Pub Date : 2024-10-10eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae060
Guangyao Lin, Stella Lim Jin Yie, Lianwei Xu
{"title":"Emerging evidence of endometrial compaction in predicting ART outcomes.","authors":"Guangyao Lin, Stella Lim Jin Yie, Lianwei Xu","doi":"10.1093/hropen/hoae060","DOIUrl":"10.1093/hropen/hoae060","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 4","pages":"hoae060"},"PeriodicalIF":8.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-10eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae059
Aşina Bayram, Ibrahim Elkhatib, Erkan Kalafat, Andrea Abdala, Virginia Ferracuti, Laura Melado, Barbara Lawrenz, Human Fatemi, Daniela Nogueira
<p><strong>Study question: </strong>Can modelling the longitudinal morphokinetic pattern of euploid embryos during time-lapse monitoring (TLM) be helpful for selecting embryos with the highest live birth potential?</p><p><strong>Summary answer: </strong>Longitudinal reference ranges of morphokinetic development of euploid embryos have been identified, and embryos with steadier progression during TLM are associated with higher chances of live birth.</p><p><strong>What is known already: </strong>TLM imaging is increasingly adopted by fertility clinics as an attempt to improve the ability of selecting embryos with the highest potential for implantation. Many markers of embryonic morphokinetics have been incorporated into decision algorithms for embryo (de)selection. However, longitudinal changes during this temporal process, and the impact of such changes on embryonic competence remain unknown. Aiming to model the reference ranges of morphokinetic development of euploid embryos and using it as a single longitudinal trajectory might provide an additive value to the blastocyst morphological grade in identifying highly competent embryos.</p><p><strong>Study design size duration: </strong>This observational, retrospective cohort study was performed in a single IVF clinic between October 2017 and June 2021 and included only autologous single euploid frozen embryo transfers (seFET).</p><p><strong>Participants/materials setting methods: </strong>Reference ranges were developed from [hours post-insemination (hpi)] of the standard morphokinetic parameters of euploid embryos assessed as tPB2, tPNa, tPNf, t2-t9, tSC, tM, tSB, and tB. Variance in morphokinetic patterns was measured and reported as morphokinetic variance score (MVS). Nuclear errors (micronucleation, binucleation, and multinucleation) were annotated when present in at least one blastomere at the two- or four-cell stages. The blastocyst grade of expansion, trophectoderm (TE), and inner cell mass (ICM) were assessed immediately before biopsy using Gardner's criteria. Pre-implantation genetic diagnosis for aneuploidy (PGT-A) was performed by next-generation sequencing. All euploid embryos were singly transferred in a frozen transferred cycle and outcomes were assessed as live birth, pregnancy loss, or not pregnant. Association of MVS with live birth was investigated with regression analyses.</p><p><strong>Main results and the role of chance: </strong>TLM data from 340 seFET blastocysts were included in the study, of which 189 (55.6%) resulted in a live birth. The median time for euploid embryos to reach blastulation was 109.9 hpi (95% CI: 98.8-121.0 hpi). The MVS was calculated from the variance in time taken for the embryo to reach all morphokinetic points and reflects the total morphokinetic variability it exhibits during its development. Embryos with more erratic kinetics, i.e. higher morphokinetic variance, had higher rates of pregnancy loss (<i>P</i> = 0.004) and no pregnancy (<i>P</i> < 0.001)
{"title":"Steady morphokinetic progression is an independent predictor of live birth: a descriptive reference for euploid embryos.","authors":"Aşina Bayram, Ibrahim Elkhatib, Erkan Kalafat, Andrea Abdala, Virginia Ferracuti, Laura Melado, Barbara Lawrenz, Human Fatemi, Daniela Nogueira","doi":"10.1093/hropen/hoae059","DOIUrl":"10.1093/hropen/hoae059","url":null,"abstract":"<p><strong>Study question: </strong>Can modelling the longitudinal morphokinetic pattern of euploid embryos during time-lapse monitoring (TLM) be helpful for selecting embryos with the highest live birth potential?</p><p><strong>Summary answer: </strong>Longitudinal reference ranges of morphokinetic development of euploid embryos have been identified, and embryos with steadier progression during TLM are associated with higher chances of live birth.</p><p><strong>What is known already: </strong>TLM imaging is increasingly adopted by fertility clinics as an attempt to improve the ability of selecting embryos with the highest potential for implantation. Many markers of embryonic morphokinetics have been incorporated into decision algorithms for embryo (de)selection. However, longitudinal changes during this temporal process, and the impact of such changes on embryonic competence remain unknown. Aiming to model the reference ranges of morphokinetic development of euploid embryos and using it as a single longitudinal trajectory might provide an additive value to the blastocyst morphological grade in identifying highly competent embryos.</p><p><strong>Study design size duration: </strong>This observational, retrospective cohort study was performed in a single IVF clinic between October 2017 and June 2021 and included only autologous single euploid frozen embryo transfers (seFET).</p><p><strong>Participants/materials setting methods: </strong>Reference ranges were developed from [hours post-insemination (hpi)] of the standard morphokinetic parameters of euploid embryos assessed as tPB2, tPNa, tPNf, t2-t9, tSC, tM, tSB, and tB. Variance in morphokinetic patterns was measured and reported as morphokinetic variance score (MVS). Nuclear errors (micronucleation, binucleation, and multinucleation) were annotated when present in at least one blastomere at the two- or four-cell stages. The blastocyst grade of expansion, trophectoderm (TE), and inner cell mass (ICM) were assessed immediately before biopsy using Gardner's criteria. Pre-implantation genetic diagnosis for aneuploidy (PGT-A) was performed by next-generation sequencing. All euploid embryos were singly transferred in a frozen transferred cycle and outcomes were assessed as live birth, pregnancy loss, or not pregnant. Association of MVS with live birth was investigated with regression analyses.</p><p><strong>Main results and the role of chance: </strong>TLM data from 340 seFET blastocysts were included in the study, of which 189 (55.6%) resulted in a live birth. The median time for euploid embryos to reach blastulation was 109.9 hpi (95% CI: 98.8-121.0 hpi). The MVS was calculated from the variance in time taken for the embryo to reach all morphokinetic points and reflects the total morphokinetic variability it exhibits during its development. Embryos with more erratic kinetics, i.e. higher morphokinetic variance, had higher rates of pregnancy loss (<i>P</i> = 0.004) and no pregnancy (<i>P</i> < 0.001)","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 4","pages":"hoae059"},"PeriodicalIF":8.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-03eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae054
