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PREGNANCY SAFETY: L-ARGININE
Dr. Niranjan Chavan
MD, FCPS, DGO, DFP, MICOG, DICOG, FICOG
Professor and Unit Chief, L.T.M.M.C & L.T.M.G.H
Chairperson, FOGSI Oncology and TT Committee (2012-2014)
Treasurer, MOGS (2017- 2018)
Chair and Convener, FOGSI Cell- Violence against Doctors (2015-2016)
Chief Editor, AFG Times (2015-2017)
Editorial Board, European Journal of Gynecologic Oncology
Editor of FOGSI FOCUS, MOGS, AFG & IAGE Newsletters
Member, Managing Committee, IAGE (2013-2017)
Member , Oncology Committee, AOFOG (2013 -2015)
Recipient of 6 National & International Awards
Author of 15 Research Papers and 19 Scientific Chapters
Course Co-Ordinator, of 11 batches, of MUHS recognized Certificate Course of
Basic Infertility Management Including Endoscopy (BIMIE) at LTMGH
• Arginine (abbreviated as Arg or R)
• Semiessential or conditionally essential amino acid
• Important role in cell division, the healing of wounds,
removing ammonia from the body, immune function, and
the release of hormones
• L-arginine is generally recognized as safe (GRAS-status) at
intakes of up to 20 g/d
L – ARGININE TRANSFER AND METABOLISM
• L - arginine are released into the fetal
circulation from fetal tissues
• Disposal of fetal amino acid is divided into
direct flux back into the placenta and flux into
fetal tissues
• This flux is further divided into l arginine
oxidation and protein synthesis which can be
further degraded
L -
Arginine
Reduces diastolic BP
in Pre - eclampsia
Benfits in IUGR
Luteal phase defect
Oligohydramnios
L-ARGININE IN PRE - ECLAMPSIA
• According to NICE guidelinea,Pre-
eclampsia is new hypertension
presenting after 20 weeks with
significant proteinuria
• In the absence of proteinuria,
hypertension together with evidence of
systemic disease (such as
thrombocytopenia or elevated levels of
liver transaminases) is required for
diagnosis.
• Complicates 10-17% of pregnancy
INTRODUCTION
In pre eclampsia , due to abnormal invasion, there is placental
ischemia & endothelial dysfunction and decreased NO – leading to
increased peripheral resistance and HTN
L – arginine is a nitrous oxide (NO) donor
vasodilatation
Improves placental
circulation
Decreases oxidative stress
• Increases diastolic BP
• Improves renal function : decreases proteinuria
• Decreases risk of IUGR
• Facchinetti et al.’s study had demonstrated that the L-arginine supplement could
significantly decrease blood pressure in preeclampsia patients
• According to meta-analysis of the various studies, L-arginine supplementation is
superior to placebo in lowering diastolic pressure and prolonging pregnancy in
patients with gestational hypertension with or without proteinuria, but the effect on
lowering systolic pressure was not statistically significant.
L – ARGININE IN IUGR
• IUGR represents a
pathophysiological condition in
which a fetus is restricted from
reaching its genetically
determined size
• IUGR is a major health problem
worldwide, representing 11% of
all newborns in developing
countries
INTRODUCTION
L- Arginine
Nitrous oxide polyamines
endothelium-derived
vasodilator
key regulators of DNA and
protein synthesis
Increases utero-placental blood flow
More transfer of nutrients from mother to fetus
Helps in IUGR
• L-arginine (3 g po daily) administered in intrauterine growth restriction seemed to
improve estimated fetal weight in a study by Pace et al.
• In the past high doses of intravenous L-arginine was used to stimulate growth
hormone secretion.
