ICMR BULLETIN VOL.8-No.-3-MARCH-1978.pdf

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9

COMMUNITY HEALTH CELL
47/1, (First Floor) St. Marks Road
BANGAORE -560 001

326, V Main, I Block

Koramangala

Vol. 8 No. 3

Bangalore-560034 •
India

March, 1978

RESEARCH IN THE FIELD OF REPRODUCTIVE BIOLOGY
AND CONTRACEPTIVE TECHNOLOGY

Indian Council of Medical Research has
been supporting research in the field of
reproductive biology and contraceptive techno­
logy for a number of years.
Work on these
aspects was undertaken mainly at the Council’s
Institute for Research in Reproduction (IRR),
Bombay,
and also' at many other institutions
all over the country. . Research activities in
this field can be broadly
classified as
contraceptive research, ‘ application oriented
basic research and developmental research.

Because of the lower incidence of the side
effects with the ‘T‘ device and the finding
that intrauterine copper had antifertility
properties', the idea of utilization of the 1T'
device as a carrier for copper emerged and the
’second’ generation of IUDs developed.
Evalu­
ation of the efficacy and safety of several of
these devices was, therefore, undertaken with
a view to be able to provide an IUD which
would be better accepted than the Lippes loop.

Copper T 200:
CONTRACEPTIVE RESEARCH

INTRAUTERINE DEVICES
Ample evidence exists today to indicate
that no single intrauterine contraceptive de­
vice (IUD) made-from an inert material has
advantages over others.
Pregnancies,
expulsions,
removals have been
variable with
different devices.
Studies have shown that
larger the surface area of the device,
the
lesser the number of pregnancies,
but greater
the number of removals because of bleeding and
pain. Unlike the rate of metrorrhagia,expul ­
sion rate has been suggested to be inversely
proportional to the rigidity of the IUD.
The
*T!
device was originally introduced with a
view of providing a design which could best
adapt itself to the uterine cavity even when
it contracted maximally.
Results of prelimi­
nary investigations showed that the ‘T‘ device
made of polyethylene produced 5 times less
pain and bleeding and had about half the ex­
pulsion rate when compared with the Lippes
loop-. / However,
pregnancy rate was higher.

Clinical trials with Copper T (CuT) 200
were initiated at 19 centres. A total of 4,357
women were observed for 82,384 woman months.
Majority of acceptors were in the age group of
20-34 years, and had borne 2-3 children, indi­
cating that the intrauterine device was by and
large used as a method for spacing.
It was
also seen that fewer women who had no living
son came for insertion as compared to those
who had no living daughter.
The number of
acceptors who had no living son was lower
irrespective of the number of living daught­
ers,
supporting the hypothesis that most
couples desired atleast one male living child.
The net cumulative rate for pregnancy at
the end of 54 months was 1.8 per 100 users
which did not increase substantially after the
first year of use.
Expulsion and bleeding
episodes were more frequent in the first year
and declined during successive years of use.
Expulsions were more frequent in the grand
multiparous women.
Pelvic infections were
observed mainly during the first two years of

use. There were four perforations. Continua­
tion rate at the end of 54 months was only
25.5 per 100 users. Removals due to non-medical reasons such as planning pregnancy,
husband/family objections, lack of confidence and
change to other methods were 42.0 per 100
users.
Copper coils were found broken and frag­
ments missing in many devices that were re­
moved after 4 years. This device is presently
being used in the national programme.
Chang­
ing of the device after four years has been
recommended.

Copper T 220:
In order to lengthen the life span of the
device and to reduce expulsions by making the
device more rigid, copper wire was replaced by
copper sleeves (CuT 220). Clinical trials with
CuT 220 were initiated and a total of 875 wo­
men were observed for 10,724 woman months.
Analysis of data at the end of 24 months,
using life-table method, gave.a net cumulative
continuation rate of 55.7 per 100 users. Preg­
nancy was 0.2, and expulsion-displacement 8.9
per 100 users. Performance of this device was
in no way superior to the CuT 200.
Replace­
ment of the latter device after 4 years en­
sured to some extent,
contact with acceptors
who would otherwise have been lost to follow­
up.

Copper T 380 and Copper Y devices:
Randomized trials with CuT 200,
CuT 220,
CuT 380 (combination of copper wire and copper
sleeves) and CuY were also initiated.
These
were evaluated in the (i) post-abortal
(con­
current) and (ii) non-puerperal groups.
Ana­
lysis of data at 12 months indicated that the
cumulative rate for expulsion-displacement and
bleeding was higher with all the devices in
the post-abortal group as compared to nonpuerperal group.

In the post-abortal group expulsions were
least with CuT 200 (8.2 per 100 users)
and
maximum with CuY (17.3 per 100 users).
The
difference
was
statistically
significant
(P<0.05).
Expulsions with CuT 220 and CuT 380
did not show significant difference when com­
pared with CuT 200.
Although bleeding was
higher with CuT 220 as compared to CuT 200 and
CuY,
this difference was not statistically
significant.
No pregnancies occurred with
CuT 200 and CuY.
In the non-puerperal group,
expulsions were least with CuT 200 and maximum
with CuY (P<0.05).
CuT 380 also gave higher

2

expulsions as compared to CuT 200 (P<0.05).
Bleeding was less with CuT 200 and CuY and
maximum with CuT 220.
A total of 4 perfora­
tions occurred,
one each with CuT 220 in the
post-abortal group and CuY in the non-puerperal group, and the remaining 2 occurred'with
CuT 200 in the non-puerperal group.
Comparing the
overall performance of
these devices in both the groups,
CuT 200
appeared to be a better device with regard to
expulsions and side-effects.
Although bleed­
ing was less with CuY, higher incidence of ex­
pulsions and breaking of the terminal thread
made it less suitable for practical use.
Addition of more copper in the CuT 220 and 380
did increase the efficacy of the device but
side-effects such as bleeding and pain were
observed more frequently.
Furthermore,
the
rigidity of the device did not lower the inci­
dence of expulsion to a meaningful extent.

Copper T 200 Ag:
Long-term study with CuT 200 has indi­
cated that the copper wire tends to fragment
when it is left in utero for a period of more
than 4 years.
To avoid this complication, a
new copper T device, where the core of the
copper wire is made of silver, was investi­
gated.
This pilot study compared
the new
device with the standard CuT 200 with regard
to safety and efficacy.
A total of 199 women
were enrolled.
CuT 200 was inserted in 101,
CuT 200 Ag in 98. Data analysis at the end of
six months indicated that expulsion and bleeding were slightly higher with CuT 200 Ag,
as
compared to CuT 200.

Long term effects of IUD:
At the request of the Department of
Family Welfare, Ministry of Health, a collaborative study was undertaken to investigate the
effects of intrauterine ' device used
beyond
five years.
Data were collected from 10
centres on 1,181 women.
Complaints such as
cramps,
backache, bleeding and vaginal dis­
charge varied between 12 to 26 per cent during the first year and gradually declined with
time indicating that the 8 years use of the
device did not have a serious deleterious
effect.
HORMONAL CONTRACEPTIVES
The combination oral contraceptive pill
is still the most effective large scale method

available for fertility control.
While oral
pills are still popular in western countries,
the wide acceptance of this method in our
country is still debatable.
There is, there­
fore,
a constant search for developing a
method which would obviate the need for moti­
vation for daily pill intake.

Injectables:
Although use of a large dose of norethi­
sterone enanthate intramuscular injection once
every three months has been favoured by women
in many countries,
side-effects such as ir­
regular bleeding,
has dissuaded its use.
Therefore, phase II trials using one-tenth the
amount as monthly injections,
were initiated
with the objective of achieving antifertility
effect
without
inhibiting
ovulation - an
approach similar to the mini pill. ’Prelimi­
nary six month data analysed by life-table
method, on extended trial with norethisterone
enanthate 20 mg monthly, on 213 women observed
for 728 woman months gave a net cumulative
rate for pregnancy of 5.0 and closures due to
menstrual disorders 19.4.
Bioavailability and
endometrial histology studies are in progress.

