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Background: Due to the specific nature of interstitial pregnancy (IP), there are significant risks to both the mother and the foetus in women with a heterotopic interstitial pregnancy (HIP). IP alone has been analysed as a site-specific ectopic pregnancy (EP) in previous studies; however, according to the latest European Society of Human Reproduction and Embryology criteria, IP is classified as a tubal pregnancy. If IP can be classified as a tubal pregnancy, then there is no difference in the effects of these two methods on intrauterine pregnancies (IUPs). Under the premise of timely surgery, disposing of IPs and tubal pregnancy (excluding IPs) should also have no differential effect on IUPs., Methods: Patients with heterotopic fallopian tubal pregnancy (HP-tube) and HIP seen at our hospital from January 2005 to December 2020 were included. All included patients were diagnosed by transvaginal sonography (TVS), and EPs were confirmed by surgery and pathological analysis. The IUP outcomes after surgical treatment of the EPs were compared between the HP-tube group (n = 464) and the HIP group (n = 206). The outcomes of IUPs were evaluated in patients with HIP who underwent either laparoscopy (169 cases) or laparotomy (36 cases)., Results: There was no significant difference in postoperative miscarriage (6.90% vs. 6.80%, odds ratio (OR) = 1.859, 95% confidence interval (CI) (0.807-4.279), p = 0.145); early spontaneous miscarriage (19.61% vs. 18.93%, OR = 0.788, 95% CI (0.495-1.255), p = 0.316); or late miscarriage (0.43% vs. 0.49%, OR = 0.823, 95% CI (0.070-9.661), p = 0.877) between the HP-tube group and the HIP group. There was no significant difference between the two groups in terms of preterm birth (7.33% vs. 6.80%, OR = 1.044, 95% CI (0.509-2.139), p = 0.907), live birth rate (71.60% vs. 73.30%, OR = 1.010, 95% CI (0.670-1.530), p = 0.980), or perinatal mortality rate (2.00% vs. 0.65%, OR = 0.580, 95% CI (0.030-3.590), p = 0.620). Compared to laparotomy for HIPs, laparoscopic treatment was associated with similar rates of postoperative miscarriage (5.33% vs. 13.90%, p = 0.076), live birth rate (72.80% vs. 75.00%, p = 0.948), caesarean Sect. (83.90% vs. 77.80%, p = 0.414)., Conclusions: After early diagnosis and treatment of EPs, patients in the HP-tube and HIP groups achieved comparable outcomes. Laparotomy and laparoscopy for treating HIPs yielded similar pregnancy outcomes., Competing Interests: Declarations Ethics approval and consent to participate This study was approved by the Ethics Committee of CITIC Xiangya Reproductive and Genetic Hospital (Changsha, People’s Republic of China, LL-SC-2023-016). All methods were carried out in accordance with relevant guidelines and regulations, such as the Declaration of Helsinki. The need for informed consent was waived by the Ethics Committee of CITIC Xiangya Reproductive and Genetic Hospital because of the retrospective nature of the study. 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.

An improved understanding of the cfDNA fragmentomics has proved it as a promising biomarker in clinical applications. However, biological characteristics of cfDNA in spent embryos culture medium (SECM) remain unsolved obstacles before the application in non-invasive in-vitro embryo selection. In this study, we developed a Tn5 transposase and ligase integrated dual-library construction sequencing strategy (TDual-Seq) and revealed the fragmentomic profile of cfDNA of all sizes in early embryonic development. The detected ratio of long cfDNA (>500 bp) was improved from 4.23 % by traditional NGS to 12.80 % by TDual-Seq. End motif analysis showed long cfDNA molecules have a more dominance of fragmentation intracellularly in apoptotic cells with higher predominance of G-end, while shorter cfDNA undergo fragmentation process both intracellularly and extracellularly. Moreover, the mutational pattern of cfDNA and the correlated GO biological process were well differentiated in cleavage and blastocyst embryos. Finally, we developed a multiparametric index (TQI) that employs the fragmentomic profiles of cfDNA, and achieved an area under the ROC curve of 0.927 in screening top quality embryos. TDual-Seq strategy has facilitated characterizing the fragmentomic profile of cfDNA of all sizes in SECM, which are served as a class of non-invasive biomarkers in the evaluation of embryo quality in in-vitro fertilization. And this improved strategy has opened up potential clinical utilities of long cfDNA analysis., 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.)

Objective: To investigate the effects of in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) on the clinical outcomes of non-male factor patients aged >35 with three or fewer oocytes retrieved., Design: Retrospective cohort study., Setting: Reproductive centre of a university-affiliated hospital in China., Participants: 547 women with non-male factor infertility who underwent assisted reproductive technology (ART) treatment with three or fewer oocytes retrieved were identified from June 2019 to May 2022. Of these 547 patients, 334 were treated with IVF and 213 with ICSI., Outcome Measures: The primary outcomes were normal fertilisation rate, live birth rate per transfer and cumulative live birth rate per retrieval., Results: The baseline characteristics were comparable between the two groups, except for the proportion of primary infertility, which was higher in the ICSI group (17.66% vs 32.86%, p=0.000). Compared with the IVF group, the ICSI group showed higher normal fertilisation rate and lower cycle cancellation rate (65.99% vs 76.56%, p=0.002; 33.53% vs 24.41%, p=0.023). However, no significant differences were found in clinical pregnancy rate per transfer (23.86% vs 18.92%, p=0.545), miscarriage rate per fresh embryo transfer (19.05% vs 28.57%, p=0.595), live birth rate per transfer (17.05% vs 13.51%, p=0.623), cumulative clinical pregnancy rate per retrieval (12.87% vs 11.27%, p=0.576) and cumulative live birth rate per retrieval (9.28% vs 6.57%, p=0.261) between the two groups (p>0.05)., Conclusions: In non-male factor ART cycles, ICSI was not associated with improved pregnancy outcomes in older women with a low number of oocytes retrieved. Routine use of ICSI is not recommended in older women who are infertile due to non-male factors., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Advanced maternal age is associated with decreased oocyte quantity and quality and in vitro fertilization (IVF) success rates. This study aimed to investigate whether melatonin supplementation can improve IVF outcomes in women of advanced maternal age by modulating cuproptosis and ferroptosis., Methods: This prospective cohort study included 161 women aged 35-45 years undergoing IVF-frozen embryo transfer cycles. Participants were assigned to either melatonin (n = 86, 2 mg daily for ≥ 8 weeks) or control (n = 75) groups. Cumulus cells were analyzed for cuproptosis and ferroptosis-related gene expression. Additional experiments were conducted on the HGL5 human granulosa cell line to assess mitochondrial function and metabolic reprogramming., Results: Melatonin supplementation significantly improved IVF outcomes in women aged ≥ 38 years, increasing clinical pregnancy rates (46.0% vs. 20.3%, P < 0.01), ongoing pregnancy rates (36.5% vs. 15.3%, P < 0.01), and live birth rates (33.3% vs. 15.3%, P < 0.05). In cumulus cells from patients, gene expression analysis revealed that melatonin modulated cuproptosis and ferroptosis-related genes, including ATP7B and GPX4, with more pronounced effects in the ≥ 38 years group. This suggests melatonin enhances cellular resilience against oxidative stress and metal-induced toxicity in the ovarian microenvironment. In vitro studies using HGL5 cells showed melatonin reduced oxidative stress markers, improved mitochondrial function, restored expression of glycolysis and TCA cycle-related genes and modulated cuproptosis and ferroptosis-related gene expression. These findings provide mechanistic insight into melatonin's protective effects against regulated cell death in ovarian cells, potentially explaining the improved IVF outcomes observed., Conclusions: Melatonin supplementation significantly improved IVF outcomes in women of advanced maternal age, particularly those ≥ 38 years old, likely by modulating cuproptosis and ferroptosis and enhancing mitochondrial function in cumulus and granulosa cells. These results suggest that melatonin could be a promising adjuvant therapy for improving IVF success rates in older women., (© 2024. The Author(s).)

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).)

The incidence of multiple pronuclei (≥ 3PN) zygotes and blastomere multinucleation was found to be elevated in the presence of increased estradiol (E 2 ) levels and a greater number of retrieved oocytes. This implies a potential link between the incidence of multinucleation at the two-cell stage (MN2) and a higher proportion of ≥ 3PN zygotes. We aimed to investigate the effect of high proportion of ≥ 3PN zygotes on MN2 incidence during conventional in vitro fertilization (C-IVF) by using time-lapse monitoring. This study included 1195 patients from January 2020 to December 2022. The patients were categorized into three groups: Group 1 comprised patients with no ≥ 3PN zygotes (n = 422), Group 2 included those with 0-25% ≥3PN zygotes (n = 617), and Group 3 consisted of patients with more than 25% ≥3PN zygotes (n = 156). The MN2 rate, types of MN2 and clinical outcomes were compared among the three groups. Our data indicated that the MN2 rate was significantly lower in groups 1 and 2 compared to group 3 (18.33 versus 25.62%; p < 0.001 and 19.45 versus 25.62%; p < 0.001). The MN2 embryos exhibited similar rates of high-quality embryos (42.27 versus 43.50 versus 40.67%; p = 0.401) and available embryos (84.96 versus 84.04 versus 83.21%; p = 0.460) rates among the three groups. There were no significant differences in the proportion of MN2 with different types among the three groups (p > 0.05). The embryos displaying binucleated at the two-cell stage in one blastomere (2BI1) and true multinucleated at the two-cell stage in one blastomere (2MULTI1) showed significantly higher blastocyst formation rates compared to embryos exhibiting true multinucleated at the two-cell stage in both blastomeres (2MULTI2) (59.50 versus 45.40%; p < 0.001 and 59.40 versus 45.40%; p < 0.001). In conclusion, the occurrence of MN2 events might be associated with high proportion of ≥ 3PN zygotes incidence. The types of MN2 had significant reference value when selecting embryos for transfer during the cleavage stage., (© 2024. The Author(s).)

