Polycystic Ovarian Syndrome:

Is there a role of Inositols?

PCOS: A Vicious Cycle
 Potential Therapeutic Targets of PCOS

Int. J. Mol. Sci. 2022, 23(8), 4110

Why Inositols ?
 Inositols

• Inositols are chemically identified as hexahydroxy cyclohexane and include a family of nine

stereoisomers

• Myo inositol (MI) and D-chiro inositol (DCI), are most abundant

• Inositols act as second messengers and mediate many metabolic actions of insulin and many

other hormones like FSH, cell differentiation, cell growth, oocyte maturation

Rojas J, Chavez M, Olivar L, Rojas M, Morillo J, Mejias J, et al. Polycystic ovary syndrome, insulin resistance, and obesity: Navigating the pathophysiologic labyrinth. Int J Reprod Med. 2014;2014:719050.
Nordio M, Proietti E. The combined therapy with myo-inositol and D-chiro-inositol reduces the risk of metabolic disease in PCOS overweight patients compared to myo-inositol supplementation alone. Eur Rev Med Pharmacol Sci. 2012 May;16(5):575–81.
Homburg R. The management of infertility associated with polycystic ovary syndrome. Reprod Biol Endocrinol. 2003 Nov 14;1:109.
 Inositols as Mediators in Insulin Pathway

Regulates Blood Glucose

Insulin

Glucose Cell Uptake Glycogen Synthesis

Promoted by
second messengers
Myo inositol
D-Chiro inositol
Present in ↑ levels
Liver, muscles, fat
In high energy tissues like
brain, ovary, heart
In glycogen storage
tissues
Kalra B et al. The inositols and polycystic ovary syndrome.Indian J Endocrinology & Metabolism.2016; 20(5):720;
 Epimerase Enzyme
● The enzyme epimerase converts MI to DCI, maintaining a
physiological ratio, which varies from tissue to tissue.
● The three target organs of insulin, i.e., adipose tissue, liver,
and skeletal muscle have a different ratio of the main
inositol isomers.
○ A high concentration of MI is required to ensure
healthy oocyte maturation in the ovary.
○ A relatively higher proportion of DCI is required to
maintain homeostasis.

Kalra B et al. The inositols and polycystic ovary syndrome.Indian J Endocrinology & Metabolism.2016; 20(5):720;
 Inositols
● Relative concentration of MI and DCI varies in health and disease condition like
PCOS

● The relative concentrations are organ specific

● Discovery that impaired insulin signalling in PCOS could be due to defect in

inositol pathway opened new horizons
● In PCOS defect in tissue availability and altered metabolism may contribute to IR
 THE
DCI
PARADOX !!
 DCI Paradox

• Three target organs of insulin , adipose tissue, liver and skeletal muscle require a high

concentration of DCI for maintaining homeostasis

• The epimerase activity is reduced due to IR and there is relative deficiency of DCI which in

turn promotes IR

• Ovary however remains sensitive to insulin as it is immune to IR

• So MI conversion to DCI is accelerated leading to MI deficiency and DCI excess in ovary

 DCI Paradox
● Altered MI to DCI ratio in ovary leads to shift in FSH to LH ratio
● Increase granulosa cell sensitivity to LH
● Leading to excess androgen production
● High insulin in PCOS thus impede ovulation in PCOS probably through inositols
 Inositols Deficiency in PCOS

Deficiency of MI and DCI and Insulin Resistance

1
2

Baillargeon JP, et al. Diabetes care. 2006; 29 (2): 300-5.

Heimark, et al. Endocrine journal 2014, 61(2), 111-117
 Inositol Supplementation in PCOS

MI + DCI supplementation

Increase in INS2 second messengers

Enhanced insulin activity & glucose utilization

Increase in insulin sensitivity

Ameliorates symptoms of PCOS

Biochimie 95 (2013) 1811e1827;

The Journal of Clinical Pharmacology54(10) 1079–1092
The Right Combination:
Myo inositol and
D Chiro inositol
 Limitations of Currently available Inositol Formulations

All brands containing MI-DCI in 40:1 ratio

• 40:1 is a physiological ratio ‐ PCOS is pathological condition

• 40:1 is not a universal ratio ‐

– It varies from tissue to tissue (healthy condition vs PCOS)

