{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:42:26Z","timestamp":1760060546027,"version":"build-2065373602"},"reference-count":54,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: The role of luteal phase support (LPS) in frozen\u2013thawed embryo transfer (FET) cycles has garnered increasing interest, particularly regarding its influence on uterine perfusion and pregnancy outcomes. This study aimed to investigate the effect of different oral LPS regimens on first-trimester uterine artery Doppler indices and their association with early pregnancy outcomes in naturally conceived and FET pregnancies. Methods: This retrospective cohort study included 289 singleton pregnancies comprising spontaneous conceptions, FET cycles supported with oral micronised progesterone, and FET cycles supported with oral dydrogesterone. The uterine artery pulsatility index (PI) was measured via Doppler ultrasound during the first trimester. Group comparisons were performed using non-parametric tests. Multivariable regression analyses were used to assess independent predictors of PI and associations with gestational diabetes and low birth weight. Results: Uterine artery PI values differed significantly among the groups (p &lt; 0.001). The lowest PI was observed in the dydrogesterone group, followed by the naturally conceived and micronised progesterone groups. A higher maternal body mass index (BMI) was independently associated with lower PI (p = 0.009), while maternal age showed no significant effect. No significant associations were found between PI or maternal characteristics and adverse outcomes such as gestational diabetes or low birth weight. Conclusions: Dydrogesterone was associated with more favorable uterine artery Doppler indices in early pregnancy, suggesting improved uteroplacental adaptation in FET cycles. These findings support further prospective research to determine the clinical impact of LPS regimens on placental development and perinatal health.<\/jats:p>","DOI":"10.3390\/diagnostics15172223","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T08:23:38Z","timestamp":1756801418000},"page":"2223","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["First-Trimester Uterine Artery Doppler Indices and Pregnancy Outcomes in Naturally Conceived and Frozen\u2013Thawed Embryo Transfer Cycles"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3737-7250","authenticated-orcid":false,"given":"Elif Ganime","family":"Ayg\u00fcn","sequence":"first","affiliation":[{"name":"Acibadem Mehmet Ali Aydinlar University, Atakent Hospital, Istanbul 34303, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edis","family":"Kahraman","sequence":"additional","affiliation":[{"name":"Acibadem Mehmet Ali Aydinlar University, Atakent Hospital, Istanbul 34303, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.fertnstert.2016.06.028","article-title":"A fresh(er) perspective on frozen embryo transfers","volume":"106","author":"Pereira","year":"2016","journal-title":"Fertil. Steril."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"34","DOI":"10.47102\/annals-acadmedsg.2023226","article-title":"Oocytes on Ice: Exploring the Advancements in Elective Egg Freezing for Women","volume":"53","author":"Ong","year":"2024","journal-title":"Ann. Acad. Med. Singap."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Martinez-Rodero, I., Gallardo, M., Pisaturo, V., Scarica, C., Conaghan, J., Liebermann, J., and Cuevas-Saiz, I. (2025). Shorter Protocols for Vitrification and Post-Warming Dilution of Human Oocytes and Embryos: A Narrative Review. Reprod. Biomed. Online, 51.","DOI":"10.1016\/j.rbmo.2025.104857"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.1093\/humrep\/17.9.2287","article-title":"Luteal Phase Support in Infertility Treatment: A Meta-Analysis of the Randomized Trials","volume":"17","author":"Pritts","year":"2002","journal-title":"Hum. Reprod."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1159\/000084546","article-title":"Luteal Phase Support in In Vitro Fertilization: Meta-Analysis of Randomized Trials","volume":"60","author":"Nosarka","year":"2005","journal-title":"Gynecol. Obstet. Investig."},{"key":"ref_6","first-page":"761","article-title":"Luteal-Phase Support in Assisted Reproductive Technology: An Ongoing Challenge","volume":"19","author":"Dashti","year":"2021","journal-title":"Int. J. Reprod. Biomed."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Stavridis, K., Balafoutas, D., Kalampokas, T., Benetou, V., Samoli, E., Vlahos, N., and Kasdagli, M.I. (2025). Oral Dydrogesterone Versus Vaginal Progesterone for Luteal Phase Support in Frozen-Thawed Embryo Transfer Cycles: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J. Clin. Med., 14.","DOI":"10.3390\/jcm14093238"},{"key":"ref_8","first-page":"913","article-title":"Comparison of Oral Dydrogesterone with Suppository Vaginal Progesterone for Luteal-Phase Support in In Vitro Fertilization (IVF): A Randomized Clinical Trial","volume":"11","author":"Salehpour","year":"2013","journal-title":"Iran J. Reprod. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e-rbgo18","DOI":"10.61622\/rbgo\/2024AO18","article-title":"Real-World Utilization Pattern of Dydrogesterone in 7287 Indian Women with Obstetric and Gynecological Conditions: Data from Multicentric, Retrospective Study","volume":"46","author":"Tank","year":"2024","journal-title":"Rev. Bras. Ginecol. Obstet."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Griesinger, G., Blockeel, C., Kahler, E., Pexman-Fieth, C., Olofsson, J.I., Driessen, S., and Tournaye, H. (2020). Dydrogesterone as an Oral Alternative to Vaginal Progesterone for IVF Luteal Phase Support: A Systematic Review and Individual Participant Data Meta-Analysis. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0241044"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"S55","DOI":"10.1016\/S0301-2115(03)00173-8","article-title":"Uterine Blood Flow\u2014A Determinant of Fetal Growth","volume":"110","author":"Lang","year":"2003","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Tian, Y., and Yang, X. (2022). A Review of Roles of Uterine Artery Doppler in Pregnancy Complications. Front. Med., 9.","DOI":"10.3389\/fmed.2022.813343"},{"key":"ref_13","first-page":"649","article-title":"Qualitative Assessment of Uteroplacental Blood Flow: Early Screening Test for High-Risk Pregnancies","volume":"68","author":"Campbell","year":"1986","journal-title":"Obstet. Gynecol."},{"key":"ref_14","first-page":"369","article-title":"Individualized Risk Assessment for Adverse Pregnancy Outcome by Uterine Artery Doppler at 23 Weeks","volume":"98","author":"Lees","year":"2001","journal-title":"Obstet. Gynecol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1055\/s-0038-1660777","article-title":"Uterine Artery Doppler in Screening for Preeclampsia and Fetal Growth Restriction","volume":"40","author":"Pedroso","year":"2018","journal-title":"Rev. Bras. Ginecol. Obstet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/j.ajog.2004.06.057","article-title":"The Influence of Obesity and Diabetes on the Risk of Cesarean Delivery","volume":"191","author":"Ehrenberg","year":"2004","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Fuchs, F., Senat, M.V., Rey, E., Balayla, J., Chaillet, N., Bouyer, J., and Audibert, F. (2017). Impact of Maternal Obesity on the Incidence of Pregnancy Complications in France and Canada. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-11432-5"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1097\/AOG.0000000000002504","article-title":"Risk of Adverse Pregnancy Outcomes at Advanced Maternal Age","volume":"131","author":"Frederiksen","year":"2018","journal-title":"Obstet. Gynecol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"219","DOI":"10.20344\/amp.11057","article-title":"Advanced Maternal Age: Adverse Outcomes of Pregnancy, A Meta-Analysis","volume":"32","author":"Pinheiro","year":"2019","journal-title":"Acta Med. Port."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1002\/uog.21969","article-title":"Uterine Artery Doppler in Singleton Pregnancies Conceived after In-Vitro Fertilization or Intracytoplasmic Sperm Injection with Fresh vs Frozen Blastocyst Transfer: Longitudinal Cohort Study","volume":"56","author":"Cavoretto","year":"2020","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2428","DOI":"10.1093\/humrep\/deaa235","article-title":"Prospective Longitudinal Cohort Study of Uterine Arteries Doppler in Singleton Pregnancies Obtained by IVF\/ICSI with Oocyte Donation or Natural Conception","volume":"35","author":"Cavoretto","year":"2020","journal-title":"Hum. Reprod."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/j.placenta.2005.12.006","article-title":"The Uterine Spiral Arteries in Human Pregnancy: Facts and Controversies","volume":"27","author":"Pijnenborg","year":"2006","journal-title":"Placenta"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1152\/physiol.00033.2008","article-title":"Maternal Uterine Vascular Remodeling during Pregnancy","volume":"24","author":"Osol","year":"2009","journal-title":"Physiology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.placenta.2009.02.009","article-title":"Rheological and Physiological Consequences of Conversion of the Maternal Spiral Arteries for Uteroplacental Blood Flow during Human Pregnancy","volume":"30","author":"Burton","year":"2009","journal-title":"Placenta"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.bpobgyn.2011.01.008","article-title":"Colour Doppler Ultrasound