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The implementation of non-invasive PGT-A offers a new strategy to genetically assess the preimplantation embryo and to enhance IVF results. The extraction of DNA from the embryo culture medium has been sufficiently demonstrated, and the ability to obtain chromosomal information as a result is particularly interesting. As morphological criteria have proven to have a weak correlation with embryo ploidy status, this technique emerges as a promising alternative for embryo selection. It also appears reasonable that avoiding biopsy may enhance further embryo development. However, there are growing concerns regarding several aspects of this technique, such as the origin of this cell free DNA, the degree of representativeness of the whole embryo, the need for extended culture or the absence of standardized protocols. Despite the published data on good prognosis couples are promising, niPGT-A is yet to be considered a substitute for trophectoderm biopsy. The current SWOT analysis aims to summarize both resolved and unresolved issues, as well as limiting aspects of niPGT-A., Competing Interests: Declarations. Ethical Approval: Not applicable. Consent to Participate: Not applicable. Consent for Publication: Not applicable. Conflict of Interest: The authors do not declare any conflict of interest., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Purpose: The objective of this study was to investigate the correlation between the pronuclear/cytoplasmic (PN/C) ratio and the number of chromosomes in mouse zygotes to understand the implications of pronuclear size regulation in early embryonic development., Methods: A combination of enucleation and aggregated chromosomes/chromatin (AC) transfer was utilized to create oocytes with varying numbers of chromosomes. Time-lapse imaging and immunofluorescence staining were employed to analyze pronuclear dynamics and chromosomal configurations., Results: Higher chromosome numbers correspond to a larger PN/C ratio. Oocytes with a higher number of chromosomes exhibited larger pronuclei., Conclusion: The study underscores the complexity of pronuclear size regulation and its correlation with the number of chromosomes. The findings suggest potential applications in ART, where assessing the PN/C ratio could serve as a biomarker for zygote quality and aneuploidy., Competing Interests: Declarations. Ethics approval: All animal experiments conducted in this study were approved by the Committee of Animal Care and Use at Okayama University (OKU–2022975). Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Map the nuclear error phenotypes in the two-cell embryo after assisted reproduction using time lapse images and the effect on good quality blastocyst formation., Methods: Retrospective cohort study using time lapse images, categorizing 2331 two-cell embryos from 392 patient couples and 504 ART cycles categorizing each embryo as mononucleated, multinucleated, micronucleated, binucleated, split nucleation or mixed error. Correlating nuclear error phenotype with good quality blastocyst formation rate (BFR) using contingency tables and unadjusted odds ratio., Results: An overall nuclear error rate of 47.1% was observed in two-cell embryos. The most frequent error was multi-nucleation (14.2%) followed by mixed error (11%), micro-nucleation (8.6%), bi-nucleation (7.4%) and split nucleation (5.8%). Blastocyst formation rate (BFR) was reduced in embryos with nuclear errors, 46.2% for embryos with one cell affected, 27.6% for embryos with both cells affected, compared to 58.6% for mononucleated cells, p < 0.001 for both. Binucleated embryos were as likely as mononucleated embryos to become clinically useful blastocysts (56.8% vs 58.6%, n.s., unadjusted OR 0.94), whereas all the other phenotypes were less likely to develop into good quality blastocysts. The worst outcome was noted for embryos with split nucleation, with just 12.4% BFR, OR 0.12 (0-08-0.21), p < 0.001., Conclusion: Nuclear errors are common at the two-cell stage. Overall, presence of nuclear errors reduces the likelihood of becoming good quality blastocysts. Both the number of affected cells and the different nuclear error phenotypes have impact on blastocyst formation rate, except binucleated embryos., Competing Interests: Declarations. Ethics approval: This research study was conducted retrospectively from data obtained for clinical purposes. It was done in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments. The study was approved by the Swedish Ethical Review Authority, ID 023-01153-0. Consent to participate: Patients had the option to consent to participation in quality assurance and/or methodological improvements prior to their assisted reproduction treatment. Only patients actively consenting to research and/or evaluation of treatments were included in this retrospective study. This approach was deemed satisfactory to the ethical committee, and no additional consent to participate in this retrospective study was required. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: The female genital tract microbiome has become a particular area of interest in improving assisted reproductive technology (ART) outcomes with the emergence of next-generation sequencing (NGS) technology. However, NGS assessment of microbiomes currently lacks uniformity and poses significant challenges for accurate and precise bacterial population representation., Objective: As multiple NGS platforms and assays have been developed in recent years for microbiome investigation-including the advent of long-read sequencing technologies-this work aimed to identify current trends and practices undertaken in female genital tract microbiome investigations., Results: Areas like sample collection and transport, DNA extraction, 16S amplification vs. metagenomics, NGS library preparation, and bioinformatic analysis demonstrated a detrimental lack of uniformity. The lack of uniformity present is a significant limitation characterised by gap discrepancies in generation and interpretation of results. Minimal consistency was observed in primer design, DNA extraction techniques, sample transport, and bioinformatic analyses., Conclusion: With third-generation sequencing technology highlighted as a promising tool in microbiota-based research via full-length 16S rRNA sequencing, there is a desperate need for future studies to investigate and optimise methodological approaches of the genital tract microbiome to ensure better uniformity of methods and results interpretation to improve clinical impact., Competing Interests: Declarations. We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us. We confirm that we have given due consideration to the protection of intellectual property associated with this work and that there are no impediments to publication, including the timing of publication, with respect to intellectual property. In so doing, we confirm that we have followed the regulations of our institutions concerning intellectual property. We understand that the corresponding author is the sole contact for the Editorial process (including Editorial Manager and direct communications with the office). He is responsible for communicating with the other authors about progress, submissions of revisions and final approval of proofs. We confirm that we have provided a current, correct email address which is accessible by the corresponding author. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s).)

