Testis cell pyroptosis mediated by CASP1 and CASP4: possible sertoli cell-only syndrome pathogenesis.

BACKGROUND: Sertoli cell-only syndrome (SCOS) is the most serious pathological type of non-obstructive azoospermia. Recently, several genes related to SCOS have been identified, including FANCM, TEX14, NR5A1, NANOS2, PLK4, WNK3, and FANCA, but they cannot fully explain the pathogenesis of SCOS. This study attempted to explain spermatogenesis dysfunction in SCOS through testicular tissue RNA sequencing and to provide new targets for SCOS diagnosis and therapy. METHODS: We analyzed differentially expressed genes (DEGs) based on RNA sequencing of nine patients with SCOS and three patients with obstructive azoospermia and normal spermatogenesis. We further explored the identified genes using ELISA and immunohistochemistry. RESULTS: In total, 9406 DEGs were expressed (Log2|FC|≥ 1; adjusted P value < 0.05) in SCOS samples, and 21 hub genes were identified. Three upregulated core genes were found, including CASP4, CASP1, and PLA2G4A. Thus, we hypothesized that testis cell pyroptosis mediated by CASP1 and CASP4 might be involved in SCOS occurrence and development. ELISA verified that CASP1 and CASP4 activities in the testes of patients with SCOS were significantly higher than those in patients with normal spermatogenesis. Immunohistochemical results showed that CASP1 and CASP4 in the normal spermatogenesis group were mainly expressed in the nuclei of spermatogenic, Sertoli, and interstitial cells. CASP1 and CASP4 in the SCOS group were mainly expressed in the nuclei of Sertoli and interstitial cells because of the loss of spermatogonia and spermatocytes. CASP1 and CASP4 expression levels in the testes of patients with SCOS were significantly higher than those in patients with normal spermatogenisis. Furthermore, the pyroptosis-related proteins GSDMD and GSDME in the testes of patients with SCOS were also significantly higher than those in control patients. ELISA also showed that inflammatory factors (IL-1 ß, IL-18, LDH, and ROS) were significantly increased in the SCOS group. CONCLUSIONS: For the first time, we found that cell pyroptosis-related genes and key markers were significantly increased in the testes of patients with SCOS. We also observed many inflammatory and oxidative stress reactions in SCOS. Thus, we propose that testis cell pyroptosis mediated by CASP1 and CASP4 could participate in SCOS occurrence and development.

Blood metal/metalloid concentration of male subjects undergoing IVF/ICSI treatment outcomes: A prospective cohort study.

BACKGROUND: Previous epidemiology studies reported that heavy metal/metalloid exposure is associated with the impairment of semen quality. However, it is still not clear whether the in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment outcome will be affected after the heavy metal/metalloid exposure of the male partners. METHODS: A prospective cohort study with a 2-year followed-up was conducted in a tertiary IVF center. A total of 111 couples undergoing IVF/ICSI treatment were initially recruited from November 2015 to November 2016. Male blood concentrations of heavy metal/metalloid including Ca, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Mo, Cd, Hg, and Pb were measured by inductively coupled plasma mass spectrometry, and the lab and pregnancy outcome data were followed up. The associations between male blood heavy metal/metalloid concentration and the clinical outcomes were analyzed by Poisson regression analysis. RESULTS: Our results showed that none of the heavy metal/metalloid of male partners we investigated are significantly associated with the oocyte fertilization and good embryo (P ≥ 0.05); however, antral follicle count (AFC) was a protective factor for the oocyte fertilization (RR: 1.07, 95 % CI: 1.04-1.10). The blood Fe concentration of the male partner was positively associated (P < 0.05) with pregnancy in the first fresh cycle (RR:170.93, 95 % CI: 4.13-7082.04), cumulative pregnancy (RR: 23.61, 95 % CI: 3.25-171.64) and cumulative live birth (RR: 36.42, 95 % CI: 1.21-1092.54). In the first frozen embryo cycles, pregnancy was significantly associated (P < 0.05) with the blood Mn (RR: 0.01, 95 % CI:0.00-0.11) and Se concentration (RR: 0.01, 95 % CI:8.25 E-5-0.47) and female age (RR: 0.86, 95 % CI:0.75-0.99); live birth was significantly associated (P < 0.05) with the blood Mn concentration (RR: 0.00, 95 % CI: 1.14E-7-0.51). CONCLUSIONS: Our results suggested that the higher male blood Fe concentration was positively associated with pregnancy in the fresh embryo transfer cycle, cumulative pregnancy, and cumulative live birth, whereas the higher male blood Mn and Se concentration were associated with lower chance of pregnancy and live birth in the frozen embryo transfer cycle. However, the underline mechanism of this finding still needs further investigation.

