Semir Gül, Veerle Vloeberghs, Inge Gies, Ellen Goossens
<p><strong>Study question: </strong>Do testis-specific cells have a normal karyotype in non-mosaic postpubertal Klinefelter syndrome (KS) patients with focal spermatogenesis and in non-mosaic prepubertal KS boys?</p><p><strong>Summary answer: </strong>Spermatogonia have a 46, XY karyotype, and Sertoli cells surrounding these spermatogonia in postpubertal patients also have a 46, XY karyotype, whereas, in prepubertal KS boys, Sertoli cells surrounding the spermatogonia still have a 47, XXY karyotype.</p><p><strong>What is known already: </strong>A significant proportion of patients with non-mosaic KS can have children by using assisted reproductive techniques thanks to focal spermatogenesis. However, the karyotype of the cells that are able to support focal spermatogenesis has not been revealed.</p><p><strong>Study design, size, duration: </strong>Testicular biopsy samples from non-mosaic KS patients were included in the study. Karyotyping for sex chromosomes in testis-specific cells was performed by immunohistochemical analysis of inactive X (Xi) chromosome and/or fluorescent in situ hybridization (FISH) analysis of chromosomes 18, X, and Y.</p><p><strong>Participants/materials, setting, methods: </strong>A total of 22 KS patients (17 postpubertal and 5 prepubertal) who were non-mosaic according to lymphocyte karyotype analysis, were included in the study. After tissue processing, paraffin embedding, and sectioning, the following primary antibodies were used for cell-specific analysis and Xi detection; one section was stained with MAGE A4 for spermatogonia, SOX9 for Sertoli cells, and H3K27me3 for Xi; the other one was stained with CYP17A1 for Leydig cells, ACTA2 for peritubular myoid cells, and H3K27me3 for Xi. Xi negative (Xi-) somatic cells (i.e. Sertoli cells, Leydig cells, and peritubular myoid cells) were evaluated as having the 46, XY karyotype; Xi positive (Xi+) somatic cells were evaluated as having the 47, XXY. FISH stain for chromosomes 18, X, and Y was performed on the same sections to investigate the karyotype of spermatogonia and to validate the immunohistochemistry results for somatic cells.</p><p><strong>Main results and the role of chance: </strong>According to our data, all spermatogonia in both postpubertal and prepubertal non-mosaic KS patients seem to have 46, XY karyotype. However, while the Sertoli cells surrounding spermatogonia in postpubertal samples also had a 46, XY karyotype, the Sertoli cells surrounding spermatogonia in prepubertal samples had a 47, XXY karyotype. In addition, while the Sertoli cells in some of the Sertoli cell-only tubules had 46, XY karyotype, the Sertoli cells in some of the other Sertoli cell-only tubules had 47, XXY karyotype in postpubertal samples. In contrast to the postpubertal samples, Sertoli cells in all tubules in the prepubertal samples had the 47, XXY karyotype. Our data also suggest that germ cells lose the extra X chromosome during embryonic, fetal, or neonatal life, while Sertoli c
研究问题:在有局灶性精子生成的非嵌合型青春期后克氏综合征(KS)患者和非嵌合型青春期前克氏综合征男孩中,睾丸特异性细胞的核型是否正常?青春期后患者精原细胞的核型为46,XY,围绕这些精原细胞的Sertoli细胞的核型也为46,XY,而在青春期前的KS男孩中,围绕精原细胞的Sertoli细胞的核型仍为47,XXY:已经知道的是:相当一部分非马赛克 KS 患者可以通过辅助生殖技术,利用局灶性精子发生技术生儿育女。然而,能够支持局灶性精子发生的细胞的核型尚未揭示:研究包括非马赛克 KS 患者的睾丸活检样本。通过免疫组化分析非活性X(Xi)染色体和/或荧光原位杂交(FISH)分析18、X和Y染色体,对睾丸特异性细胞中的性染色体进行核型分析:研究共纳入了 22 名 KS 患者(17 名青春期后,5 名青春期前),根据淋巴细胞核型分析,这些患者均为非马赛克患者。组织处理、石蜡包埋和切片后,使用以下一抗进行细胞特异性分析和Xi检测:一张切片用MAGE A4染色以检测精原细胞,用SOX9染色以检测Sertoli细胞,用H3K27me3染色以检测Xi;另一张切片用CYP17A1染色以检测Leydig细胞,用ACTA2染色以检测管周肌细胞,用H3K27me3染色以检测Xi。Xi阴性(Xi-)体细胞(即Sertoli细胞、Leydig细胞和管周肌细胞)被评估为具有46, XY核型;Xi阳性(Xi+)体细胞被评估为具有47, XXY核型。对同一切片进行了 18、X 和 Y 染色体的 FISH 染色,以研究精原细胞的核型,并验证体细胞的免疫组化结果:根据我们的数据,青春期后和青春期前非嵌合型KS患者的所有精原细胞似乎都是46, XY核型。然而,在青春期后的样本中,精原细胞周围的 Sertoli 细胞也是 46 XY 核型,而在青春期前的样本中,精原细胞周围的 Sertoli 细胞却是 47 XXY 核型。此外,在青春期后样本中,部分仅有 Sertoli 细胞的小管中的 Sertoli 细胞核型为 46 XY,而其他一些仅有 Sertoli 细胞的小管中的 Sertoli 细胞核型为 47 XXY。与青春期后样本相反,青春期前样本中所有小管中的 Sertoli 细胞都是 47, XXY 核型。我们的数据还表明,生殖细胞在胚胎期、胎儿期或新生儿期会失去额外的X染色体,而Sertoli细胞在青春期前后会失去额外的X染色体。在青春期后的患者和青春期前的男孩中,管周肌细胞和雷迪格细胞也可能是马赛克的,但这还需要进一步研究:含有精原细胞的青春期前睾丸样本数量有限,因此需要更多样本才能得出明确结论。并非所有细胞核都与切片平面重合,这限制了通过免疫组化和 FISH 在某些细胞中准确检测 X 染色体。为克服这一限制,可采用不同技术对从新鲜组织中分离出来的完整细胞进行 X 染色体分析。此外,没有证据表明胚胎发育过程中生殖细胞迁移过程中 Xi 激活后 X 染色体失活会再次发生,这限制了通过 H3K27me3 预测生殖细胞中 X 染色体含量:我们的发现将为开展新的临床重要研究奠定基础,这些研究将探讨精原细胞和Sertoli细胞中额外的X染色体究竟何时以及通过何种机制丢失:本研究得到了土耳其科学技术研究理事会(TUBITAK)(2219--土耳其公民国际博士后研究奖学金计划)和布鲁塞尔自由大学战略研究计划(SRP89)的资助。作者声明不存在利益冲突:不适用。
{"title":"Testicular mosaicism in non-mosaic postpubertal Klinefelter patients with focal spermatogenesis and in non-mosaic prepubertal Klinefelter boys.","authors":"Semir Gül, Veerle Vloeberghs, Inge Gies, Ellen Goossens","doi":"10.1093/humrep/deae192","DOIUrl":"10.1093/humrep/deae192","url":null,"abstract":"<p><strong>Study question: </strong>Do testis-specific cells have a normal karyotype in non-mosaic postpubertal Klinefelter syndrome (KS) patients with focal spermatogenesis and in non-mosaic prepubertal KS boys?</p><p><strong>Summary answer: </strong>Spermatogonia have a 46, XY karyotype, and Sertoli cells surrounding these spermatogonia in postpubertal patients also have a 46, XY karyotype, whereas, in prepubertal KS boys, Sertoli cells surrounding the spermatogonia still have a 47, XXY karyotype.</p><p><strong>What is known already: </strong>A significant proportion of patients with non-mosaic KS can have children by using assisted reproductive techniques thanks to focal spermatogenesis. However, the karyotype of the cells that are able to support focal spermatogenesis has not been revealed.</p><p><strong>Study design, size, duration: </strong>Testicular biopsy samples from non-mosaic KS patients were included in the study. Karyotyping for sex chromosomes in testis-specific cells was performed by immunohistochemical analysis of inactive X (Xi) chromosome and/or fluorescent in situ hybridization (FISH) analysis of chromosomes 18, X, and Y.