ACS (Antenatal corticosteroids) which agent to choose ??

Q. 1: What is AFI & what is its relevance? Ans:-The amniotic fluid index (AFI) has been an integral component of fetal assessment during antepartum ultrasound examination for >20 years. The other methods are subjective movement of Foetal movements (Daily Foetal Movement Counts-DFMC). Decreased amniotic fluid or oligohydramnios, is typically defined as an AFI below 5-cm, which represents the value below the first percentile. In term and near-term gestations, this 5-cm threshold has been associated with increased rates of complications, including small for gestational age neonate, nonreassuring fetal heart rate (FHR), stillbirth, and neonatal death. The amniotic fluid volume is most abundant in the early third trimester, subsequently decreasing until term.

Q.2: What is preterm births? Ans;-   The term of preterm birth is  used to define the premature neonates considering pregnancies age of less than 34 weeks and corticosteroids are commonly prescribed to promote embryos  lung maturity.

How best to define decreased AFI?? Ans:-Decreased amniotic fluid or oligohydramnios, is typically defined as an AFI below 5-cm, which represents the value below the first percentile.

Q.3: When to administer ACS ( ante natal corticosteroids)?  Ans:- The preferred gestational age for administration of dexamethasone and betamethasone is usually 28-34 weeks.

Q.4.Why  we are worried  if  AFI is < 5 Cm ? Why this threshold or cutoff points?  Ans:-In term and near-term gestations, this 5-cm threshold has been associated with increased rates of complications, including small for gestational age neonate, nonreassuring fetal heart rate (FHR), stillbirth, and neonatal death. The amniotic fluid volume is most abundant in the early third trimester, subsequently decreasing until term. Before 34 weeks, the value of 8-cm is below the fifth percentile for gestational age.    

Q.5.  What is the normal AFI range?? Ans .normal range of AFI in fetus is 8-23 cm and its average is 12.8-cm in Jackson study. Jackson et al measured the effect of corticosteroids on AFI in cases where in the study population about 72% of cases the AFI was decreased. Before 34 weeks, the value of 8-cm is below the fifth percentile for gestational age. AFI values between 5- and 8-cm have been termed “borderline.”

.

 Q.6: What are the   potential threats to foetus associated with borderline amniotic fluid in the preterm period ? Ans: Well, the potential risks associated with borderline amniotic fluid in the preterm period are not fully understood. AFI has no significant change before and after corticosteroids administration.

Q.7: What is the dose of antenatal corticosteroids( A N C) ?? The usual dose of betamethasone is 0.17 mg/kg daily for 2 doses.

Q.8: What arte the observed advantages of ante natal corticosteroids i.e. N C??  Ans:-Dexamethasone and betamethasone cause to produce surfactant in fetus lung and thereby it reduces the resistant between layers of airways and sacs to simply slide on each other and eventually easily breathing of neonate after birth preventing respiratory distress syndrome in neonate. Moreover ,ANC  reduces the risk of  1) intraventricular hemorrhage, 2) chronic lung diseases, 3) necrotizing enterocolitis, and 4)retinopathy of prematurity, 5) sepsis, and 6) admission in  Neonatal Intensive Care Unit.

 Q.9: Which steroid is preferred?? Ans:-Imagine if both drugs are freely available in the area where U practice then one has to select the most optimum agent, most beneficial for foetus . Ans:-The question that we the obstetrician have to address in such a situation are  what changes may follow in foetus after the injection of either betamethasone or dexamethasone? The clinicians, therefore should be familiar with changes that may ensue after the doses of steroids be it Dexa or betamethasone.  We the practitioner must be fully aware of  the usual effects  of betamethasone versus dexamethasone on the AFI in the women when administered  to at risk of preterm labor thereby  the best decision may be made for each patient.

.   Ill effects , which may occasionally be demonstrable as a minor transient side effects on foetus induced by steroid injection: Ans;-Few studies have been done to evaluate the side effects of dexamethasone and betamethasone. The indices were Corticosteroid administration to mother & effect on BPP_-1) BPP:-Biophysical profile parameters (BPP) consists of five parameters including:

1. Fetal tone,

2. Fetal gross movement,

3. Fetal breathe,

4. AFI,

5. Nonstress test (NST) changes, each of these parameters is assigned number 0-2.

The normal score of BPP is 8-10 and 6-8 is unclear and below 6 considers as abnormal. BPP for the most of the fetus (95.95%) is normal. In the Jackson study that measured BPP after administration of corticosteroids, fetal gross movement and AFI score were decreased in 44% and 87% of cases, respectively..

