{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T22:50:06Z","timestamp":1768690206437,"version":"3.49.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T00:00:00Z","timestamp":1647388800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>With the increasing use of frozen embryo transfer (FET), the best endometrial preparation protocol is continuously being discussed. The hormone replacement therapy (HRT) cycle and letrozole-induced ovulation (L-OI) cycle are available protocols for patients with abnormal ovulation. Previous comparisons of the two protocols have focused on pregnancy outcomes, with less attention to perinatal outcomes, and population heterogeneity was large; thus, convincing conclusions about which protocol is more appropriate could not be drawn.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a retrospective cohort study using propensity score matching (PSM) analysis for a population of patients undergoing FET cycles in the reproductive center of the Third Affiliated Hospital of Zhengzhou University from January 2016 to September 2020. The main outcome measures were clinical pregnancy rate, live birth rate, very preterm delivery (VPTD), preterm delivery (PTD), low birth weight (LBW), macrosomia, small for gestational age (SGA), large for gestational age (LGA), hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), premature rupture of membranes (PROM), placenta previa, and congenital abnormality.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 8010 women were enrolled. Due to the large heterogeneity among the patients, we conducted 1:1 PSM, and 1461 women matched in each group. Compared with the HRT group, the L-OI group had a smaller proportion of thin endometrium (27.38% vs. 41.07%) and thicker endometrium on the day of embryo transfer (9.63 \u00b1 1.82 vs. 8.91 \u00b1 1.38). There were no significant differences in clinical pregnancy rate, early abortion rate or live birth rate between the groups. There was no significant difference in perinatal outcomes of singleton live birth, including VPTD, PTD, postterm delivery, LBW, macrosomia, SGA, LGA, GDM, HDP, placenta previa, and congenital malformation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>For women with abnormal ovulation, the pregnancy and perinatal outcomes of HRT and L-OI protocols are reassuring. It seems that both protocols are safe and effective for endometrial preparation in frozen-thawed embryo transfer in the clinic.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2022.837731","type":"journal-article","created":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T06:43:35Z","timestamp":1647413015000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Comparison of Perinatal Outcomes of Letrozole-Induced Ovulation and Hormone Replacement Therapy Protocols in Patients With Abnormal Ovulation Undergoing Frozen-Thawed Embryo Transfer: A Propensity Score Matching Analysis"],"prefix":"10.3389","volume":"13","author":[{"given":"Wenjuan","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaozhao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junwei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingnan","family":"Ren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manman","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yichun","family":"Guan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(16)48029-5","article-title":"Two Pregnancies Following Transfer of Intact Frozen-Thawed Embryos","volume":"42","author":"Zeilmaker","year":"1984","journal-title":"Fertil Steril"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dey242","article-title":"ART in Europe, 2014 Results Generated From European Registries by ESHRE The European IVF-Monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE)","volume":"33","author":"De Geyter","year":"2018","journal-title":"Hum Reprod"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2018.02.135","article-title":"Programming the Endometrium for Deferred Transfer of Cryopreserved Embryos: Hormone Replacement Versus Modified Natural Cycles","volume":"109","author":"Groenewoud","year":"2018","journal-title":"Fertil Steril"},{"key":"B4","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1016\/j.fertnstert.2012.05.019","article-title":"Obstetric and Perinatal Outcomes in Singleton Pregnancies Resulting From the Transfer of Frozen Thawed Versus Fresh Embryos Generated Through In Vitro Fertilization Treatment: A Systematic Review and Meta-Analysis","volume":"98","author":"Maheshwari","year":"2012","journal-title":"Fertil Steril"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/16.6.1140","article-title":"Elective Single Embryo Transfer: The Value of Cryopreservation","volume":"16","author":"Tiitinen","year":"2001","journal-title":"Hum Reprod"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmu027","article-title":"Fresh Versus Frozen Embryo Transfer: Backing Clinical Decisions With Scientific and Clinical Evidence","volume":"20","author":"Evans","year":"2014","journal-title":"Hum Reprod Update"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dew120","article-title":"A Randomized Controlled, Non-Inferiority Trial of Modified Natural Versus Artificial Cycle for Cryo-Thawed Embryo Transfer","volume":"31","author":"Groenewoud","year":"2016","journal-title":"Hum