Luteaal phase support lifecare centre


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Luteaal phase support lifecare centre

  1. 1. LUTEAL PHASE SUPPORT IN ART -- & Recurrent Miscarriages Dr. Jyoti Bhaskar Dr. Jyoti Agarwal Dr. Sharda Jain Directors -
  2. 2. • LPD - 5 - 10 % • Unexplained infertility - 15- 20 % • A large fraction of unexplained infertility may be because of LPD which is difficult to diagnose • Recurrent pregnancy loss – 8 -12 % • 40% of women with recurrent pregnancy loss may be having LPD HARD FACTS
  3. 3. LPD is characterized by failure to develop fully mature secretory endometrium LPD ----DEFINITION Decreased progesterone receptors in endometrium Inadequate Secretion of progesterone by Corpus luteum
  4. 4. Poor Secretory response Inadequate Luteal Phase Follicular Phase Secretory Phase Inadequate FSH secretion Abnormal Gonadotrophin pulses Defective Folliculogenesis Inadequate Estrogen Insufficient endometrial priming by estrogen Poor mid cycle LH surge Hyperprolactinemia Inadequate LH secretion Inadequate Progesterone receptors Defects in CL Decreased Progesterone synthesis
  5. 5. PROBLEMATIC AND CONTROVERSIAL as No practical diagnostic method has been validated LPD --- Diagnosis
  6. 6. LPD -- Diagnosis When the luteal phase is shorter than 12 days, it is usually treated Midluteal progesterone level of less than 10 ng/mL was considered to be abnormal, the probability of falsely diagnosing LPD was as low as 4%
  7. 7. SONOGRAPHIC CRITERIA •Rupture of follicle < 17 mm •Poorly formed or ill defined dominant follicle •Luteinised unruptured follicle •Lutein cyst formation •Absence of corpus luteum •Lack of endometrial echogenicity on 7th postovulatory day LPD -- Diagnosis
  8. 8.  Endometrial biopsy --- was GOLD STANDARD It is imprecise, invasive, not reproducible LPD -- Diagnosis Currently there is no reproducible, physiologically relevant and practical clinical standard test to diagnose LPD
  9. 9. • Correction of underlying causes • Emperical – supplemental progesterone or HCG Treatment Ovulation induction strategies improve fertility by inducing multiple ovulation and not correcting LPD
  10. 10. • Confirmed cases of luteal phase defect • Unexplained infertility • Advanced reproductive age • ART techniques – IUI / IVF / ICSI • Hyper- prolactinaemia • All down regulated cycles • Recurrent pregnancy loss • PCOS • Women with strenous exercises and underweight Who require Luteal support ?
  11. 11. • Supraphysiological estrogen levels may induce premature luteolysis • Follicular phase downregulation may impair luteal phase LH release • Pure FSH protocols lead to low LH values • OPU causes granulosa cell disruption • COH accelerates endometrial maturation • To overcome any LPD if present Why in ART Cycles
  12. 12. Luteal Phase Insufficiency in Recurrent Miscarriages Luteal Phase Support with progesterone • There is insufficient evidence to evaluate the effect of progesterone supplementation in pregnancy to prevent a miscarriage (RCOG- Green Top Guidelines2011)
  13. 13. • It was only in 2011 that Cochrane meta analysis suggested that progesterone supplementation has beneficial effects in patients with Recurrent Pregnancy Loss. • It dose, route, frequency & duration does not effect the outcome Cochrane 2011 for Recurrent Miscarriages
  14. 14. PROMISE PROgesterone in MIScarriagE trial Newer Evidence is coming up as large multicentre study PROMISE is currency on the Way
  15. 15. – PROGESTERONE – Human Chorionic Gonadotropins – Estrogen and Progesterone – GnRH agonist – Adjuvants Luteal Support : Drug ?
  16. 16. It should be luteomimatic and not luteolytic Progesterone is the drug of choiceProgesterone is the drug of choice Ideal Drug
  17. 17. • Promotes secretary transformation of the endometrium • It causes local vasodilatation • Induces uterine musculature quiescence How Does Progesterone Act?