Congcong Ma, Xiaoyu Long, Liying Yan, Xiaohui Zhu, Lixue Chen, Rong Li, Ying Wang, Jie Qiao
<p><strong>Study question: </strong>Does ovarian stimulation and the ovarian response affect embryo euploidy?</p><p><strong>Summary answer: </strong>Ovarian stimulation and the ovarian response in women undergoing preimplantation genetic testing for monogenic disorders (PGT-M) cycles did not affect the rates of blastocyst euploidy.</p><p><strong>What is known already: </strong>Whether or not ovarian stimulation in IVF-embryo transfer has potential effects on embryo euploidy is controversial among studies for several reasons: (i) heterogeneity of the study populations, (ii) biopsies being performed at different stages of embryo development and (iii) evolution of the platforms utilized for ploidy assessment. Patients who undergo PGT-M cycles typically have no additional risks of aneuploidy, providing an ideal study population for exploring this issue.</p><p><strong>Study design size duration: </strong>A retrospective cohort study including embryos undergoing PGT-M was conducted at a single academically affiliated fertility clinic between June 2014 and July 2021.</p><p><strong>Participants/materials setting methods: </strong>A total of 617 women with 867 PGT-M cycles involving 12 874 retrieved oocytes and 3106 trophectoderm biopsies of blastocysts were included. The primary outcome of the study was median euploidy rate, which was calculated by dividing the number of euploid blastocysts by the total number of biopsied blastocysts for each cycle. Secondary outcomes included the median normal fertilization rate (two-pronuclear (2PN) embryos/metaphase II oocytes) and median blastulation rate (blastocyst numbers/2PN embryos).</p><p><strong>Main results and the role of chance: </strong>Comparable euploidy rates and fertilization rates were observed across all age groups, regardless of variations in ovarian stimulation protocols, gonadotropin dosages (both the starting and total dosages), stimulation durations, the inclusion of human menopausal gonadotrophin supplementation, or the number of oocytes retrieved (all <i>P</i> > 0.05). Blastulation rates declined with increasing starting doses of gonadotropins in women aged 31-34 years old (<i>P</i> = 0.005) but increased with increasing gonadotrophin starting doses in women aged 35-37 years old (<i>P</i> = 0.017). In women aged 31-34, 35-37, and 38-40 years old, blastulation rates were significantly reduced with increases in the number of oocytes retrieved (<i>P</i> = 0.001, <0.001, and 0.012, respectively).</p><p><strong>Limitations reasons for caution: </strong>Limitations include the study's retrospective nature and the relatively small number of patients of advanced age, especially patients older than 40 years old, leading to quite low statistical power. Second, as we considered euploidy rates as outcome measures, we did not analyze the effects of ovarian stimulation on uniform aneuploidy and mosaicism, respectively. Finally, we did not consider the effects of paternal characteristics on embryo euploidy s
{"title":"Effects of ovarian stimulation on embryo euploidy: an analysis of 12 874 oocytes and 3106 blastocysts in cycles with preimplantation genetic testing for monogenic disorders.","authors":"Congcong Ma, Xiaoyu Long, Liying Yan, Xiaohui Zhu, Lixue Chen, Rong Li, Ying Wang, Jie Qiao","doi":"10.1093/hropen/hoae054","DOIUrl":"https://doi.org/10.1093/hropen/hoae054","url":null,"abstract":"<p><strong>Study question: </strong>Does ovarian stimulation and the ovarian response affect embryo euploidy?</p><p><strong>Summary answer: </strong>Ovarian stimulation and the ovarian response in women undergoing preimplantation genetic testing for monogenic disorders (PGT-M) cycles did not affect the rates of blastocyst euploidy.</p><p><strong>What is known already: </strong>Whether or not ovarian stimulation in IVF-embryo transfer has potential effects on embryo euploidy is controversial among studies for several reasons: (i) heterogeneity of the study populations, (ii) biopsies being performed at different stages of embryo development and (iii) evolution of the platforms utilized for ploidy assessment. Patients who undergo PGT-M cycles typically have no additional risks of aneuploidy, providing an ideal study population for exploring this issue.</p><p><strong>Study design size duration: </strong>A retrospective cohort study including embryos undergoing PGT-M was conducted at a single academically affiliated fertility clinic between June 2014 and July 2021.</p><p><strong>Participants/materials setting methods: </strong>A total of 617 women with 867 PGT-M cycles involving 12 874 retrieved oocytes and 3106 trophectoderm biopsies of blastocysts were included. The primary outcome of the study was median euploidy rate, which was calculated by dividing the number of euploid blastocysts by the total number of biopsied blastocysts for each cycle. Secondary outcomes included the median normal fertilization rate (two-pronuclear (2PN) embryos/metaphase II oocytes) and median blastulation rate (blastocyst numbers/2PN embryos).</p><p><strong>Main results and the role of chance: </strong>Comparable euploidy rates and fertilization rates were observed across all age groups, regardless of variations in ovarian stimulation protocols, gonadotropin dosages (both the starting and total dosages), stimulation durations, the inclusion of human menopausal gonadotrophin supplementation, or the number of oocytes retrieved (all <i>P</i> > 0.05). Blastulation rates declined with increasing starting doses of gonadotropins in women aged 31-34 years old (<i>P</i> = 0.005) but increased with increasing gonadotrophin starting doses in women aged 35-37 years old (<i>P</i> = 0.017). In women aged 31-34, 35-37, and 38-40 years old, blastulation rates were significantly reduced with increases in the number of oocytes retrieved (<i>P</i> = 0.001, <0.001, and 0.012, respectively).</p><p><strong>Limitations reasons for caution: </strong>Limitations include the study's retrospective nature and the relatively small number of patients of advanced age, especially patients older than 40 years old, leading to quite low statistical power. Second, as we considered euploidy rates as outcome measures, we did not analyze the effects of ovarian stimulation on uniform aneuploidy and mosaicism, respectively. Finally, we did not consider the effects of paternal characteristics on embryo euploidy s","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 4","pages":"hoae054"},"PeriodicalIF":8.3,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11470209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142486110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-30eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae058
