The Effects of Acetyl-L-Carnitine and Myo/Chiro-Inositol in Patients With PCOS

The large number of women in their child bearing age is affected by Polycystic ovarian syndrome (PCOS) leading to infertility. However it is considered as a multisystem disorder with comorbidities rather than a gynecological and a dermatological problem. Patient mostly have anovulation presented as oligomennorhea or amenorrhea and hyperandrogenism presented as hirsutism along with hyperinsulinemia and insulin resistance. Many etiological factors are reported but those actually responsible for PCOS in females still need to be explored. However hyperandrogenism and insulin resistance being the key triggering condition apart from cardiovascular disease, type 2 diabetes, hypertension and obesity. World Health Organization (WHO) has considered Infertility's as public health problem. Researchers reported the obesity role in occurrence of PCOS and its Infertility's relation . PCOS is not a simple pathophysiologic process for which one treatment address all manifestation. Treatment should target specific manifestations and individualized patient goals. First-line agents for ovulation induction and treatment of infertility in patients with PCOS include metformin and clomiphene alone or in combination. It has been approved as category "A "to regulate ovulation and improves pregnancy rates in women with PCOS . Mostly it result in complication like multiple follicle recruitment rate, multiple pregnancy and thinning of endometrial wall leading to early abortion and endometrial cancers. The use of naturally occurring compounds like myoinositol, D-chiro- inositol and L- carnitine which are already part of human body are expected to produce significant results without any side effects . The proposed study will provide an alternative to current treatments available for infertility due to PCOS. The expected project execution time is 2 years. Thus, the present project will discover new insights about treatment of infertility and thus generate new knowledge which will help Academia, scientists and health care professionals. Results of the study will be disseminated on different forums including to policy makers , Pharmaceutical, national and international agencies. The result will be published in journal both national and international with good impact factors. The outcome of the project will be used as publication in high impact international journals, filling of patents and will also be presented in national and international forums.

Sex

Female

Minimum age

18 Years

Maximum age

35 Years

Inclusion Criteria:Married women with PCOS aged ≥18 years to ≤35 years who is infertile (primary and secondary) and have a wish to conceive will be included in the study. The diagnosis of PCOS will be made according to the NIH 2012 extension of ESHRE/ASRM 2003 criteria (21). Identification of specific phenotypes will be included:

A. Hyperandrogenism plus Ovulatory dysfunction plus Polycystic Ovarian Morphology (HA +OD+PCOM) B. Hyperandrogenism plus Ovulatory dysfunction (HA+OD) C. Hyperandrogenism plus Poly Cystic Ovarian Morphology (HA+PCOM). D. Ovulatory dysfunction plus Polycystic Ovarian Morphology (OD+PCO)

Couple inclusion criteria; Being a sterility trial couples ensuing to do their semen analysis regularly or provide record showing their sperm concentration to be at least 15 million /ml in at least one ejaculation during the past one year with some motile sperm. Similarly, couples having ability and readiness to perform sexual intercourse as and when directed by the investigator will be included. Female subjects should have at least one open fallopian tube and normal uterus from inside on hysterosalpingography /hysteroscopy/laparoscopy or have normal course of conception, delivery during the past 03 years. Patients should have no history of tubal ligation or vasectomy procedure that has been reversed

Exclusion Criteria: Females having history of having an infertile male partner in the past, Cushing syndrome, diabetes, thyroid disorders, hyperprolactinemia, ovarian tumors, congenital adrenal hyperplasia, androgen-producing tumors, history of seizures, pregnancy undiagnosed vaginal bleeding History of suspected cervical or endometrial carcinoma breast carcinoma using contraceptive anti-coagulants, antiplatelet, isoproterenol and potassium sparing diuretics, anti-depressants and medications that alters the biochemical or hormonal profile will be excluded. Participants who have been prescribed hormones during the past at least 3 months before the study will not be included in the study. Patient who is willing to participate in the study is using any medicine that can be discontinued (e.g., oral contraceptive or ovulation induction agents (GnRH agonist and antagonist; gonadotropins, HCG) will be allowed wash out period of 02 months before being included in the study.

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• BACKGROUNDRubin KH, Glintborg D, Nybo M, Abrahamsen B, Andersen M. Development and Risk Factors of Type 2 Diabetes in a Nationwide Population of Women With Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2017 Oct 1;102(10):3848-3857. doi: 10.1210/jc.2017-01354. PMID 28938447
• BACKGROUNDOrio F, Palomba S. Reproductive endocrinology: New guidelines for the diagnosis and treatment of PCOS. Nat Rev Endocrinol. 2014 Mar;10(3):130-2. doi: 10.1038/nrendo.2013.248. Epub 2013 Dec 10. PMID 24322653
• BACKGROUNDAkram M, Roohi N. Endocrine correlates of polycystic ovary syndrome in Pakistani women. J Coll Physicians Surg Pak. 2015 Jan;25(1):22-6. PMID 25604364
• BACKGROUNDChauhan B, Kumar G, Kalam N, Ansari SH. Current concepts and prospects of herbal nutraceutical: A review. J Adv Pharm Technol Res. 2013 Jan;4(1):4-8. doi: 10.4103/2231-4040.107494. PMID 23662276
• BACKGROUNDAn H, He L. Current understanding of metformin effect on the control of hyperglycemia in diabetes. J Endocrinol. 2016 Mar;228(3):R97-106. doi: 10.1530/JOE-15-0447. Epub 2016 Jan 7. PMID 26743209
• BACKGROUNDMansfield R, Galea R, Brincat M, Hole D, Mason H. Metformin has direct effects on human ovarian steroidogenesis. Fertil Steril. 2003 Apr;79(4):956-62. doi: 10.1016/s0015-0282(02)04925-7. PMID 12749437
• BACKGROUNDMorley LC, Tang T, Yasmin E, Norman RJ, Balen AH. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database Syst Rev. 2017 Nov 29;11(11):CD003053. doi: 10.1002/14651858.CD003053.pub6. PMID 29183107
• BACKGROUNDTauqir S, Israr M, Rauf B, Malik MO, Habib SH, Shah FA, Usman M, Raza MA, Shah I, Badshah H, Ehtesham E, Shah M. Acetyl-L-Carnitine Ameliorates Metabolic and Endocrine Alterations in Women with PCOS: A Double-Blind Randomized Clinical Trial. Adv Ther. 2021 Jul;38(7):3842-3856. doi: 10.1007/s12325-021-01789-5. Epub 2021 May 28.