Donald School Journal of Ultrasound in Obstetrics and Gynecology

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VOLUME 15 , ISSUE 1 ( January-March, 2021 ) > List of Articles

REVIEW ARTICLE

Implantation and the Fetal Health

Aleksandar Ljubic, Dušica Ljubić, Tatjana Bozanovic

Citation Information : Ljubic A, Ljubić D, Bozanovic T. Implantation and the Fetal Health. Donald School J Ultrasound Obstet Gynecol 2021; 15 (1):81-86.

DOI: 10.5005/jp-journals-10009-1684

License: CC BY-NC 4.0

Published Online: 01-03-2021

Copyright Statement:  Copyright © 2021; The Author(s).


Abstract

Dysfunctional implantation and the formation of the placenta can endanger life and health of both the fetus and the mother, during prenatal life and decades after delivery. The changes that lead to the insufficient implantation should be sought in the preimplantation period, in relation between the embryo and the endometrium. Prepregnancy approaches such as weight management, blood pressure and blood sugar control, smoking cessation, and optimization of the pregnancy interval may improve implantation and placentation, and lead to better pregnancy outcomes. Gametes: The birefringence properties of the meiotic spindle and the zona pellucida are indicative of good health of the oocyte. Very useful data can be obtained from the application of studying gene expression from cumulus cells, using microarrays, as biomarkers for oocyte viability. The metabolomic profiling of oocyte spent culture media by mass spectroscopy has shown differences related to oocyte maturation, embryo development and implantation success. Oocyte quality can be assessed by the measurement of oocyte oxygen consumption. The role of the number and function of mitochondria in the development of quality oocytes is surely very important. The correction of the gene signaling, or autologous tissue genetic bioengineering is certainly a step forward in obtaining the quality gametes. The stem cells can be influenced by the stem cell therapy in order to obtain the intracellular communication with existing ovarian primordial oogonia. The sperm chromatin and DNA integrity are necessary to ensure normal embryo development. Magnetic-activated cell sorting technology for sperm could improve obstetric and perinatal outcomes. Embryo: The invasive technology means preimplantation genetic testing (PGT), the aneuploidy screening or diagnosis of specific genetic disorders of the embryo before the transfer by using next-generation sequencing (NGS). Noninvasive time-lapse embryo monitoring allows continuous embryo observation without the need to remove the embryo from optimal culturing conditions. Recently, the developed strategies including the genomic, transcriptomic, and proteomic approaches, have been applied in assisted reproduction. Their goal is to identify a “molecular profile” of embryo development by detecting the chemical components in the oocyte, granulosa cells, follicular fluid, and embryo culture medium. Endometrium: The medical treatment with estrogens, vasodilators, sildenafil citrate has neither led to significant improvements of morphological parameters nor to the results in terms of increasing of implantation and reduction of the number of miscarriages. There have been reports of trials with immunoglobulins and anticoagulants in pregnancy complication prevention, as well as the intrauterine administration of autologous peripheral blood mononuclear cells (PBMCs), especially when pretreated with corticotropin-releasing hormone (CRH) that acts by regulating apoptosis of activated T-lymphocytes at the implantation site. The quality of endometrial thickness, implantation rate and pregnancy success, and the reduction of the complications, miscarriage rate, is attempted by flushing uterus cavity with autologous platelet-rich plasma (PRP) in preparation for the implantation during IVF process.