In ovary Healthy condition PCOS condition

MI/DCI 100:1 0.2:1

Unfer V et al. Reprod Sci. 2014 Feb 4;21(7):854‐858

Clinical Evidence
Myo inositol in PCOS
 Myo inositol Supplementation in PCOS
A study used MI 2 g and folic acid, twice daily, continuously, till the end of study (6 months) or a
positive pregnancy test was obtained.
Of 25 women with PCOS:
● 22 (88%) : First menstrual cycle after 34.6–5.5 days.
○ 18 : Regular menstruation and spontaneous ovulation.
○ The length of successive cycles improved to 31.7 ± 3.2 days
○ Significant fall in serum testosterone and free testosterone.
● A total of ten biochemical pregnancies occurred during 6 months.
● No multiple gestations were noted.

MI can be used as a safe means of induction of ovulation in women with PCOS.

Papaleo E, Unfer V, Baillargeon JP, De Santis L, Fusi F, Brigante C,et al. Myo‑inositol in patients with polycystic ovary syndrome: A novel method for ovulation induction. Gynecol Endocrinol 2007;23:700‑ 3.
 Myo inositol Supplementation in PCOS

Objective: To evaluate the effects the administration of myo-inositol (MYO) on

hormonal parameters in a group of polycystic ovary syndrome (PCOS) patients.
N: 50 overweight PCOS patients were enrolled after informed consent.
Interventions: For 12 weeks;
● Group A: MYO 2 g plus folic acid 200 mg every day (study group)
● Group B: folic acid 200 mg every day. (control group)
Main outcome measures: Plasma LH, FSH, PRL, E2, 17OHP, A, T, glucose, insulin, C
peptide concentrations, BMI, HOMA index and glucose-to-insulin ratio.

Artini PG, Di Berardino OM, Papini F, Genazzani AD, Simi G, Ruggiero M, et al. Endocrine and clinical effects of myo‑inositol administration in polycystic ovary syndrome. A randomized study. Gynecol Endocrinol 2013;29:375‑ 9.
 Myo inositol Supplementation in PCOS
Results: After 12 weeks of myo inositol administration,
● Reduction of risk of ovarian hyperstimulation syndrome with ovulation ‑induction protocols.
● Significant reduction in concentrations of LH, prolactin, androstenedione, insulin, and LH/FSH
ratio.
● Improvement in insulin sensitivity.
●MyoThe duration
inositol of ovulation induction
administration improvesandreproductive
dose requirement
axisoffunctioning
recombinant
inFSH were
PCOS patients
significantly
reducing lower.
the hyperinsulinemic state that affects LH secretion.
● MI administration achieved lower oocyte retrieval, but had a greater proportion of large
dimension (top quality) oocytes, which translated to a higher pregnancy rate.
● In MI treated patients, results in Pregnancy were, 15 with biochemical pregnancy, 10 with
clinical pregnancy and 8 with successful delivery as compared to 8, 4, and 3 in non ‑MI ‑treated
participants.
● All these differences were statistically significant.
Artini PG, Di Berardino OM, Papini F, Genazzani AD, Simi G, Ruggiero M, et al. Endocrine and clinical effects of myo‑inositol administration in polycystic ovary syndrome. A randomized study. Gynecol Endocrinol 2013;29:375‑ 9.
 Myo inositol Supplementation in PCOS

An Iraqi study on 95 participants reported that a combination of inositol 500 mg, with choline 500
mg and metformin 850 mg, all administered twice daily for 6 months led to significant decrease in:
● Body mass index (BMI),
● Serum leptin,
● Serum anti‑Mullerian hormone (AMH),

as compared to metformin monotherapy and lifestyle management alone.

Data also support the use of myoinositol in gestational diabetes mellitus (GDM).

Ali LQ, Luaibi NM, Majeed BJ. Used inositol decreased anti‑Mullerian hormone (AMH) in polycystic ovary syndrome women. Int J Adv Res 2015;3:857‑ 69.
 Myo inositol Supplementation in PCOS

Objective: The objective of the meta-analysis was to assess the effects of MI alone or combined
with d-chiro-inositol (DCI) on the endocrine and metabolic abnormalities of women with PCOS.

