Ignite Creation Date:
2025-12-25 @ 5:04 AM
Ignite Modification Date:
2025-12-26 @ 4:06 AM
Study NCT ID:
NCT05578118
Status:
COMPLETED
Last Update Posted:
2025-04-15
First Post:
2022-10-10
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Health of Children Born From ICSI With AOA (AOA-BABIES)
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D007246', 'term': 'Infertility'}], 'ancestors': [{'id': 'D000091662', 'term': 'Genital Diseases'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}]}}, 'protocolSection': {'designModule': {'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 63}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2022-10-23', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-08', 'completionDateStruct': {'date': '2023-03-30', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-04-10', 'studyFirstSubmitDate': '2022-10-10', 'studyFirstSubmitQcDate': '2022-10-10', 'lastUpdatePostDateStruct': {'date': '2025-04-15', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2022-10-13', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2023-03-30', 'type': 'ACTUAL'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Gestational age at delivery', 'timeFrame': 'At birth', 'description': 'Gestational age at delivery'}, {'measure': 'Mode of delivery', 'timeFrame': 'At birth', 'description': 'Vaginal birth or C-section'}, {'measure': 'Birth weight', 'timeFrame': 'At birth', 'description': 'Weight of baby born'}, {'measure': 'Length circumference', 'timeFrame': 'At birth', 'description': 'Length circumference after birth'}, {'measure': 'Head circumference', 'timeFrame': 'At birth', 'description': 'Head circumference after birth'}, {'measure': 'Rate of congenital anomalies', 'timeFrame': 'At birth', 'description': 'Any congenital anomalies detected in baby born'}, {'measure': 'Length of neonatal intensive care unit (NICU) admission', 'timeFrame': 'Up to 28 days after birth', 'description': 'Number of admission days to NICU'}, {'measure': 'Rate of Respiratory distress syndrome', 'timeFrame': 'Up to 28 days after birth', 'description': 'Respiratory distress syndrome (RDS), diagnosed as the presence of tachypnoea \\>60/minute, sternal recession and expiratory grunting, need for supplemental oxygen, and a radiological picture of diffuse reticulogranular shadowing with an air bronchogram'}, {'measure': 'Rate of Periventricular haemorrhage', 'timeFrame': 'Up to 28 days after birth', 'description': 'Periventricular haemorrhage II B or worse, will be diagnosed by repeated neonatal cranial ultrasound by the neonatologist according to the guidelines on neuro-imaging described by de Vries et al.'}, {'measure': 'Rate of Necrotizing enterocolitis', 'timeFrame': 'Up to 28 days after birth', 'description': 'Necrotizing enterocolitis (NEC) will be diagnosed according to Bell.'}, {'measure': 'Rate of Proven sepsis', 'timeFrame': 'Up to 28 days after birth', 'description': 'Proven sepsis, will be diagnosed on the combination of clinical signs and positive blood cultures.'}, {'measure': 'Rate of Composite of poor perinatal outcomes', 'timeFrame': 'Up to 28 days after birth', 'description': 'Composite of poor perinatal outcomes, defined as intraventricular haemorrhage, respiratory distress syndrome, necrotizing enterocolitis or neonatal sepsis.'}, {'measure': 'Rate of long-term illness and chronic conditions', 'timeFrame': 'Up to 28 days after birth', 'description': 'Any long-term illness and chronic condition appears in a child.'}], 'primaryOutcomes': [{'measure': 'The percentage of abnormal ASQ-3 score', 'timeFrame': '12 months after birth', 'description': 'ASQ-3 (Ages and Stages Questionaires®) has 5 aspects: Communication, Gross Motor, Fine Motor, Problem-solving, and Personal-Social Each element has 6 questions. If the answer is Yes, score = 10, Sometimes = 5, and Not yet = 0.