DEC 2011 - Issue No

A SECOND CHANCE AT MOTHERHOOD
As India gave birth to the world's seven- billionth baby on October 31st 2011, the first thought that crossed
my mind was “Why are we always forefront in the population explosion business!” . As I read the article
further, I was proud that it happened to be a female child, in a country where infanticide still existed in
infamous proportions and in a village that already had a skewed sex ratio.
Then my thoughts drifted over to our country's population statistics, male to female birth ratio, disparities
among sexes, child labor, poverty line, unemployment, illiteracy- the list was endless. I snapped out of it
and shifted focus to the fact that this is a newsletter I was writing and not an article. What is the medical
topic of interest that I could share with the numerous doctors and professionals that I mail these to and
what is the response I am going to get?
Till date, we have received positive feedback for our interesting case presentations and statistics. This
time, I have deviated from conventional medical scenarios in assisted reproduction.
Our primary service is to cater to those who are childless, then we include those who need a second child
and lastly, in the past five years there has been a new trend. Parents that have lost a child or children in
natural disasters, illness, road traffic accidents and suicide have been approaching fertility specialists, to
get that second chance at motherhood. Majority of them are cases that have undergone family planning
after their second or third childbirth.
So with failure of a tubal recanalization surgery, or increasing age of the mother being the stumbling
blocks, their only means to somehow bear a child in the memory of their lost ones is through assisted
reproduction.
Mrs. S, 39 years old, stood in front of me, absolutely calm. She is a very good looking woman, who had
borne two children, a boy and a girl. The girl now 21 years was, clearly in their social background, of
marriageable age. The boy was only 17 when he died in a bike accident two years ago. She had denied him
permission to go to a friend's house on his father's bike, which had provoked the youngster to steal the keys
and it proved fatal. She never bothered to see his body or listen to any information regarding his death. “I
still don't know anything doctor, I simply refused to see or hear any details”. “I only remember him asking
me permission to go out and am happy my memory is frozen in time”.
Nothing was going to stop her now from having another child which she believes would be his second
coming. “I know you can do it doctor, please give me this second chance” she said.
Mrs. SL, 30 years old, came to us in March 2011, having lost two beautiful daughters in a road accident in
November 2008.They were aged only four and three respectively. She was inconsolable. Two failed
attempts of IVF at Kerala had brought her to us. Now pregnant after IVF, she still breaks down at the
slightest memories of her daughters.
Similarly, Mrs. D, aged 49 years, lost her 24 year old daughter in an accident at Nasik in May 2010.
Within 4 months of her death, the couple came seeking treatment. A picture of her daughter adorns her
antenatal file, as she gazes anxiously at her scan findings confirming a twin pregnancy.
Mrs. JJ, aged 41 years, came to us in February 2006 for treatment after having lost two sons aged 16 and
12 years within a span of 2 years. The elder son had died of an electric
shock and the younger one died of a head injury after having been beaten by his school teacher. Tubal
recanalization had failed owing to adhesions obscuring the fallopian tubes. She was persistent with her
treatment having failed 2 attempts of IVF, followed by a break of 3 years and another failure. She finally
conceived twins in her fourth attempt and became a proud mother of a girl and a boy on 22/09/2011.
The devastating tsunami of 2004 saw many couples scramble for treatment, especially with hope for tubal
recanalization. We had 9 couples of whom 5 conceived and delivered. We had decided to forego the
treatment cycle costs for such couples.
Mrs. CT, aged 43 years had lost both her son and daughter in a drowning accident in the US in December
2006. She was a staff nurse by profession and came to us in July 2007, few months before the first death
anniversary of the children. She conceived in the second attempt with us and delivered twin girls on
2/4/2009 in her hometown of Kerala.
Mrs. G S, aged 45 years, came to us exactly a year after her 18 year old son was killed in a hit and run by a
lorry on a main road, just across their home in February 2010. She was subsequently operated for multiple
fibroids in her uterus and signed up for a donor oocyte programme. There are other issues to be dealt with
besides a huge emotional overlay.
Most of these women have succumbed to stress and lifestyle related disorders such as Hypertension and
Diabetes. In the case of Mrs. G S, she also had partial phrenic nerve palsy which makes it difficult where
anesthesia is concerned. Age is also an obvious deterrent where biological conception is concerned,
making donor oocyte programme easily acceptable among the couples.
Such is the trend where loss of the only child or its sibling brings forth couples to try fertility treatment.
What is heart rending is that while they are calm and collected stating what they have come for, we are left
fighting tears that threaten to spill, trying to appear just as brave! We have presented the statistics below to
show how many such couples have sought help, become pregnant and delivered and the ones undergoing
treatment.
January 2005 - August 2011
Type of
Disasters
No of
patients
No of
pregnancies
Delivered
Ongoing
Fetal
loss
Tsunami
9
5 (56%)
5 (100%)
-
-
Drowning
5
2 (40%)
2 (100%)
-
-
Accident
27
8 (30%)
3 (38%)
3
2
Suicide
2
1 (50%)
1 (100%)
-
-
Illness
14
3 (21%)
2 (67%)
1
-
Total no of patients
57
Pregnancies achieved
19 (33.3%)
Delivered
13 (68.4%)
Ongoing
