In spite of substantial scientific progress achieved during the past half century, there are still many features of abortion waiting to enter clinical obstetrics. The main pathogenic mechanism of pregnancy failure is still largely ignored or misinterpreted. As a consequence, there is a high and increasing rate of wrongly managed recurrent abortion. The so called ‘guidelines’, indeed, reflect the widespread ignorance of the significant scientific progress, thus hindering its application in clinical practice.
For a correct therapy the following statements should be undertstood:
1) There is no convincing evidence of a significant role of progesterone neither in the prevention nor in the cure of abortion. Although the hormone is needed to prepare the uterine mucosa for implantation, its administration in the clinical management of abortion should be abandoned, as I did over forty years ago.
2) Although infection can cause abortion, it rarely occurs. There is sound evidence in the literature on the absence of bacterial and viral role in the pathogenic mechanism of abortion.
3) There is sound evidence of a leading role of inflammation in the pathogrnic mechanism of abortion.
4) Thyroid function does not have any direct relation with the abortion pathogenic mechanism.
5) There is no convincing evidence of a role of vitamin D in the protection of pregnancy.
6) Although some maternal diseases are linked with an increased incidence of abortion, successful pregnancies can occur in these patients, privided that the fetus is able to overcome maternal rejection.
7) As modulation of maternal organism is a foetal task, therapy of either sporadic or recurrent abortion should be addressed to the foetus.
8) Obstetrical Inflammation is to be considered as an imbalance of citokines and prostanoids. It represents the leading cause of either euploid or aneuploid both sporadic and recurrent abortion.
Explanation of the above mentioned statements is largely reported in several papers authored by myself and others. The main articles are listed below. It is my intention to explain little by little, in future chapters, the leading reasons for a correct prevention and management of abortion and the other inflammatory complications of pregnancy. Furthermore it is possible to consult me for specific problems by mail or by phone at the following addresses:
Prof. Fortunato Vesce
Via del pozzo, 2
44121 Ferrara
Italia
+39 366 9775874
ves@unife.it
BIBLIOGRAPHY
The articles listed below represent a small part of the relevant literature addressed to explain the reason for a correct management of pregnancy complications.
SKirrat GM1. Recurrent miscarriage.
Lancet 1990 Se15;336(8716):673-5.
kwak-kim J, Yang K M, Gilman-Sachs A. Recurrent pregnancy loss: a disease of inflammation and coagulation. J Obstet Gynaecol Res 2009 Aug; 35(4):609-22
Lunghi L, Ferretti ME, Medici S, Biondi C, Vesce F. Control of human trophoblast function. Reprod Biol Endocrinol. 2007 Feb 8;5:6
Lunghi L1, Pavan B, Biondi C, Paolillo R, Valerio A, Vesce F, Patella A. Use of glucocorticoids in pregnancy. Curr Pharm Des. 2010;16(32):3616-37
Vesce F, Giugliano E, Cagnazzo E., Bignardi S., Mossuto E., Servello T., Marci R. The role of glucocorticoids in pregnancy: four decades experience with use of betamethasone in the prevention of pregnancy loss. In “Glucocorticoids. New recognition of our familiar friend”. Edited by Xiaoxiao Qian, INTECH, November 2012, Croatia, pag 407-48
Raghupathy R1. Th1-type immunity is incompatible with successful pregnancy.
Immunol Today. 1997 Oct;18(10):478-82
Makhseed M1, Raghupathy R, Azizieh F, Omu A, Al-Shamali E, Ashkanani L. Th1 and Th2 cytokine profiles in recurrent aborters with successful pregnancy and with subsequent abortions. Hum Reprod. 2001 Oct;16(10):2219-26
Queenby S, Farquharson R, Young M, Vince G. Successful pregnancy outcome following 19 consecutive miscarriages: case report. Hum Reprod (2003)18:2562-4
Vesce F, Scapoli C, Giovannini G, Tralli L, Gotti G, Valerio A, Piffanelli A.
