Myo-inositol for the Management of Poor Ovarian Responders: A Prospective Randomized Controlled Trial

American University of Beirut Medical Center

Status and phase: Unknown; Phase 3; Phase 2

Conditions: Poor Ovarian Response

Treatments: Drug: Myo-inositol

Study type: Interventional

Funder types: Other

Identifiers

NCT04273256

BIO-2018-0357

Details and patient eligibility

About

The management of poor ovarian responders (POR) remains the most challenging in In-Vitro Fertilization (IVF). The incidence of POR ranges between 9 and 24% (Caprio F, et al, 2015).

POR refers to a reduction in the quantity of primordial follicle pool in reproductive age group (Jirge, P. R., 2016, Sunkara, S. K., et al, 2014), in addition to a higher risk of implantation failure (Kailasam C, et al, 2004).

To overcome this condition, fertility treatments using controlled ovarian stimulation along with IVF is needed to achieve pregnancy. Despite the use of various treatments including high dose gonadotropins, patients with POR have lower rates of pregnancy compared to patients with normal ovarian response (Oudendijk, J. F., et al, 2011). Studies now suggest a variety of regimens like the use of growth hormones, DHEA or androgens to improve the outcomes (Kyrou D, et al, 2009). The main interest of this study is the use of myo-inositol prior to IVF cycles for improvement of reproductive outcomes in poor ovarian responders.

Full description

The management of poor ovarian responders (POR) remains the most challenging in In-Vitro Fertilization (IVF). The incidence of POR ranges between 9 and 24% (Caprio F, et al, 2015).

POR refers to a reduction in the quantity of primordial follicle pool in reproductive age group (Jirge, P. R., 2016, Sunkara, S. K., et al, 2014), in addition to a higher risk of implantation failure (Kailasam C, et al, 2004).

To overcome this condition, adjuvant fertility treatments using controlled ovarian stimulation along with IVF is needed to achieve pregnancy. Despite the use of various treatments including high dose gonadotropins, patients with POR have lower rates of pregnancy compared to patients with normal ovarian response (Oudendijk, J. F., et al, 2011). Studies now suggest a variety of regimens like the use of growth hormones, DHEA or androgens to improve the outcomes (Kyrou D, et al, 2009).

Inositol belongs to the vitamin B group, precursor for the synthesis of phosphatidylinositol polyphosphates (PIPs). PIPs belong to the signal transduction system involved in the regulation of different cellular functions such as signal transduction, cell morphogenesis and cytogenesis (Kutateladze TG, 2010). It is involved in cell membrane formation, lipid synthesis and cell growth (Unfer V, et al, 2012). It has been extensively studied in patients with insulin resistance, as inositol has an insulin sensitizing action (Croze ML & Soulage CO, 2013). In addition, researchers have hypothesized different mechanisms of action on different cell types especially at the level of the ovaries. An international consensus has confirmed that myo-inositol pre-treatment is able to improve the oocyte and the embryo quality via enhancing the intracellular Ca2+ oscillation with meiotic progression of germinal vesicle oocytes. Therefore, it acts on improving the oocyte maturation and embryo development (Nestler JE, et al, 1999, Papaleo E, et al, 2009).

Previous studies showed that higher concentrations of myo-inositol in follicular fluid are correlated with a better oocyte quality (Chiu TT, et al, 2002). A study by Jiang demonstrated that inositol supplementation reduces oxidative stress by different agents such as increasing superoxide dismutase and catalase levels (Jiang WD, et al, 2011). In view of its effects on oocyte maturation and quality, the use of myo-inositol in women with POR is promising. However, data is still sparse whether supplementation with myo-inostiol prior to IVF cycles does improve the pregnancy outcomes.

The main interest of this study is the use of myo-inositol prior to IVF cycles for improvement of reproductive outcomes in poor ovarian responders.

Enrollment: 226 estimated patients

Sex: Female

Ages: 18 to 44 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age: 18-44 years at the time of interview

• POR patients defined as: AMH<1.5 ng/nl, AFC of 7 or less, 5 oocytes or less retrieved in a previous cycle

• Patients undergoing controlled ovarian stimulation for any indication:

  • Male factor
  • Female factor

Exclusion criteria

• Patients with diabetes, thyroid dysfunction
• Patients with abnormal uterine cavity

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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226 participants in 2 patient groups

Myo-inositol arm

Experimental group

Description:

Patients will be supplemented with 2 grams of Myo-inositol + at least 400 μg of folic acid (received from routinely prescribed multivitamins) every day for 3 months before the IVF cycle.

Treatment:

Drug: Myo-inositol

Control arm

No Intervention group

Description:

Patients will receive at least 400 μg of folic acid from routinely prescribed multivitamins every day for 3 months before the IVF cycle.