Pub Date : 2024-09-19DOI: 10.1007/s10815-024-03262-y
Sönmezer Meltem, Gemici Ali, Şükür Yavuz Emre, Turan Hande, Alimogulları Ebru, Avşar Betül, Atabekoğlu Cem Somer, Özmen Batuhan, Turan Volkan, Sönmezer Murat
Purpose
Is it safe and effective to perform controlled ovarian stimulation (COS) and oocyte retrieval (OR) in prepubertal and peripubertal patients?
Methods
In this retrospective cohort study, data of 20 pre-/peripubertal patients who underwent COS and OR for the purpose of oocyte cryopreservation (OC) between 2008 and 2023 were reviewed. Following COS, all OR procedures were performed transabdominally using a vaginal ultrasound probe. Ovarian reserve was assessed by serum FSH, LH, estradiol, AMH, and antral follicle counts (AFC) in all subjects. All mature oocytes were vitrified.
Results
Mean age of the patients was 15.05 ± 1.87, mean AMH was 0.84 ± 0.8 ng/ml, mean FSH was 6.39 ± 3.95 IU/L, mean estradiol was 61.6 ± 51.9 pg/ml, mean LH was 4.69 ± 3.46 IU/L, and mean AFC was 5.5 ± 5.82. Among the patients, 12 had regular menstrual cycle, 5 had irregular menstrual cycle, whereas 3 patients still did not have their menarche yet. The indications for OC were as follows: primary ovarian insufficiency (n = 7), ovarian surgery for ovarian tumors (n = 5) or ovarian torsion (n = 1), mosaic Turner syndrome (n = 2), acute lymphoblastic leukemia (n = 1) anaplastic B-cell lymphoma (n = 1), Ewing’s sarcoma (n = 1), Noonan syndrome (n = 1), and Thalassemia (n = 1). The mean number of oocytes retrieved, MII oocytes frozen, and maturation rate were 5.11 ± 5.0, 3.92 ± 4.48, and 75.1 ± 25.6%, respectively. Stepwise linear regression analysis demonstrated a positive correlation between AFC and number of total oocytes retrieved and number of MII oocytes. In the case diagnosed with Noonan syndrome, all 7 retrieved oocytes were MI and all frozen at MI phase. No patient had any complication related to COS or OR.
Conclusion
Even though number of the enrolled subjects is limited and mean AMH is lower in our cohort, we demonstrated that performing COS and OR is safe in pre-/peripubertal patients. If required, transabdominal route can be performed in this age group for OR. AFC appears as a prognostic factor for stimulation outcome in this age group. Pediatric patients or young adolescents at risk for primary ovarian insufficiency should not be discouraged from utilizing OC.
{"title":"Safety and effectiveness of controlled ovarian stimulation and oocyte retrieval during prepubertal and peripubertal period","authors":"Sönmezer Meltem, Gemici Ali, Şükür Yavuz Emre, Turan Hande, Alimogulları Ebru, Avşar Betül, Atabekoğlu Cem Somer, Özmen Batuhan, Turan Volkan, Sönmezer Murat","doi":"10.1007/s10815-024-03262-y","DOIUrl":"https://doi.org/10.1007/s10815-024-03262-y","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>Is it safe and effective to perform controlled ovarian stimulation (COS) and oocyte retrieval (OR) in prepubertal and peripubertal patients?</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>In this retrospective cohort study, data of 20 pre-/peripubertal patients who underwent COS and OR for the purpose of oocyte cryopreservation (OC) between 2008 and 2023 were reviewed. Following COS, all OR procedures were performed transabdominally using a vaginal ultrasound probe. Ovarian reserve was assessed by serum FSH, LH, estradiol, AMH, and antral follicle counts (AFC) in all subjects. All mature oocytes were vitrified.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Mean age of the patients was 15.05 ± 1.87, mean AMH was 0.84 ± 0.8 ng/ml, mean FSH was 6.39 ± 3.95 IU/L, mean estradiol was 61.6 ± 51.9 pg/ml, mean LH was 4.69 ± 3.46 IU/L, and mean AFC was 5.5 ± 5.82. Among the patients, 12 had regular menstrual cycle, 5 had irregular menstrual cycle, whereas 3 patients still did not have their menarche yet. The indications for OC were as follows: primary ovarian insufficiency (<i>n</i> = 7), ovarian surgery for ovarian tumors (<i>n</i> = 5) or ovarian torsion (<i>n</i> = 1), mosaic Turner syndrome (<i>n</i> = 2), acute lymphoblastic leukemia (<i>n</i> = 1) anaplastic B-cell lymphoma (<i>n</i> = 1), Ewing’s sarcoma (<i>n</i> = 1), Noonan syndrome (<i>n</i> = 1), and Thalassemia (<i>n</i> = 1). The mean number of oocytes retrieved, MII oocytes frozen, and maturation rate were 5.11 ± 5.0, 3.92 ± 4.48, and 75.1 ± 25.6%, respectively. Stepwise linear regression analysis demonstrated a positive correlation between AFC and number of total oocytes retrieved and number of MII oocytes. In the case diagnosed with Noonan syndrome, all 7 retrieved oocytes were MI and all frozen at MI phase. No patient had any complication related to COS or OR.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Even though number of the enrolled subjects is limited and mean AMH is lower in our cohort, we demonstrated that performing COS and OR is safe in pre-/peripubertal patients. If required, transabdominal route can be performed in this age group for OR. AFC appears as a prognostic factor for stimulation outcome in this age group. Pediatric patients or young adolescents at risk for primary ovarian insufficiency should not be discouraged from utilizing OC.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":"42 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
As a cause of primary female infertility, oocyte maturation arrest (OMA) is characterized by failure to obtain mature oocytes due to abnormal meiosis. We aimed to identify pathogenic variants in two sisters with OMA phenotype from a non-consanguineous family.