Corticosteroid administration to mother & effect on NST:_-To evaluate the effect of corticosteroids on NST, the parameters that change in NST are a short and long beat to beat which are decreased generally, and it can be neglect the corticosteroids effect on acceleration.

What are the changes that may follow after ACS, dexamethasone in particular ??  Ans:-The difference between dexamethasone and betamethasone on 1) NST, 2)  AFI, 3) and BPP, WE should keep in mind that there are some changes, albeit rare after administration of this about dexamethasone injection  . Prior information about such minor transient changes   changes prevents rash decision for patients. In a study made by  Comparison of the effect of betamethasone versus dexamethasone on the amniotic fluid index in the women at risk of preterm labor

Conclusion 1:-What about foetal activity(DFMC)  & AFI changes that may follow after Dexamethasone ?? Ans;-dexamethasone has no clear effect on NST, AFI, and BPP

Conclusion 2 -What about foetal activity(DFMC)  & AFI changes that may follow after Betamethasone?? What about Betamethasone?? Ans;- Betamethasone usually 1) decreases AFI in 63% of cases, 2) short beat to beat in NST in all cases and 3) fetal movement in 80% cases but other parameters have no changes.

Studies have been made to check, analyze, and compare the effect of betamethasone and dexamethasone on fetal index including AFI, BPP, NST in pregnant women with the pregnancy age of 28-34 weeks experiencing prematurity Thus because of the importance of NST, AFI, and BPP on decision for the fetus, the changes after administration of dexamethasone and betamethasone on BPP, NST, and AFI and differences between their effects on the BPP, AFI, NST are important for us.

Knowing of these changes prevents rash decision for patients.  

Rh antigens are of several dozens : Where are they(rh antigens ) located on cells??

 Point 1:-There are total  45  blood group system of which Rh is one. Rh system ,therefore is  one of forty-five known human blood group systems. The Rh blood group system again consists of 49 defined blood group antigens, among which the five antigens D, C, c, E, and e are the most important. We know that there is no d antigen. and Rh negative refer to the Rh(D) antigen only.

 Antibodies to Rh antigens can be involved in hemolytic transfusion reactions and antibodies to the Rh(D) and Rh(c) antigens confer significant risk of hemolytic disease of the fetus and newborn.

Mistake 1:--The term "Rh" was originally an abbreviation of "Rhesus factor." It was discovered in 1937 by Karl Landsteiner and Alexander S. Wiener, who, at the time, believed it to be a similar antigen found in rhesus monkey red blood cells which was found later to be not true. . It was subsequently learned the human factor is not identical to the rhesus monkey factor. Thus, notwithstanding it is a misnomer, the term survives (e.g., rhesus blood group system and the obsolete terms rhesus factor, rhesus positive, and rhesus negative – all three of which actually refer specifically and only to the Rh D factor and are thus misleading when unmodified.

 Mistake got corrected by  Philip Levine and Rufus Stetson:-à  

The first rhesus blood type was discovered in 1937 by Landsteiner and Wiener, who named it after a similar factor found in rhesus monkey blood. The significance of the discovery was not immediately apparent and was only realized in 1940, after subsequent findings by Philip Levine and Rufus Stetson.  

It was recognized that the Rh factor was just one in a system of various antigens. Based on different models of genetic inheritance, two different terminologies were developed; both of them are still in use.

What was the  clinical significance of this highly immunizing D antigen (i.e., Rh factor) was soon realized.Ans:- Some keystones were to recognize its importance for blood transfusion (including reliable diagnostic tests), hemolytic disease of the newborn (including exchange transfusion), and very importantly the prevention of it by screening and prophylaxis.

What is new?? The discovery of fetal cell-free DNA in maternal circulation by Holzgrieve et al. led to the noninvasive genotyping of fetal Rh genes in many countries.

