups were evaluated together. Thus, ICSI is not suggested for patients with these causes of infertility if their partner has normal semen parameters.

Objective: Studies suggest that men who undergo assisted reproductive technologies (ART) may have a higher risk of cardiovascular disease; however, limited data on this matter is available. This observational pilot study aimed to investigate the overall vascular health of fathers with history of intracytoplasmic sperm injection (ICSI) compared to fathers whose partners conceived spontaneously., Methods: Diet quality, physical activity, sedentary behavior as well as overall vascular function including the assessment of pulse wave analysis, intima-media thickness (cIMT), arterial stiffness of the common carotid artery (CCA) and blood lipids, were evaluated., Results: A total of 34 fathers with history of ICSI and 29 controls (48.49 [46.32 - 57.09] years vs. 47.19 [40.62 - 55.18] years, p  = 0.061) were included. After adjusting for age, no significantly increased cardiovascular risk was detected regarding vascular function., Conclusions: The results suggest an unaltered cardiovascular risk profile in fathers with history of ICSI. In the future, prospective multicenter studies are required to validate these preliminary results.

Infertility is a highly prevalent disease affecting 1 in 6 couples worldwide. While there are numerous treatment options available to treat infertility, in vitro fertilization (IVF) is the most successful therapy available. IVF traditionally involves superovulation of the ovaries followed by ultrasound (US)-guided oocyte retrieval, fertilization of oocytes in vitro, and culture of resultant embryos. Embryo(s) are then either transferred into the uterus or cryopreserved. There have been tremendous advances in each step of this process over the past 40 years, however, much work still remains to be done. This review discusses the history and current techniques involved in oocyte fertilization and embryo culture. Highlighted areas include conventional insemination and intracytoplasmic sperm injection (ICSI), embryo culture, and laboratory assessment. Areas of past and present research including time-lapse imaging and in vitro maturation are also discussed.

Objective: To determine whether ultrasonic manifestations of Hashimoto's thyroiditis (HT) related to embryo qualities or pregnancy outcomes in women with thyroid autoimmunity (TAI) undergoing in vitro fertilization/intracytoplasmic sperm injection., Methods: Our study was a retrospective cohort study. A total of 589 euthyroid women enrolled from January 2017 to December 2019. 214 TAI women and 375 control women were allocated in each group according to serum levels of thyroid peroxidase antibodies (TPOAb) and/or anti-thyroglobulin antibodies (TgAb). Basal serum hormone levels and thyroid ultrasound were assessed, embryo qualities, pregnancy outcomes were collected from medical records. Diagnosis of thyroid ultrasound was used for subanalysis. Logistic regression was used to evaluate outcomes of embryo development and pregnancy., Results: Implantation rate was significantly lower in euthyroid women with TAI compared with control group (TAI group: 65.5% vs. Control group: 73.0%, adjusted OR (95% CI): 0.65 (0.44, 0.97), p  = 0.04). We further stratified TAI group into two groups: one group with HT features under ultrasound and another group with normal thyroid ultrasound. After regression analysis, TAI women with HT morphological changes had a lower chance of implantation compared with control group (TAI group with HT: 64.1% vs. Control group: 73.0%, adjusted OR (95% CI): 0.63 (0.41, 0.99), p  = 0.04), while there was no significant difference on implantation rate between TAI women with normal thyroid ultrasound and control group. Other outcomes, such as embryo qualities and pregnancy rate, were comparable between TAI and control groups., Conclusions: A higher risk of implantation failure was seen among euthyroid women with TAI, especially women with HT morphological changes under ultrasound. The underlying mechanisms of implantation failure among euthyroid HT patients need further research.

