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Objective: To study the effect of the descend range of estradiol (E2) at 48 h after oocyte retrieval compared with 24 h before oocyte retrieval on the pregnancy outcomes of fresh embryo transfer in the antagonist regimen. Methods: A retrospective study was done on the clinical data from 413 cycles of fresh embryo transfer, from January 2017 to March 2021. According to the descend range of E2 48 h after oocyte retrieval compared with 24 h before oocyte retrieval, they were divided into four groups according to the quartile method. Group A: The descend range is 0-25.0% of the overall descend range; Group B: 25.1%-50.0%; Group C: 50.1%- 75.0%; Group D: 75.1%-100.0%. The ovulation induction, embryological outcome and pregnancy outcomes were compared, and the relationship between E2 reduction and live birth rates was analyzed by logistic regression. Results ：There were significant differences in the total amount of Gn, days of antagonist use, live birth rates, implantation rates and clinical pregnancy rates among the four groups (all P＜0.05). The live birth rate of group A was higher than group D, group B was higher than those of group C and group D, and the implantation rates of group A and group B were higher than group D (all P＜0.008 3). After adjusting for the factors of differences among groups, the live birth rates of groups A and B were significantly higher than those of group D (OR=2.079, 95%CI: 1.138-3.799, P=0.017; OR=2.187, 95%CI: 1.213-3.944, P=0.009). Conclusions: In the antagonist regimen, the live birth rate of fresh embryo transfer in patients with a greater descend range of E2 at 48 h after oocyte retrieval is lower than that in patients with less descend range of E2. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the results of microdissection testicular sperm extraction (micro‐TESE) and intracytoplasmic sperm injection (ICSI) for treatment of non‐obstructive azoospermia (NOA). Materials and methods: We retrospectively analysed data of 88 consecutive patients with clinical NOA who were treated with micro‐TESE by a single surgeon, between August 2014 and September 2020, in Melbourne, Victoria. Upon a successful sperm retrieval, sperm was either used fresh for ICSI, frozen for future use or both. The outcome measures were sperm retrieval rate (SRR), and in vitro fertilisation (IVF)/ICSI results. Furthermore, SRR was calculated for the predominant causes and histopathological patterns. Results: The overall SRR was 61.2%. It was significantly higher in patients with a history of cryptorchidism and other childhood diseases (100%) than in the other NOA groups (P < 0.05). Patients with Klinefelter syndrome had a 75% SRR. Among the different types of testicular histology, the highest SRR were noted in patients with complete hyalinisation (100%) and hypospermatogenesis (92.9%), and low with Sertoli cell‐only syndrome (46.3%). The SRR has significantly increased from 33.3% in 2015–2016 to 73.6% in 2019–2020 (P = 0.009). Of the 52 patients with SSR, 47 underwent IVF/ICSI. Fertilisation rate was 42.4%. Twenty‐nine couples achieved at least one good‐quality embryo and had embryo transfer. Nineteen achieved pregnancy (40.4%), and in three patients a miscarriage resulted. Conclusions: This is the first report from Australia showing that micro‐TESE is an effective treatment for NOA with high SRR. The increasing success rates over several years indicate the importance of surgical skill and laboratory staff experience. [ABSTRACT FROM AUTHOR]

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.)

Introduction: Micronutrients influence female fertility, thus adequate levels are important for oocyte quality, maturation, fertilisation and implantation. This study prospectively evaluated the impact of oral multinutrient supplementation on fertility outcomes in In vitro fertilisation or Intracytoplasmic sperm injection (IVF/ICSI)., Materials and Methods: This was a pilot study of N=50 women, who were planning for IVF treatment in University Malaya Medical Centre, Kuala Lumpur, Malaysia from July to December 2023. Women without prior nutritional treatment were consented and assigned to either the multinutrient supplementation (Omega 3, coenzyme Q10, folic acid, selenium, vitamin E, catechins) as the study group or 5mg folic acid daily as control group for at least a month prior to their IVF treatment. All women were treated using an antagonist protocol and ovarian stimulation was started with 200 -300IU of urinary HMG and or recombinant FSH. Antagonists (Ganirelix) commenced when the leading follicle reached a diameter of 11 mm. Triggering with hCG or GnRH agonist when at least 3 follicles of 17 mm in diameter were achieved. Oocyte retrieval was performed 36th hour after trigger. Conventional IVF/ICSI was used for fertilisation. All parameters recorded and analysed using SPSS., Results: The mean age (36.44 ± 3.33 vs 35.32 ± 3.47 years) and body mass index (25.28 ± 4.12 vs 24.80 ± 4.36 kg/m2) of women in multinutrient supplementation group was similar to control group. The Follicular Output Rate (FORT) in women on multinutrient supplementation showed a trend towards benefit compared to control group, although it is not statistically significant (68.12 ± 19.47 vs 64.91 ± 20.06, p=0.493). The mean number of MII oocytes retrieved from mature follicles and number of good quality embryo on day 3 after fertilisation were not statistically significant between the two groups (6.65 ±3.84 vs 6.09 ± 3.01, p=0.626 and 4.00 ± 3.10 vs 3.45 ± 2.30, p=0.549, respectively). In addition, there were no differences in endometrial thickness before embryo transfer in both groups (10.35 ± 1.32mm vs 10.36 ± 2.04mm, p=0.320). However, the total dose of follicle stimulating hormone and duration of controlled ovarian stimulation were lower in the study group compared to control group (2410 ± 656.82 IU vs 2706.82 ± 536.15 IU, p= 0.119 and 8.90 ± 2.13 days vs 9.68 ± 1.29 days, p=0.164, respectively)., Conclusion: A multinutrient supplementation given for a minimum of 28 days, may have a positive effect on FORT and lower use of gonadotropin. More and larger sample research is warranted to prove this effect.

