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PCOS Treatment Guidelines  &  Review of  Newer Medical Treatment in Infertility Dr. Sharda Jain
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PCOS Treatment Guidelines & Review of Newer Medical Treatment in Infertility Dr. Sharda Jain


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  • 1. PCOS Treatment Guidelines & Review of Newer Medical Treatment in Infertility Dr. Sharda Jain Dr. Jyoti Agarwal Dr. Jyoti Bhaskar
  • 2. ESHRE/ ASRM sponsored PCOS Consensus Workshop • 1st workshop (2004) on Diagnosis • 2nd workshop (2008) on Infertility • 3rd workshop (2011) Women’s Health Aspects of PCOS Must Reading for all of you
  • 3. PCOS Phenotypes as per Rotterdam criteria PCOS Phenotype Oligo – or an ovulation Biochemical hyperandrogene mia or clinical manifestation of hyperandrogene mia Polycystic ovaries in transvaginal ultrasound 1- Severe PCOS + + + 2- Oligo – or anovulation and hyperandrogene mia + + - 3- ovulatory PCOS - + + 4- MILD pcos + - +
  • 4. MENSTRUAL DISORDERS: PCOS mostly produces oligomenorrhea or amenorrhea. INCREASED LH/FSH RATIO - Prevents follicular maturation resulting in anovulation HIGH LEVELS OF ANDROGEN HORMONE: The most common signs are acne, acanthosis nigricans, androgenic alopecia & hirsutism. METABOLIC SYNDROME: This appears as a tendency towards central obesity and other symptoms associated with insulin resistance. Common Symptoms of PCOS Other than INFERTILITY Serum insulin, insulin resistance and homocysteine levels are higher in women with PCO.
  • 6. Management of Infertility in PCOS WHO Group – II Ovulation Disorder Classic PCOS Anovulatory PCOS Ovulatory PCOS NICE/ ASRM Guidelines
  • 7. Women with WHO group II anovulatory infertility with PCOS who have a BMI of 30 or over must lose weight. Inform them that this alone may restore ovulation, improve their response to ovulation induction agents, and have a positive impact on pregnancy outcomes Life style management of Weight Reduction (NICE 2013)
  • 8. Life style management of Weight Reduction • 50% treatment of PCOS is simply – weight control. • Even if one loses 5-10 kg - the effect is tremendous . Experience
  • 9. One of the following treatments taking into account potential adverse effects, ease and mode of use, the women’s BMI • Clomifene Citrate or • Metformin or • A combination of the above ESRE / ASRM consensus workshop on PCOS Anovulatory Infertility Cycle clinical follicle monitoring needed: (NICE 2013)
  • 10. Clomifene Citrate • For women who are taking clomifene citrate, do not continue treatment for longer than 6 months •Women prescribed metformin should be informed of the side effects associated with its use (such as nausea, vomiting and other gastrointestinal disturbances) (NICE 2004) (NICE 2013)
  • 11. Experience of Infertility Experts on Role of Metformin in PCOS • CC compared with metformin aloneresults in higher ovulation , conception, pregnancy & live birth rate • CC + Metformin results in no substantial benefits except, patients with BMI >35 or abnormal GTT Fertile sterile 2008,89;505
  • 12. PCOS Patients with Anovulation & Ovulation disorder RESISTANT TO CLOMIFENE CITRATE: For women with PCOS who are known to be resistant to clomifene citrate, consider one of the following SECOND – LINE TREATMENT, depending on clinical circumstances and the women’s preference • Laparoscopic Ovarian drilling or • Combined treatment with clomifene citrate and metformin if not already offered as fist – line treatment or • Gonadotrophines (NICE 2013)
  • 13. CLOMIFENE CITRATE + Metformin However, Recent Study showed CC+ metformin combination therapy results in hyper rates of LIVE BIRTHS compared with other treatments. Jungheim et. all fertil steril 2010;94:2659
  • 14. Caution Women with PCOD who are being treated with gonadotrophins should not be offered treatment with gonadotrophin – releasing hormone agonist concomitantly because it does not improve pregnancy rates and it is associated with an increase risk of ovarian hyperstimulation (NICE 2004)
  • 15. The use of Adjuvant Growth Hormone treatment with gonadotrophins – releasing hormone agonist and / or human menopausal gonadotrophin during ovulation induction in women with PCOS who do not respond to clomifene citrate is not recommended because it does not improve pregancy rates Caution (NICE 2004)
  • 16. INTRODUCING Concepts & Rationale of A NEW LINE OF TREATMENT ↓ Still not approved by NICE GUIDELINES & ASRM
  • 18. Oxidative Stress & Infertility
  • 19. Basis of Newer Drugs use
  • 20. Summary of Review of literature shows
  • 21. MELATONIN •Recent entry •Melatonin is also known as N-acetyl-5 methoxytryptamine •An hormone secreted during the dark hours by pineal gland. •Regulates a variety of important central and peripheral •actions related to circadian rhythms and reproduction.