Mature Cystic Teratoma: An Integrated Review.

Ovarian dermoid cysts, also called mature cystic teratomas (MCTs), account for 69% of ovarian germ cell tumors in young women. The tumors are formed by tissues derived from three germ layers, and sebaceous materials are most commonly seen. The origin of MCTs is widely considered to be the germ cell origin, which completes meiosis I. The clinical symptoms vary widely, but 20% of tumors could be asymptomatic. The diagnosis of MCTs is usually made without difficulty by ultrasound and confirmed by histopathology post-operatively. The imaging findings have a high diagnostic value. The typical characteristics present in the sonographic images, including a dermoid plug or Rokitansky nodule, are considered strong evidence for a teratoma. Although the malignant transformation of MCTs is rare, it can occur in some cases, especially in women of advanced age. The treatment of MCTs depends on the risk of malignancy, the age of the patient, and the patient's fertility reserve requirement. In this article, we review the epidemiology, clinical symptoms, diagnosis criteria, cellular origin, and treatment of mature cystic teratomas.

Mate-pair genome sequencing reveals structural variants for idiopathic male infertility.

Currently, routine genetic investigation for male infertility includes karyotyping analysis and PCR for Y chromosomal microdeletions to provide prognostic information such as sperm retrieval success rate. However, over 85% of male infertility remain idiopathic. We assessed 101 male patients with primary infertility in a retrospective cohort analysis who have previously received negative results from standard-of-care tests. Mate-pair genome sequencing (large-insert size library), an alternative long-DNA sequencing method, was performed to detect clinically significant structural variants (SVs) and copy-number neutral absence of heterozygosity (AOH). Candidate SVs were filtered against our in-house cohort of 1077 fertile men. Genes disrupted by potentially clinically significant variants were correlated with single-cell gene expression profiles of human fetal and postnatal testicular developmental lineages and adult germ cells. Follow-up studies were conducted for each patient with clinically relevant finding(s). Molecular diagnoses were made in 11.1% (7/63) of patients with non-obstructive azoospermia and 13.2% (5/38) of patients with severe oligozoospermia. Among them, 12 clinically significant SVs were identified in 12 cases, including five known syndromes, one inversion, and six SVs with direct disruption of genes by intragenic rearrangements or complex insertions. Importantly, a genetic defect related to intracytoplasmic sperm injection (ICSI) failure was identified in a patient with non-obstructive azoospermia, illustrating the additional value of an etiologic diagnosis in addition to determining sperm retrieval rate. Our study reveals a landscape of various genomic variants in 101 males with idiopathic infertility, not only advancing understanding of the underlying mechanisms of male infertility, but also impacting clinical management.

The Sperm Small RNA Transcriptome: Implications beyond Reproductive Disorder.