\n\nASQ-3 average = average score of 5 aspects.'}], 'secondaryOutcomes': [{'measure': 'Score of Communication', 'timeFrame': '12 months after birth', 'description': '6 questions, if the answer is Yes, score = 10, Sometimes = 5 and Not yet = 0. Total score will be used: minimum = 0 and maximum = 60. Each aspect in each stage has an alternative threshold.'}, {'measure': 'Score of Gross motor', 'timeFrame': '12 months after birth', 'description': '6 questions, if the answer is Yes, score = 10, Sometimes = 5 and Not yet = 0. Total score will be used: minimum = 0 and maximum = 60. Each aspect in each stage has an alternative threshold.'}, {'measure': 'Score of Fine motor', 'timeFrame': '12 months after birth', 'description': '6 questions, if the answer is Yes, score = 10, Sometimes = 5 and Not yet = 0. Total score will be used: minimum = 0 and maximum = 60. Each aspect in each stage has an alternative threshold.'}, {'measure': 'Score of Problem-solving skill', 'timeFrame': '12 months after birth', 'description': '6 questions, if the answer is Yes, score = 10, Sometimes = 5 and Not yet = 0. Total score will be used: minimum = 0 and maximum = 60. Each aspect in each stage has an alternative threshold.'}, {'measure': 'Score of Personal-Social', 'timeFrame': '12 months after birth', 'description': '6 questions, if the answer is Yes, score = 10, Sometimes = 5 and Not yet = 0. Total score will be used: minimum = 0 and maximum = 60. Each aspect in each stage has an alternative threshold.'}, {'measure': 'The rate of children who have at least one red flag sign(s):', 'timeFrame': '12 months after birth', 'description': 'For children at 12 months: they\n\n* No response when being called by their name\n* Does not understand "no"\n* Can not stand even when being supported\n* Apathy or non-observance of the caregiver\n* Does not look at the point where the caregiver points'}, {'measure': 'Duration of breastfeeding', 'timeFrame': '12 months after birth', 'description': 'Duration of breastfeeding'}, {'measure': 'Infant age at which weaning starts', 'timeFrame': '12 months after birth', 'description': 'Infant age at which weaning starts'}, {'measure': 'Name of diseases that lead to hospital admission', 'timeFrame': '12 months after birth', 'description': 'Name of diseases that lead to hospital admission'}, {'measure': 'Number of hospital admission', 'timeFrame': '12 months after birth', 'description': 'Number of hospital admission'}, {'measure': 'Weight', 'timeFrame': '12 months after birth', 'description': 'Weight on the examination date'}, {'measure': 'Height', 'timeFrame': '12 months after birth', 'description': 'Height on the examination date'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['ICSI', 'Total fertilization failure', 'AOA', 'ASQ-3', 'Health of children'], 'conditions': ['Infertility', 'Intracytoplasmic Sperm Injection']}, 'referencesModule': {'references': [{'pmid': '11732839', 'type': 'RESULT', 'citation': 'Alberio R, Zakhartchenko V, Motlik J, Wolf E. Mammalian oocyte activation: lessons from the sperm and implications for nuclear transfer. Int J Dev Biol. 2001 Oct;45(7):797-809.'}, {'pmid': '9073459', 'type': 'RESULT', 'citation': 'Bos-Mikich A, Whittingham DG, Jones KT. Meiotic and mitotic Ca2+ oscillations affect cell composition in resulting blastocysts. Dev Biol. 1997 Feb 1;182(1):172-9. doi: 10.1006/dbio.1996.8468.'}, {'pmid': '26658129', 'type': 'RESULT', 'citation': 'Capalbo A, Ottolini CS, Griffin DK, Ubaldi FM, Handyside AH, Rienzi L. Artificial oocyte activation with calcium ionophore does not cause a widespread increase in chromosome segregation errors in the second meiotic division of the oocyte. Fertil Steril. 