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19. Prevalence of Chronic Endometritis in Patients with Infertility due to Hydrosalpinx or Pelvic Peritubal Adhesions and Effect of Laparoscopic Surgical Correction on Pregnancy Rates post in vitro Fertilization

Author

Osada, Hisao, primary, Seto, Michiharu, additional, Nakase, Kaori, additional, Ezoe, Kenji, additional, Miyauchi, Osamu, additional, Fujita, Hiroshi, additional, Miyakawa, Yasuji, additional, Nagaishi, Masaji, additional, Kato, Keiichi, additional, Teramoto, Shokichi, additional, and Shozu, Makio, additional

Published
2023
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23. The destinies of human embryos reaching blastocyst stage between Day 4 and Day 7 diverge as early as fertilization.

Author

Coticchio, Giovanni, Ezoe, Kenji, Lagalla, Cristina, Zacà, Carlotta, Borini, Andrea, and Kato, Keiichi

Subjects
*HUMAN embryos, *BLASTOCYST, *EMBRYO implantation, *EMBRYO transfer, *MALE infertility
Abstract

STUDY QUESTION What clinical and laboratory differences emerge from parallel direct comparison of embryos reaching the blastocyst stage between Days 4, 5, 6, and 7 (Days 4–7)? SUMMARY ANSWER Increasing times to blastocyst formation are associated with a worse clinical outcome and perturbations in developmental patterns appear as early as the fertilization stage. WHAT IS KNOWN ALREADY Previous evidence indicates that later times to blastocyst development are associated with a worse clinical outcome. However, the vast majority of these data concern Day 5 and Day 6 blastocysts, while Day 4 and Day 7 blastocysts remain less thoroughly investigated. In addition, studies comparing in parallel the developmental patterns and trajectories of Day 4–7 blastocysts are lacking. This leaves unanswered the question of when and how differences among such embryos emerge. Acquisition of such knowledge would significantly contribute to understanding the relative impact of intrinsic and extrinsic causes of embryo developmental kinetics and competence. STUDY DESIGN, SIZE, DURATION This retrospective study involved time-lapse technology (TLT) monitoring of Day 4 (N = 70), Day 5 (N = 6147), Day 6 (N = 3243), and Day 7 (N = 149) blastocysts generated in 9450 ICSI cycles. Oocyte retrievals were carried out after clomiphene citrate-based minimal ovarian stimulation, between January 2020 and April 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS Couples included in the study presented with different diagnoses, mainly male factor and unexplained infertility. Cases involving cryopreserved gametes or surgically retrieved sperm were excluded. Microinjected oocytes were assessed by a combined TLT-culture system. Day 4–7 blastocyst groups were compared in terms of morphokinetics (pronuclear dynamics, cleavage patterns and timings, and embryo quality) and clinical outcome. Clinically usable blastocysts were cryopreserved and transferred in single vitrified-warmed blastocyst transfers (SVBT). MAIN RESULTS AND THE ROLE OF CHANCE From 19 846 microinjected oocytes, 17 144 zygotes (86.4%) were obtained. Overall, the blastocyst development rate was 56.0%. Rates of blastocysts formation on Days 4, 5, 6, and 7 were 0.7%, 64.0%, 33.8%, and 1.6%, respectively. The average expanded blastocyst development times were 98.4 ± 0.4, 112.4 ± 0.1, 131.6 ± 0.1, and 151.2 ± 0.5 h in the Day 4–7 groups, respectively. Female age was positively associated with longer times to blastocyst development. Rates of both inner cell mass (ICM) and trophectoderm (TE) morphological grade A blastocysts were negatively associated with the day of blastocyst development (P  < 0.0001). The differences in development times and intervals increased progressively until blastocyst expansion (P  < 0.0001 for all development times). Strikingly, such differences were already markedly evident as early as the time of pronuclear fading (tPNf) (20.6 ± 0.3, 22.5 ± 0.0, 24.0 ± 0.0, 25.5 ± 0.3; Days 4–7, respectively; P  < 0.0001). Rates of cleavage anomalies (tri-/multi-chotomous mitosis or rapid cleavage) occurring at the first or second/third division cycles were also positively associated with longer times to blastocyst development. Implantation, ongoing pregnancy, and live birth rates were progressively reduced with increasing blastocyst development times (P  < 0.0001), even after stratification for maternal age. When controlled for female age, male age, number of previous embryo transfer cycles, morphological grade of the ICM and TE, and progesterone supplementation, the probabilities of implantation, clinical, and ongoing pregnancy and live birth were significantly decreased in Day 6 blastocysts in comparison to Day 5 blastocysts. Follow-up data on birth length, weight, and malformations were comparable among the four blastocyst groups. LIMITATIONS, REASONS FOR CAUTION The study is limited by its retrospective design. Having been obtained from a single centre, the data require independent validation. WIDER IMPLICATIONS OF THE FINDINGS This study extends previous data on the relation between time of blastocyst formation and clinical outcome. It also indicates that differences in developmental times and patterns of Day 4–7 blastocysts occur as early as the fertilization stage, possibly dictated by intrinsic gamete-derived factors. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the participating institutions. The authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Published
2023
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24. Maternal age affects pronuclear and chromatin dynamics, morula compaction and cell polarity, and blastulation of human embryos

