TREATMENT OF OLIGOSPERMIA WITH
CLOMIPHENE CITRATE OR WITH FORTEGE (ALARSIN) AND CROSSOVER TREATMENT WHERE
NECESSARY.
(A Retrospective study - 1977-84)
BY
Dr. Dhiraj
Gada, M.D:; Obstetrician and
Gynaecologist,
Dr. C.M. Shah, M.S.,
Gada Nursing Home, 70, Jawahar Marg,
The Antiseptic: Vol : 84,5, P P 267 to 274, Mar 1987
INTRODUCTION
Treatment
of infertility forms a major work-load in the practice of a Gynecologist in
This study
was undertaken to assess or compare the efficacy of Clomiphene or Fortege.
These drugs were randomly used in the management of oligospermia without
knowing how far these were useful. The analysis is made retrospectively and the
findings are given in this study.
COMPOSITION OF FORTEGE (Alarsin) :
Herbal Drug
y;iachtablet contains in mg.:- Kamboji
(Breynia Patens) : 56.(., ,G Kauncha
Beej (Mucuna Pruriens): 30.0; Suddha Kachura (Detoxicated Strychnos Nuxvomica):30:0, Samudra Sosh beej
(Argyreia speciosa): 15.0, Vardhara beej (Rourea Santaloides-seeds): 15.0, Asan (Withania Somnifera):15.0, Vardhara mool (Rourea San taloides-root): 15.0, Laving (Caryophyllus
aromaticus): 7.5, Pipar
(Piper Longum):7.5, Vacha (Acorus Calamus): 7.5, Mari (Piper
Nigrum, Black Piper): 7.5, Sunth
(Zingiber Off icinalis):
7.5, Chini Kabab (Cubeb Officinalis): 7.5, Akalakara {Anacylus pyrethrum}: 7.5, Sukhed ver (Santalum album): 7.5, Jaifal (Myristica Fragrans):
4.5, Javantri (Myristica Fragrans-arillus): 3.0 and Jeevanti . (Leptadenia Reticulata): 56.5.
The
properties of Fortege are given as follows:
Safe and non hormonal drug to relieve Fatigue (muscular, nervous,
sexual, physical, mental), Stress and Strain. Corrects sperm
defects. Improves quality and quantity of semen.
Tones up neuro-glandular, neuro-muscular, genito-urinary
and gastro-intestinal systems. No draw-backs like stimulation and
excitation followed by exhaustion id depression. No euphoria, no drowsiness, no
hangover. Relieves constipation. Controls hyper-excitability of higher and
lower sex centres. Improves sex, performance. Keeps
one fresh, alert, active and vigorous. Gives a sense of
well-being.
MATERIALS AND METHODS
This study
covered a period of eight years from 1977 to 1984 and a total number of 1578
cases of infertility were registered during the period. When a female partner
was registered for infertility we insisted on investigating the husband first
and later investigated the wife as a routine. Only those cases of uncomplicated
oligospermia whose wives were found normal were taken up for this study.
Semenogram
was done in every case and at least two semenograms were
done before confirming the diagnosis as a case of oligospermia. Then treatment
was given with Clomiphene Citrate or Fortege randomly, continuously for three
months when semen analysis was repeated. Those cases who
showed considerable improvement were continued with the same drug for a further
period-of 3-6 months. Those cases who showed no
improvement with the first course were changed to the other drug, that is those
who received Clomiphene before were given Fortege and vice versa. This was
continued for 3-6 months before final assessment was made. Semen analysis was
made every three months.
No other
drug other than Clomiphene or Fortege was used in these patients. However, in a
few patients who showed significant number of pus cells under HPF antibiotics
were used for a limited period in the beginning.
All the
patients were instructed to avoid tight undergarments, hot water bath, tobacco
and alcohol.
INVESTIGATIONS
The following
investigations were done:
Semen
analysis before starting treatment and repeated every three months upto end of nine months. Haemogram:
Blood Sugar: VDRL; Urine Examination.
X-Ray chest: prostatic smear examination. Hormonal
investigations could not be done for want of facilities.
MALE INFERTILITY
Those cases
that showed sperm count of 15-40 million/ml and/ or sperm motility of less than
40 per cent were labeled as Mild type of oligospermia. If the sperm count was
less than 15 millions/ml and/or sperm motility of less than 15 per cent, these
cases were labeled as of severe type of oligospermia. Two or more semenograms were taken before final diagnosis.
