1 / 99

What is recurrent miscarriage?

Pregnancy loss - notion, diagnostic s, treatment TO BE OR NOT TO BE Petar Ivanov, MD, PhD, Assoc. Prof., OB/GYNs Clinical Institute for Reproductive Medicine, IVF Unit Medical University Pleven, Biochemistry Department. Happy pregnant. Try again. Few week later Pain, bleeding loss.

samanthah
Download Presentation

What is recurrent miscarriage?

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Pregnancy loss - notion, diagnostics, treatment TO BE OR NOT TO BEPetar Ivanov, MD, PhD, Assoc. Prof., OB/GYNsClinical Institute for Reproductive Medicine, IVF UnitMedical University Pleven, Biochemistry Department

  2. Happy pregnant Try again Few week later Pain, bleeding loss Recover What is recurrent miscarriage? • Understanding • Definition • Classification • Pathogenesis • Investigation and Diagnosis • Treatment

  3. Terms . . . • Miscarriage ( = Abortion = Pregnancy loss) • Abortion (< 20 wg) • Pregnancy loss (3-42 wg) • Stillbirth (20-28 wg)

  4. Historical perspective • Sporadic miscarriage rate is 15% • RM rate 0.153 = 0.3-0.4%. • The actual prevalence of RM is 1-3%

  5. Recurrent Pregnancy Loss (RPL) - Definition • Occurrence of 2/3 or more clinically recognized consecutive or nonconsecutive pregnancy losses before 20 weeks from last menstrual period • Primary- No previous full term pregnancy • Secondary- At least one successful pregnancy

  6. Warburton D, Fraser FC: Am J Human Genet 16:1, 1964 Miscarriage Recurrence Risk

  7. Maternal Age and Risk of Miscarriage • 12 – 19 years • 20 – 24 years • 25 – 29 years • 30 – 34 years • 35 – 39 years • 40 – 45 years • >45 years • 13% • 11% • 12% • 15% • 25% • 51% • 93%

  8. Classification

  9. Classification • Pre-implantation RPL (3-4 wg) • Implantation PL (Recurrent Implantation Failure, RIF) (4-6 wg) • Embryonic Failure (6-8 wg) • First trimester loss (8-12-14 wg) • Second trimester loss (>14 wg)

  10. Mechanism miscarriage ? • Excessive oxidative stress • (Burton and Jauniaux J Soc Gynecol Investig 2004;11:342–5)

  11. Recurent Miscarriage Etiology Explained • Anatomic (Sporadic) 12%-16% • Endocrine 17%-20% • Luteal phase deficiency • Uncontrolled DM • PCOS • Immunological 10%-16% • Anti phospholipid syndrome • Environmental • Alcohol, Smoking • Genetic factors 3.5-5% Un-explained 50% • Thrombophilic • Infectious factors

  12. EGG 80% Venn diagram of the responsibilities of Reproductive Failure SPERM 10% UTERUS 10%

  13. Causes of Recurrent Pregnancy Loss

  14. Etiology - Environmental Factors • Confirmed association • Ionizing irradiation • Organic solvents • Alcohol • Mercury • Lead • Suspected association • Caffeine (> 300 mg/day) • Hyperthermia/fever • Cigarette smoking • Unknown association • Pesticides Gardella & Hill Semin Reprod Med 2000;18(4):407-424

  15. Diagnostic x-rays Air travel Microwave ovens Diagnostic ultrasounds Electromagnetic fields Video display terminals Aspartame Chocolate Drinking water BGH Phytoestrogens Phthalates Herbicides Hair dyes Nail polish Saccharin Etiology - Environmental Factors

  16. Anatomical Factors • What are the congenital & acquireduterine anomalies leading to RSA? • How will you manage?

  17. Uterine Abnormalities • CONGENITAL (Mullerian Duct abnormalities) • UTERINE NEOPLASMS (Growth) • IATROGENIC (Acquired)

  18. ANATOMICAL CAUSES • Septateuterus (early pregnancy loss) • Bicornuateut (unequal horns)(second trimester pregnancy loss) • Unicornuate uterus • T shaped uterus • Submucousfibroids • Large endometrial polyps • . . . Adenomyosis . . . . . . . • . . .Cervical insufficiency . . . • . . .Intrauterine adhesions . . .