</p><p><strong>Participants/materials, setting, methods: </strong>A total of 22 KS patients (17 postpubertal and 5 prepubertal) who were non-mosaic according to lymphocyte karyotype analysis, were included in the study. After tissue processing, paraffin embedding, and sectioning, the following primary antibodies were used for cell-specific analysis and Xi detection; one section was stained with MAGE A4 for spermatogonia, SOX9 for Sertoli cells, and H3K27me3 for Xi; the other one was stained with CYP17A1 for Leydig cells, ACTA2 for peritubular myoid cells, and H3K27me3 for Xi. Xi negative (Xi-) somatic cells (i.e. Sertoli cells, Leydig cells, and peritubular myoid cells) were evaluated as having the 46, XY karyotype; Xi positive (Xi+) somatic cells were evaluated as having the 47, XXY. FISH stain for chromosomes 18, X, and Y was performed on the same sections to investigate the karyotype of spermatogonia and to validate the immunohistochemistry results for somatic cells.</p><p><strong>Main results and the role of chance: </strong>According to our data, all spermatogonia in both postpubertal and prepubertal non-mosaic KS patients seem to have 46, XY karyotype. However, while the Sertoli cells surrounding spermatogonia in postpubertal samples also had a 46, XY karyotype, the Sertoli cells surrounding spermatogonia in prepubertal samples had a 47, XXY karyotype. In addition, while the Sertoli cells in some of the Sertoli cell-only tubules had 46, XY karyotype, the Sertoli cells in some of the other Sertoli cell-only tubules had 47, XXY karyotype in postpubertal samples. In contrast to the postpubertal samples, Sertoli cells in all tubules in the prepubertal samples had the 47, XXY karyotype. Our data also suggest that germ cells lose the extra X chromosome during embryonic, fetal, or neonatal life, while Sertoli c","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142092814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exploring the impact of fertility-preserving treatment on pregnancy: key issues in patients with endometrial cancer and atypical hyperplasia.","authors":"Wei-Zhen Tang, Tai-Hang Liu","doi":"10.1093/humrep/deae187","DOIUrl":"10.1093/humrep/deae187","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiaan Huang, Yao Lu, Yaqiong He, Yuan Wang, Qinling Zhu, Jia Qi, Ying Ding, Xinyu Li, Ziyin Ding, Steven R Lindheim, Yun Sun
<p><strong>Study question: </strong>Do obstetric and perinatal complications vary according to different blastocyst developmental parameters after frozen-thawed single-blastocyst transfer (SBT) cycles?</p><p><strong>Summary answer: </strong>Pregnancies following the transfer of a blastocyst with a grade C trophectoderm (TE) were associated with an increased risk of placenta previa compared to those with a blastocyst of grade A TE.</p><p><strong>What is known already: </strong>Existing studies investigating the effect of blastocyst morphology grades on birth outcomes have mostly focused on fetal growth and have produced conflicting results, while the risk of obstetric complications has rarely been reported. Additionally, growing evidence has suggested that the appearance of TE cells could serve as the most important parameter for predicting implantation and live birth. Given that the TE ultimately develops into the placenta, it is plausible that this independent predictor may also impact placentation.</p><p><strong>Study design, size, duration: </strong>This retrospective cohort study at a tertiary-care academic medical center included 6018 singleton deliveries after frozen-thawed SBT cycles between January 2017 and December 2021.</p><p><strong>Participants/materials, setting, methods: </strong>Singleton pregnancies were grouped into two groups according to blastocyst developmental stage (Days 5 and 6), four groups according to embryo expansion (Stages 3, 4, 5, and 6), three groups according to inner cell mass (ICM) quality (A, B, and C), and three groups according to TE quality (A, B, and C). The main outcomes included pregnancy-induced hypertension, preeclampsia, gestational diabetes mellitus, preterm premature rupture of membrane, placenta previa, placental abruption, placenta accreta, postpartum hemorrhage, preterm birth, low birth weight, small for gestational age, and birth defects. Multivariate logistic regressions were performed to evaluate the effect of blastocyst developmental stage, embryo expansion stage, ICM grade, and TE grade on measured outcomes adjusting for potential confounders.</p><p><strong>Main results and the role of chance: </strong>No association was found between blastocyst developmental stage and obstetric or perinatal outcomes both before and after adjusting for potential confounders, and similar results were found with regard to embryo expansion stage and ICM grade. Meanwhile, the incidence of placenta previa derived from a blastocyst with TE of grade C was higher compared with those derived from a blastocyst with TE of grade A (1.7%, 2.4%, and 4.0% for A, B, and C, respectively, P = 0.001 for all comparisons). After adjusting for potential covariates, TE grade C blastocysts had 2.81 times the likelihood of resulting in placenta previa compared to TE grade A blastocysts (adjusted odds ratio 2.81, 95% CI 1.11-7.09). No statistically significant differences were detected between any other measured outcomes and TE grades
研究问题:冷冻解冻单囊胚移植(SBT)周期后,产科和围产期并发症是否因囊胚发育参数的不同而不同?与移植 A 级滋养层(TE)囊胚的孕妇相比,移植 C 级滋养层(TE)囊胚的孕妇发生前置胎盘的风险更高:关于囊胚形态等级对分娩结局影响的现有研究主要集中在胎儿生长方面,结果相互矛盾,而产科并发症风险方面的研究则鲜有报道。此外,越来越多的证据表明,TE 细胞的出现可作为预测植入和活产的最重要参数。鉴于TE最终会发育成胎盘,这一独立的预测因素也可能会影响胎盘:这项回顾性队列研究在一家三级医疗学术医学中心进行,纳入了 2017 年 1 月至 2021 年 12 月间经过冷冻解冻 SBT 周期的 6018 例单胎分娩:根据囊胚发育阶段(第5天和第6天)将单胎妊娠分为两组,根据胚胎扩张情况(第3、4、5和6阶段)分为四组,根据内细胞团(ICM)质量(A、B和C)分为三组,根据TE质量(A、B和C)分为三组。主要结果包括妊娠高血压、子痫前期、妊娠糖尿病、早产胎膜早破、前置胎盘、胎盘早剥、胎盘早剥、产后出血、早产、低出生体重、胎龄小和出生缺陷。通过多变量逻辑回归评估囊胚发育阶段、胚胎扩张阶段、ICM 分级和 TE 分级对测量结果的影响,并对潜在的混杂因素进行调整:主要结果和偶然性的作用:在调整潜在混杂因素之前和之后,均未发现囊胚发育阶段与产科或围产期结果之间存在关联,胚胎膨大期和 ICM 分级也发现了类似的结果。同时,TE 为 C 级的囊胚与 TE 为 A 级的囊胚相比,前置胎盘的发生率更高(A、B 和 C 级分别为 1.7%、2.4% 和 4.0%,所有比较的 P = 0.001)。调整潜在的协变量后,TE C 级囊胚导致前置胎盘的可能性是 TE A 级囊胚的 2.81 倍(调整后的几率比 2.81,95% CI 1.11-7.09)。无论调整前还是调整后,其他测量结果与 TE 等级之间均未发现有统计学意义的差异:该研究的局限性在于其回顾性的单中心设计。此外,虽然研究组的样本量相对较大,但某些亚组的样本量相对较小,缺乏足够的力量,尤其是 ICM C 级组。因此,在解释这些结果时应谨慎:本研究扩展了我们对 TE 分级对胎盘异常的潜在下游影响的认识:本研究得到了国家重点研发计划(2023YFC2705500, 2023YFC2705501, 2023YFC2705505, 2019YFA0802604)、国家自然科学基金(82130046, 82320108009, 82371660, 32300710)、上海市领军人才计划、创新研究团队等的资助;上海市领军人才计划、上海市地方高校高水平创新研究团队(SHSMU-ZLCX20210201、SHSMU-ZLCX20210200、SHSMU-ZLCX20180401)、上海交通大学医学院附属仁济医院临床科研创新培养基金项目(RJPY-DZX-003)、上海市科学技术委员会(23Y11901400)、上海市重中之重研究中心建设项目(2023ZZ02002)、上海市加强公共卫生体系建设三年行动计划(GWVI-11.1-36).作者无利益冲突:不适用。