Study Question: Does advanced male partner's age impact live birth rates (LBRs) in IVF treatment when female partner's age is factored in?, Summary Answer: In fresh IVF cycles LBRs decline with male partner's age ≥40 years when the female partner is aged 35-39 years, irrespective of the presence or absence of male factor; but not when the female partner is <35 years or ≥40 years of age; this decline is not observed in ICSI cycles., What Is Known Already: Advanced paternal age is associated with declining sperm parameters, impaired embryo development, compromised pregnancy outcomes, and abnormalities in the offspring in IVF/ICSI cycles. However, data on the interaction between maternal and paternal age on IVF outcomes are very limited and inconsistent. No significant effect of male partner's age on pregnancy outcomes has been noted in donor oocyte cycles., Study Design, Size, Duration: Retrospective analysis of all eligible autologous IVF/ICSI cycles with oocyte retrieval and intended fresh embryo transfer (ET) from the UK's national anonymized registry, published online by the Human Fertilisation and Embryology Authority (HFEA). There were 59 951 cycles that qualified the inclusion criteria in the study period: 1 January 2017 to 31 December 2018., Participants/materials, Setting, Methods: Couples underwent IVF (n = 27 226) or ICSI (n = 32 725) treatment with partner's sperm followed by fresh ET due to unexplained (n = 31 846), tubal (n = 6605), or male infertility (n = 22 905). Treatment cycles with endometriosis (n = 5563), ovulatory disorders (n = 9970), female partner aged >44 years (n = 636), and PGT (n = 280) were excluded. Women were stratified by age in the following groups: <35, 35-39, 40-42, and 43-44 years; male partner's age as <35 (reference group), 35-37, 38-39, 40-42, 43-44, 45-50, 51-55, 55-60, and >55 years as presented by the HFEA. Some age-groups were merged in the analysis to increase the population size. Chi-square test was used to compare binominal data; and multiple logistic regression to find any association between male and female age-groups on live birth adjusting for other confounders that had a significant effect on this outcome., Main Results and the Role of Chance: LBRs per oocyte retrieval as well as per ET were no different across the male partners' age-groups when the female partners were aged <35 years or in 40- to 44-year age-group, whether male-factor infertility was included or excluded and whether it was IVF or ICSI cycle. However, when IVF was the method of insemination in the female partner's age-group of 35-39 years, LBRs per oocyte retrieval dropped significantly from 27.0% in the male age-group of <35 years (reference group) to 22.9% (P = 0.002), 22.0% (P = 0.006), and 18.8% (P = 0.004) in 40-44, 45-50, and >50 years age-group, respectively in population that included male-factor infertility. Likewise, LBR per retrieval declined from 27.6% in 35 years age-group to 23.5% (P = 0.002) and 22.2% (P = 002) in 40-44 years and older groups, respectively in cycles without male infertility. However, there was no impact of male age on LBR in any female partner's age-group when ICSI was performed in either the presence or the absence of male infertility. A similar decline in the LBR per retrieval and per ET was observed in female age-group of 35-39 years in the analyses with IVF and ICSI cycles combined. The inference remained unchanged when only the first treatment cycle was included (per patient analysis) or when single blastocyst transfer cycles were analysed, eliminating the impact of the number and stage of embryo transferred. After adjusting for confounders including male age, female age, number of previous treatment cycles, previous live birth, insemination method (IVF or ICSI), number of embryos transferred, and day (stage) of ET, male partner's age remained significantly associated with LBR in the female age-group of 35-39 years, but not when women were in <35 years or 40- to 44-year age-group, in population including as well as excluding male infertility. Miscarriage rates per single ET trended to rise (non-significantly) in IVF as well as ICSI cycle only when men were over 55 years and female partners aged <40 years, particularly when male infertility was excluded., Limitations, Reasons for Caution: Information on ovarian reserve and stimulation protocols was not available. This probably would have had little impact, given the large size of the population studied. The ages of female and male partners were given in groups necessitating taking them as ordinal variable in the regression analysis. Cumulative LBRs could not be determined as the information on subsequent frozen-thawed ET cycles could not be traced and the severity or cause of abnormal semen parameters were not present in the HFEA database. Some age-groups with small number of patients were merged to obtain a reliable result., Wider Implications of the Findings: This is the largest clinical data to support the laboratory evidence of the ability of oocytes from young women to reverse the age-related deterioration of sperm quality. As the ageing oocytes lose this reparatory mechanism, the ageing sperm exert a detrimental effect on the LBR. The message of this study is important in counselling of patients and planning out treatment. Further research on interaction between male and female age will increase our understanding of this matter and help to establish whether ICSI procedure is more appropriate for older male partners even when there is no apparent semen abnormality., Study Funding/competing Interest(s): No funding was required. There is no competing interest., Trial Registration Number: N/A (retrospective analysis)., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Introduction: Infertility related to polycystic ovary syndrome (PCOS) represents a significant challenge for women of reproductive age. Over the last few years, evidence-based medicine has driven new approaches for treating infertility in patients with PCOS, changing rapidly and deeply the clinical practice., Areas Covered: The authors provide an in-depth examination of recent developments in drug treatment strategies that have impacted the clinical practice and changed the previous approach to infertility in patients with PCOS., Expert Opinion: The authors identify four primary areas of interest that have impacted clinical practice in the last few years. Specifically, they discuss the current role of metformin administration in women with PCOS and infertility, the choice for using clomiphene citrate or letrozole as first-line treatment for ovulation induction, the use of new gonadotropin formulations for in vitro fertilization (IVF) program, and the elective embryo transfer in IVF cycles as golden standard treatment for patients with PCOS at high-risk for ovarian hyperstimulation syndrome.

Nowadays, the most adopted technique to address infertility problems is in vitro fertilisation (IVF). However, its success rate is limited, and the associated procedures, known as assisted reproduction technology (ART), suffer from a lack of objectivity at the laboratory level and in clinical practice. This paper deals with applications of Artificial Intelligence (AI) techniques to IVF procedures. Artificial intelligence is considered a promising tool for ascertaining the quality of embryos, a critical step in IVF. Since the oocyte quality influences the final embryo quality, we present a systematic review of the literature on AI-based techniques used to assess oocyte quality; we analyse its results and discuss several promising research directions. In particular, we highlight how AI-based techniques can support the IVF process and examine their current applications as presented in the literature. Then, we discuss the challenges research must face in fully deploying AI-based solutions in current medical practice. Among them, the availability of high-quality data sets as well as standardised imaging protocols and data formats, the use of physics-informed simulation and machine learning techniques, the study of informative, descriptive yet observable features, and, above all, studies of the quality of oocytes and embryos, specifically about their live birth potential. An improved understanding of determinants for oocyte quality can improve success rates while reducing costs, risks for long-term embryo cultures, and bioethical concerns., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: With remarkable deficiency in both oocyte stock and competence, the prognosis of IVF-ET in diminished ovarian reserve (DOR) is obstinately poor, underscoring warranted optimization to current procedures. We compared the efficacy of dual-trigger (hCG plus GnRH-a) and hCG alone on the outcomes for DOR patients., Study Design: A total of 381 couples and 857 controlled ovarian stimulation (COS) cycles, and 222 couples and 366 frozen embryo transfer (FET) ones were included. The intermediate outcomes during oocyte retrieval and in vitro culture were compared based on COS dataset, while outcomes after embryo transfer analyzed based on FET dataset. The marginal effect of all study factors and covariates were evaluated with a cluster-weighted GEE model., Results and Conclusion: Neither the intermediate nor implantation outcomes were improved by dual-trigger. The OR values were 1.08 (95 % CI: 0.41-2.78) for retrieval cancellation, 1.33 (95 % CI: 0.89-2.00) for oocyte harvest, 1.04(95 %CI: 0.94-1.15) for viable embryo and 1.03(95 %CI: 0.88-1.19) for top-quality embryo. Similarly, the ORs were 0.90 (95 %CI: 0.62-1.30) for implantation and 0.97 (95 %CI: 0.56-1.69) for clinical pregnancy. This equivalence remained unchanged after adjusting for the covariates such as age, BMI, controlled ovarian stimulation protocols, etc. Thus, dual-trigger cannot provide significant advantage over hCG in related to immediate or clinical outcomes of IVF-ET treatments in DOR patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Recently, progesterone has been used to prevent LH surge instead of GnRH analogues during ART treatments, which is known as progesterone-primed ovarian stimulation (PPOS) protocol. During ART treatment, highly purified human menopausal gonadotropin (HP-hMG) and recombinant follicle stimulating hormone (rFSH) are two of the agents used for stimulation of antral follicles. The aim of this study is to compare the efficacy and success of HP-hMG and rFSH agents in the ovarian stimulation step of the PPOS protocol, which has not been previously reported in the literature., Methods: This retrospective study was conducted at a university hospital with patients who underwent IVF treatment using PPOS protocols in between January 2019 and July 2021. For ovarian stimulation, rFSH was used in group I and HP-hMG was used in group II. Mature oocyte ratio was the primary outcome, and live birth rate was the secondary outcome. Mann-Whitney and Chi-square tests were used for statistical analysis. All p values below 0.05 were considered significant., Results: Total numbers of follicles, oocytes, MII, and 2PN numbers obtained were similar between the two groups. The fertilization rates were 66.7% in the rFSH group and 64.3% in the HP-hMG group (p > 0.05). The pregnancy rates were 53.5% and 46.7% in the rFSH and HP-hMG groups, respectively. There was no statistically significant difference between pregnancy, abortus, and live birth rates., Conclusion: In this study, it is demonstrated that stimulation of oocytes with either rFSH or hMG in the PPOS protocol, which has been added to IVF treatment protocols in recent years, had no statistical difference regarding mature oocyte numbers and live birth rates between the two groups. These results are consistent with the previous literature which compared rFSH and hMG in GnRH agonist and antagonist protocols., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Study Question: What is the impact of male age- and sperm-related factors on embryonic aneuploidy?, Summary Answer: Using a 3-fold analysis framework encompassing patient-level, embryo-level, and matching analysis, we found no clinically significant interactions between male age and sperm quality with embryo ploidy., What Is Known Already: While the effect of maternal age on embryo chromosomal aneuploidy is well-established, the impact of male age and sperm quality on ploidy is less well-defined., Study Design, Size, Duration: This retrospective cohort study analyzed autologous preimplantation genetic testing for aneuploidy (PGT-A) and frozen embryo transfer cycles from December 2014 to June 2021. The study involved 11 087 cycles from 8484 patients, with a total of 35 797 embryos., Participants/materials, Setting, Methods: The aneuploidy rate, calculated as the ratio of aneuploid blastocysts to the total number of blastocysts biopsied in a single treatment cycle, was evaluated. In the embryo-level analysis, the main outcome measure was the ploidy state of the embryos. The study employed a multifaceted analytical approach that included a patient-level analysis using generalized linear mixed models, an embryo-level analysis focusing on chromosomal ploidy, and a propensity score matching analysis contrasting groups with distinct ploidy rates (0% and 100%). There were no interventions as this was an observational study of PGT-A cycles., Main Results and the Role of Chance: No clinically relevant factors influencing ploidy rate related to male and sperm quality were revealed. In contrast, female age (coefficient = -0.053), BMI (coefficient = 0.003), prior ART cycle (coefficient = -0.066), and number of oocytes retrieved (coefficient = -0.018) were identified at the patient level. Embryo analysis identified age (coefficient = -0.1244) and ICSI usage (coefficient = -0.0129) as significant factors. Despite these, no significant interactions between male and female assessed factors on the ploidy rate emerged. Propensity score matching between maximal (100% vs 0%) euploid rates did not reveal significant differences of influence by male age and sperm quality., Limitations, Reasons for Caution: The focus on patients having blastocyst biopsy for PGT-A may not reflect the broader IVF population. Other semen quality parameters like DNA fragmentation were not included. Exclusion of embryo mosaicism from the analysis could affect aneuploidy rate interpretations. There may also be unmeasured influences like lifestyle or environmental factors., Wider Implications of the Findings: Male age and sperm quality parameters were consistent across both maximal and minimal ploidy rate comparisons. No significant clinical characteristics related to the factors assessed for the male-influenced blastocyst ploidy status, confirming the dominancy of the oocyte and female age., Study Funding/competing Interest(s): The study was not funded. There are 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.)