Methods
Whole-exome sequencing and Sanger sequencing were conducted to identify and validate the disease-causing gene variant. Additionally, we performed a minigene assay, quantitative reverse transcription PCR, and Western blotting to assess the effects of the variant.
Results
We identified a novel homozygous splicing variant (c.1021-11T>C) in TRIP13, which followed a recessive inheritance pattern. Minigene assay showed that the variant could disrupt the integrity of TRIP13 mRNA, as evidenced by the production of an alternative transcript with intron10 intermediate retention of 79 bp. Compared to normal controls, the expression of TRIP13 mRNA and abundance of TRIP13 protein were also significantly decreased in Epstein-Barr virus-immortalized lymphoblastoid cells derived from affected individuals.
Conclusion
Our findings confirm the contribution of genetic factors to OMA and expand the mutation spectrum of TRIP13 in female infertility.
目的 作为原发性女性不孕症的原因之一，卵母细胞成熟停滞（OMA）的特点是由于减数分裂异常而无法获得成熟的卵母细胞。我们的目的是在一个非近亲结婚的家庭中，在两个具有 OMA 表型的姐妹中找出致病变体。方法我们进行了全外显子组测序和桑格测序，以找出并验证致病基因变体。结果我们在 TRIP13 中发现了一个新的同基因剪接变异（c.1021-11T>C），该变异具有隐性遗传模式。迷你基因测定显示，该变异可破坏 TRIP13 mRNA 的完整性，表现为产生了内含子 10 中间保留 79 bp 的替代转录本。与正常对照组相比，TRIP13 mRNA的表达量和TRIP13蛋白的丰度也明显降低。
{"title":"Identification of a novel splicing variant of thyroid hormone receptor interaction protein 13 (TRIP13) in female infertility characterized by oocyte maturation arrest","authors":"Jia Chen, Yuxin Liu, Xingwu Wu, Yiwei Zhang, Wen Huang, Wenbo Han, Ge Chen, Qiang Xu, Houyang Chen, Qiongfang Wu, Jiawei Wang, Jialyu Huang","doi":"10.1007/s10815-024-03219-1","DOIUrl":"https://doi.org/10.1007/s10815-024-03219-1","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>As a cause of primary female infertility, oocyte maturation arrest (OMA) is characterized by failure to obtain mature oocytes due to abnormal meiosis. We aimed to identify pathogenic variants in two sisters with OMA phenotype from a non-consanguineous family.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Whole-exome sequencing and Sanger sequencing were conducted to identify and validate the disease-causing gene variant. Additionally, we performed a minigene assay, quantitative reverse transcription PCR, and Western blotting to assess the effects of the variant.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>We identified a novel homozygous splicing variant (c.1021-11T>C) in <i>TRIP13</i>, which followed a recessive inheritance pattern. Minigene assay showed that the variant could disrupt the integrity of <i>TRIP13</i> mRNA, as evidenced by the production of an alternative transcript with intron10 intermediate retention of 79 bp. Compared to normal controls, the expression of <i>TRIP13</i> mRNA and abundance of TRIP13 protein were also significantly decreased in Epstein-Barr virus-immortalized lymphoblastoid cells derived from affected individuals.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Our findings confirm the contribution of genetic factors to OMA and expand the mutation spectrum of <i>TRIP13</i> in female infertility.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":"186 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abnormal cell death due to superficial trophoblast dysfunction caused by placental hypoxia plays a vital role in the development of preeclampsia (PE). Lactic acid stimulates gene transcription in chromatin through lactate modification of histone lysine. Nevertheless, the content and function of lactate in PE development remains largely unclear.
Methods
The contents of lactic acid and copper in 30 PE and 30 normal placentas were determined by kit colorimetry. Real-time quantitative fluorescent PCR (qRT-PCR) and Western blot were used to detect the expression of SLC31A1 in cells and tissues. Cell proliferation, apoptosis, and invasion were detected by cell counting kit 8 (CCK-8), MTS assay, colony formation assay, and Transwell assay. The transcriptional regulation between Grhl2 and SLC31A was verified by the luciferase reporter gene method and ChIP. The H3K18la modification level was detected by ChIP-PCR.