2016 Mar;105(3):807-814.e2. doi: 10.1016/j.fertnstert.2015.11.017. Epub 2015 Dec 1.'}, {'pmid': '24861451', 'type': 'RESULT', 'citation': "D'haeseleer E, Vanden Meerschaut F, Bettens K, Luyten A, Gysels H, Thienpont Y, De Witte G, Heindryckx B, Oostra A, Roeyers H, Sutter PD, van Lierde K. Language development of children born following intracytoplasmic sperm injection (ICSI) combined with assisted oocyte activation (AOA). Int J Lang Commun Disord. 2014 Nov;49(6):702-9. doi: 10.1111/1460-6984.12100. Epub 2014 May 26."}, {'pmid': '12376103', 'type': 'RESULT', 'citation': 'Ducibella T, Huneau D, Angelichio E, Xu Z, Schultz RM, Kopf GS, Fissore R, Madoux S, Ozil JP. Egg-to-embryo transition is driven by differential responses to Ca(2+) oscillation number. Dev Biol. 2002 Oct 15;250(2):280-91.'}, {'pmid': '25376461', 'type': 'RESULT', 'citation': 'Ebner T, Oppelt P, Wober M, Staples P, Mayer RB, Sonnleitner U, Bulfon-Vogl S, Gruber I, Haid AE, Shebl O. Treatment with Ca2+ ionophore improves embryo development and outcome in cases with previous developmental problems: a prospective multicenter study. Hum Reprod. 2015 Jan;30(1):97-102. doi: 10.1093/humrep/deu285. Epub 2014 Nov 5.'}, {'pmid': '30099496', 'type': 'RESULT', 'citation': 'Fawzy M, Emad M, Mahran A, Sabry M, Fetih AN, Abdelghafar H, Rasheed S. Artificial oocyte activation with SrCl2 or calcimycin after ICSI improves clinical and embryological outcomes compared with ICSI alone: results of a randomized clinical trial. Hum Reprod. 2018 Sep 1;33(9):1636-1644. doi: 10.1093/humrep/dey258.'}, {'pmid': '19079959', 'type': 'RESULT', 'citation': 'Heytens E, Soleimani R, Lierman S, De Meester S, Gerris J, Dhont M, Van der Elst J, De Sutter P. Effect of ionomycin on oocyte activation and embryo development in mouse. Reprod Biomed Online. 2008 Dec;17(6):764-71. doi: 10.1016/s1472-6483(10)60403-8.'}, {'type': 'RESULT', 'citation': 'Hirata, K., Nakamura, Y., Hattori, H., Kuchiki, M., Sakamoto, E., & Kyono, K. (2013). Follow-up child growth regarding new technologies: Testicular sperm extraction (TESE), in vitro maturation (IVM), and assisted oocyte activation (AOA). Fertility and Sterility, 100(3), S470. https://doi.org/10.1016/j.fertnstert.2013.07.445'}, {'pmid': '24769204', 'type': 'RESULT', 'citation': 'Kashir J, Nomikos M, Lai FA, Swann K. Sperm-induced Ca2+ release during egg activation in mammals. Biochem Biophys Res Commun. 2014 Aug 1;450(3):1204-11. doi: 10.1016/j.bbrc.2014.04.078. Epub 2014 Apr 21.'}, {'pmid': '21431324', 'type': 'RESULT', 'citation': 'Kim BY, Yoon SY, Cha SK, Kwak KH, Fissore RA, Parys JB, Yoon TK, Lee DR. Alterations in calcium oscillatory activity in vitrified mouse eggs impact on egg quality and subsequent embryonic development. Pflugers Arch. 2011 May;461(5):515-26. doi: 10.1007/s00424-011-0955-0. Epub 2011 Mar 23.'}, {'pmid': '18675447', 'type': 'RESULT', 'citation': 'Koo OJ, Jang G, Kwon DK, Kang JT, Kwon OS, Park HJ, Kang SK, Lee BC. Electrical activation induces reactive oxygen species in porcine embryos. Theriogenology. 2008 Oct 15;70(7):1111-8. doi: 10.1016/j.theriogenology.2008.06.031.'}, {'pmid': '27143515', 'type': 'RESULT', 'citation': 'Miller N, Biron-Shental T, Sukenik-Halevy R, Klement AH, Sharony R, Berkovitz A. Oocyte activation by calcium ionophore and congenital birth defects: a retrospective cohort study. Fertil Steril. 2016 Sep 1;106(3):590-596.e2. doi: 10.1016/j.fertnstert.2016.04.025. Epub 2016 Apr 30.'}, {'pmid': '11222146', 'type': 'RESULT', 'citation': 'Ozil JP, Huneau D. Activation of rabbit oocytes: the impact of the Ca2+ signal regime on development. Development. 2001 Mar;128(6):917-28. doi: 10.1242/dev.128.6.917.'