The purpose of our study was to determine the influence of lead and cadmium in concentrations commonly found in the environment on the redox system of the follicular fluid (FF) and on the results of assisted reproduction. A prospective study of 113 patients with unexplained infertility who qualified for intracytoplasmic sperm injection (ICSI). Patients with moderate or severe endometriosis or poor ovarian reserve were excluded from the study. Biochemical analyses and heavy metal assays of follicular fluid and serum (blood) were followed by statistical analyses of dependencies between lead and cadmium and the components of redox system and results of assisted reproduction. A highly significant linear correlation of lead (Pb) and cadmium (Cd) concentrations in serum and in FF was stated. The number of retrieved oocytes and MII (metaphase II stage) oocytes depended on the malondialdehyde (MDA), catalase (CAT), catalase/g of protein (CAT/g of protein), and glutathione reductase (GR) concentrations. Among biochemical factors, MDA was the only factor that correlated negatively with cadmium concentration in serum and FF and simultaneously influenced the number of retrieved oocytes and MII oocytes. The fertilization rate of MII oocytes was influenced by thiol groups-SH, SH/g of protein, CAT, CAT/g of protein, and glutathione peroxidase/g of protein (GPx/g of protein). The Pb and Cd concentrations in FF did not significantly influence the fertilization rates. Lead as well as cadmium at concentrations commonly found in women of reproductive age despite some adaptive changes in the redox system in follicular fluid do not cause large changes in the ovarian follicular environment as a whole and do not significantly worsen the final results of assisted reproduction., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To determine the optimal number of fresh donor oocytes to expose to sperm for patients who want to prioritize reducing surplus embryos while preserving the live birth rate., Design: Cross-sectional study., Setting: University., Patient(s): Patients who underwent their first in vitro fertilization of fresh donor oocytes at a single academic institution between January 2013 and November 2022. Patients were excluded if they used a directed oocyte donor, donor aged >32 years, gestational carrier, surgically retrieved sperm, or preimplantation genetic testing., Intervention(s): Number of fresh mature donor oocytes fertilized via intracytoplasmic sperm injection., Main Outcome Measure(s): The primary outcome was the number of cryopreserved supernumerary blastocysts. The number of supernumerary blastocysts was defined as the number of blastocysts remaining after the first live birth, or if the patient did not have a live birth, the number of supernumerary blastocysts was determined by the number of blastocysts remaining after the last transfer cycle. The Kruskal-Wallis rank sum test was used to determine differences in number of supernumerary blastocysts., Result(s): A total of 543 patients who underwent 750 embryo transfer cycles using fresh donor oocytes were included. The average recipient age was 42.9 ± 3.8 years, and the average oocyte donor age was 26.6 ± 3.0 years. For our cohort, patients received a median of 10 (interquartile range [IQR], 8-14) mature donor oocytes; 8 (IQR, 6-11) were injected with sperm, 4 (IQR, 3-6) usable embryos were developed, and 2 (IQR, 0-5) supernumerary blastocysts remained. Patients were then divided into four quartiles on the basis of the number of mature donor oocytes received (≤7, 8-10, 11-14, or ≥15). There was a significant increase in the median number of cryopreserved supernumerary blastocysts as the number of mature donor oocytes exposed to sperm increased (1 vs. 2 vs. 3 vs. 6 blastocysts in the first, second, third, and fourth quartiles, respectively). There were no statistically significant differences in live birth rates between the quartiles., Conclusion(s): The number of supernumerary blastocysts significantly increased as more mature donor oocytes were exposed to sperm. This study can serve as a counseling tool for patients with concerns regarding excess cryopreserved embryos when using fresh donor oocytes., Competing Interests: Declaration of Interests S. Spring has nothing to disclose. S.T. has nothing to disclose. Z.V. has nothing to disclose. S. Spandorfer reports honoraria and travel support related to Society for Assisted Reproductive Technologies presidency and American Society for Reproductive Medicine board membership and payment for expert testimony., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Data regarding the impact of adenomyosis on the outcomes after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment are conflicting. Standardized diagnostic criteria are prerequisites for studying a potential association between adenomyosis and IVF/ICSI treatment outcomes. This study aims to examine the cumulative live birth rate (CLBR) after the first IVF/ICSI treatment in women with or without direct or indirect features of adenomyosis, using the revised Morphological Uterus Sonographic Assessment (MUSA) group definitions., Material and Methods: This was a prospective cohort study of 1037 women aged 25-≤39 years, undergoing their first IVF/ICSI treatment between January 2019 and October 2022. The presence of MUSA features of adenomyosis was assessed prior to treatment start., Results: The CLBR after the first IVF/ICSI treatment was 424/1037 (40.9%, 95% CI, 37.9-43.8) in the total cohort. Women with direct features of adenomyosis had lower CLBR, 25/102 (24.5%; 95% CI, 17.5-31.5) than women without, 399/935 (42.7%; 95% CI, 39.5-45.8), p < 0.001. The adjusted relative risk (aRR) for live birth for women with direct features of adenomyosis compared to women without was 0.62 (95% CI, 0.43-0.88), p = 0.007. Direct features were associated with a higher risk of miscarriage after frozen embryo transfer, aRR 2.88 (95% CI, 1.49-5.57), p = 0.002. Women with indirect features had a lower CLBR [50/188 (26.6%, 95% CI, 20.3-32.9)] than women without [399/935, (42.7%, 95% CI, 39.5-45.8)], aRR 0.58 (95% CI, 0.45-0.75), p < 0.001. For features located in the inner myometrium, the aRR for live birth was 0.29 (95% CI 0.11-0.74), p = 0.010 and for the outer myometrium 2.61 (95% CI 1.42-4.8), p = 0.002. An interrupted junctional zone was the single feature that impacted CLBR the most., Conclusions: The presence of direct or indirect MUSA features of adenomyosis correlates to reduced live birth rates in women undergoing their first IVF/ICSI treatment. Features located in the inner myometrium, particularly an interrupted junctional zone, reduced the chance of live birth the most, whereas location in the outer myometrium was associated with higher chances of live birth. Systematic ultrasound examinations should be considered for women scheduled for IVF/ICSI treatment, for adequate counseling on the chances of successful treatment., (© 2024 The Author(s). Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Human reproduction is a complex process involving gamete maturation, fertilization, embryo cleavage and development, blastocyst formation, implantation, and live birth. If any of these processes are abnormal or arrest, reproductive failure will occur. Infertility is a state of reproductive dysfunction caused by various factors. Advances in molecular genetics, including cell and molecular genetics, and high-throughput sequencing technologies, have found that genetic factors are important causes of infertility. Genetic variants have been identified in infertile women or men and can cause gamete maturation arrest, poor quality gametes, fertilization failure, and embryonic developmental arrest during assisted reproduction technology (ART), and thus reduce the clinical success rates of ART. This article reviews clinical studies on repeated in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) failures caused by ovarian dysfunction, oocyte maturation defects, oocyte abnormalities, fertilization disorders, and preimplantation embryonic development arrest due to female genetic etiology, the accumulation of pathogenic genes and gene pathogenic loci, and the functional mechanism and clinical significance of pathogenic genes in gametogenesis and early embryonic development., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Epigenetic mechanisms, including DNA methylation and histone modifications, govern chromatin arrangement in sperm, enhancing motility and safeguarding DNA integrity for accurate epigenetic inheritance. Abnormal methylation is linked to poor sperm quality and fertility issues, underscoring the need to study sperm DNA methylation and its impact on sperm function and embryo development in assisted reproductive technology. In this study, processed spermatozoa from 75 normozoospermic and 15 abnormal ejaculates were examined for sperm global DNA methylation levels using a colourimetric absorbance method. Although semen characteristics were poor in abnormal ejaculates, no significant correlation was found between sperm global DNA methylation levels and sperm characteristics in either normozoospermic or abnormal cohorts. However, mean global DNA methylation levels were significantly lowered in abnormal sperm samples compared to normozoospermic samples ( p  < 0.05). Furthermore, injecting spermatozoa from these patients (N = 50) into donor oocytes did not show a significant relationship between sperm global DNA methylation and embryo developmental competence. These findings highlight the limitation of sperm global DNA methylation as a biomarker for embryo development and quality.