After over 20 years of progressively increasing clinical utilization of PGT-A (and its precursors), the American Society for Reproductive Medicine (ASRM) and its daughter society, the Society for Assisted Reproduction (SART), for the first time published a committee opinion clearly acknowledging that "the value of PGT-A as a routine screening test for patients undergoing in vitro fertilization (IVF) has not been demonstrated." This statement is timely and welcome but requires some additions and raises some new questions, among those why, if PGT-A in a general population does not improve IVF cycle outcomes, the routine clinical utilization of PGT-A should continue., Competing Interests: Declarations. Competing interests: N.G. and D.H.B. are listed as co-owners of several already awarded and still pending U.S. patents, some claiming benefits from androgen supplementation in women with low functional ovarian reserve, a topic addressed in this manuscript. Others relate to diagnostic and potential therapeutic benefits of AMH, also marginally addressed in this manuscript. N.G. is a shareholder in Fertility Nutraceuticals, LLC, which produces a DHEA product, and is the owner of The CHR., where much of the research reported in this manuscript was performed. N.G. and D.H.B. also receive patent royalties from Fertility Nutraceuticals, LLC. N.G. and D.H.B. in the past have received research support, travel funding, and lecture fees from various Pharma and medical device companies, none, however, over the last three years and none in any way related to this manuscript., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Zinc is known to influence chromatin stability, motility and protection against oxidative stress. While swim-up remains the preferred method for selecting sperm in Assisted Reproductive Technologies (ART), concerns arise regarding sperm DNA fragmentation associated with this procedure. Given zinc's significant role in protecting sperm DNA integrity and motility, we aimed to investigate the impact of zinc supplementation during the swim-up process on sperm quality., Methods: Semen samples from 203 normozoospermic men were used. Samples were divided into fractions and swim-up procedure was applied using human tubal fluid (mHTF) supplemented with three different concentrations of zinc or medium without supplementation as control. DNA fragmentation, chromatin maturity, reactive oxygen species (ROS) levels, motility and protein phosphorylation levels analyses were addressed to each fraction., Results: The sperm DNA fragmentation was reduced in sperm recovered by swim-up in media with all concentrations of zinc assayed with respect to the control (p < 0.0001). Aniline blue staining showed better chromatin maturity in sperm recovered with 2.5- and 3.5-mM zinc (p = 0.045; p = 0.021). Kinematic parameters such as curvilinear velocity and beat-cross frequency showed improvement with 2.5 mM zinc (p = 0.0080 and p = 0.0400), whereas straightness, linearity, and hypermotility showed improvement with 5 mM zinc (p = 0.0075, p = 0.0069, and p = 0.0244). Protein phosphorylation patterns showed changes associated with treatment with zinc, and only 5 mM zinc treatment showed a decrease in ROS levels., Conclusion: The addition of zinc to mHTF provided optimal physiological conditions for sperm recovered through swim-up. This supplementation should be considered for selecting sperm for use in ART., Competing Interests: Declarations. Ethics approval: The study was approved by the Institutional Review Board of Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario (No. 6060/359). Consent to participate: For this study, all participants signed informed consent in compliance with ethical standards. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease primarily impacting women of childbearing age. While pregnancy and hormonal stress can trigger SLE flare-ups, the effects of assisted reproductive therapies (ARTs) on SLE patients are not well defined. We conducted a search of PubMed/Medline, Embase, and CENTRAL until March 20, 2024, to find observational studies assessing the prevalence of SLE flares and pregnancy outcomes following ARTs. Our analysis included random-effects meta-analysis and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach for evaluating evidence quality. Five studies involving 237 SLE women who underwent ARTs were eligible. The meta-analysis indicated a prevalence of SLE flares at 17% (95% CI: 10-25%) with moderate-quality evidence. The pooled prevalence of arthritis flares was 7% (95% CI: 0-25%) with low-quality evidence. Successful pregnancy rates were 58% (95% CI: 43-72%), and live birth rates were 96% (95% CI: 83-100%), both with low-quality evidence. Moderate-quality evidence showed pregnancy complications, including preterm premature rupture of membranes (PPROM) at 8% (95% CI: 3-16%), miscarriages at 2% (95% CI: 0-9%), intrauterine fetal demise (IUFD) at 4% (95% CI: 0-11%), and preeclampsia at 7% (95% CI: 1-17%). Low-quality evidence showed preterm labor at 10% (95% CI: 0-32%) and ovarian hyperstimulation syndrome (OHSS) at 2% (95% CI: 0-11%). SLE flares, as well as pregnancy complications such as IUFD, miscarriage, PPROM, and preeclampsia in ART recipients, are equivalent to those in spontaneous conception. This indicates that ART is relatively safe for SLE patients with meticulous pregnancy planning. Key Points • Systemic lupus erythematosus (SLE) is a chronic autoimmune disease primarily impacting women of childbearing age. • Pregnancy in women with SLE poses elevated maternal and fetal risks compared to healthy women. • SLE flares and pregnancy complications while receiving ART are equivalent to those in spontaneous conception and ART is relatively safe for SLE patients., Competing Interests: Declarations. Disclosures: None. Disclaimer: The perspectives and opinions presented in this article belong solely to the authors and do not necessarily represent the official stance or policy of any organization or institution., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Early embryonic arrest (EEA) is a critical impediment in assisted reproductive technology (ART), affecting 40% of infertile patients by halting the development of early embryos from the zygote to blastocyst stage, resulting in a lack of viable embryos for successful pregnancy. Despite its prevalence, the molecular mechanism underlying EEA remains elusive. This review synthesizes the latest research on the genetic and molecular factors contributing to EEA, with a focus on maternal, paternal, and embryonic factors. Maternal factors such as irregularities in follicular development and endometrial environment, along with mutations in genes like NLRP5, PADI6, KPNA7, IGF2, and TUBB8, have been implicated in EEA. Specifically, PATL2 mutations are hypothesized to disrupt the maternal-zygotic transition, impairing embryo development. Paternal contributions to EEA are linked to chromosomal variations, epigenetic modifications, and mutations in genes such as CFAP69, ACTL7A, and M1AP, which interfere with sperm development and lead to infertility. Aneuploidy may disrupt spindle assembly checkpoints and pathways including Wnt, MAPK, and Hippo signaling, thereby contributing to EEA. Additionally, key genes involved in embryonic genome activation-such as ZSCAN4, DUXB, DUXA, NANOGNB, DPPA4, GATA6, ARGFX, RBP7, and KLF5-alongside functional disruptions in epigenetic modifications, mitochondrial DNA, and small non-coding RNAs, play critical roles in the onset of EEA. This review provides a comprehensive understanding of the genetic and molecular underpinnings of EEA, offering a theoretical foundation for the diagnosis and potential therapeutic strategies aimed at improving pregnancy outcomes., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Postovulatory aging (POA) of oocytes is clinically significant as it mirrors the degeneration observed in maternally aged oocytes, leading to substantial impairments in oocyte quality and the success rates of artificial reproductive technology (ART). The molecular alterations associated with POA, such as the degeneration of the first polar body, an increase in perivitelline space, reactive oxygen species (ROS) accumulation, energy depletion, and chromosomal and DNA damage, underscore the urgency of finding interventions to mitigate these effects. This study aims to identify whether nicotinamide riboside (NR) can prevent POA during the process of in vitro culture and raise the success rates of ART., Method: Taking advantage of an in vitro postovulatory oocyte aging model, we examined the morphological integrity and NAD + levels of ovulated mouse MII oocytes after 24 h of culturing. Following in vitro fertilization, we assessed the embryonic developmental potential of oocytes affected by POA. Using immunofluorescence and confocal microscopy, we measured the levels of ROS, mitochondrial function, and γH2AX. We also evaluated spindle assembly and chromosome alignment. Additionally, we detected the distribution of cortical granules to assess the metabolic and quality changes in POA oocytes with the supplementation of NR. To further our analysis, quantitative real-time PCR was conducted to measure the mRNA expression levels of antioxidant enzymes Sod1 and Gpx1 in the oocytes., Results: With 200 μM NR supplementation during in vitro culture for 24 h, the oocytes from POA demonstrated reduced signs of aging-related decline in oocyte quality, including reduced ROS accumulation, improved mitochondrial function, and corrected mis-localization of cortical granules. This improvement in oocyte quality is likely due to the inhibition of oxidative stress via the NAD + /SIRT1 signaling pathway, which also helped to restore normal spindle assembly and chromosome alignment, as well as reduce the elevated levels of γH2AX, thereby potentially enhancing the embryonic development potential., Conclusion: Current research provides evidence that NR is an efficient and safe natural component that prevents the process of POA and is thus a potential ideal antiaging drug for raising the success rates of ART in clinical practice., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Endometriosis (EMT) -related infertility has been a challenge for clinical research. Many studies have confirmed that abnormal alterations in the immune microenvironment and glycolysis are instrumental in causing EMT-related infertility. Recently, our research team identified several key glycolysis-immune-related genes in the endometrial cells of EMT patients. This study aimed to further investigate the expression patterns of pyruvate dehydrogenase kinase 3 (PDK3), glypican-3 (GPC3), and alcohol dehydrogenase 6 (ADH6), which are related to glycolysis and immunity, in the follicular microenvironment of infertile patients with EMT using enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR) assays. According to the results, compared to the patients with tubal factor infertility, the concentrations of PDK3 and GPC3 were considerably increased in the follicular environment of EMT patients, while ADH6 expression was significantly reduced. The number of oocytes retrieved, the transferable embryo rate, and the cumulative clinical pregnancy rate of EMT patients were significantly reduced, and there was a correlation with the level of PDK3, GPC3, and ADH6 in Follicular Fluid (FF). The area under the receiver operating characteristic (ROC) curve for predicting clinical pregnancy in infertile patients with EMT for PDK3, GPC3, ADH6, and their combination was 0.732, 0.705, 0.855, and 0.879, respectively (P < 0.05). In conclusion, our research indicates that glycolysis-immune-related genes may contribute to infertility in EMT patients through immune infiltration, and disruption of mitochondrial and oocyte functions. The combined detection of PDK3, GPC3, and ADH6 in FF helps to predict clinical pregnancy outcomes in infertile patients with EMT., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Purpose: This study aimed to assess whether assisted reproductive technology alters DNA methylation levels at the H19 promoter and H19 imprinting control element (ICE) in fetal tissues obtained after multifetal pregnancy reduction., Methods: Fetal tissues from multiple pregnancies were obtained, including fresh and frozen-thawed embryos: nine from conventional in vitro fertilization (c-IVF), four from intracytoplasmic sperm injection (ICSI), ten from cryopreserved IVF embryos (cryo-IVF), and six from cryopreserved ICSI (cryo-ICSI) embryos. Next-generation sequencing-based bisulfite PCR was used to determine the DNA methylation status of three CpG islands (H19-1, H19-2, and H19-3) in the H19 promoter and H19 ICE. The primary outcome was H19-1 DNA methylation status, whereas secondary outcomes assessed H19-2, H19-3, and ICE methylation., Results: The ICSI (β = -3.189, 95% CI = -5.034 to -1.345, p = 0.0026), cryo-IVF (β = -2.150, 95% CI = -3.706 to -0.593, p = 0.0129), and cryo-ICSI (β = -2.238, 95% CI = -3.817 to -0.659, p = 0.0110) groups exhibited significantly lower methylation levels in the primary outcome H19-1 region than the c-IVF group after adjustment. For the secondary outcome H19-2 region, significant decreases were observed in the cryo-IVF (β = -2.132, 95% CI = -4.071 to -0.192, p = 0.0425) and cryo-ICSI groups (β = -2.598, 95% CI = -4.566 to -0.630, p = 0.0168)., Conclusions: These findings further indicate that embryo cryopreservation and potentially ICSI can lower the methylation level of the H19 promoter, advocating for careful use of these techniques when necessary., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflict of interest., (© 2024. The Author(s).)