Cytokine imbalance in pregnancies with fetal chromosomal abnormalities. Hum Reprod. 2002 Mar;17(3):803-8.
Vesce F, Scapoli C, Giovannini G, Piffanelli A, Geurts-Moespot A, Sweep FC.
Plasminogen activator system in serum and amniotic fluid of euploid and aneuploid pregnancies. Obstet Gynecol. 2001 Mar;97(3):404-8
Vesce F, Farina A, Jorizzo G, Tarabbia C, Calabrese O, Pelizzola D, Giovannini G, Piffanelli A. Raised level of amniotic endothelin in pregnancies with fetal aneuploidy. Fetal Diagn Ther. 1996 Mar-Apr;11(2):94-8
Laresgoiti-Servitje E1, Gómez-López N, Olson DM. An immunological insight into the origins of pre-eclampsia. Hum Reprod Update. 2010
Sep-Oct;16(5):510-24
Sidhu R. K. Corticosteroids in pregnancy. In Drugs and Pregnancy, Edited by D. F. Hawkins. Chapter 11, 166-79 CHURCHILL LIVINGSTONE 1987
Hankins GD, Clark SM, Munn MB. Cesarean section on request at 39 weeks: impact on shoulder dystocia, fetal trauma, neonatal encephalopathy, and intrauterine fetal demise. Semin Perinatol. 2006 Oct;30(5):276-87.
Hunt J S, Chen H L, Miller l. Tumor necrosis factors: pivotal components of pregnancy? Biol Reprod 1996; 54 (3):554-63.
Serum IgG Antibodies from Pregnant Women Reacting to Mimotopes of Simian Virus 40 Large T Antigen, the Viral Oncoprotein.
Mazzoni E, Di Stefano M, Fiore JR, Destro F, Manfrini M, Rotondo JC, Casali
MV, Vesce F, Greco P, Scutiero G, Martini F, Tognon MG.
Front Immunol. 2017 Apr 10;8:411. doi: 10.3389/fimmu.2017.00411. eCollection
Influence of vaginal lactoferrin administration on amniotic fluid cytokines and its role against inflammatory complications of pregnancy.
Maritati M, Comar M, Zanotta N, Seraceni S, Trentini A, Corazza F, Vesce F,
Contini C. J Inflamm (Lond). 2017 Feb 15;14:5. doi: 10.1186/s12950-017-0152-9. eCollection 2017.
Vaginal Lactoferrin Modulates PGE2, MMP-9, MMP-2, and TIMP-1 Amniotic
Fluid Concentrations. Trentini A, Maritati M, Cervellati C, Manfrinato MC, Gonelli A, Volta CA, Vesce F, Greco P, Dallocchio F, Bellini T, Contini C.
Mediators Inflamm. 2016;2016:3648719. Epub 2016 Oct 31.
The behaviour of the peripheral natural killer cells in the foetal growth
restriction. Vesce F, Cagnazzo E, Giugliano E, Mossuto E, Marci R. Eur Rev Med Pharmacol Sci. 2014 Aug;18(16):2248-52.
The risk factors for failure of labor induction: a cohort study.
Giugliano E, Cagnazzo E, Milillo V, Moscarini M, Vesce F, Caserta D, Marci R.
J Obstet Gynaecol India. 2014 Apr;64(2):111-5. doi: 10.1007/s13224-013-0486-z. Epub 2013 Dec 1.
Vaginal lactoferrin administration before genetic amniocentesis decreases
amniotic interleukin-6 levels. Vesce F, Giugliano E, Bignardi S, Cagnazzo E, Colamussi C, Marci R, Valente N, Seraceni S, Maritati M, Contini C. Gynecol Obstet Invest. 2014;77(4):245-9. doi: 10.1159/000358877. Epub 2014 Mar 7.
Low dose of betamethasone throughout the whole course of pregnancy and fetal growth: a clinical study. Vesce F, Giugliano E, Cagnazzo E, Mossuto E, Marci R. Eur Rev Med Pharmacol Sci. 2014;18(4):593-8.
