Inositol for women with a diagnosis of polycystic ovary syndrome and subfertility

Review question

We looked at whether women who have polycystic ovary syndrome (PCOS) and were having difficulty getting pregnant would benefit from taking supplements of inositol.

Background

Women with PCOS who are trying to get pregnant are more likely to face difficulties as a result of their condition. These women who are finding it difficult to get pregnant can be offered different treatments. One of the treatments that can be offered is supplements. Inositol is one of the supplements thought to increase the chance of getting pregnant. At the moment, we are unsure whether taking inositol will actually help these women get pregnant, and whether any harms are associated with taking these supplements.

Search date

We searched for studies published up to July 2018.

Study characteristics

In total, we found 13 randomised controlled trials involving 1472 subfertile women with PCOS. All of these studies included women with PCOS who were having difficulty conceiving. All of the women included in these studies were receiving usual prenatal care. In addition to this, women were given myo-inositol (a form of inositol) and then were compared to women who were receiving no treatment or were receiving melatonin, metformin, clomiphene citrate, or D-chiro-inositoI (another form of inositol). In 11 studies, all women were also having in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI), and in the remaining two studies, women were undergoing ovulation induction.

Key results

Myo-inositol plus folic acid versus folic acid (standard treatment) as pre-treatment to IVF (low- or very low-quality evidence)

Few studies on this comparison are available, and the quality of these studies is low to very low. Based on currently available evidence, we were unable to show that taking myo-inositol increases the chances of becoming pregnant or having a baby among women with PCOS. Our findings suggest that if the chance of having a baby, for women undergoing pre-treatment to IVF, with standard treatment (folic acid alone) was 12%, the chance among women using myo-inositol could be as low as 9%, or could be as high 51%. We are unclear on whether myo-inositol could lower miscarriage rates, as these results are based on only two studies, one of which reported unusually high rates of miscarriage among women who were not receiving myo-inositol; therefore, we are not confident that this is the true effect of this treatment. MI may produce little or no difference in multiple pregnancy rates.

We were unable to assess the benefit or harm of taking myo-inositol for women with PCOS undergoing ovulation induction, as we had identified only two trials, and each performed a different comparison.

Quality of the evidence

We assessed the quality of the evidence as ranging from low to very low due to poor explanations of how these trials were run and the small number of trials that we could include. Also, reporting on issues that are important for subfertile couples was poor; these include the chance of having a baby when taking myo-inositol, and whether its use leads to harmful effects.

Authors' conclusions: 

In light of available evidence of very low quality, we are uncertain whether MI improves live birth rate or clinical pregnancy rate in subfertile women with PCOS undergoing IVF pre-treatment taking MI compared to standard treatment. We are also uncertain whether MI decreases miscarriage rates or multiple pregnancy rates for these same women taking MI compared to standard treatment. No pooled evidence is available for use of MI versus placebo, another antioxidant, insulin-sensitising agents, ovulation induction agents, or another type of inositol for women with PCOS undergoing pre-treatment to IVF. No pooled evidence is available for use of MI in women undergoing ovulation induction.

Read the full abstract...
Background: 

Subfertile women are highly motivated to try different adjunctive therapies to have a baby, and the widespread perception is that dietary supplements such as myo-inositol (MI) and D-chiro-insoitol (DCI) are associated with only benefit, and not with harm. Many fertility clinicians currently prescribe MI for subfertile women with polycystic ovary syndrome (PCOS) as pre-treatment to in vitro fertilisation (IVF) or for ovulation induction; however no high-quality evidence is available to support this practice. This review assessed the evidence for the effectiveness of inositol in subfertile women with a diagnosis of PCOS.

Objectives: 

To evaluate the effectiveness and safety of oral supplementation of inositol for reproductive outcomes among subfertile women with PCOS who are trying to conceive.

Search strategy: 

We searched the following databases (to July 2018): Cochrane Gynaecology and Fertility Group (CGFG) Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and AMED. We also checked reference lists and searched the clinical trials registries.

Selection criteria: 

We included randomised controlled trials (RCTs) that compared any type, dose, or combination of oral inositol versus placebo, no treatment/standard treatment, or treatment with another antioxidant, or with a fertility agent, or with another type of inositol, among subfertile women with PCOS.

Data collection and analysis: 

Two review authors independently selected eligible studies, extracted data, and assessed risk of bias. The primary outcomes were live birth and adverse effects; secondary outcomes included clinical pregnancy rates and ovulation rates. We pooled studies using a fixed-effect model, and we calculated odds ratios (ORs) with 95% confidence intervals (CIs). We assessed the overall quality of the evidence by applying GRADE criteria.

Main results: 

We included 13 trials involving 1472 subfertile women with PCOS who were receiving myo-inositol as pre-treatment to IVF (11 trials), or during ovulation induction (two trials). These studies compared MI versus placebo, no treatment/standard, melatonin, metformin, clomiphene citrate, or DCI. The evidence was of 'low' to 'very low' quality. The main limitations were serious risk of bias due to poor reporting of methods, inconsistency, and lack of reporting of clinically relevant outcomes such as live birth and adverse events.

We are uncertain whether MI improves live birth rates when compared to standard treatment among women undergoing IVF (OR 2.42, 95% CI 0.75 to 7.83; P = 0.14; 2 RCTs; 84 women; I² = 0%). Very low-quality evidence suggests that for subfertile women with PCOS undergoing pre-treatment to IVF who have an expected live birth rate of 12%, the rate among women using MI would be between 9% and 51%.

We are uncertain whether MI may be associated with a decrease in miscarriage rate when compared to standard treatment (OR 0.40, 95% CI 0.19 to 0.86; P = 0.02; 4 RCTs; 535 women; I² = 66%; very low-quality evidence). This suggests that among subfertile women with PCOS with an expected miscarriage rate of 9% who are undergoing pre-treatment to IVF, the rate among women using MI would be between 2% and 8%; however this meta-analysis is based primarily on one study, which reported an unusually high miscarriage rate in the control group, and this has resulted in very high heterogeneity. When we removed this trial from the sensitivity analysis, we no longer saw the effect, and we noted no conclusive differences between MI and standard treatment.

Low-quality evidence suggests that MI may be associated with little or no difference in multiple pregnancy rates when compared with standard treatment (OR 1.04, 95% CI 0.63 to 1.71; P = 0.89; 2 RCTs; 425 women). This suggests that among subfertile women with PCOS who are undergoing pre-treatment to IVF, with an expected multiple pregnancy rate of 18%, the rate among women using inositol would be between 12% and 27%.

We are uncertain whether MI may be associated with an increased clinical pregnancy rate when compared to standard treatment (OR 1.27, 95% CI 0.87 to 1.85; P = 0.22; 4 RCTs; 535 women; I² = 0%; very low-quality evidence). This suggests that among subfertile women with PCOS who are undergoing pre-treatment to IVF, with an expected clinical pregnancy rate of 26%, the rate among women using MI would be between 24% and 40%. Ovulation rates were not reported for this comparison.

Other comparisons included only one trial in each, so for the comparisons MI versus antioxidant, MI versus an insulin-sensitising agent, MI versus an ovulation induction agent, and MI versus another DCI, meta-analysis was not possible.

No pooled evidence was available for women with PCOS undergoing ovulation induction, as only single trials performed comparison of the insulin-sensitising agent and the ovulation induction agent.

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