4
Miscarriages
2
As the numbers increase and as I hold the positive pregnancy test of Mrs. S who lost her teenage son, I am
left wondering if it's a privilege or not to enable miracles, surpassing fate or nature's unpredictable ways
DR. PRIYA SELVARAJ MD MNAMS MCE
Mrs. LD, aged 36 years, married for 11 years came to us for primary infertility on 2/8/2010. She was a
known case of polycystic ovarian syndrome and also gave history of two previous early miscarriages in the
years 2007 and 2008. She was already on treatment for borderline hypothyroidism since 3 years. Her
earlier infertility work up included two diagnostic laparoscopies at two different hospitals for which her
reports were not available. Her husband's semen analysis was normal except for mild asthenospermia.
She then underwent a diagnostic laparoscopy with us in August 2010 which revealed bilateral patent tubes,
save for few adhesions owing to previous procedures. After few unsuccessful attempts at IUI she was
finally taken up for an IVF cycle in September 2011. She underwent controlled ovarian hyperstimulation
following down regulation with a GnRH analogue and had mild hyperstimulation syndrome. Four embryos
in total, including two blastocysts (grade III) were transferred. She tested positive for pregnancy on
September 19th with a serum beta HCG value of 106.2 miu/ml.
Her first scan to detect a gestational sac was performed on the 38th day, when twin sacs were noted. The
weekly scans saw corresponding growth and the fetal heart pulsations were recorded. Owing to our
previous experience with Heterotopic pregnancies, the adnexae were also scanned during the first three
visits. Unfortunately as she approached the 9th week of gestation she went in for a missed miscarriage. She
underwent a D&C on 25th October and was discharged on the same day.
On November 5th she developed pain lower abdomen and vomiting and was taken to another tertiary care
centre, closer to her home, outside of Chennai, as an emergency.
Following her previous history as well as clinical presentation, a suspicion of heterotopic pregnancy was
concurred and a pelvic examination was performed. An ultrasound revealed the presence of a mass
measuring 7x4cm with heterogenous echogenicity and free fluid in the hepatorenal pouch. Since the
patient was hemodynamically stable, she was admitted and observed for a period of two days after which a
repeat ultrasound was performed on November 7th. The adnexal mass had reduced to 3x3cm with very
minimal free fluid. The patient was then discharged at request from this centre.
She presented to us once again on November 10th with pain abdomen and tachycardia and after a
confirmatory ultrasound, she was taken up for endoscopic intervention. Hemoperitoneum with a right
isthmo-cornual ectopic was observed. A right salphingectomy was performed and abdomen wash was
given. She was discharged the next day.
Discussion
Heterotopic pregnancies occur with an incidence of 1:15000 to 1:30000 in general population and are
definitely increased following ART procedures to almost 1:100. The common reasons observed is the
increase in tubal factors owing to Pelvic inflammatory disease, endometriosis and factors that general
contributed to ovarian pathology or peritubal distortion. Intra procedure reasons cited are increases in
length of transfer catheter or in the volume of media in
which the embryos are loaded. When a heterotopic
pregnancy is diagnosed, the first determinant, if it
should be managed conservatively, with injection of
potassium chloride transvaginally depends largely on
the period of gestation and presentation of the patient.
In most cases since the location is isthmo- cornual, it
remains undiagnosed until 8th or 9th week of gestation
and surgical intervention is needed. But in some
instances a conservative approach is feasible.
Intervention is almost always the rule and it is either
surgical or medical with injection of potassium chloride
into the ectopic sac. Expectant management with
periodic monitoring of patients blood counts, vitals and
size of an adnexal mass may eventually lead to a
surgical intervention at the onset of symptoms or a catastrophic event like rupture.
Hence this case was presented to not only highlight importance of clinical diagnosis but also the need to
implement the right decision of medical versus surgical intervention. Expectant management may not be
feasible unless it is detected early enough and can be prolonged till a sign of cardiac activity is noted. But
once noted, an intervention would be the rule of the day, in which case the purpose is unserved.
DR. PRIYA SELVARAJ MD MNAMS MCE
SIGNIFICANCE OF KARYOTYPE IN COUPLES WITH
IDIOPATHIC INFERTILITY
In an earlier newsletter of ours dated October 2009, we had commented briefly on karyotype
polymorphisms in couples presenting with primary infertility. More so, the occurrence of polymorphism in
either of the partners or both in cases of idiopathic infertility has been presented. The criteria for assessing
karyotype, besides cases of bad obstetric history, consanguinity or known repeated genetic malformations
in the abortuses or still borns or live births, has been extended to include chronic failures following ART
and idiopathic cases of more than 5 years duration of infertility.
The most commonly encountered polymorphisms are a lengthening or shortening of the heterochromatin
of the long arm of chromosomes which are designated as 1, 9, 16, qh+. Among the female karyotypes, a
lengthening of the heterochromatin on the long arm of chromosome 9 appeared to be the commonest
followed by inversions. Other variations include an increase in satellite or stalks on short arm of
chromosomes 13, 14, 15, 21, 22 ps+ or pstk+. The men in the idiopathic group were found to have 46 X,
Yqh+ as the commonest occurring variant considering that it is mostly associated or seen in men with
azoospermia or olizoospermia.
An analysis of cases in idiopathic infertility is being presented to note if:

