The Role of Metformin in Women with Polycystic Ovarian
Syndrome as a Treatment of Infertility
Hanan Abdul Al Jabar Altaee
College of Medicine, University of Babylon, Hilla, Iraq.
This study was conducted to study the therapeutic benefit of metformin in achieving ovulation in
women with ploy cystic ovarian syndrome (PCOS). Twenty eight women received metformin,
ovulation rate was (60.2%). While it was (100%) when we add clomiphene citrate to it. So over all
ovulation rate was (100%) and overall pregnancy rate was (10.8%) which was with metformin alone.
اجريت هذه الدراسة لتحديد مدى كفاءة دواء الميتفورمين في تحريض االباضة في مريضات العقم الومواتي
يعانين من عد حدوث االباضة بسبب متالزمة المبيض المتعدد التكيسات0 ت بحث 28 مريضة ث اعطماهم
هذا الدواء و كانت نسبة حدوث تحريض االباضة (%2.06) و كانت النسمبة (%001)عنمد اضمافة دواء
الكوومفين ستريت لوبرنامج العالجي. اما نسبة الحمل كانت (% 8.01) في همذه الدراسمة عنمد اسمت دا
Introduction insulin sensitizing biguanide
P oly cystic ovarian syndrome
(PCOS), also known as stein-
leventhal syndrome or functional
commonly used for treatment of type II
diabetes mellitus (D.M) . Metformin
decreases hyperandrogenism and
ovarian hyperandrogenism, is insulin resistance, also it improves
characterized by an ovulation, ovulation rate, cervical score and
infertility and hyperandrogenism, with pregnancy rate . This study shows
clinical manifestation of irregular the therapeutic benefit of metformin in
menstrual cycles, hirsutism and acne achieving ovulation in PCOS women.
. This condition affects about 5-10%
of women with reproductive age ; Materials and Method
although this varies depending on the Twenty eight women were studied in
diagnostic criteria used . These Al-amal center for infertility
women have increased prevalence of management from March 2007 until
cardiovascular risk factors and insulin May 2009. These women were
resistance [4, 5]. diagnosed as having PCOS according
The use of metformin for women with to ESHRE/ASRM criteria . Clinical
PCOS has aroused a tremendous criteria of women involved are listed in
amount of interest. Metformin is an table (1).
Table 1 clinical data of women involved in the study:
Mean age 27.6 years
Mean duration of infertility 2.4 years
Number with primary infertility 26
Number with secondary infertility 2
Percentage with acne 35
Percentage with hirsutism 56
Percentage with irregular menses 65
Mean body weight\kilogram(mean) 78
Tubal patency was proved by evaluate her by measurement of the
HysteroSalpinigioGraphy (HSG), base laboratory tests that were abnormal at
line Follicular Stimulating Hormone the initial evaluation. If after 9 months
(FSH), Luteizing Hormone (LH) no ovulation or pregnancy achieved we
DiHydroEpinadrosteron, (DHEA) or add clomiphen citrate (C.C) to the
testosterone and serum prolactin was protocol in a dose of 50 mg tablet
assesed by cycle day 2. Male partner twice daily from CD2-CD5, and we
have normal sremiogram according to follow the patients for ovulation, and
WHO criteria . Diet management, we check B-subunit of human chronic
exercise and life style readjustment gonado tropin (B-HCC) for pregnancy.
were discussed with these patients.
Treatment protocol: Results
All patients under went base line Seventeen women of the twenty eight
ultrasound (u\s) for ovarian volume, (17/28) achieved ovulation within a
follicular size, numbers and period from 3-9 months (60.2%) with
endometrial thickness. Five hundred metformin alone. Three of them (3/28)
milligrams (mg) tablet of metformin have conceived and have live birth
with meal was started for 1 week, then baby within the span of treatment.
2 tablets of 500 mg metformin twice Pregnancy rate (10.8%) the other 11
daily for another week. Then after we patients succeeded to have ovulation
started the full dose of 1 tablets 3 times when we add C.C to the protocol and
daily, by this regimen the women will ovulation rate was 100% within a
have less side effects. period of 12 months; but no pregnancy
How did we monitor the therapy? achieved in this group (0%).