Nine RCTs involving 247 cases and 249 controls were included.

Results:
● Significant decreases in fasting insulin and homeostasis model assessment (HOMA) index.
● A slight trend toward a reduction of testosterone concentration by MI with respect to controls
was found.
● The trial sequential analysis of insulin meta-analysis illustrates that the cumulative z-curve
crossed the monitoring boundary, providing firm evidence of the intervention effect.
● Throughout a subgroup’s metaanalysis, a significant increase in serum SHBG was observed
only in those studies where MI was administered for at least 24 weeks.
Unfer, Vittorio, et al. "Myo-inositol effects in women with PCOS: a meta-analysis of randomized controlled trials." Endocrine Connections 6.8 (2017): 647-658.
 Myo inositol Supplementation in PCOS

The present meta-analysis of nine RCTs revealed that MI alone or combined with DCI
improves the metabolic profile of women with PCOS, also increasing SHBG when
supplementation lasted at least 24 weeks.

The z-curve after the fourth trial crossed the sequential monitoring boundary providing firm evidence of
an effect of MI on fasting insulin compared to controls
Unfer, Vittorio, et al. "Myo-inositol effects in women with PCOS: a meta-analysis of randomized controlled trials." Endocrine Connections 6.8 (2017): 647-658.
 D Chiro Inositol
(150 mg) in PCOS
 DCI (150 mg)
Safety and Efficacy in PCOS
The amount of D chiro-inositol in muscle is lower in subjects with type 2 diabetes
mellitus than in normal subjects.
A higher dose of D-Chiro-inositol increases the action of insulin in patients with the
polycystic ovary syndrome without causing side effects.
DCI dose of 150 mg twice daily for 6-8 weeks causes

2 2 3

1. Fertility and Sterility.2001:76( 3suool):S110-111, 2. Endocr Pract. 2002 Nov-Dec;8(6):417-23 3. Gynecol Endocrinol 2014 Jun;30(6): 438-43 4.Nestler, John E., et al. "Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome." New England Journal of
Medicine 340.17 (1999): 1314-1320.
 Study design
• Effects of DCI 300 to 1200 mg/day or placebo on ovulatory rate and circulating
total testosterone (T) and free T levels in 223 women who were oligomenorrheic
and obese were assessed for 2 months.
Conclusions:
• 32% of the women who entered the trial were hyperandrogenemic based on the
criteria of both elevated T and free T levels.
• There was a statistically significant decrease in androgen levels in those
women who ovulate while receiving high dose of DCI.
• No study drug-related serious adverse events were reported.
Fertility and Sterility September 2001Volume 76, Issue 3, Supplement 1, Pages S110–S111
 ● DCI treatment has been found to reduce insulin levels, lipids, and blood
pressure, in women with PCOS.
● In a study conducted on 68 participants, women with PCOS were
pretreated before ovarian stimulation with DCI 500 mg b.d. DCI improved
the maturity and quality of oocytes significantly, while reducing oxidative
stress (as measured by amino acidic free ‑ SH group labeling). The usage
of DCI was not associated with any adverse effect in this study.

● Inositol is generally regarded as safe and can be used in pregnancy.

Kalra, et al.: Journal of Endocrinology and Metabolism, August 26, 2016

D Chiro inositol (150 mg)
in
Obese PCOS
 Modulatory role of DCI on luteinizing hormone and
insulin secretion in obese patients with PCOS
Objective: Study (N = 22) to determine the efficacy DCI on hormonal parameters
and insulin sensitivity in obese subjects (BMI > 26) with PCOS
Method: Participants were administered 500 mg of DCI, daily for at least 12 weeks
Results: DCI administration caused:
• Improvement in several endocrine parameters
Administration of DCI is effective in restoring better insulin sensitivity and an
improved• hormonal
Marked pattern
improvement
in obesein hyperinsulinemic
insulin sensitivity and GnRH
patients with PCOSinduced LH
response
• Decrease in BMI
• PCOS subjects with diabetic relatives exhibited greater improvement
with DCI therapy

