- Luteinisation of
granulose cells
- Maturation of oocyte
- Liberation of
prostaglandins for follicular rupture.
If there is inadequate LH or
inadequate LH receptors.
¯
Ineffective corpus luteum
At the time of ovulation is
excessive vascularisation.
Theca interna proliferates
quickly in the presence of excess of vascular
endothelial growth factor.
¯
This can result in corpus luteum
haemetoma.
Hence, fast vascularisation will untimely
lead to inadequate luteal phase.
®
Post Ovulatory phase
Development of progesterone
nuclear receptors is dependant on adequacy of
estrogen in the follicular phase as well as in the luteal phase.
If there are inadequate
progesterone receptors, even if corpus luteum is
adequately producing progesterone, luteal phase
cannot be effective.
Any excessive or deficient
functioning of hypothalamus or pituitary can
lead to LPD.
LPD can be produced as an
outcome of ovulation induction treatment and
more predominantly during ART treatment.
In the habitual aborter
luteal function is apparently sufficient to
promote endometrial maturation, but is
quantitavely inadequate to support the pregnancy
during the transitional period of the luteo
placental shift.
Pathophysiological mechanisms
Follicular phase events
Abnormalities of gonadotropin
pulsation
Quantitatively deficient follicular
phase FSH levels.
Alterations in inhibin feedback
Defective granulose cells
Inadequate endometrial estrogen
priming
Luteal phase events
Deficient midcycle surge and luteal
phase CH level
Hyperprolactinemic
Accelerated luteotropic stimulus
Intrinsic cellular defects of the
corpus luteum
Inadequate endometrial progesterone
receptors.
- AGENTS FOR EARLY PREGNANCY SUPPORTS
:
· Natural progesterone
Micronized progesterone
Oral
Vaginal
Rectal
Intramuscular natural
progesterone
Micronized progesterone
The clinical usefulness
of progesterone has been limited by its poor
absorptions after oral administration and
rapid first pass liver metabolism.
Synthetic oral
progesterones have been developed but their
use in pregnancy has been condemned because
they may have luteolytic effect on the
corpus luteum and can produce glandular
stromal disparity thereby worsening the
situation.
Micronisation in
combination with lipophilic vehicle enhances
absorption
Mechanism of action
Progesterone is lipophilic in
nature & diffuses freely into cells & bind to
receptors. Then this steroid receptor complex
binds to DNA in nucleus thereby inducing the
synthesis of specific proteins.
Route of administration
It can be oral, vaginal,
rectal or parenteraly. Oral progesterone has
low bioavailability & can produce
significant hypnotic effects; vaginal
suppositories are associated with unpleasant
discharge.
Intramuscular route is
most reliable but uncomfortable & can lead
to marked inflammation at the injection site
resulting in sterile abscess formation.
Pharmacokinetics of
natural progesterone absorption
With vaginal or rectal
route max conc. reach with in 1-8 hr. and
then decline over 24 hr.
With oral route rise in
progesterone start from first hour and
higher plasma level reach after 1-3 hr.
High plasma conc. is
reached within 8 hr. serum progestin levels
are more sustained with intramuscular route.
It has distribution half
life of 3 – 6 min f/b elimination half life
of 19 -95 min. mainly metabolized in liver
by hydroxylation and conjugation.
Metabolites of progesterone are mainly
excreted in urine as glucuronide conjugates.
Dose
Oral progesterone varies
from 200-400 mg per day in the divided doses
one hour before or after meals
Vaginal
200 – 600 mg in to thus
divided doses immediately after ovulation and
continued till 12 weeks of pregnancy.
· Human Chorionic
Gonadotropin
Introduction:
- Produced by
syncytiotrophoblast of the placenta.
- HCG & polypeptide
hormone produced by human placenta is
composed of an alpha and a beta sub unit.
- The alpha sub unit is
identical to alpha sub units of human
pituitary gonadotropins LH, TSH as well as
to the alpha sub unit of human TSH.
- It is available as a
water soluble glycoprotein derived from
human pregnancy urine.
- Used within 30 days.
Effect:
- Administration of HCG
stimulates the corpus luteum to produce P.
- In situations when the
LH receptor population is inadequate that it
may not be effective.
- A specific defect in
postovulatory LH secretion or in
trophoblastic HCG production, then exogenous
administration of HCG would be useful.
- HCG has a longer half
life than LH, which is an advantage in
treating inadequate luteal function.
Disadvantage
- More expensive
- Cannot be self
administered
Dose
- To achieve complete
luteinisation of preovulatory follicle, -
10,000 IV of HCG administered at the
approximate time of ovulation.
Followed by
1500 – 5000 IV every 3 –
4days.
- Treatment is stopped
after 12th postovulatory day
¯
To avoid high incidence
of pseudopregnancy
- When HCG treatment ®
after the LH surge
¯
No increase in E2 & P
concentration
- When HCG treatment ® Midluteal
phase
¯
Circulating levels of P –
Normally observed
E2 levels remain elevated
- When HCG treatment ® Late Luteal
phase
¯
p response – brief.
Because of this uncertainty
of response along with mode of administration &
problem of detecting on early pregnancy – hCG is
not a first choice
But nonavailability of
natural progesterone
¯
hCG - better option
Safety
- Category ‘c’ of the FDA
classification
- HCG should be given to
a pregnant woman only if clearly needed.
· Alleylestrenol
Agents for early pregnancy support
- Extensively used in the
part as support in early pregnancy.
Mechanism of action:
Stimulates placental
progesterone synthesis and increases the
secretion of placental hormones.
Human chorionic
somatomammotropin levels showed a levels
significant increase within 10 to 12 days of
alleylestrenol therapy used in healthy
pregnant women in the 5th to 8th
months of gestation.
Dose: 5 mg three times a
day.
Safety: associated with
congenital anomalies such as club foot and
hypospadias.
· DYDROGESTERONE
Introduction:
It is pure orally active progestin.
Kind of progesterone derivative
Pharmacokinetic:
Plasma half life is short
rapidly eliminated from body either given orally
or intramuscularly.
Mechanism of action:
Produce complete secretory
endometrium in estrogen primed uterus.
Dose:
5 mg tablet (Duphastone)
30 mg daily
Action:
Preparation of uterus for
nidation and maintenance of pregnancy.
Adverse reaction:
Mental depression, weight
gain, breast discomfort, allergic, skin
rash, Acne, fluid retention.
Safety in pregnancy is
controversial.
8th weeks post
conception can cause virilization of female
fetus.
Poor antiovulatry action
Contraindication:
Undiagnosed vaginal bleeding
Women with history of thrombo
embolism
Advantage:
Not inhibit ovulation
Mildly catabolic action
Preferred when contraceptive
effects are not required.
· 17 a
HYDOTREATMENTY PROGESTERONE CAPROATE
Introduction:
Pure progestin mainly available in
depot form.
Mechanism of Action:
Production of placental hormones by
direct stimulation on placenta.