Background: Vitamin D plays various roles in different stages of reproduction, and abnormalities in its levels are associated with diseases such as polycystic ovary syndrome (PCOS). This study aimed to determine the relationship between initial vitamin D levels and in vitro fertilization (IVF) outcomes in PCOS patients., Methods: This retrospective cohort study included 1174 PCOS patients who consulted the Acıbadem Maslak Hospital IVF Clinic between January 2015 and March 2021. We investigated the effect of preconceptional vitamin D levels on IVF outcomes using data analysis with SigmaPlot 14.5., Results: We found a significant positive correlation between preconceptional vitamin D levels and positive clinical pregnancy rates (p < 0.001) as well as increased endometrial thickness (EMT) on human chorionic gonadotropin (hCG) day (p < 0.001, r = 0.262). The optimal vitamin D cut-off value for predicting positive hCG test results was identified as 13.24 ng/mL, as determined by receiver operating characteristic curve analysis (sensitivity = 0.839, specificity = 0.677). No association was observed with other IVF outcome parameters, miscarriage rates, or clinical pregnancy rates based on EMT., Conclusions: The study suggests that PCOS patients with vitamin D levels above 13.24 ng/mL are more likely to achieve positive hCG results after IVF. These findings highlight the potential importance of vitamin D supplementation in improving pregnancy outcomes for PCOS patients. Additionally, increased EMT on hCG day may explain the higher clinical pregnancy rates associated with elevated vitamin D levels., (© 2024 Japan Society of Obstetrics and Gynecology.)

Background: Ovulation induction for in vitro fertilization (IVF) may increase intravascular thromboses among patients with antiphospholipid autoantibodies (aPLs) or antiphospholipid syndrome (APS) due to the high estrogen levels. While natural or modified natural IVF treatment cycles (MNC) are sometimes used instead of stimulated cycles with empiric anticoagulant treatment among these infertile patients, their efficacy is unclear., Materials and Methods: A retrospective cohort study including all IVF cycles of patients diagnosed with aPLs or APS in a tertiary, university-affiliated hospital between 2012 and 2022. The outcomes of stimulated cycles with anticoagulants and MNC and natural IVF cycle attempts were compared., Results: 121 oocyte retrievals from 38 women were analyzed: 93 stimulated and 28 MNC or natural IVF cycles. The rates of cycle cancellation (0 % vs. 17.9 %, p < 0.001) and cycles in which no oocytes were retrieved (0 % vs. 43.5 %, p < 0.001) were significantly lower following stimulated cycles vs. natural and MNC. In parallel, positive β-hCG (31.9 % vs. 10.9 %, p = 0.03), clinical pregnancy rate (23.6 % and 3.6 %, p < 0.001) and live birth rates (18.1 % vs. 3.6 %, p = 0.01) were significantly higher following stimulated cycles. No thrombotic events or bleeding occurred in any cycle., Conclusion: Ovarian stimulation for IVF is more effective for successful pregnancy and delivery than natural cycles and MNC and can be safely undertaken in aPLs or APS women undergoing IVF. Rates of complication from hormonal treatment are not increased when treated with LMWH during ovarian stimulation., Competing Interests: Declaration of competing interest We have confirmed that all manuscript authors contributed to the concept, design, results interpretation, and manuscript drafting. None of the authors of this study have any conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier Ltd.)

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.)

