PG Classroom - Seminar - The First Trimester


- Sites of Implantation

Implantation occurs in the endometrium of the anterior or posterior wall of the body near the fundus on 6th day which corresponds to the 20th day of regular menstrual cycle.

Normal – Uterine wall – Posterior, Lateral or Superior wall.

Abnormal – ectopic abnormal implantation can occur due to premature implantation.


Fertilization of human ovum by spermatozoa occurs in fallopian tube within minutes to few hours after ovulation. By end of 6 -7 days (20 -21 day of regular cycle) after fertilization.



Endometrium normally prepared by progesterone on anterior or posterior wall of fundus

Other site


fallopian tube, ovary, peritoneum, Very rarely spleen

Functional Changes during Implantation

Blastocytst :

Zona pellucida disappear so blastocysts becomes deriving force


Inflammatory process in blastocysts


Increase prostaglandin platelet activating factors plasminogen activator (help in decidual reaction).

Decidualization of endometrium

Trophoblast produce metalloproteinase

Degradation of endometrium cell

Endometrium in secretory phase has decrease effect of progesterone.

Receptive phase the endometrium acquires ability to implant developing embryo:

a. Compact layer: Implantation occurs in this layer. Structurally it is composed of dense stromal cells, uterine gland necks, capillaries of spiral arteries.

b. Spongy layer consists of swollen stromal cell, uterine gland bodies, and spiral arteries.

c. Basal layer: is the retained layer and is responsible for regeneration.

Anatomical Changes of implantation:

Fertilized egg in the blastocyst stage travels through fallopian tube and enter in uterine cavity.

Increase no. of blood vessels (neo angiogenesis) in endometrium.

Zona Pellucida disappears and increase adhesiveness of blastocyst cell to endometrium cell.

Penetration: Blastocyst is burrowed more an more inside stratum compactum of decidua (interstitial implantation). Further penetration stopped by maternal immunological factors and process completed by 10-12 day of cycle.

Vacuoles appear in the advancing syncytium which fuses to form large lacunae. Maternal blood enters in the lacunar space.


Formation of physical and nutritional contact of growing embryo with endometrium.

Nutritional obtained from aerobic metabolic pathway from maternal blood.


Endometrium acquires the ability to implant the developing embryo within specific time window termed the "receptive phase". During this period there is increased structural and secretory activity of the endometrium that is brought about in response to progesterone following implantation is known as decidual reaction & is consist of 3 layers.

Superficial compact layer: Implantation occurs in this layer it consists of compact mass of decidual cells, gland ducts and dilated capillaries of spiral arteries.
Intermediate spongy layer (cavernous layer) contains dilated uterine glands, decidual cells & spiral.
Thin basal layer – Contains basal portions of the glands and is apposed to uterine muscle this is the retained layer and is responsible for regeneration.

Implantation occurs in the endometrium of the anterior or posterior wall of the body near the fundus on the 6th day which corresponds to the 20th day of a regular menstrual cycle.

Implantation basically occurs in two stages.

a) Attachment
Attachment of blastocyst trophoblast to endometrial epithelium is known as a decidualization.
Decidualization results in an increased vascular permeability & secretory activity of stromal cells thus allowing efficient placentation at the same time restricting trophoblastic invasion going to deep.

b) Adplantation
It is the invasion of deciduas by trophoblastic cells.
Within hours of attachment trophoblast destroys epithelial cells. The trophoblastic villi invade the deciduas & blood vessels walls resulting in the blood filled lacunae in the bathing trophoblast in maternal blood.

Nutrition is obtained by aerobic metabolic pathway from the maternal blood.

Further penetration is stopped by the maternal immunological factor and the original point of entry is scaled by fibrin clot and later by epithelium.

The process is completed by 10th or 11th day.
On the day 7 after fertilization, the syncitio trophoblasts secrete proteolytic enzymes. These enzymes breakdown extracellular matrix around cells & allow passage of blastocyst into endometrial wall.

The trophoblastic cells secrete human chorionic gonadotropin that maintains deciduas and corpus luteum.

Secretory products of the glandular epithelium function to support the nascent embryo & begin the early communication that continuous into pregnancy.

Maximal uterine receptivity – 20-24 day of cycle.
The basic structure of placenta is formed by about 5 week’s gestation.

Pinopodes – Hairy like cell microvilli fuse to a single flowerlike membrane projection.
Their numbers correlate with implantation.
Formation of pinopodes is on day 20-21 in natural cycle.

Detection of pinopodes is a potential clinical marker to assess endometrial receptivity.