Results
Herein, we detected increased lactic acid levels in the PE placental tissue, which inhibit the proliferation and invasion of trophoblasts. Interestingly, lactic acid increases intracellular copper content by enhancing the expression of SLC31A1, a key protein of copper ion transporters. Lentivirus knockdown of SLC31A1 blocked the lactate-induced proliferation and invasion of trophoblasts by inhibiting cell cuproptosis. Mechanically, we identified that Grhl2 mediated SLC31A1 expression through transcription and participated in SLC31A1-inhibited proliferation, invasion, and cuproptosis of trophoblasts. Furthermore, the high lactate content increased Grhl2 expression by enhancing lactate modification of histone H3K18 in the Grhl2 promoter region.
Conclusions
Blocking the lactate-regulated Grhl2/SLC31A1 axis and trophoblastic cuproptosis may be a potential approach to prevent and treat PE.
{"title":"Blocking lactate regulation of the Grhl2/SLC31A1 axis inhibits trophoblast cuproptosis and preeclampsia development","authors":"Xue-Yan Shen, Jing Huang, Li-Li Chen, Man-Ting Sha, Jing Gao, Hong Xin","doi":"10.1007/s10815-024-03256-w","DOIUrl":"https://doi.org/10.1007/s10815-024-03256-w","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>Abnormal cell death due to superficial trophoblast dysfunction caused by placental hypoxia plays a vital role in the development of preeclampsia (PE). Lactic acid stimulates gene transcription in chromatin through lactate modification of histone lysine. Nevertheless, the content and function of lactate in PE development remains largely unclear.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>The contents of lactic acid and copper in 30 PE and 30 normal placentas were determined by kit colorimetry. Real-time quantitative fluorescent PCR (qRT-PCR) and Western blot were used to detect the expression of SLC31A1 in cells and tissues. Cell proliferation, apoptosis, and invasion were detected by cell counting kit 8 (CCK-8), MTS assay, colony formation assay, and Transwell assay. The transcriptional regulation between Grhl2 and SLC31A was verified by the luciferase reporter gene method and ChIP. The H3K18la modification level was detected by ChIP-PCR.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Herein, we detected increased lactic acid levels in the PE placental tissue, which inhibit the proliferation and invasion of trophoblasts. Interestingly, lactic acid increases intracellular copper content by enhancing the expression of SLC31A1, a key protein of copper ion transporters. Lentivirus knockdown of SLC31A1 blocked the lactate-induced proliferation and invasion of trophoblasts by inhibiting cell cuproptosis. Mechanically, we identified that Grhl2 mediated SLC31A1 expression through transcription and participated in SLC31A1-inhibited proliferation, invasion, and cuproptosis of trophoblasts. Furthermore, the high lactate content increased Grhl2 expression by enhancing lactate modification of histone H3K18 in the Grhl2 promoter region.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>Blocking the lactate-regulated Grhl2/SLC31A1 axis and trophoblastic cuproptosis may be a potential approach to prevent and treat PE.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":"113 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-17DOI: 10.1007/s10815-024-03235-1
Lu Luo, Wenjun Wang, Yan Xu, Yuanyuan Yang, Limei Zhang, Jun Gao, Jiayi Mai, Qiong Wang, Fei Gong
Purpose
Comprehensive chromosomal status of blastocyst from women with polycystic ovary syndrome (PCOS) was limited. This study aimed to identify possible differences in the preimplantation blastocyst chromosome aberrations between PCOS women and controls receiving preimplantation genetic testing (PGT).
Methods
This was a multi-center retrospective cohort study including a total of 707 blastocysts from 147 PCOS women and 3006 blastocysts from 821 control women receiving PGT between 2015 and 2021. Embryonic chromosomal aberration spectrums were compared between PCOS and controls. Mixed effects generalized linear model was conducted to explore possible influence of PCOS-related endocrinological disorders on embryonic chromosomal abnormalities.
Results
Blastocysts from PCOS demonstrated significantly lower aneuploidy rate (15.2% vs. 25.2% per women, P < 0.001; 14.7% vs. 25.4% per blastocyst, P < 0.001) but greater mosaicism rate (12.5% vs. 8.0% per women, P = 0.007; 16.5% vs. 8.7% per blastocyst, P < 0.001). Mixed effects generalized linear model identified PCOS as an independent protective factor against embryonic aneuploidy (adjusted odds ratio = 0.68, 95% confidence interval, 0.50–0.93, P = 0.014) but a risk factor for embryonic mosaicism (adjusted odds ratio = 1.52, 95% confidence interval 1.11–2.10, P = 0.009). Further model analysis suggested that insulin resistance could be responsible for the increased risk of embryonic mosaicism among PCOS women (adjusted odds ratio = 2.17, 95% confidence interval, 1.10–4.31, P = 0.026).
Conclusion
PCOS is associated with a lower aneuploidy risk but an increased mosaicism risk in preimplantation blastocysts, and insulin resistance should be investigated as a potential cause.