  19. How they affect……. • Smaller Uterine Cavities • Fewer suitable implantation sites • Aberrations of vascularisation • May be accompanied by cervical incompetence Lead to both early & later pregnancy losses

  20. Septate Uterus • Most COMMON anomaly 55% • May be complete/ incomplete/segmental 25% early abortions 6.2% late abortions & Premature labors

  21. Unicornuate Uterus • 20% of anomalies • Agenesis or hypoplasia of one Mullerian duct • May be alone or accompanied by Rudimentary horn With presence / absence of cavity Communicating / Non communicating • Associated Renal anomalies occur in 40% patients Ipsilateral to hypoplastic horn

  22. Unicornuate Uterus • Abortion Rate 51%, Premature labours, malpresentations, IUGR, Uterine rupture & ectopic pregnancies common • Cervical encerclage to improve pregnancy outcome • Rudimentary Horn resected to prevent dysmenorrhoea, haematometra,ectopic pregnancy

  23. Uterus Didelphys • Least common anomaly -5-7% • Failure of lateral fusion of uterus & vagina • Abortion rate 43%, Premature birth rate 38% • Resection of Vaginal septum if there is difficulty in intercourse / vaginal delivery • Strassmann Operation not indicated

  24. Bicornuate Uterus • 10% of anomalies • Incomplete fusion of Uterine horns at level of fundus • Two separate but communicating endometrial cavities • Abortion rate 32% Preterm labour 21% • Strassman Metroplasty / Place IUCD in one horn

  25. Arcuate Uterus • Near complete resorption of u-v septum • Mild concave indentation at fundus • ? Anomaly / ? Anatomic variant • Data conflicting Abortion rates ?45% ?13% • Treatment expectant

  26. T shaped Uterus • Diethylstilbestrol treatment for Premature labour started 1940 Banned 1970 • 69% female foetuses suffered Uterine anomaly • T-Shaped uterus, small uterus, constriction rings, • Cervical hypoplasia, cervical incompetence, Anterior Cervical collar, pseudopolyps • 2 fold increase in abortion rates & 9 fold increase in Ectopic pregnancy rates

  27. Uterine Neoplasms • Endometrial Polyps

  28. Leiomyomas (Fibroids) most common…. 20-50% of reproductive women When will you considerfibroids responsible ?

  29. Preconception myomectomy to improve reproductive outcome can be considered on an individual basis • It is likely to have a place only in women who have recurrent pregnancy loss, • large submucosal fibroids, and no other identifiable cause for recurrent miscarriage Ouyang DW, Obstet Gynecol Clin North Am. 2006

  30. Iatrogenic… Intrauterine adhesions ,“Asherman’s Syndrome” • Lead to Poor implantation, • Decreased blood supply , • infection Abortion rates 40% Preterm labour 23% Management :-Hysteroscopic excision of adhesions

  31. HYSTEROSCOPIC CORRECTION • All of the above have a good pregnancy rate post hysteroscopic correction • ExceptASHERMANS SYNDROME

  32. Cervical insufficiency - Causes Congenital • Mullerian tube defects (bicornuate uterus, septate uterus, unicornuate uterus) • Diethylstilbestestrol exposure in utero • Abnormal collagen tissue (Ehlers Danlos syndrome, Marfans syndrome ) Acquired • Forceful mechanical cervical dilatations • Cervical lacerations • Cervical cone or LEEP procedure (IATROGENIC) Alimentary/Life style Smoking Cu, vit C deficiency

  33. Anatomical Factors • When will you label a patient as a case of incompetent Cervix? • What are the different surgical procedures? • Role of prophylactic surgery?