Objective: Multinucleated blastomeres at the two-cell stage (2MNB) represent a frequently observed nuclear abnormality in early human embryos. This abnormality has been reported to significantly impact on the embryo's developmental potential to reach the blastocyst stage. However, our understanding of the embryo's developmental potential and the morphokinetics of 2MNB remains limited. This study investigates the influence of 2MNB and its subtypes on the blastocyst formation., Study Design: A non-interventional retrospective study was performed in the Reproductive Medical Center of the First Affiliated Hospital of Hainan Medical University, using a time-lapse incubator. The study involved the evaluation of 4416 embryos, including 628 multinucleated embryos, from 1521 intracytoplasmic sperm injection (ICSI) cycles conducted between October 2019 and October 2021. The morphokinetic characteristics of multinucleated embryos were analyzed., Results: The results show multinucleation was the most common abnormal mitotic event during embryo development (14.22 %) in 4416 embryos. A control group of 3210 developmentally normal embryos was used in the study. The multinucleated blastomeres caused a lower blastocyst rate (52.48 % VS 64.02 %) compared to the control group. Whereas, 2MNBcause a higher blastocyst rate thanthemat the 4-cell stage (4MNB) (58.89 % VS 43.64 %). 2MNB can be further be further divided into 2MNB 1/2cell and 2MNB 2/2cell based on one multinucleated blastomere or two multinucleated blastomere appeared. Time to pronuclei fading (tPNf) is significantly longer in 2MNB 2/2cell compared to 2MNB 1/2cell . Furthermore, the 2MNB 1/2cell embryos were divided into four subgroups (Bi-: two nuclei with almost the same size, Micro-: two nuclei with varying sizes, Poly-: more than two nuclei with almost the same size, and Cluster-: more than two nuclei with varying sizes) based on the number of nuclei and relative size. The results show that the Bi- and Micro- groups had a significantly increased blastocyst rate. The Cluster-, and Poly- groups showed significantly delayed embryonic development compared to normal controls. Bi-group has significant delays at t3, t5, and t8 and the Micro-group had a significant delay only at t8., Conclusion: 2MNB cause higher blastocyst rate than them at 4MNB. 2MNB 1/2cell shows shorter tPNf compared to 2MNB 2/2cell . Moreover, the Micro-, Bi- groups had a significantly increased blastocyst rate and different kinetic parameters compared to Cluster-, Poly-groups, suggesting that it is necessary to distinguish the nucleus status within 2MNB to increase the blastocyst rate. When selecting embryos for transformation from the 2MNB 1/2cell , Micro- is the best choice., 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 effect of embryo morphology score on 14-day β-HCG levels and 14-18-day β-HCG doubling values, and do they have differences in day-3 embryo or day-5 blastocyst transfers?, Design: Retrospective analysis of 4434 fresh cycles of single embryo transfers (SET) with β-HCG ≥15 mIU/ml on day 14 after transfer via IVF and ICSI. The correlation between embryo morphology score and 14-day β-HCG was examined. Doubling of 14-18 day β-HCG was analysed in 2628 cycles to determine correlations with embryo morphology score., Results: In day-3 SET, number of embryonic cells was positively correlated with 14-day post-transfer β-HCG values (R = 0.076; P = 0.013). No significant correlation was observed between the grade of the transferred embryos and the 14-18-day serum β-HCG doubling values. In day-5 single blastocyst transfers, the degree of blastocyst expansion, trophoblast cell and inner cell mass (ICM) grades demonstrated a significant positive correlation with 14-day post-transfer β-HCG (P < 0.001, P = 0.014, P = 0.003). Degree of blastocyst expansion was significantly correlated with 14-18-day β-HCG doubling values (R = -0.051, P = 0.027). Grades of the ICM and trophoblast cells showed no significant correlation with 14-18-day β-HCG doubling values., Conclusion: In fresh SET, embryo morphology score influences 14-day β-HCG values in day-3 embryos and day-5 blastocyst transfers. Embryo morphology score in day-3 SET does not affect 14-18-day β-HCG doubling values. Degree of blastocyst expansion significantly affects 14-18-day β-HCG doubling values in day-5 blastocyst transfers., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: The aim was to analyze the clinical characteristics, controlled ovarian stimulation status, pregnancy outcomes, and major factors influencing live births in patients with endometrial hyperplasia (EH) undergoing IVF/ICSI for assisted reproduction, so as to identify potential intervention measures., Study Design: Patients with EH who achieved complete remission (CR) after conservative treatment and who were undergoing their first IVF/ICSI cycle were included in this matched-pair study. Patients with normal endometriums were matched at a 1:2 ratio with the control group for the first cycle of controlled ovarian stimulation. Matching was based on age, and reproductive outcomes were analyzed., Results: Among the 263 patients (including 51 cases with atypical endometrial hyperplasia) in the study group, the pregnancy rate after the first controlled ovarian stimulation cycle was 48.67 % (128/263), and the live birth rate was 34.98 % (92/263). Multiple logistic regression analysis revealed that maternal age, body mass index (BMI), and endometrial thickness were significantly associated with live births (P<0.001). Specifically, being aged ≥ 35 years (OR 0.450, 95 % CI 0.223-0.907) and having a BMI≥28 kg/m 2 (OR 0.358, 95 % CI 0.161-0.798) were identified as unfavorable factors for a clinical live birth, while an endometrial thickness ≥ 10 mm was found to be a favorable factor., Conclusion(s): ART is effective in patients with EH who have achieved CR after conservative treatment. Avoiding unnecessary intrauterine procedures, controlling body weight appropriately, and choosing suitable ART methods as soon as possible may be beneficial for clinical 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: Melatonin, a hormone found in various bodily fluids and cells, is known for its potent antioxidative, anti-apoptotic, and endocrine regulatory properties. This study aimed to analyze melatonin levels in patients with diminished ovarian reserve (DOR) and its impact on embryo quality., Methods: We enrolled 85 women who were undergoing in vitro fertilization or intracytoplasmic sperm injection procedures, including normal ovarian reserve (NOR, n = 27), pathological DOR (DOR-Path, n = 25), and physiological DOR (DOR-Phy, n = 33). Melatonin levels in patient serum and follicular fluid were assessed using ELISA, and correlations between melatonin levels and indicators of embryo quality were examined., Results: Our findings indicate that melatonin levels in the follicular fluid and basal serum of the DOR-Path and DOR-Phy groups were lower compared to the NOR group (P < 0.05). However, no significant differences in melatonin levels were found between the DOR-Path and DOR-Phy groups (P > 0.05). Additionally, the concentration of melatonin in the follicular fluid of the NOR group was significantly higher than in their serum (P < 0.001). Lastly, a significant correlation was discovered between melatonin levels in serum and follicular fluid and parameters of ovarian reserve and embryonic development (P < 0.05)., Conclusions: Melatonin levels in DOR patients may impact embryo quality, offering insights into potential DOR pathogenesis and opportunities to enhance treatment outcomes in these patients., (© 2024. The Author(s).)

Background: While most research has focused on the association between intracytoplasmic sperm injection (ICSI) and neurodevelopmental disorders in children, relatively little attention has been given to its metabolic effects. Previous studies have reported that low serum lipid levels are associated with mental health problems. Our objective was to analyze the impact of ICSI on metabolic alterations compared to their in vitro fertilization (IVF) counterparts in male offspring, as well as its interaction with paternal overweight/obesity., Methods: We recruited families between January 2006 and December 2017 at the Center for Reproductive Medicine, Shandong University, China. Prospective data of offspring were obtained for body mass index (BMI), blood pressure, glucose, and lipid profile in their 0-11 years old. Linear mixed models were utilized to compute the mean difference and 95% confidence intervals (CI)., Results: A total of 14,196 offspring visits were identified. In offspring aged 4-11 years, ICSI-conceived offspring exhibited significantly lower fasting glucose z-scores, total cholesterol z-scores, and low-density lipoprotein cholesterol (LDL-C) z-scores compared with their IVF counterparts (fasting glucose z-score: adjusted mean difference: - 0.13, 95% CI: - 0.23 to - 0.03; total cholesterol z-score: adjusted mean difference: - 0.13, 95% CI: - 0.23 to - 0.02; LDL-C z-score: adjusted mean difference: - 0.12, 95% CI: - 0.22 to - 0.01). Paternal overweight/obesity significantly influenced the relationship between ICSI and metabolic changes in offspring. In offspring born from fathers with overweight/obesity, ICSI-conceived offspring displayed significantly lower fasting glucose and total cholesterol z-scores than their IVF controls (fasting glucose z-score: adjusted mean difference: - 0.20, 95% CI: - 0.32 to - 0.08; total cholesterol z-score: adjusted mean difference: - 0.15, 95% CI: - 0.27 to - 0.02). In offspring born to fathers with normal weight, ICSI-conceived offspring showed significantly lower systolic blood pressure z-scores compared to those conceived via the IVF procedures (adjusted mean difference: - 0.21, 95% CI: - 0.37 to - 0.05)., Conclusions: The findings of this study suggested that ICSI was associated with altered glucose and lipid profiles compared to their IVF controls, characterized by lower fasting glucose z-scores, total cholesterol z-scores, and LDL-C z-scores. Encouraging fathers to reduce their body weight could potentially improve the metabolic health of their ICSI-conceived children., (© 2024. The Author(s).)

Background: The management of Non-Obstructive (NOA) Azoospermia or Obstructive Azoospermia (OA) patients relies on testicular sperm extraction (TESE) followed by intracytoplasmic sperm injection (ICSI). In NOA patients the sperm recovery is successful in only 50% of cases and therefore the ability to predict those patients with a high probability of achieving a successful sperm retrieval would be a great value in counselling the patient and his partner. Several studies tried to suggest predictors of a positive TESE (e.g. FSH concentration), but most concluded that diagnostic testicular biopsy (histology) is best., Methods: This is a retrospective analysis of 526 TESE patients. After the extraction of the testis, the resulting sample was immediately given to the embryologist, who examined the tubules for sperm cryopreservation. During the same procedure, a different specimen was destined to the histological analysis. The comparison between the two methodological approaches was carried out through a score., Results: Concordance between TESE and testicular histology outcomes was found in 70,7% of patients; discordance was found in 29,3% of patients. Among the discordance outcomes, in approximately 95% we found at least 1 sperm in the TESE retrieval, while the histology report did not find any spermatozoa or found not enough compared to our evaluation; in only 5% of cases we did not find any spermatozoa or found not enough compared to what was detected in the testicular histology., Conclusion: Based on our experience, to increase diagnostic accuracy, a larger biopsy should be sent to the histopathology laboratory; another option may be to use TESE cell suspension (the same embryologists employ for cryopreservation) for cytological evaluation of spermatogenesis., 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 © 2024 Castellano, Tondo, Bulbul, Aprea, Monti, Carnesi, Levi Setti and Albani.)

Background: Obesity poses a significant global health challenge, with profound implications for women's reproductive health. The relationship between ovarian reserve and body mass index (BMI) remains a subject of debate. While obesity is generally associated with poorer outcomes in assisted reproductive technology (ART), the evidence remains inconclusive. This study aimed to investigate the effect of pre-pregnancy BMI on ovarian reserve and ART outcomes in infertile patients., Methods: We conducted a retrospective cohort study involving women who underwent in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) procedures at Tongji Hospital between 2016 and 2023. The study included 30,746 initial fresh cycles and 5,721 singleton deliveries. Patients were stratified by age and further categorized into four BMI groups: lean (< 18.5 kg/m²), normal weight (18.5-24.9 kg/m²), overweight (25.0-29.9 kg/m²), and obese (≥ 30.0 kg/m²). The primary endpoints of the study were pregnancy and perinatal outcomes. To explore the association between BMI and these outcomes, we adjusted for relevant confounding factors and utilized multivariate linear regression models, complemented by multifactorial logistic regression analyses., Results: Anti-Müllerian hormone (AMH) levels were significantly lower in the overweight and obese groups compared to the normal weight group. After adjusting for age, a negative correlation was found between AMH and BMI in the age subgroups of 20-30 and 30-35 years. Among women aged 20-35 years, those in the overweight and obese groups had significantly fewer retrieved oocytes, mature oocytes, and two-pronuclear (2PN) embryos than their normal weight counterparts. Despite these differences, pregnancy outcomes in the overweight and obese groups were comparable to those in the normal weight group across all age categories. Additionally, obesity was linked to an increased risk of gestational diabetes mellitus, hypertensive disorders of pregnancy, and macrosomia., Conclusions: An age-related decrease in AMH levels was evident with increasing BMI. Although being overweight or obese is associated with poorer embryo and perinatal outcomes, it does not seem to have a substantial impact on fertility., (© 2024. The Author(s).)