目的对多囊卵巢综合征（PCOS）妇女胚泡染色体状况的全面研究有限。本研究旨在确定接受胚胎植入前基因检测（PGT）的多囊卵巢综合征（PCOS）女性和对照组在胚胎植入前囊胚染色体畸变方面可能存在的差异。方法这是一项多中心回顾性队列研究，包括 2015 年至 2021 年间接受 PGT 的 147 名 PCOS 女性的 707 个囊胚和 821 名对照组女性的 3006 个囊胚。比较了多囊卵巢综合征和对照组的胚胎染色体畸变谱。混合效应广义线性模型探讨了 PCOS 相关内分泌紊乱对胚胎染色体异常的可能影响。2% vs. 25.2% per women, P < 0.001; 14.7% vs. 25.4% per blastocyst, P < 0.001），但嵌合率较高（12.5% vs. 8.0% per women, P = 0.007; 16.5% vs. 8.7% per blastocyst, P < 0.001）。混合效应广义线性模型确定多囊卵巢综合征是胚胎非整倍体的独立保护因素（调整后的几率比 = 0.68，95% 置信区间为 0.50-0.93，P = 0.014），但却是胚胎嵌合的危险因素（调整后的几率比 = 1.52，95% 置信区间为 1.11-2.10，P = 0.009）。进一步的模型分析表明，胰岛素抵抗可能是 PCOS 妇女胚胎嵌合风险增加的原因（调整后的几率比 = 2.17，95% 置信区间为 1.10-4.31，P = 0.026）。
{"title":"Differences in preimplantation blastocyst chromosomal aberrations between polycystic ovary syndrome women and controls: a multi-center retrospective cohort study","authors":"Lu Luo, Wenjun Wang, Yan Xu, Yuanyuan Yang, Limei Zhang, Jun Gao, Jiayi Mai, Qiong Wang, Fei Gong","doi":"10.1007/s10815-024-03235-1","DOIUrl":"https://doi.org/10.1007/s10815-024-03235-1","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>Comprehensive chromosomal status of blastocyst from women with polycystic ovary syndrome (PCOS) was limited. This study aimed to identify possible differences in the preimplantation blastocyst chromosome aberrations between PCOS women and controls receiving preimplantation genetic testing (PGT).</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>This was a multi-center retrospective cohort study including a total of 707 blastocysts from 147 PCOS women and 3006 blastocysts from 821 control women receiving PGT between 2015 and 2021. Embryonic chromosomal aberration spectrums were compared between PCOS and controls. Mixed effects generalized linear model was conducted to explore possible influence of PCOS-related endocrinological disorders on embryonic chromosomal abnormalities.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Blastocysts from PCOS demonstrated significantly lower aneuploidy rate (15.2% vs. 25.2% per women, <i>P</i> < 0.001; 14.7% vs. 25.4% per blastocyst, <i>P</i> < 0.001) but greater mosaicism rate (12.5% vs. 8.0% per women, <i>P</i> = 0.007; 16.5% vs. 8.7% per blastocyst, <i>P</i> < 0.001). Mixed effects generalized linear model identified PCOS as an independent protective factor against embryonic aneuploidy (adjusted odds ratio = 0.68, 95% confidence interval, 0.50<i>–</i>0.93, <i>P</i> = 0.014) but a risk factor for embryonic mosaicism (adjusted odds ratio = 1.52, 95% confidence interval 1.11<i>–</i>2.10, <i>P</i> = 0.009). Further model analysis suggested that insulin resistance could be responsible for the increased risk of embryonic mosaicism among PCOS women (adjusted odds ratio = 2.17, 95% confidence interval, 1.10<i>–</i>4.31, <i>P</i> = 0.026).</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>PCOS is associated with a lower aneuploidy risk but an increased mosaicism risk in preimplantation blastocysts, and insulin resistance should be investigated as a potential cause.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":"28 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-14DOI: 10.1007/s10815-024-03241-3
Hui Mu, Haikun Yu, Song Yan, Jie Lu, Jiaqin Mao, Dan Sun, Ni Jin, Zheng Fang, Xueyan Lu, Jie Dong, Ying Su, Shuqiang Chen, Xiaohong Wang
Objective
High serum estrogen concentrations after controlled ovarian hyperstimulation (COH) and fresh embryo transfers are associated with the increased risk of pregnancy complications resulting from aberrant placentation. Uterine natural killer (uNK) cells are important for establishment of pregnancy and normal placentation. It has been found that the proliferation and function of uNK cells are compromised by COH. However, the underlying role of high concentration of estrogen following COH in the abnormalities of uNK cells is poorly understood.
Methods
Expression of cytokines and immunophenotype study of uNK was performed by flow cytometry analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to quantify RNA expression; Western blot was performed to quantify protein levels.