Anja Pinborg, Christophe Blockeel, Giovanni Coticchio, Juan Garcia-Velasco, Pietro Santulli, Alison Campbell
{"title":"Speaking up for the safety of the children following frozen embryo transfer.","authors":"Anja Pinborg, Christophe Blockeel, Giovanni Coticchio, Juan Garcia-Velasco, Pietro Santulli, Alison Campbell","doi":"10.1093/hropen/hoae058","DOIUrl":"https://doi.org/10.1093/hropen/hoae058","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 4","pages":"hoae058"},"PeriodicalIF":8.3,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142486112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-28eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae057
Arantxa Cardona Barberán, Ramesh Reddy Guggilla, Cora Colenbier, Emma Van der Velden, Andrei Rybouchkin, Dominic Stoop, Luc Leybaert, Paul Coucke, Sofie Symoens, Annekatrien Boel, Frauke Vanden Meerschaut, Björn Heindryckx
<p><strong>Study question: </strong>What is the frequency of <i>PLCZ1</i>, <i>ACTL7A</i>, and <i>ACTL9</i> variants in male patients showing fertilization failure after ICSI, and how effective is assisted oocyte activation (AOA) for them?</p><p><strong>Summary answer: </strong>Male patients with fertilization failure after ICSI manifest variants in <i>PLCZ1</i> (29.09%), <i>ACTL7A</i> (14.81%), and <i>ACTL9</i> (3.70%), which can be efficiently overcome by AOA treatment with ionomycin.</p><p><strong>What is known already: </strong>Genetic variants in <i>PLCZ1</i>, and more recently, in <i>ACTL7A</i>, and <i>ACTL9</i> male genes, have been associated with total fertilization failure or low fertilization after ICSI. A larger patient cohort is required to understand the frequency at which these variants occur, and to assess their effect on the calcium ion (Ca<sup>2+</sup>) release during oocyte activation. AOA, using ionomycin, can restore fertilization and pregnancy rates in patients with <i>PLCZ1</i> variants, but it remains unknown how efficient this is for patients with <i>ACTL7A</i> and <i>ACTL9</i> variants.</p><p><strong>Study design size duration: </strong>This prospective study involved two patient cohorts. In the first setting, group 1 (N = 28, 2006-2020) underwent only <i>PLCZ1</i> genetic screening, while group 2 (N = 27, 2020-2023) underwent <i>PLCZ1, ACTL7A</i>, and <i>ACTL9</i> genetic screening. Patients were only recruited when they had a mean fertilization rate of ≤33.33% in at least one ICSI cycle with at least four MII oocytes. Patients underwent a mouse oocyte activation test (MOAT) and at least one ICSI-AOA cycle using calcium chloride (CaCl<sub>2</sub>) injection and double ionomycin exposure at our centre. All patients donated a saliva sample for genetic screening and a sperm sample for further diagnostic tests, including Ca<sup>2+</sup> imaging.</p><p><strong>Participants/materials setting methods: </strong>Genetic screening was performed via targeted next-generation sequencing. Identified variants were classified by applying the revised ACMG guidelines into a Bayesian framework and were confirmed by bidirectional Sanger sequencing. If variants of uncertain significance or likely pathogenic or pathogenic variants were found, patients underwent additional determination of the sperm Ca<sup>2+</sup>-releasing pattern in mouse (MOCA) and in IVM human (HOCA) oocytes. Additionally, ACTL7A immunofluorescence and acrosome ultrastructure analyses by transmission electron microscopy (TEM) were performed for patients with <i>ACTL7A</i> and/or <i>ACTL9</i> variants.</p><p><strong>Main results and the role of chance: </strong>Overall, the frequency rate of <i>PLCZ1</i> variants was 29.09%. Moreover, 14.81% of patients carried <i>ACTL7A</i> variants and 3.70% carried <i>ACTL9</i> variants. Seven different <i>PLCZ1</i> variants were identified (p.Ile74Thr, p.Gln94*, p.Arg141His, p.His233Leu, p.Lys322*, p.Ile379Thr, and p.Ser500Leu), five o
{"title":"High rate of detected variants in male <i>PLCZ1</i> and <i>ACTL7A</i> genes causing failed fertilization after ICSI.","authors":"Arantxa Cardona Barberán, Ramesh Reddy Guggilla, Cora Colenbier, Emma Van der Velden, Andrei Rybouchkin, Dominic Stoop, Luc Leybaert, Paul Coucke, Sofie Symoens, Annekatrien Boel, Frauke Vanden Meerschaut, Björn Heindryckx","doi":"10.1093/hropen/hoae057","DOIUrl":"https://doi.org/10.1093/hropen/hoae057","url":null,"abstract":"<p><strong>Study question: </strong>What is the frequency of <i>PLCZ1</i>, <i>ACTL7A</i>, and <i>ACTL9</i> variants in male patients showing fertilization failure after ICSI, and how effective is assisted oocyte activation (AOA) for them?</p><p><strong>Summary answer: </strong>Male patients with fertilization failure after ICSI manifest variants in <i>PLCZ1</i> (29.09%), <i>ACTL7A</i> (14.81%), and <i>ACTL9</i> (3.70%), which can be efficiently overcome by AOA treatment with ionomycin.</p><p><strong>What is known already: </strong>Genetic variants in <i>PLCZ1</i>, and more recently, in <i>ACTL7A</i>, and <i>ACTL9</i> male genes, have been associated with total fertilization failure or low fertilization after ICSI. A larger patient cohort is required to understand the frequency at which these variants occur, and to assess their effect on the calcium ion (Ca<sup>2+</sup>) release during oocyte activation. AOA, using ionomycin, can restore fertilization and pregnancy rates in patients with <i>PLCZ1</i> variants, but it remains unknown how efficient this is for patients with <i>ACTL7A</i> and <i>ACTL9</i> variants.</p><p><strong>Study design size duration: </strong>This prospective study involved two patient cohorts. In the first setting, group 1 (N = 28, 2006-2020) underwent only <i>PLCZ1</i> genetic screening, while group 2 (N = 27, 2020-2023) underwent <i>PLCZ1, ACTL7A</i>, and <i>ACTL9</i> genetic screening. Patients were only recruited when they had a mean fertilization rate of ≤33.33% in at least one ICSI cycle with at least four MII oocytes. Patients underwent a mouse oocyte activation test (MOAT) and at least one ICSI-AOA cycle using calcium chloride (CaCl<sub>2</sub>) injection and double ionomycin exposure at our centre. All patients donated a saliva sample for genetic screening and a sperm sample for further diagnostic tests, including Ca<sup>2+</sup> imaging.