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CTRI Number  CTRI/2018/05/014196 [Registered on: 29/05/2018] Trial Registered Prospectively
Last Modified On: 26/12/2020
Post Graduate Thesis  Yes 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Active Controlled Trial 
Public Title of Study   A study to compare the efficacy of two drugs on the success of assisted reproductive therapy in women with polycystic ovarian syndrome and undergoing treatment with IVF 
Scientific Title of Study   Randomised Control Trial comparing the effects of Metformin to Myoinositol on ART outcome in women with PCOS undergoing IVF cycles  
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  keerthana rajasekaran 
Designation  junior resident 
Affiliation  AIIMS 
Address  dept of obs and gynae AIIMS New Delhi

New Delhi
DELHI
110029
India 
Phone  9600163683  
Fax    
Email  keerthana01@gmail.com  
 
Details of Contact Person
Scientific Query  
Name  NEENA MALHOTRA 
Designation  PROFESSOR 
Affiliation  AIIMS 
Address  DEPT OF OBS & GYNAE AIIMS New Delhi

New Delhi
DELHI
110029
India 
Phone  9891557707  
Fax    
Email  malhotraneena@yahoo.com  
 
Details of Contact Person
Public Query  
Name  NEENA MALHOTRA 
Designation  PROFESSOR 
Affiliation  AIIMS 
Address  DEPT OF OBS & GYNAE AIIMS New Delhi

New Delhi
DELHI
110029
India 
Phone  9891557707  
Fax    
Email  malhotraneena@yahoo.com  
 
Source of Monetary or Material Support  
AIIMS hospital and research centre , New Delhi  
 
Primary Sponsor  
Name  AIIMS 
Address  New Delhi  
Type of Sponsor  Research institution and hospital 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
KEERTHANA RAJASEKARAN   AIIMS  3RD FLOOR IVF LAB, EMERGENCY BLOCK DEPT OF OBS AND GYNAE
New Delhi
DELHI 		 9600163683

keerthana01@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Institute Ethics committee for post graduate research, AIIMS, New Delhi  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  PCOS PATIENTS UNDERGOING IVF,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  drug  tab Myoinositol 2 gm 1 bd for 3 months 
Comparator Agent  drug  tab Metformin 850mg 1 bd for 3 months 
 
Inclusion Criteria  
Age From  22.00 Year(s)
Age To  38.00 Year(s)
Gender  Female 
Details  ALL PCOS WOMEN RECRUITED FOR IVF 
 
ExclusionCriteria 
Details  ENDOMETRIOSIS
ANY CONDITIONS COMPROMISING IMPLANTATION LIKE FIBROID
OVARIAN SURGERY
DERRANGED LFTs, KFTs
HYPERSENSITIVITY TO MYOINOSITOL
WOMEN WITH UNCONTROLLED THYROID DISEASE
PATIENTS UNDERGOING FROZEN EMBRYO TRANSFER
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Pre-numbered or coded identical Containers 
Blinding/Masking   Participant Blinded 
Primary Outcome  
Outcome  TimePoints 
PERCENTAGE OF WOMEN DEVELOPING OHSS
PREGNANCY RATES 		 2 YEARS 
 
Secondary Outcome  
Outcome  TimePoints 
ART OUTCOMES
BIOCHEMICAL AND HARMONAL OUTCOMES 		 2 YEARS 
 
Target Sample Size   Total Sample Size="100"
Sample Size from India="100" 
Final Enrollment numbers achieved (Total)= "102"
Final Enrollment numbers achieved (India)="102" 
Phase of Trial   Phase 2 
Date of First Enrollment (India)   15/06/2018 
Date of Study Completion (India) 15/03/2020 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Date Missing 
Estimated Duration of Trial   Years="2"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  		 Not Applicable 
Recruitment Status of Trial (India)  Completed 
Publication Details   not done 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Brief Summary
Modification(s)  

Study question:

Does Myoinositol in comparison to metformin in infertile PCOS women, improves the ART outcomes, oocyte quality, pregnancy rates and decreases the incidence of OHSS  

Summary answer:

Myoinositol reduces unsuitable oocytes, improves the menstrual pattern, insulin resistance, hormone profile, quality of embryos, IVF outcomes and clinical pregnancy without significant change in OHSS. 