The efficacy of in vitro embryo production (IVEP) in equines is relatively limited compared to other species due to the lack of a reliable superovulation technique, limited availability of cumulus oocyte complexes (COCs), low in vitro oocyte maturation (IVM) and fertilization rates. Extracellular vesicles (EVs), which are nanoparticles involved in intercellular signaling in the ovarian environment, have shown potential as supplements to improve oocyte development during IVM. This study tested the hypothesis that EVs from small (< 20 mm) ovarian follicles could enhance fertilization rates in mares. Follicular fluid was collected postmortem, and EVs were isolated and characterized. The IVM process was conducted with or without EVs (200 µg EV protein/ml). EV internalization during IVM was examined using fluorescent labeling and confocal microscopy. Following intracytoplasmic sperm injection (ICSI), presumptive zygotes were cultured in a time-lapse system. Confocal microscopy confirmed EV internalization by COCs. Nanoparticle tracking analysis showed that obtained EVs were submicron-sized, and flow cytometry identified surface markers CD81 and CD63 on a subpopulation of EVs. Transmission electron microscopy revealed the characteristic disk shape of EV isolates. After culture, 196 oocytes (36.84 %) exhibited a first polar body and were subjected to ICSI. The EV-treated group showed a significantly higher fertilization rate (34.7 % vs. 20.2 %; P < 0.05), reduced degeneration, and increased cleavage efficiency (P < 0.1). Despite early embryonic arrest in both groups, these results suggest that follicular fluid-derived EVs could play a supportive role in equine IVF procedures., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To determine the clinical and embryo laboratory factors that affect the clinical pregnancy rate of infertile patients with endometriosis (EMs), and establish a model for predicting clinical pregnancy., Study Design: An observational study. Place and Duration of the Study: Reproductive Medicine Centre, Jiangxi Provincial Maternal and Child Health Hospital, China, from January 2016 to December 2023., Methodology: Inclusion criteria were EMs patients diagnosed and treated through laparoscopic surgery, aged 22 - 37 years, who did not undergo surgery within 3 months before oocyte retrieval, and received fresh embryo transfer; and the causes of infertility included male factors, tubal infertility, intrauterine adhesions, and others. The exclusion criteria were EMs patients with combined uterine adenomyosis, chromosomal abnormalities, abnormal uterine structure, endocrine diseases, cardiovascular diseases and autoimmune diseases. The research variables included clinical and embryonic factors that affect clinical pregnancy rates, such as age, duration of infertility, type of infertility, and sex hormone levels. The outcome variable was the clinical pregnancy rate., Results: The clinical pregnancy rate was 61.84%. This predictive model was built on the basis of the number of high-quality cleavage embryos, number of embryos transferred, progesterone on HCG day, infertility duration, female age, number of oocytes retrieved, and body mass index showing good calibration and discriminatory abilities, with the area under the curve of receiver operating characteristic curve of 0.641 (95% CI = 0.599 - 0.684) for training set and 0.583 (95% CI = 0.515 - 0.650) for testing set. The Hosmer-Lemeshow test showed no significant difference (p >0.05) between the predicted and the true clinical pregnancy probabilities. The clinical decision curve analysis showed that both the training and testing sets achieved maximum net benefit within a threshold probability range of 0.4 - 0.8, indicating good clinical efficacy within this threshold probability range., Conclusion: The model for predicting clinical pregnancy in patients with EMs after fresh IVF/ICSI-ET had high accuracy, and can provide useful guidance for clinical doctors and individual adjuvant treatment of patients., Key Words: Endometriosis, Predictive model, Clinical pregnancy, Nomogram, In vitro fertilisation.

Objective: To investigate the effect of body mass index (BMI) on progesterone (P) level on trigger day in gonadotropin-releasing hormone antagonist (GnRH-ant) cycles., Methods: This study was a retrospective cohort study. From October 2017 to April 2022, 412 in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) patients who were treated with GnRH-ant protocol for controlled ovarian hyperstimulation (COH) in the reproductive center of our hospital were selected as the research objects. Patients were divided into three groups according to BMI level: normal weight group ( n  = 230):18.5 kg/m 2 ≤BMI < 24 kg/m 2 ; overweight group ( n  = 122): 24 kg/m 2 ≤BMI < 28 kg/m 2 ; Obesity group ( n  = 60): BMI ≥ 28 kg/m 2 . Variables with p  < .10 in univariate analysis (BMI, basal FSH, basal P, FSH days, Gn starting dose and E 2 level on trigger day) and variables that may affect P level on trigger day (infertility factors, basal LH, total FSH, HMG days and total HMG) were included in the multivariate logistic regression model to analyze the effect of BMI on P level on trigger day of GnRH-ant protocol., Results: After adjustment for confounding factors, compared with that in normal weight patients, the risk of serum P elevation on trigger day was significantly lower in overweight and obese patients (OR = 0.434 and 0.199, respectively, p  < .05)., Conclusion: The risk of P elevation on trigger day in GnRH-ant cycles decreased with the increase of BMI, and BMI could be used as one of the predictors of P level on trigger day in GnRH-ant cycles.

Sperm-derived genetic material contributes half of the genome to the embryo, hence it's crucial to investigate which sperm parameter influences blastocyst formation in the intracytoplasmic sperm injection (ICSI) cycles with severe male infertility. The retrospective study analyzed 296 ICSI cycles with severe oligoasthenoteratozoospermia (OAT) and 99 ICSI cycles with preimplantation genetic testing for aneuploidy (PGT-A). Following the correlation analysis, data stratifications were performed in the OAT ICSI subgroup. The results showed that the matching blastocyst in the OAT ICSI cycles had inferior sperm parameters. DFI and sperm morphology had an influence on the blastocyst formation rate and the high-quality blastocysts formation rate on Day6, but no significant effect on the blastocyst development on Day 5. The high-quality blastocysts formation rate and ratio of high-quality blastocyst on Day 6 were demonstrably better in the subgroup of the teratozoospermic morphology when DFI was within the normal range. In the case of the normal sperm morphology, no statistically significant difference was found in blastocyst development, although there were numerical differences within different DFI subgroups. It was concluded that the blastocyst quality and development declined with the decreased sperm qualities.