Apart from the paternal half of the genetic material, the male gamete carries assorted epigenetic marks for optimal fertilization and the developmental trajectory for the early embryo. Recent works showed dynamic changes in small noncoding RNA (sncRNA) in spermatozoa as they transit through the testicular environment to the epididymal segments. Studies demonstrated the changes to be mediated by epididymosomes during the transit through the adluminal duct in the epididymis, and the changes in sperm sncRNA content stemmed from environmental insults significantly altering the early embryo development and predisposing the offspring to metabolic disorders. Here, we review the current knowledge on the establishment of the sperm sncRNA transcriptome and their role in male-factor infertility, evidence of altered offspring health in response to the paternal life experiences through sperm sncRNA species and, finally, their implications in assisted reproductive technology in terms of epigenetic inheritance.

Common dysmorphic oocytes and embryos in assisted reproductive technology laboratory in association with gene alternations.

Amorphic or defected oocytes and embryos are commonly observed in assisted reproductive technology (ART) laboratories. It is believed that a proper gene expression at each stage of embryo development contributes to the possibility of a decent-quality embryo leading to successful implantation. Many studies reported that several defects in embryo morphology are associated with gene expressions during in vitro fertilization (IVF) treatment. There is lacking literature review on summarizing common morphological defects about gene alternations. In this review, we summarized the current literature. We selected 64 genes that have been reported to be involved in embryo morphological abnormalities in animals and humans, 30 of which were identified in humans and might be the causes of embryonic changes. Five papers focusing on associations of multiple gene expressions and embryo abnormalities using RNA transcriptomes were also included during the search. We have also reviewed our time-lapse image database with over 3000 oocytes/embryos to show morphological defects possibly related to gene alternations reported previously in the literature. This holistic review can better understand the associations between gene alternations and morphological changes. It is also beneficial to select important biomarkers with strong evidence in IVF practice and reveal their potential application in embryo selection. Also, identifying genes may help patients with genetic disorders avoid unnecessary treatments by providing preimplantation genetic testing for monogenic/single gene defects (PGT-M), reduce embryo replacements by less potential, and help scientists develop new methods for oocyte/embryo research in the near future.

Myostatin: a multifunctional role in human female reproduction and fertility - a short review.

Myostatin (MSTN) is member of the transforming growth factor ß (TGF-ß) superfamily and was originally identified in the musculoskeletal system as a negative regulator of skeletal muscle growth. The functional roles of MSTN outside of the musculoskeletal system have aroused researchers' interest in recent years, with an increasing number of studies being conducted in this area. Notably, the expression of MSTN and its potential activities in various reproductive organs, including the ovary, placenta, and uterus, have recently been examined. Numerous studies published in the last few years demonstrate that MSTN plays a critical role in human reproduction and fertility, including the regulation of follicular development, ovarian steroidogenesis, granule-cell proliferation, and oocyte maturation regulation. Furthermore, findings from clinical samples suggest that MSTN may play a key role in the pathogenesis of several reproductive disorders such as uterine myoma, preeclampsia (PE), ovary hyperstimulation syndrome (OHSS), and polycystic ovarian syndrome (PCOS). There is no comprehensive review regarding to MSTN related to the female reproductive system in the literature. This review serves as a summary of the genes in reproductive medicine and their potential influence. We summarized MSTN expression in different compartments of the female reproductive system. Subsequently, we discuss the role of MSTN in both physiological and several pathological conditions related to the female fertility and reproduction-related diseases.

Ultrasound-guided Manual Vacuum Aspiration is an optimal method for obtaining products of conception from early pregnancy loss for cytogenetic testing.

