{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T07:49:51Z","timestamp":1793778591249,"version":"4.6.1"},"reference-count":49,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,9,4]],"date-time":"2022-09-04T00:00:00Z","timestamp":1662249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>In recent years, the growing use of ART (assisted reproductive techniques) has led to a progressive improvement of protocols; embryo freezing is certainly one of the most important innovations. This technique is selectively offered as a tailored approach to reduce the incidence of multiple pregnancies and, most importantly, to lower the risk of developing ovarian hyperstimulation syndrome when used in conjunction with an ovulation-triggering GnRH antagonist. The increase in transfer cycles with frozen embryos made it possible to study the effects of the technique in children thus conceived. Particularly noteworthy is the increase in macrosomal and LGA (large for gestational age) newborns, in addition to a decrease in SGA (small for gestational age) and LBW (low birth weight) newborns. The authors aimed to outline a broad-ranging narrative review by summarizing and elaborating on the most important evidence regarding the neonatal outcome of children born from frozen embryos and provide information on the medium and long-term follow- up of these children. However, given the relatively recent large-scale implementation of such techniques, further studies are needed to provide more conclusive evidence on outcomes and implications.<\/jats:p>","DOI":"10.3390\/medicina58091218","type":"journal-article","created":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T22:33:01Z","timestamp":1662503581000},"page":"1218","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Neonatal Outcomes and Long-Term Follow-Up of Children Born from Frozen Embryo, a Narrative Review of Latest Research Findings"],"prefix":"10.3390","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4269-4269","authenticated-orcid":false,"given":"Giuseppe","family":"Gullo","sequence":"first","affiliation":[{"name":"IVF Unit, Department of Obstetrics and Gynecology, Villa Sofia Cervello Hospital, University of Palermo, 90146 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6411-7983","authenticated-orcid":false,"given":"Marco","family":"Scaglione","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal-Child Sciences, University of Genoa, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaspare","family":"Cucinella","sequence":"additional","affiliation":[{"name":"IVF Unit, Department of Obstetrics and Gynecology, Villa Sofia Cervello Hospital, University of Palermo, 90146 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vito","family":"Chiantera","sequence":"additional","affiliation":[{"name":"Unit of Gynecologic Oncology, ARNAS \u201cCivico-Di Cristina-Benfratelli\u201d, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonino","family":"Perino","sequence":"additional","affiliation":[{"name":"IVF Unit, Department of Obstetrics and Gynecology, Villa Sofia Cervello Hospital, University of Palermo, 90146 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Elisabetta","family":"Greco","sequence":"additional","affiliation":[{"name":"IVF Unit, Department of Obstetrics and Gynecology, Villa Sofia Cervello Hospital, University of Palermo, 90146 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1543-2802","authenticated-orcid":false,"given":"Antonio Simone","family":"Lagan\u00e0","sequence":"additional","affiliation":[{"name":"Unit of Gynecologic Oncology, ARNAS \u201cCivico-Di Cristina-Benfratelli\u201d, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7104-8744","authenticated-orcid":false,"given":"Enrico","family":"Marinelli","sequence":"additional","affiliation":[{"name":"Department of Medico-Surgical Sciences and Biotechnologies, \u201cSapienza\u201d University of Rome, 04100 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Basile","sequence":"additional","affiliation":[{"name":"IRCCS Orthopedic Institute Galeazzi, 20161 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5741-7139","authenticated-orcid":false,"given":"Simona","family":"Zaami","sequence":"additional","affiliation":[{"name":"Department of Anatomical, Histological, Forensic and Orthopedic Sciences, \u201cSapienza\u201d University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,4]]},"reference":[{"key":"ref_1","first-page":"2","article-title":"Psychological impact of gynecological diseases: The importance of a multidisciplinary approach","volume":"30","author":"Valenti","year":"2018","journal-title":"Ital. J. Gynaecol. Obstet."