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  1. Nicolaides K. A model for a new pyramid of prenatal care based on the 11 to 13 weeks’ assessment. Prenat Diagn 2011;31(1):3–6. DOI: 10.1002/pd.2685.
  2. Wright D, Syngelaki A, Bradbury I, et al. First-trimester screening for trisomies 21, 18 and 13 by ultrasound and biochemicaltesting. Fetal Diagn Ther 2014;35(2):118–126. DOI: 10.1159/000357430.
  3. Sonek JD, Cuckle HS. What will be the role of first-trimester ultrasound if cell-free DNA screening for aneuploidy becomes routine? Ultrasound Obstet Gynecol 2014;44(6):621–630. DOI: 10.1002/uog.14692.
  4. Renna MD, Pisani P, Conversano F, et al. Sonographic markers for early diagnosis of fetal malformations. World J Radiol 2013;5(10):356–371. DOI: 10.4329/wjr.v5.i10.356.
  5. Stoll C, Clementi M, Euroscan study group Prenatal diagnosis of dysmorphic syndromes by routine fetal ultrasound examination across Europe. Ultrasound Obstet Gynecol 2003;21(6):543–551. DOI: 10.1002/uog.125.
  6. Rydberg C, Tunón K. Detection of fetal abnormalities by second-trimester ultrasound screening in a non-selected population. Acta Obstet Gynecol Scand 2017;96(2):176–182. DOI: 10.1111/aogs.13037.
  7. Datta MR, Raut A. Efficacy of first-trimester ultrasound parameters for prediction of early spontaneous abortion. Int J Gynaecol Obstet 2017;138(3):325–330. DOI: 10.1002/ijgo.12231.
  8. Wu Y, He J, Guo C, et al. Serum biomarker analysis in patients with recurrent spontaneous abortion. Mol Med Rep 2017;16(3):2367–2378. DOI: 10.3892/mmr.2017.6890.
  9. Greco E, Lange A, Ushakov F, et al. Prediction of spontaneous preterm delivery from endocervical length at 11 to 13 weeks. Prenat Diagn 2011;31(1):84–89. DOI: 10.1002/pd.2640.
  10. Conde-Agudelo A, Romero R. Predictive accuracy of changes in transvaginal sonographic cervical length over time for preterm birth: a systematic review and metaanalysis. Am J Obstet Gynecol 2015;213(6):789–801. DOI: 10.1016/j.ajog.2015.06.015.
  11. Poon LC, Nicolaides KH. Early prediction of preeclampsia. Obstet Gynecol Int 2014;1:1–11. DOI: 10.1155/2014/297397.
  12. Akolekar R, Syngelaki A, Sarquis R, et al. Prediction of early, intermediate and late pre-eclampsia from maternal factors, biophysical and biochemical markers at 11–13 weeks. Prenat Diagn 2011;31(1):66–74. DOI: 10.1002/pd.2660.
  13. Mihailovič M, Cvetkovč M, Ljubič A, et al. Selenium and malondialdehyde content and glutathione peroxidase activity in maternal and umbilical cord blood and amniotic fluid. Biol Trace Elem Re 2000;73(1):47–54. DOI: 10.1385/BTER:73:1:47.
  14. Ćetković A, Miljic D, Ljubić A, et al. Plasma kisspeptin levels in pregnancies with diabetes and hypertensive disease as a potential marker of placental dysfunction and adverse perinatal outcome. Endocr Res 2012;37(2):78–88. DOI: 10.3109/07435800.2011.639319.
  15. Giguère Y, Charland M, Bujold E, et al. Combining biochemical and ultrasonographic markers in predicting preeclampsia: a systematic review. Clin Chem 2010;56(3):361–375. DOI: 10.1373/clinchem.2009.134080.
  16. Duley L, Henderson-Smart DJ, Meher S, et al. Antiplatelet agents for preventing pre-eclampsia and its complications. Cohrane Database Syst Rev 2007;2:CD0004659. DOI: 10.1002/14651858.CD004659.pub2.
  17. Karagiannis G, Akolekar R, Sarquis R, et al. Prediction of small-for-gestation neonates from biophysical and biochemical markers at 11-13 weeks. Fetal Diagn Ther 2011;29(2):148–154. DOI: 10.1159/000321694.
  18. Poon LCY, Karagiannis G, Stratieva V, et al. First-trimester prediction of macrosomia. Fetal Diagn Ther 2011;29(2):139–147. DOI: 10.1159/000318565.
  19. Baltaci V, Baltaci E. Genetic aspects of recurrent miscarriages. JSM Invitro Fertil 2016;1:1002.
  20. Chabra S. Estimates of perinatal death: a global initiative!. J Perinat 2017;37(11):1248. DOI: 10.1038/jp.2017.81.
  21. Rolnik DL, O’Gorman N, Roberge S, et al. Early screening and prevention of preterm pre-eclampsia with aspirin: time for clinical implementation. Ultrasound Obstet Gynecol 2017;50(5):551–556. DOI: 10.1002/uog.18899.
  22. Gregory EC, MacDorman MF, Martin JA. Trends in fetal and perinatal mortality in the United States, 2006-2012. NCHS Data Brief 2014;169:1–8.
  23. Ananth CV, Keyes KM, Wapner RJ. Pre-eclampsia rates in the United States, 1980-2010: Age-period-cohort analysis. BMJ 2013;347(nov07 15):f6564. DOI: 10.1136/bmj.f6564.