Dose:
Injection Proluton depot 500 mg / 2
ml
Tablet 10 mg & 5 mg
Caution:
Prescribing 17 HPE during
early pregnancy to prevent miscarriage is
not advisable.
It has mildly catabolic
action.
HYPEREMESIS GRAVIDARUM
- Definition
Defined as vomiting during
first trimester of pregnancy severe enough to
cause 5 % of weight loss and ketoacidosis &
incapacitate the women for her day to day
activities.
Nausea & vomiting affect 75 %
of pregnant women in first 14 week however
vomiting severe enough to require admission has
been found to be present in 0.3 to 2% cases.
- Etiology
It is mostly related to
the first trimester
More common in first
pregnancy, with a tendency to recur again in
subsequent pregnancies.
Familial History – mother
and sister also suffer from the same
manifestation.
More prevalent in
Hydatidiform mole. Choriocarcinoma, multiple
pregnancy, associated metabolic disorders
like diabetes.
It is more common in
unplanned pregnancy.
Theories
Hormonal :
Excess of chorionic
gonadotropin
Hyperestrinism
Progesterone excess
leading to relaxation of the cardiac
sphincter and simultaneous retention of
gastric fluids due to impaired gastric
motility.
Adrenocortical
insufficiency
Psychogenic
Psychosocial stressors
Personality disorder
Coping
mechanisms
Stress intolerance
It probably aggravates the
nausea once it begins. But neurological element
may be present.
Dietetic deficiency: due
to low carbohydrate reserve, as it happens
after a night without food.
- Deficiency of vitamin B6,
B1 and proteins
Allergic: may be related
to some products secreted from the ovum.
Immunological basis
Cause of initiation of
vomiting
¯
Aggravated by the
neurogenic element
Features of
dehydration and carbohydrate starvation
supervene and a vicious cycle of
vomiting appears
Vomiting
¯
Carbohydrate
starvation
¯
Ketoacidosis
¯
Vomiting
Other causes of
vomiting are ruled out
Hyperthyroidism,
gastroenteritis, cholicystitis,
appendicitis, pancreatitis, hepatitis,
peptic ulcer, pyelonephritis,
Central Nervous
disorders, Malaria, Meningitis
- Citric Acid Cycle
Synonyms: TCA cycle
(tricarboxylic acid cycle) Krebs’ cycle, Krebs’
citric acid cycle.
Characteristic Features:
It is a cyclic process.
The cycle involves a
sequence of compounds interrelated by
oxidation – reduction and other reactions
which finally produces CO2 and H2O.
It is the final common
pathway of break down/catabolism of
carbohydrates, fats and protein. (Phase III
of metabolism).
Acetyl CoA derived mainly
from oxidation of either glucose or
b -oxidation of FA and partly from certain
amino-acids combines with oxaloacetic acid
(OAA) to form ‘citrate’ the first reaction
of citric acid cycle. In this reaction
acetyl-CoA transfers its acetyl group (2-C)
to OAA.
By step wise
dehydrogenations and loss of two molecules
of CO2, accompanied by internal
re-arrangements, the citric acid is
reconverted to OAA, which again starts the
cycle by taking up another acetyl group from
acetyl CoA.
A very small ‘catalytic’
amount of OAA can bring about the complete
oxidation of active acetate.
Enzymes are located in
mitochondrial matrix, either free or
attached to the inner surface of the inner
mitochondrial membrane, which facilitates
the transfer of reducing equivalents to the
adjacent enzymes of the respiratory chain.
The whole process is
aerobic, requiring O2, as the
final oxidant of the reducing equivalents.
Absence of O2 (anoxia) or
partial deficiency of O2 (hypoxia) causes
total or partial inhibition of the cycle.
The H atoms removed in
the successive dehydrogenations are accepted
by corresponding coenzymes. Reduced
coenzymes transfer the reducing equivalents
to electron-transport system, where
oxidative phosphorylation produces ATP
molecules.
Biomedical Importance Of Citric Acid
Cycle
Final common pathway for
carbohydrates. Proteins and fats, through
formation of 2 carbon unit acetyl - CoA.
Acetyl – CoA is oxidized
to CO2 and H2O giving
out energy (III phase of catabolism)
intermediates of TCA
cycle play a major role in synthesis also
like heme formation, formation of
non-essential amino acids, FA synthesis,
cholesterol and steroid synthesis.
- Management
Principles
To remove the neurogenic
elements
To correct the fluids,
electrolytes & other metabolic disturbances
effectively.
To prevent or to detect
at the earliest ominous complications.
Investigations
Complete hemogram with
peripheral smear examination.
To r/o parasitic infection i.e.
Malaria
To r/o acute infection
Microscopic examination
of urine
To r/o UTI
Presence of Ketone
bodies.
Blood biochemistry –
Glucose
Kidney function
Parameters
Liver function tests
Ultrasonography pelvis
Fundoscopic examination
of retina: To detect early changes of
vasculopathy.
Treatment
- Hospitalization
- Fluids -
Intravenous fluids for 24 hrs.
- Orally foods are
given
- Diet - Dry
carbohydrate foods biscuits & bread
- Drugs –
Prochloreperaizine
- Oral Liquid
antacids.
- Parenteral H-2
blockers
- Recently –
Ondansetron drugs
- Vitamins
- To maintain hyperemesis chart
Fluid intake & output for
24 hrs.
Character of vomitus
Urine examination
I) Acetone
ii) Chloride
iii) Protein & bile
Weight Monitoring
ECG
Ophthalmoscopic
examination
- Clinical features of
improvement evidenced by
Subsidence of vomiting
Feeling of hunger
Better look
Disappearance of acetone
from the breath & urine
Moist tongue
Falling pulse rate &
rising blood pressure.
Increase in urine output
- Termination of pregnancy
Indications
Steady deterioration in
spite of therapy
Rising pulse rate of
100/minute.
Temperature >38°C (100-
4°F)
Gradually increasing
oliguria & proteinuria.
Appearance of jaundice.
Appearance of
neurological complications.
Below 12 weeks – suction
evacuation.
PAIN AND BLEEDING IN EARLY PREGNANCY
Twisted ovarian cyst with pregnancy
Pain is usually unilateral, intermittent
and associated with vomiting. Usually occurs between 8 -10
wk of pregnancy as the tumor is out of pelvis. Treatment is
by laparoscopic de-torsion of the adenexa.
OHSS:
This is typically seen in pregnancies
following assisted reproduction.
Pain may be due to intraperitoneal
hemorrhage, rupture of a cyst or torsion of a cyst.
Prevention
Characterized by ovarian enlargement
2o to the development of multiple luteal cysts.
< 6 mm - No risk
~ 8 mm - Mild
> 10 mm - Moderate to severe
Early OHSS – Day 3 & day 7 post
HCG injection
Late OHSS – day 12 to day 17 post
HCG injection
Patients at risk
younger age < 35 years
Thin
PCOS
Oligomenorrhic anovulation
Use of hMG
Use of GnRH agonist
USG appearance of the developing
follicle on the day of hCG administration.