Purpose: Currently, assisted reproduction clinics employ various sperm selection techniques to identify the best sperm for fertilization. However, these techniques may not assess crucial sperm traits that can substantially impact embryonic quality. To address this, we propose analyzing diverse histone modifications as potential markers of sperm functionality and success in assisted reproduction techniques., Methods: Cross-sectional pilot study including infertile male patients attending an infertility clinic in CABA, Argentina between April and August 2019 was performed. We used immunofluorescence techniques to evaluate post-translational modifications of histones in sperm and established correlations with in vitro fertilization outcome and embryo quality., Results: Our findings indicate a negative correlation between H3K4me3 and H3K4me2 marks and fertilization rate and showed a positive correlation of this parameter with H3K9me mark. In addition, there was a positive correlation between H3K27me3 and good embryo quality., Conclusions: This pilot study proposes a non-invasive strategy to predict embryo quality by analyzing spermatozoa prior to fertilization. The assessment of histone post-translational modifications in sperm samples could provide useful information for the recognition of epigenetic marks that could predict the health of the embryo of an assisted fertilization treatment., Competing Interests: Declarations. Ethical approval: The IBYME Ethics Committee approved this study, and the procedures used in this research comply with the principles of the Declaration of Helsinki. Conflict of interest: The authors declare that there are no conflicts of interest that could be seen as affecting the objectivity of the research presented., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study aimed to investigate the effect of diagnosis and treatment of chronic endometritis (CE) on the outcome of assisted reproductive technology (ART) with or without repeated implantation failure (RIF). This retrospective analysis included patients who underwent pathological examination for diagnosis of CE at Yamagata University Hospital. The examination was performed for all patients planned for ART with or without RIF. Patients who were examined within 6 months of the first oocyte retrieval or embryo transfer were included. We counted the number of CD138-positive cells within the endometrial stroma in patients' specimens and analyzed the patients' clinical information. Clinical rates of pregnancy and implantation were determined. A total of 80 women met the inclusion criteria: 13 CE-negative patients (17.3%) and 67 CE-positive patients (83.7%). A significant decrease was noted in the CD138-positive cell count between the first biopsy and second biopsy after CE treatment (p < 0.001). In addition, no significant differences were noted in ongoing pregnancy rates between the CE-negative patients and those who underwent CE treatment. The CD138-positive cell counts at first biopsy tended to be lower in each pregnancy group than in the non-pregnancy group. For patients planned to undergo ART, examination for diagnosis of CE with or without RIF could be considered. Pathological CD138-positive cell counts were considered useful for CE diagnosis and treatment decision-making. The study findings suggest the efficacy of antimicrobial agents in CE treatment, contributing to improved pregnancy outcomes., (© 2024. The Author(s).)

Purpose: This retrospective cohort study aims to investigate whether high-normal fasting blood glucose (FBG) affects assisted reproductive technology (ART) outcomes undergoing single blastocyst frozen-thawed embryo transfer (FET) cycles in women with normal body mass index (BMI)., Methods: 944 women with normal BMI and FBG levels undergoing single blastocyst FET cycles were enrolled. Based on the median of FBG (4.97 mmol/L, 1 mmol/L = 18 mg/dL), the subjects were categorized into the low-normal group (3.90 ≤ FBG ≤ 4.97 mmol/L, n = 472) and the high-normal group (4.97 < FBG < 6.10 mmol/L, n = 472). Multivariable logistic regression and receiver operating characteristic (ROC) were used to analyze the relationship between high-normal FBG and ART outcomes., Primary Outcome: live birth rate (LBR)., Results: LBR was significantly lower in the high-normal group than in the low-normal group (36.8% vs. 45.1%, p = 0.010), and the miscarriage rate was considerably higher than that in the low-normal group (23.9% vs. 16.5%, p = 0.041). High-normal FBG of female was an independent predictor of live birth (adjusted OR:0.747, 95% CI: 0.541-0.963, p = 0.027) and miscarriage (adjusted OR:1.610, 95% CI: 1.018-2.547, p = 0.042). ROC analyses showed that the cut-off values of FBG (endpoints: live birth and miscarriage) were 5.07 mmol/L, and 5.01 mmol/L, respectively., Conclusions: In women with normal BMI, high-normal FBG is an independent risk factor for lower LBR and higher miscarriage rate in single blastocyst FET cycles. Attention to preconception FBG monitoring in this particular population may allow early intervention to improve ART outcomes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

No increased risk of postpartum major depression (PPMD) was reported in women conceiving through assisted reproductive technologies (ART). However, ART may be associated with a higher risk of parenting difficulties in women with PPMD. In 359 women with a PPMD admitted to a Mother-Baby Unit (MBU), ART-women (4.2%) showed a 5-fold higher rate of parenting difficulties than those with spontaneous pregnancy (73.33% vs. 35.17%, multivariate ORa = 5.09 [1.48-17.48] p = 0.01). Specific support for mother-child relationship should be implemented in ART-women with PPMD., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Purpose: We examined the association between progesterone (P4), estradiol (E2), and human chorionic gonadotropin (hCG) levels in early pregnancy and the development of hypertensive diseases of pregnancy among women undergoing assisted reproduction., Methods: Retrospective study including patients who underwent frozen embryo transfer (FET), ovarian stimulation (OS), or unassisted conception (UC) and had a live singleton birth. The primary outcome was the development of hypertensive diseases of pregnancy (gestational hypertension, preeclampsia, HELLP, or eclampsia). Secondary outcomes were the development of fetal intrauterine growth restriction (IUGR), gestational diabetes mellitus, birth weight, and pre-term birth. Hormone levels and the development of the outcomes were correlated., Results: A total of 681 patients were included; 189 had FET, 193 had OS, and 299 had UC. Patients undergoing FET or OS were not more likely to develop hypertensive diseases of pregnancy compared with UC patients. While median levels of E2 and P4 were significantly different between P-FET and NC-FET patients (E2: 252 vs 317 pg/mL, P4: 64 vs 29 ng/mL, respectively; both p < 0.01), rates of hypertensive diseases of pregnancy did not significantly differ between those two groups. In the multivariate analyses, P4, E2, and hCG were not associated with the development of hypertensive diseases of pregnancy, but progesterone levels were significantly higher among those with IUGR. This remained consistent when the analysis was limited to FET patients., Conclusion: P4, E2, and hCG levels did not correlate with the development of hypertensive diseases of pregnancy but elevated progesterone levels did correlate with the development of IUGR., (© 2024. The Author(s).)