</p><p><strong>Participants/materials setting methods: </strong>Genetic screening was performed via targeted next-generation sequencing. Identified variants were classified by applying the revised ACMG guidelines into a Bayesian framework and were confirmed by bidirectional Sanger sequencing. If variants of uncertain significance or likely pathogenic or pathogenic variants were found, patients underwent additional determination of the sperm Ca<sup>2+</sup>-releasing pattern in mouse (MOCA) and in IVM human (HOCA) oocytes. Additionally, ACTL7A immunofluorescence and acrosome ultrastructure analyses by transmission electron microscopy (TEM) were performed for patients with <i>ACTL7A</i> and/or <i>ACTL9</i> variants.</p><p><strong>Main results and the role of chance: </strong>Overall, the frequency rate of <i>PLCZ1</i> variants was 29.09%. Moreover, 14.81% of patients carried <i>ACTL7A</i> variants and 3.70% carried <i>ACTL9</i> variants. Seven different <i>PLCZ1</i> variants were identified (p.Ile74Thr, p.Gln94*, p.Arg141His, p.His233Leu, p.Lys322*, p.Ile379Thr, and p.Ser500Leu), five o","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 4","pages":"hoae057"},"PeriodicalIF":8.3,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11479693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142486111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-18eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae056
Lisa De Witte, Machteld Baetens, Kelly Tilleman, Frauke Vanden Meerschaut, Sandra Janssens, Ariane Van Tongerloo, Virginie Szymczak, Dominic Stoop, Annelies Dheedene, Sofie Symoens, Björn Menten
<p><strong>Study question: </strong>To what extent can genotype analysis aid in the classification of (mosaic) aneuploid embryos diagnosed through copy number analysis of a trophectoderm (TE) biopsy?</p><p><strong>Summary answer: </strong>In a small portion of embryos, genotype analysis revealed signatures of meiotic or uniform aneuploidy in those diagnosed with intermediate copy number changes, and signatures of presumed mitotic or putative mosaic aneuploidy in those diagnosed with full copy number changes.</p><p><strong>What is known already: </strong>Comprehensive chromosome screening (CCS) for preimplantation genetic testing has provided valuable insights into the prevalence of (mosaic) chromosomal aneuploidy at the blastocyst stage. However, diagnosis of (mosaic) aneuploidy often relies solely on (intermediate) copy number analysis of a single TE biopsy. Integrating genotype information allows for independent assessment of the origin and degree of aneuploidy. Yet, studies aligning both datasets to predict (putative mosaic) aneuploidy in embryos remain scarce.</p><p><strong>Study design size duration: </strong>A single TE biopsy was collected from 1560 embryos derived from 221 couples tested for a monogenic disorder (n = 218) or microdeletion-/microduplication syndrome (n = 3). TE samples were subjected to both copy number and genotyping analysis.</p><p><strong>Participants/materials setting methods: </strong>Copy number and SNP genotyping analysis were conducted using GENType. Unbalanced chromosomal anomalies ≥10 Mb (or ≥20 Mb for copy number calls <50%) were classified by degree, based on low-range intermediate (LR, 30-50%), high-range intermediate (HR, 50-70%) or full (>70%) copy number changes. These categories were further subjected to genotyping analysis to ascertain the origin (and/or degree) of aneuploidy. For chromosomal gains, the meiotic division of origin (meiotic I/II versus non-meiotic or presumed mitotic) was established by studying the haplotypes. The level of monosomy (uniform versus putative mosaic) in the biopsy could be ascertained from the B-allele frequencies. For segmental aneuploidies, genotyping was restricted to deletions.</p><p><strong>Main results and the role of chance: </strong>Of 1479 analysed embryos, 24% (n = 356) exhibited a whole-chromosome aneuploidy, with 19% (n = 280) showing full copy number changes suggestive of uniform aneuploidy. Among 258 embryos further investigated by genotyping, 95% of trisomies with full copy number changes were identified to be of meiotic origin. For monosomies, a complete loss of heterozygosity (LOH) in the biopsy was observed in 97% of cases, yielding a 96% concordance rate at the embryo level (n = 248/258). Interestingly, 4% of embryos (n = 10/258) showed SNP signatures of non-meiotic gain or putative mosaic loss instead. Meanwhile, 5% of embryos (n = 76/1479) solely displayed HR (2.5%; n = 37) or LR (2.6%; n = 39) intermediate copy number changes, with an additional 2% showi
研究问题：基因型分析能在多大程度上帮助对通过滋养层外胚层（TE）活检拷贝数分析诊断出的（镶嵌）非整倍体胚胎进行分类？在一小部分胚胎中，基因型分析显示，被诊断为中等拷贝数变化的胚胎具有减数分裂或均匀非整倍体的特征，而被诊断为完全拷贝数变化的胚胎具有假定有丝分裂或假定镶嵌非整倍体的特征：用于胚胎植入前基因检测的染色体全面筛查（CCS）为了解胚泡阶段（马赛克）染色体非整倍体的发生率提供了宝贵的信息。然而，（马赛克）非整倍体的诊断通常仅依赖于对单个 TE 活检的（中间）拷贝数分析。整合基因型信息可对非整倍体的起源和程度进行独立评估。然而，将这两个数据集进行整合以预测胚胎（假定镶嵌）非整倍体的研究仍然很少：从 221 对夫妇的 1560 个胚胎中采集单个 TE 活检样本，这些夫妇均接受了单基因疾病（n = 218）或微缺失/微重复综合征（n = 3）检测。对 TE 样本进行了拷贝数和基因分型分析：使用 GENType 进行拷贝数和 SNP 基因分型分析。不平衡染色体异常≥10 Mb（或拷贝数调用70%≥20 Mb）拷贝数变化。对这些类别进一步进行基因分型分析，以确定非整倍体的来源（和/或程度）。对于染色体增益，通过研究单倍型确定起源的减数分裂（减数分裂 I/II 与非减数分裂或假定有丝分裂）。活组织检查中的单倍性（均匀或假定镶嵌）可通过 B 等位基因频率来确定。对于节段性非整倍体，基因分型仅限于缺失：在分析的 1479 个胚胎中，24%（n = 356）表现出全染色体非整倍体，19%（n = 280）表现出全拷贝数变化，提示为均匀非整倍体。在通过基因分型进一步研究的 258 个胚胎中，95% 的全拷贝数变化三体被确定为减数分裂源。至于单倍体，97%的病例在活检中观察到完全的杂合性缺失（LOH），胚胎水平的吻合率为 96%（n = 248/258）。有趣的是，有 4% 的胚胎（n = 10/258）显示出非减数分裂增益或假定镶嵌丢失的 SNP 特征。同时，5% 的胚胎（n = 76/1479）只显示 HR（2.5%；n = 37）或 LR（2.6%；n = 39）中间拷贝数变化，另有 2% 的胚胎同时显示中间和完全拷贝数变化。在可以进行基因分型的具有 HR 中间拷贝数变化的胚胎中（n = 25/37），92%（n = 23/25）的 SNP 特征与假定的镶嵌非整倍体一致。然而，有 8%（n = 2/25）的活检结果显示存在减数分裂三体（9%）或完全 LOH（7%）。在 LR 中间组中，33 个基因分型胚胎中有 1 个（3%）显示完全 LOH。此外，在 7% 的胚胎（n = 108/1479）（或 9%（n = 139）的胚胎中检测到节段性非整倍体，并伴有全染色体非整倍体）。这些错误通常（52%）以中间拷贝数值为特征，在检查时与基因分型数据密切吻合（94%-100%）：不适用：研究结果基于单个 TE 活检，且未通过胚胎解剖验证嵌合的真实程度。此外，三体综合征缺乏减数分裂起源的证据不应被视为有丝分裂错误的确凿证据。此外，由于缺乏辨别减数第二次分裂三体和非减数第一次分裂三体所需的重组事件，或无法获得父母双方的 DNA，基因分型诊断并非总能实现：研究结果的更广泛影响：仅将单个 TE 活检的（中间）拷贝数变化解释为胚胎（马赛克）非整倍体的证据仍不理想。将基因型信息与拷贝数状态结合起来，可以更全面地评估胚胎的遗传组成，包括单个 TE 活检的范围和范围。通过识别减数分裂畸变，特别是在假定的马赛克胚胎中，我们强调了基因分型分析作为去选择工具的潜在价值，最终努力减少不良临床结果：L.D.W.得到了佛兰德研究基金会（FWO；1S74621N）的资助。M.B.、K.T.、F.V.M.、S.J.、A.V.T.、V.S.、D.S.、A.D.和 S.S. 由根特大学医院资助。B.M. 由根特大学资助。作者无利益冲突。