Author

Ezoe, Kenji, primary, Miki, Tetsuya, additional, Akaike, Hikari, additional, Shimazaki, Kiyoe, additional, Takahashi, Tsubasa, additional, Tanimura, Yuko, additional, Amagai, Ayumi, additional, Sawado, Ayano, additional, Mogi, Mai, additional, Kaneko, Shigeru, additional, Ueno, Satoshi, additional, Coticchio, Giovanni, additional, Cimadomo, Danilo, additional, Borini, Andrea, additional, Rienzi, Laura, additional, and Kato, Keiichi, additional

Published
2023
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28. Association between a deep learning-based scoring system with morphokinetics and morphological alterations in human embryos

Author

Ezoe, Kenji, primary, Shimazaki, Kiyoe, additional, Miki, Tetsuya, additional, Takahashi, Tsubasa, additional, Tanimura, Yuko, additional, Amagai, Ayumi, additional, Sawado, Ayano, additional, Akaike, Hikari, additional, Mogi, Mai, additional, Kaneko, Shigeru, additional, Okimura, Tadashi, additional, and Kato, Keiichi, additional

Published
2022
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31. Preimplantation Genetic Testing for Aneuploidy for Recurrent Pregnancy Loss and Recurrent Implantation Failure in Minimal Ovarian Stimulation Cycle for Women Aged 35–42 Years: Live Birth Rate, Developmental Follow-up of Children, and Embryo Ranking

Author

Kato, Keiichi, primary, Kuroda, Tomoko, additional, Yamadera-Egawa, Rie, additional, Ezoe, Kenji, additional, Aoyama, Naoki, additional, Usami, Akemi, additional, Miki, Tetsuya, additional, Yamamoto, Toshiyuki, additional, and Takeshita, Toshiyuki, additional

Published
2022
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32. Human 1PN and 3PN zygotes recapitulate all morphokinetic events of normal fertilization but reveal novel developmental errors

Author

Ezoe, Kenji, primary, Takahashi, Tsubasa, additional, Shimazaki, Kiyoe, additional, Miki, Tetsuya, additional, Tanimura, Yuko, additional, Amagai, Ayumi, additional, Sawado, Ayano, additional, Akaike, Hikari, additional, Mogi, Mai, additional, Kaneko, Shigeru, additional, Kato, Mizuki, additional, Kato, Keiichi, additional, Tarozzi, Nicoletta, additional, Borini, Andrea, additional, and Coticchio, Giovanni, additional

Published
2022
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34. Additional file 3 of Letrozole-induced endometrial preparation improved the pregnancy outcomes after frozen blastocyst transfer compared to the natural cycle: a retrospective cohort study

Author

Ezoe, Kenji, Fukuda, Junichiro, Takeshima, Kazumi, Shinohara, Kazunori, and Kato, Keiichi

Abstract

Additional file 3: Supplementary Table 1. P-values of univariate logistic regression analysis between confounders and outcomes Supplementary Table 2. Embryonic outcomes stratified by the ovarian stimulation method Supplementary Table 3. Pregnancy outcomes after SVBT in natural and letrozole cycles, stratified by the female age Supplementary Table 4. Congenital anomalies stratified by the ovarian stimulation method.

Published
2022
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39. Spatiotemporal perturbations of pronuclear breakdown preceding syngamy affect early human embryo development: a retrospective observational study

Author

Ezoe, Kenji, primary, Coticchio, Giovanni, additional, Takenouchi, Hitomi, additional, Taoda, Shota, additional, Namerikawa, Shima, additional, Honda, Kasumi, additional, Miki, Tetsuya, additional, Okimura, Tadashi, additional, Kobayashi, Tamotsu, additional, Borini, Andrea, additional, and Kato, Keiichi, additional

Published
2021
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41. Additional file 1 of Characteristics of the cytoplasmic halo during fertilisation correlate with the live birth rate after fresh cleaved embryo transfer on day 2 in minimal ovarian stimulation cycles: a retrospective observational study

Author

Ezoe, Kenji, Miki, Tetsuya, Okimura, Tadashi, Uchiyama, Kazuo, Yabuuchi, Akiko, Kobayashi, Tamotsu, and Kato, Keiichi

Subjects
animal structures, embryonic structures
Abstract

Additional file 1: Table S1. Characteristics of embryos. Table S2. Logistic regression analysis of presence of cytoplasmic halo and live births after fresh-cleavage embryo transfers. Table S3. Correlation of different time intervals with live births after fresh cleaved embryo transfers. Table S4. Multiple linear regression coefficients for time interval from tHc to tHr during fertilisation.

Published
2021
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46. Additional file 1 of Anti-Müllerian hormone is correlated with cumulative live birth in minimal ovarian stimulation with clomiphene citrate: a retrospective cohort study

Author

Ezoe, Kenji, Xiaowen Ni, Kobayashi, Tamotsu, and Kato, Keiichi

Subjects
endocrine system, urogenital system, female genital diseases and pregnancy complications, hormones, hormone substitutes, and hormone antagonists
Abstract

Additional file 1: Table S1. Cohort characteristics. Table S2. Patient characteristics stratified by the serum AMH level. Table S3. IVF outcomes of the first cycles, stratified by the serum AMH level. Table S4. Pregnancy outcomes of the first cycle stratified by the serum AMH level. Table S5. Pregnancy outcomes of the first cycle stratified by the serum AMH level. Table S6. Adjusted odds ratio for the blastocyst cryopreservation/live birth rate in the first cycle. Table S7. Hazard ratio for cumulative live birth rate per treatment period. Table S8. Cumulative live birth rates in the first IVF cycles.

Published
2020
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