OBJECTIVE: The culture failure rate of conventional karyotyping in products of conception evacuated from early pregnancy loss by traditional electrical vacuum aspiration and/or dilation & curettage remains high. We aim to determine whether obtaining products of conception from early pregnancy loss via another evacuation approach, ultrasound-guided manual vacuum aspiration, could decrease the culture failure rate of karyotyping. METHODS: For patients with early pregnancy loss, ultrasound-guided manual vacuum aspiration (Case group) and traditional electrical vacuum aspiration and/or dilation & curettage (Control group) were applied as surgical methods for pregnancy loss management respectively. The evacuated products of conception were subjected to cytogenetic karyotyping analysis. The primary outcome was the culture failure rate of karyotyping. Secondary outcomes included the chromosomal abnormality spectrum, maternal cell contamination, and complications from the manual vacuum aspiration procedure. RESULTS: For the case group, 132 products of conception were genetically analyzed by conventional karyotyping. The culture failure rate was significantly lower than that of the control cohort (2.3% vs 7.4%, p = 0.027). 65.2% of cases were abnormal within the detection scope of karyotyping. The euploid female to male ratio was 0.82 (18:22), suggesting a lower likelihood of maternal cell contamination. The efficacy in achieving complete evacuation was 99.6%. There were no significant complications from the procedure. CONCLUSION: Ultrasound-guided manual vacuum aspiration approach significantly decreased the culture failure rate of karyotyping and decreased maternal cell contamination tendency, enabling a high and accurate cytogenetic diagnosis. It is especially crucial when the cytogenetic analysis is required in the early pregnancy loss clinics.

RETRACTED: Parallel bimodal single-cell sequencing of transcriptome and methylome provides molecular and translational insights on oocyte maturation and maternal aging.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. It has been brought to our attention that the authors of the article "Parallel bimodal single-cell sequencing of transcriptome and methylome provides molecular and translational insights on oocyte maturation and maternal aging" cannot agree on who should be listed as an author of the article. Further inquiry by the journal revealed that the authorship was also changed at the revision stages of the article without notifying the handling Editor, which is contrary to the journal policy on changes to authorship. The journal considers this unacceptable practice, and the Editor-in-Chief decided to retract the article.

Development and Validation of a Novel Prognostic Nomogram Combined With Desmoplastic Reaction for Synchronous Colorectal Peritoneal Metastasis.

Purpose: The prognostic value of desmoplastic reaction (DR) has not been investigated in colorectal cancer (CRC) patients with synchronous peritoneal metastasis (SPM). The present study aimed to identify whether DR can predict overall survival (OS) and develop a novel prognostic nomogram. Methods: CRC patients with SPM were enrolled from a single center between July 2007 and July 2019. DR patterns in primary tumors were classified as mature, intermediate, or immature according to the existence and absence of keloid-like collagen or myxoid stroma. Cox regression analysis was used to identify independent factors associated with OS and a nomogram was developed subsequently. Results: One hundred ninety-eight and 99 patients were randomly allocated into the training and validation groups. The median OS in the training group was 36, 25, and 12 months in mature, intermediate, and immature DR categories, respectively. Age, T stage, extraperitoneal metastasis, differentiation, cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC), and DR categorization were independent variables for OS, based on which the nomogram was developed. The C-index of the nomogram in the training and validation groups was 0.773 (95% CI 0.734-0.812) and 0.767 (95% CI 0.708-0.826). The calibration plots showed satisfactory agreement between the actual outcome and nomogram-predicted OS probabilities in the training and validation cohorts. Conclusions: DR classification in the primary tumor is a potential prognostic index for CRC patients with SPM. The novel prognostic nomogram combined with DR classification has good discrimination and accuracy in predicting the OS for CRC patients with SPM.

Effects of nonoxynol-9 (N-9) on sperm functions: systematic review and meta-analysis.