These polymorphisms have a role at the cellular kinetic level during gamete cross talk or impending
fertilization?

It can be used as a predictor for future miscarriages or anomalies if they were to conceive with
treatment?
It can be a strong basis for counseling regarding need for a gamete change in case they are also poor
responders?

FROM JAN 2009- JULY 2011
Total no of Idiopathic patients :1459
Total no of female Karyotype :740(50.71%)
Total no of Male Karyotype :719(49.28%)
FEMALE POLYMORPHISMS (62)
Female (740)
Male (719)
Normal
678 (91.62%)
585 (81.36%)
Polymorphisms
62 (8.37%)
133 (18.49%)
Polymorphisms
Female KT
(62)
Male KT
(133)
Pregnancy
Outcome Female
(4)
Pregnancy
Outcome Male
(7)
Normal Variant
26 (46.77)
70(52.63)
1
6
Chromosomal
Abnormalities
14(22.58)
24(18.04)
1
-
Male factor
-
31(23.02)
-
-
Repeated pregnancy
loss
13(20.96)
2(1.50)
2
-
Gonadal Dysgenesis
6(9.67)
5(3.75)
-
1
FEMALE POLYMORPHISMS (62)
NORMAL VARIANT(29)
No. of cases
46,XX,ADD(22)
2
46,XX,21PS+
7
46,XX,13PS+
4
46,XX, DEL(22) (P1 2-PTER)
1
46,XX,16QH+
2
46, XX, ADD(13)
3
46,XX,14PSTK+
1
46, XX,INV(9)(P 11;Q13)
5
46,XX,15PS+
2
46,XX,DEL(13)(P11.1-PTER)
1
46,XX,DEL(9)(Q12)
1
Pregnancy
Delivered
1(50)
1(100)
CHROMOSOMAL
ABNORMALITIES(14)
No. of
cases
Pregnancy
Delivered
46,XX,1QH+
1
1(100)
1(100)
Ongoing
46,XX,T(10;16)(Q26;P13.2)
1
46,XX,T(7;17)(P22;Q12)/46,XX
1
46, XX,9QH+
8
45,XX,DER(13;14)(Q10;Q10)
1
47,XXX
1
46,XX,16QH+
1
GONADAL
DYSGENESIS(6)46,XX,22PS+
6
RECURRENTABORTIONS(13)46,
XX,ADD(15)
8
1(12.5)
MOS 47,XXX/46,XX
4
1(25)
MOS47,XX,+MAR/46,XX
1
1(100)
1(100)
Baby girl G, conceived by Intra cytoplasmic Sperm injection and subsequent blastocyst transfer was
delivered by emergency LSCS on June 2011 at 29 weeks
FUNGAL SEPSIS IN AN EXTREMELY LOW BIRTH WEIGHT
(ELBW) BABY
GA with a birth weight of 700g. The indication being a high risk antenatal course of placental dysfunction
leading to severe intra-uterine growth retardation, oligohydramnios and absent diastolic flow. The infant
cried well at birth, but soon developed severe respiratory distress, for which surfactant and ventilator
support were given for 7 days. Subsequently, the baby was extubated and started on nasogastric feeds of
expressed breastmilk. In addition, partial parenteral nutrition was given via a central line. The infant had
one episode of sepsis and was treated with IV meropenem. Weekly IV fluconazole therapy was given as
fungal prophylaxis.
On day 40 of life, the infant, who was stable on full feeds and room air, developed shock, severe apneic
episodes and bilious vomiting requiring immediate ventilation. X-ray was suggestive of necrotizing
enterocolitis.
IV Meropenem and fluconazole were restarted. There was thrombocytopenia with clinical bleeds, and
plasma and platelet transfusions were administered according to requirements and with diligence. Inotrope
support was initiated for shock. The blood culture sent to 2 different labs grew Candida tropicalis: in one
lab, the strain was reported as sensitive to amphothericin-B, and in another lab as resistant to amphotericinB.
Hence, after discussion with infectious diseases expert, the infant was started on IV micofungin. However,
the infant showed severe anaphylactic reactions to this drug, in the form of near-arrest episodes. This was
explained to the parents, and amphotericin-B was restarted. After 5 days of amphotericin-B therapy, the
blood culture tested negative, IV Meropenem was stopped and the central line was removed.
IV Amphotericin-B was continued for 28 days, and the infant gradually improved. Feeds were started after
7 days and gradually advanced. Blood counts and electrolytes were periodically monitored. After 3 weeks,
the infant was extubated following adequate weight gain, paladai feeds were started followed by direct
breastfeeds. An opthalmologist opinion for retinal screen showed no retinal lesions due to Candida and the
ultrasound of the abdomen was normal.
USG brain showed no significant bleeds. ECHO showed no vegetations in the heart. The infant was
discharged with a weight of 1kg after a course of 3 months in the NICU .This case illustrates the risk
factors and management of fungal sepsis in extremely low birth weight babies (ELBW) and also
demonstrates the limited evidence about use of new antifungal drugs such as micofungin in such babies. A
review of literature about fungal sepsis in ELBW babies follows