Rh nomenclatur

Rh haplotype notation
Fisher–Race	Wiener
Dce	R0
DCe	R1
DcE	R2
DCE	RZ
dce	r
dCe	r′
dcE	r″
dCE	rY

Kinds of nomenclature: One is general  name (Srimanta) by which one is acquainted in the society in general . Another is nick name(SIMU):-The Rh blood group system , similarly has two sets of nomenclatures: one developed by A) Ronald Fisher and R. R. Race, the B) other by Wiener. Both systems reflected alternative theories of inheritance.

  Nomenclature 1:-The  Fisher–Race system, which is more commonly in use today, uses the CDE nomenclature. This system was based on the theory that a separate gene controls the product of each corresponding antigen (e.g., a "D gene" produces D antigen, and so on). However, the d gene was hypothetical, not actual.

Nomenclature 2:-The Wiener system used the Rh–Hr nomenclature. This system was based on the theory that there was one gene at a single locus on each of the 2 copies of chromosome 1, each contributing to production of multiple antigens. In this theory, a gene R₁ is supposed to give rise to the “blood factors” Rh₀, rh′, and rh″ (corresponding to modern nomenclature of the D, C, and E antigens) and the gene r to produce hr′ and hr″ (corresponding to modern nomenclature of the c and e antigens). Notations of the two theories are used interchangeably in blood banking (e.g., Rho(D) meaning RhD positive). Wiener's notation is more complex and cumbersome for routine use. Because it is simpler to explain, the Fisher–Race theory has become more widely used.

Discovery :- The first rhesus blood type was discovered in 1937 by Landsteiner and Wiener, who named it after a similar factor found in rhesus monkey blood.  Mistake 1:-The significance of the discovery was not immediately apparent and was only realized in 1940, after subsequent findings by Philip Levine and Rufus Stetson.  

It was recognized that the Rh factor was just one in a system of various antigens. Based on different models of genetic inheritance, two different terminologies were developed; both of them are still in use.

The clinical significance of this highly immunizing D antigen (i.e., Rh factor) was soon realized. Some keystones were to recognize its importance for blood transfusion (including reliable diagnostic tests), hemolytic disease of the newborn (including exchange transfusion), and very importantly the prevention of it by screening and prophylaxis

 Geography Rh antigens? Ans:-There are total  45  blood group system of which Rh is one. Rh system therefore is  one of forty-five known human blood group systems. The Rh blood group system again consists of 49 defined blood group antigens, among which the five antigens D, C, c, E, and e are the most important. Is your head reeling?? We know that there is no d antigen. and Rh negative refer to the Rh(D) antigen only. Why we need to knw Rh antigens?? Ans;- Antibodies to Rh antigens can be involved in hemolytic transfusion reactions and antibodies to the Rh(D) and Rh(c) antigens confer significant risk of hemolytic disease of the fetus and newborn.The term "Rh" was originally an abbreviation of "Rhesus factor." It was discovered in 1937 by Karl Landsteiner and Alexander S. Wiener, who, at the time, believed it to be a similar antigen found in rhesus monkey red blood cells which was found later to be not true.  It was subsequently learned the human factor is not identical to the rhesus monkey factor. Thus, notwithstanding it is a misnomer, the term survives (e.g., rhesus blood group system and the obsolete terms rhesus factor, rhesus positive, and rhesus negative – all three of which actually refer specifically and only to the Rh D factor and are thus misleading when unmodified.

.

What is the  latest news on  Rh antigens?? Ans:-The discovery of fetal cell-free DNA in maternal circulation by Holzgrieve et al. led to the noninvasive genotyping of fetal Rh genes in many countries.

Rh haplotype notation
Fisher–Race	Wiener
Dce	R0
DCe	R1
DcE	R2
DCE	RZ
dce	r
dCe	r′
dcE	r″
dCE	rY

How many ways we can express Rh antigens?? Ans:-The Rh blood group system has two sets of nomenclatures: one developed by Ronald Fisher and R. R. Race, the other by Wiener. Both systems reflected alternative theories of inheritance. The  Fisher–Race system, which is more commonly in use today, uses the CDE nomenclature. This system was based on the theory that a separate gene controls the product of each corresponding antigen (e.g., a "D gene" produces D antigen, and so on). However, the d gene was hypothetical, not actual.