Background: This study aimed to analyse the expression of microRNA-223 (miR-223) in embryo culture medium and its correlation with pregnancy outcomes., Methods: Two hundred and two patients undergoing in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) were divided into clinical pregnancy group (n = 101) and non-pregnant group (n = 101). The baseline data, clinical indicators, and the expression level of miR-223 in the embryo medium were compared between the two groups. Logistic regression analysis was used to analyse the relationship between each index and the pregnancy outcome. Receiver operator characteristic curve was carried out to evaluate the differential ability of miR-223 in pregnancy status. Bioinformatics methods were used to identify the target genes of miR-223 and elucidate their functions., Results: Compared with pregnancy group, the non-pregnancy group exhibited a reduction in miR-223 expression ( p  < 0.001). Multivariate analysis revealed that miR-223 reduction was an independent factor for pregnancy failure ( p  < 0.05). The ROC curve demonstrated the discriminative capability of miR-223 in distinguishing pregnancy and non-pregnancy. In addition, bioinformatics analysis indicated that the target genes of miR-223 were predominantly located in the endocytic vesicle membrane and were primarily enriched in adenosine monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signalling pathways., Conclusion: In this study, levels of miR-223 in the embryo culture medium predicted pregnancy outcomes in subjects undergoing IVF/ICSI. Low expression of miR-223 was a risk factor for adverse pregnancy outcomes in subjects.

Objective: Methylenetetrahydrofolatereductase (MTHFR) is important for folate metabolism, which is involved in DNA synthesis and cell growth. However, the relationship between Maternal MTHFR polymorphisms and outcomes in assisted reproduction remains controversial. This is the first study to explore the effect of MTHFR polymorphisms on the embryological outcomes in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles in Korean patients with infertility., Materials and Methods: This retrospective cohort study included 173 women who underwent MTHFR genotyping between July, 2021 and June, 2022. The embryologic outcomes of 301 IVF/ICSI cycles were compared between groups according to MTHFR polymorphisms using ANOVA and Chi-square test., Results: Oocyte maturation rates were 80.0%, 75.0%, and 71.4% for MTHFR 677CC, 677CT, and 677TT, respectively. Cleaved embryo formation and transplantable embryo rates were comparable across various maternal MTHFR 677 genotypes. Good-quality embryo (GQE) rate was higher for MTHFR 677CT than those for 677CC and 677TT (40.0% vs. 29.4%, p  = 0.001 and 40.0% vs. 33.3%, p  = 0.025, respectively). When analyzing the combined MTHFR genotypes, the oocyte maturation rate was significantly lower in 677TT than in 677CC 1298AA/677CC 1298AC and 677CC 1298CC/677CT 1298AA/677CT 1298AC (71.4% vs. 76.7%, p  = 0.012 and 71.4% vs. 75.7%, p  = 0.029, respectively). The MTHFR 677CC/1298CC, 677CT/1298AA, and 677CT/1298AC genotypes had the highest GQE rates., Conclusions: MTHFR 677TT genotype, which had the lowest enzymatic activity, had the lowest oocyte maturation rate. The combined MTHFR 677CC/1298CC, 677CT/1298AA, and 677CT/1298AC genotypes with intermediate enzyme activities had higher GQE rates. However, no differences were observed in the transplantable embryo rate between MTHFR genotypes.

This publication reports, for the first time, the birth of a healthy child after intracytoplasmic sperm injection (ICSI) of motile spermatozoa after conventional ("slow") freezing of epididymal spermatozoa using 5% polyvinylpyrrolidone (PVP) of high molecular weight (360 kDa). Cryopreservation solution with 10% PVP was added to 30 µL of spermatozoa suspension in a 1:1 ratio, with a final PVP concentration of 5%. Then, polycarbonate capillaries for oocyte denudation with a diameter of 170 µm were filled with 60 µL of the resulting sperm suspension. After that, the capillaries were placed for 10 minutes at a height of 15 cm above liquid nitrogen and immersed into liquid nitrogen. To warm the spermatozoa, the capillaries were immersed in a water bath at a temperature of 40°C for 30 seconds. Oocyte fertilization was performed by ICSI. Zygotes were cultured in vitro for 5 days to the blastocyst stage. More than 100 spermatozoa were obtained after percutaneous epidydimal sperm aspiration, of which 80% were motile. After cryopreservation, storage for 3 months in liquid nitrogen, and thawing, 72% of the total sperm cells remained motile. Ten oocyte-cumulus complexes were found after follicle puncture, and eight metaphase II stage oocytes were fertilized using ICSI. After 18 hours, two pronuclei were found in seven (88%) of the oocytes. An analysis of the morphological characteristics of 5-day-old embryos showed that four (57%) of them reached the blastocyst stage. One embryo was transferred, and the remaining embryos were cryopreserved (vitrified). The onset of pregnancy was detected on the 14th day after embryo transfer, and one healthy girl (3300 g) was born at term.

