Recurrent pregnancy loss

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<ul><li>1.{ Recurrent Pregnancy Loss Dr. Priya Bhave Chittawar Professor and Head, Reproductive Medicine, Sri Aurobindo Institute of Medical Sciences </li></ul> <p>2. Dr. Priya Bhave Chittawar MBBS 1999( Gandhi Medical College, Bhopal): with distinction in 8 subjects and 15 gold medals. Awarded 'Dr.Vishal Vikram Singh Award' for highest marks in MBBS (1994-1999). President of India Dr. Shankar Dayal Sharma Award for the Best Outgoing student MBBS (1994-1999). Served in various capacities in the Students Union and awarded " Dr. Suresh Kak Memorial Award for best All Rounder MBBS 1994-1999) Fellowship in Reproductive Medicine (Christian Medical College, Vellore) 2008- 2010 : passed with distinction Awarded by the Chief Minister Shri Shivraj Singh Chouhan in June 2008 for exemplary work in emergency Obstetrics Best Paper award for thesis on Role of GnRH antagonists in IUI- ISAR 2010 Best Paper award in ISAR 2012 for paper on Hysteroscopic Management of adenomyotic myometrial cysts Author of Cochrane review ( Menstrual disorder and subfertility group) Author of Cochrane sexually transmitted infections group. 3. Nagpur Obs Gyne society Dr. D. K. Tank Foundation AOFOG Merck Serono Thanks! 4. The stories that end badly are sad, sadder still are the ones that never began. 5. What we know: KNOWN KNOWN What we know we do not know: KNOWN UNKNOWN What we know but do not do: UNKNOWN KNOWN What we do not know that we do not know UNKNOWN UNKNOWN OUTLINE. 6. Ohh No! 7. {Recurrent miscarriages The Known Known 8. Three or more consecutive miscarriages Risk of miscarriage in is 30% after 2 losses, 33% after 3 losses among patients without a history of a live birth. 15% sporadic miscarriage By chance alone 1 in 300 couples What? 9. Age Genetic : embryonic and parental Immune: autoimmune/alloimmune Anatomic Endocrine Others Why? 10. 12-19 year:13% 20 -24 year: 11% 25-30 year: 12% 31-35 year: 15% 36-40 year: 25% &gt;40 year: 50% Previous miscarriage Age 11. Nondisjunction during meiosis Autosomal trisomy, monosomy X, triplody, tetraploidy, translocations Incidence increases with maternal age 60% of conceptus Genetic: Embryonic 12. Carriers of balanced chromosomal abnormalities 3-5% of RPL couples Risk of severely handicapped child due to aneuploidy Chances of miscarriage greater than those of RPL couples who are not carriers ( 49% vs. 30%). (Franssen,BMJ;2006) Genetic: paternal 13. Balanced translocation: carrier 14. { Mechanism of abnormal embryonic karyotype in offspring of carriers of balanced translocations 15. Antiphospholipid antibody syndrome: 15% women with RPL vs 2% with low risk Obs. hist ACA, LA , anti beta2 glycoprotein 1 antibody Trophoblast function, activation complement at fetal maternal interface, thrombosis at placental villi Without heparin, LBR2.2%) (ESHRE) Parental Karyotyping 27. Low maternal age at second miscarriage, A history of three or more miscarriages A history of two or more miscarriages in a brother or sister A history of two or more miscarriages in the parents of either partner increase the probability of carrier status( Jauniaux, HR,2006) Parental Karyotyping 28. 1. Normal karyotype in the conceptus 2. Carrier status of same balanced structural abnormality 3. Unbalanced structural abnormality1% ( Miscarriage, Stillbirth, child with handicap) chances of having a healthy child are as high as for non-carrier couples (over 80%) Chances of subsequent miscarriage higher (50%) compared to non carrier couples with RPL (30%) (Franssen,BMJ;2006) Consequences of carrier state 29. LBR in PGD group 31% LBR in natural conception 55.5% Miscarriage rate in PGD group 0- 50% ( median 0%) Miscarriage rate in natural conception 34% ( Franssen, HR,2011) PGD for carrier couples 30. Cochrane: A statistically significant benefit in using hCG (risk ratio (RR) 0.51, 95% confidence interval (CI) 0.32 to 0.81; five studies, 302 women ( Jan 2013) HCG for RPL 31. { Generate evidence Evaluate evidence Apply evidence Read the fine print! 32. High heterogeneity ( 39%) After excluding data from poorly designed studies, revised RR 0.74 (CI 0.44 to 1.23). Small numbers Chromosomal analysis not carried out HCG for RPL 33. PROMISE trial underway 760 women randomised Immunomodulatory action: upregulate TGF- secretion in response to trophoblast, blocks Thl immunity to trophoblast. Upregulates STAR Myometrial relaxation Progesterone for RPL 34. Three small non randomized trials (Stray-Pederson, Liddel 1991, Clifford 1997) Control groups not matched and small No testing for APS Livebirth rates claimed to increase by 50% for groups receiving TLC Tender loving care 35. Combined aspirin/heparin treatment versus placebo in women with unexplained RM ( Kaandorp2010, NEJM) NO difference in LBR Significant side effects in treatment group Anticoagulation for unexplained RPL 36. HepASA trial: no difference in LBR between ASA alone versus ASA and heparin (Laskin, Journal of Rheumatology,2009) Trial stopped prematurely due to equivalent LBR in both groups. Anticoagulation for RPL with ANA/thrombophilia 37. {Recurrent pregnancy loss The Unknown Unknown.. 38. Real knowledge is to know the extent of ones ignorance 39. Luteal phase defect Early fetal demise and early embryonic demise Karyotying of POC Parental karyotyping HCG and progesterone for RPL TLC Anticoagulation for unexplained RPL Anticoagulation for ANA/thrombophilia 40. Type 1 unexplained RPL: occurring by chance Type 2 unexplained RPL: due to an underlying pathology that is not currently identified by routine clinical investigations or due to significant environmental and lifestyle risk factors. Younger women, higher order miscarriages (Saravelos, HR2012) Unexplained RPL 41. Now we know.. What we dont know 42. Think septum! A good 2D TVS. HSG/office hysteroscopy LBR 85% after septal resection. Doing what we know 43. Pool our knowledge and patient base Well designed RCT looking at treatments for RPL Multicentric Trying to know the unknown.. 44. When you know something, to hold that you know it. When you do not know a thing, to allow that you do not know it, this is knowledge Confuscious THANKS !!! </p>

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