{"title":"Aligning genotyping and copy number data in single trophectoderm biopsies for aneuploidy prediction: uncovering incomplete concordance.","authors":"Lisa De Witte, Machteld Baetens, Kelly Tilleman, Frauke Vanden Meerschaut, Sandra Janssens, Ariane Van Tongerloo, Virginie Szymczak, Dominic Stoop, Annelies Dheedene, Sofie Symoens, Björn Menten","doi":"10.1093/hropen/hoae056","DOIUrl":"10.1093/hropen/hoae056","url":null,"abstract":"<p><strong>Study question: </strong>To what extent can genotype analysis aid in the classification of (mosaic) aneuploid embryos diagnosed through copy number analysis of a trophectoderm (TE) biopsy?</p><p><strong>Summary answer: </strong>In a small portion of embryos, genotype analysis revealed signatures of meiotic or uniform aneuploidy in those diagnosed with intermediate copy number changes, and signatures of presumed mitotic or putative mosaic aneuploidy in those diagnosed with full copy number changes.</p><p><strong>What is known already: </strong>Comprehensive chromosome screening (CCS) for preimplantation genetic testing has provided valuable insights into the prevalence of (mosaic) chromosomal aneuploidy at the blastocyst stage. However, diagnosis of (mosaic) aneuploidy often relies solely on (intermediate) copy number analysis of a single TE biopsy. Integrating genotype information allows for independent assessment of the origin and degree of aneuploidy. Yet, studies aligning both datasets to predict (putative mosaic) aneuploidy in embryos remain scarce.</p><p><strong>Study design size duration: </strong>A single TE biopsy was collected from 1560 embryos derived from 221 couples tested for a monogenic disorder (n = 218) or microdeletion-/microduplication syndrome (n = 3). TE samples were subjected to both copy number and genotyping analysis.</p><p><strong>Participants/materials setting methods: </strong>Copy number and SNP genotyping analysis were conducted using GENType. Unbalanced chromosomal anomalies ≥10 Mb (or ≥20 Mb for copy number calls <50%) were classified by degree, based on low-range intermediate (LR, 30-50%), high-range intermediate (HR, 50-70%) or full (>70%) copy number changes. These categories were further subjected to genotyping analysis to ascertain the origin (and/or degree) of aneuploidy. For chromosomal gains, the meiotic division of origin (meiotic I/II versus non-meiotic or presumed mitotic) was established by studying the haplotypes. The level of monosomy (uniform versus putative mosaic) in the biopsy could be ascertained from the B-allele frequencies. For segmental aneuploidies, genotyping was restricted to deletions.</p><p><strong>Main results and the role of chance: </strong>Of 1479 analysed embryos, 24% (n = 356) exhibited a whole-chromosome aneuploidy, with 19% (n = 280) showing full copy number changes suggestive of uniform aneuploidy. Among 258 embryos further investigated by genotyping, 95% of trisomies with full copy number changes were identified to be of meiotic origin. For monosomies, a complete loss of heterozygosity (LOH) in the biopsy was observed in 97% of cases, yielding a 96% concordance rate at the embryo level (n = 248/258). Interestingly, 4% of embryos (n = 10/258) showed SNP signatures of non-meiotic gain or putative mosaic loss instead. Meanwhile, 5% of embryos (n = 76/1479) solely displayed HR (2.5%; n = 37) or LR (2.6%; n = 39) intermediate copy number changes, with an additional 2% showi","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 4","pages":"hoae056"},"PeriodicalIF":8.3,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-17eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae055
Wen-Hong Dong, Xia Wang, Fan Yuan, Lei Wang, Tian-Miao Gu, Bing-Quan Zhu, Jie Shao
<p><strong>Study question: </strong>How many couples with at least one child under 3 years would like to have another one or more child(ren) in Eastern China and will an in-cash subsidy be conducive to couple's fertility intentions?</p><p><strong>Summary answer: </strong>In sum, only 15.1% of respondents had further fertility intentions (FFI) before learning about the subsidy, and the planned in-cash subsidy policy increased respondents' overall FFI by 8.5%.</p><p><strong>What is known already: </strong>Fertility has been declining globally and has reached a new low in China. The reasons why the Chinese three-child policy was under-realized, and how couples will react to a planned monthly ¥1000 (€141.2) subsidy policy, are not fully understood.</p><p><strong>Study design size duration: </strong>During January and February 2022, a cross-sectional online survey aiming to understand families' expenses of raising a child under 3 years old, and couples' FFI, was conducted. During the survey period, 272 510 respondents scanned the QR code. This study reports the findings pertaining to questions on respondents' sociodemographic characteristics, household factors, FFI, and changes in intention from negative to positive after learning about the planned in-cash subsidy. After exclusion, 144 893 eligible responses were included.</p><p><strong>Participants/materials setting methods: </strong>Respondents' FFI, the effect of a planned ¥1000/month*36 months' in-cash subsidy (€5083.2 in total) on people with a negative FFI before the subsidy, and potential reasons for persistent negative FFI after learning about the subsidy were collected through an anonymous online survey. Stepwise binary logistic regression models were used to select associated factors. The potential fertility rate change and government costs were estimated. A stratified analysis by current child number and sensitivity analysis were also conducted.</p><p><strong>Main results and the role of chance: </strong>In sum, 15.7% (22 804/144 893) of respondents were male, 15.1% of respondents reported a positive FFI, and 10.0% (12 288/123 051) without an FFI at first changed their intention after learning about the planned in-cash subsidy policy. For those who still said 'no FFI', 46.5%, 20.6%, and 14.7% chose pressure on housing status, expenses on children's education, and lack of time or energy for caring for another child as their first reasons. FFI was strongest in participants receiving the most financial support from their parents, i.e. grandparents (OR = 1.73, 95% CI = 1.63-1.84 for the >¥100 000/year group), and weakest in those already having two children (OR = 0.23, 95% CI = 0.22-0.24). For those with no FFI before learning about the subsidy policy, respondents with the highest house loan/rent (>¥120 000/year, OR = 1.27, 95% CI = 1.18-1.36) were more likely to change their FFI from 'No' to 'Yes', and those with the highest household income (>¥300 000/year, OR = 0.65, 95% CI = 0.60-0.71) were