Treatment - Supportive
- Maintain intravascular volume
- Avoid the complication associated with
hypercoagulability
Mild OHSS - Regular follow up
- Close observation
- Usually resolves spontaneously within 2
– 3 weeks
Moderate to severe OHSS – immediate
hospitalization
Monitoring protocols - Temperature,
Pulse, Blood pressure
- Daily weight, Abdominal girth
- Input / Output chart
- Plasma & urine osmolarity
- Blood urea
- Serum electrolytes
- Coagulation profile
- liver function test
- USG: pelvis, abdomen
- Chest X-ray
Medical management
Maintaining the intravascular volume
Intravenous colloids, solutions,
including 20% albumin,
Anticoagulant – Heparin if
abnormal clotting time
Dopamine if associated oliguric
indicating renal hypoperfusion
Antihistamines
Diuretics if pulmonary edema
Surgical Therapy: - Transabdominal
sonography
- Transvaginal sonography
- For intraperitoneal hemorrhage
- Rupture / Torsion of ovarian cyst
Laparoscopy / Laparotomy may be
necessary.
Complication of OHSS
Vascular – Haemoconcentration
Can lead to cerebrovascular &
cardiovascular embolic phenomena
Liver dysfunction
GIT – Nausea, vomiting, diarrhea
Pain in abdomen
Adnexal Torsion
Renal - pre-renal failure
- Hydroureter
Respiratory system – pleural
effusion
-
Respiratory distress
- ARTS
Gestational Appendicitis:
Incidences:
1. 0.05 – 0.07 %
2. Most common surgical complication
3. Increased gestational age –
increase of changes perforation
Sign symptoms:
Resent onset of lower abdomen pain
Rebound tenderness & guarding
High WEB count
Conclusion:
Considerable fetal loss found (inevitable
abortion) or PTVD
¯
After appendicectomy in 1st &
2nd trimester
Medical Causes
Gall Bladder Disease
Sign / symptoms
- Griping pain in the right upper
quadrant or epigastria – radiate to the back or shoulder
tip
- Nausea & vomiting
On examination
- Tenderness & guarding in right
hypochondria
Investigation
- Ultrasound of gall bladder is a
safe and accurate method of diagnosing gall stones.
- Raised WBC count
- Abnormal liver function tests
- Raised amylase
Treatment
- Conservative treatment
Surgical treatment – Laparoscopic
cholecystectomy
UTI
Incidence of urinary tract infection in
pregnant women is found to be 4 %. Although pregnancy does
not increase the prevalence of asymptomatic bacteriuria in
women, it does enhance the progression rate from
asymptomatic to symptomatic disease.
Presence of infection can be
suggested by complain of hematuria, dysuria, supra pubic
discomfort urinary frequency, and urgency.
Direct microscopy of urinary sediment
for white cells, red cells or bacteriuria is useful to
make diagnosis. Organisms isolated are similar to those
in cases of asymptomatic bacteriuria.
After sending mid stream urine sample
for culture and sensitivity aggressive antibiotic
therapy with amoxycillin, ampicillin with cephalosporin
must be initiated.
Pancreatitis
Incidence: 0.1/1000 pregnancies
Rarely seen in early pregnancy
- Causes: gallstones
Medications
Infections
Alcohol
Hyperlipidemic
- Symptoms: Severe epigastric pain
radiating to the back
- Nausea
- Vomiting S/o acute pancreatitis
- Fever
- Patient tries to decrease discomfort by
assuming a position of flexed knees, hips and truth.
- Investigation: elevated amylase (in
pregnancy, cholicystitis, bowel obstruction, rupture ectopic
pregnancy)
- creatinine clearance
- USG show dilated pancreatic ducts
- Management: Early suspicion
- confirm pregnancy its sites and fetal
viability
- conservative management is preferable
Intestinal Obstruction
Uncommon in pregnancy
|
Incidence |
: |
1 in 1500 to 1 in 66,431
pregnancies |
|
Causative factor |
: |
Volvulus, adhesions, previous
LSCS |
|
High risk patient |
: |
Past history of surgery on
abdomen
Previous LSCS
Tuberculosis (Intestinal)
Worm infestation |
Differential diagnosis
Intestinal obstruction – Nausea and
vomiting (feculent) in character
Remark
Mortality and morbidity to both mother
and fetus is high.
Gastro – Esophageal Reflux
Sign / symptoms
- Epigastric pain
- Heartburn
- Nausea
Pain
- Worse on an empty stomach
- Relieved with antacids or food.
Treatment
Conservative
- Diet
- Lifestyle changes
- Antacids – H2 receptor antagonists
most commonly used.
Ranitidine
Cimetidine
Surgical – Laparoscopies
Sucralfate and omeprazoles avoided in the
first trimester.
Gastroscopy is better postponed to second
trimester.
GENETIC COUNSELING
Definition :
Defined as "The process by which the
patients or relatives at risk of a disorder that may be
hereditary are given information about the consequences of
that disorder, the probability of developing or transmitting
and the ways in which it may be prevented or ameliorated".
Who Delivers Genetic Counseling?
Many health settings with trained
persons
Genetic counselors
Primary care obstetricians
Family general practitioners
Perinatologists
Medical genetics
Who Receives Genetic Counseling
Maternal age >35 years was the first
to be used because of its association with fetal
aneuploidy.
Previous affected child – with a
birth defect, inherited disorder – Mental retardation.
Parent having chromosomal anomaly.
Family history of a single gene
disorder.
Previous miscarriage, fetal deaths,
still births and neonatal deaths.
Teratogen exposures.
Couple who are first cousins.
Known disorders in certain ethnic
groups.
e.g. Thalassemia - Asia Mediterranean
Tay Sach’s diseases - Jews
Routine Sonographic / Serum screen
used to identify fetuses at risk.
Methods of genetic counseling
Directive counseling :
Directing couples to do what the
counselor feels is the best in the interest of the
community suitable for low status. Counselor advices,
expresses opinion and selectivity reinforce the couples
behaviour, thoughts and actions.
Non directive counseling
- For counseling both members of a couple
should be present.
- Joint decision - making about testing
or about continuing or stopping.
- Allow adequate time in a setting which
is free from disturbance.
- For this, one must establish accurate
diagnosis and mode of inheritance before counseling.
In non directive counseling all
information provided and decision making is entirely by the
couple.
Information Guidance Counseling
Recently introduced method
Calculating risk:
The mathematical ‘risks of recurrence’
can usually be derived with certainty for a single gene
disorder.
Risk figure has two components: The
probability of the condition occurring
Burden of the disease
Whether the disease is mild to severe and
whether screening and treatment is available needs to be
discussed.
Explaining risk:
Genetics give the risk figures in the
form of a fraction or odds or percentage. This has the
advantage that it is less likely to lead to confusion.
Explaining about how inheritances works
Dominant disorders
Each child gets half of its genes
from each parent. If parent has gene for dominant
condition there are 50 % chance that child will have
same condition. Dominant disorders have symptoms ranging
from none to severe. Both defects caused by dominant
inheritances include Achondroplasia, Marfan syndrome
polydactyly.