Objective: To compare the effect of a fully undisturbed culture strategy over a sequential one on embryo in vitro development and clinical outcomes in intracytoplasmic sperm injection (ICSI) cycles., Design: Retrospective cohort study., Setting: University-affiliated private IVF center., Patient(s): This study included 4,564 ICSI cycles performed over 5 years, including autologous and oocyte donation treatments with extended embryo culture until blastocyst in one of the two defined culture strategies., Intervention(s): Embryo cohorts were cultured in one of two culture systems: a fully undisturbed culture, including an incubator with integrated time-lapse technology, a one-step culture medium and embryo selection assisted by semi-automatic tools on the basis of embryo morphokinetics, or a sequential culture, using a conventional benchtop incubator, sequential media and traditional morphological evaluation under optical microscope. The effect of the culture strategies on embryo development and clinical outcomes was quantified by generalized estimated equations, controlling for possible confounders through the inverse probability of the treatment weighting method., Main Outcome Measure(s): Weighted odds ratios (ORs) and 95% confidence intervals (CIs) for live birth rate after fresh single embryo transfer and the cumulative live birth rate. In addition, blastocyst development and morphology and other intermediate outcomes were also assessed., Result(s): A significant positive association was found between the employment of undisturbed embryo culture and higher live birth rate in the first embryo transfer in both autologous (OR, 1.617; 95% CI, 1.074-2.435) and oocyte donation cycles (OR, 1.316; 95% CI, 1.036-1.672). Cumulative live birth rate after 1-year follow-up was also positively associated with the undisturbed culture strategy in oocyte donation cycles (OR, 1.5; 95% CI, 1.179-1.909), but not in autologous cycles (OR, 1.051; 95% CI, 0.777-1.423). Similarly, blastocyst rate, good morphology blastocyst rate, and utilization rate were positively associated with the employment of undisturbed culture in oocyte donation cycles, but not in autologous cycles., Conclusion(s): These findings imply that a culture system combining integrated time-lapse incubators with a one-step culture medium may enhance the success rates of patients undergoing ICSI treatment by increasing the production of higher quality blastocysts and improving embryo selection while streamlining laboratory procedures and workflow., Competing Interests: Declaration of Interests M.A.V. reports funding from Agencia Valenciana de Innovació and European Social Fund, for the submitted work; travel support from Genea Biomedx; in the last 11 months, is an employee of Genea Biomedx, outside the submitted work. A.G. reports funding from European Union’s Horizon 2020-MSCA-ITN-2018 program under grant agreement No. 812660, for the submitted work. L.B. reports funding from CIAPOT/2022/23, outside the submitted work. F.M. has nothing to disclose. J.M.d.l.S. has nothing to disclose. In the last 5 years, M.M. received speaker fees from Vitrolife, Merck, Ferring, Gedeon Richter, Angelini, Genea Biomedx, FUJIFILM, AIVF, Fairtility, and Theramex. has nothing to disclose., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Telomeres maintain chromosome stability, while telomerase counteracts their progressive shortening. Telomere length varies between cell types, with leukocyte telomere length (LTL) decreasing with age. Reduced telomerase activity has been linked to reproductive issues in females, such as low pregnancy rates and premature ovarian failure, with recent studies indicating correlations between telomere length in granulosa cells and IVF outcomes., Objectives: The study aims to explore the relationship between telomere length, telomerase activity, and euploid blastocyst rate in infertile women undergoing IVF/ICSI PGT-A cycles., Methods: This prospective study involves 108 patients undergoing controlled ovarian stimulation and PGT-A. Telomere length and telomerase activity were measured in peripheral mononuclear cells and granulosa cells (GC), respectively., Results: The telomere repeat copy number to single gene copy number ratio (T/S) results respectively 0.6 ± 0.8 in leukocytes and 0.7 ± 0.9 in GC. An inverse relationship was found between LTL and the patient's age ( p  < .01). A higher aneuploid rate was noticed in patients with short LTL, with no differences in ovarian reserve markers ( p  = .15), number of oocytes retrieved ( p  = .33), and number of MII ( p  = 0.42). No significant association was noticed between telomere length in GC and patients' age ( p  = 0.95), in ovarian reserve markers ( p  = 0.32), number of oocytes retrieved ( p  = .58), number of MII ( p  = .74) and aneuploidy rate ( p  = .65)., Conclusion: LTL shows a significant inverse correlation with patient age and higher aneuploidy rates. Telomere length in GCs does not correlate with patient age or reproductive outcomes, indicating differential telomere dynamics between leukocytes and granulosa cells.

Background: Prolidase is a manganese (Mn)-dependent cytosolic exopeptidase that degrades imidodipeptides with C-terminal proline or hydroxyproline. Prolidase recycling from imidodipeptides plays a critical role in collagen resynthesis and extracellular matrix (ECM) remodelling. Following an increase in gonadotropins, ovarian and follicular collagen undergo substantial degradation. Abnormal ovarian ECM composition is associated with polycystic ovary syndrome (PCOS). This study aimed to examine prolidase activity in the serum and follicular fluid (FF) of women undergoing in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) treatment, comparing those with PCOS to those with normal ovarian function. Methods: This prospective study enrolled 50 participants, of whom 44 were included. PCOS diagnosis followed the Rotterdam consensus criteria, with 20 patients constituting the study group. The control group comprised 24 individuals with mild-to-moderate male infertility. Prolidase enzyme activity in serum and FF was measured using the Chinard reagent via spectrophotometric analysis and compared between the groups. Results: Serum and FF prolidase levels were significantly lower in patients with PCOS ( p  < 0.05). A direct correlation was observed between serum and FF prolidase levels ( p  < 0.05). Although blastocyst quality scoring (BQS) significantly decreased in PCOS patients, no statistical difference was observed in the clinical pregnancy rate between the groups ( p  < 0.05) ( p  > 0.05). A negative correlation existed between serum prolidase levels and total antral follicle (AF) count ( p  < 0.05). Conversely, both serum and FF prolidase levels positively correlated with BQS ( r  = 0.574)( p  < 0.05) ( r  = 0.650)( p  < 0.05). Conclusions: Patients with PCOS showed lower serum and FF prolidase levels, indicating abnormal degradation of ovarian and follicular collagen, potentially causing anovulation.

Retrotransposable elements are implicated in genome rearrangements and gene expression alterations that result in various human disorders. In the current study, we sought to investigate the potential effects of long interspersed elements-1 (LINE-1) overexpression on the integrity and methylation of DNA and on the expression of three major pluripotency factors (OCT4, SOX2, NANOG) during the preimplantation stages of human embryo development. Human MI oocytes were matured in vitro to MII and transfected through intracytoplasmic sperm injection (ICSI) either with an EGFP vector carrying a cloned active human LINE-1 retroelement or with the same EGFP vector without insert as control. The occurrence of retrotransposition events was screened by fluorescent microscopy. The in vitro preimplantation development as well as the methylation, pluripotency, and DNA double-strand breaks (DSBs) of the transfected embryos were examined. LINE-1 retrotransposons gave rise to new retrotransposition events in the transfected embryos. LINE-1 injected embryos were characterized by accelerated asymmetrical cell division, multiple cellular fragments, cleavage arrest, and degeneration. Early OCT4 expression remained unaltered, but cleavage arrest and a high fragmentation rate hindered the expression of SOX2/NANOG at the morula stage. Increased DNA DSBs were observed in cleavage-stage blastomeres, while no methylation changes were detected before the cleavage arrest. Our data provide evidence that LINE-1 retrotransposition in human preimplantation embryos may induce DNA DSBs, while at the same time, it appears to interfere with the expression patterns of pluripotency factors. The morphological, structural, and cleavage abnormalities of the transfected embryos show that aberrant retroelement expression may negatively affect human embryo development.

