Reprinted from The Medicine & Surgery Vol X XI I I No. 2 February 1983

Paper presented at the Second Congress, Indian Society of Perinatology, Reproductive Biology & Planned Parenthood, Jammu (J&K), 27-29, Sept.80.

Treatment Of Threatened Abortion With Progesterone And Leptaden And Outcome Of Pregnancy

(A Controlled Study)

by

Dr. (Mrs) Florence S. Philips, DGO., FRCOG.,Professor 'of Obst. & Gynaee., Madras Medical College, & Director and Superintendent, Inst. of Obst. & Gynaec, & Govt. Hospital for Women & Children, MADRAS-8

Miss Agnes Mary Poobalarayal, MD , DGO., Asst. Professor of Obst. & Gynaec., College & Hospital, TIRUNELVELI. T.Nadu.

Introduction

Threatened Abortion is a clinical entity characterized by symptoms of vaginal spotting and abdominal discomfort in the absence of significant cervical dilatation.

Claims have been made about the beneficial effects of different therapeutic regimes, varying from simple bed rest and sedation to the use of vitamins and progesterones. About 30% of the untreated cases abort at this stage.

The major hormonal deficiency which may be held responsible for the loss of pregnancy is the insufficient production of progesterone by the corpus Iuteum during the early stages of pregnancy or by the placenta once it takes over the task of secreting it. A hormonal deficiency involving progestogens in most likely to occur in the first trimester of pregnancy at the time when the main output of progesterone is taken over by the placenta from the corpus Iuteum. Pregnanedion is the chief metobolite of progesterone.The poor correlation between plasma progesterone levels and the fetal state can be to some extent be accounted for by the high variability of plasma progesterone levels from time to time in the same subject. Progesterone is not made denovo in the placenta, but by enzymatic transformation of maternal or fetal cholesterol on pregnaneolone. Even when the fortus is dead the supply of precursor from maternal sources is enough to maintain progesterone synthesis at a normal rate.

Place of Progesterone in Threatened Abortion

Progestational agents are extensively used in an effort to salvage pregnancy in cases of threatened abortion. A controversial report alleges a teratogenic effect (Phocomelia) from progestational agents which are administered during pregnancy.

Progestational Replacement Therapy

Pregnanediol is the chief metabolite of progesterone and is mainly excreted through urine. If the pregnanediol urinary excretion is low for the stage of pregnancy, the pregnant lady is given replacement therapy. Progesterone is administered as a capsule (Synerone), one capsule 3-4 times a day, up to 36 weeks or as Medroxy progesterone acetate, (Depot Provera) 80 mg/day in divided doses for 36 weeks. However, 11 alpha hydroxv progesterons caproate is the drug commonly used as intramuscular inj. 250 mg500 mg weekly up to 36 weeks.

Objects Of The Study

The object of this study was to analyze results of the outcome of pregnancy in patients who were hospitalized for Threatened Abortion and treated with Progesterone & Leptaden or Leptaden only. We also tried to assess the usefulness of vaginal smear studies.
Leptaden

Each tablet of Leptaden contains:
Jeevanti (Leptadenia retieulata) : 150 mg.Kamboji (Breynia patents) : 150 mg.

Leptaden helps proper implantation of fertilized ovum. Helps sustenance of pregnancy to Full Term and ensures FTLB (Full Term Live Birth) and a child that survives and thrives. Useful in the management of Threatened Abortion and High Risk Pregnancy and in cases with bad obstetric history of Threatened Abortion, Habitual Abortion and Premature Birth.

Table I : Review of Some Research Studies on Leptaden

	Series	Overall Observations
1.	Patel N.V. (1947).	Leptaden has helped even in cases with history of 4-10 previous abortions.
2.	Naik M. C. (1957).	Even in some cases with positive WR & Kahn tests (Syphilitic), results were surprisingly good. *
3.	Mangeshikar S.N. (1965).	Leptaden normalises environmental factors for proper implantation of fertilised ovum.
4,	Patel M. C. (1965).	Leptaden helps to sustain pregnancy to Full Term and a child that survives and thrives.*
5	Kamala Achari (1966 & 1975).	Leptaden gives better results than the conventional therapy. Leptaden has no side effects and safe to the mother and child. Simple dosage. No necessity for Laboratory tests to control the dosage

Table 1 I : Success Rate In Cases Threatened Abortion : Some Studies.

Series FTLB (Full
Kamala Achari (1975) .... 80% to 88%
Florence Philips (l977) .... 84.3°/ 0
Savitri & Venkata Rao (1977) .. 82 5%

Saxena (1979) . . . . 86.2%

LEPTADEN: EXPERIMENTAL STUDIES ON GUINEA PIGS

Leptaden inhibits Prostaglandin Fz alpha biosynthesis of the uterine tissue.

Experimental research was done on Leptaden by Sharma at the Trinity College, Dublin (Ireland), guinea pigs of known fertility. using latest sensitive radio-immunoassay methods, he found that the amount of Prostaglandin F_R alpha extracted from the Leptaden treated group was significantly lower i that of untreated group, while uterine weights of both the pro did not show any statistical difference. This indicated that Leptaden inhibits F2 alpha biosynthesis a this helps to prevent abortion since any increase to prostaglandins causes abortion or premature delivery.