Results
The secretion level of pro-angiogenic factors in uNK cells is significantly reduced by co-culture with decidual stromal cells (DSCs) induced by high estrogen. It was discovered that COH and supraphysiologic levels of estrogen downregulated IL-11 in decidual tissue of mice. Additionally, we found that the downregulation of IL-11 is a major factor contributing to the downregulation of VEGF and PLGF in uNK cells. Moreover, we found that uNK cells may acquire IL-11Rα sequentially during differentiation and that only a portion of uNK cells are IL-11Rα positive. Lastly, we discovered that IL-11 may regulate VEGF and PLGF secretion in uNK cells via the ERK signaling pathway.
Conclusion
These results suggested the downregulation of IL-11 expression in DSCs caused by high estrogen levels affects the secretion of pro-angiogenic factors in uNK cells, which provided an explanation for the pregnancy complications caused by COH.
{"title":"High concentration of estrogen resulted by COH may affect the secretion of pro-angiogenic factors in uNK cells by downregulating the expression of IL-11 in decidual stromal cells","authors":"Hui Mu, Haikun Yu, Song Yan, Jie Lu, Jiaqin Mao, Dan Sun, Ni Jin, Zheng Fang, Xueyan Lu, Jie Dong, Ying Su, Shuqiang Chen, Xiaohong Wang","doi":"10.1007/s10815-024-03241-3","DOIUrl":"https://doi.org/10.1007/s10815-024-03241-3","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Objective</h3><p>High serum estrogen concentrations after controlled ovarian hyperstimulation (COH) and fresh embryo transfers are associated with the increased risk of pregnancy complications resulting from aberrant placentation. Uterine natural killer (uNK) cells are important for establishment of pregnancy and normal placentation. It has been found that the proliferation and function of uNK cells are compromised by COH. However, the underlying role of high concentration of estrogen following COH in the abnormalities of uNK cells is poorly understood.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Expression of cytokines and immunophenotype study of uNK was performed by flow cytometry analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to quantify RNA expression; Western blot was performed to quantify protein levels.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The secretion level of pro-angiogenic factors in uNK cells is significantly reduced by co-culture with decidual stromal cells (DSCs) induced by high estrogen. It was discovered that COH and supraphysiologic levels of estrogen downregulated IL-11 in decidual tissue of mice. Additionally, we found that the downregulation of IL-11 is a major factor contributing to the downregulation of VEGF and PLGF in uNK cells. Moreover, we found that uNK cells may acquire IL-11Rα sequentially during differentiation and that only a portion of uNK cells are IL-11Rα positive. Lastly, we discovered that IL-11 may regulate VEGF and PLGF secretion in uNK cells via the ERK signaling pathway.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>These results suggested the downregulation of IL-11 expression in DSCs caused by high estrogen levels affects the secretion of pro-angiogenic factors in uNK cells, which provided an explanation for the pregnancy complications caused by COH.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":"24 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-14DOI: 10.1007/s10815-024-03245-z
Zhaowen Zang, Jianan Lyu, Yuchen Yan, Mingwei Zhong, Qian Zhang, Guangyong Zhang, Yan Li, Junhao Yan
Purpose
Multiple factors have been shown to influence the rate of clinical pregnancy after FET in IVF treatment, including embryo quality, synchronization of embryo and endometrium, and endometrial receptivity (ER). The subendometrial blood flow conditions could also contribute potentially major effects toward the establishment and maintenance of pregnancy. We conducted a retrospective cohort study to examine the correlation between subendometrial blood flow, as determined by Doppler ultrasound, and pregnancy outcomes in IVF patients with a thin endometrium (endometrium thickness [EMT] ≤ 0.7 cm).
Methods
This was a retrospective cohort study conducted at a university-affiliated reproductive hospital from January 2017 to April 2023. The EMT and subendometrial blood flows were assessed using transvaginal color Doppler ultrasound and evaluated by experienced clinical ultrasound physicians on the endometrial transformation day. The pregnancy outcomes were followed up and documented in clinical medical records through the IVF cohort study at our center.
Results
In the patients with 0.5 cm ≤ EMT ≤ 0.7 cm, the embryo implantation rate was statistically significant increased in the patients with the presence of subendometrial blood flow (OR 1.484; 95% CI, 1.001–2.200; P = 0.049; aOR 1.425; 95% CI, 1.030–2.123; P = 0.003). Patients with discernible subendometrial blood flow have superior live birth (P = 0.028), clinical pregnancy (P = 0.049), and embryo implantation (P = 0.027) compared to the patients without subendometrial blood flow when the EMT is ≤ 0.7 cm.
Conclusions
The presence of subendometrial blood flow detected by ultrasound was positively associated with successful embryo implantation and favorable pregnancy outcomes in patients with thin endometrium undergoing FET.