Important events following fertilization
0 hours - fertilization
30 hours - 2 cell stage (Blastomeres)
40-50 hours - 4 cell stage
72 hours - 12 cell stage
96 hours - 16 cell stage, morula enters the uterine cavity
5th day - Blastocyst
6-7th day - Zona pellucida disappears
interstitial implantation occurs
9th day - Lacunar period
Endometrial vessels tapped
10-11th day - Implantation completed


Success of blastocyst implantation is dependant on signaling between the embryo and the receptive endometrium. Inter cellular signaling molecules which include hormones, growth factor and cytokines, participate in the maternal embryonic dialogue. These biologically active molecules may target uterine and / or embryonic tissues in a biochemical cascade that co-ordinates the two developmental programs during implantation

The molecules involved in implantation include.

Cell- cell and cell-extracellular matrix interaction are fundamental processes involved in cell migration and tissue remodeling. Both the cyclic regeneration of the human endometrium during the menstrual cycle as well as the process of embryo implantation involves such dynamic interactions. Integrin adhesion molecules expressed on the surface of cells play critical roles in the transmission of signals from the extracellular milieu to the cells. Both cell-cell and cell-matrix interactions are important for trophoblast invasion of the decidual stroma and decidual spiral arteries. Cell-matrix adhesions are mediated by specific receptors, mostly belonging to the family of integrins. Signals transduced to the cells from the matrix via integrins could play a pivotal role in the control of cellular behaviour and gene expression, such as metalloproteinase that facilitate matrix degradation and tissue remodeling.
During implantation and early placentation the invasiveness of trophoblasts appears to be controlled in part by the switching of the integrin subunits expressed on these cells. Cells invade the uterine wall a Ib 1 integrin (collagen type IV / laminin receptor) is up regulated. Blocking antibodies to this integrin or its ligands retard invasion in the in vitro assays and placental cytotrophoblasts from late gestation, which are less invasive lack expression of a Ib 1. Experiments indicate that fibronectin and its receptor act to restrain invasiveness of the cytotrophoblasts.

TROAP is also called trophin associated protein or trophin assisting protein or Tastin. It may play an important role in implantation. The initial attachment of the trophoblast to the endometrial epithelium during implantation occurs via the apical cell membranes of the embryonic and maternal cells. Recent molecular approaches to elucidate the mechanism of embryo implantation: trophinin, bystin, and tastin as molecules involved in the initial attachment of blastocysts to the uterus in humans. Trophinin is a membrane protein strongly expressed both on the apical surface of the trophectoderm of simian blastocyst and at a putative implantation site of the human endometrium. Bystin and tastin are cytoplasmic proteins that associated with trophinin by presumably forming active adhesion machinery.

The cytokines that are generally maximally expressed in human endometrium with maximal production in the secretory phase, particularly during the "window of implantation", but functional studies of their role in implantation in women and other primates are still required.
It is an endometrial protein with proposed immunomodulatory activity during human embryonic nidation.
GTP ases:
The Rho family of small GTP ases occupies a key position in the control of cell motility and morphology in response to extracellular stimuli. Rho proteins trigger the formation of contractile stress fibers, resulting in regulation of cell motility. RhoA in decidual cells may be important for embryonic development and differentiation after attachment.
Others are calcitonin and heparin binding epidermal growth factor like growth factor.

Apoptosis and implantation:
Apoptosis is a mechanism of cell death in which cells undergo a genetically determined programme.

In order to make trophoblastic invasion possible, cells of the endometrium must make room for the embryonic cells by sacrificing themselves in a process of programmed cell death or apoptosis. The implanting blastocyst has to appose and adhere to the endometrial epithelium and subsequently invade it. In vitro experiments have shown that when the blastocyst adheres to the Endometrial Epithelial cell monolayer it induces a paracrine apoptotic reaction.


1. Age: Mother maternal age Normal implantation rate 25 – 30 yr, 30 %
> 40 yr. < 10 %
Paternal not related to paternal age
Factors disfavoring implantation:
1. Fibroid : Submucosal or poly fibroid
2. Abnormal : Development of endometrium
3. Anti phospholipid antibody in mother
4. Genetic programming of embryo


Diagnostic tests


Help to identify potential implantation problems

Tests include


Hysterosalpingogram (HSG)



Saline – infusion sonogram



Endometrial biopsy



Transvaginal ultrasound

Endometrial biopsy
- To asses endometrial development
- Looking for abnormalities
Such as – stromal glandular dyssynchrony
- Luteal phase defects
- Abnormal integrin expression
Transvaginal ultrasound
- To asses the thickness of endometrium
- Uterine blood flow in relation to endometrial receptivity
In normal cycles – Uterine blood flow rises in the luteal phase
Coinciding with timing of implantation

Biochemical studies and estimation of molecules involved in implantation may occupy an increasingly important place in diagnosis of implantation problems in future.