}, {'pmid': '16996050', 'type': 'RESULT', 'citation': 'Ozil JP, Banrezes B, Toth S, Pan H, Schultz RM. Ca2+ oscillatory pattern in fertilized mouse eggs affects gene expression and development to term. Dev Biol. 2006 Dec 15;300(2):534-44. doi: 10.1016/j.ydbio.2006.08.041. Epub 2006 Aug 25.'}, {'pmid': '8206704', 'type': 'RESULT', 'citation': 'Swann K, Ozil JP. Dynamics of the calcium signal that triggers mammalian egg activation. Int Rev Cytol. 1994;152:183-222. doi: 10.1016/s0074-7696(08)62557-7. No abstract available.'}, {'pmid': '24639711', 'type': 'RESULT', 'citation': 'Eftekhar M, Janati S, Rahsepar M, Aflatoonian A. Effect of oocyte activation with calcium ionophore on ICSI outcomes in teratospermia: A randomized clinical trial. Iran J Reprod Med. 2013 Nov;11(11):875-82.'}, {'pmid': '7672149', 'type': 'RESULT', 'citation': 'Tesarik J, Sousa M. Key elements of a highly efficient intracytoplasmic sperm injection technique: Ca2+ fluxes and oocyte cytoplasmic dislocation. Fertil Steril. 1995 Oct;64(4):770-6. doi: 10.1016/s0015-0282(16)57853-4.'}, {'pmid': '23081875', 'type': 'RESULT', 'citation': 'Vanden Meerschaut F, Leybaert L, Nikiforaki D, Qian C, Heindryckx B, De Sutter P. Diagnostic and prognostic value of calcium oscillatory pattern analysis for patients with ICSI fertilization failure. Hum Reprod. 2013 Jan;28(1):87-98. doi: 10.1093/humrep/des368. Epub 2012 Oct 18.'}, {'pmid': '23482335', 'type': 'RESULT', 'citation': 'Vanden Meerschaut F, Nikiforaki D, De Roo C, Lierman S, Qian C, Schmitt-John T, De Sutter P, Heindryckx B. Comparison of pre- and post-implantation development following the application of three artificial activating stimuli in a mouse model with round-headed sperm cells deficient for oocyte activation. Hum Reprod. 2013 May;28(5):1190-8. doi: 10.1093/humrep/det038. Epub 2013 Mar 12.'}, {'pmid': '24656559', 'type': 'RESULT', 'citation': 'Vanden Meerschaut F, Nikiforaki D, Heindryckx B, De Sutter P. Assisted oocyte activation following ICSI fertilization failure. Reprod Biomed Online. 2014 May;28(5):560-71. doi: 10.1016/j.rbmo.2014.01.008. Epub 2014 Jan 31.'}, {'type': 'RESULT', 'citation': 'WHO child growth standards: Length/height-for-age, weight-for-age, weight-for-length, weight-for-height and body mass index-for-age: Methods and development. (n.d.). Retrieved June 10, 2022, from https://www.who.int/publications-detail-redirect/924154693X'}, {'pmid': '1302268', 'type': 'RESULT', 'citation': 'Yoshida S, Plant S. Mechanism of release of Ca2+ from intracellular stores in response to ionomycin in oocytes of the frog Xenopus laevis. J Physiol. 1992 Dec;458:307-18. doi: 10.1113/jphysiol.1992.sp019419.'}]}, 'descriptionModule': {'briefSummary': 'The investigators follow up on the development of children born from ICSI-AOA using the Developmental Red Flags and Ages \\& Stages Third Edition (ASQ-3) Questionnaires to give strong evidence about the safety of AOA in assisted reproductive technology.', 'detailedDescription': 'Intracytoplasmic sperm injection (ICSI) is the most widely utilized assisted reproductive technique (ART) worldwide. Fertilization rates obtained after ICSI treatment are reported between 70 and 80%, representing the most efficient ART; however, complete post-ICSI fertilization failure still occurs in 3-5% of cases.\n\nThe leading cause of failed fertilization is failure to achieve oocyte activation, a crucial stage in the initiation of embryo development during fertilization. Assisted oocyte activation (AOA) using a calcium ionophore has been used for over a decade following ICSI fertilization failure. AOA is not considered a routine practice of ART yet, which is only suitable for patients with proper indications, including (i) total fertilization failure or low fertilization rate (\\<30%) in the previous IVF; (ii) severe male factor infertility; (iii) patients with a history of embryo arrest or poor embryo quality in previous IVF cycle.