INCIDENCE OF FUNGAL SEPSIS IN ELBW BABIES
Invasive fungal disease : 3-20%

Mortality from fungal sepsis: 20-30%

CLINICAL AND LABORATORY FEATURE
Increase in apnea and/or bradycardia - 63%

Increase in oxygen requirement - 56%

Increase in assisted ventilation - 52%

Lethargy and / or hypotonia - 39%

GI symptoms - gastric aspirates, distension, bloody stools -30%

Hypotension - 15%

Thrombocytopenia:platelet<100000/µL - 84%

Immature-total neutrophil ratio of>0.2 - 77%

Glucose concentration >140 mg/dL - 13%

WBC count >20,000/µL - 12%

Metabolic acidosis- 11%

Absolute neutrophil count <1500/µL - 3%

Elevated C-reactive protein

DIAGNOSTIC INVESTIGATIONS
Blood culture for fungemia

USG abdomen for fungal balls

ECHO for vegetations

Eye exam for retinal lesions

ANTI-FUNGALS
1. Amphotericin-B:
Drug of choice: It has good tissue penetration, and resistance is extremely rare

Dose: 1.5 mg/ kg IV Q24H for 25 to 30 days

No test dose needed in neonates

Infusion over 2-6 hours, protected from light

Toxicity: Decrease Glomerula Filtration Rate (GFR), injures renal tubules
RISK FACTORS FOR FUNGAL SEPSIS IN ELBW BABIES

2. Fluconazole
Good tissue and CNS penetration

Dose : 6mg/ kg Q24h to 72h IV

Side-effect: Reversible derangement of LFT

Concern about resistance, especially to Candida non-albicans

3. Liposomal Amphotericin-B
Accumulates in MPS, to higher dose is needed

Dose : 5mg/ kg over 2 hours daily

Less nephrotoxic

Expensive

Indian Liposomal Amphotericin B derived from neutral lipids L-Amp-LRC-1: economical

