Title of the Dissertation: Effect of
supplementing Myoinositol and Vitamin D
3 on clomiphene citrate induced
ovulation in Infertile women with polycystic ovarian syndrome -A Randomized
control trial.
Introduction (up to150 words): PCOS also referred to as stein -Leventhal
syndrome is a heterogenous endocrine disorder in women of reproductive age and
is associated with a broad range of health conditions including hypertension,
dyslipidemia, insulin resistance, hyperandrogenemia and type 2 diabetes
mellitus. Globally the prevalence of PCOS is estimated between 5.5 % to
12.6%. In India the prevalence estimates are between 8.2% and 22.5% .
PCOS is characterized by anovulation, hyperandrogenism, hirsutism and
polycystic ovaries on USG. These women are at risk of developing Type 2
diabetes mellitus than their age and weight matched counterparts without PCOS.
Obesity and insulin resistance also contribute to anovulation and menstrual
irregularities in women with PCOS. This syndrome is currently recognized as the
leading cause of anovulatory infertility accounting for more than 80% of the
cases .Clomiphene citrate is a SERM and has long been assumed as the standard
first line agent in ovulation induction of PCOS patients due to satisfying
ovulation rate of 85 % and pregnancy rate exceeding 35% . Recent evidence
has shown that Myoinositol, which is a nutrient belonging to vit B family may
improve hormone profile and the metabolic disorders accompanying PCOS, probably
through the amelioration of preexisting of insulin resistance. Vitamin D deficiency is common
in PCOS. Vitamin D status is linked to reproductive function, metabolic
alterations and mental health. Vitamin D therapy decreases serum androgen in
PCOS patients and it decreases endometrial thickness. They have positive effect
on menstrual cycle and on folliculogenesis. Women demonstrating increased VDR
expression in the endometrium were more likely to get pregnant than their
counterparts with decreased VDR expression. VDR expression of the granulosa
cells and vitamin D content of the follicular fluid are decreased in PCOS,
which also suggests that vitamin D supplementation may aid the treatment of
infertility in PCOS. Hence this study has been designed to study the effect
of using Myoinositol with Clomiphene Citrate on the ovulation in infertile
women with PCOS Objective
Primary objective: a. To compare the
ovulation induction rate of Myoinositol and Vitamin D3 with Clomiphene Citrate with the ovulation induction rate of
clomiphene citrate only.
Secondary objective:
a. To compare the pregnancy rates
between the groups.
b. To compare the first trimester pregnancy
outcome between the groups.
Research question/hypothesis: Myoinositol and Vitamin D3 used with
Clomiphene Citrate improves the ovulation and pregnancy rates in infertile women with
PCOS. Sample size in each group: The sample size
is 94.
Mention for each group: 47 for each group.
Inclusion criteria
Women in the age group of 20 -35
years.
Diagnosed as PCOS according to Rotterdam s criteria.
Infertility exclusion criteria Women with other causes of infertility. Women who received treatment in the past 3 months.
Sampling technique/ selection of
subjects for the study Block
randomization technique will be followed to ensure equal allocation of subjects
to both the groups. .Drugs to be used, if any :
Group 1 – Myoinositol, vitamin D3 and
Clomiphene citrate
Group 2 _Clomiphene citrate
.Methodology: After obtaining
approval , the study will be started on PCOS
patients with infertility undergoing ovarian stimulation in OG Department. Patient satisfying the inclusion criteria will be randomized into two
groups. The first group of patients will receive Myoinositol and vitamin D3 with
Clomiphene Citrate and will be identified as the MI +CC group. The second group
of patients will receive Clomiphene Citrate alone and will be identified as the
CC group. In the MI+CC group patients will Myoinositol 2000mg and Vitamin D3
1000 IU orally from the first day of menstruation and Clomiphene Citrate 100 mg
orally from the 2nd day to the 6th day of the cycle for a
maximum of three successive cycles. In both the groups follicular monitoring will be done by transvaginal (TVS)
on alternate days from day 9 of menstrual cycle until a mature follicle
detected. Follicle considered mature when attained 20mm in size or more by
averaging inner two diameters of the follicle. A Single injection of 5000 IU
HCG will be given, if at least one follicle attained 20mm. TVS will be done
after 48 hours of HCG injection to determine follicle rupture. If the follicle
found unruptured, TVS will be done after 72 hours of the HCG injection to
detect whether follicle has ruptured or not. The following parameters will be compared between both the groups: 1.Ovulation rate- Ovulation rate is assessed by number of mature follicle
(diameter 20 -22 mm) per cycle 2. Response of endometrium- Endometrial thickness of 7mm considered a
satisfactory response of the endometrium. 3. Follicular rupture is ascertained by
the following criteria: a.
Disappearance or sudden decrease in follicular size. b. Increased echogenicity inside the follicle, indicating corpus luteum formation. c.
Free fluid in pelvis (or pouch of Douglas) d. Replacement of triple -line appearance of endometrium by
homogenous, hyperechoic “luteinized’’ endometrium. e.
Chemical pregnancy – Pregnancy when diagnosed by positive beta HCG. f. Ongoing pregnancy – Viable pregnancy
diagnosed by ultrasound. Expected
outcome of the study: The
ovulation rate,endometrial response follicular rupture and pregnancy rates will
be expected to be higher in the MI+CC group. If the results are statistically
significant the addition of Myoinositol and Vitamin D3 with Clomiphene Citrate
may be considered in the Ovulation induction protocols for the infertile women
with PCOS.
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