Patients will be asked to return 2
months after initial therapy. If she Discussion
resumes her cycle we monitor her although PCOS is heterogeneous
ovulation at cycle day 11 (CD 11) by syndrome, the final common pathway
u\s or cervical score assessment . If seems to involve a dysregulation of
the patient ovulated we ask her to have enzyme responsible for androgen
regular intercourse, and to continue biosynthesis, possibly influenced by
therapy for another 3 months to see if insulin growth factor and L.H. A single
she can conceived; if not; we re- gene defect, inherited as an autosomal
dominant pattern has been proposed manse . Metformin is a bigunide
. Since 1999 national institute of insulin sensitizer which is not used
health sponsored a conference on only for the treatment of all PCOS
PCOS, it has been appreciated that the related disturbances, but also for the
syndrome encompasses abrader prevention of the syndromes [16, 17].
spectrum of signs and symptoms of This study conclusively points out the
ovarian dysfunction than those defined beneficial effect of metformin in case
by the original diagnostic criteria. The of PCOS. Seventeen of 28 patients
2003 Rotterdam Consensus Workshop (60.2%) achieved ovulation with
concluded that PCOS is a syndrome of meformin alone with a period of 3-9
ovarian dysfunction along the cardinal months, this result is better than those
features of hyperandrogenism and of Hague, etal; who achieved 46%
PCOS morphology . PCOS remains ovulation rate with metformin in a
a syndrome and as such no single period of 6 months . This
diagnostic criteria is sufficient for difference in the result may be due to
clinical diagnosis. Its clinical the longer duration of the study of our
manifestation may include menstrual patients and the mean weight which
irregularities, a sign of androgen was lower than those of Hague, etal;
excess and obesity. Insulin resistance (78 kg vs. 90 kg); since non obese
which is thought to be a key factor in patients respond better than obese ones
the development of the metabolic to metformin . The 100%
syndrome ; elevated LH levels are ovulation rate gained by combination
also a common feature in PCOS. of metformin and clomiphen citrate
PCOS is associated with increased risk was surprising result accomplished
of type II DM and cardiovascular within 12 months of the treatment,
events , and it may represent a since no previous research had such
major risk factor for psychological result. Hague, etal; ; found that
problems . Endometrial and breast ovulation rate was 76% when they use
cancer are also common in these metformin and C.C, but the duration of
patients so seeking treatment is critical the treatment was shorter than those of
. Treatment of PCOS depends on our study group (4 months vs. 12
symptoms, age, whether or not patients months), while castello et al;;
want to get pregnant, and the degree of achieved 57% ovulation rate with
ovarian-adrenal excess. First line metformin and C.C when they used
management includes diet this protocol but for shorter duration,
modification, weight loss and stress and their study group was larger. Other
reduction, since obesity and stress can researcher achieved ovulation rate of
contribute to androgen excess . 75% . The 100% ovulation rate we
Other management and treatment are have was the outcome (harvest) of the
directed at addressing specific complete corporation between the
symptoms. Infertility treatment patients and our staff, since they were
includes in addition to ovarian sincere in losing weight by diet
stimulation medication, an ongoing restriction, and taking the medication
increasing evidence that endocrine as it was prescribed and they were
abnormalities can be reversed by the aware that metformin is not "weight
widely available standard medication losing drug" . Other reviewrs have
used for treatment of adult onset DM. described ovulation rate of 40-85%
"Metformin" and results can be seen with C.C alone . Although
within 2 months. By six months over resistance to C.C is more in women
90% women will resume regular who are overweight, which common
situation with PCOS [23, 24]. The 5. Reavan,G.;Syndromx;(1999):10
pregnancy rate achieved with years after drugs. Lancet 58:519-82.
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8. The Roterdam ESHERE\ASRM-
benefit on variable metabolic
syndrome [7, 25] and there's no report sponsored PCOS consensus workshop
of abnormal babies in women who group(2004):Revised(2003).Consensus
conceived using metformin and all on diagnostic criteria and long term
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W.H.O Laboratory manual for
relatively low cost of therapy and
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surgical interventions such as ovarian sperm mucus interaction,Cambridge
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