What is known already:

Metformin reduces  testosterone concentrations, optimises IVF outcome, reduces risk of OHSS in PCOS but is associated with gastrointestinal side effects and lactic acidosis resulting in reduced patients compliance. Myoinositol improves ovarian function, oocyte quality, LH/FSH ratio, reduces serum androgens, improves ovulation and fertility outcome without the side effects of metformin. Myoinositol acts at the level of insulin receptors and improves hyperinsulinemia, positively correlate with quality and maturity of oocytes reducing mean number of immature and degenerated oocytes, quantity of gonadotropins or units of FSH necessary for ovarian stimulation in IVF protocols. 

Study design, size, duration:

A single centre, double blind randomized controlled clinical study in women with PCOS receiving Myoinositol or Metformin, 12 weeks prior to treatment cycle, was completed in 22 months (May 2018 to February 2020) randomizing 102 women allotting, 50 and 52 in group 1(Myoinositol) and group 2(Metformin) respectivelyParticipants/materials, setting, methods:

Recruited patients received myoinositol 2gm twice daily(group1) and metformin 850mg twice daily(group 2). Pre and post treatment clinical(menstrual pattern, BMI), hormonal profile(LH, FSH, Testosterone, prolactin, AMH), biochemical parameters(HOMA IR, fasting glucose, insulin) and side effect profile assessed. After 3 months of therapy, patients were recruited for IVF cycles involving controlled ovarian stimulation, cycle monitoring, oocyte recovery, insemination of oocytes and follow up with fertilisation, cleavage, transfer of good grade cleavage embryos or blastocysts pregnancy outcomes and OHSS incidence.

 

Main results and role of chance:

There was no significant difference in baseline characteristics, hormonal and biochemical parameters between two groups of women.Myoinositol group had increased regularity in menstrual pattern(0.001) and improvement in fasting insulin (p 0.001),HOMA IR (p 0.001),Serum AMH(p 0.001) and Serum SHBG(p 0.032) thereby suggesting decreased insulin resistance.

The rate of OHSS was not different between groups, with 5 cases of mild OHSS in Myoinositol group and 10 case of mild OHSS in metformin group (Myoinositol (Myo) 10%, Metformin (Met) 20%, 13.1(-2.5,28.7) p 0.10. The clinical pregnancy rate (Myo 18(36.0) (n=50), Met 9(18.0) (n=50) p 0.04) and Cumulative pregnancy rate including FET (Myo 16(43.2) (n=37) Met 10(22.7) (n=44) p 0.05) was significantly more in Myoinositol group. Spontaneous conception (Myo 13(26.0) (n=50), Met 6(12.0) (n=50) p 0.07) prior to treatment cycle was also more in Myoinositol group.

 

No between group difference was found in the ovarian stimulation outcomes including duration (Myo 11(9-15), Met 12(8-18) p 0.14) and dosage of gonadotropins (Myo 2200(1233-4596), Met 2420(1121-4230), p 0.09), E2 (Myo 4163(557-13003), Met 4229(217-13493) p 0.84) and P4 (Myo 1.2(0.16-4.9), Met 1.3(0.07-4.8),p 0.50) levels and number of follicles more than 14 mm on day of trigger (Myo 16(3-25), Met 15(2-20), p 0.09). The number of oocytes retrieved (Myo 14(0-18) (n=37), Met 12(0-16) (n=16) p 0.09), grade of maturity (Myo 8(0-15) (n=37), Met 6.5(0-11) (n=44) p 0.09) were similar between both groups. The fertilization (Myo 71(40-100) (n=37), Met 47(0-87) (n=44) p <0.001) and cleavage rate (Myo 96.0±10.0(n=37), Met 85.5±16.9(n=44) p 0.008) were significantly higher as were the number of all and good grade embryos (Myo 3(0-15) (n=37), Met 2(0-18) (n=44) p 0.04) in the myoinositol group. However, the implantation rate (Myo 12(0-100) (n=27), Met 6.52(0-50) (n=50) p 0.53), number of embryos for freezing (Myo 3.14(0-15) (n=37), Met 3.14(0-15) p 0.50) were not different between groups.

Limitation, reason for caution:

Most patients with PCOS recruited in our study were brittle PCOS, with high LH, AMH and hyperandrogenemia with sub optimal response during ovulation induction and IUI hence leading to low pregnancy outcome.

 

Wider implications of the findings:

Myoinositol in comparison to metformin in infertile PCOS women has better IVF outcome and oocyte quality, however to make these results more robust, a large multi-centric trial with larger sample size and longer duration is necessary.

 
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