{"title":"Trophectoderm grade is associated with the risk of placenta previa in frozen-thawed single-blastocyst transfer cycles.","authors":"Jiaan Huang, Yao Lu, Yaqiong He, Yuan Wang, Qinling Zhu, Jia Qi, Ying Ding, Xinyu Li, Ziyin Ding, Steven R Lindheim, Yun Sun","doi":"10.1093/humrep/deae172","DOIUrl":"10.1093/humrep/deae172","url":null,"abstract":"<p><strong>Study question: </strong>Do obstetric and perinatal complications vary according to different blastocyst developmental parameters after frozen-thawed single-blastocyst transfer (SBT) cycles?</p><p><strong>Summary answer: </strong>Pregnancies following the transfer of a blastocyst with a grade C trophectoderm (TE) were associated with an increased risk of placenta previa compared to those with a blastocyst of grade A TE.</p><p><strong>What is known already: </strong>Existing studies investigating the effect of blastocyst morphology grades on birth outcomes have mostly focused on fetal growth and have produced conflicting results, while the risk of obstetric complications has rarely been reported. Additionally, growing evidence has suggested that the appearance of TE cells could serve as the most important parameter for predicting implantation and live birth. Given that the TE ultimately develops into the placenta, it is plausible that this independent predictor may also impact placentation.</p><p><strong>Study design, size, duration: </strong>This retrospective cohort study at a tertiary-care academic medical center included 6018 singleton deliveries after frozen-thawed SBT cycles between January 2017 and December 2021.</p><p><strong>Participants/materials, setting, methods: </strong>Singleton pregnancies were grouped into two groups according to blastocyst developmental stage (Days 5 and 6), four groups according to embryo expansion (Stages 3, 4, 5, and 6), three groups according to inner cell mass (ICM) quality (A, B, and C), and three groups according to TE quality (A, B, and C). The main outcomes included pregnancy-induced hypertension, preeclampsia, gestational diabetes mellitus, preterm premature rupture of membrane, placenta previa, placental abruption, placenta accreta, postpartum hemorrhage, preterm birth, low birth weight, small for gestational age, and birth defects. Multivariate logistic regressions were performed to evaluate the effect of blastocyst developmental stage, embryo expansion stage, ICM grade, and TE grade on measured outcomes adjusting for potential confounders.</p><p><strong>Main results and the role of chance: </strong>No association was found between blastocyst developmental stage and obstetric or perinatal outcomes both before and after adjusting for potential confounders, and similar results were found with regard to embryo expansion stage and ICM grade. Meanwhile, the incidence of placenta previa derived from a blastocyst with TE of grade C was higher compared with those derived from a blastocyst with TE of grade A (1.7%, 2.4%, and 4.0% for A, B, and C, respectively, P = 0.001 for all comparisons). After adjusting for potential covariates, TE grade C blastocysts had 2.81 times the likelihood of resulting in placenta previa compared to TE grade A blastocysts (adjusted odds ratio 2.81, 95% CI 1.11-7.09). No statistically significant differences were detected between any other measured outcomes and TE grades ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142092815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Koen Wouters, Ileana Mateizel, Ingrid Segers, Hilde Van de Velde, Lisbet Van Landuyt, Anick De Vos, Celine Schoemans, Danijel Jankovic, Christophe Blockeel, Panagiotis Drakopoulos, Herman Tournaye, Neelke De Munck
<p><strong>Study question: </strong>Is there a difference in clinical pregnancy rates (CPRs) in good prognosis patients after single embryo transfer (SET) on Day 5, in case of stable culture at 36.6°C or 37.1°C?</p><p><strong>Summary answer: </strong>CPR (with heartbeat at 7 weeks) after blastocyst transfer do not differ after culturing at 36.6°C or 37.1°C.</p><p><strong>What is known already: </strong>Since the beginning of IVF, embryo culture has been performed at 37.0°C; however, the optimal culture temperature remains unknown. Changes in incubator types have led to significant improvements in temperature control. Stable temperature control, i.e. with temperature differences of max. 0.1°C between chambers, is possible in some incubators. A previous prospective pilot study showed that embryo development on Day 5/6 was not affected when embryos were cultured at a stable temperature of 36.6°C or 37.1°C, but culture at 37.1°C resulted in an increased CPR when compared to culture at 36.6°C (74.2% vs 46.4%).</p><p><strong>Study design, size, duration: </strong>A prospective randomized controlled trial was performed in a tertiary fertility centre between February 2017 and November 26, 2022. A sample size of 89/89 patients with fresh single embryo transfer (SET) was required to achieve 80% power to detect a difference of 0.22 between group proportions (0.43-0.65) at a significance level of 0.05 using a two-sided z-test with continuity correction.</p><p><strong>Participants/materials, setting, methods: </strong>Patients were recruited on the day of oocyte retrieval based on inclusion criteria with final randomization after denudation once six mature oocytes were present. The primary endpoint was CPR (heartbeat at 7 weeks); secondary endpoints were fertilization rate, blastocyst development, biochemical pregnancy rate, live birth rate (LBR), and cumulative live birth rate (CLBR).</p><p><strong>Main results and the role of chance: </strong>A total of 304 patients were eligible for the study; of these 268 signed the consent, 234 (intention-to-treat) were randomized and 181 (per-protocol) received a SET on Day 5: 90 received culture at 36.6°C and 91 at 37.1°C. Patients were on average 32.4 ± 3.5 versus 32.5 ± 4.2 years old, respectively. No differences were observed in embryological outcomes per cycle between culture at 36.6°C versus 37.1°C: 12.0 ± 3.8 vs 12.1 ± 3.8 COCs retrieved (P = 0.88), 10.0 ± 3.1 versus 9.9 ± 2.9 mature oocytes inseminated (P = 0.68), with a maturation rate of 84.2% (901/1083) versus 83.5% (898/1104) (P = 0.87); and 8.0 ± 3.1 versus 7.9 ± 2.7 normally fertilized oocytes with a fertilization rate of 79.7% (720/901) vs 80.5% (718/898) (P = 0.96), respectively. On average 1.5 ± 1.7 versus 1.4 ± 1.9 (P = 0.25) and 1.1 ± 1.1 versus 0.9 ± 1.0 (P = 0.45) supernumerary blastocysts were vitrified on Day 5 and Day 6, respectively. The utilization rate per fertilized oocyte was 46.1% vs 41.5% (P = 0.14). A SET was performed for 181 patients, l