Can Doppler study of the ovarian artery predict the fertility outcome of
intrauterine insemination? Giugliano E, Cagnazzo E, Giugliano B, Vesce F, Caserta D, Moscarini M, Marci R. J Clin Ultrasound. 2014 Jul-Aug;42(6):331-5. doi: 10.1002/jcu.22140. Epub 2014 Feb 13.
Methylation loss at H19 imprinted gene correlates with methylenetetrahydrofolate reductase gene promoter hypermethylation in semen samples from infertile males. Rotondo JC, Selvatici R, Di Domenico M, Marci R, Vesce F, Tognon M, Martini F. Epigenetics. 2013 Sep;8(9):990-7. doi: 10.4161/epi.25798. Epub 2013 Jul 24.
17-β-Estradiol counteracts the effects of high frequency electromagnetic fields on trophoblastic connexins and integrins. Cervellati F, Valacchi G, Lunghi L, Fabbri E, Valbonesi P, Marci R, Biondi C, Vesce F. Oxid Med Cell Longev. 2013;2013:280850. doi: 10.1155/2013/280850. Epub 2013 May 30.
Downregulation of A(1) and A(2B) adenosine receptors in human trisomy 21 mesenchymal cells from first-trimester chorionic villi. Gessi S, Merighi S, Stefanelli A, Mirandola P, Bonfatti A, Fini S, Sensi A, Marci R, Varani K, Borea PA, Vesce F. Biochim Biophys Acta. 2012 Nov;1822(11):1660-70. doi:
10.1016/j.bbadis.2012.07.013. Epub 2012 Jul 31.
Betamethasone, progesterone and RU-486 (mifepristone) exert similar effects on connexin expression in trophoblast-derived HTR-8/SVneo cells.
Cervellati F, Pavan B, Lunghi L, Manni E, Fabbri E, Mascoli C, Biondi C, Patella A, Vesce F. Reprod Fertil Dev. 2011;23(2):319-28. doi: 10.1071/RD10077.
Use of glucocorticoids in pregnancy. Lunghi L, Pavan B, Biondi C, Paolillo R, Valerio A, Vesce F, Patella A. Curr Pharm Des. 2010;16(32):3616-37. Review.
cAMP efflux from human trophoblast cell lines: a role for multidrug resistance protein (MRP)1 transporter. Biondi C, Ferretti ME, Lunghi L, Medici S, Cervellati F, Pavan B, Vesce F, Morano D, Adinolfi E, Bertoni F, Abelli L. Mol Hum Reprod. 2010 Jul;16(7):481-91. doi: 10.1093/molehr/gaq023. Epub 2010 Mar 15.
Effect of high-frequency electromagnetic fields on trophoblastic connexins.
Cervellati F, Franceschetti G, Lunghi L, Franzellitti S, Valbonesi P, Fabbri E,
Biondi C, Vesce F. Reprod Toxicol. 2009 Jul;28(1):59-65. doi: 10.1016/j.reprotox.2009.03.010. Epub 2009 Apr 5.
Somatostatin as a regulator of first-trimester human trophoblast functions.
Biondi C, Ferretti ME, Lunghi L, Medici S, Cervellati F, Abelli L, Bertoni F,
Adinolfi E, Vesce F, Bartolini G, Papi A, D’Andrea S, Berton S, Baldassarre G.
Placenta. 2008 Aug;29(8):660-70. doi: 10.1016/j.placenta.2008.05.009. Epub 2008 Jul 9.
Control of human trophoblast function. Lunghi L, Ferretti ME, Medici S, Biondi C, Vesce F. Reprod Biol Endocrinol. 2007 Feb 8;5:6. Review.
Expression and characterization of vitamin C transporter in the human
trophoblast cell line HTR-8/SVneo: effect of steroids, flavonoids and NSAIDs.
Biondi C, Pavan B, Dalpiaz A, Medici S, Lunghi L, Vesce F. Mol Hum Reprod. 2007 Jan;13(1):77-83. Epub 2006 Nov 8.