Genazzani et al 2014
D Chiro inositol (150 mg)
in
Lean PCOS
 Effects of DCI in lean patients with PCOS

Objective: Study (N = 20) to assess the effect of DCI on concentration of circulating

insulin, the levels of serum androgens, & frequency of ovulation in lean patients with
PCOS
Method: Participants (BMI 20.0 - 24.4 kg/m2) treated with either 600 mg of DCI
(N=10) or placebo (N=10) orally once daily for 6 -8 weeks
In lean women with PCOS, D - chiro-inositol:
Reduces
Results: Whenthe circulating
compared insulin &group,
to placebo decreases serum
DCI group androgens
had:
Ameliorates certain metabolic abnormalities
• Marked decrease in the mean area under the plasma insulin curve after oral
administration of glucose
• Reduction (73%) in serum free testosterone concentration
• Spontaneous Ovulation (60%)
• Significant drop in systolic, diastolic BP & plasma triglyceride concentration.
Iuorno MJ, Jakubowicz DJ, Baillargeon JP, Dillon P, Gunn RD, Allan G, et al. Effects of d-chiro-inositol in lean women with the polycystic ovary syndrome. Endocr Pract. 2002 Nov–Dec;8(6):417–23.
Myo inositol (550 mg) and
D Chiro inositol (150 mg) in
Infertility associated PCOS
 Is there any comparative evidence of
Right dose vs. Low Dose DCI ??
Comparison of the effect of two combinations of myo-inositol and
D-chiro-inositol in women with polycystic ovary syndrome
undergoing ICSI
Results: Clinical Study …2018
MI 550 mg
MI 550 mg +
Right Dose Low Dose
+ DCI 13.8mg
DCI DCI
DCI 150 mg (40:1 ratio)

8 centers of recruitment; 6 regions in

Spain.
Principal Investigator: Dr. Nicolás
Status: 56 women completed the study
Mendoza (Granada,Spain)
Randomized Controlled Trial Double Blind Study
P. Llaneza et al. Comparison of the effect of two combinations of myoinositol and D-chiro-inositol in women with polycystic ovary syndrome who undergo ICSI. ESHRE annual meeting 1-4 July 2018. Available from http://www.eshre.eu/eshre 2018.aspx
 Right Dose DCI-150 mg
Effect on Pregnancy Rate

P. Llaneza et al. Comparison of the effect of two combinations of myoinositol and D-chiro-inositol in women with polycystic ovary syndrome who undergo ICSI. ESHRE annual meeting 1-4 July 2018. Available from http://www.eshre.eu/eshre 2018.aspx
 Right Dose DCI-150 mg
Effect on Live Birth Rate

P. Llaneza et al. Comparison of the effect of two combinations of myoinositol and D-chiro-inositol in women with polycystic ovary syndrome who undergo ICSI. ESHRE annual meeting 1-4 July 2018. Available from http://www.eshre.eu/eshre 2018.asp
 Comparison of the effect of a combination MYO:DCI (ratio 3.6:1; 550mg:150mg) versus
the combination of MYO with low DCI (ratio 40:1; 550mg:13.8mg) on oocyte quality
and pregnancy rates in women suffering Polycystic ovary syndrome (PCOS).

8 centers of recruitment; 6 regions in Spain.

Principal Investigator: Dr. Nicolás Mendoza (Granada)

Status: 56 women recruited, 6 dropouts

29 women completed the study, 21 women ongoing

Gynecol Endocrinol. 2019 Aug;35(8):695-700.

 Intermediate evaluation: Results of 29 women who have completed the
study

GROUP 1 GROUP 2
GROUP 1 Insulin HOMA GROUP 2 Insulin HOMA
(uU/mL) (uU/mL)
Base line 12.07±6.8 2.64±1.4 Base line 7.12±2.7 1.61±0.7
T 12 9.01±4.8 1.90±1.1 T 12 weeks 7.70±3.9 1.64±0.9
weeks
p-value 0.644 0.926
p-value 0.008 0.006
Product 1 reduced after 12 weeks of treatment around
25% the level of insulin and 28% HOMA index

No significant differences were observed after 12 weeks

treatment with product 2
Gynecol Endocrinol. 2019 Aug;35(8):695-700.
 Rate of clinical pregnancy

+185%

57%
20%

Pregnancy success improved 185% after 12 weeks

treatment with product 1 (p=0.039)

Gynecol Endocrinol. 2019 Aug;35(8):695-700.