Recessive conditions
Manifests only in homozygous state.
If both parents are heterozygous child has 1 in 4 chance
of being affected. Disorders are often very serious and
may lead to early death e.g. sickle cell anemia,
thalassemia.
X Linked inheritances.
A disorder arising from abnormal gene on
one of the X chromosomes. An apparently normal mother with
an abnormal genes on one chromosome has 50 % chance of
passing it to a female child or a male child e.g.
hemophilia, Red green colour blindness, Duchene muscular
dystrophy.
Carriers
If a person has one copy of a recessive
disorder, that person is called carrier. There is always the
chance of genetic disease in any child of two carriers or
son born to a mother carrying x linked defect.
Chromosomal disorders
Occasionally an extra chromosome or a
chromosome is missing. The resulting imbalanced genetic
material can give baby too little on too much genetic
information which may translate into abnormal body
structures or functions as well as mental retardation.
Establishing the mode of inheritances
Autosomal Dominant
Male & females equally affected
Transmitted from one generation
to next.
Autosomal recessive
Male & females equally affected
Consanguinity in parents provides
further support.
X linked recessive inheritance
Males affected almost
exclusively.
Transmitted through carrier
females to their sons.
Affected males cannot transmit
the disorder to their son.
X linked dominant inheritance
Females are usually less severely
affected than males.
Affected females can transmit the
disorder to male and female children but affected
males transmit only to their daughters.
Inherited chromosomal anomalies
May give a pattern of unaffected
family members having children with multiple
abnormalities with growth & development retardation.
May give a pattern of multiple
pregnancy loss
An apparently isolated case
New dominate mutation
More severe expression in a child
of a dominant disorder in a parent
Chromosomal anomaly
A combination of environmental
influences on a genetic predisposition.
Malformation syndrome
May be due to chromosomal abnormally
genetic defects or teratogens. Prenatal diagnosis is
available for some with a biochemical basis where gene
has been found or where due to micro deletion.
Single gene disorders
Diagnosed by DNA techniques
One must identify families through
Previously affected child
Family history
Carrier screening programmes for
autosomal recessive disease.
If they wish to proceed with further
testing, biochemical assays, ultrasound & DNA diagnosis
could be offered.
Genetic Counseling of the Apparently
Normal Couple
- A screening questionnaire can be
useful but patient to be sure she has understood the
questions.
- Inquire about the health of couple
First degree relatives (sibs,
parents, offspring)
Second degree relatives (uncles,
aunts, nephews, nieces)
Third degree relatives (first
cousins)
- Consanguinity of the couple of
(relationship by descent from a common ancestor) may not
be volunteered.
- Abnormal reproduction outcomes
Spontaneous abortions
Fetal deaths should be exposed
Anomalous live born infants
- Women’s & spouse’s exposure to
drugs, both those used currently & toxins.
(e.g. Radio/chemotherapy) to which
the individual was exposed in past should be determined.
- Parental ages – should be
determined
Advanced maternal age – most common
indication for counseling and antenatal diagnosis.
Advanced paternal age – increased
risk for a child with a new dominant mutation such as
Marfan syndrome
- Ethnic origin must be discussed
Because certain genetic disorders at
high frequencies in particular ethnic groups.
- Both parents prove to be
heterozygous – prenatal diagnosis should be offered e.g.
Ashkenazi Jews are at increased risk compared with
general population for offspring with Tay – Sach’s
disease.
E.g. - Prenatal testing for sickle
cell disease, thalassemia common disorders in African,
American.
- Screening for cystic fibrosis
heterozygotic may be appropriate in some Caucasian
populations.
Genetic counseling of the couple with a mentally retarded
child :
Counseling should begin with a complete history
of the pregnancy and the affected child.
Maternal illness
Infection
Use of prescription and illicit drugs
Alcohol ingestion
Details of the delivery, condition of the neonate
at birth
Presence of other anomalies in the retarded child
Reports of cytogenic studies including fragile x-
testing
Metabolic studies
Pattern of early childhood development and
hospitalization
Possibility of early abuse or neglect should be
reviewed.
If no etiology for the
retardation can be determined, parents can be
offered empiric recurrence risks.
Recurrence risks are increased
for families with more than retarded child. For
brothers of male index cases, and for sibs of index
cases without other neurological abnormalities.
In the absence of a specific
diagnosis, prenatal diagnosis is not possible.
Parents should be informed that amniotic fluid or
chorionic villus cannot exclude a recurrence.
Pedigree charting
It involves the construction of a
family tree in a precise manner.
The family member who first brings
the family to the doctor for medical advice and
attention is called propositus (if male) and proposita
(if female). It provides vital information regarding the
type and pattern of inheritance and thus is of
tremendous help in genetic counseling.
- Counseling Of Consanguineous Couple
Definition:
Consanguinity means relationship by
decent from a common ancestor.
High Risk factor:
Numbers of couples are themselves
closely related of 1st cousin marriage.
Offspring of first cousin marriage
increase two fold of perinatal death, malformation &
mental retardation as compared to normal population.
Familiar disorder for which carrier
testing is possible & heterozygous testing is positive.
Both parents have heterozygous for
recessive trait.
- Genetic counseling in spontaneous
abortions
The first step in counseling couples
experiencing fetal wastage is education One should
inform patients that at least 15 % of clinically,
recognized pregnancies terminate in fetal loss.
About 50 % of abortuses less than 13
wks of gestational age and 20 % of abortuses 13-26 wks
show chromosome abnormalities, prevention of abortion in
such situations is impossible and indeed, undesirable.
If a couple has at least one live
born and one or more pregnancy losses at less than 13
wks of gestation, the likelihood of another loss is
25-30 %.
If a couple has no liveborn or if
their abortus is known to have been chromosomally
abnormal, the risk rises of a maximum of 40-45 %.
Balanced translocations or inversion
accounts for 2-5 % of repetitive abortions
Evaluation of repetitive abortion is
indicated after two or three loses in first 4 months,
however the occurrence of an unexplained fetal death or
anomalous live born infant necessitates evaluation
irrespective of the number of prior abortion.
Discussions with individuals found to
carry chromosomal rearrangements should include the role
of prenatal chromosomal studies (chorionic villus
sampling, amniocentesis) in future pregnancies.
Luteal phase deficiency, uterine and
cervical abnormalities, maternal disease and infection
are potential non genetic causes of fetal wastage and
should be sought if genetic studies are normal.
- Genetic Counseling after birth of
an abnormal child
- Confirmation of diagnosis
- The child should be examined,
by an experienced physician or geneticist to confirm
the diagnosis.
- If chromosomal abnormality
suspected, cytogenetic studies are necessary.
- Complete family history
- Examination of first degree
relatives – If an autosomal dominant disorder is
suspected.
- in cases of an unexplained or
anomalous fetal or neonatal death the physician
should attempt to obtain photographs and reports of
autopsy, cytogenetic biochemical, and X-ray studies.
A good counselor should have the
following qualities.
- He should have strong knowledge of
principles of genetics.
- He should be aware of disease of
genetic origin.