},{"key":"ref_2","first-page":"39","article-title":"Infertility in the Global South: Raising Awareness and Generating Insights for Policy and Practice","volume":"9","author":"Gerrits","year":"2017","journal-title":"Facts Views Vis. ObGyn"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"10952","DOI":"10.18632\/aging.102497","article-title":"Global, Regional, and National Prevalence and Disability-Adjusted Life-Years for Infertility in 195 Countries and Territories, 1990\u20132017: Results from a Global Burden of Disease Study, 2017","volume":"11","author":"Sun","year":"2019","journal-title":"Aging"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1163\/15718093-12530378","article-title":"Gamete Donation: Are Children Entitled to Know Their Genetic Origins? A Comparison of Opposing Views. The Italian State of Affairs","volume":"25","author":"Vergallo","year":"2018","journal-title":"Eur. J. Health Law"},{"key":"ref_5","first-page":"896","article-title":"Medical and ethical basis for embryo cryopreservation","volume":"142","author":"Crosby","year":"2014","journal-title":"Rev. Med. Chile"},{"key":"ref_6","first-page":"e39","article-title":"Assisted Heterologous Fertilization and the Right of Donorconceived Children to Know Their Biological Origins","volume":"169","author":"Zaami","year":"2018","journal-title":"La Clin. Ter."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1016\/j.fertnstert.2017.03.010","article-title":"Assessing Reproductive Choices of Women and the Likelihood of Oocyte Cryopreservation in the Era of Elective Oocyte Freezing","volume":"107","author":"Milman","year":"2017","journal-title":"Fertil. Steril."},{"key":"ref_8","first-page":"3537","article-title":"Elective Egg Freezing: Can You Really Turn Back the Clock?","volume":"19","author":"Zaami","year":"2015","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1016\/j.fertnstert.2016.07.1066","article-title":"How Does Closed System Vitrification of Human Oocytes Affect the Clinical Outcome? A Prospective, Observational, Cohort, Noninferiority Trial in an Oocyte Donation Program","volume":"106","author":"Papatheodorou","year":"2016","journal-title":"Fertil. Steril."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1159\/000506803","article-title":"Closed vs. Open Oocyte Vitrification Methods Are Equally Effective for Blastocyst Embryo Transfers: Prospective Study from a Sibling Oocyte Donation Program","volume":"85","author":"Gullo","year":"2020","journal-title":"Gynecol. Obstet. Investig."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1093\/humrep\/deaa304","article-title":"High Birth Weight and Large-for-Gestational-Age in Singletons Born after Frozen Compared to Fresh Embryo Transfer, by Gestational Week: A Nordic Register Study from the CoNARTaS Group","volume":"36","author":"Terho","year":"2021","journal-title":"Hum. Reprod."},{"key":"ref_12","first-page":"CD011184","article-title":"Fresh versus Frozen Embryo Transfers in Assisted Reproduction","volume":"2","author":"Zaat","year":"2021","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1080\/01443615.2021.1882973","article-title":"Is Frozen Embryo Transfer Better than Fresh Embryo Transfer in Women Undergoing Intracytoplasmic Sperm Injection over the Age of Thirty-Five? A Single Referral Centre Experience","volume":"42","author":"Acet","year":"2022","journal-title":"J. Obstet. Gynaecol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.fertnstert.2020.05.012","article-title":"Children Born from Frozen Embryo Transfers: Is There a Difference?","volume":"114","author":"Pirtea","year":"2020","journal-title":"Fertil. Steril."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.fertnstert.2020.04.041","article-title":"Development of Children Born from Freeze-Only versus Fresh Embryo Transfer: Follow-up of a Randomized Controlled Trial","volume":"114","author":"Vuong","year":"2020","journal-title":"Fertil. Steril."