Importance: Adenomyosis can reduce the chance of clinical pregnancy in women undergoing assisted conception. Treatment with prolonged gonadotrophin-releasing hormone analogue (GnRHa) downregulation prior to IVF/ICSI has been postulated to improve pregnancy outcomes., Objective: We aimed to evaluate the effectiveness and safety of prolonged GnRHa treatment (minimum one month) versus no pre-treatment in women with adenomyosis undergoing IVF/ICSI using a systematic review and meta-analysis., Data Sources: We searched electronic databases: Embase (OVID), MEDLINE® (OVID), APA PsycInfo (OVID), Maternity & Infant Care Database (MIDIRS (OVID), HMIC Health Management Information Consortium (OVID) and ClinicalTrials.gov from inception until 27th of March 2023., Study Selection and Synthesis: We included studies that reported on women with adenomyosis receiving GnRHa to down-regulate the hypothalamic-pituitary-ovarian axis for one to six months before IVF/ICSI. We pooled data using the Haensel-Mantel method and reported using Odds Ratio (OR) with 95 % confidence intervals (CI). We assessed the quality of included studies using the Newcastle-Ottowa Scale and confidence in evidence using the GRADE criteria. Bias analysis was conducted via the Cochrane recommended tool (RevMan Web, Academic License)., Main Outcomes and Results: We screened 365 citations and eight retrospective studies were included in the meta-analysis (n = 2422 women). The median age was 34 years [IQR 31.95-35.05], median BMI 21.30 kg/m 2 [IQR 21.05-23.55] and median duration of GnRHa downregulation was 2.5 months [Range 1-4; IQR 1.37-3]. Women with adenomyosis receiving prolonged GnRHa treatment had a higher implantation rate 1/OR 1.69 [95 % CI 1.09, 2.56], I 2  = 81 %, (P = 0.02) and clinical pregnancy rate 1/OR 1.42 [95 % CI 1.03, 2.0], I 2 70 %, P = 0.03. There was no overall difference in live birth rate 1/OR 1.12 [95 % CI 0.70, 1.79], I 2  = 78 %, p = 0.63), miscarriage rate 1/OR 0.92 [95 % CI 0.63, 1.28, P = 0.61, I 2 0 % or mean number of oocytes retrieved (10 oocytes [IQR 8.95; 11.15] vs. 9.28 [IQR 8; 10.20], p = 0.22) between groups., Conclusions and Relevance: The benefit of prolonged GnRHa treatment in women with adenomyosis undergoing assisted conception treatment is uncertain based on existing retrospective studies. Implantation and clinical pregnancy rates were higher following prolonged downregulation in this population, though there was no statistically significant difference in live birth and miscarriage rates. Given the limited, low-quality existing data, there is a need for a well-designed, prospective randomised controlled trial to precisely evaluate the effectiveness of prolonged GnRHa treatment in this population., 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 Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: To explore the application possibility of macrocephalic sperm from a patient with 100% macrocephalic sperm and AURKC gene variations., Methods: We diagnosed a case of macrozoospermia with 100% macrocephalic sperm and 39.5% multi-tailed spermatozoa by morphological analysis. Whole-exome sequencing (WES) was used for the patient and his wife. Sanger sequencing technique was used to verify the AURKC mutations in the patient's parents and his offspring. Sperm's ploidy was tested by flow cytometry. The couple asked for intra-couple ART therapy., Results: The patient presented novel compound heterozygous AURKC mutations (c.434C > T, c.497A > T) by WES. Sanger sequencing validation showed that variant of c.434C > T was observed in his father and c.497A > T was observed in his mother. Flow cytometry revealed that there existed a certain proportion of haploid sperm. Macrocephalic spermatozoa whose heads were smaller than the diameter of injection needle were selected for microinjection. A singleton pregnancy was achieved after embryo transfer. Prenatal diagnosis revealed that the fetus had normal chromosomal karyotype. Sanger sequencing technique showed that the fetus carried a c.434C > T mutation in one AURKC allele. A 3730 g healthy male fetus was delivered at term., Conclusion: Our study reported a successful live birth from a patient with definite AURKC gene variants and may provide insights for such patients to choose donor sperm or their own sperm., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The aim of the study was to determine the expression pattern of long pentraxin 3 (PTX3) mRNA in cumulus cells (CCs) isolated from metaphase II oocytes of women with unilateral endometrioma undergoing controlled ovarian stimulation using a gonadotropin-releasing hormone antagonist (GnRHa) protocol., Patients and Methods: A total of 60 CC samples, 30 from the affected ovary and 30 from the contralateral ovary, were collected from 12 patients with unilateral endometrioma who underwent flexible GnRHa protocol with recombinant human chorionic gonadotropin (rhCG) trigger. Thirty CC samples collected from the left ovary of 12 women with male factor infertility were used as external controls. Long PTX3 mRNA expression in each group was analyzed by real-time polymerase chain reaction (RT-PCR). Relative gene expression (fold-change) was calculated according to the 2-ΔΔCt equation. Fertilization rates after intracytoplasmic sperm injection (ICSI) were recorded for each group., Results: CC-PTX3 mRNA expression in the unilateral endometrioma group was significantly lower than the mRNA expression of the disease-free ovary (0.90±0.01 vs. 0.25±0.02, p<0.01). CC-PTX3 mRNA expression of MII oocytes of the disease-free ovary was found to be similar to the control group (1.02±0.03 vs. 0.90±0.01, p=0.107). A significant 3.6-fold downregulation was observed in the CC-PTX3 mRNA expression of the endometrioma group compared to the CC-PTX3 mRNA expression in the contralateral ovary. CC-PTX3 mRNA expression in the endometrioma group was downregulated 4.08-fold compared to the CC-PTX3 mRNA expression of the control group (1.02±0.03 vs. 0.25±0.02, p<0.001). The cumulus morphologies of the endometrioma group with low CC-PTX3 expression and the groups with normal CC-PTX3 levels were similar. Fertilization rates of the endometrioma group were similar to the contralateral ovary and control groups., Conclusions: Unilateral endometrioma reduces CC-PTX3 expression but does not affect disease-free ovaries. The GnRHa protocol improved the fertilization rates, suggesting that failed CC-PTX3 expression is an in vivo pathology.

Background: The increased use of gestational carriers has expanded family-building opportunities for people and couples unable to carry pregnancies on their own. National American Society of Reproductive Medicine guidelines for gestational carriers have changed over time to reflect advances in reproductive technology and mounting evidence supporting the medical benefits associated with singleton gestations., Objective: Assess changes in gestational carrier cycle practice patterns and resultant pregnancy outcomes in the United States in relation to changing national American Society of Reproductive Medicine guidelines, which changed in 2013 and 2017., Study Design: This retrospective study used data from the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System and included all cycles that were reported from 2014-2020 involving an embryo transfer to a gestational carrier. Binomial regression models evaluated trends in preimplantation genetic testing for aneuploidy, American Society of Reproductive Medicine guideline adherence, number of embryos transferred, and pregnancy outcomes over time., Results: Of the 40,177 gestational carrier transfer cycles from 2014-2020, there was a significant increase in frozen-thawed cycles (41.3% increase), use of assisted hatching (53.4% increase), intracytoplasmic sperm injection (50.0% increase), and preimplantation genetic testing for aneuploidy (155.7% increase). The likelihood of preimplantation genetic testing for aneuploidy was higher in 2020 than in 2014 for autologous oocyte transfers to gestational carriers, both for those aged ≥38 years (adjusted relative risk, 2.38 [95% confidence interval, 2.11-2.70]) and than those aged <38 years (adjusted relative risk, 2.85 [95% confidence interval, 2.58-3.15]). As preimplantation genetic testing for aneuploidy usage increased, single embryo transfer rose for both autologous (adjusted relative risk, 2.22 [95% confidence interval, 1.94-2.50]) and donor cycles (relative risk, 1.91 [95% confidence interval, 1.81-2.02]). This shift toward single embryo transfer corresponded with a decrease in multiple embryo transfer by 79.2% and subsequent decreases in multiple gestations by 68.8% in donor and 73.6% in autologous oocyte cycles from 2014-2020. Gestational carrier cycles remained highly adherent to changing American Society of Reproductive Medicine guidelines throughout the study period. Among live births, there was a 19.4% and 7.9% increase in term deliveries among donor and autologous oocyte cycles, respectively, from 2014 to 2020., Conclusion: Practice patterns have drastically changed throughout the study period, with major increases in the use of preimplantation genetic testing for aneuploidy, intracytoplasmic sperm injection, assisted hatching, and frozen transfers. In response to changing American Society of Reproductive Medicine guidelines, the use of multiple embryo transfers has decreased for gestational carrier cycles with subsequent decreases in multiple gestations and miscarriages and slight increases in live birth rates., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Apolipoprotein E (APOE) is the most important precursor for the production of steroid hormones and is also involved in regulating the function of steroid hormones, hence playing a significant role in reproductive processes. So, APOE gene expression may be correlated with the implantation process. This study tries to make a better clarification of the correlation between APOE gene polymorphisms and recurrent implantation failure (RIF), where we compared the frequency of APOE polymorphisms in RIF patients, assisted reproductive treatment (ART) success cases and fertile women., Method: In all, 100 women with successful ART who got pregnant (fetal heart rate positive) in their first or second cycle of in vitro fertilization or intracytoplasmic sperm injection, 100 infertile RIF cases, and 100 normal fertile control cases with at least one live birth were included in present study. Following DNA extraction, genotypes were determined through polymerase chain reaction-restriction fragment length polymorphism method using HhaI restriction enzyme. Finally, statistical analysis was performed by chi-squared (χ 2 ) test in SPSS software (P < 0.05)., Results: The RIF group showed significantly higher frequency for E3/E4 genotype (29%) compared with the other two control groups (fertile = 15%, ART success [ART+] = 13%) (P = 0.007). There was also a significantly higher frequency of the E4 allele in the RIF group (14.5%) compared with both of the control groups (fertile = 7.5%, ART+ = 6.5%) (P = 0.018)., Conclusion: APOE4 is correlated with recurrent failure in the process of embryo implantation and, accordingly, it may potentially be considered a possible risk factor to the implantation process. The presence of E4 can be proposed as a predictive indicator in determining the results of assisted reproductive techniques., (© 2024 International Federation of Gynecology and Obstetrics.)

