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

Phase 2

Completed

Conditions: PCOS PATIENTS UNDERGOING IVF

Registration Number: CTRI/2018/05/014196

Lead Sponsor: AIIMS

Brief Summary: **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) respectively**Participants/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 96.0Â±10.0(n=37), Met 85.5Â±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.

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Female

Target Recruitment: 100

Inclusion Criteria

ALL PCOS WOMEN RECRUITED FOR IVF.

Exclusion Criteria

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.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
PERCENTAGE OF WOMEN DEVELOPING OHSS	2 YEARS
PREGNANCY RATES	2 YEARS

Secondary Outcome Measures

Name	Time	Method
ART OUTCOMES	BIOCHEMICAL AND HARMONAL OUTCOMES

Trial Locations

Locations (1): AIIMS
🇮🇳
Delhi, DELHI, India
AIIMS
🇮🇳Delhi, DELHI, India
KEERTHANA RAJASEKARAN
Principal investigator
9600163683
keerthana01@gmail.com