Biodegradable pellets:
One of the major disadvantages of using
oily preparations
is the need for the rela­
tively frequent administration of the drug.
The use of subdermal implants made up of si­
lastic capsules containing steroids was consi­
dered as an alternate approach.
However,
migration from injection site and difficulty
in removing the empty capsule are its major
drawbacks.
To overcome these,
biodegradable
polymers incorporating
steroids have been
suggested as a method for the slow release of
the drug from the injection site. The Council
is at present evaluating the
efficacy
of
pellets which contain 85 per cent steroid in
combination with cholesterol.

lation.
So far,
results have been satis­
factory with vaginal rings containing estra­
diol.
Pharmacokinetic
and bioavailability
studies with these rings are in progress.

Studies on bioavailability:
Despite the widespread use of oral pills,
little is known regarding the bioavailability
of steroids under different nutritional condi­
tions.
This information is considered very
important for assessing the correct dosage of
contraceptive drugs so that toxic side-effects
could be minimized in malnourished popula­
tions .

Bioavailability of steroids from vaginal
rings containing norgestrel was done at the
National Institute of Nutrition, Hyderabad and
Institute for Research in Reproduction,Bombay.
Blood levels of norgestrel (dNg), progesterone
and estradiol were estimated.
dNg levels
ranged from l ng to 3 ng/ml in all subjects.
Cervical mucus score remained low in all the
cycles.
Plasma levels of progesterone and
estradiol were found to be very low indicating
suppression of steroidogenesis and ovulation.
Bioavailability of steroids from bio­
degradable pellets was estimated at the Insti­
tute for Research
in Reproduction,
Bombay.
After an initial spurt,
release of steroids
was found to be steady during the 6 month
period of observation.
These studies are in
progress.

Studies to determine the bioavailability
of steroids
with norethisterone enanthate
(NET) 200 mg given 3 monthly were carried out
at Chandigarh and Calcutta.
Results have
indicated that peak norethisterone levels are
attained by 2nd week reaching low levels by
Sth to 12th week. Endometrial biopsies showed
atrophy of endometrium in some women which was
accompanied by low levels of plasma proges­
terone.

Vaginal rings:
A new approach for delivering the pro­
gestogen at low dose levels is the vaginal
ring. These rings are made of silicone poly­
mer containing the steroid,
which is slowly
released and absorbed through the vaginal
mucosa.
The efficacy and safety of two types of
rings are being tested - one containing nor­
gestrel alone;
and the other norgestrel
in
combination
with
estradiol.
Release of
steroids from both types of rings inhibit ovu­

Bioavailability studies were also carried
out with low dose oral pills
(NET 0.35 mg and
1 .0 mg).
Results indicated that the steady
state levels reached with both were almost in
the same range after 12 hours. At the National
Institute of Nutrition,
Hyderabad,
data on
women who received a single pill containing
0.35 mg NET indicated that the rate of drug
elimination was related to wt/ht2 and skin
However,
these observations
fold thickness.
have to be confirmed on a larger number of wo­
men before any such relationship can be consi­
dered established.

3

It is proposed to extend
studies to malnourished women.

all

Effects of hormonal contraceptives
immunological status of women:

these

on the

Studies on experimental models as well as
the human host have demonstrated that hormonal
agents alter the
immunological response humoral as also cell mediated - to bacterial
antigens.
These responses would be governed
by the genetic make up of the host, the nature
of the antigen against which the immunological
response is directed, and also the biological
activity and the chemical nature of the hor­
mone.
Earlier work had indicated that combi­
nation type of hormonal steroids when adminis­
tered for long periods lowered the immunologi­
cal response even to a potent immunogen as
tetanus toxoid.
Current investigations have
indicated that neither HI nor CMI to typhoid
vaccine was altered in women who used hormonal
contraceptives for a period of only 3 to 4
months.
The immunological consequences of
long term use of hormonal contraceptives are
presently being investigated.
This informa­
tion would prove invaluable and would indicate
the need or otherwise of additional prophy­
lactic care of women using hormonal contra­
ceptives.

Interaction
variables:

of

steroids

with other health

A study on the interaction of contracep­
tive agents and methods with nutritional,
in­
fectious and
other health variables
was
carried out at two ICMR centres. The main aim
was to find how women with lower nutritional
status reacted metabolically
to steroidal
contraceptives.
So far,
430 subjects are
being followed up at regular intervals. Basal
levels of the parameters studied before start­
ing the therapy have been established. Uptill
now, data on 91 patients have been obtained
with respect to all parameters.
Preliminary
results indicate that worm infestations did
not adversely affect plasma steroid levels.
Attempts to assess the effect of oral pills on
vitamin B status indicated that these potent
antifertility agents might create a sub-clini­
cal vitamin deficiency state in the host. The
effect of oral pills on the levels of other
vitamins is under investigation.

Centchroman:
Clinical trial with Centchroman developed
by CDRI, Lucknow as an antifertility agent was
undertaken.
A total of 205 women were given

4

120 mg centchroman weekly and were observed
for 674 cycles.
The trial was discontinued as
25 women became pregnant. Most of these preg­
nancies occurred during the first cycle of
use. Therefore, phase II trial was initiated
with 60 mg weekly schedule with an additional
tablet administered on the first day of the
menstrual period.
Similarly
an additional
tablet was given on the first day of all
subsequent cycles.
No
pregnancies
have
occurred in the 59 women observed so far.
Irregular cycle control appears to be the
major problem.
Pharmacokinetic studies with
45 mg are in progress.

Technical evaluation of lUD/oral pill national
programme:

Technical evaluation of the lUD/oral pill
programme was initiated at the request of the
Ministry of Health § Family Welfare, with the
objective of evaluating the practical useful-'
ness of different contraceptive methods in the
existing infrastructure of the National Family
Welfare Programme.
This would thus enable
necessary midcourse corrections for the proper
implementation and better acceptance of these
programmes in the country. Several centres in
the country were selected.
Equal number of
rural and urban clinics, under the administra­
tive control of State Family Welfare Bureaux
were attached as feeding units to each of the
coordinating centres.
Enrollment was much
below the anticipated number and only 2,659
women got IUD insertions done and 833 regis­
tered for oral pills.
Analysis of data at
six months gave a lower net rate for expulsion
and bleeding as compared to the results of the
larger study conducted by the ICMR contracep­
tive testing unit network.
Removals due to
personal reasons were maximum,
although the
overall continuation rate was better.
The
validity of these conclusions
warrants a
larger number of acceptors with long followup. Of the 833 pill users,
continuation rate
at the end of six months was 74.5 per 100
users, discontinuation due to medical reasons
13.4 per cent and personal reasons 11.3 per
cent.
CONVENTIONAL CONTRACEPTIVES

The modern contraceptives either hormonal
preparations or intrauterine
devices
are
contra-indicated in some women because of
their endocrine status
or due to
other
reasons: Therefore,
the improvement in the
efficacy of conventional contraceptives cannot
be ignored.
The IRR,
Bombay,
therefore,
continues to do the laboratory and clinical

testing of jellies,
other drugs.

creams,

foam tablets and

LONG TERM EFFECTS CF STERILIZATION PROCEDURES
The evaluation of the long term effects
of sterilization methods is extremely impor­
tant with reference to the health and well­
being of individuals accepting these pro­
cedures.

Tubal sterilization:
Morbidity following tubal sterilization
depends upon several factors, timing of steri­
lization and other surgical procedures done
concurrently.
In India, medical facilities
vary considerably from region to region and
from hospital to hospital.
It was, therefore,
considered necessary to evaluate the minimum
facilities and expertise required for perform­
ing tubal ligations with least complications.
With this in view,
a multicentric study was
initiated to collect data on the incidence of
non-fatal early and late complications follow­
ing tubal sterilization,
on a countrywide
basis.