Purpose: The purpose of this study was to compare the efficacy of Follitropin alpha (Gonal-F) and Follitropin beta (Puregon) on cumulative live birth rate (CLBR), defined as the percentage of the number of patients who delivered for the first time in a single ovarian stimulation cycle and the number of patients in all oocyte retrieval cycles., Methods: A retrospective cohort study including 2864 infertile patients who underwent ovarian stimulation with Puregon (group A, n=1313) and Gonal-F (group B, n=1551) was conducted between July 2015 and June 2021 at a university-affiliated reproductive medicine center. Reduce potential confounding factors between groups, propensity scores and multivariable logistic regression analyses were estimated to obtain unbiased estimates of outcomes. The primary outcome was the difference in CLBR between the two groups., Results: Each group identified 1160 individuals after propensity score matching (PSM). Baseline characteristics were similar between groups after PSM. The total gonadotrophin (Gn) dose (2400 vs 2325), p=0.038) and cost of Gn usage (5327.9¥ vs 7547.2¥, p<0.001) between the Puregon and Gonal-F groups were statistically significant. Nevertheless, the pregnancy outcomes between the two groups were comparable after fresh embryo transfer and subsequent frozen-thawed embryo transfer. Additionally, there was also no difference observed in the primary outcome of CLBR (52.8% vs 55.7%, p=0.169). Multivariable regression analysis revealed that the type of Gn was not associated with CLBR (p = 0.912)., Conclusion: Gonal-F may be a reasonable option for infertile patients who are hesitant to receive more Gn dosage injections. Furthermore, Puregon can eliminate unneeded anxiety and expenses while also administering more flexibility. Taken together, these findings could well be utilized in everyday clinical practice to better inform patients when deciding on an ovarian stimulation strategy., Competing Interests: No potential conflict of interest was reported by the authors., (© 2024 Cao and Song.)

Objective: To investigate effect of preimplantation genetic testing for aneuploidies (PGT-A) on the reproductive outcomes of women of advanced maternal age (AMA) (≥38 years), and to analyze factors influencing the live birth rate in AMA women who have received PGT-A., Methods: A retrospective cohort study was conducted. AMA women undergoing PGT-A were enrolled in the PGT-A group. All of them underwent their first oocyte retrieval cycle between January 2019 and June 2023. AMA women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) and their first oocyte retrieval cycle over the same period of time were enrolled in the control group (the non-PGT-A group) via propensity score matching. The PGT-A group and the non-PGT-A group each included 193 cycles, which were followed up until January 2024. Follow-up concerning live births was completed for all oocyte retrieval cycles conducted between January 2019 and October 2022. The reproductive outcomes were compared between the two groups. The primary outcome indicator was cumulative live birth rate (CLBR) per oocyte retrieval, while the secondary outcome indicators were cumulative clinical pregnancy rate (CCPR) per oocyte retrieval and spontaneous abortion rate. For the 145 cycles in the PGT-A group with completed live birth follow-up, binary logistic regression analysis and receiver operator characteristic (ROC) curves were used to analyze the influencing factors of live birth rates., Results: A total of 145 cycles in the PGT-A group and 161 cycles in the non-PGT-A group completed follow-up for live births. The CLBR per oocyte retrieval of the PGT-A group was 25.52% (37/145), while that of the non-PGT-A group was 28.50% (46/161), with no significant difference being observed between the two groups ( P <0.05). Of the 193 oocyte retrieval cycles in each group, 53 cycles in the PGT-A group and 72 cycles in the non-PGT-A group resulted in clinical pregnancies, with the difference in the CCPR per oocyte retrieval being statistically significant (27.46% vs. 37.31%, P <0.05). Concerning clinical pregnancies, the spontaneous abortion rate of the PGT-A group was lower than that of the non-PGT-A group, with the difference being statistically significant (7.55% vs. 25.00%, P <0.05). In AMA women who had undergone PGT-A for reproductive assistance, maternal age (odds ratio [OR]=0.786, 95% confidence interval [CI]: 0.635-0.973) and the antral follicle count (AFC) (OR=1.110, 95% CI: 1.013-1.216) were correlated with the outcome of live births outcome. The probability of live births decreased with increasing maternal age and decreasing AFC. When the female age was ≥42 years or when AFC≤8, the expected live birth outcome of PGT-A assisted pregnancy was poor., Conclusion: PGT-A does not affect the CLBR per oocyte retrieval in AMA women, but it can effectively reduce the risks of implantation failure and spontaneous abortion due to fetal aneuploidies. For PGT-A-assisted pregnancy in AMA women, maternal age and AFC are important factors affecting the live birth outcomes., Competing Interests: 利益冲突　所有作者均声明不存在利益冲突, (© 2024《四川大学学报（医学版）》编辑部 版权所有Copyright ©2024 Editorial Office of Journal of Sichuan University (Medical Sciences).)

Objective: To compare outcomes in patients with repeated implantation failure undergoing Intracytoplasmic Sperm Injection/In vitro fertilization (IVF/ICSI) plus immunosuppressants such as prednisolone, prednisone, or cyclosporine A versus the use of IVF/ICSI alone., Data Source: Databases were systematically searched in PubMed, Cochrane, and Embase databases in September 2023., Study Selection: Randomized clinical trials and observational studies with the outcomes of interest were included., Data Collect: We computed odds ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs). Heterogeneity was assessed using I 2 statistics. Data were analyzed using Review Manager 5.4.The main outcomes were live birth, miscarriage, implantation rate, clinical pregnancy, and biochemical pregnancy., Data Synthesis: Seven studies with 2,829 patients were included. Immunosuppressive treatments were used in 1,312 (46.37%). Cyclosporine A improved implantation rate (OR 1.48; 95% CI 1.01-2.18) and clinical pregnancy (1.89, 95% CI 1.14-3.14). Compared to non-immunosuppressive treatment, prednisolone and prednisone did not improve live birth (OR 1.13, 95% CI 0.88-1.46) and miscarriage (OR 1.49, 95% CI 1.07-2.09). Prednisolone showed no significant effect in patients undergoing IVF/ICSI, clinical pregnancy (OR 1.34; 95% CI 0.76-2.36), or implantation rate (OR 1.36; 95% CI 0.76-2.42)., Conclusion: Cyclosporine A may promote implantation and clinical pregnancy rates. However, given the limited sample size, it is important to approach these findings with caution. Our results indicate that prednisolone and prednisone do not have any beneficial effects on clinical outcomes of IVF/ICSI patients with repeated implantation failure., Prospero: CRD42023449655., Competing Interests: Conflicts to interest: none to declare.