The Wiener system used the Rh–Hr nomenclature. This system was based on the theory that there was one gene at a single locus on each of the 2 copies of chromosome 1, each contributing to production of multiple antigens. In this theory, a gene R₁ is supposed to give rise to the “blood factors” Rh₀, rh′, and rh″ (corresponding to modern nomenclature of the D, C, and E antigens) and the gene r to produce hr′ and hr″ (corresponding to modern nomenclature of the c and e antigens). Notations of the two theories are used interchangeably in blood banking (e.g., Rho(D) meaning RhD positive). Wiener's notation is more complex and cumbersome for routine use. Because it is simpler to explain, the Fisher–Race theory has become more widely used.

Where are you, my dear Rh antigens? Where is your dwelling site??  .I know you have 49 sisters!!!  Ans: The proteins which carry the Rh antigens are transmembrane proteins, whose structure suggest that they are ion channels. The main antigens are D, C, E, c and e, which are encoded by two adjacent gene loci, the RHD gene which encodes the RhD protein with the D antigen (and variants) and the RHCE gene which encodes the RhCE protein with the C, E, c and e antigens (and variants). There is no d antigen. Lowercase "d" indicates the absence of the D antigen (the gene is usually deleted or otherwise nonfunctional).

1. This is the Rh-positive blood cell. 2. This is the Rh-negative blood cell. 3. These are the antigens on the Rh-positive blood cell that make it positive. The antigens allow the positive blood cell to attach to specific antibodies.

 Can a mother produce antibodies despite having anti-D inj at full dose, in time & inj was from a good manufacturing house (Brand & make). This Q stems from the fact that there are about 49 defined blood group antigens, among which the five antigens D, C, c, E, and e are more common. Have any members ever  come across  HbD Punjab,HBF texas(in these cases anaemia remains resistant to oral Fe therapy and the exact nature of Hb variant cant be diagnosed    unless gentic testing is done. Can the same philosophy be applicable to Rh antigen and inability of anti D to protect the foetus  ?

Does anti-D , which we commonly administer say after ectopics, Thr abortion, CVS, amnio, Pre-labour or post delivery covers all the known antigens or some antigens are not covered by the immunoglobulin which we adminster only to face poor consequences in next preg despite previous immuno protection??  The Rh blood group system again consists of 49 defined blood group antigens, among which the five antigens D, C, c, E, and e are the most important??

Probable genotype Rh phenotypes are readily identified through the presence or absence of the Rh surface antigens. As can be seen in the table below, most of the Rh phenotypes can be produced by several different Rh genotypes. The exact genotype of any individual can only be identified by DNA analysis. Regarding patient treatment, only the phenotype is usually of any clinical significance to ensure a patient is not exposed to an antigen they are likely to develop antibodies against. A probable genotype may be speculated on, based on the statistical distributions of genotypes in the patient's place of origin. We know cystic fibrosis mutation is of many types and we also known that there are more than 400 gene mutations have been identified in haemoglobin chain  variants.   Members opinion please? I have no answer to this dilemma !!!

Newer causes of me=ale or female subferrtlity or Rec preg losses=What may be the causes??

Is recurrent pregnancy loss and infertility do have same common associated etiology which can cause either or singularly  both  ?

There is  overlap   between infertility    & recurrent   pregnancy  losses  due to similar   pathophysiology needs  to be addressed  to get the best pregnancy  outcome for these  patients whose  desire  is to achieve a successful pregnancy. Many are of opinion that subfertility and recurrent pregnancy  loss are  considered  mutually of same etiology.   Infertility, as members are aware that subfertility is  defined  as the inability  to conceive   after  12  months or more    of unprotected intercourse while RPL  is ambivalently characterized by a history of  2 or 3  clinically documented pregnancy loss.  Not only   do these patients   share the same unfulfilled   desire to deliver a baby in many cases they also share a common etiologic   characteristics, diagnosis & management. Instance 1 :-For instance a women with partial or complete septum or a bicornuate or unicornate   uterus may face either infertility or  recurrent pregnancy   losses because   of poor vascularity of the septum  &   disordered  myometrial   contractions. A hysteroscopic septal   ablation would give a successful live birth rate in 85% of   cases solving   both these issues. Instance 2:-Patient with genital koch’s    may face either infertility or   subsequent   recurrent pregnancy loss due to a thin endometrium.  A full course of Anti Tubercular   treatment   would go  a long  way in treating both  these conditions.