  34. USG follow up weekly in cases of prior 2nd trimester loss • Funneling of >25% cervical length and/or <2.5 cm cervical length before 24 weeks of pregnancy • Cervical cerclage reduces the rate of preterm birth Carp et al, 2007 • Emergency cerclage: beneficial if no infection or uterine contractions

  35. What is the miscarriage rate in patients with ADENOMYOSIS? • 11% • Mechanism: Nitric Oxide

  36. Genetic Etiology • Chromosomal 3.5%-5% • Fetal chromosomal abnormalities • Parentalbalanced chromosomal rearrangement • Single gene disorders • Alpha thalassemia major • Thrombophilia (fetal) • X linked dominant disorders

  37. Risk Factors for Karyotypic abnormalities Gestational age Higher in early gestation 90% in anembryonic preg/Blighted ova 50% at 8-11wk 30% at 16-19 wk 6-12% >20wk

  38. Risk Factors for RM • Advanced maternal age • Affects ovarian function, giving rise to a decline in the number of good quality oocytes, resulting in chromosomally abnormal conceptions that rarely develop further. • RM risk -75% in women >45years • Previous number of miscarriages

  39. Spontaneous Miscarriage (sporadic) • 10-15% of recognized pregnancies • Mostly sporadic; 80% losses in 1st 12 wks • 50-70% due to chromosomal anomalies • Autosomal trisomy 50-60% • 13,16,18,21,others • Monosomy X-20% • Triploidy –15% • Tetraploidy-5% • Unbalanced translocation-3-5%

  40. In Recurrent Miscarriage (RM) • Fetal chromosomal abnormality in only 25-32% of product of conception (POC) • This may be due to abnormalities in the egg, sperm or both. • The  most common chromosomal defects are Trisomy, Monosomy, Polyploidy • Sperm aneuploidy(13,18,21,X,Y ) directly influences the rate of aneuploidy in the conceptus (Carrell et al 2003)

  41. In Recurrent Miscarriage • Parental chromosomal abnormality (Balanced chromosomal rearrangements) • General population 6 in 1000 (0.6%) • RM4.1-11% *3-5% of couples with RSA are carriers of balanced chromosomal rearrangements

  42. Parental Chromosomal Abnormalities • Translocation (commonest) (1in 500) • Reciprocal [50%] • Robertsonian [24%] • Mosaicism for a numeric aberration[12%] • Inversion

  43. Diagnosis • Karyotype of the abortus ( fetal/placental tissue) • Peripheral blood Karyotyping of the parents in all couples with RM

  44. Karyotype of Products of Conception • No definite recommendations for routinely obtaining abortus karyotype (ACOG 2001) • Karyotype analysis of abortus tissue for couples with a subsequent second or third pregnancy loss(Hogge, et al 2003) • If abortus is aneuploid, maternal cause is excluded (ACOG, 2001) • If POC karyotype not possible, do parental karyotype

  45. Single Gene Disorders in RM • Second and 3rd trimester losses • Alpha Thalassemia • Myotonicdystrophy • X linked Dominant disorder • IncontinentiaPigmenti • Chondrodysplasiapunctata • Focal dermal hypoplasia of Goltz • Rett Syndrome • Aicardi Syndrome

  46. Single Gene Disorders in RM • FETUS thrombophilia • First and later trimester losses • Microthrombosis in placenta; Impaired uteroplacental circulation • Factor V Leiden gene mutation Evidence based Prothrombin G 20210A mutation inc. risk • Protein C,S deficiency • Antithrombin III No significant association • MTHFR C677T mutation • Combination of any of above-Increased risk

  47. Role of Infections

  48. Doubtful causes of RPL • TORCH infections • Endocrine and metabolic disease • Untreated adrenal hyperplasia, hypothyroidism & diabetes mellitus. • Exogenous causes • Environmental factors, alcohol, street drugs, anesthesia gases etc

More Related