Materials & Methods

Only definite cases of threaten abortion who were hospitalized v studied. Doubtful cases were excluded from the study. The total number of cases studied were 110 they were divided in two groups Group A, received Progesterone and Leptaden and Group B received only Leptaden. There were 62 cases Group A ( Prog. + Lep. ), and cases in Group B (only Leptaden Group). All 110 patients were given Leptaden 2 tabs. thrice daily from the day of admission for threaten abortion till full term, or till spontaneous termination of pregnancy earlier. Group A, in addition to Leptaden received 17 alpha hydroxy caproate 250 mg to 500 mg/week up to 36 weeks or till spontaneous termination of pregnancy if earlier.Patients were aged between 18. years. They belonged to primigravids to para V. Patients admitted for threatened abortion had amenorrhoea ranging from 10 to 28 weeks.

Previous History of Abortion

on By

There were 42 patients with pa history ofabortions and in 68 casE there was no previous history c abortion (Primary Threatened Abo3 tion). The majority of cases ha one abortion before (Table (II).

Table III : History of Previous Abortions

Abortions before	No. of cases
One abortion before :	21	19.1%
Two abortions before :	11	10.0%
Three abortions before :		4.5%
More than three abortions before :	5	4.5%
No previous history :	68	61.9%
Total :	110	100.0%

Progestational Status based on Vaginal Cytology -

Vaginal cytology was done in all 110 cases of threatened abortion after hospitalization. Based on vaginal cytology, the progestational status was classified as Good, Fair and Poor. Twenty-ore patients (19.1%) had Good progestational status, 24 patients (11.8%) had Fair progestational status & 65 patients (59.1%) had Poor pragestational status. (Table IV)

Table I V : Progestational Status based on vaginal cytology before treatment.

Prog. Status	Group A (Prog & Lep.) %		Group B (Leptaden only) %		Total	%
Good :	0		21	43.7%	21	19.1%
Fair :	16	25.8%	8	16.7%	24	21.8%
Poor :	46	74.2%	19	39.6%	65	59.1%
Total :	62	140.0%	48	100.0%	110	100.0%

Table V Outcome of pregnancy in cases of Threatened Abortion
Group A (Prog. & Lep) & Group B (only Lep)

Outcome of pregnancy	Group A (Prog. & Lep) %		Group B (Only Leptaden) %
Progressed to Full Term	49	79.0%	35	72.9%
Preterm delivery	2	32%	5	10.4%
Ended in Abortion	11	17.' %	8	16,7%
Total :	62	100.0%		100.0%

Dosage Regimen of Leptaden & Progesterone

Leptaden : All the 110 cases of Threatened Abortion were given Leptaden 2 tabs thrice daily till full term or up to spontaneous termination of pregnancy if earlier.
Progesterone ; Sixty-two cases of Group A, received, Leptaden, 2 tabs thrice daily & 17 alpha hydroxy caproate i.m. 250 mg-500 mg once a week up to ?6 weeks of pregnancy. This treatment was stopped if there was any spontaneous termination of pregnancy before full term.

Outcome of Pregnancy in Threatened Abortion : Group A (Progesterone and Leptaden) And Group B (Only Leptaden)

Among 62 cases of Group A (Prog & Lep.) there was Full Term Delivery in 49 cases (79.0%). Among 48 cases of Group B who received only Leptaden, 35 cases (72.9%) had Full Term Delivery. The advantage of Prog. & Leptaden combined therapy was 6.1%. The abortion rate in both the groups was about the same, thus indicating the addition of progesterone had not helped in the decrease of abortions in cases of Threatened Abortion. As such, in the treatment of Threatened Abortion where facilities for investigations are not available, Leptaden therapy can beneficially be used without hormonal treatment.The details of outcomeof pregnancy in Group A (Prog. & Lep.) and in Group B (only Lep.) are given in Table V.

Outcome of Pregnancy with Reference to Progestational Status.

Group A (Leptaden & Progesterone):

In this group patients having good progestational status were not included as they did not require progesterone replacement therapy. There were 16 cases with Fair progestatienal status and 46 patients with poor progestational status. Out of 16 cases of Fair Progestational status of this group, 14 patients (87.50%) had Full Term delivery, one was pre-term (6.25%) and there was one abortion (6.25%).

Out of 46 patients with Poor progestational status, 35 patients (76.09%) had Full Term delivery, one was pre-term (2.17%) and 10 patients (21.74%) had abortion. The overall Full Term delivery rate was 79.0% Table VI)

Table VI : Outcome of pregnancy with reference to progestational Status

Group A (Lep + Prog )

Proa.