{"title":"Will a government subsidy increase couples' further fertility intentions? A real-world study from a large-scale online survey in Eastern China.","authors":"Wen-Hong Dong, Xia Wang, Fan Yuan, Lei Wang, Tian-Miao Gu, Bing-Quan Zhu, Jie Shao","doi":"10.1093/hropen/hoae055","DOIUrl":"https://doi.org/10.1093/hropen/hoae055","url":null,"abstract":"<p><strong>Study question: </strong>How many couples with at least one child under 3 years would like to have another one or more child(ren) in Eastern China and will an in-cash subsidy be conducive to couple's fertility intentions?</p><p><strong>Summary answer: </strong>In sum, only 15.1% of respondents had further fertility intentions (FFI) before learning about the subsidy, and the planned in-cash subsidy policy increased respondents' overall FFI by 8.5%.</p><p><strong>What is known already: </strong>Fertility has been declining globally and has reached a new low in China. The reasons why the Chinese three-child policy was under-realized, and how couples will react to a planned monthly ¥1000 (€141.2) subsidy policy, are not fully understood.</p><p><strong>Study design size duration: </strong>During January and February 2022, a cross-sectional online survey aiming to understand families' expenses of raising a child under 3 years old, and couples' FFI, was conducted. During the survey period, 272 510 respondents scanned the QR code. This study reports the findings pertaining to questions on respondents' sociodemographic characteristics, household factors, FFI, and changes in intention from negative to positive after learning about the planned in-cash subsidy. After exclusion, 144 893 eligible responses were included.</p><p><strong>Participants/materials setting methods: </strong>Respondents' FFI, the effect of a planned ¥1000/month*36 months' in-cash subsidy (€5083.2 in total) on people with a negative FFI before the subsidy, and potential reasons for persistent negative FFI after learning about the subsidy were collected through an anonymous online survey. Stepwise binary logistic regression models were used to select associated factors. The potential fertility rate change and government costs were estimated. A stratified analysis by current child number and sensitivity analysis were also conducted.</p><p><strong>Main results and the role of chance: </strong>In sum, 15.7% (22 804/144 893) of respondents were male, 15.1% of respondents reported a positive FFI, and 10.0% (12 288/123 051) without an FFI at first changed their intention after learning about the planned in-cash subsidy policy. For those who still said 'no FFI', 46.5%, 20.6%, and 14.7% chose pressure on housing status, expenses on children's education, and lack of time or energy for caring for another child as their first reasons. FFI was strongest in participants receiving the most financial support from their parents, i.e. grandparents (OR = 1.73, 95% CI = 1.63-1.84 for the >¥100 000/year group), and weakest in those already having two children (OR = 0.23, 95% CI = 0.22-0.24). For those with no FFI before learning about the subsidy policy, respondents with the highest house loan/rent (>¥120 000/year, OR = 1.27, 95% CI = 1.18-1.36) were more likely to change their FFI from 'No' to 'Yes', and those with the highest household income (>¥300 000/year, OR = 0.65, 95% CI = 0.60-0.71) were","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 4","pages":"hoae055"},"PeriodicalIF":8.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-11eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae053
Josianne Nunes Carriço, Catarina Inês Gonçalves, Asma Al-Naama, Najeeb Syed, José Maria Aragüés, Margarida Bastos, Fernando Fonseca, Teresa Borges, Bernardo Dias Pereira, Duarte Pignatelli, Davide Carvalho, Filipe Cunha, Ana Saavedra, Elisabete Rodrigues, Joana Saraiva, Luisa Ruas, Nuno Vicente, João Martin Martins, Adriana De Sousa Lages, Maria João Oliveira, Cíntia Castro-Correia, Miguel Melo, Raquel Gomes Martins, Joana Couto, Carolina Moreno, Diana Martins, Patrícia Oliveira, Teresa Martins, Sofia Almeida Martins, Olinda Marques, Carla Meireles, António Garrão, Cláudia Nogueira, Carla Baptista, Susana Gama-de-Sousa, Cláudia Amaral, Mariana Martinho, Catarina Limbert, Luisa Barros, Inês Henriques Vieira, Teresa Sabino, Luís R Saraiva, Manuel Carlos Lemos
<p><strong>Study question: </strong>What is the contribution of genetic defects in Portuguese patients with congenital hypogonadotropic hypogonadism (CHH)?</p><p><strong>Summary answer: </strong>Approximately one-third of patients with CHH were found to have a genetic cause for their disorder, with causal pathogenic and likely pathogenic germline variants distributed among 10 different genes; cases of oligogenic inheritance were also included.</p><p><strong>What is known already: </strong>CHH is a rare and genetically heterogeneous disorder characterized by deficient production, secretion, or action of GnRH, LH, and FSH, resulting in delayed or absent puberty, and infertility.</p><p><strong>Study design size duration: </strong>Genetic screening was performed on a cohort of 81 Portuguese patients with CHH (36 with Kallmann syndrome and 45 with normosmic hypogonadotropic hypogonadism) and 263 unaffected controls.</p><p><strong>Participants/materials setting methods: </strong>The genetic analysis was performed by whole-exome sequencing followed by the analysis of a virtual panel of 169 CHH-associated genes. The main outcome measures were non-synonymous rare sequence variants (population allele frequency <0.01) classified as pathogenic, likely pathogenic, and variants of uncertain significance (VUS).</p><p><strong>Main results and the role of chance: </strong>A genetic cause was identified in 29.6% of patients. Causal pathogenic and likely pathogenic variants were distributed among 10 of the analysed genes. The most frequently implicated genes were <i>GNRHR</i>, <i>FGFR1</i>, <i>ANOS1</i>, and <i>CHD7</i>. Oligogenicity for pathogenic and likely pathogenic variants was observed in 6.2% of patients. VUS and oligogenicity for VUS variants were observed in 85.2% and 54.3% of patients, respectively, but were not significantly different from that observed in controls.</p><p><strong>Large scale data: </strong>N/A.</p><p><strong>Limitations reasons for caution: </strong>The identification of a large number of VUS presents challenges in interpretation and these may require reclassification as more evidence becomes available. Non-coding and copy number variants were not studied. Functional studies of the variants were not undertaken.</p><p><strong>Wider implications of the findings: </strong>This study highlights the genetic heterogeneity of CHH and identified several novel variants that expand the mutational spectrum of the disorder. A significant proportion of patients remained without a genetic diagnosis, suggesting the involvement of additional genetic, epigenetic, or environmental factors. The high frequency of VUS underscores the importance of cautious variant interpretation. These findings contribute to the understanding of the genetic architecture of CHH and emphasize the need for further studies to elucidate the underlying mechanisms and identify additional causes of CHH.</p><p><strong>Study funding/competing interests: </strong>This research was fun
