Myoinositol versus metformin pretreatment in GnRH-antagonist cycle for women with PCOS undergoing IVF: a double-blinded randomized controlled study

Abstract

Objective

To study the effects of myoinositol (Myo) in comparison to metformin (Met), in reducing the risk of OHSS and improving ART outcome in PCOS women undergoing IVF.

Design

Double-blinded randomized controlled trial (CTRI/2018/05/014196).

Setting

ART Clinic, AIIMS, New Delhi patients: 102 infertile PCOS women undergoing IVF cycles were enrolled after evaluating for eligibility and allotted as 50 in group 1 (Myo) and 52 in group 2 (Met) after randomization.

Interventions

Recruited patients received Myo 2 g twice daily (group 1) and Met 850 mg twice daily (group 2). Pre- and post-treatment clinical (menstrual pattern, BMI), hormonal profile (LH, FSH, testosterone, prolactin [PRL], and AMH), biochemical parameters (HOMA IR, fasting glucose, and insulin), ovarian with antral follicle count (AFC) and side effect profile were assessed. After 3 months of therapy, patients were recruited for IVF cycle by antagonist protocol was involving controlled ovarian stimulation, cycle monitoring, oocyte recovery, insemination of oocytes and follow up with fertilization, cleavage, transfer of good grade cleavage embryos, or blastocysts pregnancy outcomes and OHSS incidence and medications was continued until the day of OPU.

Main outcome measures

Primary outcome was OHSS and clinical pregnancy rate including spontaneous, IVF, and cumulative pregnancy rate including FET. Secondary outcome was ART outcomes and the change in biochemistry and hormonal profile between groups and inter group after medications at 12 weeks.

Results

Incidence of OHSS (Myo 5 (10.0) (n = 50), Met 10 (20.0) (n = 50) p .07) was not statistically different between groups. Clinical pregnancy rate (Myo 18 (36.0) (n = 50), Met 9 (18.0) (n = 50) p .04) cumulative pregnancy rate including FET (Myo 16 (43.2) (n = 37) vs. Met 10) 22.7) (n = 44) p .05) and spontaneous conception (prior to IVF) Myo 13 (26.0) (n = 50), Met 6 (12.0) (n = 50) p .07) was significantly high in Myo group. No between group difference in ovarian stimulation outcomes including duration and dosage of gonadotropins, E2, P4 levels, number of follicles >14 mm on day of trigger. Number of oocytes retrieved and grade of maturity were similar between groups. Fertilization, cleavage and number of good grade embryos were significantly higher in Myo group. However, implantation rate and number of embryos for freezing were similar between groups. Myo had improvement in fasting insulin, HOMA, Sr.AMH, and SHBG suggesting decreased insulin resistance

Conclusions

Myo is equally beneficial as Met in reducing the risk of OHSS and has better ART outcome in PCOS women undergoing antagonist cycles.

肌醇与二甲双胍预处理在多囊卵巢综合征（PCOS）患者体外受精GnRH拮抗剂周期中的作用：一项双盲随机对照研究 摘要

目的：探讨肌醇（Myo）与二甲双胍（metformin, Met）在降低多囊卵巢综合征（PCOS）患者体外受精（IVF）风险和改善辅助生殖（ART）结局方面的作用。

设计：双盲随机对照试验（CTRI/2018/05/014196）。

背景：新德里AIIMS辅助生殖诊所患者：102名接受IVF周期的多囊卵巢综合征不孕女性在评估符合标准后被纳入研究, 随机分为第1组（Myo）50名和第2组（Met）52名。

干预措施：入组患者服用Myo2g每天两次（第1组）, 服用Met850mg每天两次（第2组）。评估治疗前后的临床情况（月经模式、身体质量指数[BMI]）、激素水平（LH、FSH、睾酮、催乳素[PRL]和抗缪勒管激素[AMH]）、生化指标（胰岛素抵抗指数[HOMA IR]、空腹血糖和胰岛素）、卵巢窦卵泡计数（AFC）和副作用情况。治疗3个月后, 招募GnRH拮抗剂方案进行IVF周期的患者, 包括控制性卵巢刺激、周期监测、取卵、卵母细胞受精, 并随访受精、卵裂、移植优质卵裂胚胎, 或囊胚妊娠结局、卵巢过渡刺激征（OHSS）发生率和持续到取卵（OPU）当天药物治疗情况。

主要观察指标：主要观察指标为OHSS和临床妊娠率（包括自发妊娠、体外受精）以及累积妊娠率（包括冷冻胚胎移植）。第二个结局是ART结局, 以及组间和组间在12周用药后生化和激素水平的变化。

Keywords:

• PCOS
• myoinositol
• metformin
• OHSS
• IVF

Author contributions

M.N. and K.R. conceived and designed the study. K.R. drafted the manuscript. M.N. and R.M. revised it critically and approved the final version of publication. M.K. helped with statistical analysis.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

No external funding was either sought or obtained for this study.