目的在试管婴儿治疗中，有多种因素被证明会影响 FET 后的临床妊娠率，包括胚胎质量、胚胎与子宫内膜的同步性以及子宫内膜接受性（ER）。子宫内膜下血流条件也可能对妊娠的建立和维持产生潜在的重大影响。我们开展了一项回顾性队列研究，以探讨多普勒超声测定的子宫内膜下血流与子宫内膜薄（子宫内膜厚度 [EMT] ≤ 0.7 厘米）的 IVF 患者的妊娠结局之间的相关性。使用经阴道彩色多普勒超声评估 EMT 和子宫内膜下血流，并由经验丰富的临床超声医生在子宫内膜转化日进行评估。结果 在 0.5 cm ≤ EMT ≤ 0.7 cm 的患者中，存在子宫内膜下血流的患者的胚胎植入率显著增加（OR 1.484; 95% CI, 1.001-2.200; P = 0.049; aOR 1.425; 95% CI, 1.030-2.123; P = 0.003）。结论 超声检测到的子宫内膜下血流与接受 FET 的薄子宫内膜患者的胚胎成功着床和良好妊娠结局呈正相关。
{"title":"Subendometrial blood flow detected by Doppler ultrasound associates with pregnancy outcomes of frozen embryo transfer in patients with thin endometrium","authors":"Zhaowen Zang, Jianan Lyu, Yuchen Yan, Mingwei Zhong, Qian Zhang, Guangyong Zhang, Yan Li, Junhao Yan","doi":"10.1007/s10815-024-03245-z","DOIUrl":"https://doi.org/10.1007/s10815-024-03245-z","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>Multiple factors have been shown to influence the rate of clinical pregnancy after FET in IVF treatment, including embryo quality, synchronization of embryo and endometrium, and endometrial receptivity (ER). The subendometrial blood flow conditions could also contribute potentially major effects toward the establishment and maintenance of pregnancy. We conducted a retrospective cohort study to examine the correlation between subendometrial blood flow, as determined by Doppler ultrasound, and pregnancy outcomes in IVF patients with a thin endometrium (endometrium thickness [EMT] ≤ 0.7 cm).</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>This was a retrospective cohort study conducted at a university-affiliated reproductive hospital from January 2017 to April 2023. The EMT and subendometrial blood flows were assessed using transvaginal color Doppler ultrasound and evaluated by experienced clinical ultrasound physicians on the endometrial transformation day. The pregnancy outcomes were followed up and documented in clinical medical records through the IVF cohort study at our center.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>In the patients with 0.5 cm ≤ EMT ≤ 0.7 cm, the embryo implantation rate was statistically significant increased in the patients with the presence of subendometrial blood flow (OR 1.484; 95% CI, 1.001–2.200; <i>P</i> = 0.049; aOR 1.425; 95% CI, 1.030–2.123; <i>P</i> = 0.003). Patients with discernible subendometrial blood flow have superior live birth (<i>P</i> = 0.028), clinical pregnancy (<i>P</i> = 0.049), and embryo implantation (<i>P</i> = 0.027) compared to the patients without subendometrial blood flow when the EMT is ≤ 0.7 cm.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>The presence of subendometrial blood flow detected by ultrasound was positively associated with successful embryo implantation and favorable pregnancy outcomes in patients with thin endometrium undergoing FET.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":"10 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The purpose of this study is to determine whether intrauterine infusion of autologous platelet-rich plasma (PRP) gel increases endometrial thickness (EMT) and improves the outcomes of frozen-thawed embryo transfer (FET) in women with thin endometrium.
Methods
This study included 111 women (aged 25–44 years) who had thin endometrium. All patients had at least one previous cycle canceled because of thin endometrium or previous embryo transfer cycles and an EMT < 7 mm. Forty-seven women underwent intrauterine infusion of autologous PRP gel on three occasions during endometrial preparation and the remaining women served as controls. The final EMT was measured by ultrasound before the start of the luteal phase, and FET-related outcome parameters were monitored.
Results
Mean EMT was greater in women who received PRP gel than in those who did not (6.7 mm vs. 6.3 mm, respectively, p < 0.05). FET was attempted in all women. The 47 women who underwent infusion of PRP had a significantly higher pregnancy rate (18 pregnancies (38.3%), with 17 (36.2%) ongoing) compared with 64 control women (ten pregnancies (18.5%), nine (16.7%) ongoing). However, there was no significant reduction in the miscarriage rate.
Conclusion
Intrauterine infusion of autologous PRP gel during endometrial preparation for FET cycles can improve the EMT, clinical pregnancy rate, and ongoing pregnancy rate in women with thin endometrium.