{"title":"Genetic architecture of congenital hypogonadotropic hypogonadism: insights from analysis of a Portuguese cohort.","authors":"Josianne Nunes Carriço, Catarina Inês Gonçalves, Asma Al-Naama, Najeeb Syed, José Maria Aragüés, Margarida Bastos, Fernando Fonseca, Teresa Borges, Bernardo Dias Pereira, Duarte Pignatelli, Davide Carvalho, Filipe Cunha, Ana Saavedra, Elisabete Rodrigues, Joana Saraiva, Luisa Ruas, Nuno Vicente, João Martin Martins, Adriana De Sousa Lages, Maria João Oliveira, Cíntia Castro-Correia, Miguel Melo, Raquel Gomes Martins, Joana Couto, Carolina Moreno, Diana Martins, Patrícia Oliveira, Teresa Martins, Sofia Almeida Martins, Olinda Marques, Carla Meireles, António Garrão, Cláudia Nogueira, Carla Baptista, Susana Gama-de-Sousa, Cláudia Amaral, Mariana Martinho, Catarina Limbert, Luisa Barros, Inês Henriques Vieira, Teresa Sabino, Luís R Saraiva, Manuel Carlos Lemos","doi":"10.1093/hropen/hoae053","DOIUrl":"10.1093/hropen/hoae053","url":null,"abstract":"<p><strong>Study question: </strong>What is the contribution of genetic defects in Portuguese patients with congenital hypogonadotropic hypogonadism (CHH)?</p><p><strong>Summary answer: </strong>Approximately one-third of patients with CHH were found to have a genetic cause for their disorder, with causal pathogenic and likely pathogenic germline variants distributed among 10 different genes; cases of oligogenic inheritance were also included.</p><p><strong>What is known already: </strong>CHH is a rare and genetically heterogeneous disorder characterized by deficient production, secretion, or action of GnRH, LH, and FSH, resulting in delayed or absent puberty, and infertility.</p><p><strong>Study design size duration: </strong>Genetic screening was performed on a cohort of 81 Portuguese patients with CHH (36 with Kallmann syndrome and 45 with normosmic hypogonadotropic hypogonadism) and 263 unaffected controls.</p><p><strong>Participants/materials setting methods: </strong>The genetic analysis was performed by whole-exome sequencing followed by the analysis of a virtual panel of 169 CHH-associated genes. The main outcome measures were non-synonymous rare sequence variants (population allele frequency <0.01) classified as pathogenic, likely pathogenic, and variants of uncertain significance (VUS).</p><p><strong>Main results and the role of chance: </strong>A genetic cause was identified in 29.6% of patients. Causal pathogenic and likely pathogenic variants were distributed among 10 of the analysed genes. The most frequently implicated genes were <i>GNRHR</i>, <i>FGFR1</i>, <i>ANOS1</i>, and <i>CHD7</i>. Oligogenicity for pathogenic and likely pathogenic variants was observed in 6.2% of patients. VUS and oligogenicity for VUS variants were observed in 85.2% and 54.3% of patients, respectively, but were not significantly different from that observed in controls.</p><p><strong>Large scale data: </strong>N/A.</p><p><strong>Limitations reasons for caution: </strong>The identification of a large number of VUS presents challenges in interpretation and these may require reclassification as more evidence becomes available. Non-coding and copy number variants were not studied. Functional studies of the variants were not undertaken.</p><p><strong>Wider implications of the findings: </strong>This study highlights the genetic heterogeneity of CHH and identified several novel variants that expand the mutational spectrum of the disorder. A significant proportion of patients remained without a genetic diagnosis, suggesting the involvement of additional genetic, epigenetic, or environmental factors. The high frequency of VUS underscores the importance of cautious variant interpretation. These findings contribute to the understanding of the genetic architecture of CHH and emphasize the need for further studies to elucidate the underlying mechanisms and identify additional causes of CHH.</p><p><strong>Study funding/competing interests: </strong>This research was fun","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 3","pages":"hoae053"},"PeriodicalIF":8.3,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11415827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-10eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae052
Maria Winkler-Dworak, Kryštof Zeman, Tomáš Sobotka
<p><strong>Study question: </strong>What are the factors influencing the decline in the birth rates observed in higher-income countries in the later phase of the COVID-19 pandemic?</p><p><strong>Summary answer: </strong>Our results suggest that economic uncertainty, non-pharmaceutical policy interventions, and the first wave of the population-wide vaccination campaign were associated with the decline in birth rates during 2022.</p><p><strong>What is known already: </strong>During the COVID-19 pandemic, birth rates in most higher-income countries first briefly declined and then shortly recovered, showing no common trends afterwards until early 2022, when they unexpectedly dropped.</p><p><strong>Study design size duration: </strong>This study uses population-wide data on monthly total fertility rates (TFRs) adjusted for seasonality and calendar effects provided in the Human Fertility Database (HFD). Births taking place between November 2020 and October 2022 correspond to conceptions occurring between February 2020 and January 2022, i.e. after the onset of the pandemic but prior to the Russian invasion of Ukraine. The data cover 26 countries, including 21 countries in Europe, the USA, Canada, Israel, Japan, and the Republic of Korea.</p><p><strong>Participants/materials setting methods: </strong>First, we provided a descriptive analysis of the monthly changes in the TFR. Second, we employed linear fixed effects regression models to estimate the association of explanatory factors with the observed seasonally adjusted TFRs. Our analysis considered three broader sets of explanatory factors: economic uncertainty, policy interventions restricting mobility and social activities outside the home, and the progression of vaccination programmes.</p><p><strong>Main results and the role of chance: </strong>We found that birth trends during the COVID-19 pandemic were associated with economic uncertainty, as measured by increased inflation (<i>P</i> < 0.001), whereas unemployment did not show any link to births during the pandemic (<i>P</i> = 0.677). The stringency of pandemic policy interventions was linked to a postponement of births, but only in countries with lower institutional trust and only in the early phase of the pandemic (<i>P</i> = 0.003). In countries with higher trust, stricter containment measures were positively associated with birth rates, both for conceptions in the first year of the pandemic (<i>P</i> = 0.019) and, albeit only weakly significant, for conceptions later in the pandemic (<i>P</i> = 0.057). Furthermore, we found a negative association between the share of the population having received the first dose of the COVID-19 vaccination and TFRs (<i>P</i> < 0.001), whereas the share of the population having completed the primary vaccination course (usually consisting of two doses) was linked to a recovery of birth rates (<i>P</i> < 0.001).</p><p><strong>Large scale data: </strong>N/A.</p><p><strong>Limitations reasons for caution: </strong>
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Pub Date : 2024-09-09eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae050