Background: This study aimed to investigate the obstetric and perinatal outcomes of singleton deliveries following frozen embryo transfer (FET) cycles using different endometrial preparation methods., Methods: We analyzed data on 44,118 singleton pregnant women who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI), resulting in delivery or abortion, from the South Korean National Health Insurance Service database. Stratification was based on the type of embryo transfer, viz. fresh embryo transfer and FET cycles, using International Classification of Diseases (Tenth Revision) diagnostic codes, national procedural codes, and prescription medication data within the IVF/ICSI pregnancy cohort. FET was subcategorized into artificial cycle-FET (AC-FET), natural cycle-FET (NC-FET), and stimulated cycle-FET (SC-FET) for comparative analyses of the pregnancy, obstetric, and perinatal outcomes., Results: AC-FET was associated with higher risks of hypertensive disorders of pregnancy, preeclampsia, placenta accreta, and postpartum hemorrhage compared with NC-FET; the risk of macrosomia showed no significant differences. SC-FET was associated with a lower risk of miscarriage and higher rate of term birth beyond 37 weeks compared with NC-FET. However, SC-FET was associated with elevated risks of gestational hypertension and postpartum hemorrhage when compared to NC-FET., Conclusion: The rate of adverse obstetric and perinatal outcomes was higher in AC-FET compared to NC-FET, highlighting NC-FET as a valuable option owing to better maternal and fetal safety. In cases where NC-FET is not feasible, SC-FET presented as a favorable alternative, exhibiting lower miscarriage rates than NC-FET and better obstetric outcomes than AC-FET., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Background: Prior research showed that elevated serum uric acid (SUA) levels in women with polycystic ovary syndrome (PCOS) before in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) treatment can lead to a lower rate of live birth and an increased risk for low birthweight. Nonetheless, it is not known whether elevated SUA results in similar reproductive outcome in women without PCOS. This study aimed to exploring the relationship between pre-pregnancy SUA levels and reproductive outcomes in non-PCOS women undergoing IVF/ICSI treatment., Methods: This single-center, retrospective study included 13,325 women without PCOS undergoing their first IVF/ICSI fresh embryo transfer cycles from January 2014 to December 2022 at a university-affiliated reproductive medicine center in China. The trends for pregnancy, obstetric and perinatal outcomes across quartiles of SUA levels were assessed. A logistic regression analysis was applied to control for baseline and cycle characteristics. Generalized addition model was used to draw spline smoothing plot., Results: There was no significant decreasing or increasing trend in the clinical pregnancy rate and live birth rate with the increase in quartiles of SUA levels. For Obstetric and perinatal outcomes following a single live birth, the percentage of hypertensive disorders in pregnancy (1.6-4.1%, P trend <0.001), gestational diabetes mellitus (5.9-13.9%, P trend <0.001), premature rupture of membranes (0.6-1.5%, P trend =0.016), preterm birth (6.3-9.2%, P trend =0.009), macrosomia (2.3-5.5%, P trend <0.001), large for gestational age (10.8-14.9%, P trend =0.002) all increased significantly from the lowest quartile to the highest. Logistic regression results showed that compared with those in quartile 1, the risk of maternal and infant complications mentioned above was still significantly higher in quartile 4 after adjusting for reproductive related factors. When further confounding factors were added, including body mass index (BMI), blood pressure, fasting blood glucose, and blood lipids related indicators, only gestational diabetes mellitus and macrosomia showed a significant increase., Conclusion: In women without PCOS, SUA levels before IVF/ICSI treatment do not affect the probabilities of clinical pregnancy and live birth. An elevated SUA level is associated with an increased risk for hypertensive disorders in pregnancy, gestational diabetes mellitus, premature rupture of membranes, preterm birth, macrosomia, and large for gestational age. For gestational diabetes mellitus and macrosomia, the association is independent of BMI, blood pressure, blood glucose, and blood lipid., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Reproductive Medicine Ethics Committee of Jiangxi Maternal and Child Health Hospital (SZYX-202411). Written informed consent for participation was not required due to the retrospective nature of this study, in accordance with the national legislation and institutional requirements. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

This study aimed to evaluate the effect of astaxanthin compound nutrient (ACN) complementary therapy on pregnancy outcomes in polycystic ovary syndrome (PCOS) patients undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). This study enrolled 92 patients with PCOS who were continuously supplemented with ACN for three months prior to IVF/ICSI treatment from 2021 to 2023, and selected 92 patients who did not receive the treatment during the same period as controls. Baseline characteristics, ovulation induction outcomes, and pregnancy outcomes were compared between the two groups. In addition, the body mass index (BMI), anti-Müllerian hormone (AMH), antral follicle counting (AFC), fasting blood glucose (FBG), fasting insulin (FINS), homeostasis model assessment of insulin resistant (HOME-IR), and basal sex hormones of the supplementary group patients before and after treatment were compared. The results showed that there were no significant differences in the patient's duration of stimulation, total gonadotropin dose, peak E2 levels, and number of retrieved oocytes between the two groups. However, the number of 2 pronucleus (PN) fertilization, transferable embryos, and high-quality embryos was significantly higher in the ACN group compared with the control group. For both fresh and frozen embryo transplantation, positive pregnancy outcomes increased in PCOS patients who received supplementation of ACN for 3 months. In addition, after 3 months of supplementing with ACN, the patient's BMI, AMH, fasting insulin, HOME-IR, basal luteinising hormone (bLH), and basal testosterone (bT) decreased compared to before treatment. This study suggested that ACN improved insulin resistance, hormone levels, embryo quality and pregnancy outcomes in PCOS patients.

Obesity is a multifactorial disease present worldwide and correlated with hormonal alterations that may cause a decrease in reproductive outcomes and seminal quality. However, the specific mechanisms involved are unknown. This led us to examine the relationship between paternal body mass index (BMI) and clinical reproductive outcomes by evaluating the cumulative live birth rates (CLBRs) per number of embryo transfers (ETs), embryos replaced (EmbRs), and oocytes used (OUs) in consecutive treatments until achieving the first newborn. A retrospective study was performed, and Kaplan-Meier survival curves were created to observe CLBRs with regard to the paternal BMI, adjusted by relevant confounders through Cox regression models. The participants were couples undergoing intracytoplasmic sperm injection (ICSI) and ET in Spanish IVIRMA clinics using autologous gametes. The cohort was subdivided based on paternal BMI: normal (18.5-24.99 kg/m 2 ) (N), overweight (25-29.99 kg/m 2 ) (OV), or obese (≥30 kg/m 2 ) (OB) patients. A total of 4750 ICSI cycles were included, encompassing 49,485 mature oocytes, 23,963 blastocysts, and 3048 ETs. When calculating CLBRs based on the number of ETs carried out until live birth was achieved, no statistically significant differences were found ( p = 0.72). After adjusting for maternal age and BMI, female infertility diagnosis, the use of preimplantation genetic testing, and the number of ETs, Cox regression showed that there were no statistically significant differences between the BMI groups (HR: 0.94 [95% CI: 0.7-1.2]; p = 0.59). When calculating CLBRs considering EmbRs, there was a similarity between the BMI groups ( p = 0.57). However, there were no statistically significant differences in the adjusted Cox regression (HR: 0.93 [95% CI: 0.7-1.2]; p = 0.51). Finally, when calculating CLBRs considering OUs, the results were comparable among BMI subgroups ( p = 0.75), and there were no statistically significant differences with adjusted Cox regression (HR: 0.95 [95% CI: 0.8-1.2]; p = 0.66). In conclusion, paternal BMI was not associated with clinical reproductive outcomes when considering the ETs, EmbRs, or OUs needed to reach the first liveborn (LB).