of Spiral Artery Blood Flow in the Prediction of Pre-Eclampsia and Intrauterine Growth Restriction","volume":"25","author":"Gebb","year":"2011","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e009909","DOI":"10.1136\/bmjopen-2015-009909","article-title":"Utero-Placental Vascularisation in Normal and Preeclamptic and Intra-Uterine Growth Restriction Pregnancies: Third Trimester Quantification Using 3D Power Doppler with Comparison to Placental Vascular Morphology (EVUPA): A Prospective Controlled Study","volume":"6","author":"Duan","year":"2016","journal-title":"BMJ Open"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Schiffer, V., Evers, L., de Haas, S., Ghossein-Doha, C., Al-Nasiry, S., and Spaanderman, M. (2020). Spiral Artery Blood Flow during Pregnancy: A Systematic Review and Meta-Analysis. BMC Pregnancy Childbirth, 20.","DOI":"10.1186\/s12884-020-03150-0"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Siargkas, A., Tsakiridis, I., Kappou, D., Mamopoulos, A., Papastefanou, I., and Dagklis, T. (2025). The Association Between Uterine Artery Pulsatility Index at Mid-Gestation and the Method of Conception: A Cohort Study. Medicina, 61.","DOI":"10.3390\/medicina61061093"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1093\/humupd\/dmad011","article-title":"Obstetric and Neonatal Outcomes after Natural Versus Artificial Cycle Frozen Embryo Transfer and the Role of Luteal Phase Support: A Systematic Review and Meta-Analysis","volume":"29","author":"Zaat","year":"2023","journal-title":"Hum. Reprod. Update"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1002\/uog.14918","article-title":"Placental Volume and Uterine Artery Doppler Evaluation at 11 + 0 to 13 + 6 Weeks\u2019 Gestation in Pregnancies Conceived with In-Vitro Fertilization: Comparison between Autologous and Donor Oocyte Recipients","volume":"47","author":"Rizzo","year":"2016","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.rbmo.2018.12.023","article-title":"Placental Volume and Other First-Trimester Outcomes: Are There Differences between Fresh Embryo Transfer, Frozen-Thawed Embryo Transfer and Natural Conception?","volume":"38","author":"Choux","year":"2019","journal-title":"Reprod. Biomed. Online"},{"key":"ref_32","first-page":"6809","article-title":"Fresh vs. Frozen Embryo Transfer in Assisted Reproductive Techniques: A Single Center Retrospective Cohort Study and Ethical-Legal Implications","volume":"27","author":"Gullo","year":"2023","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"464.e1","DOI":"10.1016\/j.ajog.2024.10.033","article-title":"First-Trimester Uterine Artery Pulsatility Index and Preeclampsia Risk in Pregnancies after Artificial Frozen Embryo Transfer: Analysis of over 27,000 Pregnancies","volume":"232","author":"Donno","year":"2025","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Naghshineh, E., Ghasemi Tehrani, H., Sharifian, F., and Haghighat, S. (2023). A Comparison of Oral Dydrogesterone with Vaginal Progesterone for Luteal-Phase Support in In Vitro Fertilization: A Randomized Controlled Trial. Adv. Biomed. Res., 12.","DOI":"10.4103\/abr.abr_253_22"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"8","DOI":"10.31083\/j.ceog5001008","article-title":"Randomized Clinical Trial Comparing Oral Dydrogesterone to Micronized Vaginal Progesterone for Endometrial Preparation in Frozen-Thawed Embryo Transfer Cycle","volume":"50","author":"Dzik","year":"2023","journal-title":"Clin. Exp. Obstet. Gynecol."},{"key":"ref_36","first-page":"232","article-title":"Pregnancy Success Predictive Value of Endometrial and Uterine Doppler Markers When Using Oral Ovarian Induction Medication in Subfertile Patients","volume":"8","author":"Almamou","year":"2020","journal-title":"J. Res. Med. Dent. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Vidal, A., Dhakal, C., Werth, N., Weiss, J.M., Lehnick, D., and Kohl Schwartz, A.S. (2023). Supplementary Dydrogesterone Is Beneficial as Luteal Phase Support in Artificial Frozen-Thawed Embryo Transfer Cycles Compared to Micronized Progesterone Alone. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1128564"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.fertnstert.2006.07.1506","article-title":"Uteroplacental Circulation in Early Pregnancy Complicated by Threatened Abortion Supplemented with Vaginal Micronized Progesterone or Oral Dydrogesterone","volume":"87","author":"Czajkowski","year":"2007","journal-title":"Fertil. Steril."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1111\/jog.12456","article-title":"Assessment of Sub-Endometrial Blood Flow Parameters Following Dydrogesterone and Micronized Vaginal Progesterone Administration in Women with Idiopathic Recurrent Miscarriage: A Pilot Study","volume":"40","author":"Ghosh","year":"2014","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1515\/hmbci-2015-0062","article-title":"Dydrogesterone and the Immunology of Pregnancy","volume":"27","author":"Raghupathy","year":"2016","journal-title":"Horm. Mol. Biol. Clin. Investig."