{"title":"Clinical pregnancy rates after blastocyst culture at a stable temperature of 36.6°C versus 37.1°C: a prospective randomized controlled trial.","authors":"Koen Wouters, Ileana Mateizel, Ingrid Segers, Hilde Van de Velde, Lisbet Van Landuyt, Anick De Vos, Celine Schoemans, Danijel Jankovic, Christophe Blockeel, Panagiotis Drakopoulos, Herman Tournaye, Neelke De Munck","doi":"10.1093/humrep/deae193","DOIUrl":"10.1093/humrep/deae193","url":null,"abstract":"<p><strong>Study question: </strong>Is there a difference in clinical pregnancy rates (CPRs) in good prognosis patients after single embryo transfer (SET) on Day 5, in case of stable culture at 36.6°C or 37.1°C?</p><p><strong>Summary answer: </strong>CPR (with heartbeat at 7 weeks) after blastocyst transfer do not differ after culturing at 36.6°C or 37.1°C.</p><p><strong>What is known already: </strong>Since the beginning of IVF, embryo culture has been performed at 37.0°C; however, the optimal culture temperature remains unknown. Changes in incubator types have led to significant improvements in temperature control. Stable temperature control, i.e. with temperature differences of max. 0.1°C between chambers, is possible in some incubators. A previous prospective pilot study showed that embryo development on Day 5/6 was not affected when embryos were cultured at a stable temperature of 36.6°C or 37.1°C, but culture at 37.1°C resulted in an increased CPR when compared to culture at 36.6°C (74.2% vs 46.4%).</p><p><strong>Study design, size, duration: </strong>A prospective randomized controlled trial was performed in a tertiary fertility centre between February 2017 and November 26, 2022. A sample size of 89/89 patients with fresh single embryo transfer (SET) was required to achieve 80% power to detect a difference of 0.22 between group proportions (0.43-0.65) at a significance level of 0.05 using a two-sided z-test with continuity correction.</p><p><strong>Participants/materials, setting, methods: </strong>Patients were recruited on the day of oocyte retrieval based on inclusion criteria with final randomization after denudation once six mature oocytes were present. The primary endpoint was CPR (heartbeat at 7 weeks); secondary endpoints were fertilization rate, blastocyst development, biochemical pregnancy rate, live birth rate (LBR), and cumulative live birth rate (CLBR).</p><p><strong>Main results and the role of chance: </strong>A total of 304 patients were eligible for the study; of these 268 signed the consent, 234 (intention-to-treat) were randomized and 181 (per-protocol) received a SET on Day 5: 90 received culture at 36.6°C and 91 at 37.1°C. Patients were on average 32.4 ± 3.5 versus 32.5 ± 4.2 years old, respectively. No differences were observed in embryological outcomes per cycle between culture at 36.6°C versus 37.1°C: 12.0 ± 3.8 vs 12.1 ± 3.8 COCs retrieved (P = 0.88), 10.0 ± 3.1 versus 9.9 ± 2.9 mature oocytes inseminated (P = 0.68), with a maturation rate of 84.2% (901/1083) versus 83.5% (898/1104) (P = 0.87); and 8.0 ± 3.1 versus 7.9 ± 2.7 normally fertilized oocytes with a fertilization rate of 79.7% (720/901) vs 80.5% (718/898) (P = 0.96), respectively. On average 1.5 ± 1.7 versus 1.4 ± 1.9 (P = 0.25) and 1.1 ± 1.1 versus 0.9 ± 1.0 (P = 0.45) supernumerary blastocysts were vitrified on Day 5 and Day 6, respectively. The utilization rate per fertilized oocyte was 46.1% vs 41.5% (P = 0.14). A SET was performed for 181 patients, l","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Julia Uraji, Juan J Fraire-Zamora, Claudia Massarotti, Sofia Makieva, George Liperis, Kashish Sharma, Sarah Martins da Silva, Raevti Bole, Jackson C Kirkman-Brown, Omar Farhan Ammar
{"title":"Is AMH a promising predictive biomarker for mTESE success in iNOA patients?","authors":"Julia Uraji, Juan J Fraire-Zamora, Claudia Massarotti, Sofia Makieva, George Liperis, Kashish Sharma, Sarah Martins da Silva, Raevti Bole, Jackson C Kirkman-Brown, Omar Farhan Ammar","doi":"10.1093/humrep/deae179","DOIUrl":"10.1093/humrep/deae179","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oisin Fitzgerald, Jade Newman, Luk Rombauts, Alex Polyakov, Georgina M Chambers
<p><strong>Study question: </strong>Can we develop a prediction model for the chance of a live birth following the transfer of an embryo created using donated oocytes?</p><p><strong>Summary answer: </strong>Three primary models that included patient, past treatment, and cycle characteristics were developed using Australian data to predict the chance of a live birth following the transfer of an embryo created using donated oocytes; these models were well-calibrated to the population studied, achieved reasonable predictive power and generalizability when tested on New Zealand data.</p><p><strong>What is known already: </strong>Nearly 9% of ART embryo transfer cycles performed globally use embryos created using donated oocytes. This percentage rises to one-quarter and one-half in same-sex couples and women aged over 45 years, respectively.</p><p><strong>Study design, size, duration: </strong>This study uses population-based Australian clinical registry data comprising 9384 embryo transfer cycles that occurred between 2015 and 2021 for model development, with an external validation cohort of 1493 New Zealand embryo transfer cycles.</p><p><strong>Participants/materials, setting, methods: </strong>Three prediction models were compared that incorporated patient characteristics, but differed in whether they considered use of prior autologous treatment factors and current treatment parameters. We internally validated the models on Australian data using grouped cross-validation and reported several measures of model discrimination and calibration. Variable importance was measured through calculating the change in predictive performance that resulted from variable permutation. The best-performing model was externally validated on data from New Zealand.