A total of 21,772 cases have been en­
rolled so far,
and preliminary screening of
these cases showed that 37.5 per cent of the
sterilizations were done in the post-partum
period,
28.8 per cent were concurrent,
of
which 24.3 per cent were concurrent with abor­
tion and 4.3 per cent concurrent with caesa­
rean section.
29.5 per cent sterilizations
were done in the interval period, 4.0 per cent
in post-abortal period and 0.2 per cent in the
antenatal period.
In most of the cases (76.6
per cent)
the procedure for sterilization was
laparotomy, followed by laproscopy in 16.7 per
cent of cases. Techniques used for tubal liga­
tion were Pomeroy in 78.1 per cent of cases
and electrocoagulation/electrocauterization in
15.8 per cent.
In the remaining cases,
tech­
niques used were salpingectomy, Uchida, rings,
clips,etc. or a combination of two techniques.
The study is presently in progress and de­
tailed analysis on the short and long term
sequelae will be available only after complet­
ing the enrollment of all the 30,000 cases.
Vasectomy:

A cross-sectional study was carried out
on the hormonal, physiological, and endocrine
status following vasectomy.
Gonadotropin,
testosterone and oestrogen levels were assayed
using radioimmunoassay techniques.
Results

revealed
that there
were no significant
changes in the circulating levels of either
gonadotropins or oestrogens.
The androgen
levels in some cases however,
showed a slight
increase.
These results indicate that vasec­
tomy does not adversely affect the hormonal
status.
The study on the other hand revealed
that vasectomy might lower prostate function,
as evaluated by the activity of the enzyme
maltase, which is present in semen.
The re­
sults further suggested that vasectomy might
prevent benign hypertrophy of the prostate.
A study in a larger group needs to be carried
out to confirm these preliminary findings.

Immunological status following vasectomy:
Research on the
immunological conse­
quences of vasectomy has revealed that humoral
(circulating antibodies)
as well as cell
mediated immunity (CMI) to spermatozoa deve­
lop in some individuals following vasectomy.
It.was, however,
noted that the immunity was
not directed against any other organ or cell
of the body.
Such immunity to spermatozoal
antigens has also been encountered in certain
cases of male infertility.

ANTIFERTILITY DRUGS AND PLANTS

Drugs:
The antiandrogen
cyproterone acetate,
has been shown to inhibit fertility in the
male rat as also man.
Results of the studies
at the Institute for Research in Reproduction,
Bombay, with cyproterone acetate and another
antiandrogen flutamide,
have indicated that
the latter would be the better choice for in­
hibiting male fertility because the compound
does not have any hormonal activity in compa­
rison to cyproterone acetate, which has some
progestational activity.
Studies with a-chlorhydrin,
cyproterone,
and danazol were undertaken at the University
of Rajasthan, Jaipur,
to study their anti­
fertility effect.
Studies on a-chlorhydrin
led to reversible male sterilization with
normal liver function.
Synergistic action of
two different drugs
a-chlorhydrin and K1 33828 (Methallibure) was also studied and
found to be effective in inhibiting spermato­
genesis.
Antifertility effect of a-chlorhydrin was also studied on human ejaculated
spermatozoa.
It was found that a-chlorhydrin
caused inhibition of sperm motility in vitrei
as shown by a significant drop in motility of
sperms at a concentration of 30 mg and 40 mg
per cent.

5

Plants:
Of the various plants screened,
three,
namely
Embelia ribes,
Piper tongwn
and
Lawsonia inermis significantly inhibited pregnancy in female rats.
Antifertility activity
of the various extracts of E.ribes have how­
ever not given conclusive results. The aqueous
and alcoholic extracts obtained after cold
percolation have failed to show any contracep­
tive effect.
Studies in monkeys have indi­
cated that larger doses of E.ribes are nece­
ssary to inhibit spermatogenesis than for the
functional depression of the accessory sex
glands.

Screening of plants for antifertility
drugs has also been carried out at the Central
Drug Research Institute,
Lucknow and College
of Veterinary Sciences, Tirupati. It was found
that seeds of CrotaLaria juncea Linn possess
83.3 per cent antifertility activity in albino
rats.
This is being further investigated.
Two other plants which have been investigated
are Pittosporwn nitghrense and Cattha puLustris. On systematic fractionization of these
plant extracts, four saponins were obtained
which showed spermicidal action against rat
and human spermatozoa.
With a view to finding an oral non-toxic
indigenous drug with antifertility effect, two
fractions from the extract of the roots of the
plant Aristolochic. indica were investigated at
the Indian Institute of Experimental Medicine,
Calcutta.
The extracts studied were sesqui­
terpene and methyl ester, both were found to
have abortificient effect in early pregnancy.
Sesquiterpene also had an anti-implantation
effect at a certain dose level.
The com­
pounds were subjected to toxicity studies and
found to have very little toxic effect.

Indigenous preparations:
During the year,
several indigenous pre­
parations were evaluated.
These included
Garbh Pipu^
Karkoti^ Banjhouri^
Eeerodhdk
Vati, Biswajit, etc.
Of those tested, none
has so far proved to be as effective as
claimed.

STUDIES GN ABORTION

Study on sequelae of abortions:
The demand for abortion - for medical,
eugenic, humanitarian and social reasons - has
progressively increased since the enactment of
the Pregnancy- Termination Act in 1972.
Any

6

procedure used to induce an abortion may im­
pair health if it is not selected and carried
out properly. Therefore, abortion is emerging
as a potentially important maternal health
issue. The incidence and severity of complica­
tions associated with abortion are related to
several factors, e.g. period of gestation,
method used, operative facilities, operator’s
experience, etc.
Although several investi­
gators in India, have reported their data on
complications following abortions,
it was
difficult to compare or compile these results
because of the great disparity in the methodo­
logy for data collection and reporting.
Inci­
dence of rare complications of commonly used
methods and complications of comparatively in­
frequently used methods could not be assessed
from these small studies.
Realizing the need
for obtaining data on the safety of various
procedures in a comparatively short time,
a
multicentric nationwide prospective study wase
undertaken in 16 teaching hospitals on the

sequelae of abortions.
A total of 17,628 women who had medical
termination of pregnancy (MTP) were enrolled
for the study.
Majority of abortion seekers
had pre-college or college education and came
from families with per capita income Rs.30-150
per month. Seventy per cent were between 20-35
years of age.
Teenagers requesting abortion
formed only 5.2 per cent and unmarried nulli­
para constituted less than 8 per cent.
Over
90 per cent of women were married and had
one or more children and 37.5 per cent had 3
or more children at the time of MTP.
Women
who gave history of previous induced abortion
formed only 6.5 per cent.

Majority of the women came for MTP during
first trimester
(85.9 per cent).
Second
trimester abortion seekers consisted mainly of)
illiterate women from lower socio-economic”
group, single or widowed women, teenage nullipara, and grand multipara beyond 35 years of
age.
Suction evacuation was the most common
method used for inducing abortions
(71.1 per
cent),
followed by D&C
(11.7 per cent),
hysterotomy (6.0 per cent),
intra-amniotic
saline (2.9 per cent),
prostaglandin insti­
llation by various routes
(7.1 per cent) and
extra-amniotic rivanol (0.9 per cent).
Prior
to abortion, only 24.2 per cent of the abortion seekers had used some form of contraception.
However, 63.1 per cent accepted effec­
tive concurrent contraceptive measures at the
time of abortion.

tions

Overall incidence
at the time of

of immediate complicaMTP were low.
Haemo­

rrhage (3.3/1000), cervical injury (1.3/1000),
uterine injury (3.1/1000),
other organ injury
(0.7/1000).
Other major complications were
noted in 2.2/1000 and minor complications
occurred in 31.3/1000.
Infection was the most
commonly noted delayed complication.
Pelvic
infection occurred in 26.6/1000, urinary in­
fection in 3.5/1000 and other infections in
19.9/1000.
Incidence of incomplete abortion
at follow-up was noted in 14.0/1000.
Other
major complications were reported in 1.7/1000
cases.
Post-abortal bleeding in 13.9/1000
and minor complications like abdominal pain,
vaginal discharge etc., occurred in 105.4/1000
cases.
Analysis of complications in relation to
methods used in the first trimester abortions,
showed that D&C and suction evacuation were
the two common methods used for the induction
of abortion during the first trimester.
In
the overall analysis,
D&C and vacuum suction
appeared to have similar complication rates
but severity of complications seemed to be
greater in the D&C group.
Methods used for
second trimester abortions included intraamniotic saline, prostaglandin instillation by
various routes and hysterotomy.