  18. 18. Progesterone Supplementation
  19. 19. Oral Intramuscular Vaginal Easy route Micronized form Only 10 % absorbs Not very effective. First hepatic pass Side effects like sedation & hypnosis P4 in oil base, Reliable & consistent plasma level of P4 Rapidly absorb in 2-8 hrs. P4 level maintain for > 72 hrs. Difficult & very painful inj Local reaction & abscess. Non compliance by pt. Targeted organ delivery High conc. In uterus & endometrium First uterine pass effect Minimal systemic side effect Good Pt. compliance Self administration, no prick of needle Various routes
  20. 20. • Immunomodulator • High affinity for progesterone receptors • Safe, well tolerated, non androgenic, less side effects • Orally active at lower doses Oral Dydrogesterone Dose : 20 – 30 mg orally per day
  21. 21. • Not too early / not too late – both are detrimental • Acceptable window 0f 24 – 48 hrs after oocyte retrieval / release • From the same day/next day of IUI When to Start ?
  22. 22. • 300-600 mg / day seen to provide same effect as with 90 mg of vaginal gel • Most studies demonstrated equal efficacy involving 600 mg micronized vaginal progesterone •25-50 mg of progesterone intramuscularly daily How much?
  23. 23. Not established firmly Often continued unnecessarily till 12 week Most evidence based studies suggest to continue till 9 weeks gestation How long ?
  24. 24. - Optimal route of administration has not been established - Equal number of studies support both vaginal & intramuscular route - Recent Cochrane review concluded that no significant difference between different routes. Outcome of different studies remains controversial
  25. 25. • Exact mechanism not known • Single dose of 0.5 mg S/C on 6 th day after ICSI • Increases implantation rate, CPR per transfer, increases live birth rate Single dose GnRH agonist Addition of GnRH agonist to progesterone improved outcome of live birth, clinical pregnancy and ongoing pregnancy -- Cochrane 2011
  26. 26. • Most of the time, luteal cells are incompetent – HCG is not effective • HCG supplementation is effective when specific defect of post ovulatory secretion of LH exists Why HCG is not an ideal choice? 10,000 iu for ovulation and then 2500 u every 3-4 days HCG associated with higher risk of OHSS – Avoid it ( Cochrane 2011)
  27. 27. • When GnRH agonist is used as a trigger • When E2 levels are greater than 2500 on day of trigger • All Antagonist cycles Ostrogen in LPS
  28. 28. • Significant effect in favor of Progesterone • (Dydrogesterone) fares better than micronized progesterone • No evidence favouring a specific route or duration of administration of progesterone. • HCG, or hCG plus progesterone, was associated with a higher risk of OHSS. The use of hCG should therefore be avoided. Luteal phase support for assisted reproduction cycles COCHRANE 2011
  29. 29. • Benefit from addition of GnRH agonist to progesterone • Overall, the addition of other substances such as estrogen or hCG did not seem to improve outcomes Progesterone seems to be the best option as luteal phase support,
  30. 30. • Abnormal Luteal Phase may occur due to medical conditions – Thyroid and prolactin disorders . • Mid Luteal phase progesterone assessment and endometrial biopsy are presently being used by most Gynaecologists for diagnosis of LPD • No treatment for LPD has shown to improve pregnancy rates in unstimulated, natural cycles Take Home Message
  31. 31. • CC stimulated cycles – 50% have LPD but evidence does not support LPS • ALL PATIENTS OF IUI NEED LUTEAL SUPPORT • Micronized Vaginal progesterone at dose of 200-400 mg /day from day of IUI Take home message IUI
  32. 32. • IN ART LUTEAL SUPPORT IS A MUST • VAGINAL progesterone is equally efficacious and better tolerated than I.M. preparations • Adequate dosage – 600 mg must be prescribed to achieve better outcome Take Home Message For IVF - ICSI
  33. 33. 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 &