Objective: Premature Progesterone Rise (PPR) is characterized by elevated serum progesterone concentrations either towards the end of the follicular phase or on the trigger day, surpassing a pre-defined threshold value. Aim of the study is to evaluate the impact of PPR exceeding 1.5 ng/ml at the time of hCG-trigger on embryo morphokinetic parameters and to identify predictive biomarkers of in IntraCytoplasmic Sperm Injection (ICSI) cycles outcomes., Methods: It is a retrospective study including patients underwent ICSI cycles in the period 2020-2023. 58 patients were recruited in the study group showing P levels in the trigger day greater than or equal to 1.5 ng/ml. A matching control group of 58 patients with P levels below 1.5 ng/ml was after selected. The general characteristics of these patients, including age, Body Mass Index (BMI), antral follicle count (AFC), anti-Müllerian hormone (AMH) and follicle-stimulating hormone (FSH) levels, the type of infertility and smoking/non-smoking patients, were recorded on the day of their initial visit. Subsequently, data were collected regarding the number of eggs retrieved, mature eggs, successfully fertilized eggs, and embryos reaching the blastocyst stage. Additionally, the timing of embryonic development and the quality of obtained blastocysts, as assessed by the degree of expansion and the characteristics of the inner cell mass (ICM) and trophectoderm (TE), were evaluated using Time-Lapse technology., Results: Elevated P levels exceeding 1.5 ng/ml on the trigger day were directly associated with a significantly larger number of antral follicles, consequently leading to a higher count of retrieved eggs, mature eggs, successfully fertilized eggs and embryos reaching the blastocyst stage. Furthermore, the analysis of morphokinetic parameters indicated faster division times and a notably greater number of high-grade blastocysts in the study group compared to the control group., Conclusions: P levels ≥ 1.5 ng/ml on the trigger day did not negatively impact embryonic morphokinetic parameters, instead resulting in faster embryo development in the initial stages., (© 2024. The Author(s).)