- He should be tactful and have a
sympathetic and kind approach.
Counseling
Initially the parents may
experience denial, shock, bewilderment, grief, fear
or anger.
Counseling should explaining the
nature of the infant’s disorder and the prognosis,
providing answers to questions and offering
emotional support.
The counselor should accept
emotional outbursts with sympathy and empathy, while
maintaining professional objectivity.
Timing of subsequent genetic counseling
varies, depending on the readiness of the couple.
- Genetic Counseling And Screening In
Artificial Insemination
Principle:
Even two individual heterozygous for
same autosomal recessive trait have a 75 % likelihood
that a given child will phenotypically normal.
If donor is heterozygous for one of
the disorder (e.g. sickle cell disease, thalassemia, Tay
- Sachs disease, Cystic fibrosis) he need not necessary
to be rejected, however it should be counseled that the
recipient should not heterozygous for the same disorder.
Despite appropriate screening it is
impossible to guarantee normal offspring.
Screening of donor:
Principle
to select ‘genetically’ perfect donor as impossibility but
rather to eliminate donors whose likelihood of producing
genetically abnormal offspring.
Age: increase age decrease number of
sperms and change in normal morphology.
Health Status of donor
Degree of relation – 1st 2nd
3rd
Any congenital anomalous baby by
donor in his past.
Abortion
Absolute genetic ground for excluding
donor
Present of disorders / in donor
resulting form single mutant gene (Mendelian disorder)
e.g. Marfan syndrome, Retinitis
Pigmentosa.
Presence of certain Mendelian
disorders in a relative, if it is not possible to
exclude donor’s as heterozygous.
e.g. Huntington’s disease in the
donor’s parent, Werding – Hoffman disease in a sib.
Chromosomal abnormality in donor.
E.g. balanced translocation, inversion
P/h of trisomic offspring
Presence of serious polygenic /
multifactorial in the donor or his 1st or 2nd
degree relatives.
e.g. Spina bifida, Cardiac anomaly
Donor’s blood group that is
incompatible with that of recipient blood group.
Relative indicate of exclusion
Age > 40
Serious polygenic disorder in donor’s
1st, 2nd, 3rd degree
relatives.
Less serious polygenic disorder in
the donor (peptic ulcer disease).
P/h of unexplained stillborn or anomalous
liveborn to a donor or his near relative.
- GENETIC SCREENING
Purpose
- To test a population to identify
individuals at elevated risk for a genetic disorder.
e.g. Maternal Serum fetoprotein
screening increased risk for fetus with neural tube
defect.
Pre-requisites
Individuals to be screened should
Understand - Purpose of screening
- Potential risks
- benefits
Formal written consent programs
Verbal consent should be obtained.
Most cases screening is not
warranted if no intervention is possible.
e.g. Screening neonates for Tay
Sach’s diseases.
The screening test should be
– reliable
– Simple to perform
– Inexpensive
Resources:
- Available to follow through in
individuals whose screen is positive.
- Counselors must also be sensitive
to the need to avoid stigmatization of individuals found
to carry abnormal genetic traits.
There is an increasingly strong case for
promoting genetic screening and counseling in primary health
care.
PREGNANCIES AT EXTREMES OF AGE
PROBLEMS OF EARLY PREGNANCY
Psycho sociological Problem :
Mostly unmarried adolescence - so issue
not accepted in society.
Adolescent child bearing described as
‘syndrome of failure’ with respect to education,
establishing a vocation & becoming independent.
Poverty promotes a feeling of
helplessness & unwanted pregnancy leads to anxiety &
depression
Obstetric complication :
Due to inadequate nutrition
poverty : undernourished mother - IUGR baby
Poor health before pregnancy.
Other risk factor associated with
teenage mothers which complicate pregnancies.
Smoking alcohol: substance abuse
more amongst teenagers.
Infectious diseases higher risk
of sexually transmitted disease and HIV etc.
Intrinsic biological factors
related to young maternal age
Complications of septic abortion
Seeking termination of
pregnancies
By unstrained person
¯
Stick insertion etc.
¯
Septic abortion
Cervical dilatation : risk of
cervical injuries, incompetence & Hemorrhage
Problems related to delayed ANC
They seek ANC care due to
illiteracy and poverty
Denial to conceal pregnancy
She may not differentiate early vaginal
bleeding from normal menses & so medical consultation
delayed.
CARE FOR THE TEENAGED GRAVIDA
- Antenatal care in 1st
trimester – accurate dating.
By Ultrasound and menstrual history.
- Screening done for sexually
transmitted diseases.
- Encouragement of early referral for
prenatal care & regular attendance.
- Stress advice about diet and
adverse habits.
- Psychosocial counseling & support.
- Extra advice and education about
pregnancy & child – rearing.
- Delivery in a specialist unit by
trained health personnel.
- Timely termination of pregnancy.
AGE < 30 YEARS
Pregnancy at age more than 35 years
Problems
Currently about 10 % of pregnancies
occur in women in this age group. Earlier studies
suggest that women over 35 are at increased risk for
obstetrical complications as well as perinatal morbidity
& mortality.
For the normal weight, physically fit
women without medical problems, however, the risks are
much lower than previously reported.
Complications
Early pregnancy loss in increased
because of higher incidence of spontaneous abortion and
chromosomal abnormalities.
Age increases all trisomies,
aneuploidy are seen in almost 1 in 50 pregnant women of
age 40 years.
Chronic hypertension has been
reported to complicate 10-20 % of pregnancies in women
over 35 yr. Risk of pregnancy induced hypertension also
increases over 35 years.
Diabetes either gestational or overt
is 2 -3 times more common in older gravida. All these
women should be screened for gestational diabetes.
Incidence of monozygotic twins does
not vary with maternal age however of dizygotic twinning
increases after age of 25 year.
Incidence of leiomyomata increases
with age. Ageing by itself may cause sclerotic changes
in blood vessels leading to inadequate vascular
perfusion of fetomaternal unit.
An increased incidence of GTD has
been reported in women > 40 years & < 15 years of age.
Maternal mortality rate is overall
increased due to preexisting medical conditions in older
gravida.
Care: Two groups of patients
One with high fecundity – a women
married late but conceives soon after.
One with low fecundity – women
married early but conceives long after marriage.
They require meticulous antenatal
supervision and should have a mandatory hospital
delivery.
Management
Result of induction is
unsatisfactory and caesarean section if preferred
alternative.
Sonography is to be done prior to
caesarean section to exclude congenital
malformations of the fetus
Antenatal care during first
trimester would involve an early ultrasound to date
the pregnancy and diagnose conditions like twin
pregnancy, vesicular mole and missed abortion.
History of any pre existing
medical disorder should be taken and patient should
be screened for hypertension and gestational
diabetes mellitus.
If detected both these disorders
require to be controlled early to prevent fetal and
maternal complications later on.
Supervised delivery should be
emphasized
Patient should be counseled
regarding a higher rate of spontaneous abortions and
chromosomal abnormalities in the baby.
Screening for down syndrome by
means of ‘triple test’ at 15-17 weeks gestation can
be planned.