</p><p><strong>Main results and the role of chance: </strong>The best-performing model had an internal validation AUC-ROC of 0.60 and Brier score of 0.20, and external validation AUC-ROC of 0.61 and Brier score of 0.23. While these results indicate ∼15% less discriminatory ability compared to models assessed on an autologous cohort from the same population the performance of the models was clearly statistically significantly better than random, demonstrated generalizability, and was well-calibrated to the population studied. The most important variables for predicting the chance of a live birth were the oocyte donor age, the number of prior oocyte recipient embryo transfer cycles, whether the transferred embryo was cleavage or blastocyst stage and oocyte recipient age. Of lesser importance were the oocyte-recipient parity, whether donor or partner sperm was used, the number of prior autologous embryo transfer cycles and the number of embryos transferred.</p><p><strong>Limitations, reasons for caution: </strong>The models had relatively weak discrimination suggesting further features need to be added to improve their predictive power. Variation in donor oocyte cohorts across countries due to differences such as
{"title":"Development of an IVF prediction model for donor oocytes: a retrospective analysis of 10 877 embryo transfers.","authors":"Oisin Fitzgerald, Jade Newman, Luk Rombauts, Alex Polyakov, Georgina M Chambers","doi":"10.1093/humrep/deae174","DOIUrl":"10.1093/humrep/deae174","url":null,"abstract":"<p><strong>Study question: </strong>Can we develop a prediction model for the chance of a live birth following the transfer of an embryo created using donated oocytes?</p><p><strong>Summary answer: </strong>Three primary models that included patient, past treatment, and cycle characteristics were developed using Australian data to predict the chance of a live birth following the transfer of an embryo created using donated oocytes; these models were well-calibrated to the population studied, achieved reasonable predictive power and generalizability when tested on New Zealand data.</p><p><strong>What is known already: </strong>Nearly 9% of ART embryo transfer cycles performed globally use embryos created using donated oocytes. This percentage rises to one-quarter and one-half in same-sex couples and women aged over 45 years, respectively.</p><p><strong>Study design, size, duration: </strong>This study uses population-based Australian clinical registry data comprising 9384 embryo transfer cycles that occurred between 2015 and 2021 for model development, with an external validation cohort of 1493 New Zealand embryo transfer cycles.</p><p><strong>Participants/materials, setting, methods: </strong>Three prediction models were compared that incorporated patient characteristics, but differed in whether they considered use of prior autologous treatment factors and current treatment parameters. We internally validated the models on Australian data using grouped cross-validation and reported several measures of model discrimination and calibration. Variable importance was measured through calculating the change in predictive performance that resulted from variable permutation. The best-performing model was externally validated on data from New Zealand.</p><p><strong>Main results and the role of chance: </strong>The best-performing model had an internal validation AUC-ROC of 0.60 and Brier score of 0.20, and external validation AUC-ROC of 0.61 and Brier score of 0.23. While these results indicate ∼15% less discriminatory ability compared to models assessed on an autologous cohort from the same population the performance of the models was clearly statistically significantly better than random, demonstrated generalizability, and was well-calibrated to the population studied. The most important variables for predicting the chance of a live birth were the oocyte donor age, the number of prior oocyte recipient embryo transfer cycles, whether the transferred embryo was cleavage or blastocyst stage and oocyte recipient age. Of lesser importance were the oocyte-recipient parity, whether donor or partner sperm was used, the number of prior autologous embryo transfer cycles and the number of embryos transferred.</p><p><strong>Limitations, reasons for caution: </strong>The models had relatively weak discrimination suggesting further features need to be added to improve their predictive power. Variation in donor oocyte cohorts across countries due to differences such as","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hannes Syryn, Julie Van de Velde, Griet De Clercq, Hannah Verdin, Annelies Dheedene, Frank Peelman, Andrew Sinclair, Katie L Ayers, Ross A D Bathgate, Martine Cools, Elfride De Baere
<p><strong>Study question: </strong>Does RXFP2 disruption impair male fertility?</p><p><strong>Summary answer: </strong>We identified biallelic variants in RXFP2 in patients with male infertility due to spermatogenic arrest at the spermatid stage, supporting a role of RXFP2 in human spermatogenesis, specifically in germ cell maturation.</p><p><strong>What is known already: </strong>Since RXFP2, the receptor for INSL3, plays a crucial role in testicular descent during prenatal development, biallelic variants lead to bilateral cryptorchidism, as described in four families to date. While animal models have also suggested a function in spermatogenesis, the postnatal functions of RXFP2 and its ligand INSL3, produced in large amounts by the testes from puberty throughout adulthood, are largely unknown.</p><p><strong>Study design, size, duration: </strong>A family with two male members affected by impaired fertility due to spermatogenic maturation arrest and a history of bilateral cryptorchidism underwent clinical, endocrinological, histological, genomic, in vitro cellular, and in silico investigations.</p><p><strong>Participants/materials, setting, methods: </strong>The endocrinological and histological findings were correlated with publicly available single-cell RNA sequencing (scRNA-seq) data. The genomic defects have been characterized using long-read sequencing and validated with in silico modeling and an in vitro cyclic AMP reporter gene assay.