Reprod"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/den254","article-title":"Neonatal Outcome of 937 Children Born After Transfer of Cryopreserved Embryos Obtained by ICSI and IVF and Comparison With Outcome Data of Fresh ICSI and IVF Cycles","volume":"23","author":"Belva","year":"2008","journal-title":"Hum Reprod (Oxf Engl)"},{"key":"B9","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1186\/s12958-016-0211-8","article-title":"Risk of Adverse Pregnancy and Perinatal Outcomes After High Technology Infertility Treatment: A Comprehensive Systematic Review","volume":"14","author":"Palomba","year":"2016","journal-title":"Reprod Biol Endocrinol"},{"key":"B10","doi-asserted-by":"publisher","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: Off J Am Fertil Soc Pac Coast Fertil Soc Can Fertil Androl Soc"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2017.08.035","article-title":"Embryo Cryopreservation and Preeclampsia Risk","volume":"108","author":"Sites","year":"2017","journal-title":"Fertil Steril"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2016.08.047","article-title":"Obstetric and Perinatal Outcomes After Either Fresh or Thawed Frozen Embryo Transfer: An Analysis of 112,432 Singleton Pregnancies Recorded in the Human Fertilisation and Embryology Authority Anonymized Dataset","volume":"106","author":"Maheshwari","year":"2016","journal-title":"Fertil Steril"},{"key":"B13","doi-asserted-by":"publisher","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"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2020.12.016","article-title":"Endometrium Preparation and Perinatal Outcomes in Women Undergoing Single-Blastocyst Transfer in Frozen Cycles","volume":"115","author":"Hu","year":"2021","journal-title":"Fertil Steril"},{"key":"B15","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1186\/s12884-021-03791-9","article-title":"Perinatal Outcomes of Neonates Born From Different Endometrial Preparation Protocols After Frozen Embryo Transfer: A Retrospective Cohort Study","volume":"21","author":"Li","year":"2021","journal-title":"BMC Pregnancy Childbirth"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2019.04.014","article-title":"Letrozole Use During Frozen Embryo Transfer Cycles in Women With Polycystic Ovary Syndrome","volume":"112","author":"Zhang","year":"2019","journal-title":"Fertil Steril"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.29252\/ijrm.15.2.83","article-title":"Can Letrozole Plus HMG Protocol Improve Pregnancy Outcomes in Frozen-Thawed Embryo Transfer? An RCT","volume":"15","author":"Aleyasin","year":"2017","journal-title":"Int J Reprod Biomed"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(00)01705-2","article-title":"Use of an Aromatase Inhibitor for Induction of Ovulation in Patients With an Inadequate Response to Clomiphene Citrate","volume":"75","author":"Mitwally","year":"2001","journal-title":"Fertil Steril"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-2350","article-title":"Diagnosis and Treatment of Polycystic Ovary Syndrome: An Endocrine Society Clinical Practice Guideline","volume":"98","author":"Legro","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/der452","article-title":"Endometrial Receptivity Defects During IVF Cycles With and Without Letrozole","volume":"27","author":"Miller","year":"2012","journal-title":"Hum Reprod"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2012.09.042","article-title":"The Use of Aromatase Inhibitors in Invitro Fertilization","volume":"98","author":"Garcia-Velasco","year":"2012","journal-title":"Fertil Steril"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmn033","article-title":"Use of Letrozole in Assisted Reproduction: A Systematic Review and Meta-Analysis","volume":"14","author":"Requena","year":"2008","journal-title":"Hum Reprod Update"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dev224","article-title":"Frozen-Thawed Embryo Transfer in a Natural or Mildly Hormonally Stimulated Cycle in Women With Regular Ovulatory Cycles: A RCT","volume":"30","author":"Peeraer","year":"2015","journal-title":"Hum Reprod"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2020.10.039","article-title":"Adverse Obstetric and Perinatal Outcomes in 1,136 Singleton Pregnancies Conceived After Programmed Frozen Embryo Transfer (FET) Compared With Natural Cycle FET - ScienceDirect","volume":"115","author":"Llaa","year":"2021","journal-title":"Fertil Steril"},{"key":"B25","doi-asserted-by":"publisher","first-page":"e104779","DOI":"10.1371\/journal.pone.0104779","article-title":"Birth Weight Reference Percentiles for Chinese","volume":"9","author":"Dai","year":"2014","journal-title":"PloS One"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2003.03.001","article-title":"Effects of Letrozole on Superovulation With Gonadotropins in Women Undergoing Intrauterine Insemination","volume":"80","author":"Healey","year":"2003","journal-title":"Fertil Steril"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1007\/s00404-013-3044-0","article-title":"Letrozole Ovulation Induction: An Effective Option in Endometrial Preparation for Frozen-Thawed Embryo Transfer","volume":"289","author":"Li","year":"2014","journal-title":"Arch Gynecol