RETROSPECTIVE STUDY
Among the
total of 1578 eases registered for infertility 226 cases(16.8
per cent) were lost to follow-up. Before completion of investigations, 196
female partners conceived. Both partners were normal in 234 cases (14.8 per cent)
Both partners were abnormal (Couple Infertility) in
110 cases (7.0 per cent). There were 278 cases (17.6 per cent) of Female
Factor. . 494 cases (31.3 per cent) were of Male Infertility where the female
partner was normal and the Infertility was solely due to the male factor. Among
the cases of sterility, Primary and Secondary Sterility were in the ratio of
5:3 respectively. (Table I)
Table-1:
Couples registered for treatment of Infertility 177-84 :1578
No.
%
Lost to
follow up
: 266
16.9%
No abnormalities
detected
Both partners
had Abnormality :
110
7.0%
Only Male
Factor :
494 31.3%
Only Female
Factor : 278 17.6%
Total : 1578 100.0
Primary
Sterility: Secondary Sterility 5:3
ANALYSIS OF ABNORMAL SEMENOGRAM
There were
494 cases of abnormal semenogram whose wives were
investigated and found normal. Among these, 65 cases were of azoospermia, 10 cases of necrospermia,
9 cases of oligospermia with bilateral varicocele and
410 cases of uncomplicated oligospermia (229 cases of Mild Oligospermia and 181
cases of Severe Oligospermia). All the 84 complicated cases were referred to
the Surgeon for testicular biopsy and follow-up. Those 410 uncomplicated cases
of oligospermia were taken up in this study. (Table.
II)
Table-II :
Only Male Factor (494): Semenogram Remark
Semenogram . No.of
cases % Remarks
Azoospermia : 65
13.2% Referred to Surgeon
Necrospermia : 10
2.0% for testicular Biopsy
Surgical Pathology: 9 1.8%. and Follow-up
Mild ((229)
and
Severe
(181) 410 83.0% Analyzed
Oligospermia for
this study
Total: 494 100.0%
AGE GROUPS
The age
group of 31-40 years was the largest with 159 cases (38.78%).
Table - III: Age Groups (410 cases
of Oligospermia)
Age group No. of cases %
20-30 Years 100 24.39%
31-40 Years 159 38.78%
41-45 Years 99 24.15%
46-50Years 52 12.68%
Above 50
Years 0
Total 410 100.00
CLOMIPHENE CITRATE AND FORTEGE
GROUPS: Mild and
Severe cases of Oligospermia:
There were
104 cases of Clomiphene treated cases and 125 cases of Fortege treated cases
among the total of 229 cases of Mild Oligospermia and among 181 cases of severe
Oligospermia 86 cases were in the Clomiphene group and 95 cases were in the
Fortege Group. Total cases treated with Clomiphene Citrate were 190 and total
cases treated with Fortege were 220. (Table IV)
Table-IV:
Clomiphene and Fortege Groups: Mild and Severe cases
Group Total
cases Mild % Severe %
Clomiphene
cases 190 104 54.7% 86 45.3%
Fortege
cases 220 125 56.8%
95 43.2%
Total 410 229 55.9% 181 44.1%
DOSAGE OF CLOMIPHENE CITRATE
In the Group
which was started with Clomiphene Citrate, the dose of Clomiphene Citrate was
50 mg per day for the first three months. Improved cases were continued with
Clomiphene Citrate for a further period of 3-6 months in the same dosage. It
was discontinued if the wife conceived before that period. Those cases which
showed no improvement with the first course were changed
DOSAGE OF FORTEGE
In the
group where treatment was started with Fortege, the dose of Fortege was 2 tabs,
three times a day for the first three months. Improved cases were continued
with Fortege in the same dosage for a further period of 3-6 months. The drug
was discontinued in case the wife conceived before that period. Those cases that
did not show improvement with the first course of three months were changed to
Clomiphene Citrate.
ASSESSMENT OF IMPROVEMENT OF SEMEN
The case
was classified as improved if the sperm count increased to over 40 millions/ml
and with sperm motility of 50 percent -.and over.
RESULTS OF CLOMIPHENE GROUP:
First three
months
Out of 104
cases of Mild Oligospermia, 32 cases (30.8 per cent) showed improved semenogram and 72 cases (69.2 per cent) showed -No
Improvement. Out of 86 cases of Severe Oligospermia, 19 cases (22.1 per cent)
showed improvement and 67 cases (77.9 per cent) showed No Improvement. Taking all the 190 cases. 51 cases (26.8 per cent) showed
improvement and 139 cases (73.2 per cent) showed No Improvement. (Table V)
TABLE-V: Results of Clomiphene
treatment (I Course).