Termination of pregnancy during first
trimester was found to be safer than termina­
tion during second trimester.
Even within
each trimester,
there was a progressive in­
crease in the incidence of both immediate and
delayed complications with increasing period
of gestation.
Termination done earlier than
8 weeks of gestation had the lowest incidence
of complications while termination of preg­
nancy beyond 16 weeks had the highest compli­
cation rate.
Analysis of complications in relation to
concurrent
contraception
indicated
that
tubectomy done concurrently
with abortion
appeared to be associated with an increase in
some of the immediate complications like in­
jury to other organs and anaesthetic compli­
cations. Among the delayed complications, in­
fections were more common in the concurrent
sterilization group inspite of prophylactic
antibiotic therapy.
Concurrent IUD inser­
tion was not associated with any increase in
sepsis rate.
However,
incidence of postabortion bleeding was higher in the concurrent
IUD acceptor group. Concurrent pill acceptors
and non-acceptors of contraception had the
least rate for delayed complications.

tion

Among women who did not accept contracep­
at' the time of follow-up only 20.5 per

cent accepted some form of effective contra­
ception at 3 months.
It is conceivable,
therefore, that among those who did not accept
contraception at the time of abortion, the
risk of unwanted pregnancy and subsequent re­
quests for repeated abortions would be subs­
tantially higher.

Prostaglandins:
Although effective methods are available
for the termination of first trimester preg­
nancy, a large percentage of women seek second
trimester abortions.
The available alter­
natives for this group include hysterotomy,
hypertonic saline, urea and prostaglandins.
Hysterotomy is a major surgical procedure
which has its own associated risks.
Hyper­
tonic saline has been claimed to be effective
but has the risk of coagulation failure and
hypernatremia.
Scant clinical data is avail­
able in India on the use of urea as an abortifacient.
The safety and efficacy of prostaglandins
and their analogues for the termination of
midtrimester pregnancy has been established by
WHO Task-Force on Prostaglandin.
However, in
order to evaluate their safety in the context
of conditions existing in our country, multi­
centric studies were undertaken at centres
attached to teaching hospitals.
One trial
compared the use of single shot intra-amniotic
50 mg PGF2, and 2.5 mg 15(S)15-methyl PGF2a
for termination of pregnancy between 15-20
weeks.
The second trial was the administra­
tion of a single shot extra-amniotic 0.92 mg
15(8)15-methyl PGF2a for termination of preg­
nancy between 10-20 weeks.
Intra-amniotic route:
A total of 885 women
were enrolled in the first trial, of which 430
women had PGF2a and 455 had 15-methyl PGF2a.
Success rate at the end of 48 hours was 88.1
per cent (379 women) with PGF2a and 93.0 per
cent (423 women) with 15-methyl PGF2a.
Mean
induction-abortion interval with PGF2a was

19.2 hours and with 15-methyl PGF2a it was
19.3 hours. Abortion was complete in 48.8 per
cent (185 women) with PGF2a and in 56 per cent
(237 women) with 15-methyl PGF2a.
Vomiting
was reported in 42.9 - 45.3 per cent cases and
diarrhoea was reported by 24 per cent cases in
the two groups.
Extra-amniotic route:
In the second trial, a
total of 1,648 women were given extra-amniotic
15(S)15-methyl PGF2a and 1,225 (78.1 per cent)
women aborted within 36 hours.
Mean induc­
tion-abortion interval was 14.8 hours.
Abor­

7

tion was complete in 282 (23 per cent) women,
incomplete in 582 (47.5 per cent)
women.
Incidence of vomiting was 36.5 per cent and
diarrhoea 33.7 per cent.
Cervical injury was
reported in 0.6 per cent women.
Vaginal route: Prostaglandin vaginal supposi­
tory is an alternate to intra-amniotic and
extra-amniotic administration of prostaglan­
dins for the termination of midtrimester preg­
nancy. The vaginal route has the advantage of
being simple and the drug can be self adminis­
tered.
This approach could, therefore, be
used at non-teaching hospitals and even at the
primary health centre level.
In order to
evaluate the efficacy and safety of this
approach,
vaginal suppositories containing
3 mg 15-methyl PGF2a methyl ester were used
for the termination of pregnancy between 10-20
weeks of gestation in 288 women.
Of these
79.2 per cent women aborted within 30 hours.
Mean induction-abortion interval was 14.7
hours. Abortion was complete in 133 (58.3 per
cent) women.
Incidence of vomiting was 72.3
per cent and diarrhoea 76,8 per cent; cervical
injury was reported in one women.
These
trials are in progress.

Ethacridine lactate:
Alternate approaches for terminating sec­
ond trimester pregnancy include intra/extraamniotic instillation of solutions containing
prostaglandins, hypertonic saline, urea, etc.
While-the safety and efficacy of some of these
is still not established, the expense and non­
availability deters the use of others.
A
clinical trial for assessing the safety and
efficacy of ethacridine lactate was,therefore,
undertaken since this preparation is appa­
rently inexpensive and more readily available
within the country.

Although
several clinical trials
to
terminate pregnancy between 12-20 weeks with
ethacridine lactate and ethacridine lactate in
combination with oxytocics have been reported,
it was difficult to interpret and compare
clinical events as data of these trials were
not collected in an identical manner. Differ­
ent strengths,
combination of drugs, time
period of catheter in position, etc. were
used.
In order to evaluate the safety
and
efficacy of ethacridine lactate alone or in
combination with spartine sulphate,
a study
was undertaken in a few centres.
Analysis of
the data in 386 women revealed that ethacri­
dine lactate alone and/or in combination with
spartine sulphate was safe and effective in
terminating approximately 70 per cent pregnan­

8

cies between 12-20 weeks in 48 hours.
This
was comparable to the extra-amniotic prosta­
glandin approach and was inferior to intraamniotic prostaglandins.

The cumulative success at the end of 24
hours with ethacridine lactate was only 32.3
per cent compared to 69 per cent with extraamniotic
prostaglandin and
intra-amniotic
PGF20.
With intra-amniotic 15-methyl PGF2Q
it was 74.9 per cent.

The mean induction-abortion interval with
extra-amniotic 15-methyl PGF20 was 14.8 hours,
with intra-amniotic PGF2a it was 19.2 hours
and with intra-amniotic 15-S-methyl PGF2a it
was 19.3 hours. With ethacridine lactate alone
it was 26.3 hours and in combination with
spartine sulphate it was 26.7 hours. The most
common side effects with prostaglandin viz.
vomiting and diarrhoea were markedly less
noticeable with ethacridine lactate. Complete
abortions were 69.3 per cent with ethacridine
lactate and in combination with spartine sul­
phate 59.6 per cent.
With extra-amniotic 15S-methyl PGF2a only 31.8 per cent women abor­
ted completely and with intra-amniotic PGF2o
it was 80 per cent and with 15-methyl PGF2a it
was 75 per cent.
Presently, prostaglandins are not avail­
able in India and storage as well as trans­
portation may pose problems although development of newer analogues may overcome this
especially as is the case with vaginal suppository.

The other alternative to terminate midtrimester
pregnancy is intrauterine saline.
The success rate with saline as repotted by
various investigators was about 85 per cent at
the end of 48 hours and 90 per cent at 72
hours with 66 per cent complete abortion.
The
mean induction-abortion interval was approximately 30 hours.
Hypertonic saline is known
for the added risk of coagulation failure and
hypernatremia.
Deaths have been reported in
cases where abortion was induced with hypertonic saline.
Furthermore,
intra-amniotic
instillation is
difficult in 12-15 weeks
pregnancy.
Except for rigor (7.5 per cent
approximately)
no
adverse
effects
with
ethacridine lactate were noted and contraindications for the use of ethacridine lactate
are very few.
Low cost is an advantage as
also the bactericidal property of ethacridine
lactate.
This drug has now been recommended
for marketing and use for terminating pregnancies.

a))

Y

Isapgol cervical dilators:
Many centres in the country today use
bougies and laminaria tents as cervical di­
lators for inducing abortions.
Laminaria
tents made of sea weeds are being imported at
present and are expensive. Furthermore, their
availability within the country is restricted.
CDRI,
Lucknow has succeeded in developing a
cervical
dilator
from Isapgol
(Plantago
ovata).
The cost of this dilator is fifty
times lower as compared to the imported di­
lator.
Limited studies have indicated that
these dilators are effective and induce 10 mm
dilatation within 8 hours.
Further studies
with these and bougies are in progress.
APPLICATION ORIENTED BASIC RESEARCH

MALE REPRODUCTION

Studies on Inhibin:
It is known that FSH is concerned with
spermatogenic function and -LH in that of
testosterone production. Selective inhibition
of FSH would, therefore, be one of the possi­
bilities of inhibiting spermatogenesis without
affecting androgen production.
Investigations
carried out at the Council‘s
Institute for
Research in Reproduction, Bombay,have revealed
that testis has two non-steroidal protein
components,
one of which inhibits FSH secre­
tion and the other IB secretion. These compo­
nents termed Inhibin have been isolated from
ram testis and semi-purified.
Studies are in
progress to examine the species specificity of
the FSH inhibiting moiety and its use in
controlling fertility in the male.
A study has also been undertaken at the
Central Drug Research Institute, Lucknow, with
the objective to separate, purify and identify
the principle from a suitable source and then
subject it to biological standardization for
its anti-FSH activity.
Results so far indi­
cate that an anti-FSH factor is present in the
testis, which is most probably identical with
Inhibin and it is possible to raise antibodies
against this testicular factor.
Further work
is in progress.