Evidence for the presence of N-formyl-methionyl-leucyl-phenylalanine (fMLP) receptor ligands in human amniotic fluid and fMLP receptor modulation by physiological labour. Biondi C, Pavan B, Dalpiaz A, Valerio A, Spisani S, Vesce F. J Reprod Immunol. 2005 Dec;68(1-2):71-83. Epub 2005 Oct 19.
Prostaglandin E2 inhibits proliferation and migration of HTR-8/SVneo cells, a human trophoblast-derived cell line. Biondi C, Ferretti ME, Pavan B, Lunghi L, Gravina B, Nicoloso MS, Vesce F, Baldassarre G. Placenta. 2006 Jun-Jul;27(6-7):592-601. Epub 2005 Sep 12.
The role and modulation of the oxidative balance in pregnancy. Biondi C, Pavan B, Lunghi L, Fiorini S, Vesce F. Curr Pharm Des. 2005;11(16):2075-89. Review.
Inhibition of amniotic interleukin-6 and prostaglandin E2 release by ampicillin.Vesce F, Pavan B, Lunghi L, Giovannini G, Scapoli C, Piffanelli A, Biondi C. Obstet Gynecol. 2004 Jan;103(1):108-13.
Interactions between the nitric oxide and prostaglandin E2 biosynthetic
pathways in human amnion-like WISH cells. Biondi C, Fiorini S, Pavan B, Ferretti ME, Barion P, Vesce F. J Reprod Immunol. 2003 Oct;60(1):35-52.
Antenatal manifestation of congenital pancreatoblastoma in a fetus with
Beckwith-Wiedemann syndrome. Pelizzo G, Conoscenti G, Kalache KD, Vesce F, Guerrini P, Cavazzini L. Prenat Diagn. 2003 Apr;23(4):292-4. Erratum in: Prenat Diagn. 2003 Sep;23(9):771.
WISH cells as a model for the “in vitro” study of amnion pathophysiology.
Pavan B, Fiorini S, Ferretti ME, Vesce F, Biondi C. Curr Drug Targets Immune Endocr Metabol Disord. 2003 Mar;3(1):83-92. Review.
Effect of nitric oxide on arachidonic acid release from human amnion-like
WISH cells. Biondi C, Fiorini S, Boarini I, Barbin L, Cervellati F, Ferretti ME, Vesce F. Placenta. 2002 Sep-Oct;23(8-9):575-83.
Formyl-methionyl-leucyl-phenylalanine induces prostaglandin E2 release from human amnion-derived WISH cells by phospholipase C-mediated [Ca+]i rise. Biondi C, Pavan B, Ferretti ME, Corradini FG, Neri LM, Vesce F.
Biol Reprod. 2001 Mar;64(3):865-70.
Influence of oxytocin on prostaglandin E2, intracellular calcium, and cyclic
adenosine monophosphate in human amnion-derived (WISH) cells. Pavan B, Buzzi M, Ginanni-Corradini F, Ferretti ME, Vesce F, Biondi C. Am J Obstet Gynecol. 2000 Jul;183(1):76-82.
Use of the copper intrauterine device in the management of secondary
amenorrhea. Vesce F, Jorizzo G, Bianciotto A, Gotti G.Fertil Steril. 2000 Jan;73(1):162-5.
Effect of different classes of antibiotics on amniotic prostaglandin E release.
Vesce F, Pavan B, Buzzi M, Pareschi MC, Bianciotto A, Iorizzo G, Biondi C. Prostaglandins Other Lipid Mediat. 1999 Jun;57(4):207-18.
Evaluation of intrauterine growth pattern of twins by linear discriminant
analysis of the values of biparietal diameter, femur length and abdominal
circumference1. Farina A, Vesce F, Garutti P, Jorizzo G, Bianciotto A. Gynecol Obstet Invest. 1999;48(1):14-7.
Does formyl-methionyl-leucyl-phenylalanine exert a physiological role in labor in women? Buzzi M, Vesce F, Ferretti ME, Fabbri E, Biondi C. Biol Reprod. 1999 May;60(5):1211-6.