Myo inositol (550 mg) and
D Chiro inositol (150 mg)
In Indian Scenario
The study evaluated the treatment patterns, clinical effectiveness and safety of MI-DCI
combination in management of PCOS in Indian women.
Method:
Data from 50 healthcare centers across India was collected between September 2019 and
February 2020.
Total of 283 women aged 12-45 years diagnosed with PCOS, who had received MI-DCI
(550-150 mg) were included.
The outcome parameters were change in weight, luteinizing hormone (LH)/follicle stimulating
hormone (FSH) ratio, hirsutism, blood glucose and insulin levels, HOMA-IR, and lipid profile.
Vyas, Lila, et al. "Management of polycystic ovary syndrome among Indian women using myo‐inositol and D-chiro-inositol." Bioinformation 18.2 (2022): 103-110.
 80.9%
Women recorded
regularisation of
menstrual cycle

69.6% The hirsutism scores considerably

improved after treatment and the
Women reported proportion of patients with, no hirsutism
reduction in weight increased from 31.07% to 50.51% and
moderate hirsutism reduced from
32.52% to 6.12%
Vyas, Lila, et al. "Management of polycystic ovary syndrome among Indian women using myo‐inositol and D-chiro-inositol." Bioinformation 18.2 (2022): 103-110.
 MI-DCI (550-150 mg) has shown multidimensional benefits in improving the
hormonal, glycemic, and lipid profile of women with PCOS with considerable
efficacy and tolerability.

Vyas,
Vyas,
Lila,
Lila,
et et
al.al.
"Management
"Management
of of
polycystic
polycystic
ovary
ovary
syndrome
syndrome
among
among
Indian
Indian
women
women
using
using
myo
myo
‐inositol
‐inositol
andand
D-chiro-inositol."
D-chiro-inositol."
Bioinformation
Bioinformation
18.2
18.2
(2022):
(2022):
103-110.
103-110.
Objective: To compare the effect of myo-inositol and D-chiro-inositol in combination
with combined hormonal contraceptive (CHC) on menstrual regulation in young Indian
women with polycystic ovarian syndrome.

Method: N = 70 young women with PCOS aged 15-24 years with delayed cycles. They
were randomised into 2 groups and were treated for 6 months with MI + DCI (550+150
mg, 3.6:1 ratio) twice a day and CHC (ethinyl estradiol 20 mcg + drospirenone 3 mg )
once a day.

Int J Gynaecol Obstet. 2022 Aug;158(2):278-284.

Int J Gynaecol Obstet. 2022 Aug;158(2):278-284.
Change in menstrual pattern among young women treated with myo-inositol and D-
chiro-inositol combination
At 3 months of treatment with MI+DCI
Myo-inositol and D-chiro-inositol in combination spontaneous
(3.6:1 ratio)menses occured in 26
are effective in
(78.79%) young women with a mean
regularising menstrual cycles and improving insulin
cycle length resistance
of 62.81 ± 3.21 days.
Regular menstrual cycles (24-28 days)
occurred in nine (27.27%) young
women after 6 months of treatment
compared with none at presentation.
3 months after stopping treatment, 24
(85.71%) in the MI+DCI group
continued to have spontaneous
cycles
Int J Gynaecol Obstet. 2022 Aug;158(2):278-284.
 Available Treatment and Challenges
Drug Therapeutic Target Side Effect
Contraceptive in combined Menstrual disorders, vaginal Dizziness, Headache, Stomach
therapy of estrogen and bleeding, acne, hirsutism, obesity. upset, Bloating. Nausea, Weight
progestin. (COCs) Gain, Metabolic , may be
aggravated or triggered
Metformin Insulin resistance, Acne, Hirsutism, Nausea, Vomiting, Diarrhea,
Ovulation and fertility problems Abdominal Bloating
Clomiphene citrate Ovulation and Fertility problems Multiple pregnancy, High failure
rate, hot flushes, risk of ovarian
tumor
Myoinositol (MI) Insulin resistance, Acne, Hirsutism, None
Ovulation and Fertility problems
D-Chiro-Inositol(DCI) Insulin resistance None
MI+DCI Insulin resistance, ovulation and None
fertility problems, Acne Hirsutism