Studies on prolactin:
Capacitation i.e.
alteration in the mem­
brane of a spermatozoa has to take place be­
fore it can fertilize the egg.
Interference
with capacitation could result in the reduc­
tion or nullification of the
fertilizing
potential of spermatozoa.
As the sperm capa­

citates, there is a reduction in its binding
capacity to
substances like tetracycline.
Recent studies at the IRR, Bombay, have re­
vealed that prolactin affects the process of
capacitation as indicated by alteration of
tetracycline binding capacity of spermatozoa.
It seems likely that prolactin, present in
semen and cervical mucus, would play an impor­
tant role in capacitation and the consequent
fertilizing capacity of spermatozoa.
Work is
in progress to examine this possibility.
A study was undertaken at Sri Venkateswar
University, Tirupati, to find out the site of
production of prolactin and its effect alongwith other gonadotropins on the male repro­
ductive system.
Enzymatic activity patterns
were studied in metabolic (brain,
liver,
muscle and kidney) and reproductive tissues
(testes, seminal vesicles epididymis and pros­
tate gland).
It was noted that specific simi­
larities of certain enzymatic patterns existed
in the two groups of tissues.
Enzymatic res­
ponse of reproductive and non-reproductive
tissues to the extraneous hormonal factors
was also found to be identical. It was obser­
ved that the later phases of spermatogenesis
which invariably involved maturation in the
epididymis and seminal vesicles were under
similar enzymatic control as that of the
liver. Thus, the possibility of non-reproductive tissue mediating metabolic regulation of
reproductive tissues opens up a new horizon in
the relationship between reproductive and nonreproductive tissue enzymes at the molecular
level.

Studies on testes and spermatogenesis:
A study is being undertaken
at the
Banaras Hindu University, Varanasi, with the
objective of collecting basic information re­
garding inhibition of spermatogenesis in the
male by immunological methods.
There is
paucity of information regarding the effect of
intratesticular
administration of specific
antibodies.
This study provides a method for
germ cell destruction by specific antibodies,
bypassing the blood-testis barrier.
It also
provides control over the extent and duration
of damage of the tubular epithelium and on
the reversibility of spermatogenesis.
Any
possible interaction of the anti-testicular
antibodies with other vital organs was avoided
by intratesticular administration of the anti­
bodies.
A study to comprehensively evaluate cases
of oligo-azoospermia of undertermined origin
by a battery of parameters, so as to identify

9
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47/1, (First Floor)St. Marks Road
BANGALORE - 560 001

the pathophysiological mechanisms was under­
taken.
Preliminary results of the study
ascertained the
importance of
testicular
biopsy score count as a valuable tool for
determining the state of spermatogenesis.
The
study further confirmed the observation, that
the degree of spermatogenesis is inversely
proportional to gonadotropic status. However,
there is disagreement between these data and
those reported by others which have shown that
serum FSH is elevated in those cases where
gametogenesis is arrested prior to spermatid
differentiation.
In this study,
inspite of
the absence of spermatids,
serum FSH levels
were in the normal range.. Further work is in
progress at the IRR, Bombay.

A study was undertaken at the Jawaharlal
Institute of Postgraduate Medical Education
and Research,
Pondicherry,
to find out the
antifertility activity and reversibility of
5-thio-D-glucose, and to study its reaction on
the glucose metabolism of the testes and other
tissues.
Preliminary data has shown that 5thio-D-glucose acts as an antifertility agent
in mice in a very low non-toxic dose.
It is
effective for testicular suppression only when
taken orally whereas injections produce no
activity.
It inhibits testicular glucose
metabolism.
The effect is reversible if the
drug is withdrawn.

Spermatozoa:
Since spermatozoa are stored in the epi­
didymis for varying lengths of time in differ­
ent species of mammals,
a project was under­
taken at Guru Nanak Dev University, Amritsar,
to study several antiandrogens
for their
effect on this target organ.
Four drugs
namely
Ovocyclin,
chloromadinone acetate,
clomiphene citrate and cyproterone acetate
were investigated.
With Ovocyclin,
libido
remained normal and the testis,
arid accessory
reproductive organs were reduced in size.
Epididymal ductules had normal epithelium but
no sperms were seen. These atrophic
changes
were noted with chloromadinone acetate, clomi­
phene citrate and cyproterone acetate.
It is
proposed to extent this study to monkeys.
Stereotaxic studies will also be included in
this species.
A study has been undertaken at Banaras
Hindu University, Varanasi, to understand the
mechanism of maintenance of hydrolytic enzymes
of spermatozoa in a latent form.
This would
enable to identify agents which may interfere
with the fertilizing ability of sperms.

10

Studies on epididymis:
A project was carried out at the Insti­
tute of Experimental Medicine,
Calcutta, to
define hormonal mechanisms important in the
biochemical control of gene expression in
epididymis during sperm maturation. The assay
of protein kinase from rat epididymal nuclei
has been standardized. Work done so far indi­
cated significant amount of protein kinase
activity in epididymal nuclear extract.
Fur­
ther studies are in progress to purify the
nuclear protein kinase.

Male accessory glands:
A study has been undertaken at Banaras
Hindu University, Varanasi,
to enable better
understanding of the functional aspects of
accessory organs in the male,
including the
relationship of spermatozoa of the mammalian
species and accessory gland secretions. Histo-g
logy and histochemistry of the accessory gland®.

under normal condition and after administra­
tion
of
steroidal
antiandrogen,
cypro­
terone acetate,
non-steroidal antiandrogen,
N-phthalimide (DIMP), including sites of pro­
duction and content of fructose,
citric acid
and sialic acid has been investigated in
several species, including musk, shrew, Indian
mangoose, bulls, rodents, etc.
Investigations
have revealed that there is diversity in the
accessory glands even within closely related
species.
The study also emphasizes that
species also differ with regard to the site of
production and content of fructose,
citric
acid and sialic acid.

Adrenals:
Adrenocortical insufficiency results in
lowering the activity of pyridoxal 51-phos­
phate (PLP)
dependent reactions like trans- g
aminase.
These are reversed to normal when

treated with steroids or fed additional B6. To
study the role of B6 on the functions of the
adrenals, male rats were kept on B6 free diet
and compared with pair fed B6 added controls.
The rats were sacrificed after a period of 10,
20 and 60 days.
Results of this study at the
St. John1s Medical College, Bangalore, reveal
a considerable decrease in ascorbic acid, RNA,
total lipids, NEFA, hormonal secretions and a
decrease in size of the gland, but an increase
in ester cholesterol.