Instance 3:-Luteal phase defects  are known  to cause  recurrent  pregnancy  losses as well as infertility. Traditionally progesterone supplementation in the luteal  phase    has been recommended due to its  immunomodulatory  & uterine   relaxation  action. Instance 4:-This treats infertility as well as averts  recurrent   pregnancy losses  as well endocrine  disorders like PCOS untreated   hypothyroidism and poorly  controlled  diabetes  may  pose a risk for infertility as well as  recurrent   pregnancy loss and treating  these endocrine disorders  could be  a rewarding    experience for both an infertility  expert or the obstetrician dealing with RPL   Increased  & subsequent RPL in case pregnancy  happens. Thus proving  that both RPL &   infertility and RPL  . Instance 5 :- Decreased ovarian   reserves  affects  both quality  &     quantity of oocyte & is  a known  cause  for infertility  & RPL . So  infertility   experts  need to stimulate   the ovaries by  ovulation induction. The improved ovarian  response in these patients  ameliorates  infertility  &  subsequent   recurrent   pregnancy   losses  as well.

Instance 6:-Environmental factors such as smoking alcohol exposure  to toxins  or chemicals  anaesthetic gases obesity  daily caffeine intake of > 300 mg can cause   both infertility.   & subsequent   recurrent  pregnancy  losses. So    the  overlap   between infertility    & recurrent   pregnancy  losses  due to similar   pathophysiology needs  to be addressed  to get the best pregnancy  outcome for these  patients whose  desire  is to achieve a successful pregnancy.

?

Instance 6:- Less AFC , Low AMH; Dwindling ovarian reserve: Whereas in   male partner  loss of telomere( ends or caps of chromosomes)  of sperm of elderly men ---> 45 yrsà so either subfertility/RPL:-Recurrent  pregnancy  loss as well as infertility is seen increasingly  in our  daily practice in the recent  years  social and cultural  trends  especially     in urban areas have resulted   in women delaying  childbirth  thereby   making reproductive  senescence a major  health problem. Recurrent pregnancy loss : Old  problem-A   New  solution ? Again question of poor quality oocytes:à Failure to fertilize ( Fertilization failure) à fertilized but poor implantation (implantation,  disorders / embryonic  arrestà failure  to grow in orderly way after implantation!!  Can quality of oocytes be increased by  CoQ10 / DHEA ?? One million dollar Question?

Instance 7 :-Environmental toxins , workplace toxicity There is a complex  interaction of  the pro oxidants and antioxidants  resulting in the  maintenances of intracellular   homeostasis Oxidative stress dysmorphogenesis   , recurrent miscarriages and intrauterine  growth  restriction. Instance 8 Mitochondrial dysfunction : may cause either subfertility or Rec Preg loss:-:- There is supportive evidence  to the central role of mitochondrial  function   and oxygen  radicals in the process of aging and reproductive loss.

Spontaneous pregnancy  loss is the most  common  complication of pregnancy with 70% of conceptions  fail to achieve  viability clinically recognized loss occurs in 15% before   20 wks   of gestation

Treatments  that work for RPL includes

High  dose folic acid 5mg /day  progesterone 400-800 mcg/ day Aspirin  75-8 mg/day  Low molecular weight  heparin Immunosuppressant   steroids   immunoglobulins endocrine correction infection screening  and treatment   vitamin D correction and vitamins B6 , B12 and vitamin C supplementation

Supplementation with antioxidants  and cellular energizers such as  coenzyme  Q10  and Melatonin

Artificial Reproductive Techniques – IVF

Evidence   suggests that CoQ10  synthesis declines with  increasing age. Here  the role of Coenzyme Q10  as a mitochondrial rejuvenator  it deficiency  and its  supplementation to improve  outcomes  is explored.