In Brief: PLCZ1 mutations are related to total fertilisation failure (TFF) after intracytoplasmic sperm injection (ICSI), characterised by abnormal oocyte oscillations. The novel PLCZ1 compound heterozygous mutations reported by this study were associated with TFF after ICSI, with one of the mutations indicating a gene dosage effect., Abstract: Oocyte activation failure is thought to be one of the main factors for total fertilisation failure (TFF) after intracytoplasmic sperm injection (ICSI), which could be induced by abnormal calcium oscillations. Phospholipase C zeta (PLCZ), a sperm factor, is associated with Ca2+ oscillations in mammalian oocytes. To date, some mutations in PLCZ1 (the gene that encodes PLCZ) have been linked to TFF, as demonstrated by the observed reduction in protein levels or activity to induce Ca2+ oscillations. In this study, normozoospermic males whose sperms exhibited TFF after ICSI and their families were recruited. First, mutations in the PLCZ1 sequence were identified by whole exome sequencing and validated using Sanger sequencing. Then, the locations of PLCZ1/PLCZ and the transcript and protein levels in the sperm of the patients were studied. Subsequently, in vitro function analysis and in silico analysis were performed to investigate the function-structure correlation of mutations identified in PLCZ1 using western blotting, immunofluorescence, RT-qPCR, and molecular simulation. Ca2+ oscillations were detected after cRNA microinjection into MII mouse oocytes to investigate calcium oscillations induced by abnormal PLCZ. Five variants with compound heterozygosity were identified, consisting of five new mutations and three previously reported mutations distributed across the main domains of PLCZ, except the EF hands domain. The transcript and protein levels decreased to varying degrees among all detected mutations in PLCZ1 when transfected in HEK293T cells. Among these, mutations in M138V and R391* of PLCZ were unable to trigger typical Ca2+ oscillations. In case 5, aberrant localisation of PLCZ in the sperm head and an increased expression of PLCZ in the sperm were observed. In conclusion, this study enhances the potential for genetic diagnosis of TFF in clinics and elucidates the possible relationship between the function and structure of PLCZ in novel mutations.

Purpose: In this systematic review and meta-analysis, we investigated assisted reproductive technology (ART) success in infertile men with clinical varicocele and abnormal semen parameters who underwent varicocele repair (VR) before the ART procedure as compared to those who did not., Materials and Methods: A comprehensive search of the Scopus, PubMed, Embase, and Cochrane Library databases was conducted using a specific query string to identify studies examining the impact of VR on ART outcomes, including fertilization rate, clinical pregnancy, pregnancy loss, and live-birth rate, until October 2023. Outcomes were analyzed based on the type of ART. Studies on VR in infertile men with non-obstructive azoospermia and those who underwent ART only due to female factor infertility were excluded from the study., Results: Out of 1,554 articles reviewed, only 9 met the inclusion criteria for the study. All the included articles were observational studies. The variability in study quality in the included literature resulted in a moderate overall risk of bias. Data analysis showed that for intrauterine insemination, there was no difference in the clinical pregnancy rate (odds ratio [OR] 1.01, 95% confidence interval [CI]: 0.42, 2.45; p=0.97). However, for intracytoplasmic sperm injection (ICSI), men with VR showed a significant improvement in fertilization rate (mean difference 10.9, 95% CI: 5.94, 15.89; p<0.01), clinical pregnancy rate (OR 1.38, 95% CI: 1.07, 1.78; p=0.01) and live-birth rate (OR 2.07, 95% CI: 1.45, 2.97; p<0.01), compared to men who did not undergo VR., Conclusions: The findings of this systematic review and meta-analysis suggest that VR has a positive impact on pregnancy and live birth rates after ICSI. However, biases like small sample sizes and heterogeneous populations highlight the need for larger, well-designed prospective studies to validate these findings., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Assisted reproductive technologies are an emerging field in equine reproduction, with species-dependent peculiarities, such as the low success rate of conventional IVF. Here, the 'cumulome' was related to the developmental capacity of its corresponding oocyte. Cumulus-oocyte complexes collected from slaughterhouse ovaries were individually matured, fertilized by ICSI, and cultured. After maturation, the cumulus was collected for proteomics analysis using label-free mass spectrometry (MS)-based protein profiling by nano-HPLC MS/MS and metabolomics analysis by UPLC-nanoESI MS. Overall, a total of 1671 proteins and 612 metabolites were included in the quantifiable 'cumulome'. According to the development of the corresponding oocytes, three groups were compared with each other: not matured (NM; n = 18), cleaved (CV; n = 15), and blastocyst (BL; n = 19). CV and BL were also analyzed together as the matured group (M; n = 34). The dataset revealed a closer connection within the two M groups and a more distinct separation from the NM group. Overrepresentation analysis detected enrichments related to energy metabolism as well as vesicular transport in the M group. Functional enrichment analysis found only the KEGG pathway 'oxidative phosphorylation' as significantly enriched in the NM group. A compound attributed to ATP was observed with significantly higher concentrations in the BL group compared with the NM group. Finally, in the NM group, proteins related to degradation of glycosaminoglycans were lower and components of cumulus extracellular matrix were higher compared to the other groups. In summary, the study revealed novel pathways associated with the maturational and developmental competence of oocytes., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Background: Bi-allelic variants in DNAH11 have been identified as causative factors in Primary Ciliary Dyskinesia, leading to abnormal respiratory cilia. Nonetheless, the specific impact of these variants on human sperm flagellar and their involvement in male infertility remain largely unknown., Methods: A collaborative effort involving two Chinese reproductive centers conducted a study with 975 unrelated infertile men. Whole-exome sequencing was employed for variant screening, and Sanger sequencing confirmed the identified variants. Morphological and ultrastructural analyses of sperm were conducted using Scanning Electron Microscopy and Transmission Electron Microscopy. Western Blot Analysis and Immunofluorescence Analysis were utilized to assess protein levels and localization. ICSI was performed to evaluate its efficacy in achieving favorable pregnancy outcomes for individuals with DNAH11 variants., Results: In this study, we identified seven novel variants in the DNAH11 gene in four asthenoteratozoospermia subjects. These variants led the absence of DNAH11 proteins and ultrastructure defects in sperm flagella, particularly affecting the outer dynein arms (ODAs) and adjacent structures. The levels of ODA protein DNAI2 and axoneme related proteins were down regulated, instead of inner dynein arms (IDA) proteins DNAH1 and DNAH6. Two out of four individuals with DNAH11 variants achieved clinical pregnancies through ICSI. The findings confirm the association between male infertility and bi-allelic deleterious variants in DNAH11, resulting in the aberrant assembly of sperm flagella and contributing to asthenoteratozoospermia. Importantly, ICSI emerges as an effective intervention for overcoming reproductive challenges caused by DNAH11 gene variants., (© 2024. The Author(s).)

Background: Overweight women undergoing IVF treatment have lower success rates. Letrozole, an aromatase inhibitor, has been used as an adjunct for IVF treatment, but its specific effects in overweight women have not been investigated. This study was to explore the effects of letrozole co-treatment in an antagonist protocol for overweight infertile women undergoing IVF treatment., Methods: This retrospective cohort study included overweight infertile women who underwent IVF/ICSI treatment and fresh embryo transfer (ET), with or without letrozole co-treatment in an antagonist protocol, from 2007 to 2021 at Shanghai Ninth People's Hospital (Shanghai, China). A total of 704 overweight infertile women were included: 585 women were in the antagonist group, and 119 women were in the letrozole co-treatment group. The primary outcome was the live birth rate after fresh ET. Propensity score-based patient-matching was employed to balance the covariates between the groups. Multivariate logistic regression analysis was also performed to estimate odds ratio (OR) and 95% confidence interval (CI) for association of letrozole co-treatment and the live birth outcome., Results: Letrozole co-treatment induced significant changes in hormonal profile on the trigger day. The letrozole group exhibited a decrease in the total number of follicles compared to the antagonist group, but a higher proportion of large follicles at oocyte retrieval (P < 0.05). The quantity and quality of embryos were comparable between the two groups (P > 0.05). The letrozole co-treatment group had a significantly higher live birth rate than the control group (38.7% vs. 22.6%, P = 0.026). With multivariate logistic regression analysis, letrozole co-treatment was associated with higher odds of live birth after adjusting for potential confounding factors (adjusted OR = 2.00, 95% CI = 1.17-3.39, P = 0.011). Letrozole presented no significant associations with obstetrical or neonatal complications (P > 0.05)., Conclusion: Letrozole co-treatment in an antagonist protocol may offer potential benefits for overweight infertile women undergoing IVF treatment. Further research is warranted to validate these findings and explore the broader implications for letrozole co-treatment., (© 2024. The Author(s).)