Objective: To summarize the currently available phase I and II clinical trials of the effects of nonoxynol-9 (N-9) on human sperm structure and functions. Methods: A systematic review and meta-analysis aiming to evaluate the spermicidal activity of N-9 on motility, was conducted in PubMed, EMBASE, and Cochrane databases by 10 March 2021. The counted numbers of progressive motile (PR) sperm in cervical mucus and the vanguard sperm penetration distances were analyzed. Other effects on sperm structures and physiological activities were reviewed as well. Results: In the pooled results, percentages or counted numbers of PR sperm decreased after the treatment of N-9. Vanguard sperm penetration distance was shortened in treated groups. N-9 has been confirmed to damage the structures of sperm, as well as other organelles like acrosome and mitochondria. The physiological activities such as generation of reactive oxygen species, superoxide dismutase activity, acrosin activity, and hemizona binding were all inhibited in the reviewed studies. Conclusions: N-9 has several impacts on sperm owing to its potency in reducing sperm motility and cervical mucus penetration, as well as other functional competencies. Lay summary: Nonoxynol-9 (N-9) has been used worldwide as a spermicide to kill sperm for more than 60 years but can cause side effects including vaginal irritation and can increase the rate of contraceptive failure. A detailed analysis of published literature aiming to evaluate the spermicidal activity of N-9 on sperm was carried out. In the pooled results, N-9 reduced the number of active sperm and the distance they traveled. It also caused damage to the structures of sperm and to the way the sperm acted and interacted with the egg. In conclusion, N-9 impacts on sperm in a number of ways that lead to sperm death and dysfunction.

In vitro rescue immature oocytes - a literature review.

Immature oocytes retrieved from in vitro fertilization (IVF) and clinical in vitro maturation (IVM) is a common problem, especially in patients with advanced age, poor ovarian response (POR), or polycystic ovary syndrome (PCOS). Considering there is no common name to describe this group of oocytes, we suggest naming all of immature oocytes retrieved from IVF and clinical IVM cycles as 'Medical Unusable Oocytes' (MUO) as none of them will be used for subsequent treatment and will eventually be discarded. Scientists attempt to improve the clinical utilization rate of MUO instead of discarding them. Rescue IVM and mitochondria supplementation may be available approaches to mature MUO. We propose a specific definition of rescue IVM, namely the cultivation and maturation of immature oocytes in vitro collected from IVF cycles with human chorionic gonadotropin (hCG) trigger. Rescue IVM is usually mixed up with clinical IVM. Clarification of the differences between rescue IVM and clinical IVM is necessary. This manuscript aims to clarify the rather confusing IVM procedures and review existing methods of improving rescue IVM, currently available information on the success rate, and explore the future possibility of rescue IVM serving as a promising tool in reproductive medicine.

Associations between ambient air pollution and IVF outcomes in a heavily polluted city in China.

RESEARCH QUESTION: Is air pollution related to IVF outcomes in a heavily polluted city in China? DESIGN: A retrospective cohort study of 8628 fresh, autologous IVF cycles was conducted for the first time at the Reproductive Medicine Center of The Third Affiliated Hospital of Zhengzhou University between May 2014 and December 2018 (oocyte retrieval date). The exposure was divided into four periods (gonadotrophin injection to oocyte retrieval [P1], oocyte retrieval to embryo transfer [P2], 1 day after embryo transfer to embryo transfer +14 days [P3] and gonadotrophin injection to embryo transfer +14 days [P4]) and four levels (Q1-Q4 according to their 25th, 50th and 75th percentiles). RESULTS: An interquartile range increase (Q2 versus Q1) in particulate matter ≤10 µm (PM10) during P3 and P4 and sulphur dioxide (SO2) during P3 significantly decreased the clinical pregnancy rate (adjusted odds ratio [aOR] 0.81, 95% confidence interval [CI] 0.71-0.92 for PM10 of P3; aOR 0.87, 95% CI 0.76-1.00 for PM10 of P4; aOR 0.82, 95% CI 0.73-0.93 for SO2 of P3). In addition, PM10 was associated with an increased biochemical pregnancy rate (Q3 versus Q1: aOR 1.55, 95% CI 1.09-2.19 for PM10 of P1) and decreased live birth rate (Q2 versus Q1: aOR 0.88, 95% CI 0.77-0.99 for PM10 of P3). The multivariate regression results were consistent with that of multiple treatments propensity score method (PSM) for SO2 pollutants in P3 and PM10 pollutants in P4. CONCLUSION: From the early follicular stage to the pregnancy test period, high concentrations of PM10 and SO2 may have a negative impact on IVF treatment outcomes in the study area.