Other diagnostic tests for fetal
abnormalities include chorionic villus biopsy
performed between 8-14 wks gestation
Amniocentesis – Performed at
16-20 weeks of gestation.
– earliest at 8 – 15 weeks
MANAGING 1ST TRIMESTER IN ART
CONCEPTION
Diagnosis:
Same as in normal pregnancy
Beta hCG levels:
Increase serum hCG level exponentially in
early pregnancy. It doubles in 1.9 days (time remain
constant in early pregnancy. Serum Beta hCG increase by 30 –
50 % for an interval of 24 hours).
1st level done 14 days after
hCG injection or 12 days after oocyte retrieval.
|
USG findings |
form LMP |
from ovulation |
|
Gestational sac |
1 day |
|
|
Gestational sac
( 2-3 mm size echo-free structure
surrounded by reflective trophoblastic ring)
|
4 wks |
2 wks |
|
Yolk Sec (3-5 mm)
(Gestation sac double the size of
yolk sac) |
5 wks |
3 wks |
|
Heart motion demonstrated (yolk
sec 4 -5 mm) |
7 wks |
5 wks |
|
Head & limb buds (head & embryo
just distinguishable from body |
8 wks |
6 wks |
|
Cord insertion
Knee & elbow becomes obvious
umbilical cord pulsation |
9 wks |
7 wks |
b -
HCG LEVELS IN ART
Action: It increases progesterone in
normal functioning corpus luteum & therefore of no use
in patients with inadequate ovarian LH receptors & poor
follicular development.
Normal intrauterine pregnancy
It can be detected in maternal serum
or urine as early as 8 – 9 days following ovulation
In ART
Confirmation of pregnancy is by
rising
b hCG levels done at weekly intervals.
1st level - after the hCG
injection
- 12 days after oocyte
retrieval
Time required for doubling of
b - hCG levels constant – 1.9 days
Means serum quantitative
b hCG levels increase between 30 -50 % for interval of 24
hours in an normal intrauterine pregnancy.
USG
With the use of TVS, it is possible to
image a gestational sac in the uterus with in 1 day (since
last menstrual period)
Uterine cavity shows a thickened
endometrium with a gestational sac seen as a 2-3 mm echo
free structure surrounded by reflective trophoblastic
ring.
By 5 weeks the yolk sac is
demonstrable and measures between 3-5 mm. The
gestational sac is double the size of yolk sac.
By 6 weeks yolk sac diameter is 4-5
mm. Cystic spaces become visible. Most of the times
heart motion is demonstrated.
By 7 wks embryo measures 7-8 mm in
length and yolk sac 5 mm in diameter. Heart rate at this
stage is approximately 120 beats / min.
By 8 wks embryonic movements, limb
buds and central nervous system develop. The finding of
equal sized yolk sac and head are typical of this
gestation.
By 9 wks umbilical cord pulsations
are visible and a physiological umbilical herniation of
the gut and insertion of cord in the abdomen may be
seen.
At 10 wks organogenesis is complete.
By 12 wk physiological umbilical
hernia has started to reduce and disappear.
Management in 1st trimester
ART pregnancy
To improve clinical outcome with ART
progesterone and/or HCG supplementation has to be given.
Because of the ovarian
hyperstimulation progesterone is preferred.
Both administered till placental
function takes over i.e. 10-12 weeks of gestation.
Luteal phase inadequacy results
from ovarian hyperstimulation prior to follicular
aspiration, mechanical trauma to follicle, physical
removal of granulose cells resulting in decreased
progesterone secretion and luteal disruption.
Method of administration
Micronized progesterone
Pessaries: Dose 200 mg BD till menses,
400 mg BD after confirmation
IM 100 mg till menses or till 10-12 weeks
of gestation
No ill defects were noted on early
pregnancy
Side effect: sedation
Only pure progesterone has to be used for
luteal support or in the first trimester.
Human Chorionic Gonadotropin (HCG)
Dose: 1500-2000 IU in 2 days after
ovulation or 3 days after LH surge. Given every 2 days till
menses. If pregnancy confirmed it is continued in dose of
5000 IV IM twice a week till 10-12 weeks of gestation.
Increased risk in ART pregnancies
associated with patients’ characteristics such as
increased maternal age and lower previous parity
along with underlying cause of infertility and
ovulation stimulation.
After confirmation of pregnancy
estradiol valerate and progesterone has to be
continued till day 80
|
Days |
Estradiol valerate |
Progesterone |
|
Day 18-47
Day 48-67
Day 68-71
Day 72-75
Day 76-80 |
4 mg per day
8 mg per day
6 mg per day
4 mg per day
2 mg per day |
400 mg twice daily
400 mg twice daily
400 mg twice daily
400 mg twice daily
400 mg twice daily |
EARLY PREGNANCY LOSS
Pre clinical abortion or occult pregnancy
loss
A preclinical abortion, defined as a
pregnancy diagnosed by at least two beta hCG values
which ends within 28 days of fertilization.
Incidence is 8.7 % - 16.6 % of IVF
pregnancies.
Incidence of pre clinical pregnancy
loss is much less in oocyte donation group as
endometrium is manipulated to achieve almost
physiological conditions where as in women undergoing
IVF / ICSI the endometrium is subjected to
supraphysiological serum steroid level which affect
implantation.
To reduce the incidence of
implantation failure embryo transfer may be done in
natural cycle, here the embryos are cryopreserved and
then transferred in natural cycle.
Clinical abortions
A clinical abortion is defined as
spontaneous termination of pregnancy of at least 28 days
after oocyte pick up. Incidence of clinical abortion after
IVF ranges from 18.4 – 29.9 % it is similar as for ICSI.
Incidence increase from 24.1 % to
41.9 % for age more than 40 years. Incidences increase
by 2.4 % per year after age of 34 year.
Antenatal surveillance in ART
pregnancies starts earlier than in naturally conceived
pregnancies. This might explain the higher incidence of
abortion in ART as many. Pregnancies in natural
conception may go unrecorded and unnoticed.
75 % of total pregnancy losses in ART
occur in first trimester.
1ST TRIMESTER PROBLEMS IN ART
- Ectopic pregnancy
The first pregnancy after IVF-FT was
ectopic pregnancy.
|
5 % |
incidence of ectopic pregnancy
after IVF-FT in large multicentric study.
|
|
4 % |
incidence of ectopic pregnancy
after GIFT. |
| |
1.4 % |
with ejaculated spermatozoa
|
| |
0.45 % |
with testicular spermatozoa |
| |
0 % |
with epididymal spermatozoa |
|
0-1.9 % |
Incidence of ectopic pregnancy
after ICSI |
Complete tubal occlusion with diathermy
before starting IVF treatment was advocated to prevent
ectopic pregnancy.
But its drawbacks are:
Adhesions of tube following diathermy
prevent / or make difficult ultrasound guided oocyte
retrieval.
Advantage of complete tubal occlusion:
Reduce importance of laparoscopic
assessment before IVF.