Purpose: Surgical sperm retrieval (SSR) is used to extract spermatozoa for use with intracytoplasmic sperm injection in men with obstructive and non-obstructive azoospermia (NOA). The procedure may lead to segmental devascularization, postoperative fibrosis, and atrophy with a subsequent decrease in testosterone. The aim of the study is to investigate the impact of SSR on serum levels of total testosterone (TT), follicle-stimulating hormone (FSH), luteinizing hormone (LH) testicular volume, and sexual function in infertile azoospermic men., Materials and Methods: In this systematic review and meta-analysis (SRMA), we searched articles in "PubMed" and "Scopus" exploring the impact of SSR on TT, FSH, LH, and testicular volume. The full-text articles were screened to assess eligibility before data extraction, quality assessment, and meta-analysis., Results: Seventeen studies meeting the inclusion criteria were finally analyzed and included 1,685 infertile, azoospermic men. Patients underwent SSR and were followed in the postoperative period (one week to 32 months). The analysis showed a significant reduction in TT (mean difference [MD] 3.81 nmol/L, 95% confidence interval [CI] 0.55:7.06; p=0.02) compared to pre-SSR values. We also observed insignificant differences in serum FSH (MD 5.08 IU/L, 95% CI -5.6:15.8; p=0.35), LH (MD -2.96 IU/L, 95% CI -6.31:0.39; p=0.08), and no change in testicular volume (MD 0.07 mL, 95% CI -1.92:2.07; p=0.94) after SSR. Sexual dysfunction was associated with hypogonadism, depression, and anxiety, especially in men with unsuccessful SSR and Klinefelter syndrome., Conclusions: The results of this SRMA indicate a significant reduction in TT after SSR. Sexual dysfunction after testicular sperm extraction and the potential negative impact of future SSR repeat should be considered during preoperative counseling., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Purpose: To compare differences in euploidy rates for blastocysts in preimplantation genetic testing for aneuploidy (PGT-A) cycles after gonadotropin-releasing hormone agonist (GnRH-a) long and short protocols, GnRH-antagonist (GnRH-ant) protocol, progestin-primed ovarian stimulation and mild stimulation protocols, and other ovary stimulation protocols., Methods: This was a retrospective cohort study from the Assisted Reproductive Medicine Department of Shanghai First Maternity and Infant Hospital. A total of 1657 PGT-A cycles with intracytoplasmic sperm injection after different controlled ovary hyperstimulation protocols were analyzed, and a total of 3154 embryos were biopsied. Differences in euploidy rate per embryo biopsied, embryo euploidy rate per oocyte retrieved and cycle cancellation rate were compared., Results: For the PGT-A cycles, the euploidy rate per embryo biopsied was lower in the GnRH-ant protocol than in the GnRH-a long protocol (53.26 vs. 58.68%, respectively). Multiple linear regression showed that the GnRH-ant protocol was associated with a lower euploidy rate per embryo biopsied (β =  -0.079, p = 0.011). The euploidy rate per embryo biopsied was not affected by total gonadotropin dosage, duration of stimulation and number of oocytes retrieved. The embryo euploidy rate per oocyte retrieved was similar in all protocols and was negatively correlated with the total number of oocytes retrieved (β =  -0.003, p = 0.003)., Conclusion: Compared with the GnRH-a long protocol, the GnRH-ant protocol was associated with a lower euploidy rate per embryo biopsied. The total gonadotropin dosage, duration of stimulation and number of oocytes retrieved did not appear to significantly influence euploidy rates., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Poor ovarian response (POR) is associated with decreased clinical pregnancy rates, emphasizing the need for developing clinical prediction models. Such models can improve prognostic accuracy, personalize medical interventions, and ultimately enhance live birth rates among patients with POR., Objective: This study aims to develop and validate a prognostic model for predicting clinical pregnancy outcomes in individuals with POR undergoing in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI) cycles., Methods: A retrospective cohort of 969 patients with POR undergoing fresh embryo transfer cycles at the Reproductive Center of Fujian Maternal and Child Health Center from January 2018 to January 2022 was included. The cohort was randomly divided into model (n = 678) and validation (n = 291) groups in a 7:3 ratio. A single-factor analysis was performed on the model group to identify variables influencing clinical pregnancy. Optimal variables were selected using LASSO regression, and a clinical prediction model was constructed using multivariate logistic regression analysis. The model's calibration and discrimination were assessed using receiver operating characteristic (ROC) and calibration curves, while the clinical utility was evaluated using decision curve analysis., Results: Multivariate logistic regression analysis revealed that the age of the women (odds ratio [OR] 0.936, 95% confidence interval [CI] 0.898-0.976, P = 0.002), body mass index (BMI) ≤ 24 (OR 2.748, 95% CI 1.724-4.492, P < 0.001), antral follicle count (AFC) (OR 1.232, 95% CI 1.073-1.416, P = 0.003), anti-Müllerian hormone (AMH) (OR 1.67, 95% CI 1.178-2.376, P = 0.004), number of mature oocytes (OR 1.227, 95% CI 1.075-1.403, P = 0.003), number of embryos transferred (OR 1.692, 95% CI 1.132-2.545, P = 0.011), and transfer of high-quality embryos (OR 3.452, 95% CI 1.548-8.842, P = 0.005) were independent predictors of clinical pregnancy in patients with POR. According to the receiver operating characteristic (ROC) analysis, the prediction model exhibited an area under the curve (AUC) of 0.752 (0.714, 0.789) in the model group and 0.765 (0.708, 0.821) in the validation group. The clinical decision curve demonstrated that the model held maximum clinical utility in both cohorts when the threshold probability of clinical pregnancy ranged from 6-81% to 12-82%, respectively., Conclusion: Clinical pregnancy outcomes in patients with POR who underwent IVF/ICSI treatment were influenced by several independent factors, including the age of the women, BMI, AFC, AMH, number of mature oocytes, number of embryos transferred, and transfer of high-quality embryos. A clinical prediction model based on these factors exhibited favorable clinical predictive and applicative value. Therefore, this model can serve as a valuable tool for clinical prognosis, intervention, and facilitating personalized medical treatment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The study aims to elucidate the impacts of different types of male chromosomal polymorphisms (MCPs) on various outcomes of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) treatment., Methods: This retrospective cohort study included 1442 couples with normal karyotypes, 1442 couples with MCPs, 42 couples with male chromosomal rearrangements (MCRs), and 42 couples with MCRs combined with MCPs who underwent IVF/ICSI treatment at Peking University Third Hospital from 2015 to 2021. The semen quality, embryological outcomes, and clinical outcomes of different groups stratified by karyotypes were compared., Results: For couples undergoing IVF, male inv(9) was associated with a significantly lower sperm viability rate (29.41% vs 34.49%, P = 0.030), a lower progressive motility rate (25.13% vs 30.50%, P = 0.013), and a lower normal fertilization rate (52.41% vs 59.84%, P = 0.014). Male 9qh + was related to a lower sperm viability rate (27.56% vs 34.49%, P = 0.028). No MCPs were observed to compromise clinical outcomes in couples undergoing IVF. For couples undergoing ICSI, no MCPs exhibited an association with poorer semen quality and embryological outcomes. However, Yqh + and DGpstk+ were found to be significantly correlated with an increased likelihood of preterm birth (23.3% vs 9.2%, P = 0.003; 20.0% vs 9.2%, P = 0.041, respectively). In couples with MCRs, the presence of MCPs significantly reduced the sperm viability rate (19.99% vs 30.97%, P = 0.017) and progressive motility rate (8.07% vs 27.85%, P = 0.018)., Conclusion: Our study provides detailed evidence for the impacts of various MCPs on IVF/ICSI outcomes, reveals the complexity and heterogeneity of these impacts, and highlights the adverse effects of male inv(9)., (© 2024 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