CD147 deficiency is associated with impairedsperm motility/acrosome reaction and offersa therapeutic target for asthenozoospermia.

Patients with asthenozoospermia often present multiple defects in sperm functions apart from a decrease in sperm motility. However, the etiological factors underlying these multifaceted defects remain mostly unexplored, which may lead to unnecessary treatment and unsatisfactory assisted reproductive technologies (ART) outcome. Here, we show that the protein levels of CD147 were lowered in sperm obtained from asthenozoospermic infertile patients exhibiting defects in both sperm motility and the acrosome reaction. Whereas CD147 maintained sperm motility before capacitation, female tract-derived soluble CD147 interacted with sperm-bound CD147 to induce an acrosome reaction in capacitated sperm. Soluble CD147 treatment restored the acrosome reaction and improved the fertility of sperm from patients with asthenozoospermia. Mechanistically, CD147 promotes sperm motility and acrosome reaction (AR) by eliciting Ca2+ influx through soluble CD147 binding to sperm-bound CD147. Notably, the level of soluble CD147 in seminal plasma was positively correlated with the fertilization rate and pregnancy outcome in infertile couples undergoing in vitro fertilization. Our study has identified a marker for the diagnosis and a therapeutic target for the defective AR capability in asthenozoospermia and a candidate for the prediction of in vitro fertilization outcomes for male infertile patients that facilitates the development of precision medicine in ART.

Kidney Biopsy in Patients With Monoclonal Gammopathy: A Multicenter Retrospective Cohort Study.

Objectives: To analyze the clinical characteristics and renal pathological manifestations of patients with monoclonal gammopathy (MG) and kidney injury. Methods: This was a multicenter retrospective cohort study conducted at four tertiary hospitals in China. The study population comprised patients with MG admitted from January 1 2013 to December 31 2020. Hospitalization records, laboratory data, and kidney biopsy reports of all patients were collected from the electronic hospital information systems. The study outcomes included kidney disease progression and major hemorrhagic complications after kidney biopsy. Results: We identified 1,164 patients with MG, 782 (67.2%) of whom had underlying kidney injury. Of 101 patients who underwent kidney biopsy, 16 had malignant neoplasms. Amyloid nephropathy was the most common finding (n = 34, 33.7%), followed by membranous nephropathy (n = 18, 17.8%) and membranoproliferative nephritis (n = 8, 7.9%). Among 85 patients with non-malignant hematologic conditions who underwent kidney biopsy, 43 had MG of renal significance (MGRS) related lesions and 42 had MG-unrelated lesions. The risk of kidney disease progression was higher in patients with kidney injury than in patients without kidney injury. Conclusion: Among patients with MG and kidney injury, only 12.9% underwent kidney biopsy and more than 40% of these patients had MG-unrelated lesions. A kidney biopsy is safe and essential to maximize the possibility of correct diagnosis for patients with clinically suspected MG of renal significance (MGRS).

Associations between blood metal/ metalloid concentration and human semen quality and sperm function: A cross-sectional study in Hong Kong.