  24. Ljubić A. Inverted pyramid of prenatal care - is it enough? Should it be -extended inverted pyramid of prenatal care? J Perinat Med 2017;pii(7):/j/jpme.ahead-of-print/jpm-2016-0427/jpm-2016-0427.xml 10.1515/jpm-2016-0427.
  25. Urato AC, Norwitz ER. A guide towards pre-pregnancy management of defective implantation and placentation. Best Pract Res Clin Obstet Gynaecol 2011;25(3):367–387. DOI: 10.1016/j.bpobgyn.2011.01.003.
  26. Acharya S, Yasmin E, Balen AH. The use of a combination of pentoxifylline and tocopherol in women with a thin endometrium undergoing assisted conception therapies—a report of 20 cases. Hum Fertil (Camb) 2009;12(4):198–203. DOI: 10.3109/14647270903377178.
  27. Shen MS, Wang CW, Chen CH, et al. New horizon on successful management for a woman with repeated implantation failure due to unresponsive thin endometrium: use of extended estrogen supplementation. J Obstet Gynaecol Res 2013;39(5):1092–1094. DOI: 10.1111/j.1447-0756.2012.02070.x.
  28. Stephenson MD, Fluker MR. Treatment of repeated unexplained in vitro fertilization failure with intravenous immunoglobulin: a randomized, placebo-controlled Canadian trial. Fertil Steril 2000;74(6):1108–1113. DOI: 10.1016/S0015-0282(00)01622-8.
  29. Stern C, Chamley L, Norris H, et al. A randomized, double-blind, placebo-controlled trial of heparin and aspirin for women with in vitro fertilization implantation failure and antiphospholipid or antinuclear antibodies. Fertil Steril 2003;80(2):376–383. DOI: 10.1016/S0015-0282(03)00610-1.
  30. Boomsma CM, Keay SD, Macklon NS. Peri-implantation glucocorticoid administration for assisted reproductive technology cycles. Cochrane Data Base Syst Rev 2007. CD005996.
  31. Gelbaya TA, Kyrgiou M, Li TC, et al. Low-dose aspirin for in vitro fertilization: a systematic review and meta-analysis. Hum Reprod Update 2007;13(4):357–364. DOI: 10.1093/humupd/dmm005.
  32. Mekinian A, Cohen J, Alijotas-Reig J, et al. Unexplained recurrent miscarriage and recurrent implantation failure: Is there a place for immunomodulation? Am J Reprod Immunol 2016;76(1):8–28. DOI: 10.1111/aji.12493.
  33. Yu N, Zhang B, Xu M, et al. Intrauterine administration of autologous peripheral blood mononuclear cells (PBMCs) activated by hCG improves the implantation and pregnancy rates in patients with repeated implantation failure: a prospective randomized study. Am J Reprod Immunol 2016;76(3):212–216. DOI: 10.1111/aji.12542.
  34. Makrigiannakis A, BenKhalifa M, Vrekoussis T, et al. Repeated implantation failure: a new potential treatment option. Eur J Clin Invest 2015;45(4):380–384. DOI: 10.1111/eci.12417.
  35. Wurfel W. Treatment with granulocyte colony-stimulating factor in patients with repetitive implantation failures and/or recurrent spontaneous abortions. J Reprod Immunol 2015;108:123–135. DOI: 10.1016/j.jri.2015.01.010.
  36. Gleicher N, Vidali A, Barad DH. Successful treatment of unresponsive thin endometrium. Fertil Steril 2011;95(6):2123. DOI: 10.1016/j.fertnstert.2011.01.143.
  37. Chang Y, Li J, Chen Y, et al. Autologous platelet-rich plasma promotes endometrial growth and improves pregnancy outcome during in vitro fertilization. Int J Clin Exp Med 2015;8:1286–1290.
  38. Sumarac-Dumanovic M, Apostolovic M, Janjetovic K, et al. Downregulation of autophagy gene expression in endometria from women with polycystic ovary syndrome. Mol Cell Endocrinol 2016;440:116–124. DOI: 10.1016/j.mce.2016.11.009.
  39. Schoolcraft WB, Fragouli E, Stevens J, et al. Clinical application of comprehensive chromosomal screening at the blastocyst stage. Fertil Steril 2010;94(5):1700–1706. DOI: 10.1016/j.fertnstert.2009.10.015.
  40. Schoolcraft WB, Treff NR, Stevens JM, et al. Live birth outcome with trophectoderm biopsy, blastocyst vitrification, and single-nucleotide polymorphism microarray-based comprehensive chromosome screening in infertile patients. Fertil Steril 2011;96(3):638–640. DOI: 10.1016/j.fertnstert.2011.06.049.
  41. Bisignano A, Wells D, Harton G, et al. PGD and aneuploidy screening for 24 chromosomes: advantages and disadvantages of competing platforms. Reprod Biomed Online 2011;23(6):677–685. DOI: 10.1016/j.rbmo.2011.05.017.