Placental angiogenesis is a pivotal process for feto-maternal circulation and ensures efficient development of the placenta throughout pregnancy. Many factors during in vitro fertilization and embryo transfer procedures may affect placental gene expression and fetus development. The present study aimed to identify differences in angiogenesis-related gene (VEGFA, FGF2, FLT1, and KDR) expression profiles in placentas after assisted reproductive technology fertilization and natural conception in healthy women. In a case-control study, term placentas were collected from Caucasian women after assisted reproductive technology fertilization (N = 20) and after natural conception in women with uncomplicated pregnancy (N = 9). The mRNA expression in placentas was examined for VEGFA, FGF2, FLT1, and KDR genes by real-time quantitative polymerase chain reaction (RT-qPCR). Group stratification was performed for comparison of investigated genes between the type of embryo transferred (fresh/frozen), place of tissue donation (center/margin), and newborns' gender (male/female). In the ART placentas, significant down-regulation of VEGFA gene (p = 0.016) and up-regulation of FLT1 (p = 0.026) and KDR (p < 0.001) gene receptors were observed. Genes encoding VEGFA receptors were up-regulated in both fresh (ET) and frozen (FET) embryo transfer groups compared to controls. For the FLT1 gene, a statistically significant difference was observed between the frozen embryo transfer group and the controls (p = 0.032). Relative expression of KDR was significantly higher for both embryo transfer groups compared to controls (p < 0.001) and between ET and FET (p = 0.002). No statistically significant differences were observed between placental expression in different places of tissue donation and newborns' gender. We observed differences in the placental expression of VEGFA and its receptors FLT1 and KDR in pregnancies after assisted reproductive technology compared to naturally conceived pregnancies. More research is needed to clarify these alterations that may affect placental development and fetal health., (© 2024. The Author(s).)

Advanced glycation end products (AGEs) can disrupt antioxidant system and steroidogenesis, resulting in detrimental effects on assisted reproductive technology (ART) outcomes. This study aimed to investigate the association of AGEs in follicular fluid (FF) with morphokinetic parameters of embryos and ART outcomes. Fifty women undergoing ART treatment were studied. AGEs, glucose, 25(OH) vitamin D, malondialdehyde (MDA) levels and catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX) activities were evaluated in FF. The expression of 3βHSD, CYP11A1, and CYP19A1 genes were analyzed in granulosa cells (GCs) by qRT-PCR technique. Morphokinetic parameters were evaluated using time-lapse technology. The FF level of AGEs was reversely associated with CAT, SOD, and GPX activities, and total and mature oocytes number, blastocyst formation rate, and high-grade embryos number, while it showed positive correlations with the FF MDA levels, the expression of steroidogenesis genes, number of immature oocytes, morphokinetic parameters, and number of low-grade embryos. Furthermore, the level of vitamin D in FF had an inverse association with AGEs and positive correlations with ART outcomes and morphokinetic parameters. Comparison between the those with positive and negative biochemical pregnancy showed no significant differences in terms of FF factors and just the expression of 3βHSD, CYP11A1, and CYP19A1 genes were higher in pregnant women (p < 0.05). AGEs could delay blastomere division and lead to an increase in the number of low-quality embryos, while vitamin D have an adverse effect on AGEs and a protective function against AGEs negative effects., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Purpose: To evaluate whether a second biopsy, following a first diagnostic failure on blastocysts tested for preimplantation genetic testing for monogenic diseases (PGT-M), allows to obtain genetic diagnosis and to what extent this procedure can influence clinical pregnancy and live birth rates compared to the PGT-M process with a successful genetic diagnosis from the first biopsy., Methods: Embryos from women who underwent PGT-M in an infertility centre and who had been transferred after two biopsies for genetic analysis (n = 27) were matched in a 1:1 ratio accordingly to women's age (± 1 year) and fertility status (fertile vs infertile), as well as with the study period, with embryos who were transferred after receiving a conclusive PGT result straight after the first biopsy (n = 27). The main evaluated outcome was clinical pregnancy rate following embryo transfers in which healthy embryos were transferred after only one biopsy and those in which an embryo was transferred after being re-biopsied. Live birth rate was the secondary outcome., Results: Clinical pregnancy rate was 52% (95% CI: 34-69) following the transfer of a single-biopsy blastocyst and 30% (95% CI: 16-48) following the transfer of a re-biopsied blastocyst. The likelihood to have a healthy baby was 33% (95% CI: 19-52) following the transfer of a blastocyst biopsied once and 22% (95% CI: 11-41) following the transfer of a re-biopsied blastocyst., Conclusions: The re-biopsy intervention seems to considerably reduce the pregnancy potential of a blastocyst. However, a greater sample size is necessary to clarify this issue definitively., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To assess the relation between number of inseminated oocytes and cumulative live birth rate (CLBR) in order to provide guidance for limiting the number of surplus blastocysts., Methods: The study was a retrospective, single-center cohort analysis of 1223 ART complete cycles. Cycles were stratified according to female age (≤ 34, 35-38, and 39-42 years) and number of inseminated oocytes (1-5, 6-10, and > 10). Inclusion criteria were indication for IVF/ICSI with own spermatozoa and blastocyst culture up to day 6 of all embryos., Results: In patients younger than 35 years, insemination of more than ten oocytes produced an increase in overall blastocyst number, CLBR (40.3%, 54.3%, and 75.8%, respectively, for each oocyte group) and surplus embryo rate (12.9%, 27.8%, and 49.7% of cases for each group). Instead, in the middle age group, the use of more than ten oocytes was solely associated with an increase in the rate of surplus embryos (1.25%, 21.33%, and 28.68% of cases after stratification for oocyte number). In older patients, neither CLBR (9.1%, 23.9%, and 24.7%, respectively) nor rate of surplus embryos (2.0%, 7.1%, and 13.4% of cases for each group) were higher in cycles with more than ten inseminated oocytes., Conclusion: In women up to 38 years, sustainable CLBR are achieved while limiting the number of inseminated oocytes and the resulting blastocysts remaining unused. Based on this notion, novel treatment strategies could pursue high outcome rates, while alleviating the problems derived from surplus stored embryos., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Assisted reproductive technology (ART) led to the birth of 60,381 infants in 2020 in Japan. This number is set to increase as the future interest in ART is anticipated to rise. Couples receiving ART are monitoring the outcomes of these treatments to see whether any differences exist between babies conceived naturally and those conceived via ART. This study investigated the relationship between the long-term outcome of children born from ART with a focus on physical and psychomotor developments. A large volume of data concerning each relationship with ART was collected from various observational studies. Several findings indicate that, over time, the physical characteristics of babies born by ART, and those born naturally are comparable. However, some reports indicate that, until they reach school age, there may be a small difference in growth. ART and naturally conceived children do not vary in academic achievement or attention deficit hyperactivity disorder. Taken together, it is difficult to conclude with certainty that ART is the source of these differences since they may arise from the child's genetic factors or their environment., (© 2023. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

In the last four decades, advances in assisted reproductive technology (ART) have offered hope to individuals with fertility problems to conceive. However, a closer examination of the clinical outcomes of ART shows a stark contrast in Asian women compared to Caucasians, with majority of studies reporting lower reproductive success among Asian women. We performed a systematic review to elucidate the genes associated with ART clinical outcomes, with a focus on Asian ethnicities. We completed a database search to identify all studies associated with reproductive outcomes in women of different ethnic backgrounds. Following PRISMA, 128 studies were analyzed. Pathway analysis of gene sets was done using Cytoscapev3.4.0. We observed that age at menarche (AAM) was correlated with the timing of the first pregnancy, with Hawaiians having the lowest age (22.2 years) and Japanese the highest age (25.0 years). LIN28 mutations were associated with AAM and prevalent in both Chinese and American populations. FMR1 was most associated with ovarian reserve. Network analysis highlighted a close association between FMR1, FSHR, ESR1, BMP15, and INHA, through biological functions affecting menstrual cycle and hypothalamic-pituitary axis and therefore ovarian follicle development. Leveraging these findings, we propose the development of a personalized, ethnic-specific biomarker panel which would enhance patient stratification to address every woman's unique reproductive potential., (© 2023. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Purpose: Although significant improvements in assisted reproductive technology (ART) outcomes have been accomplished, a critical question remains: which embryo is most likely to result in a pregnancy? Embryo selection is currently based on morphological and genetic criteria; however, these criteria do not fully predict good-quality embryos and additional objective criteria are needed. The cumulus cells are critical for oocyte and embryo development. This systematic review assessed biomarkers in cumulus-oocyte complexes and their association with successful IVF outcomes., Methods: A comprehensive search was conducted using PubMed, Embase, Scopus, and Web of Science from inception until November 2022. Only English-language publications were included. Inclusion criteria consisted of papers that evaluated genetic biomarkers associated with the cumulus cells (CCs) in humans and the following three outcomes of interest: oocyte quality, embryo quality, and clinical outcomes, including fertilization, implantation, pregnancy, and live birth rates., Results: The search revealed 446 studies of which 42 met eligibility criteria. Nineteen studies correlated genetic and biochemical biomarkers in CCs with oocyte quality. A positive correlation was reported between oocyte quality and increased mRNA expression in CCs of genes encoding for calcium homeostasis (CAMK1D), glucose metabolism (PFKP), extracellular matrix (HAS2, VCAN), TGF-β family (GDF9, BMP15), and prostaglandin synthesis (PTGS2). Nineteen studies correlated genetic and biochemical biomarkers in CCs with embryo quality. A positive correlation was reported between embryo quality and increased mRNA expression in CCs of genes encoding for extracellular matrix (HAS2), prostaglandin synthesis (PTGS2), steroidogenesis (GREM1), and decreased expression of gene encoding for hormone receptor (AMHR2). Twenty-two studies assessed genetic and biochemical biomarkers in CCs with clinical outcomes. Increased expression of genes encoding for extracellular matrix (VCAN), and TGF-β family (GDF9, BMP15) were positively correlated with pregnancy rate., Conclusion: Genetic biomarkers from cumulus cells were associated with oocyte quality (CAMK1D, PFKP, HAS2, VCAN, GDF-9, BMP-15, PTGS2), embryo quality (GREM1, PTGS2, HAS2), and pregnancy rate (GDF9, BMP15, VCAN). These results might help guide future studies directed at tests of cumulus cells to devise objective criteria to predict IVF outcomes., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: The discontinuation of fertility treatment could decrease the chances of achieving parenthood for infertile patients and often leads to economic loss and medical resource waste. However, the evidence on the factors associated with discontinuation is unclear and inconsistent in the context of fertility treatment. This scoping review aimed to summarize the evidence on factors associated with discontinuation in fertility treatment, identify the current knowledge gap, and generate recommendations for future research., Methods: We searched PubMed, Embase, The Cochrane Library, Web of Science, CINAHL, American Psychological Association, and http://clinicaltrials.gov from inception to June 2023 without language or time restrictions. We also searched the grey literature in Open Grey and Google Scholar and hand-searched the reference lists of relevant studies to identify potentially eligible studies. Publications that studied factors associated with discontinuation in fertility treatment were included. The identified factors were mapped to the World Health Organization's treatment adherence model., Results: Thirty-seven articles involving 41,973 infertile patients from 13 countries were included in this scoping review. All studies identified the factors from the perspective of patients, except for one that described the factors from the healthcare providers' perspective. A total of 42 factors were identified, with most of them belonging to the patient-related dimension, followed by socio-economic-related, treatment-related, condition-related, and healthcare system-related dimensions. Female education level, social support, and insurance coverage decreased the likelihood of treatment discontinuation, whereas multiparous women, male infertility, depression, higher infertility duration, and treatment duration increased the likelihood of treatment discontinuation. Age, education level, and ethnicity are the commonly nonmodifiable factors for treatment discontinuation, while insurance coverage, depression, and anxiety symptoms are among some of the more commonly reported modifiable factors., Conclusion: This is the first scoping review examining and synthesizing evidence on the factors influencing of discontinuation in fertility treatment. This review could inform researchers, clinicians, and policymakers to address modifiable barriers and facilitators to develop personalized and multicomponent interventions that could improve the discontinuation in fertility treatment., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Endometrial compaction (EC) is defined as the difference in endometrial thickness from the end of the follicular phase to the day of embryo transfer (ET). We aimed to determine the role of EC in predicting assisted reproductive technology (ART) success by conducting a meta-analysis of studies reporting the association between EC and clinical outcomes of ART., Methods: MEDLINE via PubMed, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched from the date of inception to May 19, 2023. The primary outcome was live birth rate (LBR) per ET. Secondary outcomes were live birth or ongoing pregnancy per ET, ongoing pregnancy per ET, clinical pregnancy per ET, and miscarriage per clinical pregnancy., Results: Fifteen studies were included. When data from all studies reporting live birth were pooled, overall LBR rates were comparable in cycles showing EC or not [RR = 0.97, 95%CI = 0.92 to 1.02; 10 studies, 11,710 transfer cycles]. In a subgroup of studies that included euploid ET cycles, a similar LBR for patients with and without EC was noted [RR = 0.99, 95%CI = 0.86 to 1.13, 4 studies, 1172 cycles]. The miscarriage rate did not seem to be affected by the presence or absence of EC [RR = 1.06, 95%CI = 0.90 to 1.24; 12 studies]., Conclusion: The predictive value of EC in determining LBR is limited, and assessment of EC may no longer be necessary, given these findings., Trial Registration: PROSPERO CRD42023410389., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In the last four decades, the assisted reproductive technology (ART) field has witnessed advances, resulting in improving pregnancy rates and diminishing complications, in particular reduced incidence of multiple births. These improvements are secondary to advanced knowledge on embryonic physiology and metabolism, resulting in the ability to design new and improved culture conditions. Indeed, the incubator represents only a surrogate of the oviduct and uterus, and the culture conditions are only imitating the physiological environment of the female reproductive tract. In vivo, the embryo travels through a dynamic and changing environment from the oviduct to the uterus, while in vitro, the embryo is cultured in a static fashion. Importantly, while culture media play a critical role in optimising embryo development, a large host of additional factors are equally important. Additional potential variables, including but not limited to pH, temperature, osmolality, gas concentrations and light exposure need to be carefully controlled to prevent stress and permit optimal implantation potential. This manuscript will provide an overview of how different current culture conditions may affect oocyte and embryo viability with particular focus on human literature., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: This study assessed the visibility of embryologists on fertility clinic websites among Society for Assisted Reproductive Technology (SART) and the Human Fertilisation and Embryology Authority (HFEA) member clinics., Methods: During a 1-month interval (March 2022), all Society for Assisted Reproductive Technology (SART) and the Human Fertilisation and Embryology Authority (HFEA) member fertility clinic websites were evaluated. The professional representation of the primary care team was examined including specialties, the presence of headshots, and biographies., Results: A total of 446 fertility clinic websites were scanned in the search. The embryology team has the least common professional identification by their names (53.58%) compared to gynecology clinicians (96.21%, p < 0.001) and nurses (55.58%, p < 0.001). This trend also applies to other types of professional identifiers, such as headshots and biographies. Professional headshots of embryologists (50.34%) were less prominent than those of gynecology clinicians (93.51%, p < 0.001). A similar trend was observed in the biographies of the embryology team (47.20%) compared to gynecology clinicians (95.08%, p < 0.001)., Conclusion: The present study revealed that embryologists have low professional visibility on fertility clinic websites. Fertility clinics may prioritize enhancing the online visibility of their embryology laboratory team. This approach could potentially enhance the recognition of their team, foster transparency, and provide accessible information about the skills and expertise of healthcare professionals involved in the treatment process., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Research about ethical, legal, and social implications (ELSI) of assisted reproductive technologies (ART) is influenced by cultural and value-based perspectives. It impacts regulations, funding, and clinical practice, and shapes the perception of ART in society. We analyze trends in the global literature on ELSI of ART between 1999 and 2019. As most output is produced by North America, Western Europe, and Australia, we focus on international research, i.e., academic articles studying a different country than that of the corresponding author., Methods: The corpus, extracted from PubMed, Web of Science, and Scopus, includes 7714 articles, of which 1260 involved international research. Analysis is based on titles, abstracts and keywords, classification into ART fields and Topic Modeling, the countries of corresponding author, and countries mentioned in abstracts., Results: An absolute increase in the number of international studies, and their relative proportion. Trends of decentralization are apparent, yet geographic centralization remains, which reflects an unequal distribution of research funds across countries and may result in findings that do not reflect global diversity of norms and values. Preference for studying conceptual challenges through philosophical analysis, and for fields that concern only a portion of ART cycles. Less attention was dedicated to economic analysis and barriers to access, or to knowledge of and attitudes. International studies provide an opportunity to expand and diversify the scope of ELSI research., Conclusion: We call on the research community to promote international collaborations, focus on less explored regions, and divert more attention to questions of cost, access, knowledge, and attitudes., (© 2023. The Author(s).)

