Abstract:Objective Due to the promiscuous secretion of progesterone by both the ovarian corpus luteum and embryonic trophoblasts, it is unclear when human embryonic trophoblasts begin to synthesize and secrete progesterone independently during gestation.The aim of this study was to investigate dynamic changes of progesterone secreted by embryonic trophoblast independently in human serum and the time it begins to take effect for luteal support. Methods This study was performed as a prospective cohort study in the Reproductive Hospital of Guangxi Zhuang Autonomous Region in 2019.Patients, aged 20~40 years old, who had regular menstrual cycles, and underwent frozen-thawed embryo transfer were included.Natural cycle(group NC) and hormone replacement treatment(group HRT) were grouped according to endometrial preparation.Serum concentration of progesterone and β-human chorionic gonadotropin(HCG) were dynamically monitored after transplantation by Roche Elecsys electrochemiluminescence immunoassay(Elecsys ECLIA). Results Concentration of progesterone showed a significant growth trend in HRT group(P<0.05).Embryonic trophoblast cells began to secrete a small amount of progesterone since 14-21 days after transplantation, while it reached relatively abundant at 28 days after transplantation.There was no significant change in serum progesterone at 7, 14, 21, 28, and 35 days after transplantation in group NC.The progesterone concentration in group NC were significantly higher than those in group HRT(P<0.05). Conclusion A small amount of progesterone secreted by embryo trophoblasts could be detected in serum since 14-21 days after transplantation.Progesterone concentration increased significantly at 28 days after transplantation.Therefore, it is recommended to consider adjusting the dosage of exogenous luteal support 28 days after embryo transplantation.
李洁, 莫似恩, 王书佳, 莫馥华, 乃东红. 人胚胎滋养细胞独立合成并分泌孕酮时间的探讨[J]. 中国生育健康杂志, 2023, 34(6): 508-513.
LI Jie, MO Sien, WANG Shujia, MO Fuhua, NAI Donghong. Study on the time of independent synthesis and secretion of progesterone by human embryonic trophoblast cells. Chinese Journal of Reproductive Health, 2023, 34(6): 508-513.
1 Practice Committee of the American Society for Reproductive Medicine.Performing the embryo transfer:a guideline.Practice Committee of the American Society for Reproductive Medicine.Fertil Steril,2017,107:882-896. 2 Csapo AI,Pulkkinen MO,Ruttner B,et al.The significance of the human corpus luteum in pregnancy maintenance.Am J Obstet Gynecol ,1972,112 :1061-1067. 3 Duncan WC.The inadequate corpus luteum.Reprod Fertil,2021,26;2:C1-C7. 4 Devoto L,Henríquez S,Kohen P,et al.The significance of estradiol metabolites in human corpus luteum physiology.Steroids,2017,123:50-54. 5 Neumann K,Depenbusch M,Schultze-Mosgau A,et al.Characterization of early pregnancy placental progesterone production by use of dydrogesterone in programmed frozen-thawed embryo transfer cycles.Reprod Biomed Online,2020,40:743-751. 6 Fedotcheva TA.Clinical Use of Progestins and Their Mechanisms of Action:Present and Future(Review).Sovrem Tekhnologii Med,2021,13:93-106. 7 Bai L,Chang HM,Zhu YM,et al.Bone morphogenetic protein 2 increases lysyl oxidase activity via up-regulation of snail in human granulosa-lutein cells.Cell Signal,2019,53:201-211. 8 Griesinger G,Blockeel C,Tournaye H.Oral dydrogesterone for luteal phase support in fresh in vitro fertilization cycles:a new standard?.Fertil Steril,2018,109:756-762. 9 Saharkhiz N,Zamaniyan M,Salehpour S,et al.A comparative study of dydrogesterone and micronized progesterone for luteal phase support during in vitro fertilization(IVF) cycles.Gynecol Endocrinol,2016,32:213-217. 10 Griesinger G,Blockeel C,Sukhikh GT,et al.Oral dydrogesterone versus intravaginal micronized progesterone gel for luteal phase support in IVF:a randomized clinical trial.Hum Reprod,2018,33:2212-2221. 