- Bilateral tubal pregnancy
Twin pregnancies in same tube are
frequent and simultaneous extrauterine and intrauterine
pregnancies are the most frequent occurrences.
Bilateral simultaneous tubal pregnancy is
rarest form of binovular pregnancy occur during assisted
human conception.
1st case – following IVF – ET
– reported by Hewitt and Colleagues.
Risk & colleagues reported between 1985 &
1989 one unilateral twin and four bilateral tubal
pregnancies amongst.
124 extrauterine
1648 intrauterine
Gives an incidence of 1:30 extrauterine
pregnancies and 1:412 intrauterine pregnancies
- OVARIAN PREGNANCY :
Primary ovarian pregnancy is rare form of
ectopic pregnancy.
Incidence:
As low as 1: 60,000 to as high as 1:7000
pregnancies.
Management:
Conservation of normal ovarian tissue is
necessary & next pregnancy will be normal intrauterine
mostly.
- CERVICAL PREGNANCY
Cervical pregnancy after IVF occur as a
result of cervical manipulation
1st case – reported by
Brinsden & colleagues following GIFT
Brinsden believe that embryo migration
rather than cervical manipulation is responsible for
different forms of ectopic implantation.
Early diagnosis: To allow conservative
Surgical Treatment
Use of methotrexate
- HETEROTOPIC PREGNANCY
Combined intra & extrauterine pregnancy
is estimated to occur in 1 % of IVF pregnancies.
A multicentric study revealed
that the high prevalence of tubal damage and
multiple embryo transfer appeared to be the
predisposing factors for this condition.
Patient who had tubal surgery
represented a high risk group.
Transvaginal sonography is
superior to trans abdominal ultrasound in diagnosing
the extrauterine pregnancy.
Early diagnosis of viable ectopic
pregnancies before rupture is important and prevents
mortality, reduces morbidity and offers the chance of
selecting patients for conservative treatment.
OBSTETRIC COMPLICATIONS
1st trimester vaginal
bleeding: vaginal blood loss in 1st trimester
occurred more often in the IVF group as compared to the
control
1st trimester bleeding
in assisted conception was probably noted due to
early antenatal surveillance by ultrasound.
First trimester bleeding may be due to
Hormonal deficiency caused by
ovarian stimulation luteal phase defect and
increased maternal age.
Hampered endometrial receptivity
Vanishing twin syndrome
Low lying placenta
Subchorionic bleed
Presence of submucous myoma
associated with infertility.
All ART pregnancies in 1st
trimester monitor meticulously and regularly by
serial HCG levels and ultrasonography.
Administration of progesterone
and / or HCG and folinic acid is also very essential
Maternal complication – OHSS – Incidence
8 to 23 %
- Most serious iatrogenic complication of
ovulation induction.
- 1% incidence
- Follicular aspiration in assisted
conception protects against its occurrence.
- High risk of OHSS in patients with
polycystic ovarian syndrome
Classification
Main three categories and six grades
according to the severity of symptoms and signs and
laboratory findings.
|
1. Mild hyperstimulation
Grade I – Estrogen > 150 m g/day, Urine
pregnanediol excretion > 10 mg / 24 hrs
Grade II –Grade I with ovarian
enlargement |
|
2. Moderate hyperstimulation
Grade III - grade II with
abdominal distention
Grade IV - grade III with nausea,
vomiting and diarrhea |
|
3. Severe hyperstimulation
Grade V - grade IV with large
ovarian cyst and ascitis / hydrothorax
Grade VI - grade V with
haemoconcentration with or without coagulation
abnormal. |
Mild forms are net major, moderate and
serious forms are requiring hospitalization.
Classification II
|
Mild Grade I |
- |
Abdominal distention and
discomfort |
|
Grade II |
- |
Features of grade I with GIT
(Nausea / vomiting / diarrhea)
Ovaries are enlarged upto 5-12 cm |
|
Moderate III |
- |
Mild hyperstimulation with USG
evidence of ascitis. |
|
Severe IV |
- |
Moderate hyperstimulation with
clinical ascitis / hydrothorax / respiratory
difficulties. |
|
V |
- |
Change in the blood volume /
increase blood viscosity due to haemoconcentration,
coagulation defects and diminished renal perfusion. |
Classification III
|
Severe OHSS |
Critical OHSS |
|
-1 Enlarged ovaries
-2 Massive ascitis with or without
hydrothorax
-3 PCV > 45 %
-4 WBC > 15000 / cumm
-5 Oliguria
-6 Serum creatinine
1 – 1.5 mg/dl
-7 Creatinine clearance
> 50 ml / min
-8 Liver dysfunction
-9 Anasarca
|
-10 Enlarged ovaries
-11 Tense ascitis with or
without hydrothorax
-12 PCV > 55 %
-13 WBC > 25000 / cumm
-14 Oliguria
-15 > 1.6 mg/dl
-16 Creatinine clearance
< 50 ml / min
-17 Renal failure
-18 Thrombo embolic phenomena
ARDS
|
CONGENITAL MALFORMATIONS
- Women who become pregnant after ART
are usually older than their peers who conceive
naturally, a
i. have atypical
reproductive histories.
ii. high
incidence of multiple pregnancies.
iii. managed to
conceive by novel techniques.
- Incidence of congenital
malformations in general population according to
Kennedy.
From 0.83% to 4.5%.
- Major malformation was defined as
any anomaly leading to functional impairment or
necessitating surgical correction.
- Incidence of major and minor
malformations is different for different types of ART
techniques.
SPECIAL
PREGNANCY AFTER CRYOPRESERVATION
Incidence of congenital malformation
after replacement of cryopreserved embryos is similar as
what of normal control group.
Relative risk of major congenital
malformations is 1.4
Relative risk of minor congenital
malformations is 1.7
That is less then expected in general
population thus cryopreservation process itself does not
appear to have any impact on embryo health and subsequently
on the rate of congenital anomaly.
PREGNANCIES AFTER SUB ZONAL INJECTION OF
SPERMATOZOA:
The overall incidence of children
with malformation was not different from the frequency
in general population. Now-a-days ICSI had replaced SUZI
for male factor infertility.
PREGNANCY AFTER ICSI
- ICSI involves the injection of a
single sperm into the cytoplasm of oocyte.
- Pregnancy rates are in the range of
35.40.
- Introduction of ICSI has raised
concern about an increase in incidence of congenital
malformations and chromosomal aberrations.
Additional risk after ICSI procedure may
be due to
Selective mechanism against
physiological & genetically abnormal spermatozoa by
passed.
Abnormal oocytes might be
fertilized.
Altered environmental /
mechanical & chemical damage to oocyte might lead to
perturbations of meiosis & mitosis.
Various chemical or environmental
exposures might lead to point mutations, resulting in
genetic disease visible at birth.
MATERNAL COMPLICATIONS
Complications of OHSS
Vascular complications
Hypercoagulability state
Increase in fibrinogen, plasma, alpha 2,
antiplasmin complexes and reduction in anti thrombin III
concentration and significant increase in whole blood clot
lysis time, implying disruption of balance of coagulation
and thrombolysis leading increase in coagulability.