• A study in 2004 demonstrated durable improvement in fetal growth and increase in
birth weight in patients with intrauterine growth restriction treated with low doses of L-
arginine for 20 days
L –ARGININE IN OLIGOHYDRAMNIOS
INTRODUCTION
Oligohydramnios is characterized by
the following features:
• Amniotic fluid volume of less than
500 mL at 32-36 weeks' gestation
• Single deepest pocket (SDP) of less
than 2 cm
• Amniotic fluid index (AFI) of less
than 5 cm or less than the fifth
percentile
Placental ischemia/ placental insufficiency may lead to
oligohydramnios
L-arginine increases NO
Increase in uteroplacental blood flow
,improving the circulation
Improvement of oligohydramnios
0
2
4
6
8
10
placebo with l-arginine
L –arginine effect on AFI
L – ARGININE IN LUTEAL PHASE DEFECT
 Compromised corpus luteum (CL)
progesterone production acts as a
potential risk factor for prenatal
development
 Defective CL function impacts fertility by
preventing implantation, and early
embryo development in humans
 CL is highly exposed to the locally
produced ROS*
 ROS-induced apoptotic cell death is
involved in the mechanisms of CL
regression occuring at the end of the
non-fertile cycle
L- arginine decreases corpus
luteal blood flow impedance
Increased corpus luteal blood
flow
Increase in cholesterol level
causing increased
progesterone secretion
 Adequate amount of blood flow in the CL
provides luteal cells with the large amounts of
cholesterol
 This cholesterol is required for progesterone
synthesis and to deliver progesterone to the
circulation
7.6
12.8
0
5
10
15
placebo with L - arginine
treatment
PROGESTERONE LEVEL A study conducted by Takasaki et al. showed
that L-arginine 3 g is effective in:
Enhancing blood flow in CL and
significantly increasing the progesterone
concentration
• L-arginine supplementation helps in lowering diastolic pressure
and prolonging pregnancy in patients with gestational
hypertension with or without proteinuria
• Supplementation of L – arginine has been reported as a potential
solution to improve the maternal status, and reverse restricted
growth of the fetus
• L-arginine could be a potent treatment option for treatment of
oligohydramnios
• L-arginine enhances the blood flow in the CL and significantly
increases the progesterone concentration, and thus helps in LPD
CONCLUSIONS
REFERENCES
1. Lampariello C, De Blasio A, Merenda A, Graziano E, Michalopoulou A, Bruno P. [Use of arginine in intruterine growth
retardation (IUGR). Authors' experience]. Minerva Ginecol. 1997 Dec;49(12):577-81. Italian. PubMed PMID: 9557488.
2. Meher S, Duley L. Interventions for preventing pre-eclampsia and its consequences: generic protocol. Cochrane Database
Syst Rev2005;2:CD005301.
3. Mignini LE, Villar J, Khan KS. Mapping the theories of pre-eclampsia: the need for systematic reviews of mechanisms of
the disease. Am J Obstet Gynecol2006;194:317-21.CrossRefMedlineWeb of Science
4. Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet2005;365:785-99.CrossRefMedlineWeb of Science
5. Davidge S. Oxidative stress and altered endothelial cell function in pre-eclampsia. Semin Reprod Endocrinol1998;
16:65-73.MedlineWeb of Science
6. Rees DD, Palmer RM, Moncada S. Role of endothelium-derived nitric oxide in the regulation of blood pressure. Proc
Natl Acad Sci U S A1989;86:3375-8.Abstract/FREE Full Text
7. Ross MG, Cedars L, Nijland MJ, Ogundipe A. Treatment of oligohydramnios with
maternal 1-deamino-[8-D-arginine] vasopressin-induced plasma hypoosmolality. Am J
Obstet Gynecol. 1996 May;174(5):1608-13. PubMed PMID: 9065138
L arginine in pregnancy

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L arginine in pregnancy

  • 2. Dr. Niranjan Chavan MD, FCPS, DGO, DFP, MICOG, DICOG, FICOG Professor and Unit Chief, L.T.M.M.C & L.T.M.G.H Chairperson, FOGSI Oncology and TT Committee (2012-2014) Treasurer, MOGS (2017- 2018) Chair and Convener, FOGSI Cell- Violence against Doctors (2015-2016) Chief Editor, AFG Times (2015-2017) Editorial Board, European Journal of Gynecologic Oncology Editor of FOGSI FOCUS, MOGS, AFG & IAGE Newsletters Member, Managing Committee, IAGE (2013-2017) Member , Oncology Committee, AOFOG (2013 -2015) Recipient of 6 National & International Awards Author of 15 Research Papers and 19 Scientific Chapters Course Co-Ordinator, of 11 batches, of MUHS recognized Certificate Course of Basic Infertility Management Including Endoscopy (BIMIE) at LTMGH
  • 3. • Arginine (abbreviated as Arg or R) • Semiessential or conditionally essential amino acid • Important role in cell division, the healing of wounds, removing ammonia from the body, immune function, and the release of hormones • L-arginine is generally recognized as safe (GRAS-status) at intakes of up to 20 g/d
  • 4. L – ARGININE TRANSFER AND METABOLISM • L - arginine are released into the fetal circulation from fetal tissues • Disposal of fetal amino acid is divided into direct flux back into the placenta and flux into fetal tissues • This flux is further divided into l arginine oxidation and protein synthesis which can be further degraded
  • 5. L - Arginine Reduces diastolic BP in Pre - eclampsia Benfits in IUGR Luteal phase defect Oligohydramnios
  • 6. L-ARGININE IN PRE - ECLAMPSIA
  • 7. • According to NICE guidelinea,Pre- eclampsia is new hypertension presenting after 20 weeks with significant proteinuria • In the absence of proteinuria, hypertension together with evidence of systemic disease (such as thrombocytopenia or elevated levels of liver transaminases) is required for diagnosis. • Complicates 10-17% of pregnancy INTRODUCTION
  • 8.