The purpose was to determine any difference in outcomes, primarily in terms of number of retrieved oocytes per procedure, between two different needles used for oocytes retrieval procedure in Assisted Reproductive Technologies: the single-lumen needle (SLN) versus the double-lumen needle (DLN) with follicle flushing after aspiration. This randomized controlled trial included oocyte retrieval (OR) cycles for IVF and ICSI performed in 18 to 42-year-old women between March 2019 and January 2021 at a tertiary-care Fertility Center. A total of 200 ORs were randomized, 100 in each group. The mean number of retrieved oocytes was not different between groups (10.2 ± 6.5 for DLNs vs. 10.7 ± 7.0 for SLNs, p = 0.810). No significant differences were observed also in terms of number of retrieved oocytes/punctured follicles (83.0% ± 27.0% vs. 81.0% ± 22.0%, p = 0.916), number of retrieved oocytes/follicles at trigger (78.0% ± 29.0% vs. 78.0% ± 27.0%, p = 0.881), number of mature oocytes (7.6 ± 5.3 vs. 8.0 ± 5.1, p = 0.519), and pregnancy rate (27% vs. 23%, p = 0.514). However, the time required to retrieve each oocyte was longer using the DLN (1.5 ± 1.3 vs. 1.1 ± 0.9 minutes, p = 0.002). The present study confirmed the new perspectives on the sole use of SLNs in terms of saving time, without affecting the number of retrieved oocytes. Trial registration number and date of registration NCT03611907; July 26, 2018., (© 2023. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Purpose: To determine what policies exist regarding age and provision of fertility treatment in United States fertility clinics., Methods: Medical directors of the Society for Assisted Reproductive Technology (SART) member clinics were surveyed regarding clinic demographics and current policies pertaining to age and provision of fertility treatment. Univariate comparisons were performed using Chi-square and Fisher exact tests as appropriate, with significance set at P ≤ 0.05., Results: Of the 366 clinics surveyed, 18.9% (69/366) responded. A majority of clinics who responded 88.4% (61/69) reported having a policy regarding patient age and provision of fertility treatment. Responding clinics with an age policy did not differ from those without a policy on the basis of geographical location, (p = 0.5), insurance mandate status (p = 0.9), practice type (p = 0.4), or annual number of ART cycles (p = 0.7). Of all clinics who responded, 73.9% (51/69) had a maximum maternal age for autologous IVF, with a median of 45 years (range 42-54). Similarly, 79.7% (55/69) of responding clinics had a maximum maternal age for donor oocyte IVF, with a median of 52 years (range 48-56). Slightly under half, 43.4% (30/69) of responding clinics had a maximum maternal age for fertility treatment other than IVF (including ovulation induction or ovarian stimulation with or without IUI) with a median of 46 years (range 42-55). Of note, only 4.3% (3/69) of responding clinics had a policy with respect to maximum paternal age, with a median of 55 years (range 55-70). The most commonly cited reasons for having an age-limit policy were maternal risks of pregnancy, lower ART success rates, fetal/neonatal risks, and concerns about patients' ability to parent at an older age. More than half 56.5% (39/69) of responding clinics reported making exceptions to these policies, most commonly for patients who have pre-existing embryos. The majority of medical directors who responded to the survey believed there should be an ASRM guideline regarding maximum maternal age for autologous IVF 71% (49/69), donor oocyte IVF 78% (54/69) and other fertility treatments 62% (43/69)., Conclusions: Most fertility clinics who responded to this national survey reported having a policy regarding maternal age (but not paternal age) and provision of fertility treatment. Policies were based on risk of maternal/fetal complications, lower success rates at older age, and concerns about patients' ability to parent at an older age. The majority of medical directors of responding clinics believed there should be an ASRM guideline regarding age and provision of fertility treatment., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: A significant portion of the research on assisted reproductive technologies explores ethical, legal, and social implications. It has an impact on social perceptions, the evolution of norms of clinical practices, regulations and public funding. This paper reviews and maps the geographical distribution to test the hypothesis of geographical concentration and classifies the output by fields and topics., Methods: We queried PubMed, Scopus and the Web of Science for documents published between 1999 and 2019, excluding clinical trials and medical case reports. Documents were analyzed according to their titles, abstracts and keywords and were classified to assisted reproductive fields and by Topic Modeling. We analyzed geographic distribution., Results: Research output increased nearly tenfold. We show a trend towards decentralization of research, although at a slower rate compared with clinical assisted reproduction research. While the U.S. and the U.K.'s share has dropped, North America and Western Europe are still responsible for more than 70%, while China and Japan had limited participation in the global discussion. Fertility preservation and surrogacy have emerged as the most researched categories, while research about genetics was less prominent., Conclusions: We call to enrich researchers' perspectives by addressing local issues in ways that are tailored to local cultural values, social and economic contexts, and differently structured healthcare systems. Researchers from wealthy centers should conduct international research, focusing on less explored regions and topics. More research on financial issues and access is required, especially regarding regions with limited public funding., (© 2023. The Author(s).)