Monastra G et al.: Combining treatment with myo-inositol and D-chiro-inositol (40:1) is effective in restoring ovary function and metabolic balance in PCOS patients, Gynecological Endocrinology2016,
 Conclusion
● Polycystic ovary syndrome (PCOS) is associated with significant morbidity and
Insulin resistance plays a central role in pathogenesis of PCOS.
● Myo-inositol and D-chiro-inositol are capable of improving the ovarian function
and metabolism of polycystic ovary syndrome (PCOS) patients.
● D Chiro inositol in doses of (>300 mg BD) reduce insulin levels, lipids, and blood
pressure, in women with PCOS without any adverse events.
● Rather than following a ratio which is not defined, it is always better to provide the
therapeutic dose of each ingredients.
● In Indian Scenario, Myo-inositol and D-chiro-inositol in combination (3.6:1 ratio)
are effective in regularising menstrual cycles and improving insulin resistance
 Myo Inositol Deficiency in PCOS
Deficiency of MI in Ovary lead to ovulatory dysfunction and Infertility
Insulin Resistance in PCOS leads to hyperinsulinemia, which at
ovarian level causes alteration in inositols metabolism.
Enhanced MI to D-chiro-inositol (DCI) epimerization in the ovary
results in an increased DCI/MI ratio.
A sequent reduction of MI increases the isoform DCI and induces
overproduction of androgens.
Deficiency of MI in the ovary results in poor oocyte quality.
MI, a component of the vitamin B complex and insulin sensitizer:
● Improves insulin signaling
● Reduces serum insulin
● Decreases serum testosterone
● Restoring normal ovulatory function in PCOS women
● Safe and effective to prevent and correct metabolic disorders
Pkhaladze L, Barbakadze L, Kvashilava N. Myo-Inositol in the Treatment of Teenagers Affected by PCOS. Int J Endocrinol. 2016;2016:1473612.
Kalra B et al. The inositols and polycystic ovary syndrome.Indian J Endocrinology & Metabolism.2016; 20(5):720;
 DCI Deficiency in PCOS
Deficiency of DCI at the Peripheral Level
Decreased DCI concentration, and/or bioactive DCI-IPG release, contribute to Insulin
Resistance (IR).
Resultant Hyperinsulinemia & Hyperandrogenism leads to PCOS symptoms.
D-chiro inositols:
● Reduces testosterone levels
● Improves metabolic parameters
● Ameliorates systolic and diastolic blood
pressure & triglycerides levels
● Restores ovulatory function
● Alleviates dermatological signs of
hyperandrogenism
Laganà, Antonio Simone, et al. "Metabolism and ovarian function in PCOS women: a therapeutic approach with inositols." International Journal of Endocrinology 2016 (2016).
 Natural Sources of Inositols

Kalra B et al. The inositols and polycystic ovary syndrome.Indian J Endocrinology & Metabolism.2016; 20(5):720;
 The Therapeutic
Potential of Inositols
in PCOS
 Inositol Supplementation in PCOS

In 2015 International Consensus Conference on MI and DCI in Obstetrics and

Gynecology recognizes that both MI and DCI are involved in several biological

pathways, involved in PCOS pathogenesis and there is plenty clinical data

demonstrating that inositols supplementation could be beneficial for improving

metabolic and reproductive aspects of this disorder.

Kamenov Z, Gateva A. Inositols in PCOS. Molecules. 2020 Nov 27;25(23):5566. PMID: 33260918; PMCID: PMC7729761.
MI and DCI in Infertility
Associated with PCOS
 MI & DCI Rationale in Infertile PCOS cases

Unfer V et al .Effects of Inositol(s) in Women with PCOS: A Systematic Review of Randomized Controlled Trials. Int J Endocrin Volume 2016, Article ID 1849162, 12 pages
 Limitations of Currently available Inositol Formulations

• Ideal therapeutic dose of DCI is 300 mg‐ 600 mg/day.The dosage of MI 550
mg/DCI 13.8 (40:1) mg would not be sufficient.