Inhibition of amniotic prostaglandin E release by ampicillin. Vesce F, Buzzi M, Ferretti ME, Pavan B, Bianciotto A, Jorizzo G, Biondi C. Am J Obstet Gynecol. 1998 Apr;178(4):759-64.
Increased incidence of preeclampsia in pregnancies complicated by fetal malformation. Vesce F, Farina A, Giorgetti M, Jorizzo G, Bianciotto A, Calabrese O, Mollica G. Gynecol Obstet Invest. 1997;44(2):107-11.
Pemphigus in pregnancy. Virgili A, Corazza M, Vesce F, Garutti P, Mollica G, Califano A. Acta Derm Venereol. 1995 Mar;75(2):172-3. No abstract available.
The controversial role of cAMP on amnionic prostaglandin release: effect of
adenylate cyclase inhibition. Vesce F, Biondi C, Ferretti ME, Pareschi MC, Buzzi M, Colamussi ML. Gynecol Obstet Invest. 1995;40(2):73-9.
Modulation of amnionic adenylate cyclase and cAMP phosphodiesterase by prostaglandins E1 and F2 alpha. Vesce F, Tarabbia C, Farina A, Travagli S, Pareschi MC, Portolan A, Biondi C. Gynecol Obstet Invest. 1994;37(2):77-82.
Epidermal growth factor stimulation of lecithin release by human amnion. Vesce F, Biondi C, Ferretti ME, Pareschi MC, Cavallaro R, Buzzi M, Farina A. Gynecol Obstet Invest. 1994;38(2):100-3.
Betamethasone-induced lecithin release in vitro from the fetal membranes. Vesce F, Pareschi MC, Travagli S, Tarabbia C, Pansini F, Salvatorelli G, Gulinati AM, Grandi E, Biondi C. Gynecol Obstet Invest. 1992;33(3):134-7.
Contribution to the assessment of steroid therapy in the prevention of respiratory distress syndrome in the neonate. Guerrini P, Vesce F, Colla F, Travagli S, Cocilovo G. Clin Exp Obstet Gynecol. 1990;17(3-4):145-9.
Studies on amniotic prolactin: chromatographic pattern and correlation with the lecithin content. Pansini F, Bergamini CM, Bagni B, Linciano M, Condemi L, Bonaccorsi G, Vesce F. Gynecol Obstet Invest. 1989;27(3):126-8.
Prenatal diagnosis of cystic adenomatoid malformation of the lung. Vesce F, Garutti P, Grandi E, Perri G, Altavilla G. Clin Exp Obstet Gynecol. 1989;16(4):121-5.
Adenylate cyclase and cyclic AMP-phosphodiesterase activities of fetal membranes: effect of insulin. Vesce F, Biondi C, Portolan A, Condemi L, Travagli S, Campi AL, Colla F. Clin Exp Obstet Gynecol. 1989;16(2-3):65-72.
Conservative management of urinary abnormalities detected in utero. Chierici R, Riccipetitoni G, Tamisari L, Vesce F, Zanella B, Merlo L, Vigi V. Fetal Ther. 1989;4(1):43-8.
Ultrasonographic diagnosis of ectasia of the umbilical vein. Vesce F, Guerrini P, Perri G, Cavazzini L, Simonetti V. J Clin Ultrasound. 1987 Jun;15(5):346-9. No abstract available.
Sonographic picture of submembranous haematoma. Vesce F, Cocilovo G, Simonetti V. Clin Exp Obstet Gynecol. 1985;12(3-4):90-2.
alpha-L-fucosidase activity in endometrial, cervical and ovarian cancer. Vesce F, Biondi C. Eur J Gynaecol Oncol. 1983;4(2):135-8.
Amniotic fluid beta 2-microglobulin (beta 2-m) as an index of fetal maturity. Vesce F, Cocilovo G, Tataranni G, Guzzinati N, Logallo G. Clin Exp Obstet Gynecol. 1981;8(2):66-9.
