Effect of Myoinositol and Vitamin D3 on Clomiphene Citrate induced Ovulation in infertile woman with Polycystic Ovarian syndrome-A Randomized control trial

Title of the Dissertation: Effect ofsupplementing  Myoinositol and Vitamin D3  on clomiphene citrate inducedovulation in Infertile women with polycystic ovarian syndrome -A Randomizedcontrol trial.

Introduction (up to150 words): PCOS also referred to as stein -Leventhalsyndrome is a heterogenous endocrine disorder in women of reproductive age andis associated with a broad range of health conditions including hypertension,dyslipidemia, insulin resistance, hyperandrogenemia and type 2 diabetesmellitus. Globally the prevalence of PCOS is estimated between 5.5 % to12.6%. In India the prevalence estimates are between 8.2% and 22.5% .PCOS is characterized by anovulation, hyperandrogenism, hirsutism andpolycystic ovaries on USG. These women are at risk of developing Type 2diabetes mellitus than their age and weight matched counterparts without PCOS.Obesity and insulin resistance also contribute to anovulation and menstrualirregularities in women with PCOS. This syndrome is currently recognized as theleading cause of anovulatory infertility accounting for more than 80% of thecases .Clomiphene citrate is a SERM and has long been assumed as the standardfirst line agent in ovulation induction of PCOS patients due to satisfyingovulation rate of 85 % and pregnancy rate exceeding 35% . Recent evidencehas shown that Myoinositol, which is a nutrient belonging to vit B family mayimprove hormone profile and the metabolic disorders accompanying PCOS, probablythrough the amelioration of preexisting of insulin resistance. Vitamin D deficiency is commonin PCOS. Vitamin D status is linked to reproductive function, metabolicalterations and mental health. Vitamin D therapy decreases serum androgen inPCOS patients and it decreases endometrial thickness. They have positive effecton menstrual cycle and on folliculogenesis. Women demonstrating increased VDRexpression in the endometrium were more likely to get pregnant than theircounterparts with decreased VDR expression. VDR expression of the granulosacells and vitamin D content of the follicular fluid are decreased in PCOS,which also suggests that vitamin D supplementation may aid the treatment ofinfertility in PCOS. Hence this study has been designed to study the effectof using Myoinositol with Clomiphene Citrate on the ovulation in infertilewomen with PCOS

Objective

Primary objective: a. To compare theovulation induction rate of Myoinositol and  Vitamin D3 with Clomiphene Citrate with the ovulation induction rate ofclomiphene citrate only.

Secondary objective:

a. To compare the pregnancy ratesbetween the groups.

b. To compare the first trimester pregnancyoutcome   between the groups.

Research question/hypothesis: Myoinositol and Vitamin D3 used withClomiphene Citrate   improves the  ovulation  and pregnancy rates in infertile women withPCOS.

Sample size in each group:  The sample sizeis 94.

Mention for each group: 47 for each group.

Inclusion criteria

Women in the age group of 20 -35years.

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 ofsubjects for the study

Blockrandomization technique will be followed to ensure equal allocation of subjectsto both the  groups.

.Drugs to be used, if any :

Group 1 – Myoinositol, vitamin D3 andClomiphene citrate

Group 2 _Clomiphene citrate

.Methodology: After obtainingapproval , the   study will be started on PCOSpatients with infertility undergoing ovarian stimulation in OG Department.  Patient satisfying the inclusion criteria will be randomized into twogroups.

 The first group of patients will receive Myoinositol and vitamin D3 withClomiphene Citrate and will be identified as the MI +CC group. The second groupof patients will receive Clomiphene Citrate alone and will be identified as theCC group. In the MI+CC group patients will Myoinositol 2000mg and Vitamin D31000 IU orally from the first day of menstruation and Clomiphene Citrate 100 mgorally from the 2nd day to the 6th day of the cycle for amaximum 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 follicledetected. Follicle considered mature when attained 20mm in size or more byaveraging inner two diameters of the follicle. A Single injection of 5000 IUHCG will be given, if at least one follicle attained 20mm. TVS will be doneafter 48 hours of HCG injection to determine follicle rupture. If the folliclefound unruptured, TVS will be done after 72 hours of the HCG injection todetect 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 asatisfactory response of the endometrium.

3. Follicular rupture is ascertained bythe 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 byhomogenous, hyperechoic  “luteinized’’ endometrium.

e.Chemical pregnancy – Pregnancy when diagnosed by positive beta HCG.

f. Ongoing pregnancy – Viable pregnancydiagnosed by ultrasound.

       Expectedoutcome of the study: Theovulation rate,endometrial response follicular rupture and pregnancy rates willbe expected to be higher in the MI+CC group. If the results are statisticallysignificant the addition of Myoinositol and Vitamin D3 with Clomiphene Citratemay be considered in the Ovulation induction protocols for the infertile womenwith PCOS.