Reciprocal in vitro fertilization (IVF) and intravaginal culture (IVC) are two technologies that allow same-sex female couples to jointly contribute biologically to a pregnancy. This systematic review aimed to synthesize the clinical outcomes of each method including live birth rate, clinical pregnancy rate, embryo quality, and perinatal complications. A dual-reviewer protocol identified eight studies on reciprocal IVF and ten studies on IVC. In retrospective studies reporting on a total of 1,405 reciprocal IVF cycles, reciprocal IVF has demonstrated similar cycle and pregnancy outcomes to autologous IVF. One study that reported on pregnancy complications found a comparable rate of hypertensive disease in pregnancy between patients undergoing reciprocal IVF and intrauterine insemination. However, a lack of prospective studies on reciprocal IVF limits the generalizability of these results. Overall, small prospective and retrospective studies reporting on a total of 776 IVC cycles show that IVC offers good cycle and pregnancy outcomes, comparable to IVF. However, randomized prospective studies reported that the rate of quality embryo creation in IVC may be lower than in IVF. Although both reciprocal IVF and IVC show promise for same-sex female couples and the larger lesbian, gay, bisexual, transgender, intersex, asexual, and other sexual or gender minorities community, this review has highlighted the need for larger, prospective, more diverse studies on methods of shared biological contribution for family building., Competing Interests: Declaration of Interests B.D. has nothing to disclose. H.N. has nothing to disclose. K.S.N. has nothing to disclose. I.C.B. has nothing to disclose. P.B. has nothing to disclose. S.L.E. has nothing to disclose., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Research Question: Is there any difference in clinical outcomes between the progesterone-modified natural cycle (P4mNC) and hormone replacement therapy (HRT) endometrial preparation protocols after single euploid blastocyst frozen embryo transfer (FET) cycles?, Design: A retrospective cohort study was performed at a single, private, high-volume fertility centre. Patients who underwent single euploid blastocyst FET between January 2017 and December 2019 were included. A total of 1933 FET cycles were reviewed, and 723 FET cycles from 548 patients met the inclusion criteria. Two groups were compared according to endometrial preparation: 327 P4mNC-FET and 396 HRT-FET cycles. The primary outcome was the live birth rate. The secondary outcomes included the clinical pregnancy rate and the miscarriage rate., Results: There were no differences in the clinical pregnancy rate (50.2% versus 47.0%, P = 0.688), miscarriage rate (9.8% versus 14.5%, P = 0.115) and live birth rate (45.0% versus 39.6%, P = 0.331) between the P4mNC-FET and HRT-FET groups after covariate adjustments., Conclusions: There were no differences in the clinical outcomes between the P4mNC-FET and HRT-FET cycles. These results indicate that P4mNC-FET cycles produce clinical outcomes comparable to those of more traditional HRT-FET while allowing greater flexibility in the timing of embryo transfer., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Research Question: Is artificial oocyte activation (AOA) effective for patients with unexplained low or no fertilization following IVF/intracytoplasmic sperm injection (ICSI)?, Design: All IVF/ICSI cases resulting in total fertilization failure or fertilization rate ≤25% at Ninewells Assisted Conception Unit, Dundee between January 2014 and December 2021 (n = 231) were reviewed contemporaneously. After exclusion of obvious stimulation, egg, sperm and/or assisted reproductive technology laboratory factors, patients with at least one cycle of IVF/ICSI resulting in apparently unexplained fertilization abnormalities were offered research investigations, including sperm immunocytochemistry for phospholipase C zeta (PLCζ) protein expression. This retrospective case-control cohort study evaluated laboratory and clinical outcomes for 39 couples (15 attended for sperm studies research) that subsequently undertook ICSI-AOA with Ca 2+ ionophore., Results: Comparing preceding IVF/ICSI and subsequent ICSI-AOA for each patient, the number of eggs collected was similar; however, ICSI-AOA resulted in a significantly improved fertilization rate (57.2% versus 7.1%; P < 0.0001). The uplift for a subset of 10 patients identified with PLCζ deficiency was 66.3% versus 4.6% (P < 0.0001). Overall, ICSI-AOA resulted in a higher number of fresh embryo transfers (94.6% versus 33.3%; P < 0.0001), a significantly higher clinical pregnancy rate (CPR) and live birth rate (LBR; 18.9% versus 2.6%; P = 0.02), a significant increase in cycles with surplus embryos suitable for cryostorage (43.6% versus 0%; P < 0.0001), and increased cumulative CPR (41.0% versus 2.6%; P < 0.0001) and LBR (38.5% versus 2.6%; P < 0.0001)., Conclusion: AOA is a powerful tool that can transform clinical outcomes for couples experiencing apparently unexplained fertilization abnormalities. PLCζ assays have the potential to be valuable diagnostic tools to determine patient selection for ICSI-AOA, and research efforts should continue to focus on their development., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To investigate live birth rate (LBR) and cumulative live birth rate (CLBR) to achieve the first newborn per blastocyst transferred and oocyte retrieved in the first complete IVF cycle of autologous and donated oocytes and identify the possible success factors., Methods: This was a retrospective cohort study of a private IVF center. There were 1867 cycles, 1241 of which were fresh transfers and 626, their subsequent thawing transfers., Results: We found significant variables by binary logistic regression. For LBR, female infertility and the day of blastocyst transferred were relevant; however, for CLBR, the numbers of blastocysts available for future transfers, oocyte age, and maternal age were more critical. Oocyte age is a negative factor that begins to affect CLBR gradually beyond 36 years; from that age, there are significant worse results in polycystic ovary syndrome and poor responder patients., Conclusion: The LBR and CLBR were optimized for oocyte recipients when eight oocytes were retrieved (63.6%; 87.9%); at most, fourteen oocytes should be assigned to avoid freezing surplus blastocysts. Thirteen autologous oocytes (69.2%; 92.3%) were ideal for optimization. CLBR optimized after three blastocysts in donor oocytes (81.8%) and four for autologous oocyte patients (80.9%). Our outcomes are valuable for doctors and infertile couples, and they give us information on what we can expect from a first complete IVF cycle., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective(s): Assisted reproductive technology (ART) Centers and laboratories perform complex tasks with patients and their gametes/embryos daily. The degree of problems/non-conformances in such surroundings must be minimized at zero point. This study aimed to establish the proper risk management system with well-defined process steps to prevent and eliminate problems/non-conformances., Study Design: Failure mode and effect analysis (FMEA) was introduced in the ART Center and the IVF laboratory. ART Center working processes were grouped into the categories of Clinical procedures, Forms, Identification, Personnel, Patients, and Facility. Working processes in the IVF laboratory were grouped into the categories of Consumables, Media, Equipment, Personnel, Working space, and Procedures. The traceability and safety of the working processes were evaluated before and after corrective measures regarding risk priority number (RPN). The severity (S), occurrence (O), and detection (D) index of problems/non-conformance were scaled from 1 to 5. The RPN was calculated by multiplying the SOD index, and the cut-off value for RPN was ≥12., Results: The increased RPN was found in the following working processes of the ART Center: Embryo transfer and pregnancy (RPN = 18) in the category of Clinical procedures; Informed consents and agreements (RPN = 16) in the category Forms; Continuous education of the knowledge and skills (RPN = 12) in Personnel category; Space conditions (RPN = 24) and Equipment (RPN = 12) in the category Facility. In the IVF laboratory, increased RPN was found in the following working processes: Production of the plasticware (RPN = 12), Transport (RPN = 12) and Storage (RPN = 12) in the category Consumables; Media production (RPN = 16) in category Media; Alarm notification system for the critical equipment (RPN = 12) in category Equipment; Personnel number and qualifications (RPN = 12), Standard operative procedures (SOP) (RPN = 12) and Continuous education of the knowledge and skills (RPN = 12) in category Personnel; Working conditions (RPN = 18) and Security (RPN = 20) in Working space; Patient identification (RPN = 20), Biological samples identification (RPN = 20), Records (RPN = 12), ART procedure (RPN = 30), Embryo transfer (RPN = 30) and Cryopreservation and thawing of biological samples (RPN = 30) in category Procedures. According to the RPN score, corrective measures were implemented. Most RPN scores were reduced after the implementation of the electronic witnessing system in patient/sample tracing steps. Phases Patient identification and Biological sample identification showed a double reduction of RPN scores, from 20 to 10. Also, for critical steps in ART procedures, Embryo transfer, Cryopreservation, and thawing of biological samples, the RPN score was reduced from 30 to 10. Proper education of personnel was another corrective measure that significantly contributed to a reduction of RPN scores in most of the categories., Conclusion(s): The FMEA analysis is useful in recognizing the critical steps of an ART Center. The RPN scores for patient traceability were successfully reduced using the electronic witnessing system. Nonetheless, the study has certain limitations, as FMEA is highly dependent on the specific healthcare organization, adherence to national guidelines, and the subjective nature of SOD and RPN evaluations., 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. Published by Elsevier B.V.)

Research Question: What areas of manual IVF cryostorage operations are common to the safe operation of IVF cryostorage facilities and require effort from embryologists?, Design: Observational time and motion data were collected by two observers equipped with the digital cameras over 2 weeks at four well-characterized US IVF centres (sites α, β, γ and δ) from 12 participants performing cryostorage tasks. To understand the work processes of the different sites and assist in the data analysis, informal interviews were conducted with the study participants and laboratory directors. Data were analysed to identify work processes that might be eliminated or diminished by automation and software improvements., Results: On average, it took 3.4 data record queries per retrieval from cryostorage to identify a cane, while the canister was lifted an average of 1.5 times per retrieval, with a mean 11.8 ± 9.2 s per lift. Of the total time spent working with cryostorage equipment, 47.25% was of a fatiguing nature. Sites α, β and γ utilized one person to fill the liquid nitrogen storage Dewars, while site δ had two technicians working in tandem to move and fill the Dewars, with different frequencies and determination factors for refills and efficiencies., Conclusions: This time and motion study demonstrated significant time investment, task redundancy and fatiguing working conditions among embryologists using manual cryostorage processes. There was a disparity of processes and space capacity across different laboratories. Some of these issues may be addressed by the integration of automation and technology solutions., (Copyright © 2024 TMRW Life Sciences, Inc. Published by Elsevier Ltd.. All rights reserved.)

Research Question: How do perinatal outcomes differ between programmed and modified natural frozen embryo transfer (FET) cycles?, Design: A retrospective cohort study of 839 patients was undertaken at a university-affiliated fertility practice undergoing single blastocyst FET cycles between 2014 and 2020. The primary outcome measures were the incidence of ischaemic placental disease, small for gestational age (SGA), intrauterine growth restriction (IUGR), preterm delivery, birth weight, and mode of delivery., Results: When comparing programmed FET cycles with modified natural FET cycles, there was no increased risk of ischaemic placental disease [adjusted risk ratio (aRR) 0.83, 95% CI 0.61-1.14], IUGR (unadjusted RR 0.50, 95% CI 0.14-1.77), preterm delivery (aRR 1.11, 95% CI 0.72-1.70) or SGA (aRR 0.69, 95% CI 0.40-1.19). Patients in the programmed cohort had increased risk of caesarean delivery (aRR 1.32, 95% CI 1.10-1.59). These outcomes were unchanged when limited to patients undergoing their first FET cycle., Conclusions: There are no differences in patient and neonatal clinical outcomes between programmed and modified natural FET cycles. The choice of FET protocol should remain a shared decision between patient and provider., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

To assess the value of deep learning in selecting the optimal embryo for in vitro fertilization, a multicenter, randomized, double-blind, noninferiority parallel-group trial was conducted across 14 in vitro fertilization clinics in Australia and Europe. Women under 42 years of age with at least two early-stage blastocysts on day 5 were randomized to either the control arm, using standard morphological assessment, or the study arm, employing a deep learning algorithm, intelligent Data Analysis Score (iDAScore), for embryo selection. The primary endpoint was a clinical pregnancy rate with a noninferiority margin of 5%. The trial included 1,066 patients (533 in the iDAScore group and 533 in the morphology group). The iDAScore group exhibited a clinical pregnancy rate of 46.5% (248 of 533 patients), compared to 48.2% (257 of 533 patients) in the morphology arm (risk difference -1.7%; 95% confidence interval -7.7, 4.3; P = 0.62). This study was not able to demonstrate noninferiority of deep learning for clinical pregnancy rate when compared to standard morphology and a predefined prioritization scheme. Australian New Zealand Clinical Trials Registry (ANZCTR) registration: 379161 ., Competing Interests: Competing interests P.J.I. has provided paid advice to Western Australia government on medical cases and has previously (until June 2022) held shares in Virtus Health, a commercial IVF company. C.V. has received consulting fees, lecture payments and travel expenses from pharmaceutical firms with a commercial portfolio in IVF, and has previously (until June 2022) held shares in Virtus Health, a commercial IVF company. D.K.G. has received a research grant from Vitrolife to develop culture medium. S.M.N. has received consulting fees, lecture payments and travel expenses from pharmaceutical firms with a commercial portfolio in IVF. J.B. and M.G.L. are employees of Vitrolife and own shares in Vitrolife, who have a pending iDAScore patent. R.L.K. has received a grant from a pharmaceutical firm with a commercial portfolio in IVF, has received speaking fees and travel expenses from Vitrolife, who have a pending iDAScore patent. R.L. has received lecture payments and travel expenses from pharmaceutical firms with a commercial portfolio in IVF. M.M. has received lecture payments and travel expenses from pharmaceutical firms with a commercial portfolio in IVF and has previously (until June 2022) held shares in Virtus Health, a commercial IVF company. H.P. and B.T. are employed by a company where Vitrolife funded research. T.H. was previously employed by Vitrolife, who have a pending iDAScore patent. The other authors declare no competing interests., (© 2024. The Author(s).)