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3389\/fendo.2020.00019","article-title":"Is Embryo Cryopreservation Causing Macrosomia-and What Else?","volume":"11","author":"Orvieto","year":"2020","journal-title":"Front. Endocrinol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.ejogrb.2020.01.008","article-title":"Effect of Frozen and Fresh Embryo Transfers on the Birthweight of Live-Born Twins","volume":"246","author":"Chen","year":"2020","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s11689-020-09347-w","article-title":"Risk of Neurodevelopmental Disorders in Children Born from Different ART Treatments: A Systematic Review and Meta-Analysis","volume":"12","author":"Djuwantono","year":"2020","journal-title":"J. Neurodev. Disord."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s00404-020-05593-4","article-title":"Neonatal Outcomes in Singleton Pregnancies Conceived by Fresh or Frozen Embryo Transfer Compared to Spontaneous Conceptions: A Systematic Review and Meta-Analysis","volume":"302","author":"Elias","year":"2020","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_20","first-page":"2282","article-title":"Perinatal and Maternal Outcome after Vitrification of Blastocysts: A Nordic Study in Singletons from the CoNARTaS Group","volume":"34","author":"Ernstad","year":"2019","journal-title":"Hum. Reprod."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"126.e1","DOI":"10.1016\/j.ajog.2019.03.010","article-title":"Neonatal and Maternal Outcome after Frozen Embryo Transfer: Increased Risks in Programmed Cycles","volume":"221","author":"Ernstad","year":"2019","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.fertnstert.2019.05.020","article-title":"Fresh versus Frozen Embryo Transfer Has No Effect on Childhood Weight","volume":"112","author":"Ainsworth","year":"2019","journal-title":"Fertil. Steril."},{"key":"ref_23","first-page":"305","article-title":"Comparison of birth weights of children born after slow frozen embryo replacement versus fresh embryo transfer","volume":"47","author":"Maris","year":"2019","journal-title":"Gynecol. Obstet. Fertil. Senol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1016\/j.fertnstert.2019.07.010","article-title":"Health Outcomes for Massachusetts Infants after Fresh versus Frozen Embryo Transfer","volume":"112","author":"Hwang","year":"2019","journal-title":"Fertil. Steril."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1093\/humupd\/dmx031","article-title":"Is Frozen Embryo Transfer Better for Mothers and Babies? Can Cumulative Meta-Analysis Provide a Definitive Answer?","volume":"24","author":"Maheshwari","year":"2018","journal-title":"Hum. Reprod. Update"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1002\/bdr2.1219","article-title":"Large for Gestational Age and Macrosomia in Singletons Born after Frozen\/Thawed Embryo Transfer (FET) in Assisted Reproductive Technology (ART)","volume":"110","author":"Berntsen","year":"2018","journal-title":"Birth Defects Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.fertnstert.2017.10.019","article-title":"Pregnancy-Related Complications and Perinatal Outcomes Resulting from Transfer of Cryopreserved versus Fresh Embryos In Vitro Fertilization: A Meta-Analysis","volume":"109","author":"Sha","year":"2018","journal-title":"Fertil. Steril."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s13048-018-0432-x","article-title":"Fresh versus Frozen Embryo Transfer for Full-Term Singleton Birth: A Retrospective Cohort Study","volume":"11","author":"Zhang","year":"2018","journal-title":"J. Ovarian Res."},{"key":"ref_29","first-page":"CD011184","article-title":"Fresh versus Frozen Embryo Transfers in Assisted Reproduction","volume":"3","author":"Wong","year":"2017","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1016\/j.fertnstert.2017.01.021","article-title":"Perinatal Outcomes in Children Born after Fresh or Frozen Embryo Transfer: A Catalan Cohort Study Based on 14,262 Newborns","volume":"107","author":"Vidal","year":"2017","journal-title":"Fertil. Steril."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1056\/NEJMoa1513873","article-title":"Fresh versus Frozen Embryos for Infertility in the Polycystic Ovary Syndrome","volume":"375","author":"Chen","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1093\/humrep\/dew103","article-title":"Neonatal Health Including Congenital Malformation Risk of 1072 Children Born after Vitrified Embryo Transfer","volume":"31","author":"Belva","year":"2016","journal-title":"Hum. Reprod."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1093\/humrep\/det440","article-title":"Large Baby Syndrome in Singletons Born after Frozen Embryo Transfer (FET): Is It Due to Maternal Factors or the Cryotechnique?","volume":"29","author":"Pinborg","year":"2014","journal-title":"Hum. Reprod."