本研究的目的是确定宫腔内输注自体富血小板血浆（PRP）凝胶是否会增加子宫内膜厚度（EMT）并改善子宫内膜薄的女性冷冻-解冻胚胎移植（FET）的结果。所有患者以前至少有一个周期因子宫内膜薄或以前的胚胎移植周期而被取消，EMT < 7 mm。47名妇女在子宫内膜准备期间接受了三次宫腔内注射自体PRP凝胶，其余妇女作为对照组。结果接受PRP凝胶治疗的妇女的平均EMT大于未接受治疗的妇女（分别为6.7 mm vs. 6.3 mm，p <0.05）。所有女性都尝试了 FET。与 64 名对照组女性（10 人怀孕（18.5%），9 人正在怀孕（16.7%））相比，47 名输注了 PRP 的女性怀孕率明显更高（18 人怀孕（38.3%），17 人（36.2%）正在怀孕）。结论在为 FET 周期进行子宫内膜准备期间，宫腔注射自体 PRP 凝胶可改善薄子宫内膜妇女的 EMT、临床妊娠率和持续妊娠率。
{"title":"Effects of intrauterine infusion of autologous platelet-rich plasma gel on endometrial thickness and outcomes of frozen-thawed embryo transfer in women with thin endometrium","authors":"Xiufen Wang, Yangyang Wang, Jing Li, Yetao Han, Minling Wei, Aike Xu, Liaobing Xin","doi":"10.1007/s10815-024-03254-y","DOIUrl":"https://doi.org/10.1007/s10815-024-03254-y","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>The purpose of this study is to determine whether intrauterine infusion of autologous platelet-rich plasma (PRP) gel increases endometrial thickness (EMT) and improves the outcomes of frozen-thawed embryo transfer (FET) in women with thin endometrium.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>This study included 111 women (aged 25–44 years) who had thin endometrium. All patients had at least one previous cycle canceled because of thin endometrium or previous embryo transfer cycles and an EMT < 7 mm. Forty-seven women underwent intrauterine infusion of autologous PRP gel on three occasions during endometrial preparation and the remaining women served as controls. The final EMT was measured by ultrasound before the start of the luteal phase, and FET-related outcome parameters were monitored.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Mean EMT was greater in women who received PRP gel than in those who did not (6.7 mm vs. 6.3 mm, respectively, <i>p</i> < 0.05). FET was attempted in all women. The 47 women who underwent infusion of PRP had a significantly higher pregnancy rate (18 pregnancies (38.3%), with 17 (36.2%) ongoing) compared with 64 control women (ten pregnancies (18.5%), nine (16.7%) ongoing). However, there was no significant reduction in the miscarriage rate.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Intrauterine infusion of autologous PRP gel during endometrial preparation for FET cycles can improve the EMT, clinical pregnancy rate, and ongoing pregnancy rate in women with thin endometrium.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":"1 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142223048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1007/s10815-024-03251-1
Yi Wang, Yanggang Hong
{"title":"Unlocking the potential of artificial intelligence in reproductive medicine: a bibliometric analysis from 1999 to 2024","authors":"Yi Wang, Yanggang Hong","doi":"10.1007/s10815-024-03251-1","DOIUrl":"https://doi.org/10.1007/s10815-024-03251-1","url":null,"abstract":"","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":"4 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142223050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-11DOI: 10.1007/s10815-024-03250-2
Giulia Severi, Enrico Ambrosini, Luca Caramanna, Luigi Monti, Pamela Magini, Giovanni Innella
Purpose
To report an exceptional case of male-to-male transmission of genetically based non-obstructive azoospermia (NOA) and varicocele through a naturally obtained pregnancy.
Subjects and methods
A father and his son were both diagnosed with NOA after centrifugation and varicocele. The father has no other clinical concerns apart from infertility, detected after many attempts of having another child, but given his urological situation (bilateral varicocele and NOA) assisted reproductive techniques were discouraged. After genetic counseling, several genetic-chromosomal analyses were carried out in the son (karyotype, chromosome Y microdeletions, CFTR screening, NGS infertility panels, and finally array-CGH).
Results
After a series of inconclusive tests, array-CGH detected a deletion of 224–283 kb (del9p24.3) involving part of the KANK1 and DMRT1 genes, inherited from the father. Haploinsufficiency of DMRT1 was therefore considered the determining factor in the development of azoospermia in the family by a loss of function mechanism.
Conclusion
The confirmation of father-to-son transmission of a deletion including DMRT1 represents an important point for clinicians dealing with male infertility, even when complete azoospermia is repetitively detected, and must be of hope for a relevant portion of men. Inclusion criteria for the access to assisted reproductive techniques may also be reconsidered and worthy of a greater number of clinical insights. Finally, since DMRT1 alterations have been associated with NOA and abnormal testicular development, but not specifically with varicocele, further studies are required to validate this issue, as varicocele may have played a crucial role in this case.