Background: Women undergoing in vitro fertilization and embryo transfer (IVF-ET) often utilize acupuncture to enhance pregnancy outcomes. Yet, the optimal timing for acupuncture sessions and the relationship between dosage and effect remain uncertain. Objectives: To investigate the impact of the timing and dosage of acupuncture on pregnancy outcomes, drawing on existing research. Methods: A comprehensive search of eight databases was conducted from their inception to January 14th, 2023, without restrictions on language. Only randomized controlled trials comparing acupuncture with either sham acupuncture or no adjuvant treatment were selected for inclusion. This meta-analysis assessed the efficacy of acupuncture in IVF-ET, analyzing the influence of varied timing and dosage on pregnancy outcomes. Subgroup analyses were undertaken to address any heterogeneity across the studies. Results: A total of 38 RCTs involving 5,991 participants were analyzed. In infertile women undergoing IVF fresh cycles, acupuncture performed during controlled ovarian hyperstimulation (COH) significantly increased the clinical pregnancy rate (CPR) (relative risk [RR] = 1.33, 95% confidence interval [CI]: 1.07-1.65, p = 0.01), whereas acupuncture administered either before COH or on the day of ET did not demonstrate reproductive benefits. Regarding frozen cycles, acupuncture before freeze-thaw embryo transfer (FET) significantly enhanced the CPR (RR = 1.71, 95% CI: 1.36-2.16, p < 0.00001) and live birth rate (LBR) (RR = 2.40, 95% CI: 1.20-4.79, p = 0.01). Improvements in CPR were observed across all dosage groups, but only the high-dosage group showed a significant increase in LBR (RR = 1.75, 95% CI: 1.05-2.92, p = 0.03). Conclusions: Timing and dosage of acupuncture are crucial factors affecting pregnancy outcomes in IVF-ET. For women undergoing IVF fresh cycles, acupuncture during COH yielded more significant reproductive benefits. In addition, acupuncture before freeze-thaw embryo transfer (FET) was associated with improved pregnancy outcomes in frozen cycles. Furthermore, higher dosages of acupuncture were linked to more favorable outcomes.

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.)

Ovum Pick Up (OPU) is a minimally invasive technique widely used in cattle and mares for oocyte retrieval, involving ultrasound-guided puncture of ovarian follicles. It has been demonstrated that this technique is safe for its repeated use in the same female without affecting her reproductive health, allowing for the retrieval of oocytes in individuals regardless of their reproductive status. The oocytes obtained through OPU can subsequently be used for in vitro embryo production (IVP) using assisted reproductive techniques (ARTs) or be cryopreserved in biobanks for their future use. Traditionally, the minimally invasive technique of choice performed in vivo in domestic and wild felines was LOPU (laparoscopic-guided ovum pick up). The present study was designed to explore if ultrasound-guided OPU in the domestic cat is safe and effective. In an initial series of ex vivo experiments (n = 92 ovaries, n = 434 oocytes), the effect of different aspiration pressures for oocyte collection was explored. These experiments identified 43 mmHg as the optimal aspiration pressure, resulting in the highest recovery rate and a favorable maturation and blastocyst rate. Subsequently, 16 grade I and II oocytes were retrieved by OPU and 101 oocytes were retrieved following ovariectomy and slicing. Sixteen oocytes obtained with each technique were subjected to in vitro maturation (IVM) and in vitro fertilization (IVF). A total of 14 presumptive zygotes were selected for in vitro culture (IVC) from each group (OPU and slicing), obtaining a cleavage rate of 57.1 % and 64.2 %, a morula rate of 28.5 % in both groups, and a blastocyst rate of 7.14 % and 14.2 % respectively. The hormonal stimulation protocol was well-tolerated, with no adverse effects observed. Moreover, no complications arose during the ovariectomy performed post-OPU. The use of this technique in domestic cats represents a significant step forward in terms of safety, replicability, and invasiveness, serving as a valuable model for its application in wild felids species. Additional research involving a greater number of animals is required to validate these encouraging findings., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

After ejaculation, mammalian sperm undergo a series of molecular events conducive to the acquisition of fertilizing competence. These events are collectively known as capacitation and involve acrosomal responsiveness and a vigorous sperm motility called hyperactivation. When mimicked in the laboratory, capacitating bovine sperm medium contains bicarbonate, calcium, albumin and heparin, among other components. In this study, we aimed at establishing a new capacitation protocol for bovine sperm, using calcium ionophore. Similar to our findings using mouse sperm, bovine sperm treated with Ca 2+ ionophore A23187 were quickly immobilized. However, these sperm initiated capacitation after ionophore removal in fresh medium without heparin, and independent of the Protein Kinase A. When A23187-treated sperm were used on in vitro fertilization (IVF) procedures without heparin, eggs showed cleavage rates similar to standardized IVF protocols using heparin containg synthetic oviduct fluid (IVF-SOF). However, when A23187 pre-treated sperm were further used for inseminating eggs in complete IVF-SOF-heparin, a significantly higher percentage of embryo development was observed, suggesting a synergism between two different signaling pathways during bovine sperm capacitation. These results have the potential to improve current protocols for bovine IVF that could also be applied in other species of commercial interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The studies posits that there is not sufficient evidence to support the use of intrauterine platelet-rich plasma (PRP) infusion in patients with recurrent implantation failure (RIF). This study aims to investigate the effects of infusion of PRP on patients with unexplained-RIF in fresh and frozen embryo transfer (ET) cycles. A total of 80 participants were included in this study. The participants were randomly assigned to one of two groups with and without PRP infusion. Each of the PRP and control groups were also divided into fresh and frozen ET subgroups. ET outcomes were compared between groups. Clinical pregnancy rate was significantly higher in Frozen ET in PRP group than other subgroups (p < 0.0001). Miscarriage rate were significantly lower in PRP group than control group. Pregnancy complications and preterm labor were significantly higher in PRP group than control group (p < 0.0001). Live birth and healthy baby rate were significantly higher in PRP group than control group (p < 0.0001). The intrauterine infusion of 0.8-1 ml of PRP 48 h before blastocyst ET at fresh and frozen cycles can be an efficient treatment option for u-RIF patients. Also, results indicated that the clinical pregnancy rate was equal to the live birth rate at fresh ET cycles, whereas the live birth rate was lower than the clinical pregnancy rate at frozen ET cycles. Therefore, considering the superiority of fresh cycles over freeze cycles, the infusion of PRP into the uterus of patients with RIF is recommended to be done at fresh ET cycles.Trial registration: NCT, NCT03996837. Registered 25/06/2019. Retrospectively registered, http://www.clinicaltrial.gov/ NCT03996837., (© 2024. The Author(s).)

Purpose: To investigate the effects of fresh embryo transfer and frozen-thawed embryo transfer on perinatal outcomes among patients with PCOS., Method: Patients who underwent in vitro fertilization and embryo transfer at the reproductive medicine center of the Affiliated Hospital of Guangdong Medical University from February 2013 to March 2021 were retrospectively analyzed. Patients were divided into the fresh embryo transfer group and frozen-thawed embryo transfer group according to whether fresh embryo transfer was performed. According to their conditions, patients were further classified into the ET-PCOS group (group A, n = 104), ET-non-PCOS group (group B, n = 212), FET-PCOS group (group C, n = 102), or FET-non-PCOS group (group D, n = 148); the general data, laboratory indicators and pregnancy outcomes of the patients were statistically analyzed, and the perinatal outcomes and related factors between the groups were compared and analyzed., Results: The level of E2 on the HCG test day in the ET group was lower than that in the FET group. The natural birth rate of group D was lower than that of group A and group B, and the cesarean section rate was higher than that of group A and group B; the clinical pregnancy rate of group A was higher than that of group B and group D, and the difference was statistically significant (P < 0.05). There was no significant difference in the total abortion rate, early abortion rate or late abortion rate between the groups (P > 0.05). There was no significant difference in gestational age, neonatal sex or neonatal weight between the groups (P > 0.05). The incidence of placenta previa in Group B was significantly lower than that in Group D, and the difference was significant (P < 0.05). The incidence of fetal distress in Group B was significantly lower than that in Groups C and D, and the incidence of neonatal jaundice in Group D was significantly higher than that in Groups A and B (P < 0.05). In the multivariate analysis, the number of high-quality embryos was independent factors affecting clinical pregnancy, and the embryo transfer method was an independent factor affecting fetal distress and neonatal jaundice., Conclusion: Young PCOS patients without risk of OHSS have a high clinical pregnancy rate with fresh transplant cycles. PCOS disease itself has no significant effect on the perinatal outcomes of the mother or singleton infant. Frozen-thawed embryo transfer may increase the incidence of low placenta, fetal distress and neonatal jaundice., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To investigate the impact of the progesterone concentration on human chorionic gonadotropin (hCG) trigger day in fresh cycles versus thawed transfer cycles (the freeze-all strategy) with an antagonist protocol, and to compare the differences in clinical outcomes. Methods: This retrospective cohort study included a total of 2 165 cycles conducted at Henan Provincial People's Hospital with cleavage-stage embryo (at least one top-quality) transfer between January 2017 and December 2023, with serum progesterone levels on hCG trigger day all≤6.34 nmol/L (i.e. 2 ng/ml). Multivariate logsitic regression analysis and curve fitting were performed based on different serum progesterone levels on hCG trigger day [≤3.17 nmol/L (i.e. 1 ng/ml) or 1-2 ng/ml]. Results: Multivariate regression analysis, by using cycle type (either fresh or frozen-thawed cycle) as the exposure variable, showed that the clinical pregnancy rate (≤1 ng/ml: OR =0.93, 95% CI : 0.75-1.14; 1-2 ng/ml: OR =1.05, 95% CI : 0.58-1.87) and live birth rate (≤1 ng/ml: OR =0.90, 95% CI : 0.71-1.13; 1-2 ng/ml: OR =1.53, 95% CI : 0.79-3.00) had no statistically significant differences in group of progesterone concentration ≤1 ng/ml or in group of 1-2 ng/ml. Using serum progesterone levels on hCG trigger day as a continuous variable for curve fitting analysis, the clinical pregnancy rate in fresh or thawed cycles showed no significant changes with increasing progesterone levels. Conclusions: In the antagonist protocol with cleavage-stage embryo transfer (at least one top-quality), when the serum progesterone level on hCG day is ≤2 ng/ml, there are no significant differences in clinical outcomes between thawed cycles and fresh cycles, including clinical pregnancy rate and live birth rate. Transferred in fresh cycles or choosing the freeze-all strategy could be selected based on the actual situation of the patients.