Objective: To investigate the potential impact of vitamin D (VD) serum levels on couples going through in vitro fertilization treatment in terms of embryo quality and pregnancy rates., Design: A retrospective cohort study., Setting: A private human reproduction center., Patient(s): A total of 267 couples underwent intracytoplasmic sperm injections between January 2017 and March 2019., Intervention(s): The couples were categorized into four groups on the basis of 25-hydroxy VD (25OHD) levels measured at the beginning of the stimulation protocol: group 1 with 25OHD levels ≥30 ng/mL for both women and men; group 2 with 25OHD levels <30 ng/mL for both; group 3 women with 25OHD levels <30 ng/mL and men with 25OHD levels ≥30 ng/mL; and group 4 with women with 25OHD level ≥30 ng/mL and men with 25OHD level <30 ng/mL., Main Outcome Measure(s): We consider the quantity and quality of embryos during the cleavage as well as blastocyst stages as primary outcomes. Correspondingly, the clinical pregnancy rate (CPR) was regarded as a secondary outcome., Result(s): Our findings revealed no significant correlations between the studied VD groups and the evaluated outcomes. This includes the quantity and quality of embryos during the cleavage and blastocyst stages, as well as the CPR. Primary analysis revealed a small but statistically significant difference in the duration of controlled ovarian stimulation between group 1 and group 2 (95% confidence interval, 0.07-3.04) and between group 1 and group 3 (95% confidence interval, 0.05-3.23)., Conclusion(s): The present study found no correlation between the studied VD levels and the quantity as well as quality of cleavage or blastocyst stage embryos, nor did it show any impact on CPRs. Further well-designed, prospective studies are warranted to determine whether and how vitamin D affects reproductive outcomes., Competing Interests: Declaration of Interests R.D.A.A. receives eventual honoraria from Abbott, Ferring Pharmaceuticals, Besins Healthcare, and Organon for medical conferences, medical board participation, and has been sponsored to attend medical congresses (European Society of Human Reproduction and Embryology [ESHRE] and American Society for Reproductive Medicine [ASRM] annual congress by Ferring Pharmaceutical, ESHRE 2023 annual congress by Organon, and ESHRE 2024 annual conference by Besins Healthcare and Ferring Pharmaceuticals); Brazilian Society of Assisted Reproduction - SBRA – Director; Rio de Janeiro Association of Gynecology and Obstetrics - SGORJ – Director; Latin American Network of Assisted Reproduction - REDLARA - Coordinator of the Postgraduation of Assisted Reproduction for Physicians – PEC Online. M.D.C.B.S. receives eventual honoraria from Abbott, Ferring Pharmaceuticals, Merck, and Exeltis for medical conferences and medical board participation, and has been sponsored to attend medical congresses (ESHRE 2023 and 2024) from Ferring Pharmaceuticals. M.M.S. has nothing to disclose. G.P.S.M. has nothing to disclose. B.M.L.M. has nothing to disclose. A.C.A.M. has nothing to disclose. F.L.C. has nothing to disclose. T.M.O.-C. has received two research grants from FAPERJ (Carlos Chagas Filho Foundation for Research Support in the State of Rio de Janeiro, Brazil) and CNPq (Brazilian National Council for Scientific and Technological Development)., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: To examine the ability of testicular histopathology in Non-obstructive azoospermia (NOA) in predicting sperm retrieval rate (SR), sperm quality and assisted reproductive technology success., Methods: A retrospective study recruited clinically diagnosed NOA patients between 2007 and 2015. Testicular biopsy and conventional sperm extraction (TESE) were done concomitantly. Correlation between pathological categories, SR rate, sperm quality and success of intracytoplasmic sperm injection (ICSI) was studied. FSH was measured as a predictor of fertility., Results: One hundred eighteen patients were recruited. Histopathological classification was hypospermatogenesis (HS) 45 (38%), maturation arrest (MA) 22(19%), Sertoli cell only syndrome (SCOS) 34 (29%) and normal spermatogenesis (NS) 17 (14%). FSH value was above normal level in 34 (76%) of HS, 19 (86%) of MA, 32 (94%) of SCOS and 5 (29%) of NS. Positive SR was obtained in 108 (92%) patients. The highest SR rate was seen in NS group 100% and the lowest was in SCOS 26 (77%). The worst sperm quality was found in SCOS as type C represents 46%, followed by MA 40% and HS 24%. Patients had ICSI following TESE had variable success rate as success of ICSI was seen (9/15) for HS, (0/7) for MA, (5/15) for SCOS and (8/9) for NS. FSH is strongly correlated to SR, quality of sperm and success of ICSI as positive SR in normal FSH patients was obtained in 28 (100%) of normal FSH, 70 (97%) of high FSH and 10 (56%) of double high FSH ( p value < 001). The success of ICSI significantly correlates with FSH value as normal FSH has 77% success ICSI rate, high FSH (52%) and double high FSH (0%) ( p value < 0.001)., Conclusions: Testicular biopsy and histopathology findings in NOA are strongly correlated SR rate, quality of sperms, and success of ICSI. FSH is a strong noninvasive predictor of fertility in NOA patients., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Characterization of long non-coding telomeric repeat-containing RNAs in sperm of normozoospermic and oligoasthenozoospermic men as new biomarker of idiopathic male infertility. We conducted an observational prospective study with two groups of men with normal or orligoasthenozoospermic spermiogram, aged 40 and above. Fertility parameters were analyzed in men undergoing intracytoplasmic sperm injection with donor oocytes, to avoid the female factor. Telomeric RNAs and telomere length were measured by quantitative fluorescent in situ hybridization. Data from seminal parameters and in-vitro fertilization were assessed according to IVIRMA protocols. Patients with oligoasthenozoospermia, who had worse seminal parameters, also obtained embryos with lower inner-cell-mass quality (p = 0.04), despite using donor oocytes. While mean levels of telomeric RNAs were similar for both groups, the percentage of spermatozoa with more than 3 foci was higher in oligoasthenozoospermic men (p = 0.02). Regarding telomere length, oligoasthenozoospermic men had shorter mean, a higher accumulation of short telomeres (15th percentile; p = 0.03) and a lower percentage of very-long telomeres (85th percentile; p = 0.01). Finally, a positive correlation was found between telomeric-RNAs intensity and total progressive motility in the spermatozoa of normozoospermic patients (r = 0.5; p = 0.03). Telomeric parameters were altered in the spermatozoa of the oligoasthenozoospermic group, which also showed lower quality embryos. Interestingly, in the normozoospermic group, a correlation was found between progressive motility and telomeric RNA levels, suggesting that they could be a good biomarker of sperm quality. Further studies are required to confirm these results and translate them into the clinical practice.Trial registration number: 1711-MAD-109-CB, 07/07/2021., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Study Question: Do biallelic deleterious variants of Calreticulin 3 (CALR3) cause fertilization failure (FF), resulting in male infertility in humans?, Summary Answer: Biallelic mutations in CALR3 were identified in two infertile men from unrelated families and were shown to cause FF associated with failed sperm-zona pellucida (ZP) binding., What Is Known Already: In male mice, the Calr3-knockout has been reported to cause male infertility and FF. However, the mechanism behind this remains unclear in humans., Study Design, Size, Duration: Sequencing studies were conducted in a research hospital on samples from Han Chinese families with primary infertility and sperm head deformations to identify the underlying genetic causes., Participants/materials, Setting, Methods: Data from two infertile probands characterized by sperm head deformation were collected through in silico analysis. Sperm cells from the probands were characterized using light and electron microscopy and used to verify the pathogenicity of genetic factors through functional assays. Subzonal insemination (SUZI) and IVF assays were performed to determine the exact pathogenesis of FF. ICSI were administered to overcome CALR3-affected male infertility., Main Results and the Role of Chance: Novel biallelic deleterious mutations in CALR3 were identified in two infertile men from unrelated families. We found one homozygous frameshift CALR3 mutation (M1: c.17&#95;27del, p.V6Gfs*34) and one compound heterozygous CALR3 mutation (M2: c.943A>G, p.N315D; M3: c.544T>C, p.Y182H). These mutations are rare in the general population and cause acrosomal ultrastructural defects in affected sperm. Furthermore, spermatozoa from patients harbouring the CALR3 mutations were unable to bind to the sperm-ZP or they disrupted gamete fusion or prevented oocyte activation. Molecular assays have revealed that CALR3 is crucial for the maturation of the ZP binding protein in humans. Notably, the successful fertilization via SUZI and ICSI attempts for two patients, as well as the normal expression of PLCζ in the mutant sperm, suggests that ICSI is an optimal treatment for CALR3-deficient FF., Limitations, Reasons for Caution: The results are based on sperm-related findings from two patients. Further studies are required to gain insight into the developmental stage and function of CALR3 in human testis., Wider Implications of the Findings: Our findings highlight the underlying risk of FF associated with sperm defects and provide a valuable reference for personalized genetic counselling and clinical treatment of these patients., Study Funding/competing Interest(s): This study was supported by the National Key R&D Program of China (2021YFC2700901), Hefei Comprehensive National Science Center Medical-Industrial Integration Medical Equipment Innovation Research Platform Project (4801001202), the National Natural Science Foundation of China (82201803, 82371621, 82271639), Foundation of the Education Department of Anhui Province (gxgwfx2022007), Key Project of Natural Science Research of Anhui Educational Committee (2023AH053287), and the Clinical Medical Research Transformation Project of Anhui Province (202204295107020037). The authors declare no competing interests., Trial Registration Number: N/A., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)