Sarah Munk Andreasen, Lise Gehrt, Casper P Hagen, Anders Juul, Gylli Mola, Margit Bistrup Fischer, Marianne Skovsager Andersen, David Møbjerg Kristensen, Tina Kold Jensen
<p><strong>Study question: </strong>Does anogenital distance (AGD) - distance from the anus to the genitals - correlate from infancy (3 months) to the age of 9 years in boys and girls?</p><p><strong>Summary answer: </strong>In boys, AGD correlated from infancy to 9 years of age, whereas in girls, correlations were weaker, especially between infancy and later childhood.</p><p><strong>What is known already: </strong>AGD is considered a marker for prenatal androgen action. In males, reduced AGD is associated with testicular cancer, infertility, and lower sperm count. In females, AGD is associated with endometriosis and polycystic ovary syndrome.</p><p><strong>Study design size duration: </strong>In the Odense Child Cohort, a prospective population-based birth cohort, pregnant women were enrolled in early pregnancy. AGD and BMI were measured repeatedly in children at ages 3 and 18 months, as well as at 3, 5, 7, and 9 years.</p><p><strong>Participants/materials setting methods: </strong>AGD was measured from the anus to the scrotum (AGDas) and to the penis (AGDap) in 1022 boys, and to the posterior fourchette and the clitoris in 887 girls repeatedly between the age of 3 months to 9 years. In total, 7706 assessments were made. AGD was adjusted for body weight, and <i>SD scores</i> (the difference between individual AGD and the mean of AGD in the population divided by SD of AGD) were calculated for each child. Pearson correlation coefficient (<i>r</i>) of each measurement was performed to investigate whether individual AGD was stable during childhood. Short predictive values at 3 months (20th percentile) to 9 years were investigated using the AUC produced by the receiver operating characteristic curve.</p><p><strong>Main results and the role of chance: </strong>In boys, AGD/body size-index <i>SD score</i> correlated significantly between infancy and 9 years, strongest for AGDas (<i>r</i> = 0.540 <i>P</i> > 0.001). In girls, weaker significant correlation coefficients were found between AGD at infancy and 9 years; higher correlation coefficients were found between AGD from 3 to 9 years (<i>P</i> > 0.001). Short AGDas in infancy predicted short AGDas in boys aged 9 years (AUC: 0.767, sensitivity 0.71, specificity 0.71). The predictive values of short infant AGDap, penile width (in boys), and AGD (in girls) concerning short outcomes at 9 years were low.</p><p><strong>Limitations reasons for caution: </strong>The AGD measurements are less precisely measurable in girls compared to boys, especially in infancy, resulting in less reproducible measurements. Additionally, because AGD is shorter in girls, the same absolute measurement error is relatively more significant, potentially contributing to greater variability and lower reproducibility in girls. This may contribute to the weaker correlations in girls compared to boys.</p><p><strong>Wider implications of the findings: </strong>In boys, AGDas, relative to body size, correlated from infancy to 9 years, sugge
{"title":"Correlation of anogenital distance from childhood to age 9 years-a prospective population-based birth cohort-the Odense Child Cohort.","authors":"Sarah Munk Andreasen, Lise Gehrt, Casper P Hagen, Anders Juul, Gylli Mola, Margit Bistrup Fischer, Marianne Skovsager Andersen, David Møbjerg Kristensen, Tina Kold Jensen","doi":"10.1093/hropen/hoae050","DOIUrl":"10.1093/hropen/hoae050","url":null,"abstract":"<p><strong>Study question: </strong>Does anogenital distance (AGD) - distance from the anus to the genitals - correlate from infancy (3 months) to the age of 9 years in boys and girls?</p><p><strong>Summary answer: </strong>In boys, AGD correlated from infancy to 9 years of age, whereas in girls, correlations were weaker, especially between infancy and later childhood.</p><p><strong>What is known already: </strong>AGD is considered a marker for prenatal androgen action. In males, reduced AGD is associated with testicular cancer, infertility, and lower sperm count. In females, AGD is associated with endometriosis and polycystic ovary syndrome.</p><p><strong>Study design size duration: </strong>In the Odense Child Cohort, a prospective population-based birth cohort, pregnant women were enrolled in early pregnancy. AGD and BMI were measured repeatedly in children at ages 3 and 18 months, as well as at 3, 5, 7, and 9 years.</p><p><strong>Participants/materials setting methods: </strong>AGD was measured from the anus to the scrotum (AGDas) and to the penis (AGDap) in 1022 boys, and to the posterior fourchette and the clitoris in 887 girls repeatedly between the age of 3 months to 9 years. In total, 7706 assessments were made. AGD was adjusted for body weight, and <i>SD scores</i> (the difference between individual AGD and the mean of AGD in the population divided by SD of AGD) were calculated for each child. Pearson correlation coefficient (<i>r</i>) of each measurement was performed to investigate whether individual AGD was stable during childhood. Short predictive values at 3 months (20th percentile) to 9 years were investigated using the AUC produced by the receiver operating characteristic curve.</p><p><strong>Main results and the role of chance: </strong>In boys, AGD/body size-index <i>SD score</i> correlated significantly between infancy and 9 years, strongest for AGDas (<i>r</i> = 0.540 <i>P</i> > 0.001). In girls, weaker significant correlation coefficients were found between AGD at infancy and 9 years; higher correlation coefficients were found between AGD from 3 to 9 years (<i>P</i> > 0.001). Short AGDas in infancy predicted short AGDas in boys aged 9 years (AUC: 0.767, sensitivity 0.71, specificity 0.71). The predictive values of short infant AGDap, penile width (in boys), and AGD (in girls) concerning short outcomes at 9 years were low.</p><p><strong>Limitations reasons for caution: </strong>The AGD measurements are less precisely measurable in girls compared to boys, especially in infancy, resulting in less reproducible measurements. Additionally, because AGD is shorter in girls, the same absolute measurement error is relatively more significant, potentially contributing to greater variability and lower reproducibility in girls. This may contribute to the weaker correlations in girls compared to boys.</p><p><strong>Wider implications of the findings: </strong>In boys, AGDas, relative to body size, correlated from infancy to 9 years, sugge","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 3","pages":"hoae050"},"PeriodicalIF":8.3,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11415829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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