{"title":"Familial DMRT1-related non-obstructive azoospermia: a case report","authors":"Giulia Severi, Enrico Ambrosini, Luca Caramanna, Luigi Monti, Pamela Magini, Giovanni Innella","doi":"10.1007/s10815-024-03250-2","DOIUrl":"https://doi.org/10.1007/s10815-024-03250-2","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>To report an exceptional case of male-to-male transmission of genetically based non-obstructive azoospermia (NOA) and varicocele through a naturally obtained pregnancy.</p><h3 data-test=\"abstract-sub-heading\">Subjects and methods</h3><p>A father and his son were both diagnosed with NOA after centrifugation and varicocele. The father has no other clinical concerns apart from infertility, detected after many attempts of having another child, but given his urological situation (bilateral varicocele and NOA) assisted reproductive techniques were discouraged. After genetic counseling, several genetic-chromosomal analyses were carried out in the son (karyotype, chromosome Y microdeletions, <i>CFTR</i> screening, NGS infertility panels, and finally array-CGH).</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>After a series of inconclusive tests, array-CGH detected a deletion of 224–283 kb (del9p24.3) involving part of the <i>KANK1</i> and <i>DMRT1</i> genes, inherited from the father. Haploinsufficiency of <i>DMRT1</i> was therefore considered the determining factor in the development of azoospermia in the family by a loss of function mechanism.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>The confirmation of father-to-son transmission of a deletion including <i>DMRT1</i> represents an important point for clinicians dealing with male infertility, even when complete azoospermia is repetitively detected, and must be of hope for a relevant portion of men. Inclusion criteria for the access to assisted reproductive techniques may also be reconsidered and worthy of a greater number of clinical insights. Finally, since <i>DMRT1</i> alterations have been associated with NOA and abnormal testicular development, but not specifically with varicocele, further studies are required to validate this issue, as varicocele may have played a crucial role in this case.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":"29 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142223052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-10DOI: 10.1007/s10815-024-03218-2
Wenbin Wu, Menglu Ji, Jingjing Yang, Meng Zhang, Dayong Hao, Xinyan Zhao, Saisai Li, Yichun Guan, Xingling Wang
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.
目的 本研究旨在评估辅助生殖技术是否会改变多胎妊娠减胎后胎儿组织中H19启动子和H19印记控制元件（ICE）的DNA甲基化水平。方法获得了多胎妊娠的胎儿组织，包括新鲜和冷冻解冻的胚胎：9个来自常规体外受精（c-IVF），4个来自卵胞浆内单精子注射（ICSI），10个来自低温保存的体外受精胚胎（cryo-IVF），6个来自低温保存的ICSI胚胎（cryo-ICSI）。研究人员利用基于下一代测序的亚硫酸氢盐 PCR 技术确定了 H19 启动子和 H19 ICE 中三个 CpG 岛（H19-1、H19-2 和 H19-3）的 DNA 甲基化状态。结果ICSI（β = -3.189，95% CI = -5.034 to -1.345, p = 0.0026）、冷冻-体外受精（β = -2.150，95% CI = -3.706到-0.593，p = 0.0129）和冷冻-ICSI（β = -2.238，95% CI = -3.817到-0.659，p = 0.0110）组在主要结果H19-1区域的甲基化水平在调整后显著低于c-IVF组。对于次要结果 H19-2 区域，在冷冻IVF 组（β = -2.132，95% CI = -4.071 至 -0.192，p = 0.0425）和冷冻卵胞浆内单精子显微注射组（β = -2.598，95% CI = -4.566 至 -0.结论这些研究结果进一步表明，胚胎冷冻保存和潜在的 ICSI 可降低 H19 启动子的甲基化水平，提倡在必要时谨慎使用这些技术。
{"title":"ART altered DNA methylation of the imprinted gene H19 in fetal tissue after multifetal pregnancy reduction","authors":"Wenbin Wu, Menglu Ji, Jingjing Yang, Meng Zhang, Dayong Hao, Xinyan Zhao, Saisai Li, Yichun Guan, Xingling Wang","doi":"10.1007/s10815-024-03218-2","DOIUrl":"https://doi.org/10.1007/s10815-024-03218-2","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>This study aimed to assess whether assisted reproductive technology alters DNA methylation levels at the <i>H19</i> promoter and <i>H19</i> imprinting control element (ICE) in fetal tissues obtained after multifetal pregnancy reduction.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>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 (<i>H19</i>-1, <i>H19</i>-2, and <i>H19</i>-3) in the <i>H19</i> promoter and <i>H19</i> ICE. The primary outcome was <i>H19</i>-1 DNA methylation status, whereas secondary outcomes assessed <i>H19</i>-2, <i>H19</i>-3, and ICE methylation.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The ICSI (β = -3.189, 95% CI = -5.034 to -1.345, <i>p</i> = 0.0026), cryo-IVF (β = -2.150, 95% CI = -3.706 to -0.593, <i>p</i> = 0.0129), and cryo-ICSI (β = -2.238, 95% CI = -3.817 to -0.659, <i>p</i> = 0.0110) groups exhibited significantly lower methylation levels in the primary outcome <i>H19</i>-1 region than the c-IVF group after adjustment. For the secondary outcome <i>H19</i>-2 region, significant decreases were observed in the cryo-IVF (β = -2.132, 95% CI = -4.071 to -0.192, <i>p</i> = 0.0425) and cryo-ICSI groups (β = -2.598, 95% CI = -4.566 to -0.630, <i>p</i> = 0.0168).</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>These findings further indicate that embryo cryopreservation and potentially ICSI can lower the methylation level of the <i>H19</i> promoter, advocating for careful use of these techniques when necessary.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":"2 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142223051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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