  • 22. However, the discovery of melatonin as a direct free radical scavenger has greatly broadened the understanding of melatonin’s mechanisms which benefit reproductive physiology. MELATONIN
  • 23. •It has been discovered that melatonin is a powerful free radical scavenger and a broad-spectrum antioxidant. Because of its small size and highly lipophilic & hydrophilic properties, melatonin crosses all cell membranes & easily reaches subcellular compartments,including mitochondria and nuclei, where it seems to accumulate in high concentrations. •Melatonin prevents lipid peroxidation, protein, and DNA damage. MELATONIN
  • 24. Melatonin, secreted by pineal gland, is taken up into the follicular fluid from the blood. ROS produced within the follicles, especially during the ovulation process, were scavenged by melatonin, and reduced oxidative stress involved in oocyte maturation and embryo development Melatonin increases intra-follicular melatonin concentrations, reduces intra-follicular oxidative damage Elevates fertilization and pregnancy rates. MELATONIN
  • 25. Comes from the amino acid l-cysteine. Amino acids are the building blocks of protein Improves insulin sensitivity & decreases androgen level Prevents follicular cohort atresia Improves quality of cervical mucus N-ACETYLCYSTEINE
  • 26. •Decreases circulating insulin & serum total testosterone •Reduces acne & weight •Reduces hirsutism and hyperandrogenism and ameliorates the abnormal metabolic profile of women with hirsutism After 3 months of inositol administration, free testosterone, insulin and HOMA index resulted in significantly reduced. Both hirsutism and acne decreased after 6 months of therapy. MYO-INOSITOL
  • 27. Is an analogue of vitamin D used for supplementation in humans . More useful form of vitamin D supplementation, mostly due to much longer half-life and lower kidney load Improves insulin secretion. ALFACALCIDOL
  • 28. Chromium polynicotinate consists of pure niacin-bound chromium Chromium polynicotinateis more effective than other types of chromium, because it binds to niacin also know as vitamin b-3. This provides a biologically active form of chromium, and makes it easier for the body to absorb CHROMIUM POLYNICOTINATE
  • 29. •Active component of glucose tolerance factor which is responsible for binding insulin to cell membrane receptor sites •Improves insulin sensitivity •Stimulates the metabolism of sugar, fat & cholesterol CHROMIUM POLYNICOTINATE:
  • 30. Is the natural, active form of folic acid used at the cellular level for DNA reproduction and the regulation of homocysteine among other functions. Reduces homocysteine levels and prevent cardiovascular risk factors associated with PCOS. The un-methylated form, folic acid (vitamin B9), is a synthetic form of folate found in nutritional supplements. L-METHYLFOLATE
  • 31. Recap • 50% treatment of PCOS is simply – weight control. • Even if one loses 5-10 kg - the effect is tremendous . Experience
  • 32. Please Remembers There is NO approval of these drugs in NICE & ASRM Guidelines & Drugs controlled of India for Ovulation Induction Few Drug House have stared marketing NAC & combination of NAC with these drugs to be given with CC Please Note
  • 33. Summary Infertility in PCOS • Exclude other diseases & other fertility disorders in the couple. • Life style modification particularly weight loss increase exercise, smoking cessation & decrease alcohol consumption is highly recommended. • The Pharmacological treatment approved by NICE/ ASRM is CC or CC+ metformin. •Second line treatment i.e. gonadotrophines or laparoscopic ovarian drill if medical treatment fails. •NICE & ASRM do not endorse use of newer drugs (2013)
  • 34. ADDRESS 35 , Defence Enclave, Opp. Preet Vihar Petrol Pump, Metro pillar no. 88, Vikas Marg , Delhi – 110092 CONTACT US 011-22414049, 42401339 WEBSITE : E-MAIL ID