• The International brands containing 40:1 ratio is available in soft-gel capsules with
patented technology which has higher bio-availability but all Indian formulations
containing 40:1 ratio are available as a solid dosage form (tablet or sachet).

• Rather than following a ratio which is not defined , it is always better to provide the
therapeutic dose of each ingredients

Unfer V et al. Reprod Sci. 2014 Feb 4;21(7):854‐858

Isabella and Raffone Journal of Ovarian Research 2012, 5:14; World Journal of Pharmacy and Pharmaceutical Sciences. 2015 May 18;4(6):137–55
Latest Guidelines on
PCOS
 Pharmacological treatment for non-fertility indications

Pharmacological treatment for infertility

Teede, Helena J., et al. "Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome." Human reproduction 33.9 (2018): 1602-1618.
 PCOS: Introduction
Polycystic Ovarian Syndrome was first identified by Stein and Leventhal in 1935. It can
also be known as Stein – Leventhal Syndrome.

Rotterdam Criteria:
Irregular ovulation, hyperandrogenism,
and polycystic ovaries

Symptoms
Prevalence
Polycystic Ovarian Acne, amenorrhea or
Global prevalence of
oligomenorrhea,
PCOS ranges between Syndrome
hirsutism,
4% and 21%
hyperinsulinemia,
Prevalence of PCOS in
infertility, and mood
Indian adolescents is
disorders
9.13%
 ART Outcomes with Inositols in PCOS

● Inositol plays an important role in the follicular microenvironment and affects

oocyte maturation and embryo development.

● Elevated concentration of myoinositol in the follicular fluid appears to exert a

positive effect on follicular maturity and is a marker of good quality oocytes in
women.

● Myo inositol supplementation decrease the risk of ovarian hyperstimulation

syndrome in PCOS patients.

Garg, Deepika, and Reshef Tal. "Inositol treatment and ART outcomes in women with PCOS." International Journal of endocrinology 2016 (2016).
 ART Outcomes with Inositols in PCOS

Objective: To investigate the effects of the combined therapy myo-inositol (MI) plus D-chiro-inositol (DCI) or
D-chiro-inositol treatment in oocyte quality.

N: 100 women having a BMI < 28 and FSH < 10 IU/L with a diagnosis of PCOS according to Rotterdam
2003 and a normal uterine cavity undergoing IVF-ET.

Method: Patients were randomly assigned to receive myo-inositol combined with D-chiro-inositol (550 mg +
13.8 mg) (47 subjects) or D-chiro-inositol alone (500 mg) (53 subjects) orally twice daily.

Both treatments were performed for 12 weeks before rFSH administration and throughout pregnancy.

Outcomes:The number of morphological mature oocytes, total International Units (IU) of recombinant FSH
administered and the number of grade 1 embryos.
S. Colazingari, M. Treglia, R. Najjar, and A. Bevilacqua, “The combined therapy myo-inositol plus D-chiro-inositol, rather than D-chiro-inositol, is able to improve IVF outcomes: results froma randomized controlled trial,” Archives of Gynecology and Obstetrics, vol. 288, no.
6, pp. 1405–1411, 2013.
 ART Outcomes with Inositols in PCOS

Result:

● Only the MI-DCI treated group was characterized by an increase in embryo quality.

● Stimulation protocols in MI-DCI treated patients were more efficient

Myo inositol plays a crucial role in the ovary in PCOS women. The combined therapy of myo
inositol
● Lower anddoses
D-chiro-inositol
of FSH wereshould represent
administered for aa shorter
better choice.
period of time.

● The combination resulted in better embryo quality, directly increased pregnancy rate.

● Combined therapy MI-DCI, rather than DCI, was able to improve oocyte quality in PCOS women
undergoing assisted reproductive technology.

S. Colazingari, M. Treglia, R. Najjar, and A. Bevilacqua, “The combined therapy myo-inositol plus D-chiro-inositol, rather than D-chiro-inositol, is able to improve IVF outcomes: results froma randomized controlled trial,” Archives of Gynecology and Obstetrics, vol. 288, no.
6, pp. 1405–1411, 2013.