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Luteaal phase support lifecare centre
- 1. LUTEAL PHASE SUPPORTIN ART -- & Recurrent Miscarriages Dr. Jyoti Bhaskar Dr. Jyoti Agarwal Dr. Sharda Jain Directors -
- 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. LPD is characterizedby failure to develop fully mature secretory endometrium LPD ----DEFINITION Decreased progesterone receptors in endometrium Inadequate Secretion of progesterone by Corpus luteum
- 4. Poor Secretory response InadequateLuteal 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. PROBLEMATIC AND CONTROVERSIAL as Nopractical diagnostic method has been validated LPD --- Diagnosis
- 6. LPD -- Diagnosis Whenthe 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. SONOGRAPHIC CRITERIA •Rupture offollicle < 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. 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. • Correction ofunderlying causes • Emperical – supplemental progesterone or HCG Treatment Ovulation induction strategies improve fertility by inducing multiple ovulation and not correcting LPD
- 10. • Confirmed casesof 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. • Supraphysiological estrogenlevels 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. Luteal Phase Insufficiencyin 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. • It wasonly 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. PROMISE PROgesterone in MIScarriagEtrial Newer Evidence is coming up as large multicentre study PROMISE is currency on the Way
- 15. – PROGESTERONE – HumanChorionic Gonadotropins – Estrogen and Progesterone – GnRH agonist – Adjuvants Luteal Support : Drug ?
- 16. It should beluteomimatic and not luteolytic Progesterone is the drug of choiceProgesterone is the drug of choice Ideal Drug
- 17. • Promotes secretarytransformation of the endometrium • It causes local vasodilatation • Induces uterine musculature quiescence How Does Progesterone Act?
- 18.
- 19. Oral Intramuscular Vaginal Easyroute 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
- 21. • Immunomodulator • Highaffinity 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
- 22. • Not tooearly / 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 ?
- 23. • 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?
- 24. Not established firmly Oftencontinued unnecessarily till 12 week Most evidence based studies suggest to continue till 9 weeks gestation How long ?
- 25. - Optimal routeof 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
- 26. • Exact mechanismnot 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
- 27. • Most ofthe 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)
- 28. • When GnRHagonist is used as a trigger • When E2 levels are greater than 2500 on day of trigger • All Antagonist cycles Ostrogen in LPS
- 29. • Significant effectin 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
- 30. • Benefit fromaddition 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,
- 31. • Abnormal LutealPhase 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
- 32. • CC stimulatedcycles – 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
- 33. • IN ARTLUTEAL 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
- 34. ADDRESS 35 , DefenceEnclave, Opp. Preet Vihar Petrol Pump, Metro pillar no. 88, Vikas Marg , Delhi – 110092 CONTACT US 011-22414049, 42401339 WEBSITE : www.lifecarecentre.in www.drshardajain.com www.lifecareivf.com E-MAIL ID Sharda.lifecare@gmail.com Lifecarecentre21@gmail.com info@lifecareivf.com &