</p><p><strong>Main results and the role of chance: </strong>An intragenic deletion of exon 1-5 of RXFP2 (NM_130806.5) was detected in trans with a hemizygous missense variant c.229G>A, p.(Glu77Lys). The p.(Glu77Lys) variant caused no clear change in cell surface expression or ability to bind INSL3, but displayed absence of a cAMP signal in response to INSL3, indicating a loss-of-function. Testicular biopsy in the proband showed a maturation arrest at the spermatid stage, corresponding to the highest level of RXFP2 expression in scRNA-seq data, thereby providing a potential explanation for the impaired fertility.</p><p><strong>Limitations, reasons for caution: </strong>Although this is so far the only study of human cases that supports the role of RXFP2 in spermatogenic maturation, this is corroborated by several animal studies that have already demonstrated a postnatal function of INSL3 and RXFP2 in spermatogenesis.</p><p><strong>Wider implications of the findings: </strong>This study corroborates RXFP2 as gene implicated in autosomal recessive congenital bilateral cryptorchidism due to biallelic variants, rather than autosomal-dominant cryptorchidism due to monoallelic RXFP2 variants. Our findings also support that RXFP2 is essential in human spermatogenesis, specifically in germ cell maturation, and that biallelic disruption can cause male infertility through spermatogenic arrest at the spermatid stage.</p><p><strong>Study funding/competing interest(s): </strong>Funding was provided by the Bellux Society
{"title":"Biallelic RXFP2 variants lead to congenital bilateral cryptorchidism and male infertility, supporting a role of RXFP2 in spermatogenesis.","authors":"Hannes Syryn, Julie Van de Velde, Griet De Clercq, Hannah Verdin, Annelies Dheedene, Frank Peelman, Andrew Sinclair, Katie L Ayers, Ross A D Bathgate, Martine Cools, Elfride De Baere","doi":"10.1093/humrep/deae195","DOIUrl":"10.1093/humrep/deae195","url":null,"abstract":"<p><strong>Study question: </strong>Does RXFP2 disruption impair male fertility?</p><p><strong>Summary answer: </strong>We identified biallelic variants in RXFP2 in patients with male infertility due to spermatogenic arrest at the spermatid stage, supporting a role of RXFP2 in human spermatogenesis, specifically in germ cell maturation.</p><p><strong>What is known already: </strong>Since RXFP2, the receptor for INSL3, plays a crucial role in testicular descent during prenatal development, biallelic variants lead to bilateral cryptorchidism, as described in four families to date. While animal models have also suggested a function in spermatogenesis, the postnatal functions of RXFP2 and its ligand INSL3, produced in large amounts by the testes from puberty throughout adulthood, are largely unknown.</p><p><strong>Study design, size, duration: </strong>A family with two male members affected by impaired fertility due to spermatogenic maturation arrest and a history of bilateral cryptorchidism underwent clinical, endocrinological, histological, genomic, in vitro cellular, and in silico investigations.</p><p><strong>Participants/materials, setting, methods: </strong>The endocrinological and histological findings were correlated with publicly available single-cell RNA sequencing (scRNA-seq) data. The genomic defects have been characterized using long-read sequencing and validated with in silico modeling and an in vitro cyclic AMP reporter gene assay.</p><p><strong>Main results and the role of chance: </strong>An intragenic deletion of exon 1-5 of RXFP2 (NM_130806.5) was detected in trans with a hemizygous missense variant c.229G>A, p.(Glu77Lys). The p.(Glu77Lys) variant caused no clear change in cell surface expression or ability to bind INSL3, but displayed absence of a cAMP signal in response to INSL3, indicating a loss-of-function. Testicular biopsy in the proband showed a maturation arrest at the spermatid stage, corresponding to the highest level of RXFP2 expression in scRNA-seq data, thereby providing a potential explanation for the impaired fertility.</p><p><strong>Limitations, reasons for caution: </strong>Although this is so far the only study of human cases that supports the role of RXFP2 in spermatogenic maturation, this is corroborated by several animal studies that have already demonstrated a postnatal function of INSL3 and RXFP2 in spermatogenesis.</p><p><strong>Wider implications of the findings: </strong>This study corroborates RXFP2 as gene implicated in autosomal recessive congenital bilateral cryptorchidism due to biallelic variants, rather than autosomal-dominant cryptorchidism due to monoallelic RXFP2 variants. Our findings also support that RXFP2 is essential in human spermatogenesis, specifically in germ cell maturation, and that biallelic disruption can cause male infertility through spermatogenic arrest at the spermatid stage.</p><p><strong>Study funding/competing interest(s): </strong>Funding was provided by the Bellux Society ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Challenges ahead: catalyzing research for the 2% prevalence of repeated implantation failure.","authors":"Hossam Elzeiny","doi":"10.1093/humrep/deae184","DOIUrl":"10.1093/humrep/deae184","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ozgur Oktem, Yashar Esmaeilian, Ece İltumur, Sevgi Yusufoglu, Deniz Uğurlu Çimen, Said Incir, Kayhan Yakin, Baris Ata, Bulent Urman