FEMALE REPRODUCTION
Gonadotropins:
Gonadotropins play
reproductive physiology

a pivotal role in
and a better under­

standing of these processes would enable the
development of better methods for the control
of fertility,
Considerable gaps exist in our
knowledge on the regulation of gonadotropins;
their synthesis;
secretion;* amount needed to
initiate different physiological events; bio­
chemical
events initiated in the ovary and
testis including the mechanism of their action
at the molecular level;
and disposal.
In a
project undertaken at the Indian Institute of
Science,
Bangalore, highly purified antisera
have been prepared,and characterized for their
specificity in terms of their ability to
neutralize
gonadotropins.
Antibodies
to
gonadotropins have also been used to standar­
dize radioimmunoassay procedures and also for
using them as antagonists for studying gonado­
tropin action.
This approach has helped in
elucidating the mechanisms of action of FSH
and LH at the cellular and molecular level.
The model system used in the project initially
was the laboratory rodent.
During the last
few years, a good primate colony has been
built and emphasis is being switched to work
on primates.

all laboratory animals including the non-human
primate has now been unanimously accepted.
However,
the mechanism leading to luteolysis
is still unsolved.
Findings from a project
undertaken at Raja Peary Mohan College, Uttarpara, Hooghly, West Bengal, have indicated
that prolactin is capable of reversing the
luteolytic effect of PGF2a in the pregnant
rat.
Further,
PGF2a is known to stimulate
follicular estrogen from the ovaries and this
estrogen in turn exerts a consistent luteo­
lytic effect by stimulating uterine PGF2g.
In studies on the mechanism of action of
estrogen,
it has been shown that a concomi­
tant regimen of progesterone or prolactin
with estrogen is capable of reversing its
luteolytic effect and could maintain normal
pregnancy.
It is proposed to further study
the interaction between hormones of pregnancy
and prostaglandins in
sensitizing uterine
component for initiating the sequences of
labour.
Understanding of such complicated
physiology may help,
in manipulating
the
environment so that premature emptying of un­
wanted conceptus could be achieved.

In addition to this, a major effort has
been in the study of cyclical follicular matu­
ration, termination of pregnancy and lacta­
tion. Homologous and hetrologous gonadotropin
antibodies have been used. Information accrued
would help in the
development of better
methods for fertility control.

Implantation:

Ovary and oogenesis:
Allotransplantation of ovary was done in
two human cases at the R.G.
Kar Medical
College,
Calcutta.
Prior to human studies
experiments were performed in bitches and
rabbits.
Encouraged by the success,
it is
proposed to undertake
transplantation
of
ovaries in more cases.
In addition, all cases
would be
analyzed for
their
chromosome
pattern,
hormone status and immunological
responses.

The cytological and histochemical studies
of oogenesis in Swiss mice have been completed
at
the
Berhampur University,
Berhampur.
Vacuoles were observed along the periphery of
the ooplasm which dispersed as the oocyte
matured.
The vacuoles did not respond to any
histochemical tests that were used.
Further
work is necessary on the oocytes as well as
zona pellucida to draw conclusions regarding
the role of these vacuoles in the maturation
of oocyte.
The luteolytic effect

of PGF2a in almost

One of the vulnerable areas in reproduc­
tion which can be easily interrupted is the
implantation stage
of pregnancy.
Recent
studies at the IRR, Bombay, have indicated
that disruption of pregnancy in mice injected
with antibodies to luteinizing hormone is
associated with changes in the phosphatase
activity in the early decidual cells. Studies
are being extended to enzymes specific for
implantation and their inhibitors.
In the ovary, the synthesis and release
of steroid hormones is regulated by the pitui­
tary hormones IB and FSH. There is no evidence
to indicate that LH or HCG like material are
present in the rabbit blastocyst and in pre­
implantation embryo of mouse.
It has been
shown recently that these embryos contain
steroid hormones and also the machinery to
synthesize steroids. A study was,
therefore,
initiated at the All India Institute of Medi­
cal Sciences, New Delhi, to localise receptors
or binding sites for IB and HCG in the morula
and blastocyst stages of mouse embryos. Using
indirect immunocytochemical techniques, it was
shown that mouse embryos contained binding
sites for IB and HCG but not beta sub-unit of
HCG or FSH.
It was also confirmed that the
mouse blastocysts contain IB or HCG like material,using an immunoperoxidase technique. The
presence of IB/HCG and its specific receptors
in the morula and blastocyst is significant as

11

this opens up another important area where
studies on regulation of steroid synthesis in
the preimplantation embryo can be used for
fertility control.*

Pregnancy:
A project was undertaken at the K.G.
Medical College, Lucknow,to evaluate biochemi­
cal
imbalance associated with the frequent
serious condition
of toxaemias of pregnancy
(pre-eclampsia).
On the basis of work done
till now it has been shown that 5-hydroxy
tryptamine levels are consistently increased
in toxaemic cases as compared to normal cases.
Further,
in parallel with the above observa­
tion,
the MAO activity in toxaemic cases is
consistently lower than that in the normal,
accounting for the increased 5-hydroxytrypta­
mine level. Another observation is that there
appears to be a shift in the localization of
activity between the normal
and the toxaemic
tissues in as much as toxaemic tissues show
pronounced MAO activity in the nuclear frac­
tion as compared to the normal tissue where
the major activity resides
in the mitochon­
drial fraction.
Further work is in progress.

NATICNAL PITUITARY AGENCY
Advances made in the field of protein
chemistry have enabled scientists to extract
and purify various hormones which the anterior
pituitary secretes.
The availability of these
purified hormones and
the development of
sensitive techniques to detect,
assay and
characterize these, has triggered and facili­
tated research in
understanding the role
pituitary hormones play in the maintenance of
normal body functions.
The possibilities of
estimating nano and even pico grams of the
potent pituitary hormones has opened up new
vistas for research which have enabled the
understanding of the basis of metabolic and
reproductive disorders and the way of treating
these.
The availability of pure hormones from
the pituitary and development of sensitive
techniques to estimate them has made a:mew
breakthrough in the regulation of fertility in
man and in animals of economic importance to
him.
The availability of pure preparations of
pituitary hormones and antisera specific to
them has enabled man to get an insight into
how these hormones control the release of
gametes, fertilization and implantation.

With a view to have a central agency
which will provide purified hormones and re­
agents necessary for assays, a National Pitui­
tary Agency has been established at the Insti­

12

tute for Research in Reproduction,
Bombay.
The major efforts of the agency are to collect
human pituitaries on a national basis;
estab­
lish national standards for pituitary hormones
and
reagents for RIA
and their distri­
bution to different workers in India;
provide
growth hormones and gonadotropins for thera­
peutic use; and improve the existing methodo­
logy of RIAs and organize training courses
in RIA methodology.
It is heartening to report that during
the short period since its establishment,
growth hormone has already been isolated,
purified and characterized.
FSH,
LH, prolac­
tin and TSH should become available shortly.
DEVELOPMENTAL RESEARCH

The development and standardization of
methods to detect
and
assay biologically
active constituents present in vital organs,
tissues or their products,
is an important
facet of research in reproduction and ferti­
lity control.
Some of the newer developments
are:

An enzyme immunoassay
gonadotropin:

for

human

chorionic

Hormone analysis,
a procedure requiring
extensive purification of the sample and great
technical skill,
has been relatively simpli­
fied by the use of radioimmunoassays.These
specific,
sensitive assay procedures,
though
exacting to carry out,
are currently being
used all over the world for routine estimation
of HCG.
In a developing country, however, the
difficulty of getting suitable radio-active
isotopes and the costly sophisticated equip­
ment needed for performing these assays are
the major limiting factors,
even in fairly
well-equipped research institutes and hospitals,
leave alone smaller district
hospitals.
Therefore,
the possibility was explored to develop alternative assays.
In
recent years,
enzyme immunoassays are being
developed for the sensitive estimation of hormones.
The assays operate on the principle of
RIA, but with the difference that only stable
enzymes and less sophisticated equipment are
used for their execution.
Attempts were made
to develop such an enzyme immunoassay for the
estimation of HCG and to evaluate whether the
assay so developed would prove as sensitive as
the RIA assay for HCG.
An enzyme immunoassay
for HCG using alkaline phosphatase as a label
has now been standardized.
Future programmes
envisage the use of a locally available high
turn over enzyme and the development of assays
for as many hormones as possible.

Haemagglutination inhibition
technique
the detection and assay of HPL:

for

Decrease in
HPL prematurely,
spells
danger to the foetus.
A haemagglutination
inhibition immunoassay method, which is simple
and can be used even for routine testing in
small hospitals has been developed for the
assay of HPL for monitoring high risk preg­
nancies.

have indicated that both these species
prove invaluable in this respect.

will

Detection of chromosomal anomalies:
The Giemsa banding technique for identi­
fying individual chromosomes for screening of
metabolic diseases has been
standardized.
Methods to assay urinary aminoacids for the
screening of certain metabolic disorders have
also been standardized.