  • 9. In pre eclampsia , due to abnormal invasion, there is placental ischemia & endothelial dysfunction and decreased NO – leading to increased peripheral resistance and HTN L – arginine is a nitrous oxide (NO) donor vasodilatation Improves placental circulation Decreases oxidative stress • Increases diastolic BP • Improves renal function : decreases proteinuria • Decreases risk of IUGR
  • 10. • Facchinetti et al.’s study had demonstrated that the L-arginine supplement could significantly decrease blood pressure in preeclampsia patients • According to meta-analysis of the various studies, L-arginine supplementation is superior to placebo in lowering diastolic pressure and prolonging pregnancy in patients with gestational hypertension with or without proteinuria, but the effect on lowering systolic pressure was not statistically significant.
  • 11. L – ARGININE IN IUGR
  • 12. • IUGR represents a pathophysiological condition in which a fetus is restricted from reaching its genetically determined size • IUGR is a major health problem worldwide, representing 11% of all newborns in developing countries INTRODUCTION
  • 13. L- Arginine Nitrous oxide polyamines endothelium-derived vasodilator key regulators of DNA and protein synthesis Increases utero-placental blood flow More transfer of nutrients from mother to fetus Helps in IUGR
  • 14.
  • 15. • L-arginine (3 g po daily) administered in intrauterine growth restriction seemed to improve estimated fetal weight in a study by Pace et al. • In the past high doses of intravenous L-arginine was used to stimulate growth hormone secretion. • A study in 2004 demonstrated durable improvement in fetal growth and increase in birth weight in patients with intrauterine growth restriction treated with low doses of L- arginine for 20 days
  • 16. L –ARGININE IN OLIGOHYDRAMNIOS
  • 17. INTRODUCTION Oligohydramnios is characterized by the following features: • Amniotic fluid volume of less than 500 mL at 32-36 weeks' gestation • Single deepest pocket (SDP) of less than 2 cm • Amniotic fluid index (AFI) of less than 5 cm or less than the fifth percentile
  • 18. Placental ischemia/ placental insufficiency may lead to oligohydramnios L-arginine increases NO Increase in uteroplacental blood flow ,improving the circulation Improvement of oligohydramnios
  • 19. 0 2 4 6 8 10 placebo with l-arginine L –arginine effect on AFI
  • 20. L – ARGININE IN LUTEAL PHASE DEFECT
  • 21.  Compromised corpus luteum (CL) progesterone production acts as a potential risk factor for prenatal development  Defective CL function impacts fertility by preventing implantation, and early embryo development in humans  CL is highly exposed to the locally produced ROS*  ROS-induced apoptotic cell death is involved in the mechanisms of CL regression occuring at the end of the non-fertile cycle
  • 22. L- arginine decreases corpus luteal blood flow impedance Increased corpus luteal blood flow Increase in cholesterol level causing increased progesterone secretion  Adequate amount of blood flow in the CL provides luteal cells with the large amounts of cholesterol  This cholesterol is required for progesterone synthesis and to deliver progesterone to the circulation
  • 23. 7.6 12.8 0 5 10 15 placebo with L - arginine treatment PROGESTERONE LEVEL A study conducted by Takasaki et al. showed that L-arginine 3 g is effective in: Enhancing blood flow in CL and significantly increasing the progesterone concentration
  • 24. • L-arginine supplementation helps in lowering diastolic pressure and prolonging pregnancy in patients with gestational hypertension with or without proteinuria • Supplementation of L – arginine has been reported as a potential solution to improve the maternal status, and reverse restricted growth of the fetus • L-arginine could be a potent treatment option for treatment of oligohydramnios • L-arginine enhances the blood flow in the CL and significantly increases the progesterone concentration, and thus helps in LPD CONCLUSIONS
  • 25. REFERENCES 1. Lampariello C, De Blasio A, Merenda A, Graziano E, Michalopoulou A, Bruno P. [Use of arginine in intruterine growth retardation (IUGR). Authors' experience]. Minerva Ginecol. 1997 Dec;49(12):577-81. Italian. PubMed PMID: 9557488. 2. Meher S, Duley L. Interventions for preventing pre-eclampsia and its consequences: generic protocol. Cochrane Database Syst Rev2005;2:CD005301. 3. Mignini LE, Villar J, Khan KS. Mapping the theories of pre-eclampsia: the need for systematic reviews of mechanisms of the disease. Am J Obstet Gynecol2006;194:317-21.CrossRefMedlineWeb of Science 4. Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet2005;365:785-99.CrossRefMedlineWeb of Science 5. Davidge S. Oxidative stress and altered endothelial cell function in pre-eclampsia. Semin Reprod Endocrinol1998; 16:65-73.MedlineWeb of Science 6. Rees DD, Palmer RM, Moncada S. Role of endothelium-derived nitric oxide in the regulation of blood pressure. Proc Natl Acad Sci U S A1989;86:3375-8.Abstract/FREE Full Text 7. Ross MG, Cedars L, Nijland MJ, Ogundipe A. Treatment of oligohydramnios with maternal 1-deamino-[8-D-arginine] vasopressin-induced plasma hypoosmolality. Am J Obstet Gynecol. 1996 May;174(5):1608-13. PubMed PMID: 9065138