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1159\/000491576","article-title":"The Role of Progesterone in Feto-Maternal Immunological Cross Talk","volume":"27","year":"2018","journal-title":"Med. Princ. Pract."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Piccinni, M.P., Raghupathy, R., Saito, S., and Szekeres-Bartho, J. (2021). Cytokines, Hormones and Cellular Regulatory Mechanisms Favoring Successful Reproduction. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.717808"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1002\/pd.3997","article-title":"First-Trimester Uterine Artery Doppler Velocimetry in the Prediction of Birth Weight in a Low-Risk Population","volume":"33","author":"Sarmiento","year":"2013","journal-title":"Prenat. Diagn."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"32","DOI":"10.3109\/14767058.2014.985201","article-title":"The Influence of Placental Perfusion on Birthweight in Women with Gestational Diabetes","volume":"29","author":"Bugatto","year":"2016","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"80","DOI":"10.4274\/tjod.55632","article-title":"Prediction of Adverse Pregnancy Outcomes Using Uterine Artery Doppler Imaging at 22\u201324 Weeks of Pregnancy: A North Indian Experience","volume":"13","author":"Verma","year":"2016","journal-title":"Turk. J. Obstet. Gynecol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1002\/uog.29145","article-title":"Role of Routine Uterine Artery Doppler at 18\u201322 and 24\u201328 Weeks\u2019 Gestation Following Routine First-Trimester Screening for Pre-Eclampsia","volume":"65","author":"Bonacina","year":"2025","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.orcp.2014.12.001","article-title":"The Predictive Value of the Uterine Artery Pulsatility Index during the Early Third Trimester for the Occurrence of Adverse Pregnancy Outcomes Depending on the Maternal Obesity","volume":"9","author":"Kim","year":"2015","journal-title":"Obes. Res. Clin. Pract."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2246","DOI":"10.1038\/s41366-020-0627-2","article-title":"Independent Influences of Maternal Obesity and Fetal Sex on Maternal Cardiovascular Adaptation to Pregnancy: A Prospective Cohort Study","volume":"44","author":"Teulings","year":"2020","journal-title":"Int. J. Obes."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1080\/14767050400028766","article-title":"The Association between Glucose Challenge Test, Obesity and Pregnancy Outcome in 6390 Non-Diabetic Women","volume":"17","author":"Yogev","year":"2005","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1097\/OGX.0b013e31828738ce","article-title":"Obesity in Pregnancy: A Big Problem and Getting Bigger","volume":"68","author":"Mission","year":"2013","journal-title":"Obstet. Gynecol. Surv."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.placenta.2018.05.011","article-title":"Altered Maternal and Placental Lipid Metabolism and Fetal Fat Development in Obesity: Current Knowledge and Advances in Non-Invasive Assessment","volume":"69","author":"Delhaes","year":"2018","journal-title":"Placenta"},{"key":"ref_52","first-page":"113","article-title":"Relationship between Maternal Age and Uterine Artery Doppler Velocimetry","volume":"20","author":"Chanthasenanont","year":"2012","journal-title":"Thai J. Obstet. Gynaecol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1002\/uog.14789","article-title":"Uterine Artery Pulsatility Index in the Three Trimesters of Pregnancy: Effects of Maternal Characteristics and Medical History","volume":"45","author":"Tayyar","year":"2015","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1002\/uog.12465","article-title":"Is There a Role for Cervical Assessment and Uterine Artery Doppler in the First Trimester of Pregnancy as a Screening Test for Spontaneous Preterm Delivery?","volume":"43","author":"Rencoret","year":"2014","journal-title":"Ultrasound Obstet. Gynecol."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/17\/2223\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:37:41Z","timestamp":1760035061000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/17\/2223"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,2]]},"references-count":54,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["diagnostics15172223"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics15172223","relation":{},"ISSN":["2075-4418"],"issn-type":[{"type":"electronic","value":"2075-4418"}],"subject":[],"published":{"date-parts":[[2025,9,2]]}}}