This retrospective study aimed to clarify the cumulative live-birth rates (CLBRs) and cost per live-birth (LB) to evaluate the validity of frozen-thawed embryo transfer without preimplantation genetic testing for aneuploidy (PGT-A) in women aged ≥ 40 years. The study included 1,011 patients aged ≥ 40 years who underwent their first oocyte retrieval at our hospital between January 2010 and September 2017. They were followed up for up to two years or until either treatment discontinuation or a pregnancy that resulted in a live birth. The 2-year CLBRs were 55.6%, 39.0%, 31.3%, 19.1%, 10.6%, 4.4%, and 0% for patients aged 40, 41, 42, 43, 44, 45, and > 46 years, respectively. In approximately 80% of LB cases, patients aged 40-42 years and 43-44 years became pregnant by the fourth and second transfers, respectively. Costs per LB were $30,207, $49,034, $66,345, $102,759, and $195,862 for patients aged 40, 41, 42, 43, and 44, respectively. Cost per LB for each number of transfers reached $300,000 and $ 450,000 for the third transfer at 42 and 43 years of age, respectively. For cost-effectiveness, up to two ET cycles are recommended for patients aged 42-43, and none for patients aged ≥ 44 years., (© 2024. The Author(s).)

Background: At present, embryologists are attempting to use conventional in vitro fertilization (cIVF) as an alternative to intracytoplasmic sperm injection (ICSI) for preimplantation genetic testing (PGT). However, the potential parental contamination origin of sperm cells and cumulus cells is considered the main limiting factor in the inability of cIVF embryos to undergo PGT., Methods: In this study, we established an IVF-PGTA assay for parental contamination tests with a contamination prediction model based on allele frequencies and linkage disequilibrium (LD) to compute the log-likelihood ratio (LLR) under competing ploidy hypotheses, and then verified its sensitivity and accuracy. Finally, comparisons of the effectiveness of SNP-based analysis and LLR-based IVF-PGTA among 40 cIVF embryos was performed, based on both statistical analysis of the parental contamination rate and chromosomal ploidy concordance rate between TE biopsy and ICM isolations., Results: With IVF-PGTA assay, biopsies with 10% maternal contamination could be detected accurately, and contamination caused by sperm cells could be eliminated completely. Utilizing LLR-based or single Nucleotide Polymorphism (SNP) -based analyses, our comprehensive examination of 40 clinically discarded fresh cIVF embryos revealed an absence of paternal contamination. Strikingly, the LLR-based analysis uniquely revealed a mere instance of 24% maternal contamination within the trophectoderm cell (TE) biopsy of 5* embryo. Furthermore, it was solely through this analysis that embryo (9-F) was identified as a triploid of paternal origin., Conclusions: In this study, we developed a new bioinformatics analysis method for identifying parental contamination during IVF-PGT, especially for couples with nonmale factor infertility., (© 2024. The Author(s).)

Despite the rapid advancements in clinical and laboratory technologies for in vitro fertilization (IVF), a significant proportion (10%-15%) of patients continue to experience fertilization disorders, leading to low fertilization rates and the production of nonviable embryos. Short-term fertilization involves the early removal of granulosa cells to observe the extrusion of the second polar body, enabling the assessment of fertilization and early remedial measures to address low fertilization rates and complete fertilization failure. However, the observation of short-term fertilization in IVF is impeded by challenges such as excessively large unprocessed clusters of cumulus-oocyte complexes and adhesion between eggs, necessitating complex external procedures for granulosa cell removal, and prolonged observation duration. To tackle this issue, this study proposes a method of immediate partial removal of granulosa cells post egg retrieval. This approach streamlines subsequent stages of short-term fertilization and traditional fertilization monitoring, reduces the time needed for oocyte extrusion, minimizes the likelihood of external environmental impacts on the oocytes, and decreases the risk of missing the critical fertilization observation window. Consequently, the study yields novel clinical evidence aimed at enhancing the operational efficiency of embryonic laboratories in IVF.

Objective: To investigate the number of cells in D3-stage embryos of high-quality blastocysts as a contributing factor, to evaluate the clinical pregnancy outcomes in frozen-thawed embryo transfer cycles, and to determine the impact of D3-stage cell count on pregnancy outcomes., Methods: Patients under 38 years old who underwent frozen-thawed single high-quality blastocyst transfer at our center were selected. Based on the cell count of D3 cleavage-stage embryos forming blastocysts, patients were divided into three groups: ≤6 cells, 7-9 cells, and ≥10 cells. A multivariate regression analysis was used to establish the prediction model, analyzing the impact of different D3 cleavage-stage cell counts on clinical pregnancy outcomes to guide clinical laboratories in selecting blastocysts with the best pregnancy outcomes for transfer., Results: This study identified a significant association between D3 cell count, blastocyst development stage, and embryo age. Embryos with a higher D3 cell count (≥10) were more likely to reach advanced blastocyst stages and form blastocysts by D5, whereas embryos with fewer D3 cells (≤6) were more likely to form blastocysts on D6. While D3 cell count significantly influenced blastocyst stage and timing of embryo development, no significant differences were observed between groups regarding clinical pregnancy, implantation, or live birth rates. Notably, embryos with fewer D3 cells exhibited a significantly lower miscarriage rate than other groups. Multivariate regression analysis showed a significant correlation between blastocyst stage, embryo age, and D3 cell count, particularly in D5 embryos and more advanced blastocysts. The increased miscarriage rate may be related to lower D3 cell count, and inadequate endometrial preparation was associated with poorer pregnancy outcomes. The type of infertility was also linked to D3 cell count, with secondary infertility patients showing more significant influencing factors., Conclusion: D3 cell count and related factors play a critical role in pregnancy outcomes during frozen-thawed high-quality blastocyst transfer cycles. Optimizing embryo age, selecting blastocysts at different stages, and refining endometrial preparation protocols are likely to enhance clinical pregnancy and live birth rates., 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 Li, Zeng, Zhu, Yang, Luo and Jia.)

Background: Recent literature has explored the role of human chorionic gonadotropin (hCG) triggering in frozen embryo transfer (FET) cycles with natural endometrial preparation. Despite this, the impact of hCG triggering on pregnancy outcomes following endometrial preparation with mild stimulation (mST) using Letrozole and Gonadotropins remains inadequately characterized. This study aimed to elucidate the effects of hCG-trigger on pregnancy outcomes in mST-FET cycles., Methods: In the present retrospective cohort study, the pregnancy outcomes of 409 eligible patients who underwent FET cycles with endometrial preparation using a mild ovarian stimulation protocol by letrozole plus low dose gonadotropins at the Royan Institute between 2020 and 2022, were investigated. The study population were segregated into two distinct groups according to type of ovulation: the spontaneous ovulation group (n = 138) and the hCG-trigger group (n = 271). The pregnancy outcomes including implantation and clinical pregnancy rates (CPR) and live birth rates (LBR) were compared between two groups. The multivariable logistic regression was performed to detect the most significant variables related to the LBR in the mST-FET cycles., Results: Demographic and baseline characteristics were comparable between groups. No significant difference was found in terms of implantation rate (0.65 ± 0.32 vs. 0.60 ± 0.30, P-value: 0.31), CPR (37% vs. 39.7%, P-value: 0.53), and LBR (35.5% vs. 37.3%, P-value: 0.74) in the spontaneous ovulation and hCG-trigger groups, respectively. The logistic regression analysis revealed that only the stage of the transferred embryo exhibited a significant relationship with LBR (blastocyst vs. cleavage: odds ratio (OR); 2.33, 95% confidence interval (CI):1.41-3.86, P-value = 0.001)., Conclusion: Pregnancy outcomes in the mST-FET cycles, including implantation rate, CPR, and LBR are comparable in cycles with or without hCG triggering. Based on the findings from multivariate regression analysis, the sole significant predictive factor for the LBR was the transfer of blastocyst embryos. It is recommended that these results be examined and discussed in future prospective studies with a larger sample size, considering the lack of comparable research in this field., (© 2024. The Author(s).)

Objective: The present study aimed to investigate the impact of combined use of letrozole in an antagonist protocol during IVF on live birth outcomes and to assess the safety of letrozole in terms of maternal and neonatal complications., Methods: This retrospective cohort study included women undergoing IVF/ICSI and fresh embryo transfer (ET) treatment with and without letrozole co-treatment from 2007 to 2021 at Shanghai Ninth People's Hospital (Shanghai, China). The primary outcome was the live birth rate, while the incidences of maternal and neonatal complications were secondary outcomes. Logistic regression models were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the analyzed outcomes. Sensitivity analysis was performed using a propensity score-based patient-matching (PSM) model, an inverse probability weighting (IPW) model, logistic regression models with women undergoing their first IVF-ET cycle, and subgroup analysis., Results: Of the 4780 women enrolled in the study, 3887 underwent an antagonist protocol for ovarian stimulation, while 893 received letrozole co-treatment. In this cohort, letrozole co-treatment demonstrated comparable live birth rates to the use of antagonist protocol alone (logistic regression: aOR, 0.88; 95% CI, 0.71-1.08; PSM: aOR, 0.97; 95% CI, 0.77-1.22; IPW: aOR, 0.88; 95% CI, 0.71-1.10). Notably, individuals with a body mass index (BMI) exceeding 24 and those with high ovarian response experienced higher live birth rates under the letrozole co-treatment regimen (BMI ≥ 24: aOR, 1.85; 95% CI, 1.14-3.00; high response: aOR, 1.60; 95% CI, 1.02-2.50). Letrozole co-treatment was also associated with decreased risks of gestational diabetes (aOR, 0.34; 95% CI, 0.15-0.69) and small for gestational age (SGA) fetuses (aOR, 0.42; 95% CI, 0.22-0.75) in fresh ET cycles. These finding were robust in both PSM and IPW models., Conclusions: Our findings suggested that letrozole co-treatment in antagonist protocol for IVF/ICSI was associated with a comparable live birth rate following fresh ET. Further prospective randomized studies are needed to verify our results., (© 2024. The Author(s).)