Type No.of
cases % Improved % Not Improved %
Mild 104 100%
32 30.8% 72 69.2%
Severe
86 100% 19 22.1% 67 77.9%.
Total .
190 100.0%
51 26.8% 139 73.2%
RESULTS OF FORTEGE GROUP: First
three months -
Out of 125
cases of Mild Oligospermia of this group, 102 cases (81.6%) showed Improvement
and 23 cases (18.4%) showed No Improvement. Out of 95 cases of severe oligospermia,
42cases (44.2%) showed improvement and 53 cases (55.8%) showed No Improvement.
Taking all, the 220 cases of Fortege Group, 144 cases.(65.5%)
showed improvement and 76 cases(34.5%) showed No Improvement. (Table VI)
TABLE-VI:
Results of Fortege treatment (I Course).
Type No.of
cases Improved % Not
Improved %
Mild 125 102
81.6% 23 18.4%
Severe 95 42 44.2% 53 55.8%
Total 220 144 65.5% 76 34.5%
CROSSOVER(EXCHANGED)TREATMENT
Number of cases available for Clomiphene treatment and
Fortege treatment:
There were in all 215 cases of No Improvement, 139 from the_
Clomiphene group and 76 from the Fortege group. However, 42 cases were not
available for Crossover (Exchange) treatment for one reason or other. So on the
whole 63 patients were given; Clomiphene and 110 cases were given Fortege in
the Crossover treatment (II Course)(Table VII)
Table - VII: Not
improved cases available for Crossover Treatment with Clomiphene; Fortege.
Group Total
Mild Not
Treated Severe Not
Treated
cases followed
followed
Clomiphene: 76 23 0
23 53 13 40
(100%)
(24.5%)
(75.5%)
Fortege: 139
72 14
58 67 15
52
(19.4%) (80.6%) (22.4%) (76.6%)
Total: 215
95 14
81 120 28
92
(14.7%) (85.3%) (23.3%) (76.7%)
RESULTS OF CROSSOVER
TREATEMENT WITH CLOMIPHENE (II Course)
In the crossover treatment with Clomiphene 14 cases (22.2 %)
(10 of Mild type and 4 of Severe type) showed
improvement with three months of treatment and 49 cases (77.8%) (13 from Mild
type and 36 from Severe type) showed no Improvement.
(Table VIII)
Table - VIII: Results of Crossover Treatment with Clomiphene
Type Total
cases Improved % Not
Improved %
Mild 23 10 43.5% 13 56.5%
Severe . 40 4
10.0% 36 90.0%
Total . 63 14 22.2% 49 77.8%
RESULTS OF CROSSOVER
TREATMENT WITH FORTEGE (II Course)
In the
crossover treatment with Fortege, 68 cases (61.8%) (44 from Mild type and 24
from Severe type) showed improvement and 44cases (38.2%) (14 from Mild type and
28 from Severe type) showed No Improvement after three
months treatment with Fortege. (Table IX)
Table - IX: Results of Crossover
treatment with Fortege
Type Total cases Improved % Not Improved %
Mild 58 44 75.9% 14 24.1%
Severe 52 24 46.2% 28 53.8%
Total 110 68 61.8% 42 38.2%
FINAL ASSESSMENT OF RESULTS WITH
CLOMIPHENE CITRATE TREATMENT (I Course plus Crossover)
On the whole
253 cases were treated with Clomiphene. Out of them 65 cases (25.7%) (42 from
Mild Type and 23 from Severe Type) showed improvement and 188 cases (74.3%) (85
from Mild Type and 103 from Severe Type) showed no Improvement. (Table X)
TABLE - X :
Final assessment of results : Clomiphene (I and Crossover)
Type I(Course) II (C.O) Total Improved % Not
Improved %
Mild 104 23 127 42 33.1% 85 66.9%
Severe 86 40 126 23 18.3% 103 81.7%
Total 190 63 253 65 25.7% 188 74.3%
FINAL ASSESSMENT OF RESULTS WITH
FORTEGE TREATMENT (I Course plus Crossover)
On the
whole 330 cases received Fortege treatment. Out of them, 212 cases (64.2%) (146
from Mild Type and 66 from Severe Type) showed improvement and 118 cases
(35.8%) (37 from Mild Type and 81 from Severe Type) showed No Improvement
(Table XI)
Table - XI: Final assessment
of results: Fortege (Iand Crossover)
Type 1(Course) II(C.O.) Total Improved % Not Imprvd. %
Mild 125
58 183 146 79.8% 37 20.2%
Severe 95 52 147 66 44.9% 81 55.1%
Total 220 110 330 212 64.2% 118 35.8%
OVERALL RESULTS: CLOMIPHENE TREATED
CASES AND FORTEGE TREATED CASES COMPARED:
Out of 253
cases who were treated with Clomiphene Citrate, 65
cases (25.7øk) improved and 188 cases (74.3%) showed No Improvement. Out of 330
cases who were treated with Fortege, 212 cases
(64.2øk) showed improvement and 118 cases (35.8%) showed No Improvement.
