This is the third in a series of posts on the use of inositol for polycystic ovary syndrome (PCOS).

If you haven’t seen them yet, check out the first post, which provides an overview of what inositol is and why it might be helpful for PCOS, and the second post, which discusses the effects of inositol supplementation on reproductive hormone levels, metabolic health, and cardiovascular health.

This post focuses on the effects of inositol supplementation on menstrual cycle regularity, ovulation, and fertility.

Inositol and ovulation rates

The first study to test the efficacy of any form of inositol for PCOS focused on d-chiro-inositol (Nestler et al. 1999). This study recruited 44 females with PCOS and BMI’s greater than 28 (a BMI in the middle of the overweight range) from the Hospital de Clinicas Caracas in Caracas, Venezuela. Participants were randomly assigned to one of two groups:

Treatment Group: consumed 1.2 grams of d-chiro-inositol per day
Control Group: consumed 1.2 grams of placebo per day

Both groups consumed their respective substance for 6 to 8 weeks.

In this study, ovulation was tracked by measuring peak progesterone levels. After ovulation, the follicle that released the ovulated egg becomes the corpus luteum and emits progesterone (you can read more about this process here). If there is no rise in progesterone, we can be pretty certain ovulation did not occur, whereas if a rise is observed, ovulation likely occurred.

19 of the participants consuming d-chiro-inositol ovulated during the study period while only 6 in the control group did, and this difference was statistically significant.

While Nestler et al. (1999) recruited overweight or obese females with PCOS, Iuorno et al. (2002) recruited 20 females with PCOS in the “normal” BMI category (20 - 24.4).

Participants were randomly assigned to one of two groups:

Treatment Group: consumed 600 milligrams of d-chiro-inositol per day
Control Group: consumed 600 milligrams of placebo per day

Both groups consumed their respective substance for 6 to 8 weeks.

Like the previous study, ovulation was tracked through peak progesterone levels.

In this study, 6 out of the 10 females in the treatment group experienced ovulation during the study period, while only 2 of the control group ovulated. It should be noted that this difference is not statistically significant, likely due to their small sample size, but the result aligns with that of other studies.

While the first two studies discussed tracked ovulation with d-chiro-inositol supplementation, Costantino et al. (2009) considered myo-inositol supplementation. These researchers recruited 42 patients with PCOS from the Hospital of Valdagno in Vicenza, Italy.

Participants were randomly assigned to one of two groups:

Treatment Group: consumed 4 grams of myo-inositol + 400 micrograms of folic acid per day
Control Group: consumed 400 micrograms of folic acid per day

Both groups consumed their respective supplement(s) for 12 to 16 weeks.

During the study period, 16 participants in the treatment group ovulated while only 4 in the control group ovulated, and this difference is statistically significant.

inositol and pregnancy outcomes without use of in vitro fertilization (IVF)

While the studies above only tracked ovulation and not fertility outcomes, Papaleo et al. (2007) track both ovulation and fertility outcomes. These researchers recruited 25 females with PCOS who had been experiencing infertility for 14 to 16 months. All participants were screened for other potential fertility factors, and for all participants, lack of ovulation was deemed the most likely cause of their infertility.

Unfortunately, this study does not use a control group, and instead, all participants consumed 2 grams of myo-inositol plus 200 micrograms of folic acid twice per day until the end of the study period (6 months) or until they achieved a positive pregnancy test.

Out of the 25 participants, 22 successfully ovulated. On average, participants had their first menstruation 35 days after beginning supplementation, which would imply ovulation occurred, on average, 21 or 22 days after beginning supplementation.

Of the 22 who ovulated, 18 maintained regular monthly periods for the duration of the study period or until pregnancy occurred. The average cycle length among these 18 was 31.7 days.

Among all ovulatory participants, 10 achieved a positive pregnancy test (chemical pregnancy), while 9 of these 10 resulted in clinical pregnancies with the pregnancy confirmed by ultrasound. One of these clinical pregnancies resulted in a miscarriage at 7 weeks. 8 participants successfully had live births.

inositol and In Vitro Fertilization (IVF) outcomes for females with pcos

Artini et al. (2013) recruited 50 females with PCOS among patients for Assisted Reproductive Technology services at the University of Pisa Division of Obsetrics and Gynaecology. The participants were randomly assigned to one of two groups:

The treatment group: consumed 2 grams of myo-inositol + 200 micrograms of folic acid each day
The control group: consumed 400 micrograms of folic acid daily

Both groups followed their respective supplement plan for 12 weeks.

Following 12 weeks of supplementation, each participant underwent one cycle of in vitro fertilization. The table below summarizes the results of this cycle.

While the group only supplementing with folic acid had more oocytes (immature eggs) retrieved, the percent of “top-quality” oocytes was substantially lower for the folic acid only group. Both groups had similar fertilization rates, similar numbers of embryos transferred, and similar percent of top-quality embryos.

The myo-inositol group experienced higher rates of chemical pregnancies (pregnancy confirmed with pregnancy test), clinical pregnancies (pregnancy that progresses far enough along to be observed by ultrasound), and delivery rate (live birth). The group taking myo-inositol and folic acid had more than twice the likelihood of a successful live birth for the round of IVF than the group taking folic acid alone. This is a pretty substantial finding!

In vitro fertilization outcomes after 12 weeks of supplementation with either myo-inositol + folic acid or with folic acid alone. “No statistically significant difference” means that any differences found were not statistically significantly different than zero. Source: Artini et al. (2013).

Take home points

Supplementation with either d-chiro-inositol or myo-inositol has been shown to increase the likelihood of ovulation among females with polycystic ovary syndrome.

This supplementation appears to increase the likelihood of having a successful round of in vitro fertilization.

It seems likely that it also increases the likelihood of having a successful pregnancy in the absence of in vitro fertilization, but additional studies using a control group would be necessary to confirm this hypothesis.

references

Artini PG, Di Berardino OM, Papini F, Genazzani AD, Simi G, Ruggiero M, and Cela V. 2013. Endocrine and clinical effects of myo-inositol administration in polycystic ovary syndrome. A randomized study. Gynecological Endocrinology 29(4):375-379.

Costantino D, Minozzi G, Minozzi F, and Guaraldo C. 2009. Metabolic and hormonal effects of myo-inositol in women with polycystic ovary syndrome: A double-blind trial. European Review for Medical and Pharmacological Sciences, 13:105-110.

Iuorno MJ, Jakubowicz DJ, Baillargeon J, Dillon P, Gunn RD, Allan G, and Nestler JE. 2002. Effects of d-chiro-inositol in lean women with the polycystic ovary syndrome. Endocrine Practice, 8(6):417-423.

Nestler JE, Jakubowicz DJ, Reamer P, Gunn RD, and Allan G. 1999. Ovulatory and metabolic effects of d-chiro-inositol in the polycystic ovary syndrome. The New England Journal of Medicine, 340(17):1314 - 1320.

Papaleo E, Unfer V, Baillargeon J, De Santis L, Fusi F, Brigante C, Marelli G, Cino I, Redaelli A, and Farreri A. 2007. Myo-inositol in patients with polycystic ovary syndrome: A novel method for ovulation induction. Gynecological Endocrinology, 23(12): 700–703.