Full term% before Term treatment

Prog. Status before treatment	Group A (Lep. & Prog )	Full Term	%	Premature Delivery	%	Abortion
Good :	-
Fair :	16	14	87.50%	1	6.25%	1	6.25%
Poor :	46	35	76.09%		2.17%	10	21.74%
Total :	62	49	79.0%		3.2 %	11	17.8%

Outcome of Pregnancy with Reference to Progestational Status:

Group B

(Leptaden only)In the Leptaden Group (Group B) of 48 patients, 21 patients had Good progestational status before starting the treatment. Out of these 21 patients, 19 (90.4%) had Full Term delivery, one pre-term delivery (4.8%) and 1 abortion(4.8%). Out of 8 patients having Fair progestational status 7 patients (87.5) had Full Term delivery, one pre-term and there was no abortion. Out of 19 patients who had Poor progestational status, 9 patients (47.4%) had Full Term delivery, 3 patients (15.8%) had pre-term delivery and 7 patients (36.8%) had abortion.The overall Full Term delivery rate in the Leptaden alone Group was 72.9% (Table VII).

Table VII : Group B : Outcome of Leptaden only Group : Pregnancy With reference to progestational status.

Premature Delivery

% Abortion %

Progest erone statue before treatment	Group B, only Lep, Group	Full Term	%	Preterm	%	Abortion	%
Good :	21	l9	90.4%	1	48%	1	4.8%
Fair :	8	7	87.5%	1	12.5%	0	-
Poor :	19	9	47.4%		15.8%	7	36.8%
Total :	48	35	729%	5	10 4%	8	6.7%

Discussion

In Group A where Leptaden and progesterone were used, Full Term delivery rate was 79.0%, while in B, where Leptaden alone was used, the pregnancy rate was 72.9%. The advantage of addition of progesterone was to the extent of 6.1%. However, in Full Term and Pre-term deliveries are taken together, Leptaden alone Group showed 83.3% of Live Births and Leptaden and progesterone group showed 82.2% Live Births, thus showing the success rate in both the Groups are nearly the same. Abortion rate in Prog. & Leptaden Group was 17.8% while in the Leptaden alone group was 16.7%, thus showing the abortion rates in both the groups did not differ much.This study has shown that addition of progesterone therapy by way of i.m. inj. of 17 alpha hydroxy caproate once a week for 36 week along with Leptaden therapy has not shown any appreciable difference in salvage rate when compared only Leptaden therapy. The beneficial effect of Leptaden therapy over the combined treatment better appreciated, as 19 patient (39.6%) of this group had Poor progesterone status. Hence it is concluded that the salvage rate with Leptaden alone is equally good when compared to the progesterone combined therapy. This will be particular benefit in the management of Threatened Abortion where Vaginal cytology, progestetional status and other investigations cannot be done for want of facilities.

Type of Deliveries: ! nfai Mortality :

Out of 110 cases, (both group: there were 91 Live births, with ^'Full Term deliveries and 7 Pre-ter deliveries. There was spontaneous abortion in 19 patients in spite of treatment.

Caesarian delivery had to be done in 11 patients of Full Term deliver Among the 7 pre-term babies gestational age of 32-36 weeks, the weight of the babies ranged fro 1.8 kg. to 2.3 kg. Out of these 5 survived. Among the 2 babies that died, one died due to Abruptio Placenta (Group A) and the other one died due to placenta praevia. (Group B)

Of the Full Term babies, 2 babies (Group A) died, one due to asphyxia neonatorum and another due to imminent eclampsia. In Group A, there were 3 perinatal deaths while in Group B there was one perinatal death.Full Term delivery rate in the progesterone group was 79.0% while it was 72.9% which is slightly less an the former group. If these patients had not received any therapy, the salvage rate would have been far less and many would have ended in inevitable abortion.

The Uterine cramps of threatened abortion were quickly brought under control with Leptaden and this was probably due to anti-proatoglandin effect of Leptaden.

Conclusions & Summary;

Definite cases of Threatened Abortion were divided into two groups. A & B. Group A (62 patients) received progesterone and Leptaden and Group B (48 patients) received only Leptaden.Vaginal Cytology and Urinary Pregnanediol estimation were done in all the 110 cases to assess the progestational status.Group A received Leptaden and Progesterone (17 alpha hydroxy caproate) weekly injections i.m., Group B was given only Leptaden.Full Term delivery rate was 79.0% in Group A (Prog. & Lep.) while it was 72.9% in Group B (Only Leptaden), but when pre-term deliveries were included, there was no appreciable difference between both the groups, as to Live Birth rate. (Group A 82.2% and Group B 83.3%)Considering the side effects of hormonal treatment and the necessity to monitor Pregnanediol and progesterone values before and during the hormonal treatment, Leptaden a non hormonal and a safe herbal drug requires no such special and sophisticated tests during its useIn cases of Threatened Abortion Leptaden can beneficially be used without hormonal treatment, and requires no tests.There were no toxic or side effects and Leptaden is found to be safe to both mother and child.

Acknowledgement

Thanks to Alarsin Pharmaceuticals, Bombay, for their co-operation.

References :

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2 Mrs. Achari, Kamala (1975) : Use of Leptaden in High Risk Pregnancy. 2nd International Seminar on Maternal and Peri. natal Mortality, Pregnancy Termination and Sterilisation, Bombay 3-5 March, 1975.
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