4. Echinocandins
Caspofungin Micafungin, anidulafungin

Dose : 1-2 mg/kg/ dose IV

Useful in refractory candidiasis

5. Other therapies
Supportive care

Stopping antibiotics

Removing central lines
DR. DEEPA HARIHARAN MBBS, A.B (Paeds/Neo) (USA), FAAP
Neonatologist, G G Hospital.
DO WHAT CAN’T BE DONE….
DO what can’t be DONE…
Do they say then find the way to do it, can't be done?
Anything that is considered impossible is an opportunity waiting to be harvested.
Just imagine the incredible power of being able to say "I can" when everyone else is saying " I can't”
"I can't" usually means "I won't". be the person who will.
It is easy to say "NO" to avoid the challenge and the effort. Success comes to those who say
"YES" and then set about to make it happen.
Constant complaints and Excuses will keep you imprisoned in a tedius world of mediocrity.
Yet what is impossible for others, does not have to be for you.
Welcome the challenges.
Take the initiative.
Feel the satisfaction of accomplishing that which has never before been attempted.
Look for things Which can't or won't be done.
Be the one who makes them happen, and reap their enormous value.
- Ralph Marston
Dr. Priya Selvaraj MD MNAMS MCE
OUR ART BABES





Name : N.Sugunamayi

Extra curricular Activities : Bharathanatiyam. She has completed her arangetram. has also won in all
school dance programms
DOB & Age : 21/08/1995, 16 YRS
Conception : IVF ET
Class : 12th STD
Ambition : To become an I.A.S officer or Charterd Acconuntant
 Name : Ananya Ramesh
 DOB & Age : 112/2008 & 3 YRS
 Conception : IVF ET
 She speaks english fluently and is very good in singing




DOB & Age : 03/12/2007, 4 YRS
Conception : IVF ET

Extremely proactive and energetic twins
TWIN 1 : P.Siva Kamalam
TWIN 2 : P.Siva Priyam





Name : Mohana Sundari
DOB & Age : 06/01/1998, 13 YRS
Conception : IVF ET
Class : 8th STD
Ambition : To become a Doctor
 Sports (Gold medalist in running & long jump) singing, dancing and drwing
MONTHLY IUI PREGNANCIES ( JAN 2011 - OCT 2011)
OVERALL MONTHLY PREGNANCIES ( JAN 2011 – OCT
2011)
TOTAL No. OF PREGNANCIES/ MONTHLY (JANUARY 2009 JUNE 2009)
**(Easy Transfers and good quality of embryos)
MONTHLY PREGNANCIES ( JAN 2011 - OCT 2011)
Art
IUI
Natural *
42
12
19
56
10
17
45
16
14
50
20
11
32
8
10
44
19
7
46
20
8
41
21
17
56
21
17
44
18
10
456
192
150
OVERALL PREGNANCIES ( JAN 2011 – OCT 2011)
*Following medical and surgical management
ART STATISTICS (JAN 2011 - OCT 2011)
PROCEDURES
NO OF
CASES
PREGNANCIES
PREG.RATE
(% )
IUI (OWN / DONAR)
1730
207
11.96
IVF ET
2
0
0
ICSI ET
186
59
31.7
IVM ICSI ET
4
0
0
BT
5
3
60
IVF + ICSI ET
1
0
0
FROZEN ICSI ET
34
13
38.23
FROZEN IVF + ICSI ET
4
4
25
281
133
52.66
139
81
58.27
28
12
42.85
OWN
39
12
30.76
DONOR
24
9
37.5
GENERAL
FROZEN EMBRYOS
SEQUENTIAL TRANSFER (
OWN / DONOR )
DAY 2 AND DAY 5
TRANSFER (OWN)
DAY 2 AND 5 TRANSFER (
DONAR)
DAY 2 AND 5 TRANSFER
(OWN / DONAR)
RUPTURE ET
DONOR OOCYTE
PROGRAMME ( DOP )
IVF ET
3
0
0
ICSI ET
64
18
28.13
OOCYTE THAWING HRT
ICSI ET
1
0
0
5
0
0
1
1
100
16
3
18.75
5
3
60
35
11
31.42
11
2
18.18
BT
DUAL
DONOR EMBRYO
PROGRAMME
IVF ET
ICSI ET
FROZEN DET
BT
Total Number of pregnancies achieved
Total Number of patients delivered by ART
Total Number of babies delivered by ART
Total Number of ongoing pregnancies
Total Number of Fetal wastages
Lost in follow up
: 4431
: 2460
: 3360
: 210
: 1715
: 46