研究者詳細 - 上條　慎太郎

上條　慎太郎 (カミジョウ　シンタロウ)

Kamijo, Shintaro

写真a

所属（所属キャンパス）: 医学部産婦人科学教室（信濃町）

職名: 助教（有期）

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Fertility preservation after gonadotoxic treatments for cancer and autoimmune diseases

Saito S., Yamada M., Yano R., Takahashi K., Ebara A., Sakanaka H., Matsumoto M., Ishimaru T., Utsuno H., Matsuzawa Y., Ooka R., Fukuoka M., Akashi K., Kamijo S., Hamatani T., Tanaka M.

Journal of Ovarian Research （Journal of Ovarian Research) 16 （ 1 ） 2023年12月

　概要を見る

Background: The indications for fertility preservation (FP) have expanded. A few patients who underwent gonadotoxic treatment did not have the opportunity to receive FP, leading to concerns that these patients may develop premature ovarian insufficiency. However, the usefulness of FP in women with reduced ovarian reserve has also been questioned. Progestin-primed ovarian stimulation can improve the controlled ovarian stimulation (COS) protocol, but there is limited data on the efficacy of FP with progestin-primed ovarian stimulation. Methods: We conducted a prospective study of 43 women with cancer or autoimmune diseases before and after gonadotoxic treatment at the reproductive unit of Keio University Hospital, counselled between 1 January 2018 and 31 December 2021. After counselling, informed consent was obtained for FP from 43 patients, with those who underwent gonadotoxic treatment of the primary disease being prioritised. Gonadotropin-releasing hormone analogue or progestin was used to suppress luteinising hormone in COS before or after gonadotoxic treatment. The number of cryopreserved mature oocytes was the primary outcome. Results: Forty-three patients and 67 assisted reproductive technology cycles were included in the analysis. The median age at entry was 32 [inter quartile range (IQR), 29–37] years. All patients in the post-gonadotoxic treatment group had their oocytes frozen. Gonadotoxic treatment resulted in fewer oocytes [median 3 (IQR 1–4); pre-gonadotoxic treatment group: five patients, 13 cycles] vs. median 9 (IQR 5–14; pre-gonadotoxic treatment group: 38 patients, 54 cycles; P < 0.001). Although anti-Müllerian hormone levels were lower in the post-gonadotoxic treatment group (n = 5, 13 cycles, median 0.29 (IQR 0.15–1.04) pg/mL) than in the pre-gonadotoxic treatment group (n = 38, 54 cycles, median 1.89 (IQR 1.15–4.08) pg/mL) (P = 0.004), oocyte maturation rates were higher in the post-gonadotoxic treatment group [median 100 (IQR 77.5–100) %] than in the pre-gonadotoxic group [median 90.3 (IQR 75.0–100) %; P = 0.039]. Five patients in the pre-gonadotoxic treatment group had their cryopreserved embryos thawed, of which three had live births. Conclusions: Oocytes obtained for FP from women with cancer or autoimmune disease for FP are of satisfactory quality, regardless of whether they are obtained post-gonadotoxic treatment or COS protocols.
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Embryonic β-Catenin Is Required for Priming of the Uterus to Implantation

Takezawa Y., Iwai M., Fujiki Y., Yokomizo R., Kishigami H., Miyado M., Kawano N., Yamada M., Shindo M., Suzuki M., Sato B., Katano D., Kamijo S., Hamatani T., Tanaka M., Umezawa A., Kang W., Miyado K.

Laboratory investigation; a journal of technical methods and pathology （Laboratory investigation; a journal of technical methods and pathology) 103 （ 3 ） 2023年03月

　概要を見る

Repeated implantation failure is a major cause of infertility among healthy women. Uterine β-catenin (CTNNB1) plays a critical role in implantation. However, the role of embryonic CTNNB1 during implantation remains unclear. We addressed this topic by analyzing mice carrying Ctnnb1-deficient (Ctnnb1Δ/Δ) embryos. Ctnnb1Δ/Δ embryos were produced by intercrossing mice bearing Ctnnb1-deficient eggs and sperms. We found that Ctnnb1Δ/Δ embryos developed to the blastocyst stage; thereafter, they were resorbed, leaving empty decidual capsules. Moreover, leukemia inhibitory factor, a uterine factor essential for implantation, was undetectable in Ctnnb1Δ/Δ blastocysts. Furthermore, CDX2, a transcription factor that determines the fate of trophectoderm cells, was not observed in Ctnnb1Δ/Δ blastocysts. Intrauterine injection with uterine fluids (from control mice) and recombinant mouse leukemia inhibitory factor proteins rescued the uterine response to Ctnnb1Δ/Δ blastocysts. These results suggest that embryonic CTNNB1 is required for the secretion of blastocyst-derived factor(s) that open the implantation window, indicating that the uterine response to implantation can be induced using supplemental materials. Therefore, our results may contribute to the discovery of a similar mechanism in humans, leading to a better understanding of the pathogenesis of repeated implantation failure.
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Morphometric assessment of blastocysts: relationship with the ongoing pregnancy rate

Utsuno H., Ishimaru T., Matsumoto M., Sasamori C., Takahashi H., Kimura H., Kamijo S., Yamada M., Tanaka M., Hamatani T.