Purpose: Multiple morphological abnormalities of the sperm flagella (MMAF) are a severe form of sperm defect causing male infertility. Previous studies identified the variants in the CFAP69 gene as a MMAF-associated factor, but few cases have been reported. This study was performed to identify additional variants in CFAP69 and describe the semen characteristics and outcomes of assisted reproductive technology (ART) in CFAP69-affected couples., Methods: Genetic testing with next-generation sequencing (NGS) panel of 22 MMAF-associated genes and Sanger sequencing was performed in a cohort of 35 infertile males with MMAF to identify pathogenic variants. Morphological, ultrastructural, and immunostaining analyses were performed to investigate the characteristics of probands' spermatozoa. ART with intracytoplasmic sperm injection (ICSI) was carried out for the affected couples to get their own progenies., Results: We identified a novel frameshift variant in CFAP69 (c.2061dup, p. Pro688Thrfs*5) from a MMAF-affected infertile male with low sperm motility and malformed morphology of sperm. Furthermore, transmission electron microscopy and immunofluorescence staining revealed that the variant induced the aberrant ultrastructure and reduction of CFAP69 expression in the proband's spermatozoa. Moreover, the partner of the proband birthed a healthy girl through ICSI., Conclusions: This study expanded the variant spectrum of CFAP69 and described the good outcome of ART treatment with ICSI, which is beneficial to the molecular diagnosis, genetic counseling, and treatment of infertile males with MMAF in the future., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To analyze the geographic distribution of REI fellowships and clinics across the USA and to strategize ways to improve patient access to care., Methods: Cross-sectional study using population data obtained from publicly available United States Census Bureau, Society for Assisted Reproductive Technology (SART), and National Resident Matching Program websites. Outcomes include the number of REI clinics, REI fellowship-trained physicians, and REI fellowship programs., Results: In 2020, there were 643 assisted reproductive technology (ART) clinics reporting to SART and 1351 fellowship-trained REI physicians. Most clinics are located in the south (n = 209); however, the northeast has the highest density of REI clinics. Out of 301,316 in vitro fertilization (IVF) cycles in the USA in 2020, northeastern states initiated the most cycles (n = 93,565), and Midwestern states initiated the fewest cycles (n = 50,000). The northeast has the most REI physicians per million women aged 20-44 years (42.4) while the Midwest has the lowest ratio (19.5). There are fewer REI physicians per million women aged 20-44 years in states with a lower proportion of patients with health insurance (r = 0.56, 95% confidence interval ([CI] 0.34-0.73) and in states with a lower average income per resident (r = 0.65, 95% CI 0.46-0.79). Most of the 49 accredited REI fellowship programs in the USA are in the northeast (n = 18), and there are fewest in the south (n = 10) and west (n = 10)., Conclusion: Access to REI care has large geographic disparities from a clinic, physician, and training program perspective. Creative solutions are needed to remedy this problem., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Expanded carrier screening (ECS) has become a common practice for identifying carriers of monogenic diseases. However, existing large gene panels are not well-tailored to Chinese populations. In this study, ECS testing for pathogenic variants of both single-nucleotide variants (SNVs) and copy number variants (CNVs) in 330 genes implicated in 342 autosomal recessive (AR) or X-linked diseases was carried out. We assessed the differences in allele frequencies specific to the Chinese population who have used assisted reproductive technology (ART) and the important genes to screen for in this population., Methodology: A total of 300 heterosexual couples were screened by our ECS panel using next-generation sequencing. A customed bioinformatic algorithm was used to analyze SNVs and CNVs. Guidelines from the American College of Medical Genetics and Genomics and the Association for Molecular Pathology were adapted for variant interpretation. Pathogenic or likely pathogenic (P/LP) SNVs located in high homology regions/deletions and duplications of one or more exons in length were independently verified with other methods., Results: 64.83% of the patients were identified to be carriers of at least one of 342 hereditary conditions. We identified 622 P/LP variants, 4.18% of which were flagged as CNVs. The rate of at-risk couples was 3%. A total of 149 AR diseases accounted for 64.05% of the cumulative carrier rate, and 48 diseases had a carrier rate above 1/200 in the test., Conclusion: An expanded screening of inherited diseases by incorporating different variant types, especially CNVs, has the potential to reduce the occurrence of severe monogenic diseases in the offspring of patients using ART in China., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Women's infertility impacts the quality of life of both patients and couples and has multifaceted dimensions that increase the number of challenges associated with female infertility and how to face them. Female reproductive disorders, such as premature ovarian failure (POF), endometriosis, Asherman syndrome (AS), polycystic ovary syndrome (PCOS), and preeclampsia, can stimulate infertility. In the last decade, translational medicine has advanced, and scientists are focusing on infertility therapy with innovative attitudes. Recent investigations have suggested that stem cell treatments could be safe and effective. Stem cell therapy has established a novel method for treating women's infertility as part of a regeneration approach. The chief properties and potential of mesenchymal stem/stromal cells (MSCs) in the future of women's infertility should be considered by researchers. Due to their high abundance, great ability to self-renew, and high differentiation capacity, as well as less ethical concerns, MSC-based therapy has been found to be an effective alternative strategy to the previous methods for treating female infertility, such as intrauterine insemination, in vitro fertilization, medicines, and surgical procedures. These types of stem cells exert their beneficial role by releasing active mediators, promoting cell homing, and contributing to immune modulation. Here we first provide an overview of MSCs and their crucial roles in both biological and immunological processes. The next large chapter covers current preclinical and clinical studies on the application of MSCs to treat various female reproductive disorders. Finally, we deliberate on the extant challenges that hinder the application of MSCs in female infertility and suggest plausible measures to alleviate these impediments., (© 2023. The Author(s) under exclusive licence to Japan Human Cell Society.)

Purpose: To evaluate if assisted reproductive technology (ART) outcomes are different based on whether procedures - oocyte retrieval, insemination, embryo biopsy, or embryo transfer - are performed on a weekday versus weekend/holiday., Methods: Retrospective cohort study of all patients ≥ 18 years old who underwent oocyte retrieval for in vitro fertilization or oocyte banking (n = 3,197 cycles), fresh or natural-cycle frozen embryo transfers (n = 1,739 transfers), or had embryos biopsied for pre-implantation genetic testing (n = 4,568 embryos) in a large academic practice from 2015-2020. The primary outcomes were as follows: oocyte maturity for oocyte retrievals; fertilization rate for insemination; rate of no result on pre-implantation genetic testing for embryo biopsy; and live birth rate for embryo transfers., Results: The average number of procedures performed per embryologist per day was higher on weekends/holidays than weekdays. For oocyte retrievals performed on weekdays vs. weekends/holidays, there was no difference in oocyte maturity rate (88% vs 88%). There was no difference in the fertilization rate (82% vs 80%) in cycles that had intracytoplasmic sperm injection performed on weekdays vs. weekends/holidays. No difference was found in the no result rate for embryos biopsied on weekdays vs. weekends/holidays (2.5% vs 1.8%). Finally, there was no difference by weekday vs. weekend/holiday in the live birth rate per transfer among all transfers (39.6% vs 36.1%), or when stratified by fresh (35.1% vs 34.9%) or frozen embryo transfer (49.7% vs. 39.6%)., Conclusion: We found no differences in ART outcomes among women who had their oocyte retrievals, inseminations, embryo biopsies, or embryo transfers performed on weekdays versus weekends/holidays., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The aim of this study is to compare the ART (assisted reproductive technology) outcomes and cancellation rates between GnRH antagonist protocol and GnRH agonist short protocol in POSEIDON (Patient-Oriented Strategy Encompassing IndividualizeD Oocyte Number) groups 3 and 4. It is a retrospective cohort study conducted in the Department of Reproductive Medicine and Surgery of a tertiary-level hospital. Women who underwent ART treatment with either GnRH antagonist or GnRH agonist short protocol with fresh embryo transfer, between January 2012 and December 2019 belonging to POSEIDON 3 and 4 groups, were included. Among the 295 women who belonged to the POSEIDON groups 3 or 4, 138 women received GnRH antagonist and 157 women received GnRH agonist short protocol. The median total dose of gonadotropin in the GnRH antagonist protocol was not significantly different from GnRH agonist short protocol [3000, IQR (2481-3675) vs. 3175, IQR (2643-3993), p = 0.370]. There was a significant difference in the duration of stimulation between the GnRH antagonist and GnRH agonist short protocol [10, IQR (9-12) vs. 10, IQR (8-11), p = 0.002]. The median number of mature oocytes retrieved was significantly different in the cohort of women receiving GnRH antagonist protocol compared to GnRH agonist short protocol [3, IQR (2-5) vs. 3, IQR (2-4), p = 0.029]. There was no significant difference in the clinical pregnancy rate (24% vs. 20%, p = 0.503) and cycle cancellation rate (29.7% vs. 36.3%, p = 0.290) between the GnRH antagonist and agonist short protocols respectively. Live birth rate was not significantly different between the GnRH antagonist protocol (16.7%) and GnRH agonist short protocol (14.0%) [OR 1.23, 95% CI (0.56-2.68), p = 0.604]. After adjusting for the significant confounding factors, the live birth rate was not significantly associated with the antagonist protocol compared with the short protocol [aOR 1.08, 95% CI (0.44-2.63), p = 0.870]. Though GnRH antagonist protocol results in higher mature oocyte yield when compared with GnRH agonist short protocol, it does not translate into an increase in live birth in POSEIDON groups 3 and 4., (© 2023. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Background: Infertility, which is defined as the inability to conceive after at least 12 months of regular unprotected sexual intercourses, affects about 15-20% of couples worldwide and a male factor is involved in about half of the cases. The development of assisted reproductive technology (ART) made it possible to conceive also to individuals affected from severe oligospermia or azoospermia. However, the impact of the male factor on embryo development, implantation, prevalence of chromosomal abnormalities, genetic and epigenetic alterations, and clinical and obstetric outcomes is still controversial., Purpose: This narrative review examines the indications, minimum access criteria, and outcomes by individual ART technique in relation to the male factor., (© 2023. The Author(s).)