Obstet"},{"key":"B28","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1186\/s12958-020-00675-z","article-title":"The Effect of Letrozole Versus Artificial Hormonal Endometrial Preparation on Pregnancy Outcome After Frozen-Thawed Embryos Transfer Cycles: A Randomized Clinical Trial","volume":"18","author":"Hosseini-Najarkolaei","year":"2020","journal-title":"Reprod Biol Endocrinol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.664072","article-title":"Comparison of Pregnancy and Neonatal Outcomes of Single Frozen Blastocyst Transfer Between Letrozole-Induction and HRT Cycles in Patients With Abnormal Ovulation","volume":"12","author":"Zhang","year":"2021","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2007.02.062","article-title":"Clomiphene Citrate or Letrozole for Ovulation Induction in Women With Polycystic Ovarian Syndrome: A Prospective Randomized Trial","volume":"92","author":"Badawy","year":"2009","journal-title":"Fertil Steril"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dex066","article-title":"Pregnancy and Neonatal Outcomes Following Letrozole Use in Frozen-Thawed Single Embryo Transfer Cycles","volume":"32","author":"Tatsumi","year":"2017","journal-title":"Hum Reprod"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/cen.12280","article-title":"Letrozole Stimulation in Endometrial Preparation for Cryopreserved-Thawed Embryo Transfer in Women With Polycystic Ovarian Syndrome: A Pilot Study","volume":"80","author":"Hu","year":"2014","journal-title":"Clin Endocrinol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s12958-020-00601-3","article-title":"Increased Risk of Maternal and Neonatal Complications in Hormone Replacement Therapy Cycles in Frozen Embryo Transfer","volume":"18","author":"Zong","year":"2020","journal-title":"Reprod Biol Endocrinol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1007\/s10815-019-01420-1","article-title":"Increased Pregnancy Complications Following Frozen-Thawed Embryo Transfer During an Artificial Cycle","volume":"36","author":"Jing","year":"2019","journal-title":"J Assisted Reprod Genet"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dez079","article-title":"Endometrial Preparation Methods for Frozen-Thawed Embryo Transfer are Associated With Altered Risks of Hypertensive Disorders of Pregnancy, Placenta Accreta, and Gestational Diabetes Mellitus","volume":"34","author":"Saito","year":"2019","journal-title":"Hum Reprod"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-0588","article-title":"Controlled Ovarian Stimulation Induces a Functional Genomic Delay of the Endometrium With Potential Clinical Implications","volume":"93","author":"Horcajadas","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.118.12043","article-title":"Increased Preeclampsia Risk and Reduced Aortic Compliance With In Vitro Fertilization Cycles in the Absence of a Corpus Luteum","volume":"73","author":"von Versen-H\u00f6ynck","year":"2019","journal-title":"Hypertension"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.118.12046","article-title":"Absent or Excessive Corpus Luteum Number Is Associated With Altered Maternal Vascular Health in Early Pregnancy","volume":"73","author":"von Versen-Hynck","year":"2019","journal-title":"Hypertension"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1172\/JCI11975","article-title":"Relaxin is Essential for Renal Vasodilation During Pregnancy in Conscious Rats","volume":"107","author":"Novak","year":"2001","journal-title":"J Clin Invest"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2019.12.007","article-title":"Frozen-Thawed Embryo Transfer: The Potential Importance of the Corpus Luteum in Preventing Obstetrical Complications","volume":"113","author":"Singh","year":"2020","journal-title":"Fertil Steril"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00404-016-4217-4","article-title":"Comparison of Four Protocols for Luteal Phase Support in Frozen-Thawed Embryo Transfer Cycles: A Randomized Clinical Trial","volume":"295","author":"Zarei","year":"2017","journal-title":"Arch Gynecol Obstet"},{"key":"B42","article-title":"The Effect of Luteal Phase Support on Pregnancy Rates of the Stimulated Intrauterine Insemination Cycles in Couples With Unexplained Infertility","volume":"4","author":"Ebrahimi","year":"2010","journal-title":"Int J Fertil Steril"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/s0015-0282(16)56935-0","article-title":"Pharmacokinetics and Endometrial Tissue of Progesterone After Administration by Instramuscular and Vaginal Routes:a Comparative Study","volume":"62","author":"Miles","year":"1994","journal-title":"Fertil Steril"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1055\/s-0035-1545363","article-title":"Luteal Phase Support in In Vitro Fertilization","volume":"33","author":"Yanushpolsky","year":"2015","journal-title":"Semin Reprod Med"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.837731\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T06:43:37Z","timestamp":1647413017000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.837731\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,16]]},"references-count":44,"alternative-id":["10.3389\/fendo.2022.837731"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.837731","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,16]]},"article-number":"837731"}}