BACKGROUND: The association between metal/metalloid exposure on human sperm quality is still inconclusive. There is a lack of data on the effect of metal/metalloid on sperm function. METHODS: The aim of this study was to clarify the association between blood metal/metalloid concentration and traditional and functional sperm parameters, the blood concentration of Pb, Hg, Cd, As, Ni, Mo, Zn, Cu, Se, Fe, Mg, Cr and Ca of 288 men in Hong Kong were assessed by inductively coupled plasma-mass spectrometry, and sperm parameters including sperm concentration, motility, morphology, vitality, total sperm count, total motile sperm count, sperm DNA fragmentation and sperm acrosome reaction were measured. Demographic and lifestyle questionnaires were also provided for all participants. Multivariable linear regression analysis was performed to test the association between blood metal/ metalloid concentration and semen parameters after adjusting for relevant confounding variables. RESULTS: The results showed that moderate to high level of blood Pb concentration (>27.19 µg/L) appeared to be negatively associated with sperm morphology (P < 0.05); high level of blood Cd concentration (>1.44 µg/L) was negatively associated with sperm acrosome reaction (P < 0.05); Mo was positively associated with semen volume (P < 0.05), however, high level of blood Mo concentration (>13.52 µg/L) was negatively associated with sperm vitality (P < 0.05); high level of blood Zn concentration (>6.20 mg/L) was positively associated with sperm vitality (P < 0.05); moderate level of blood Fe concentration (526.89-566.63 mg/L) was positively associated with sperm acrosome reaction (P < 0.05); moderate level of blood Ca concentration (55.92-66.10 mg/L) was positively associated with semen volume (P < 0.05); however, lower level of blood Ca concentration (45.90-55.92 mg/L) was negatively associated with sperm morphology (P < 0.05). CONCLUSIONS: Our results suggested that the sperm function could be affected by blood Cd and Fe concentration and traditional sperm parameters could be affected by blood concentration of Mo, Zn, Pb and Ca.

The predictive value of endometrial thickness in 3117 fresh IVF/ICSI cycles for ectopic pregnancy.

OBJECTIVES: To evaluate the predictive value of endometrial thickness (EMT) during in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles for ectopic pregnancy (EP). METHODS: A total of 3068 patients with 3117 fresh IVF/ICSI cycles between January 2016 and February 2019 from the Reproductive Medicine Center of Sun Yat-Sen Memorial Hospital were included in this retrospective study. The patients were divided into an EP group (n = 92) and an intrauterine pregnancy (IUP) group (n = 3025). Multiple logistic regression analysis was conducted to evaluate the EP risk factors. Receiver operating characteristic (ROC) curves were used to evaluate the predictive value of the risk factors for EP and calculate the cutoff value of EMT for EP prediction. RESULTS: The incidence rate of EP was 2.95 % (92/3117). After adjustment for other factors in the logistic regression model, the incidence of EP decreased by 55 % with an EMT > 10 mm compared with an EMT ≤ 10 mm (odds ratio 0.450, 95 % confidence interval 0.296-0.684, P < 0.001). The EMT in the EP group was significantly thinner than that in the live birth (n = 2540) and spontaneous abortion (n = 485) groups (p < 0.017). The cutoff value of EMT for EP prediction was 10.65 mm, with a sensitivity of 59 % and a specificity of 63 %. CONCLUSION: A decreased risk of EP was found among the patients with an EMT > 10 mm prior to embryo transfer. A certain EMT is needed to reduce the incidence of EP.

Application of convolutional neural network on early human embryo segmentation during in vitro fertilization.

Selection of the best quality embryo is the key for a faithful implantation in in vitro fertilization (IVF) practice. However, the process of evaluating numerous images captured by time-lapse imaging (TLI) system is time-consuming and some important features cannot be recognized by naked eyes. Convolutional neural network (CNN) is used in medical imaging yet in IVF. The study aims to apply CNN on day-one human embryo TLI. We first presented CNN algorithm for day-one human embryo segmentation on three distinct features: zona pellucida (ZP), cytoplasm and pronucleus (PN). We tested the CNN performance compared side-by-side with manual labelling by clinical embryologist, then measured the segmented day-one human embryo parameters and compared them with literature reported values. The precisions of segmentation were that cytoplasm over 97%, PN over 84% and ZP around 80%. For the morphometrics data of cytoplasm, ZP and PN, the results were comparable with those reported in literatures, which showed high reproducibility and consistency. The CNN system provides fast and stable analytical outcome to improve work efficiency in IVF setting. To conclude, our CNN system is potential to be applied in practice for day-one human embryo segmentation as a robust tool with high precision, reproducibility and speed.