In 2003 and 2004, Aotearoa New Zealand enacted two key laws that regulate two very different ways in which the female body may be commodified. The Prostitution Reform Act 2003 (PRA) decriminalized prostitution, removing legal barriers to the buying and selling of commercial sexual services. The Human Assisted Reproductive Technology Act 2004 (HART Act), on the other hand, put a prohibition on commercial surrogacy agreements. This paper undertakes a comparative analysis of the ethical arguments underlying New Zealand's legislative solutions to prostitution and commercial surrogacy. While the regulation of prostitution is approached with a Marxist feminist lens with the aim to ensure the health and safety of sex workers, commercial surrogacy is prohibited outright for concerns of negative impacts on present and future persons. I ground the principles of each Act in their ethical foundations and compare these two against one another. I conclude that New Zealand's legislative approach to regulating the commodification of the female body is ethically inconsistent., (© 2023. The Author(s).)

Purpose: To assess the value of having an onsite genetic counseling service integrated into an assisted reproductive technology (ART) center., Methods: Since January 2021, we have offered genetic counseling at our ART center for couples whose medical history suggests risk of transmission of a genetic disorder. The percentage of couples referred for genetic counseling, the distribution of couples according to reasons for consultation, the mode of transmission in cases of Mendelian disorders, and the frequency of mutations for those with identified genetic disorders were determined., Results: In an 18-month period, 150 of 1340 couples (11.2%) enrolled for ART treatment were referred to the genetic counseling unit. Two-thirds (99/150, 66.0%) were referred for a known genetic risk, a family history of a genetic disorder or chromosomal abnormality, a serious condition of unknown cause, or consanguinity. The remaining couples had a putative genetic risk (diminished ovarian reserve, high incidence of oocyte immaturity, recurrent abortion, or severe male infertility). Of the 99 with known genetic risk, 62 (62.7%), were approved for ART treatment, 23 (23.2%) were recommended prenatal or preimplantation testing, and 14 (14.1%) were referred for further testing before undergoing ART., Conclusions: Our findings reveal great value in having an on-site genetic counseling unit for referral of ART patients. Such a unit makes the ART process smoother and safer for couples, and it lightens the burden of ART staff by removing responsibilities for which they are neither trained, nor should they have to assume., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study aims to assess the impact of endometrioma on embryo quality and cycle outcome in patients who undergo assisted reproductive technology (ART) treatment due to diminished ovarian reserve (DOR). Retrospective case-control study was conducted in women ≤ 40 years of age who underwent ART treatment caused by DOR, defined according to POSEIDON criteria, at a university-based infertility clinic between January 2015 and December 2020. Three groups of patients were selected: group A included patients with an idiopathic DOR, group B included patients with endometrioma(s) who underwent ovarian cystectomy, and group C included patients with endometrioma(s) without surgical treatment. A total of 351 women with DOR were included in the final analysis. Demographic characteristics, including age and AMH, were similar between the groups. Significant differences were observed among groups on mean number of MII oocytes retrieved (1.88 ± 1.59 vs. 2.84 ± 2.89 vs. 2.78 ± 2.41, respectively; p < 0.001) and mean number of embryos (1.04 ± 1.18 vs. 1.87 ± 2.01 vs. 1.66 ± 1.81, respectively; p < 0.001). However, the mean number of top-quality embryos, cycle cancellation, and live birth rates were similar between the groups. Clinical pregnancy (35 (26.5%) vs. 8 (18.2%) vs. 18 (42.9%), respectively; p = 0.038) and miscarriage rates (12 (9.1%) vs. 0 vs. 8 (19.0%), respectively; p = 0.009) were higher in endometrioma group without surgery. Women with DOR appear to have similar ART cycle outcomes regardless of the etiology, in terms of live birth rates. Infertility of endometrioma patients might be related to altered endometrium rather than to decreased oocyte quality. Cystectomy for endometrioma before IVF did not seem to affect the LBR., (© 2022. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

The major purpose of a couple at the first infertility appointment is to get a healthy baby as soon as possible. From diagnosis and decision on which assisted reproduction technique (ART) and controlled ovarian stimulation, to the selection of which embryo to transfer, the dedicated team of physicians and embryologists puts all efforts to shorten the time to pregnancy and live birth. Time seems thus central in assisted reproduction, and we can conveniently use it as a measure of treatment efficiency. How can we measure time to live birth? What timelines do we need to consider to evaluate efficiency? In this paper, we will discuss the importance of "Time" as a fundamental parameter for measuring ART success., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A 30-year-old woman presented with history of primary infertility of 8 years and multiple failed intrauterine insemination (IUI) attempts. She had the classic symptoms of Kartagener's syndrome-situs inversus, chronic sinusitis, and bronchiectasis. She had polycystic ovarian disease (PCOD) with regular menstrual cycles. Her karyotyping was normal. There was no other significant history including surgeries and the marriage was non-consanguineous. Her partner was 34 years old with normal semen and hormonal parameters. Her first intra-cytoplasmic sperm injection (ICSI) cycle with her own oocytes and husband's sperm resulted in a pregnancy but she suffered a miscarriage at 11 weeks. Her second attempt with donor oocytes and husband's sperm resulted in a pregnancy again but she miscarried at 9 weeks. The third attempt with a frozen embryo transfer with supernumerary embryos resulted in a pregnancy and she delivered a live female baby who was followed up for 8 years. This is the first report of a patient with KS undergoing assisted reproduction technologies (ART) treatment with donor oocytes. This is also the first Indian report of a female KS patient undergoing ART treatment with donor oocytes. IUI may not be the ideal treatment option in female patients with KS., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Assisted reproductive technology (ART) has experienced dramatic progress over the last 30 years, and gamete donation is routine in fertility clinics. Major advances in genetic diagnostics are part of this development due to the ability to analyze multiple genes or whole genomes fast and to an affordable prize. This requires knowledge and capability to evaluate genetic variants correctly in a clinical setting. Here we report a Menkes disease case, born after ART, where genetic screening and variant scoring failed to identify an egg donor as carrier of this fatal X-linked disorder. The gene variant is a deletion of a single base pair leading to a frameshift and premature termination of the protein, predicted to result in no or severely diminished function. The variant would be classified as likely pathogenic (class 4) and should be readily detectable by molecular genetic screening techniques. We wish to highlight this case to prevent future similar cases. IVI Igenomix has developed and embarked on an ambitious screening program to detect and prevent a large number of inherited severe childhood disorders in ART pregnancies. The company has recently achieved ISO 15189 certification with competence to evaluate and deliver timely, accurate, and reliable results. Failure to identify a pathogenic variant in the ATP7A gene leading to birth of two boys with Menkes disease invokes the required procedures to screen and detect disease-causing gene variants. This calls for ethical and legal considerations in ART diagnostics to prevent fatal errors like the present., (© 2023. The Author(s).)