This systematic review and meta-analysis aimed to evaluate the impact of ovarian endometriomas (OMA) on indirect markers of oocyte quality in patients undergoing IVF, compared with women without anatomical or functional ovarian abnormalities. The search spanned original randomized controlled trials, case-control studies and cohort studies published in MEDLINE, the Cochrane Controlled Trials Register and the ClinicalTrials.gov database up to October 2023. Thirty-one studies were included in the meta-analysis, showing no significant differences in fertilization (OR 1.10, 95% CI 0.94-1.30), blastulation (OR 0.86, 95% CI 0.64-1.14) and cancellation (OR 1.06, 95% CI 0.78-1.44) rates. However, patients with OMA exhibited significantly lower numbers of total and mature (metaphase II) oocytes retrieved (mean difference -1.59, 95% CI -2.25 to -0.94; mean difference -1.86, 95% CI -2.46 to -1.26, respectively), and lower numbers of top-quality embryos (mean difference -0.49, 95% CI -0.92 to -0.06). The Ovarian Sensitivity Index was similar between the groups (mean difference -1.55, 95% CI -3.27 to 0.18). The lack of data published to date prevented meta-analysis on euploidy rate. In conclusion, although the presence of OMA could decrease the oocyte yield in patients undergoing IVF/intracytoplasmic sperm injection, it does not appear to have an adverse impact on oocyte quality., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: Is acrosin activity related to cumulative live birth rate (CLBR) over 1 year after IVF, intracytoplasmic sperm injection (ICSI) treatment or both?, Design: Retrospective monocentric cohort study of 5704 couples who started IVF/ICSI treatments between 2016 and 2021. Acrosin activity was determined by a modified Kennedy method using a commercial kit. Patients were divided into two groups according to their acrosin activity: below 25 μIU/10 6 spermatozoa; and an acrosin activity 25 μIU/10 6 spermatozoa or above. Primary outcome was the CLBR, defined as an ongoing pregnancy leading to live birth that had arisen from all embryo transfers carried out within 1 year after the first ovum retrieval. Both conservative and optimistic methods were used for estimating CLBRs., Results: The CLBRs of patients with an acrosin activity below 25 μIU/10 6 spermatozoa were found to be significantly lower than those of patients with an acrosin activity 25 μIU/10 6 spermatozoa or above by conservative (48.5% versus 55.4%, P = 0.02) and optimistic (63.7% versus 70.3%, P = 0.047) methods after adjusting for confounders. When acrosin activity was regarded as a continuous variable, significant negative relationships between acrosin activity and CLBR were identified in subgroups: young couples (men and women aged younger than 30 years) and couples from whom no more than 10 eggs were retrieved., Conclusion: Low acrosin activity levels were correlated with decreasing CLBRs over 1 year. These findings suggest that acrosin activity can be used as a predictor for CLBRs before starting IVF/ICSI treatment to enhance the effectiveness of counselling., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Preimplantation genetic testing (PGT) involves taking a biopsy of an early embryo created through in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). Genetic testing is performed on the biopsy, in order to select which embryo to transfer. PGT began as an experimental procedure in the 1990s, but is now an integral part of assisted human reproduction (AHR). PGT allows for embryo selection which can reduce the risk of transmission of inherited disease and may reduce the chance of implantation failure and pregnancy loss. This is a rapidly evolving area, which raises important ethical issues. This review article aims to give a brief history of PGT, an overview of the current evidence in PGT along with highlighting exciting areas of research to advance this technology., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To investigate the relationship between anti-Müllerian hormone (AMH) level and early pregnancy loss in patients who underwent their first embryo transfer by hormone replacement therapy-frozen-thawed embryo transfer (HRT-FET) and analyze the threshold effect., Methods: A retrospective cohort analysis was performed on pregnant women undergoing HRT-FET at the Reproductive Medical Center of Henan Provincial People's Hospital from January 2016 to December 2021. The patients were divided into four groups based on AMH concentration according to the Poseidon criteria: group A (≤1 μg/L), group B (1-≤2 μg/L), group C (2-≤6 μg/L), and group D (>6 μg/L). Univariate analysis, multivariate logistic regression analysis, smooth curve fitting, and threshold effect analysis were applied to investigate the influence of AMH on the outcome of early pregnancy loss in in vitro fertilization/intracytoplasmic sperm injection and HRT-FET cycles., Results: Of the 6597 pregnant women, early pregnancy loss occurred in 893, giving an early pregnancy loss rate of 13.54%. Univariate regression analysis demonstrated that age, female body mass index, AMH, antral follicle count, endometrial thickness at endometrial transformation day, total retrieved oocyte number, number of pregnancies, duration of infertility, type of infertility, and the number of embryos transferred were all factors influencing the early pregnancy loss rate (P < 0.050). Multivariate logistic regression analysis, after adjusting for confounders, further stratified the analysis of patients of different ages. With group A as the control group, the results showed that when age was younger than 35 years, the pregnancy loss rates in groups B, C, and D were lower than that in group A, with statistical significance (P < 0.050); when age was 35 years or older, there was no statistically significant difference in outcome indicators between the groups (P > 0.050). A threshold effect analysis revealed that the AMH threshold was 2.83 μg/L. When the AMH concentration was less than 2.83 μg/L, the early pregnancy loss rate decreased significantly with increasing AMH concentration; the early pregnancy loss rate decreased by 21% for each unit increase in AMH (odds ratio 0.79; 95% confidence interval 0.71-0.88; P < 0.001); when the AMH concentration was 2.83 μg/L or more, there was no statistical difference in the change in early pregnancy loss rate (odds ratio 1.01; 95% confidence interval 0.99-1.03; P = 0.383)., Conclusion: For pregnant women after their first embryo transfer, there is a curvilinear relationship between the influences of AMH levels on early pregnancy loss rates in patients younger than 35 years. When the AMH level was less than 2.83 μg/L, the early pregnancy loss rate declined significantly with increasing AMH levels., (© 2024 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Background: In vitro fertilisation is a widely used reproductive technique that can be undertaken with or without intracytoplasmic sperm injection. The endometrial scratch procedure is an in vitro fertilisation ‘add-on’ that is sometimes provided prior to the first in vitro fertilisation cycle, but there is a lack of evidence to support its use. Objectives: (1) To assess the clinical effectiveness, safety and cost-effectiveness of endometrial scratch compared with treatment as usual in women undergoing their first in vitro fertilisation cycle (the ‘Endometrial Scratch Trial’) and (2) to undertake a systematic review to combine the results of the Endometrial Scratch Trial with those of previous trials in which endometrial scratch was provided prior to the first in vitro fertilisation cycle. Design: A pragmatic, multicentre, superiority, open-label, parallel-group, individually randomised controlled trial. Participants were randomised (1 : 1) via a web-based system to receive endometrial scratch or treatment as usual using stratified block randomisation. The systematic review involved searching electronic databases (undertaken in January 2020) and clinicaltrials.gov (undertaken in September 2020) for relevant trials. Setting: Sixteen UK fertility units. Participants: Women aged 18–37 years, inclusive, undergoing their first in vitro fertilisation cycle. The exclusion criteria included severe endometriosis, body mass index ≥ 35 kg/m2 and previous trauma to the endometrium. Interventions: Endometrial scratch was undertaken in the mid-luteal phase of the menstrual cycle prior to in vitro fertilisation, and involved inserting a pipelle into the cavity of the uterus and rotating and withdrawing it three or four times. The endometrial scratch group then received usual in vitro fertilisation treatment. The treatment-as-usual group received usual in vitro fertilisation only. Main outcome measures: The primary outcome was live birth after completion of 24 weeks’ gestation within 10.5 months of egg collection. Secondary outcomes included implantation, pregnancy, ectopic pregnancy, miscarriage, pain and tolerability of the procedure, adverse events and treatment costs. Results: One thousand and forty-eight (30.3%) women were randomised to treatment as usual (n = 525) or endometrial scratch (n = 523) and were followed up between July 2016 and October 2019 and included in the intention-to-treat analysis. In the endometrial scratch group, 453 (86.6%) women received the endometrial scratch procedure. A total of 494 (94.1%) women in the treatment-as-usual group and 497 (95.0%) women in the endometrial scratch group underwent in vitro fertilisation. The live birth rate was 37.1% (195/525) in the treatment-as-usual group and 38.6% (202/523) in the endometrial scratch group: an unadjusted absolute difference of 1.5% (95% confidence interval –4.4% to 7.4%; p = 0.621). There were no statistically significant differences in secondary outcomes. Safety events were comparable across groups. No neonatal deaths were recorded. The cost per successful live birth was £11.90 per woman (95% confidence interval –£134 to £127). The pooled results of this trial and of eight similar trials found no evidence of a significant effect of endometrial scratch in increasing live birth rate (odds ratio 1.03, 95% confidence interval 0.87 to 1.22). Limitations: A sham endometrial scratch procedure was not undertaken, but it is unlikely that doing so would have influenced the results, as objective fertility outcomes were used. A total of 9.2% of women randomised to receive endometrial scratch did not undergo the procedure, which may have slightly diluted the treatment effect. Conclusions: We found no evidence to support the theory that performing endometrial scratch in the mid-luteal phase in women undergoing their first in vitro fertilisation cycle significantly improves live birth rate, although the procedure was well tolerated and safe. We recommend that endometrial scratch is not undertaken in this population. Trial registration: This trial is registered as ISRCTN23800982. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 10. See the NIHR Journals Library website for further project information.