11 Hoffmann V,Pedersen PA,Philip J,et al.The effect of dydrogesterone on premenstrual symptoms.A double-blind,randomized,placebo-controlled study in general practice.Scand J Prim Health Care,1988,6:179-183. 12 Fu J,Song H,Zhou M,et al.Progesterone receptor modulators for endometriosis.Cochrane Database Syst Rev,2017,7:CD009881. 13 Devall AJ,Papadopoulou A,Podesek M,et al.Progestogens for preventing miscarriage:a network meta-analysis.Cochrane Database Syst Rev,2021,4:CD013792. 14 Yasuda K,Sumi GI,Murata H,et al.The steroid hormone dydrogesterone inhibits myometrial contraction independently of the progesterone/progesterone receptor pathway.Life Sci,2018,207:508-515. 15 Lee HJ,Park TC,Kim JH,et al.The Influence of Oral Dydrogesterone and Vaginal Progesterone on Threatened Abortion:A Systematic Review and Meta-Analysis.Biomed Res Int,2017,2017:3616875. 16 Wang S,Wang XT,Liu RH,et al.Dydrogesterone has no effect on uterine fibroids when used to prevent miscarriage in pregnant women with uterine fibroids.Ginekol Pol,2017,88:679-685. 17 Raghupathy R,Szekeres-Bartho J.Dydrogesterone and the immunology of pregnancy.Horm Mol Biol Clin Investig,2016,27:63-71. 18 Schindler AE.Progestational effects of dydrogesterone in vitro,in vivo and on the human endometrium.Maturitas,2009,65 Suppl 1:S3-11. 19 Dashti S,Eftekhar M.Luteal-phase support in assisted reproductive technology:An ongoing challenge.Int J Reprod Biomed,2021,19:761-772. 20 Baldini D,Savoia MV,Sciancalepore AG,et al.High progesterone levels on the day of HCG administration do not affect the embryo quality and the reproductive outcomes of frozen embryo transfers.Clin Ter,2018,169:e91-e95. 21 Tomic V,Tomic J,Klaic DZ,et al.Oral dydrogesterone versus vaginal progesterone gel in the luteal phase support:randomized controlled trial.Eur J Obstet Gynecol Reprod Biol,2015,186:49-53. 22 Beranič N,Lanišnik Riner T.Progestin effects on expression of AKR1C1-AKR1C3,SRD5A1 and PGR in the Z-12 endometriotic epithelial cell line.Chem Biol Interact,2013,202:218-225. 23 Kuhl H.Pharmacology of estrogens and progestogens:influence of different routes of administration.Climacteric,2005,8 Suppl 1:3-63. 24 Beranič N,Broič P,Brus B,et al.Expression of human aldo-keto reductase 1C2 in cell lines of peritoneal endometriosis:potential implications in metabolism of progesterone and dydrogesterone and inhibition by progestins.J Steroid Biochem Mol Biol,2012,130:16-25. 25 Thomsen LH,Kesmodel US,Erb K,et al.The impact of luteal serum progesterone levels on live birth rates-a prospective study of 602 IVF/ICSI cycles.Hum Reprod,2018,33:1506-1516. 26 Toorop GP.Progestational activity of dydrogesterone and its main metabolite,progesterone and medroxyprogesterone in the rabbit.Study,1991,No.H.102.104. 27 Böcker C,Husen B,Reinders JH.The effects of dydrogesterone(DYD) in 4 human nuclear receptor binding assays,in comparison to the effects of dydrogesterone metabolite 20α-hydroxydydrogesterone(DHD) and progesterone(P).Solvay Pharmaceuticals Report Study,2007,No.S102.5.001. 28 Saccone G,Schoen C,Franasiak JM,et al.Supplementation with progestogens in the first trimester of pregnancy to prevent miscarriage in women with unexplained recurrent miscarriage:a systematic review and meta-analysis of randomized,controlled trials.Fertil Steril,2017,107:430-438.e3. 29 Vaisbuch E,de Ziegler D,Leong M,et al.Luteal-phase support inassisted reproduction treatment:real-life practices reported worldwide by an updated website-based survey.Reprod Biomed Online,2014,28:330-335. 30 Engler-Chiurazzi EB,Singh M,Simpkins JW.Reprint of:From the 90's to now:A brief historical perspective on more than two decades of estrogen neuroprotection.Brain Res,2016,1645:79-82.