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    Comparison of effect of

    Clomiphene citrate alone and

    Clomiphene citrate plus Metformin

    in Polycystic ovary syndrome patients

    By

    Krishna Kumari.S.

    07 -PML 010

    Department of Advanced Zoology and Biotechnology,

    Loyola College, Chennai

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    INTRODUCTIONPolycystic (literally, many cysts) ovary

    syndrome (PCOS) is an endocrine disorder

    and a complex condition that affects theovaries.

    This disorder is characterized by changes to

    the ovaries such that multiple follicles

    accumulate in the ovaries without ovulation.

    These follicles remain immature, never

    growing to full development or ovulating to

    produce an egg capable of being fertilized.

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    What are the differentiating features of PCOS?

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    Treatment aim is to improve:

    Fertility, via the stimulation of ovulation.

    Reduction of the insulin resistance.

    Two major drugs used worldwide are

    Clomiphene Citrate to induce ovulationMetformin to improve hyperinsulinemia

    Most researches showed that addition of

    metformin to CC regulated menstrual cycles &

    pregnancies.

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    What kindled my interest on this topic??

    In general population nearly 25% of women have polycystic ovaries

    Till now no clear evidence study about the treatment effect of these

    drugs on Chennai women

    Very low pregnancy rate??

    Aim & Objective of the Study

    Estimating the blood glucose level, Leutinisng hormone, Prolactin, ovulation

    induction and rate of success in pregnancy after treatment with either CC

    alone or CC plus Metformin.

    To compare the effect of CC alone and Metformin plus CC on the above factorsin polycystic ovary syndrome.

    To determine the overall effect of treatment on the above factors in

    polycystic ovary syndrome

    To determine the rate of success in pregnancy through different methods i.e. byIUI and Natural method.

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    Materials & Methods

    Elecsys 2010 uses electrochemiluminescence immuno-assay (ECLIA) for theestimation of leutinising hormone and prolactin. Roche/Hitachi works uses Immunoturbidimetric assay for the estimation of

    blood glucose.

    Ultrasound scanning machine uses Pulse-echo principle for the diagnosis ofpolycystic ovarian syndrome and to monitor the follicle maturity.

    Statistical Tool:

    All the data are statistically analyzed by using the SPSS software The comparison of two groups of treatments i.e. CC plus Metformin and CC

    alone are analyzed through Paired T-test

    If the p0.05 it is insignificant.6

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    RESULTSIn this study 100 PCOD patients were examined and out of these 100, 21 were found to have abnormal

    blood glucose level. They were given clomiphene citrate plus metformin. These 21 patients wereassigned as Group I. Another 79 patients were given Clomiphene Citrate alone and were assigned as

    Group II.

    Blood glucose level of 10 patients was found to be high and 11 patients have low glucose before

    treatment. After treatment with metformin the 10 patients were found to have normal glucose level

    and by improving the diet the 11 patients with low blood glucose were found to be improved

    17 patients of Group I & 57 patients of Group II were found to have irregular menstrual cycle but

    after treatment with both the group of drugs the ovulation was induced in all the patients

    7

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    Results contd ..

    Both the Group of drugs showed 19% pregnancy rate

    Rate of success through natural method was high in group I (5%) whereas the rate of

    success through IUI was more in group II (16%)

    The mean LH level before treatment was found to be 8.9 mIU/ml for Group I & 8.8mIU/ml for Group II patients. After treatment the mean LH level was reduced to

    5.7 mIU/ml for both the groups of patients

    The mean level of prolactin was found to be 15.8 ng/dl for group I patients & about

    18.9 ng/dl for group II patients. After treatment the mean prolactin level was found

    to be increased to about 21.8 in group I & 28.8 in group II patients.

    8

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    Results contd.

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    Leve l o f Pro lac t in before t(va lues in ng /ml )

    1 9

    47

    23

    11

    L e s s t h a n

    10 -20

    2 0 - 3 0

    M o r e t h an

    Level of Prolactin after treat(values in ng/ml)

    7

    21

    40

    32

    Less than 10

    10 -20

    20 - 30

    More than 3

    The overall effect oftreatment on Prolactin level

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    Results contd...

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    Success in Pregnancy(Values in Nos.)

    315

    1468

    Pregnant Natural

    Pregnant IUI

    Non-Pregnant Natural

    Non-Pregnant IUI

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    Discussion

    When the previous literatures was analyzed most researches support that

    addition of metformin improves the treatment effect. In this study I found

    that both the groups of treatment have similar effects on PCOS.

    The treatment is effective in regulating the blood glucose level and also the

    level of LH. It is also effective in ovulation induction.

    But the treatment with both the groups of drugs leads to

    hyperprolactinemia. Clomiphene citrate an antioestrogen stimulates the

    synthesis of estrogen by blocking the estrogen receptors. This in turninduces the pituitary lactotropes to secrete Prolactin. This results in the

    elevation of prolactin level. The amount elevated through this mechanism is

    negligible. But in this study we found that the prolactin level is increased by

    10 times. 11

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    Discussion contd.

    So I suggest that the effect of Clomiphene citrate may differ by

    the race, climatic conditions and the physiological changes that occurin response to clomiphene citrate is different for the South- Indian

    patients affected with polycystic ovary syndrome. It is also suggested

    that, the elevation may due to stress since prolactin is a stress

    hormone.

    Most researches suggest that the success in pregnancy through these

    treatment is between 20-25% which somehow coincide with our study

    as the pregnancy rate is found to be 19%

    Though the paired t-test result shows that p

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    Discussion contd .

    From this study I suggest that

    There is no added benefits of metformin when it is used in combination

    with clomiphene citrate

    This treatment leads to hyperprolactinemia that might be the reason

    for the low pregnancy rates

    The treatment is effective in regulating the blood glucose level, level of

    LH and also helps in ovulation induction

    13

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    To detect the exact mechanism of clomiphene citrate on the elevation of

    prolactin and the relation between the low pregnancy rate andhyperrprolactinemia

    To design a drug that may not elevate the prolactin but regulates the LH level,

    induce the ovulation and increases the pregnancy rate.

    To study whether the effect of Clomiphene citrate differs with race, age andothe physiological properties

    To detect the risk & incidence of endometrial cancer due to this treatment on

    PCOD patients.

    To study whether these drugs have any effect on estradiol, FSH, DHA etc.,To detect the role of serum CA 125 and estradiol in PCOS

    To detect the rate of ovarian hyper stimulation by these drugs

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    Future Perspectives

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    Thank You