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Objective: To investigate the social capital and depression status in women undergoing in vitro fertilization/intracytoplasmic sperm injection -embryo transfer (IVF/ICSI -ET), and to analyze their relationship. Methods: 104 female patients were selected from the Reproductive Medicine Center of the First Affiliated Hospital of Anhui Medical University, who are planned the IVF/ICSI -ET treatment from December 2020 to February 2021. After the patients were trained in answering, the patients should answer the questions by themselves. The PHQ-9 scale was used to assess depression, and the "position generation method" was used to measure the social capital of patients′ strong social network. Use multiple linear regression to analyze the relationship between the social capital and depression status. Results: The median of treatment duration was 2 years in those women undergoing IVF/ICSI-ET treatment. The median of PHQ-9 score was 16.00, P25 and P75 scores were 15.00 and 18.00, and the self-reported depression symptoms rate was 52.9% (55/104). Our study defined strong social networks as spouse and relatives. The occupational value of the spouse (Median, 73.5 points) and the occupational accessibility of relatives (Median, 79 points) were associated with the increased depression level of those women undergoing IVF/ICSI treatment. Conclusions: The high social position of the strong social network of women undergoing assisted reproductive treatment is a risk factor of depression for these women. The targeted psychological interventions should be carried out to improve the quality of both fertility and life of these women and their families. [ABSTRACT FROM AUTHOR]

Non-obstructive azoospermia (NOA) is the most severe form of male factor infertility. It results form from either primary or secondary testicular failure. Here, we report cases of two patients with NOA due to maturation arrest and increased serum FSH, treated with GnRH agonist and gonadotrophins. The two NOA patients underwent a pharmacological treatment consisting of pituitary desensibilization using a GnRH agonist and testicular stimulation using menotropin. Testicular stimulation started one month after the beginning of GnRH agonist treatment. The female partner underwent controlled ovarian stimulation (COS) followed by intracytoplasmic sperm injection (ICSI). On the third day of the cycle, menotropin daily doses was administered. When at least one follicle ≥14 mm was visualized, pituitary blockage was performed using GnRH antagonist ganirelix. When three or more follicles attained a mean diameter of ≥17 mm, triptorelin acetate was administered to trigger final follicular maturation. Oocyte retrieval was performed 35 hours later. After treatment, male partner blood levels of the FSH, LH, decreased and total testosterone were increased. Spermatozoa was observed after semen collection in both cases. After COS, oocytes were retrieved and ICSI was performed. Embryos were biopsied for preimplantation genetic testing (PGT) and those considered euploidy were transferred resulting in positive implantation, ongoing pregnancy, and livebirth on both cases. In this report we present a successful strategy for hypergonadotropic hypogonadism AOA men, as an alternative approach to the surgical testicular sperm recovery. Nevertheless, prospective randomized trials are needed to confirm our findings.

Objective: To construct a repetitive implantation failure (RIF)-related competitive endogenous RNA (ceRNA) regulatory network and validate with clinical samples. Methods: RIF-related long non-coding RNA (lncRNA), microRNA (miRNA) and messenger RNA (mRNA) from the high-throughput gene expression omnibus (GEO) database Expression profile data set were obtained to construct a ceRNA regulatory network of lncRNA-miRNA-mRNA. At the same time, weighted gene co-expression network analysis (WGCNA) was used to explore hub genes in the network. This retrospective study collected RIF patients and controls (at least one pregnancy history after assisted conception) who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) for assisted pregnancy from 2020 to 2021 at the Reproductive Medicine Center of the First Affiliated Hospital of Zhengzhou University. In the endometrial tissue of patients with 1 pregnancy history, real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to verify the mRNA expression levels of RIF-related hub genes, and Western blotting and immunohistochemistry were used to verify protein expression levels of vascular cell adhesion molecule-1 (VCAM1). Results: A RIF-related ceRNA regulatory network consisting of 32 lncRNAs, 31 miRNAs and 88 mRNAs was constructed, and 7 RIF-related hub genes were identified using WGCNA. By intersecting 88 mRNAs and hub genes in the ceRNA network, two RIF-related key genes were obtained, i.e., VCAM1 and interleukin-2 receptor α (interleukin-2 receptor α, IL-2RA). In clinical verification, the ages of the control group and RIF group [ M ( Q 1 , Q 3 )] were 26.50 (25.00, 34.00) and 30.50 (25.75, 35.25) years old, respectively ( P >0.05). Compared with the control group, the mRNA [0.30 (0.15, 0.42) vs 0.99 (0.69, 1.34), P =0.001] and protein expression [0.44 (0.16, 1.27) vs 2.39 (1.58, 2.58), P <0.001] of VCAM1 in the endometrium of the RIF group were both reduced. Conclusions: This study uses bioinformatics analysis methods to construct a RIF-related ceRNA regulatory network, and it is confirmed through clinical samples that the expression level of VCAM1 in the endometrial tissue of RIF patients is significantly reduced.

Background: Genetic abnormalities like Y chromosome microdeletions are implicated in male infertility. This study investigated the association of azoospermia factor (AZF) region microdeletions with unsuccessful assisted reproductive techniques (ART), including in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI)., Methods: This cross-sectional analysis study examined 80 Iranian oligospermic men (mean age 34 years) with prior failed ICSI and IVF cycles (IR.IAU.TNB.REC.1401.041). Semen analysis evaluated quantity/quality parameters based on World Health Organization guidelines. Participants were stratified by sperm DNA fragmentation (SDF) levels into: control (SDF < 15%, n = 20), mild elevation (15% ≤ SDF ≤ 30%, n = 60), and high (SDF > 30%, n = 20). Multiplex PCR mapped AZF microdeletions in the high SDF group. The AZF-associated genes were selected by RNA Seq analysis, and the candidate genes were checked for expression level by real-time PCR., Results: High SDF individuals exhibited poorer semen metrics, including 69% lower sperm concentration (P = 0.04) than those without SDF. Of this subset, 45% (9/20 men) harboured predominately AZF microdeletions. Men with AZF microdeletions showed higher SDF (32% vs 21%, P = 0.02) and altered AZF-associated genes expression. As USP9Y 3-fold, UTY 1.3-fold, and BPY2 1-fold revealed up-regulation, while IQCF1 8-fold, CDY 6.5-fold, DAZ 6-fold, and DDX3Y 1-fold underwent down-regulation. The PAWP gene was also down-regulated (5.7-fold, P = 0.029) in the IVF/ICSI failure group., Conclusion: AZF microdeletions significantly impact male infertility and ART outcomes. High SDF individuals exhibited poorer semen metrics, with 45% AZF microdeletions. These microdeletions altered AZF-associated genes expression, affecting fertility mediator PAWP independently. Dual AZF and SDF screening enables personalized management in severe male infertility, potentially explaining IVF/ICSI failures., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Non-invasive chromosome screening (NICS) and trophectoderm biopsy preimplantation genetic testing for aneuploidy (TE-PGT) were both applied for embryo ploidy detection, However, the cumulative live birth rates (CLBR) of NICS and TE-PGT in older age groups have yet to be reported. This study aimed to ascertain whether NICS and TE-PGT could enhance the cumulative live birth rates among patients of advanced maternal age., Methods: A total of 384 couples aged 35-40 years were recruited. The patients were assigned to three groups: NICS, TE-PGT, and intracytoplasmic sperm injection (ICSI). All patients received frozen single blastocyst transfer. Patients in the NICS and TE-PGT groups underwent aneuploidy screening., Results: When compared to the ICSI group, the CLBR was significantly higher in the NICS and TE-PGT groups (27.9% vs. 44.9% vs. 51.0%, p = 0.003 for NICS vs. ICSI, p < 0.001 for TE-PGT vs. ICSI). There were no significant differences in the clinical outcomes between the NICS and TE-PGT groups. Adjusting for confounding factors, the NICS and TE-PGT groups still showed a higher CLBR than the ICSI group (adjusted odds ratio (OR) 3.847, 95% confidence interval (CI) 1.939 to 7.634; adjusted OR 3.795, 95% CI 1.981 to 7.270). Additionally, the cumulative pregnancy loss rates of the NICS and TE-PGT groups were significantly lower than that of the ICSI group (adjusted OR 0.277, 95% CI 0.087 to 0.885; adjusted OR 0.182, 95% CI 0.048 to 0.693). There was no significant difference in the birth weights of the three groups (p = 0.108)., Conclusions: In women 35-40 years old, the CLBR can be increased by selecting euploid embryos using NICS and TE-PGT. For elderly women at high risk of embryonic aneuploidy, NICS, characterized by its safety and non-invasive nature, may emerge as an alternative option for preimplantation genetic testing., (© 2024. The Author(s).)

For the intracytoplasmic sperm injection (ICSI) procedure in pigs, an electrical pulse (EP) has been used as an effective method for oocyte stimulation, but unlike sperm, EP is unable to induce Ca 2+ oscillations. In this study, we investigated the effects of generating artificial Ca 2+ oscillations with phospholipase Cζ (PLCζ) mRNA, a candidate sperm factor, on fertilization, embryonic development, and gene expression after ICSI. Firstly, the concentration of PLCζ mRNA of a fixed volume (1.0 pl) that would induce a pattern of Ca 2+ rise similar to that of in vitro fertilized (IVF) sperm was examined and determined to be 300 ng/μl. Secondly, the effects of oocyte stimulation methods on fertilization and embryonic development were investigated. ICSI-oocytes were activated by EP (EP group) or by PLCζ mRNA (PLCζ group). Furthermore, IVF-oocytes (IVF group) and ICSI-oocytes with and without an injection of buffer (buffer and untreated groups, respectively) were used as controls. It was found that the rates of normal fertilization in the PLCζ and EP groups were significantly higher than those in the buffer and untreated groups. The blastocyst formation rates did not differ among the groups. The embryo quality in the EP group was inferior to those in the PLCζ and IVF groups. Additionally, the expression level of a proapoptosis-related gene (Caspase-3) in the EP group was significantly higher than those in the PLCζ and IVF groups. Our data suggest that oocyte activation by PLCζ mRNA has the effect of improving embryo quality.