Venous compression due to enlarged
ovaries and ascitis leads to thrombo embolism
Liver dysfunction - increase liver
enzymes
-
structure remains unchanged
Respiratory system - Pleural effusion
- Respiratory distress 2o to ascitis
- Hydrothorax
- ARDS
Renal / pre renal failure and
complications of hydroureter
Gastrointestinal complications
- Nausea, vomiting, abdominal
distention, diarrhea.
5) Adnexal torsion
Pathophysiology of OHSS
Massive bilateral cystic ovarian
enlargement
Ovaries have significant degree of
stromal edema, interspersed with multiple hemorrhagic
follicular and theca-lutein cysts, areas of cortical
necrosis and neovascularization.
Enhanced capillary permeability
Resulting in ascitis and pleural
effusion
Two forms of hyperstimulation
3 – 7 days after oocyte recovery
caused by HCG
12-17 days after ovulation
stimulated by secretion of embryonic HCG
Prediction of OHSS : - Use of
ultrasound
-
endocrine monitoring of
follicular development
Factors predicting
Young patient < 35 years, thin
Polycystic ovarian disease
High serum estradiol levels > 1 =
2500 pg/ml
Ultrasonography reveals pc at
baselines scan, large number of follicles and conception
cycles particular multiple pregnancies.
Doppler – measurement of intraovarian
vascular resistance
OHSS in previous cycle.
Use of HMG & GnRH agonist.
Prevention of OHSS
withhold HCG and continue GnRHa
Delaying HCG – coasting for period’s
variable from 2 to 10 days by withdrawing gonadotropins
and allowing E2 levels to decline to 2000 pg/ml before
administering HCG.
Use of GnRHa to trigger ovulation
Dose: 200 mg three times at shores
interval
Follicular aspiration - TVS it will
empty follicle fluid & granulose cells.
Progesterone and replacement of
frozen thawed embryos at a subsequent cycle.
Gradual increase and low dose
gonadotropin protocols and laparoscopic ovarian drilling
in PCOS.
Albumin – It maintains intravascular
volume & prevents the ensuring effects of hypovolemia,
ascitis, and haemoconcentration.
Treatment
Admission in moderate and severe OHSS pt.
Strict fluid chart
Check plasma and urine osmolarity
Check urea and electrolytes
Check clotting parameters
Carry out liver function tests
Perform pregnancy tests
Perform pelvic sonography
Invasive homodynamic monitoring
Daily weight & abdominal girth, chest
X-Ray
Medical treatment
Correction of circulatory and
electrolyte imbalance use of plasma expands.
Anticoagulants if clinical or
laboratory evidence of thromboembolism.
Dopamine in oliguric patients.
Surgical treatment
Aspiration of ascetic fluid –
improves symptoms, renal function, urinary output,
venous return and cardiac output. It also shortens
hospital stay. Repeated aspiration may be required.
Laparoscopic surgery / Laparotomy
If hemorrhage, torsion, rupture of
ovarian cyst or ectopic pregnancy occurs or only for
haemostatic purpose.
VACCINES IN 1ST TRIMESTER
PREGNANCY
Besides inevitable vaccines like
following animal’s bites or exposure where antirabies serum
and vaccine use are mandatory and vaccination for travelers,
most vaccine use is elective and should be postponed beyond
the first trimester.
In general, live vaccines (measles,
mumps, rubella, varicella, OPV, BCG) should be avoided in
the periconceptional period and first trimester. However,
accidental vaccination with these agents is neither a cause
for alarm nor an indication for MTP. Other types of vaccines
using killed agents (cholera, pertussis, hepatitis A,
influenza, plague) or toxics (tetanus, diphtheria), though
theoretically safe in pregnancy, are best avoided in the
first trimester.
RECURRENT 1ST TRIMESTER
PREGNANCY LOSS
Definition
It means a case of periodic pregnancy
loss within the first trimester.
ACOG recommendations 2001 state that it
is defined as…
"At least two or three, or more
consecutive pregnancy losses in the first or early second
trimester".
When to start: investigation
Principles
|
No. of spontaneous abortion |
Percentage of having second
spontaneous abortion in next pregnancy |
|
Single |
15 – 20 % |
|
Two (in row) |
25 – 35 % |
|
3 (three) |
33 – 45 % |
|
6 or more |
53 % |
Approximately 80 % and 90 % woman
with single spontaneous abortion will deliver a
viable infant in the next pregnancy.
After 3 miscarriages a patient
receives no specific antiabortion therapy can still
hope to deliver a healthy infant subsequently in at
least 50 % of cases. Based on this information
classically, the cut off has been three or more
spontaneous abortions are termed as recurrent
spontaneous abortion to be investigated.
Gynecologist should keep in mind some
holistic perspective of the patient for when to start
investigation
Obstetric history :
Economic status :
Since tests for investigation are not
cheap and the list of investigation is more. Doctors
must consider economic status of patient.
Psychological make up
Psychological trauma and anxiety invoked
after spontaneous abortion.
WHAT ALL TO INVESTIGATE
Diabetes should be ruled our by FBS &
PPBS, when there is strong doubt of a diabetic trait,
GTT should be repeated at 32 -34 wk even when the GTT is
found to be normal in early pregnancy.
Anticardiolipin antibody assays IgG >
20 GPL 1gm > 15 MPL
Lupus anticoagulant
Beta 2 glycoprotein – 1 dependent
anticardiolipin antibody are significantly associated
with adverse pregnancy outcome.
aPTT that relies on the activation of
the prothrombin activator complex and which will be
appropriately deleted with normal plasma when abnormal.
Management
The available options are :
Prednisone, low dose aspirin, heparin and iv
immunoglobulin, low dose aspirin
Mechanism of action: decrease in
prostacyclin is the cause for thrombosis
Increase the prostacyclin to
thromboxane ratio to enhance the effect of prostacyclin.
Safe in pregnancy
Dose: 60mg /day
Heparin:
Both standard unfractionated heparin and
low molecular weight heparin are used for prophylactic
anticoagulation during pregnancy.
Dose: 5000 units / day
subcutaneous heparin dose not cross
the placenta and there fore no adverse effects on the
fetus.
On comparing heparin + aspirin with
prednisone + aspirin, both are equally effective, but
with prednisone the morbidity and the incidence of P/H
is higher. Thus aspirin + heparin are now the standard
treatment.
In patient with APL without previous
history of thrombosis the recommended treatment is to
use low dose aspirin preconceptually and to add heparin
as soon as pregnancy viability is confirmed on
ultrasound.
APLA antibody if positive on two
consecutive occasions six to eight weeks apart, the
patient should be treated with heparin and low dose
aspirin in her next pregnancy attempt.
Even successful pregnancies with this
regime, are prone to a high risk of complications like
pre-eclampsia, fetal growth restriction and preterm
birth.
Psychological causes for recurrent
miscarriage focused on personality characteristics of
the patients.
Effort should have been made to teach the
patient about the cause and treatment of her particular
problem before pregnancy.