RIA kits for the estimation of HPL:

Pre-natal sex determination:
A highly sensitive radioimmunoassay kit
for the estimation of HPL has been developed
in collaboration
with the
Bhabha Atomic
Research Centre,
Bombay.
A RIA kit for the
detection and assay of insulin in expected to
be ready soon.

Attempts to detect sex prenatally have
been highly successful. The sex of the foetus
was determined accurately in over 98 per cent
of the cases referred to the Institute.

Biodegradable polymers:
Standardization of two new immunological para­
meters to detect immunity to spermatozoa:
Migration inhibition to detect CMI and a
lymphocyte mediated antibody dependent cyto­
toxicity, both to human spermatozoa were deve­
loped and standardized.
These procedures
along with the others standardized at the IRR,
Bombay, are employed for the detection and
evaluation of the clinical significance of
antibodies to spermatozoa.

An experimental model for studying
contraceptives on lactation:

effect of

Contraceptive steroids are being
pres­
cribed to lactating women.
A number of these
steroids which increase lactation,
are also
being considered for more widespread use in
the family welfare programmes of developing
countries. In view of
conflicting reports
available on their effect on the progeny, a
systematic study is essential.
The rat has
been found to be an extremely good model to
evaluate the growth,
maturation, development
and fertility
of the progeny of mothers
administered contraceptive drugs during lacta­
tion.

The sub-human primate as a
ceptive research:

A project was undertaken by Sri Ram
Institute, Delhi, in collaboration with IRR,
Bombay, with a view to develop polymers based
on lactic acid and glycolic acid and to study
their
biodegradable
characteristics
with
reference to their application in the field of
fertility control.
Polymerization of lactic
acid and glycolic acid has been done, and
polymer samples containing 20 per cent w/w
testosterone were studied for biodegradable
and leaching rate for a period of 3 months.
In vitro studies with norethisterone acetate
and the polymer are in progress.

Synthesis of contraceptive steroids:
An effort is being made to make the coun­
try self-reliant with regard to the national
demand for steroids which are being used for
the preparation of oral contraceptive pills.
This collaborative effort at Lucknow,Calcutta,
Bangalore and Bombay,
involves the total syn­
thesis of 19 non-steroids
(1-vinyltetralol
from 6-methoxy-tetral-l-one,
thiouranium salt
from vinyltetralol, micro-biological reduction
of secodione to secol,d-secol to d-pentenol,dpentenol to d-tetraenol,
tetraenol to estrone
and norethisterone) and norgestrel.

model for contra-

Levels of reproductive hormone protein as
well as steroid have been estimated in Macaca
radiata (bonnet monkey) and Presbytis enteltus
(Langur monkey) with reference to the menstru­
al cycle in these two species.
These basic
data will prove of great value in determining
whether or not to use these as experimental
models for contraceptive research. The results

Emphasis at the centre in Calcutta has
been on the development of chemical process
for the conversion of easily available vege­
table raw-materials
to 19 non-steroids in the
total synthetic approach to the production of
estrone and 19 non-steroids,6-methoxy-tetrall-one being the key intermediate. A techni­
cally feasible mechanical method has been
developed and standardized where the prepara­
tion of this intermediate is initiated from

13

tetralin (available from petrochemicals and
coal tar products)
and involves sulphonation,
alkali fusion and methylation followed by oxi­
dation.

steroids for contraception. Fine intermediate
organic chemicals and reagents required for
this work have also been prepared through
simpler methods.

Similarly, other chemical methodologies
for partial synthesis of 19 non-steroids based
on vegetable raw materials have resulted in
substantial development on a laboratory scale.
The conversion of 16-dehydropregnenelone ace­
tate to 19-methyl group and also androstan-17one intermediate which has further 3 steps of
transformation, would give rise to 19 non­

At the collaborative centre in Bangalore
the conversion of 16-dehydropregnenelone ace­
tate (DBA) into dehydroepiandrosterone and DHA
into dienone has been achieved.

ICMR
Dr. Shanta S. Rao, Director,
Institute for
Research in Reproduction, Bombay, participated
in the meeting of the Steering Committee of
the WHO Task Force on the ‘Immunological
Methods for Fertility Regulation’ held at
Geneva between 27th February and 2nd March,
1978.

It is proposed to continue this work and
achieve the total synthesis of steroids.

NEWS
Dr. C. Gopalan, Director-General, participated
in the WHO Consultative meeting on ’Nutrition
Programme Development’ held at Geneva between g
6th and 10 th March, 1978 and in the workshop ‘
on the
’South East Asian Regional
Programme
for Applied Research in Malaria Control’
held
at New Delhi between 14th and 17th March, 1978.

***
Dr. A.D. Taskar,
Chief Statistician,
Indian
Council of Medical Research, New Delhi, was a
participant in the WBO Interregional Con­
ference on ’Teaching Statistics to Medical
Undergraduates* held at Karachi between 4th
and 9th March, 1978.

***

***

Dr. S.B. Moodbidri, Research Officer,Institute
for Research in Reproduction, Bombay, proceeded
on a WHO Research Training fellowship for one
year to U.K. and USA to study extraction and
purification of gonadotropins.

ICMR AIDED SYMPOSIA/SEMINARS/WORKSHOPS
An International Symposium on ‘Biomolecular structure, conformation,
function and
evolution* was organised at the University
of Madras, between 4th and 7th January, 1978.

A workshop on *Periodontology ’ was organised at the Dental College and Hospital,
K.G. Medical
College,
Lucknow,
from 9th to
13th January, 1978.
A workshop on ’Chemotherapy of leprosy*
was organised at the Central Leprosy Teaching
and Research Institute, Chingleput, on 21st
January, 1978.
A workshop on
’Benefit through manmachine interaction'
was organised by the
Indian Association of Occupational Health and
the Institution of Engineers (India) at Madras
between 27th and 29th January, 1978.

Symposia on *Family
situation’,
’Health for

14

care - a learning
all*
and ’Human

fluorosis’, were organised as part of 8th
Annual Conference of the Indian Association of
Preventive and Social Medicine,
at the R.N.T.
Medical College, Udaipur, between 9th and 11th
February, 1978.

An International Symposium and a Workshop
on
’Biomedical engineering’ were organised
at the Indian Institute of Technology, New
Delhi, from 15th to 22nd February, 1978.
A workshop on ’Hospital
infections with
special reference to Pseudomonas aeruginosa'
was organised by the Department of Microbiology,
All India Institute
of Medical
Sciences, New Delhi, between 20th and 27th
February, 1978.
A symposium on ’Environmental agents and
their biological effects*
is being organised
at Osmania University,
Hyderabad,
in March,
1978.

e

A symposium on Leprosy is being organised.
at the V.M. Medical College, Sholapur on 25th
and 26th March, 1978.
A workshop on ’Hydrocephalus’
is being
organised at the • All India Institute of Medi­
cal Sciences, New Delhi, between 27th and 31st
March, 1978.

A symposium on ’Anatomy in medical educa­
tion’ is being organised at the Department of
Anatomy, All India Institute of Medical Scien­
ces, New Delhi in April, 1978.

A symposium on
’Clinical pharmacoki­
netics ’
is being organised during the V
Southern Regional Conference of the Indian
Pharmacological Society at Pondicherry on 9th
and 10th September, 1978.

A symposium on ’Population structure and
human variation’ is being organised during the
International Congress of Anthropological and
Ethnological Sciences at Bombay between 19th
and 21st December, 1978.

A laboratory teaching workshop in Physio­
logy is being organised by the Department of
Physiology, All India Institute of Medical
Sciences, New Delhi,
between 17th and 29th
July, 1978.

Symposia on ’Reproductive biology’ and
’Nutrition’ are being organised during the VII
International Congress of the Primatological
Society at the Indian Institute of Science,
Bangalore between 1st and Sth January, 1979.

PROGRAMME OF SCIENTIFIC LECTURES AT THE
INDIAN COUNCIL OF MEDICAL RESEARCH, NEW. DELHI

Date

Topic

3.3.1978

Indigenously developed electronic cardiac
instruments

Surgeon Commander A.K.Deb,
Bangalore.