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2794","DOI":"10.1093\/humrep\/deu246","article-title":"Clinical Outcomes Following Cryopreservation of Blastocysts by Vitrification or Slow Freezing: A Population-Based Cohort Study","volume":"29","author":"Li","year":"2014","journal-title":"Hum. Reprod."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.1093\/humrep\/det272","article-title":"Perinatal Outcomes of Children Born after Frozen-Thawed Embryo Transfer: A Nordic Cohort Study from the CoNARTaS Group","volume":"28","author":"Wennerholm","year":"2013","journal-title":"Hum. Reprod."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1093\/humrep\/det104","article-title":"Obstetric and Neonatal Outcomes after Transfer of Vitrified Early Cleavage Embryos","volume":"28","author":"Liu","year":"2013","journal-title":"Hum. Reprod."},{"key":"ref_37","first-page":"20","article-title":"Pregnancy Rates Following the Exclusive Transfer of Twice Frozen Twice Thawed Embryos Using a Modified Slow Cool Cryopreservation Technique","volume":"40","author":"Check","year":"2013","journal-title":"Clin. Exp. Obstet. Gynecol."},{"key":"ref_38","first-page":"23","article-title":"Pregnancy Outcome Following Fresh vs Frozen Embryo Transfer into Gestational Carriers Using a Simplified Slow Freeze Protocol","volume":"39","author":"Check","year":"2012","journal-title":"Clin. Exp. Obstet. Gynecol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.1093\/humrep\/dep125","article-title":"Children Born after Cryopreservation of Embryos or Oocytes: A Systematic Review of Outcome Data","volume":"24","author":"Wennerholm","year":"2009","journal-title":"Hum. Reprod."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1093\/humrep\/15.suppl_5.18","article-title":"Cryopreservation of Embryos and Oocytes: Obstetric Outcome and Health in Children","volume":"15","author":"Wennerholm","year":"2000","journal-title":"Hum. Reprod."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1016\/S0140-6736(97)08247-0","article-title":"Postnatal Growth and Health in Children Born after Cryopreservation as Embryos","volume":"351","author":"Wennerholm","year":"1998","journal-title":"Lancet"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1093\/humrep\/12.8.1819","article-title":"Obstetric and Perinatal Outcome of Children Conceived from Cryopreserved Embryos","volume":"12","author":"Wennerholm","year":"1997","journal-title":"Hum. Reprod."},{"key":"ref_43","first-page":"485","article-title":"Myo-Inositol: From Induction of Ovulation to Menopausal Disorder Management","volume":"67","author":"Gullo","year":"2015","journal-title":"Minerva Ginecol"},{"key":"ref_44","first-page":"e932722","article-title":"D-Chiro-Inositol Induces Ovulation in Non-Polycystic Ovary Syndrome (PCOS), Non-Insulin-Resistant Young Women, Likely by Modulating Aromatase Expression: A Report of 2 Cases","volume":"22","author":"Espinola","year":"2021","journal-title":"Am. J. Case Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"8866","DOI":"10.1038\/s41598-021-88329-x","article-title":"Myoinositol plus \u03b1-Lactalbumin Supplementation, Insulin Resistance and Birth Outcomes in Women with Gestational Diabetes Mellitus: A Randomized, Controlled Study","volume":"11","author":"Corrado","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1080\/09513590.2016.1254613","article-title":"Myo-Inositol and Melatonin in the Menopausal Transition","volume":"33","author":"Santamaria","year":"2017","journal-title":"Gynecol. Endocrinol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1002\/uog.18942","article-title":"Influence of Cryopreservation on Perinatal Outcome after Blastocyst- vs. Cleavage-Stage Embryo Transfer: Systematic Review and Meta-Analysis","volume":"51","author":"Alviggi","year":"2018","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_48","first-page":"7","article-title":"Correlation between Maternal Gingivitis\/Periodontitis and Preterm Delivery: Fact or Fancy?","volume":"30","author":"Lin","year":"2018","journal-title":"Ital. J. Gynaecol. Obstet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1093\/humrep\/deh078","article-title":"Incidence of Spontaneous Abortion among Pregnancies Produced by Assisted Reproductive Technology","volume":"19","author":"Wang","year":"2004","journal-title":"Hum. 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