F and S Reports （F and S Reports) 4 （ 1 ） 85 - 92 2023年03月

　概要を見る

Objective: To explore a morphometric grading system for blastocysts that is associated with ongoing pregnancy. Design: Cross-sectional study. Setting: None. Patients(s): All consecutive vitrified blastocysts at our center from July 2018 to November 2021 that were transferred in single blastocyst transfer cycles until January 2022. Intervention(s): None. Main Outcome Measure(s): The ongoing pregnancy rate after a single vitrified-warmed blastocyst transfer. Interobserver agreement on morphometric values among embryologists. Result(s): Three morphometric variables (blastocyst diameter, area of inner cell mass [ICM], and the estimated trophectoderm cell count) were used to evaluate the expansion, ICM, and trophectoderm morphology. During the study period, 585 blastocysts were involved in this study. Of the 3 morphometric variables, ICM area (per 500 μm2, adjusted odds ratio, 1.19; 95% confidence interval, 1.09−1.30) and estimated trophectoderm cell count (per 10 cells, adjusted odds ratio, 1.25; 95% confidence interval, 1.12−1.39) were significantly associated with the ongoing pregnancy rate after adjustment for confounding factors. The ongoing pregnancy rate was 2.0% (1/49) with an ICM area of <2,500 μm2 and the estimated trophectoderm cell count <70. The ongoing pregnancy rate reached 47.8% (22/46) when the ICM area and the estimated trophectoderm cell count were >3,500 μm2 and >110, respectively. Interobserver agreement on the blastocyst diameter, ICM area, and the estimated trophectoderm cell count was excellent-to-good among 5 embryologists (intraclass correlation coefficients: 0.99, 0.87, and 0.91, respectively). Conclusion(s): Morphometric values of ICM and trophectoderm are promising predictors of pregnancy success. The high reproducibility suggests that the morphometric variables will contribute to identifying blastocysts with the highest developmental potential as well as those that will not result in a successful pregnancy.
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Artificial oocyte activation using Ca<sup>2+</sup> ionophores following intracytoplasmic sperm injection for low fertilization rate

Akashi K., Yamada M., Jwa S.C., Utsuno H., Kamijo S., Hirota Y., Tanaka M., Osuga Y., Kuji N.

Frontiers in Endocrinology （Frontiers in Endocrinology) 14 2023年

　概要を見る

This large multi-center retrospective study examined whether artificial oocyte activation (AOA) using Ca2+ ionophore following ICSI improves the live birth rate for couples with previous ICSI cycles of unexplained low fertilization rate. In this large-scale multi-center retrospective study conducted in Japan, data were collected from Keio University and 17 collaborating institutions of the Japanese Institution for Standardizing Assisted Reproductive Technology. Between January 2015 and December 2019, 198 couples were included in this study. Oocytes for both the intervention and control groups were procured from the same pool of couples. Oocytes obtained from ICSI cycles with no or low fertilization rate (<50%) with unknown causes were included in the control (conventional ICSI) group while oocytes procured from ICSI cycles followed by performing AOA were assigned to the intervention (ICSI-AOA) group. Those fertilized with surgically retrieved sperm were excluded. ICSI-AOA efficacy and safety were evaluated by comparing these two groups. Live birth rate was the primary outcome. The ICSI-AOA group (2,920 oocytes) showed a significantly higher live birth per embryo transfer rate (18.0% [57/316]) compared to that of the conventional ICSI group with no or low fertilization rate (1,973 oocytes; 4.7% [4/85]) (odds ratio 4.5, 95% confidence interval 1.6–12.6; P<0.05). A higher live birth rate was observed in younger patients without a history of oocyte retrieval. Miscarriage, preterm delivery, and fetal congenital malformation rates were similar between the two groups. ICSI-AOA may reduce fertilization failure without increasing risks during the perinatal period. AOA may be offered to couples with an ICSI fertilization rate < 50%.
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MicroRNAs secreted by human preimplantation embryos and IVF outcome

Kamijo S., Hamatani T., Sasaki H., Suzuki H., Abe A., Inoue O., Iwai M., Ogawa S., Odawara K., Tanaka K., Mikashima M., Suzuki M., Miyado K., Matoba R., Odawara Y., Tanaka M.

Reproductive Biology and Endocrinology （Reproductive Biology and Endocrinology) 20 （ 1 ） 2022年12月

　概要を見る

Objective: To generate an effective embryo prediction model and identify a non-invasive evaluation method by analyzing microRNAs (miRNAs) in embryo culture medium. Design: Analysis of microRNA profiles from spent culture medium of blastocysts with good morphology that did or did not result in pregnancy. Setting: Clinical and experimental research. Patients: Sixty patients who underwent thawed embryo transfer of blastocysts after intracytoplasmic sperm injection. Intervention(s): None. Main outcome measure(s): The association of miRNA abundance levels secreted by blastocysts in culture medium and implantation success. Results: Our RNA sequencing analysis found a total of 53 differentially expressed miRNAs in the culture media of pregnancy and non-pregnancy groups. Twenty-one miRNAs were analyzed for their potential to predict implantation success. Eight miRNAs (hsa-miR-191-5p, hsa-miR-320a, hsa-miR-92a-3p, hsa-miR-509-3p, hsa-miR-378a-3p, hsa-miR-28-3p, hsa-miR-512-5p, and hsa-miR-181a-5p) were further extracted from the results of a logistic regression analysis of qPCR Ct values. A prediction model for high-quality blastocysts was generated using the eight miRNAs, with an average accuracy of 0.82 by 5-fold cross validation. Conclusion: We isolated blastocyst miRNAs that may predict implantation success and created a model to predict viable embryos. Increasing the number of investigated cases and further studying the effect of each miRNA on embryonic development is needed to refine the miRNA-based predictive model.
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