This study aimed to investigate the influence of various sperm quality characteristics, including morphology, motility, and count, on the success rates of clinical pregnancy achieved through assisted reproductive technologies (ART) such as in-vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and intrauterine insemination (IUI). The secondary objective was to assess the impact of these sperm parameters on the clinical pregnancy rate that resulted in the detection of a fetal heartbeat during the 11th week of gestation, a crucial milestone in successful ART-derived pregnancies. The researchers employed a retrospective analysis, evaluating data from 734 couples undergoing IVF/ICSI and 1197 couples undergoing IUI across two infertility centers. Exclusion criteria included cases involving donated eggs or sperm, surrogate uteri, and infertile couples with combined male and female factors. Five ensemble machine-learning models were utilized to predict the clinical pregnancy success rates. The Random Forest (RF) model achieved the highest mean accuracy (0.72) and area under the curve (AUC) (0.80), outperforming the other models for both IVF/ICSI and IUI procedures. The Shapley Additive Explanations (SHAP) value analysis revealed that for IUI cycles, all three sperm parameters (morphology, motility, and count) had significant negative impacts on the prediction of clinical pregnancy success. In contrast, for IVF/ICSI cycles, sperm motility had a positive effect, while sperm morphology and count were negative factors. In cycles with 1 to 5 retrieved eggs, sperm motility, and count, they positively affected the clinical pregnancy rate. The study also identified cut-off values for sperm count, with 54 and 35 being the respective thresholds for IVF/ICSI and IUI. Additionally, a significant cut-off point 30 was found for the sperm morphology parameter across all procedures. This study underscores the immense potential of leveraging ensemble machine learning models with traditional sperm quality assessments. This integrated approach can elevate the precision and personalization of clinical decision-making in the field of assisted reproductive technologies, ultimately offering more hope and better outcomes for couples struggling with infertility., (© 2024. The Author(s).)

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).)

The cryopreservation of rat embryos is useful for efficiently archiving rat resources in bioresource repositories. The cryopreserved fertilized oocytes can be quickly reanimated to rats with homozygous mutations using embryo transfer. In addition, cryopreserved rat fertilized oocytes are easier to transport than live animals. Before cryopreservation, fertilized oocytes are obtained by mating or in vitro fertilization. However, it is not clear which fertilized oocytes are most suited to cryopreservation. In this study, we performed a systematic comparison of the fertilizing ability, cryotolerance, and developmental ability of cryopreserved fertilized oocytes at the pronuclear stage produced either by mating (in vivo) or in vitro fertilization (in vitro) in SD and F344 rats. In vivo-fertilized oocytes had higher cryotolerance and developmental ability than in vitro-fertilized oocytes in SD and F344 rats. Furthermore, the fertilization ability, cryotolerance, and developmental ability of vitrified-warmed fertilized oocytes differed between SD and F344 rats. In conclusion, our study suggests that in vivo-fertilized rat oocytes were more suitable for cryopreservation. Our protocol provides an optimized system for the management of rat colonies using fertilized oocytes cryopreservation and contributes to the 3Rs principle by reducing the number of animals used for research., (© 2024. The Author(s).)

After cryopreservation, reactive oxygen species (ROS) can damage sperm. Antioxidants are the primary defense against oxidative damage. Berberine is a bioactive alkaloid found in Berberis vulgaris, Curcuma longa, and Ergon grape, and is a potent antioxidant. Due to the negative effects of free radicals in oxidative stress processes, antioxidant chemicals are required to protect sperm. However, berberine has low bioavailability, making it less effective. Loading techniques on nanoparticles and nanotechnology can help overcome this limitation. Selenium nanoparticles were synthesized with barberry extract, and berberine was loaded on them. Berberine nanoparticles were then synthesized using anti-solvent precipitation with a syringe pump technique. The synthesis of nanoparticles was confirmed by EDX, UV-visible, FE-SEM, Zeta-Potential, and FTIR tests. In this experiment, we aim to investigate the impact of nano-berberine and berberine loaded on Se-NPs on goat sperm parameters after freeze-thawing. We assessed the generation of reactive oxygen species (ROS), in vitro fertility, and the subsequent embryo development of zygote with treated sperm after determining the optimal concentration of various chemicals on sperm parameters. The study found that all treatments had significant differences from the control group in terms of motility, viability, DNA and membrane integrity, ROS level, lipid peroxidation, in vitro fertility ability, and the capacity to develop inseminated oocytes (p < 0.05). The most significant outcomes were observed with berberine loaded on Se-NPs and the combination of selenium nanoparticles with berberine nanoparticles., (© 2024. The Author(s).)

Background: The impact of high body mass index (BMI) on embryo and pregnancy outcomes in women using the PPOS (progestin-primed ovarian stimulation) protocol during their first frozen embryo transfer (FET) cycles is not clear. This study is to investigate the impact of BMI on oocyte, embryo, and pregnancy outcomes in patients who underwent the PPOS protocol., Methods: This retrospective study included the first FET cycle of 22,392 patients following the PPOS protocol. The impact of BMI on oocyte and pregnancy outcomes was assessed across different BMI groups, using direct acyclic graph to determine covariates, followed by the application of multiple linear and logistic regressions to further validate this influence., Results: The high BMI groups exhibited a higher number of oocytes; however, no significant differences were observed in good-quality embryos, clinical pregnancy rate, and implantation rate. Nevertheless, the high BMI groups demonstrated a significantly elevated miscarriage rate (9.9% vs. 12.2% vs. 15.7% vs. 18.3%, P < 0.001), particularly in late miscarriages, resulting in lower live birth rates (LBR, 41.1% vs. 40.2% vs. 37.3% vs. 36.2%, P = 0.001). These findings were further confirmed through multiple liner and logistic regression analyses. Additionally, several maternal factors showed significant associations with adjusted odds ratios for early miscarriage. However, women with a BMI ≥ 24 who underwent hormone replacement cycle or hMG late stimulation protocol for endometrial preparation experienced an increased risk of late miscarriage., Conclusions: By utilizing the PPOS protocol, women with a high BMI exhibit comparable outcomes in terms of embryo and clinical pregnancies. However, an elevated BMI is associated with an increased risk of miscarriage, leading to a lower LBR. Adopting appropriate endometrial preparation protocols such as natural cycles and letrozole stimulation cycles may potentially offer benefits in reducing miscarriages., (© 2024. The Author(s).)

Aims: To assess the predictive value of estradiol (E2) related parameters on the incidence of gestational diabetes mellitus (GDM) in women undergoing fresh embryo transfer., Materials and Methods: A Post-hoc analysis of a prospective cohort study., Results: We identified an optimal E2/follicle (E2/F) ratio threshold of 246.03 pg/ml on the day of human chorionic gonadotropin (hCG) administration. Women with an E2/F ratio exceeding this threshold had significantly lower rates of GDM (12.75% vs. 20.41%, P < 0.001) and ovarian hyperstimulation syndrome (OHSS) (11.75% vs. 15.48%, P = 0.03). Additional E2 parameters were also evaluated: baseline E2, E2 on hCG day, E2 increase, and E2 fold change. Lower GDM rates were observed in women with baseline E2 above 31.50 pg/ml (13.51% vs. 19.42%, P <0.01), E2 on hCG day above 3794.50 pg/ml (12.26% vs. 19.32%, P < 0.001), and E2 increase above 3771.50 pg/ml (12.24% vs. 19.28%, P < 0.001). There were no significant differences in OHSS rates for these additional E2 parameters. After adjusting for confounders, lower E2/F ratio (OR: 1.626, 95% CI: 1.229-2.150, P <0.01), E2 on hCG day (OR: 1.511, 95% CI: 1.133-2.016, P = 0.01), and E2 increase (OR: 1.522, 95% CI: 1.141-2.031, P <0.01) were identified as risk factors for GDM., Conclusion: This study demonstrates that an E2/F ratio over 246.03 pg/ml is significantly associated with a reduced risk of both GDM and OHSS in women undergoing fresh embryo transfer, highlighting the E2/F ratio as a superior predictive biomarker compared to other E2-related parameters., 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 Chen, Liu, Xu, Hu, Cai, Gong, Lin, Kalk, Krämer and Hocher.)

Introduction: IVF is a widely-used assisted reproductive technology with a consistent success rate of around 30%, and improving this rate is crucial due to emotional, financial, and health-related implications for infertile couples. This study aimed to develop a model for predicting IVF outcome by comparing five machine-learning techniques., Method: The research approached five prominent machine learning algorithms, including Random Forest, Artificial Neural Network (ANN), Support Vector Machine (SVM), Recursive Partitioning and Regression Trees (RPART), and AdaBoost, in the context of IVF success prediction. The study also incorporated GA as a feature selection method to enhance the predictive models' robustness., Results: Findings demonstrate that AdaBoost, particularly when combined with GA feature selection, achieved the highest accuracy rate of 89.8%. Using GA, Random Forest also demonstrated strong performance, achieving an accuracy rate of 87.4%. Genetic Algorithm significantly improved the performance of all classifiers, emphasizing the importance of feature selection. Ten crucial features, including female age, AMH, endometrial thickness, sperm count, and various indicators of oocyte and embryo quality, were identified as key determinants of IVF success., Conclusion: These findings underscore the potential of machine learning and feature selection techniques to assist IVF clinicians in providing more accurate predictions, enabling tailored treatment plans for each patient. Future research and validation can further enhance the practicality and reliability of these predictive models in clinical IVF practice., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Dehghan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Studies regarding serum Progesterone (P4) concentration and Clinical Pregnancy Rates (CPR) in fresh Embryo Transfer (ET) after Controlled Ovarian Stimulation Cycles (COS) remain inconclusive. To find a P4 cutoff point on fresh ET day associated with higher CPR, and to identify predictive factors of CPR and P4, the authors conducted a prospective cohort of 106 patients who underwent COS at a public IVF center. The luteal phase was supported with vaginal micronized progesterone (200 mg, 8/8h), beginning on oocyte retrieval day. The primary outcome was CPR beyond the 8 th week of pregnancy. A ROC curve was constructed to identify the best cutoff point correlated with higher CPR. Multivariate analysis evaluated predictive variables of CPR and P4 concentration. P4 levels showed no significant differences between pregnant and non-pregnant patients (67.12 ± 31.1 ng/mL vs. 64.17 ± 61.76, p = 0.7465). The cutoff point correlated with higher CPR was P4 ≥ 28.9 ng/mL (AUC 0.5654). Women's age (OR = 0.878; 95 % CI 0.774-0.995) and top-quality embryo transfer (OR = 2.89; 95 % CI 1.148-7.316) were associated with CPR. Women's age ≥ 40 years (OR = 0.0956; 95 % CI 0.0156-0.5851), poor response to COS (OR = 0.0964; 95 % CI 0.0155-0.5966), and follicles ≥ 10 mm (OR = 1.465; 95 % CI 1.013-2.117) were associated with the cutoff point. As the ROC curve was unsatisfactory, P4 ≥ 28.9 ng/mL should not be used to infer gestational success. In fresh ET, P4 concentration may merely reflect a woman's age and individual response to COS rather than being a reliable CPR predictor., Competing Interests: Conflicts of interest All authors certify that they have no affiliations with or involvement in any organization or entity with financial or non-financial interests in the subject matter or materials discussed in this manuscript., (Copyright © 2024. Published by Elsevier España, S.L.U.)