  42. Wong CC, Loewke KE, Bossert NL, et al. Non-invasive imaging of human embryos before embryonic genome activation predicts development to the blastocyst stage. Nat Biotechnol 2010;28(10):1115–1121. DOI: 10.1038/nbt.1686.
  43. Kirkegaard K, Ahlström A, Ingerslev HJ, et al. Choosing the best embryo by time lapse versus standard morphology. Fertil Steril 2015;103(2):323–332. DOI: 10.1016/j.fertnstert.2014.11.003.
  44. Yang Z, Zhang J, Salem SA, et al. Selection of competent blastocysts for transfer by combining time-lapse monitoring and array CGH testing for patients undergoing preimplan- tation genetic screening: a prospective study with sibling oocytes. BMC Med Genomics 2014;7(1):38. DOI: 10.1186/1755-8794-7-38.
  45. Armstrong S, Arroll N, Cree LM, et al. Time-lapse systems for embryo incubation and assessment in assisted reproduction. Cochrane Database Syst Rev 2015;2:CD011320. DOI: 10.1002/14651858.CD011320.pub2.
  46. Seli E, Robert C, Sirard MA. OMICS in assisted reproduction: possibilities and pitfalls. Mol Hum Reprod 2010;16(8):513–530. DOI: 10.1093/molehr/gaq041.
  47. Menezo Y, Elder K, Benkhalifa M, et al. DNA methylation and gene expression in IVF. Reprod Biomed Online 2010;20(6):709–710. DOI: 10.1016/j.rbmo.2010.02.016.
  48. Nagy ZP, Jones-Colon S, Roos P, et al. Metabolomic assessment of oocyte viability. Reprod Biomed Online 2009;18(2):219–225. DOI: 10.1016/S1472-6483(10)60259-3.
  49. Tejera A, Herrero J, de Los Santos MJ, et al. Oxygen consumption is a quality marker for human oocyte competence conditioned by ovarian stimulation regimens. Fertil Steril 2011;96(3):618–623. DOI: 10.1016/j.fertnstert.2011.06.059.
  50. Evgeni E, Byron A. Human sperm DNA fragmentation and its correlation with conventional semen parameters. J Reprod Infertil 2014;15(1):2–14.
  51. Leach M, Aitken R, Sacks G, et al. Fragmentation abnormalities in men from couples with a history of recurrent miscarriage. Aust N Z J Obstet Gynaecol 2015;55(4):379–383. DOI: 10.1111/ajo.12373.
  52. Gil M, Shalom V, Carreras S. Sperm selection using magnetic activated cell sorting (MACS) in assisted reproduction: a systematic review and meta-analysis. J Assist Reprod Genet 2013;30(4):479–485. DOI: 10.1007/s10815-013-9962-8.
  53. Cheng Y, Feng Y, Jansson L, et al. Actin polymerization-enhancing drugs promote ovarian follicle growth mediated by the Hippo signaling effector YAP. FASEB J 2015;29(6):2423–2430. DOI: 10.1096/fj.14-267856.
  54. Johnson J, Canning J, Kaneko T, et al. Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature 2004;428(6979):145–150. DOI: 10.1038/nature02316.
  55. Afifi N, Reyad O. Role of mesenchymal stem cell therapy in restoring ovarian function in a rat model of chemotherapy-induced ovarian failure: a histological and immunohistochemical study. Egypt J Histol 2013;36(1):114–126. DOI: 10.1097/01.EHX.0000423979.18253.10.
  56. Hayashi K, Ogushi S, Kurimoto K, et al. Offspring from oocytes derived from in vitro primordial germ cell–like cells in mice. Science 2012;338(6109):971–975. DOI: 10.1126/science.1226889.
  57. Callejo J, Salvador C, González-Nuñez S, et al. Live birth in a woman without ovaries after autograft of frozen-thawed ovarian tissue combined with growth factors. J Ovarian Res 2013;6(1):33. DOI: 10.1186/1757-2215-6-33.
  58. Smeets HJ. Preventing the transmission of mitochondrial DNA disorders: selecting the good guys or kicking out the bad guys. Reprod Biomed Online 2013;27(6):599–610. DOI: 10.1016/j.rbmo.2013.08.007.
  59. Amato P, Tachibana M, Sparman M, et al. Three-parent in vitro fertilization: gene replacement for the prevention of inherited mitochondrial diseases. Fertil Steril 2014;101(1):31–35. DOI: 10.1016/j.fertnstert.2013.11.030.
  60. Mitalipov S, Wolf DP. Clinical and ethical implications of mitochondrial gene transfer. Trends Endocrinol Metab 2014;25(1):5–7. DOI: 10.1016/j.tem.2013.09.001.
  61. Kawamura K, Cheng Y, Suzuki N, et al. Hippo signaling disruption and AKT stimulation of ovarian follicles for infertility treatment. PNAS 2013;110(43):17474–17479. DOI: 10.1073/pnas.1312830110.
  62. Ljubić A, Abazović D, Vučetić D, et al. Autologous ovarian in vitro activation with ultrasound-guided orthotopic re-transplantation. Am J Clin Exp Obstet Gynecol 2017;4:51–57. (In press).
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