Overall, Fortege treatment showed an excess of 38.5% of good improvement over
those treated with Clomiphene Citrate. (Table XII)
Table - XII: Overall Results: Comiphene; Fortege.
Drug
Total cases improved %
Not Improved %` Excess Imp in
Clomiphene : 253 65 25.7% 188 74.3%
Fortege 330 212 64.2% 118 35.8% 38.5%
CONCEPTION RATE IN THE WIVES OF CLOMIPHENE
TREATED GROUP
Out of 65
improved cases with Clomiphene treatment, 20 of their wives conceived giving a
conception rate of 30.8% among improved cases only. If all the 253 cases who
received Clomiphene Citrate are considered, only 20 of their wives conceived
giving a conception rate of 7.9%. All conceptions took place in 3-9 months.
(Table XIII)
Conception Rate of the wives of
Clomiphene treated Group.
Type No-of cases Wives conceived Conception Rate
Mild impr. cases 42 16 38.1%
Severe Impr cases
23 4 17.4%
Total impr. Cases 65 20 30.8%
Total
treated cases 253 20 7.9%
CONCEPTION RATE IN THE WIVES OF
FORTEGE TREATED GROUP
Out of 212
improved cases with Fortege treatment, 103 of their wives conceived giving a
Conception Rate of 48.6%, an excess of 17.8% over Clomiphene treated Group. If
all the Fortege treated group is considered out of 330 treated, 103 of their
wives conceived, giving a conception rate of 31.2%, an excess of 23.3 % over
the Clomiphene treated group. All conceptions took place in 9 months. (Table
XIV)
TABLE -
XIV:
Conception
Rate in the wives of Fortege treated Group.
Type No
of cases Wives conceived Conception Excess
Rate Conception
cases rate in
Fortege
Group
Mild impr.cases 146 85 58.2% 20.1%
Severe impr. cases 66 18 27.3% 9.9%
Total impr. cases 212 103 48.6% 17.8%
Total
treated cases 330 103 31.2% 23.3%
SIDE EFFECTS
Mild side
effects of gastric irritation were seen in 32 cases of Clomiphene group and
only 3 cases of the Fortege group showed these Mild side effects.. Gastric irritation subsided in both groups when they were
advised to take the drug with milk.
There were
4 cases of severe side effects, two of alopecia and two of skin rash among the
Clomiphene Group, while severe side effects were nil in the Fortege Group.
CONCLUSIONS
Semenogram
improved in 65 cases out of 253 treated with Clomiphene, an improvement of 25.7
per cent. Semenogram improved in 212 cases of 330 cases treated with Fortege
showing an improvement of 64.2 per
cent, that is, an excess of 38.5 percent improvement over Clomiphene group.
2. Overall
conception rate in the Wives of Clomiphene treated group was 7.9 per cent.
Overall Conception rate in the wives of Fortege treated group was 31.2 percent
that is an excess of conception rate of 23.3 per cent over the Clomiphene
group. The increased Conception Rate in the wives of Fortege group can be contributed
to better sex performance (80 percent) and better
insemination by the Fortege treated husbands. .
3. Gastric
irritation occurred in 32 cases of Clomiphene treated groups while only 3 cases
had gastric irritation in the Fortege treated group. There were 4 cases of
alopecia and 2 cases of skin rashes in the Clomiphene group, while there were
none in the Fortege Group.
4. There
was a sense of well being in 80 per cent of Fortege treated Group while in the
Clomiphene treated Group only 40 per cent of cases had a sense of well being.
5. There is
no room for any bias in this study, because the data is taken from the records
available as a retrospective study when Clomiphene and Fortege were used
randomly even without knowing which is useful in the treatment of oligospermia.
6. This
study has shown that Fortege is a safe and highly beneficial drug in the
treatment of oligospermia compared to Clomiphene Citrate in doses of 50 mg.
daily.
AKNOWLEDGEMENT
We are
thankful for the Medical Registrars for their cooperation.
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