\n\nRegarding technique, the artificial rise of induced calcium rises cannot precisely mimic the physiologically sperm-induced calcium oscillations. Little is known yet about the possible adverse effects of ionophores on post-implantation embryo development. Numerous studies have been conducted to compare the development of children born from ICSI - AOA versus non-AOA. Thus, the investigators performed this study to investigate the physical, mental, and motor development of children born following ICSI - AOA using the Developmental Red Flags and Ages \\& Stages Third Edition (ASQ-3) Questionnaires.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD'], 'maximumAge': '12 Months', 'minimumAge': '12 Months', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'In the ICSI+AOA group, indications of AOA are:\n\n* Previous failed IVF treatment with no fertilization or poor fertilization rate (fertilized oocytes/pick-up oocytes\\<35%) or poor embryo result (number of embryos/pick-up oocytes\\<35%, \\<3 embryos, no good-quality embryo)\n* Using sperm after retrieval technique, cryptozoospermia\n\nIn the Control group, the indications of AOA for the next IVF cycle (if patients continue the next IVF cycle) are:\n\n* Currently failed IVF treatment with no fertilization or poor fertilization rate (fertilized oocytes/pick-up oocytes\\<35%) or poor embryo result (number of embryos/pick-up oocytes\\<35%, \\<3 embryos, no good-quality embryo)', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\nAll single, live babies born following ICSI with AOA and ICSI without AOA from 08/2020 to 04/2021.\n\nParents consent to participate in the study. Group ICSI+AOA: Embryos from ICSI with AOA with calcium ionophore\n\nIn the ICSI+AOA group, indications of AOA are:\n\n* Previous failed IVF treatment with no fertilization or poor fertilization rate (fertilized oocytes/pick-up oocytes\\<35%) or poor embryo result (number of embryos/pick-up oocytes\\<35%, \\<3 embryos, no good-quality embryo)\n* Using sperm after retrieval technique, cryptozoospermia Group Control: Embryos from ICSI without AOA.\n\nIn the Control group, the indications of AOA for the next IVF cycle (if patients continue the next IVF cycle) are:\n\n* Currently failed IVF treatment with no fertilization or poor fertilization rate (fertilized oocytes/pick-up oocytes\\<35%) or poor embryo result (number of embryos/pick-up oocytes\\<35%, \\<3 embryos, no good-quality embryo)\n\nExclusion Criteria:\n\nEmbryos with PGT. Oocyte donation'}, 'identificationModule': {'nctId': 'NCT05578118', 'briefTitle': 'Health of Children Born From ICSI With AOA (AOA-BABIES)', 'organization': {'class': 'OTHER', 'fullName': 'Mỹ Đức Hospital'}, 'officialTitle': 'Physical, Mental, and Motor Development of Children Born From Intracytoplasmic Sperm Injection With Assisted Oocyte Activation With Calcium Ionophore', 'orgStudyIdInfo': {'id': '10/22/DD-BVMD'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'ICSI + AOA', 'description': 'Children born after ICSI + AOA'}, {'label': 'Control', 'description': 'Children born after ICSI'}]}, 'contactsLocationsModule': {'locations': [{'zip': '70000', 'city': 'Ho Chi Minh City', 'country': 'Vietnam', 'facility': 'Mỹ Đức Hospital', 'geoPoint': {'lat': 10.82302, 'lon': 106.62965}}], 'overallOfficials': [{'name': 'Lan Vuong Ngoc, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Mỹ Đức Hospital'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Mỹ Đức Hospital', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}