<p><strong>Study question: </strong>Does medroxyprogesterone acetate (MPA) exposure in progestin-primed ovarian stimulation (PPOS) cycles cause molecular perturbations in the steroidogenic function and gonadotropin responsiveness of the granulosa cells?</p><p><strong>Summary answer: </strong>PPOS cycles are identical to traditional GnRH antagonist cycles not only for clinical IVF characteristics but also for gonadotropin receptor expression, response to gonadotropins, and steroidogenic function at the molecular level.</p><p><strong>What is known already: </strong>PPOS is increasingly used as an alternative to GnRH antagonists due to the inhibitory effect of progesterone on LH release by reducing GnRH pulsatility at the hypothalamic level. Although a growing body of evidence from clinical studies did not indicate significant differences between PPOS and antagonist protocols for IVF cycle characteristics and obstetrical outcomes, it is still unknown whether exposure of the antral follicle cohort to progesterone or its synthetic derivatives during ovarian stimulation causes any subtle molecular aberrations in terms of steroidogenesis and gonadotropin responsiveness. To address this issue, detailed comparative molecular analyses were conducted in the luteinized mural granulosa cells (GCs) obtained from normal responding IVF patients undergoing PPOS and antagonist cycles.</p><p><strong>Study design, size, duration: </strong>A clinical translational research study was conducted with IVF patients.</p><p><strong>Participants/materials, setting, methods: </strong>This study included 55 normal responding IVF patients who underwent ovarian stimulation with either PPOS using MPA (5 mg twice daily) or GnRH antagonist cetrorelix acetate. Recombinant forms of FSH and hCG were used for ovarian stimulation and ovulation triggering, respectively. Luteinized mural GCs obtained during the oocyte retrieval procedure were used for the experiments. Cell culture, quantitative real-time PCR, immunoblotting, confocal time-lapse live cell imaging, and hormone assays were used.</p><p><strong>Main results and the role of chance: </strong>Demographic and IVF cycle characteristics of the patients undergoing ovarian stimulation with PPOS and GnRH antagonist were similar, including ovarian response, mature oocyte yield, and fertilization rates. Molecular analyses revealed that the expression of the enzymes involved in sex-steroid synthesis (StAR, SCC, 3β-HSD, 17β-HSD, aromatase) and the uptake/storage/utilization of cholesterol (LDL receptor, Hormone-sensitive lipase, hydroxy-methyl glutaryl Co-enzyme-A reductase, and Sterol O-acyltransferase1) in the GCs of the PPOS cycles were comparable to those of the antagonist cycles. The expression of the receptors for gonadotropins, estrogen, and progesterone hormones was also similar. Basal and hCG-induced increases in 3β-HSD expression and progesterone production and basal and FSH-induced increases in aromatase expression and E2 output
{"title":"Exposure of antral follicles to medroxyprogesterone acetate during stimulation does not cause molecular perturbations in gonadotropin-responsiveness and steroidogenic function of granulosa cells in progestin-primed cycles.","authors":"Ozgur Oktem, Yashar Esmaeilian, Ece İltumur, Sevgi Yusufoglu, Deniz Uğurlu Çimen, Said Incir, Kayhan Yakin, Baris Ata, Bulent Urman","doi":"10.1093/humrep/deae189","DOIUrl":"10.1093/humrep/deae189","url":null,"abstract":"<p><strong>Study question: </strong>Does medroxyprogesterone acetate (MPA) exposure in progestin-primed ovarian stimulation (PPOS) cycles cause molecular perturbations in the steroidogenic function and gonadotropin responsiveness of the granulosa cells?</p><p><strong>Summary answer: </strong>PPOS cycles are identical to traditional GnRH antagonist cycles not only for clinical IVF characteristics but also for gonadotropin receptor expression, response to gonadotropins, and steroidogenic function at the molecular level.</p><p><strong>What is known already: </strong>PPOS is increasingly used as an alternative to GnRH antagonists due to the inhibitory effect of progesterone on LH release by reducing GnRH pulsatility at the hypothalamic level. Although a growing body of evidence from clinical studies did not indicate significant differences between PPOS and antagonist protocols for IVF cycle characteristics and obstetrical outcomes, it is still unknown whether exposure of the antral follicle cohort to progesterone or its synthetic derivatives during ovarian stimulation causes any subtle molecular aberrations in terms of steroidogenesis and gonadotropin responsiveness. To address this issue, detailed comparative molecular analyses were conducted in the luteinized mural granulosa cells (GCs) obtained from normal responding IVF patients undergoing PPOS and antagonist cycles.</p><p><strong>Study design, size, duration: </strong>A clinical translational research study was conducted with IVF patients.</p><p><strong>Participants/materials, setting, methods: </strong>This study included 55 normal responding IVF patients who underwent ovarian stimulation with either PPOS using MPA (5 mg twice daily) or GnRH antagonist cetrorelix acetate. Recombinant forms of FSH and hCG were used for ovarian stimulation and ovulation triggering, respectively. Luteinized mural GCs obtained during the oocyte retrieval procedure were used for the experiments. Cell culture, quantitative real-time PCR, immunoblotting, confocal time-lapse live cell imaging, and hormone assays were used.</p><p><strong>Main results and the role of chance: </strong>Demographic and IVF cycle characteristics of the patients undergoing ovarian stimulation with PPOS and GnRH antagonist were similar, including ovarian response, mature oocyte yield, and fertilization rates. Molecular analyses revealed that the expression of the enzymes involved in sex-steroid synthesis (StAR, SCC, 3β-HSD, 17β-HSD, aromatase) and the uptake/storage/utilization of cholesterol (LDL receptor, Hormone-sensitive lipase, hydroxy-methyl glutaryl Co-enzyme-A reductase, and Sterol O-acyltransferase1) in the GCs of the PPOS cycles were comparable to those of the antagonist cycles. The expression of the receptors for gonadotropins, estrogen, and progesterone hormones was also similar. Basal and hCG-induced increases in 3β-HSD expression and progesterone production and basal and FSH-induced increases in aromatase expression and E2 output","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sarai M Keestra, Nienke Van Welie, Kim Dreyer, Rik Van Eekelen, Tessa J Roseboom, Jaap Oosterlaan, Ben W Mol, Martijn J J Finken, Velja Mijatovic, Marsh Königs