17.3.1978

Endemic Fluorosis in Punjab
(Basanti Devi Amir Chand Prize Oration 1978)

Dr. S.S. Jolly,
Patiala

31.3.1978

Erythropoiesis in thyroid diseases

Dr. R.J. Dash,
Chandigarh.

7.4.1978

Advances in the management of ischaemic
heart disease
(Chaturvedi Kalawati Jagmohan Dass Memorial
Award Oration 1977)

Dr. K.K. Datey,
Bombay.

Speaker

COUNCIL’S TRAINING PROGRAMMES FOR 1978

Leprosy:

Virology:

At the Central Jalma Institute for
rosy, Agra.
Training course in Leprosy
officers:
(December, 1978).

At the Virus Research Centre, Poona.

Lep­

for medical

(1)

Diploma course in Virology
versity:
(July, 1978).

of Poona Uni­

15

(2) *Training course for
period of one year.

(3)

Technicians

Short-term course in Animal Cell
Culture:
(June, 1978).

for a

Occupational Health:
At the National Institute of Occupational
Health, Ahmedabad.

Tissue

(1) *ICMR/WHO training
Toxicology.

Reproductive Biology:
At the Institute for
duction, Bombay.

Research, in

Repro­

(1)

Training course in Reproductive Biology:
(January, 1978 to March, 1978).

(2)

Radioimmunoassay of Protein and Steroid
Hormones: (January, 1978 to March, 1978).

(3)

Training course in Genetics:
1978 to February 15, 1978).

(4)

Training course in
Basic Immunology:
(February, 1978 to March, 1978).

(5)

Training course in Contraceptive Research
and Reproductive Endocrinology:
(March,
1978).

(1)

(2)

(3)

in Industrial

(2) *Refresher course in Occupational Health
for E.S.I. medical staff.
(3)

*Training course on Chemical Hazards in
Chemical Industry organised jointly by
the NIOH and the National Safety Council.

Clinical Pharmacology:
At the Department of Pharmacology,
G.S. Medical College, Bombay.

(January 16,

Seth
a

Training course in Clinical Pharmacology:
(January 15, 1978 to February 28, 1978).

Biostatistics:
At the National Institute of Nutrition,
Hyderabad.
Annual training course in Biostatistics
for Statisticians:
(November, 1978).

Nutrition and Endocrinology:
At the National
Hyderabad.

course

Institute of Nutrition,

Laboratory Animal Technology:

M.Sc. (Applied Nutrition) course:
1978 to February, 1979) .

(June,

Annual certificate course in Endocrino­
logical Techniques and their Application:
(October, 1978 to November, 1978).

(1)

At the Virus Research Centre, Poona.
Short-term course in Breeding and Mainte­
nance of
Laboratory Mouse
Colonies:
(March, 1978).

(2)

Annual certificate course in Nutrition:
(December, 1978 to February, 1979).

e

At the National Institute of Nutrition,
Hyderabad.

Laboratory Animal Technicians Training
Course:
(August, 1978 to, September,1978) .

Haematology:
At the
Bombay.

Blood

Group

Reference

Centre,
. .

(1)

A certificate course in Blood Banking
Technology and Basic Haematology
for
medical officers:
(February 1,
1978 to
March 31, 1978).

(2)

Training course in Blood Banking Methodo­
logy for Technicians: (May 2 to 14,1978).

COURSES FOR TALENT SEARCH SCHEME FELLOWS
Haematological Techniques:
(1)

At the Department of Pathology, Christian
Medical College, Vellore:
(February 28,
1978 to March 10, 1978) .

(2)

At the Department of Haematology, Post­
graduate Institute of Medical Education
and Research,Chandigarh:(September,1978).

*Cell-Biology and Cyto-Genetics:

Clinical Pharmacology:
At the Department of Pharmacology, Post­
graduate Institute of Medical Education §
Research,
Chandigarh:
(March 6 to 15,
1978) .

*Clinical Chemistry
tion:

At
the Indian
Bangalore.

Institute

of

Science

*Principles and Methods in Medical Statistics
At the Tuberculosis Chemotherapy Centre
Madras.

and Medical Instrumenta­

is
m

At the National Institute of Nutrition,
Hyderabad.

*Methods used in Diagnostic Virology:
At the Virus Research Centre, Poona.

*Use of Radioisotopes in Medicine:
At the National Institute of Nutrition,
Hyderabad.

SOME

ICMR

*Dates to be announced later.

PUBLICATIONS

TECHNICAL REPORTS
Price
Rs.

Research in Medical Education (1970)

4.00.

Research in Health Practices (1970)

4.00

Acute Encephalopathy Syndrome in Children (1970)

4.00

Exfoliative Cytology (1971)

4.00

Symposium on Nutrition and Heart Disease

(1971)

4.00

Developments in Industrial Psychology in India (1971)

4.00

Proceedings of Seminar on Immunity and Immunoprophylaxis in Cholera (1971)

4.00

Diagnosis and Treatment of Pesticide Poisoning (1971)

4.00

Symposium on Clinical Evaluation of New Drugs (1972)

4.00

Techniques in Blood Group Serology (1972)

4.00

Laboratory Methods in Investigation of Thyroid Diseases (1972)

4.00

Proceedings of the First Annual Meeting of the Indian Academy of Cytologists
(1972)

4.00

Review of Work Done in Rural Water Supply in India (1972)

4.00

Genetics and our Health (1972)

4.00

All India.Conference on Research in Reproduction and Fertility (1973)

4.00

A Study of Morbidity Patterns and Standard of Medical Care in the
Rural Centres of West Bengal (1973)

4.00

Proceedings of the First All-India Workshop Conference on Stroke (1973)

4.00

Seminar on Infectious Hepatitis and Study Group on Australia Antigen (1973)

4.00

Atlas of Histopathology of Liver: Hepatitis and Cirrhosis (1974)

10.00

17

Price
Rs.
Studies on Pre-school Children (1974) Reprinted 1977

3.50

Studies on Weaning and Supplementary Foods (1974) Reprinted 1977

4.00

Medicinal Plants of India - Vol.1 (1976)

30.00

Alternative Approaches to Health Care (1977)
Research in Malaria - An Outline (1977)

Gratis

.

Gratis

SPECIAL REPORTS

Memorandum on the Treatment of Leprosy with Sulphones (1952)

0.37

A Supplement to the Results of Diet Surveys in India by K. Mitra (1953)

1.00

Review on Haematology with a note on criteria for averages and normals (1953)

1.00

Treatment and Hygienic Disposal of Lac Wastes by T.R. Bhaskaran (1954)

0.62

A review of work on Infant Mortality by D.M. Satur and S. Bhatia (1957)

1.00

Proteins in Foods.by S. Kuppuswamy, M. Sriniwasan and V. Subramanyan (1958)

12.00

Tuberculosis in India: A Sample Survey, 1955-58(1959)

2.00

Physiological Norms in Indians: Pulmonary Capacities* in Health by
M.N. Rao, A. Sen Gupta, P.N. Saha and A. Sita Devi (1961)

3.00

Treatment and Disposal of Sugar Factory Effluents by T.R. Bhaskaran,
R.N. Chakraborty, N. Das and S.N. Sinha (1961)

1.00

Manual of Standards of Quality for Drinking Water Supplies (1962),
Second Edition 1975

1.00

Utilization of Liquid Wastes from Molasses Distillery for Recovery of
Potassium Salts by R.N. Chakraborty and T.R. Bhaskaran (1964)

0.50

Occupational Health Research in India: A Second Review by M.N. Rao and
B.B. Chatterjee (1964)

Gratis

Nardostachys Jatamansi - A Chemical, Pharmacological and Clinical
Appraisal by R.B. Arora (1965)

4.50

Dietary Allowances for Indians by C. Gopalan and B.S. Narasinga Rao (1968)
Reprinted 1977

4.00

EDITORIAL

Chairman
Dr. C. Gopalan
Director-General

Editor
Dr. N. Medappa

BOARD
Members
Dr. S.V. Apte
Dr. Usha K. Luthra
Dr. V.N. Rao
Dr. G.V. Satyavati
Dr. A.D. Taskar
Dr. Sabita Tejuja

Printed and Published by Shri Prem Chand for the Indian Council of Medical
Research, New Delhi at the ICMR Offset Press, New Delhi.

R.N. 21813/71

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