Objective: To identify any correlations between evidence levels, adoption rates, and additional costs of in vitro fertilization (IVF) add-ons., Design: Online survey., Subjects: The survey was conducted in 621 assisted reproductive technology-registered facilities that are members of the Japanese Society of Obstetrics and Gynecology from December 22, 2021, to February 13, 2022., Exposure: The survey included details regarding the specific add-on modalities employed and their associated costs; inquiries pertained to the fertility healthcare infrastructure in Japan before the implementation of the National Health Insurance scheme., Main Outcome Measures: The correlation between the adoption rate and cost of IVF add-ons and their evidence levels were analyzed. The evidence level of the add-on treatments was classified into Green, Amber, and Red categories based on the United Kingdom's Human Fertilisation and Embryology Authority and Cochrane systematic reviews., Results: A total of 438 eligible responses were analyzed, with clinics constituting 70.9% of the respondents' facilities. A total of 18 add-ons were assessed, and 96.5% (423/438) of facilities used at least one add-on. A positive correlation of the adoption rate and an inverse correlation of the cost with the evidence level of the IVF add-on treatment were observed (not significant). Outpatient clinics, defined as medical facilities with no beds, had a significantly higher adoption rate (Amber, 65.7%; Red, 52.0%) of add-ons than other facilities, regardless of the evidence rating, although the costs were similar across all site attributes., Conclusion: Accumulating evidence on the efficacy and safety of add-ons will lead to the development of medical care with a high-cost benefit, as an increase in the adoption rate and a decrease in cost are expected when limiting to medical care with a high level of evidence., 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 Shionoya, Yamada, Harada, Shirasawa, Jwa, Kuroda, Harada and Osuga.)

Background: Frozen embryo transfer (FET) is usually recommended for women with polycystic ovary syndrome (PCOS) undergoing In vitro fertilization (IVF). While there is no consensus as to the optimal protocol of endometrial preparation for FET. The effect of gonadotropin-releasing hormone agonist (GnRH-a) pretreatment for FET among women with PCOS remains controversial., Purpose: We intend to explore whether GnRH-a pretreatment could improve clinical outcomes for women with PCOS undergoing FET., Methods: PubMed, Embase, ClinicalTrials.gov, Cochrane Library, and Web of Science were searched up to May 16, 2024. Eligible studies involved patients with PCOS undergoing FET and receiving GnRH-a pretreatment for endometrial preparation, with artificial cycle (AC) as the control therapy. Only randomized controlled trials (RCTs) published in Chinese and English were included. Data extraction was performed independently by two authors. Effect was quantified using odd ratios (ORs) with 95% confidence intervals (CIs) using random-effect models with the Mantel-Hansel (M-H) method in Revman software. Quality of outcomes was evaluated using the GRADEpro system. Primary outcomes contained the clinical pregnancy rate, miscarriage rate, and live birth rate. Secondary outcomes included the incidence of preterm labor and gestational diabetes mellitus (GDM)., Results: Ninety-seven records were initially retrieved, with 21 duplicates and 65 articles excluded after title and abstract screening. Seven studies were excluded due to retrospective design, leaving three RCTs with 709 participants. Among them, 353 received GnRH-a pretreatment as the intervention group and 356 received AC as the control group. No significant differences were observed in the clinical pregnancy rate (OR 1.09, 95% CI 0.75 to 1.56, P = 0.66), miscarriage rate (OR 0.73, 95% CI 0.28 to 1.90, P = 0.52), live birth rate (OR 0.87, 95% CI 0.61 to 1.25, P = 0.46), and the risk of preterm labor (OR 1.45, 95% CI 0.79 to 2.65, P = 0.23) and GDM (OR 0.73, 95% CI 0.37 to 1.48, P = 0.39) between the two groups., Conclusions: In this meta-analysis, GnRH-a pretreatment does not confer any advantages and appears unnecessary for women with PCOS undergoing FET. Additional RCTs should focus on maternal complications and the health of offspring., (© 2024. The Author(s).)

The study investigates whether a 3-day pretreatment course with a GnRH antagonist in the early follicular phase has an impact on the number of retrieved COCs in a GnRH antagonist stimulation protocol. This is a retrospective single center crossover study involving women who did not conceive after one GnRH antagonist stimulation cycle ("standard cycle") and proceeded with another GnRH antagonist stimulation cycle preceded by early administration of GnRH antagonist for 3 days ("pretreatment cycle") with fresh embryo transfer or frozen embryo transfer. 430 patients undergoing 860 cycles were included. The mean female age was 34.4 ± 4.8 years. Indications for fertility treatment included unexplained infertility (34.3%), male-factor infertility (33.3%), age (16.9%), PCOS (8.2%), tubal (4.7) and endometriosis (2.6%). All cycles were divided into two groups: group 1 (standard, 430 cycles) and group 2 (pretreatment, 430 cycles). The mean duration of stimulation was similar in both groups (10.3 vs 10.3 days, p = 0.28). The starting dose of gonadotropin (234.9 vs 196.8 IU, p<0.001), total amount of gonadotropin used (2419 vs 2020 IU, p<0.001), the total number of retrieved COCs (10 vs 7.8 p<0.001) and the number of mature oocytes (8 vs 5.8 p<0.001) were significantly higher in group 2 than in group 1. The Generalized estimating equation (GEE) regression analysis showed that the pretreatment strategy had a significant positive effect on the number of COCs (coefficient 2.4, p <0.001 after adjusting for known confounders (age, indication, stimulation dose, type, and duration of stimulation). In conclusion, A 3-day course of GnRH antagonist pretreatment increases the number of COCs obtained after ovarian stimulation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Federica et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: With the advancement in embryology and the introduction of time-lapse monitoring system, the embryologists' goal might be to find not only the embryo with the highest probability of live birth, but also the embryo with the highest probability to progress to a healthy full-term delivery. Thus, we aimed to investigate the association between morphokinetic time-lapse parameters and obstetrical and perinatal complications., Methods: A cohort study reviewing fertility and delivery files of all singletone births from IVF patients whose embryos were cultured in a time-lapse monitoring system and had a single fresh embryo transfer at our center between 2013-2019. We conducted multiple comparisons between complicated and uncomplicated pregnancies of each perinatal complication, including: gestational diabetes mellitus (GDM); small for gestational age (SGA); pre-eclamptic toxemia (PET); preterm labor < 37 weeks of gestation (PTL); and third stage of labor complications. A comparison between pregnancies with and without a composite outcome of placental complications including GDM, SGA, PET and PTL was also conducted. Baseline characteristics, treatment and morphokinetic parameters in complicated and uncomplicated gestations were compared. Logistic regression analysis was utilized to adjust results for potential confounders., Results: One hundred seventy-six single embryo transfers resulted in 176 live births. Morphokinetic time-lapse parameters were similar between the groups, except for a shorter time to full blastulation in the SGA group (tB-tPNf = 75.5 ± 1.3 h vs. 79.5 ± 4.8 in the non-SGA group, p < 0.001), and shorter third cell cycle duration in the PET group (CC3 = 12.4 ± 1.1 h vs. 13.6 ± 2.9 in the non-PET group, p = 0.02). On multivariate regression analysis, none of the morphokinetic parameters were found to be significantly correlated with any of the perinatal complications., Conclusion: Time-lapse morphokinetic parameters of the embryo transferred are not associated with adverse obstetric and perinatal outcomes., (© 2024. The Author(s).)

Melatonin supplementation during in vitro maturation (IVM) improves porcine oocyte maturation and embryonic development by exerting antioxidative effects. Nevertheless, the mechanism by which melatonin prevents polyspermy after in vitro fertilization (IVF) remains unclear. Here, we examined the effects of melatonin on cytoplasmic maturation and the incidence of polyspermic penetration in porcine oocytes. No statistically significant difference was observed in the rate of first polar body formation between the groups (Control, Melatonin, Melatonin + Luzindole, and Melatonin + 4-P-PDOT). Interestingly, melatonin supplementation significantly improved the cytoplasmic maturation of porcine oocytes by enhancing the normal distribution of organelles (Golgi apparatus, endoplasmic reticulum and mitochondria) and upregulating organelle-related gene expressions (P < 0.05). However, these promotional effects were counteracted by melatonin antagonists, suggesting that melatonin enhances cytoplasmic maturation through its receptors in porcine oocytes. Melatonin supplementation also significantly improved the rate of diploid and blastocyst formation after IVF by promoting the normal distribution of cortical granules (P < 0.05). In conclusion, melatonin supplementation during in vitro maturation of porcine oocyte improves fertilization efficiency and embryonic developmental competence by enhancing cytoplasmic maturation., (© 2024. The Author(s).)