<p><strong>Study question: </strong>Does preconceptional exposure to oil-based iodinated contrast media during hysterosalpingography (HSG) impact children's neurodevelopment compared with exposure to water-based alternatives?</p><p><strong>Summary answer: </strong>Our study found no large-sized effects for neurodevelopment in children with preconceptional exposure to oil-based iodinated contrast media during HSG compared with water-based alternatives.</p><p><strong>What is known already: </strong>HSG is widely used as a diagnostic tool in the female fertility work-up. Tubal flushing with oil-based iodinated contrast has been shown to enhance fertility outcomes in couples with unexplained infertility, increasing the chances of pregnancy and live birth compared with water-based alternatives. However, oil-based contrast contains higher doses of iodine and has a longer half-life, and concerns exist that iodinated contrast media can affect women's iodine status and cause temporary (sub)clinical hypothyroidism in mothers and/or foetuses. Considering that thyroid hormones are vital to embryonal and foetal brain development, oil-based contrast media use could increase the risk of impaired neurodevelopment in children conceived shortly after HSG. Here we examine neurodevelopmental outcomes in school-aged children conceived after HSG.</p><p><strong>Study design, size, duration: </strong>This is a long-term follow-up of the H2Oil trial in which oil-based or water-based contrast was used during HSG (Netherlands; 2012-2014; NTR3270). Of 369 children born <6 months after HSG in the study, we contacted the mothers of 140 children who gave consent to be contacted for follow-up. The follow-up study took place from January to July 2022 (NCT05168228).</p><p><strong>Participants/materials, settings, methods: </strong>The study included 69 children aged 6-9 years who were conceived after HSG with oil-based (n = 42) or water-based contrast (n = 27). The assessments targeted intelligence (Wechsler Intelligence Scale for Children), neurocognitive outcomes (computerized neurocognitive tests), behavioural functioning (parent and teacher questionnaires), and academic performance. Linear regression models, adjusted for age, sex, and parental educational attainment were employed to compare groups.</p><p><strong>Main results and the role of chance: </strong>School-aged children born to mothers after oil-based contrast HSG did not significantly differ from children born to mothers after water-based contrast HSG, in regards to intelligence, neurocognitive functioning, behavioural functioning, or academic performance, with the exception of better performance for visuomotor integration functions in children exposed to oil-based contrast preconception. After exploratory correction for multiple comparisons, none of the group differences was statistically significant.</p><p><strong>Limitations, reasons for caution: </strong>The small sample size of this follow-up study limited stati
{"title":"Neurodevelopmental outcomes of school-age children conceived after hysterosalpingography with oil-based or water-based iodinated contrast: long-term follow-up of a nationwide randomized controlled trial.","authors":"Sarai M Keestra, Nienke Van Welie, Kim Dreyer, Rik Van Eekelen, Tessa J Roseboom, Jaap Oosterlaan, Ben W Mol, Martijn J J Finken, Velja Mijatovic, Marsh Königs","doi":"10.1093/humrep/deae183","DOIUrl":"10.1093/humrep/deae183","url":null,"abstract":"<p><strong>Study question: </strong>Does preconceptional exposure to oil-based iodinated contrast media during hysterosalpingography (HSG) impact children's neurodevelopment compared with exposure to water-based alternatives?</p><p><strong>Summary answer: </strong>Our study found no large-sized effects for neurodevelopment in children with preconceptional exposure to oil-based iodinated contrast media during HSG compared with water-based alternatives.</p><p><strong>What is known already: </strong>HSG is widely used as a diagnostic tool in the female fertility work-up. Tubal flushing with oil-based iodinated contrast has been shown to enhance fertility outcomes in couples with unexplained infertility, increasing the chances of pregnancy and live birth compared with water-based alternatives. However, oil-based contrast contains higher doses of iodine and has a longer half-life, and concerns exist that iodinated contrast media can affect women's iodine status and cause temporary (sub)clinical hypothyroidism in mothers and/or foetuses. Considering that thyroid hormones are vital to embryonal and foetal brain development, oil-based contrast media use could increase the risk of impaired neurodevelopment in children conceived shortly after HSG. Here we examine neurodevelopmental outcomes in school-aged children conceived after HSG.</p><p><strong>Study design, size, duration: </strong>This is a long-term follow-up of the H2Oil trial in which oil-based or water-based contrast was used during HSG (Netherlands; 2012-2014; NTR3270). Of 369 children born <6 months after HSG in the study, we contacted the mothers of 140 children who gave consent to be contacted for follow-up. The follow-up study took place from January to July 2022 (NCT05168228).</p><p><strong>Participants/materials, settings, methods: </strong>The study included 69 children aged 6-9 years who were conceived after HSG with oil-based (n = 42) or water-based contrast (n = 27). The assessments targeted intelligence (Wechsler Intelligence Scale for Children), neurocognitive outcomes (computerized neurocognitive tests), behavioural functioning (parent and teacher questionnaires), and academic performance. Linear regression models, adjusted for age, sex, and parental educational attainment were employed to compare groups.</p><p><strong>Main results and the role of chance: </strong>School-aged children born to mothers after oil-based contrast HSG did not significantly differ from children born to mothers after water-based contrast HSG, in regards to intelligence, neurocognitive functioning, behavioural functioning, or academic performance, with the exception of better performance for visuomotor integration functions in children exposed to oil-based contrast preconception. After exploratory correction for multiple comparisons, none of the group differences was statistically significant.</p><p><strong>Limitations, reasons for caution: </strong>The small sample size of this follow-up study limited stati","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142092813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}