Correct implantation and placental development are essential to a successful pregnancy.

Defects in implantation/placentation process can have serious consequences for the pregnancy.

Implantation failure can result in abortions due to improper nidation, genetic defect to immunological factors including antiphospholipid antibodies & maternal age.

Pregnancy induced Hypertension

Inadequate trophoblast invasion resulting in poor perfusion with maternal blood can further lead to

Maternal hypertension / convulsions

Fetal growth restriction

Death if untreated

Placental defects resulting in accidental hemorrhage and placenta accrete.




Progressive destruction of ovarian substances by endometriotic implants.

Disturbances in patterns of GnRH pulses in the early to mild follicular level.

Hyperprolactinemia and inhibin secretion.

23 % of patients of LPD have low progesterone receptor.

The final common pathway in LPD is a disturbances in the endometrium either due to inadequate progesterone receptor induction during follicular phase or to insufficient peripheral progesterone levels reaching endometrium from ovary. Both these situations lead to abnormal implantation or early pregnancy wastage.

Mechanism of Luteal Phase Defect

Attenuated LH surge can give rise to LPD by inducing adequate progesterone secretion within the granulose cell of the follicle which will be responsible for immaturity of oocyte. Hence, even if ovulation takes place the quality of oocyte will be good enough for fertilization.

There events that precede the ovulation are brought by LH are :

- 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


Accelerated luteotropic stimulus

Intrinsic cellular defects of the corpus luteum

Inadequate endometrial progesterone receptors.


· Natural progesterone

Micronized progesterone




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.


Oral progesterone varies from 200-400 mg per day in the divided doses one hour before or after meals


200 – 600 mg in to thus divided doses immediately after ovulation and continued till 12 weeks of pregnancy.

· Human Chorionic Gonadotropin


- 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.


- 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.


- More expensive

- Cannot be self administered


- 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


- 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.



It is pure orally active progestin.

Kind of progesterone derivative


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.


5 mg tablet (Duphastone)

30 mg daily


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


Undiagnosed vaginal bleeding

Women with history of thrombo embolism


Not inhibit ovulation

Mildly catabolic action

Preferred when contraceptive effects are not required.



Pure progestin mainly available in depot form.

Mechanism of Action:

Production of placental hormones by direct stimulation on placenta.


Injection Proluton depot 500 mg / 2 ml

Tablet 10 mg & 5 mg


Prescribing 17 HPE during early pregnancy to prevent miscarriage is not advisable.

It has mildly catabolic action.


- 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.


Hormonal :

Excess of chorionic gonadotropin


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



Carbohydrate starvation





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


To remove the neurogenic elements

To correct the fluids, electrolytes & other metabolic disturbances effectively.

To prevent or to detect at the earliest ominous complications.


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.


- 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


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


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.



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.


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.


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



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


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


Gestational Appendicitis:


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


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


- Ultrasound of gall bladder is a safe and accurate method of diagnosing gall stones.

- Raised WBC count

- Abnormal liver function tests

- Raised amylase


- Conservative treatment

Surgical treatment – Laparoscopic cholecystectomy


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.


Incidence: 0.1/1000 pregnancies

Rarely seen in early pregnancy

- Causes: gallstones





- 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



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


Mortality and morbidity to both mother and fetus is high.

Gastro – Esophageal Reflux

Sign / symptoms

- Epigastric pain

- Heartburn

- Nausea


- Worse on an empty stomach

- Relieved with antacids or food.



- Diet

- Lifestyle changes

- Antacids – H2 receptor antagonists most commonly used.



Surgical – Laparoscopies

Sucralfate and omeprazoles avoided in the first trimester.

Gastroscopy is better postponed to second trimester.


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


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.


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


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


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.


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


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:

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.


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.



- 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.


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


- 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.




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.


- 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.


Pregnancy at age more than 35 years


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.


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.


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




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


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


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.


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


Estradiol valerate


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


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.


- 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


Primary ovarian pregnancy is rare form of ectopic pregnancy.


As low as 1: 60,000 to as high as 1:7000 pregnancies.


Conservation of normal ovarian tissue is necessary & next pregnancy will be normal intrauterine mostly.


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


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.


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


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.



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


- 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.



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.


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.


- 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.


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


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.


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.



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.  



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


No. of spontaneous abortion

Percentage of having second spontaneous abortion in next pregnancy


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.


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.


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


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.



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