Recurrent pregnancy loss _ a most common BOH.pptx

A case of recurrent pregnancy loss

1. RECURRENT ABORTION Dr Susanta Kumar Behera Assistant Professor

2. Spontaneous Abortion : Most common complication of pregnancy. 70 % of human conceptions fail to achieve viability 50 % are lost before the first missed menstrual period . RPL affects 0.5-2% of all women Relationship between PCOS and RPL : 20-25% increased risk for first trimester Miscarriage.

3. Advanced Maternal Age : Decrease number of good quality Oocytes , resulting in chromosomally abnormal conceptions that rarely develop further ↑ RPL in 1 st degree relatives of patients with unexplained RPL ( RUNS IN FAMILY)

4. Recurrent Abortion Three or more clinically recognized pregnancy losses before 20wks from LMP. Primary RPL : Couples that have never had a live birth Secondary RPL : Couples who have had repetitive losses following a successful pregnancy Clinical investigation : After two consecutive spontaneous abortions, especially when fetal heart activity had been identified prior to the pregnancy loss( when the women is older than 35 yrs of age)

5. Etiologies Unexplained 50% Genetic Factors Anatomic Factors Endocrine Factors Infectious Factors Immunologic Factors Other Factors RIF : Failure to achieve a pregnancy after 3 completed fresh IVF-ET cycles or failure to achieve a pregnancy after 3 IVF cycles, in which reasonably good embryos were transferred 50%

6. R epeated abortions genetic ( 5%) anatomy (6-12%) endocrine (15-20%) infections (5%) others: APCR cardiolipin unexplained 50-60%

7. Genetic Factors Balanced translocations : Most common Monosomy : In vitro fertilization Trisomy : (13, 18, 21) tolerated than monosomy . Inversion & insertions Inherited thrombophilias

8. Thrombosis on maternal side of the placenta I mpair placental perfusion Late fetal loss, IUGR, Abruption, or PIH

9. Anatomic Abnormalities Uterine( Mullerian Anomaly) Septate Uterus :Most common, Poorest outcome, Miscarriage > 60 % Subseptate Bicornuate Didelphus Hypoplastic uterus T-Shaped Uterus(DES) Acquired anomaly Adhesions Uterine fibroids- Submucosal Endometriosis-Tubal adhesion

10. SUBMUCOUS FIBROID

11. Endocrine Abnormalities Normal pregnancies : Luteal -Placental shift ( 7 to 9 weeks of gestation) LPD PCOS-Elevated androgen levels. DM - directly linked to embryonic damage Thyroid disease - Antithyroid antibodies(ATA ) Galactorrhea : Serum Prolactin

12. ENDOCRINE FACTORS LPD : Progesterone is essential for implantation and maintenance of pregnancy Diabetes mellitus Poorly controlled  early (and late) loss Mechanism Hyperglycemia Maternal vascular disease Immunologic factors (possible)

13. Insulin resistance PCOS : Miscarriage 20 - 40% vs. baseline rate 10 - 20% ↑ LH, Testosterone, and androstenedione  adversely affect the endometrium Thyroid disease and antibodies Poorly controlled hypo- or hyper- thyroidism ( Infertility & pregnancy loss) ↑ thyroid antibody, even if euthyroid . Hyperprolactinemia

14. Maternal Infections Bacterial Vaginosis TORCH Most common form : Mycoplasma Ureaplasma Chlamydia β- Streptococcus

15. Immunologic phenomena Placental Barrier consists of syncytiotrophoblast , cytotrophoblast and basement membrane. Cytotrophoblast are of two types e.g villious and extra villious / nonvillious Extravillous trophoblast migrates to uterine artery lumen. Cytotrophoblast responsible for implantation of embryo into decidua .

16. Syncytiotrophoblast is responsible for immunomodulation and endocrine function. Hormones released by Syncytiotrophoblast includes progesterone, leptin , HCG and HPL

17. Syncytiotrophoblast It contains white cells e.g lymphocytes(T and B) As it is a giant cell, prevents migration of foreign proteins to get into fetal circulation. Suppresses expression of immunity related genes like HLA-A & B(which are classically known to be expressed by nucleated cells) These genes express MHC-I ligand which act as a major binding mechanism for T-cell. By reducing translation of these genes Syncytiotrophoblast reduces chances of maternal immune system mediated by T-cells.

18. T-Cell MHC-I HLA-A & HLA-B SYNCITIOTROPHOBLAST

19. No presentation of internal or external antigens to the T cells without MHC Basement membrane contains Hofbauer cells which are capable of Phagocytosis & can trap maternal antibodies. Placenta probably offers immunological protection against rejection . - Steroid hormones have immunosuppressive effect. -VT don’t express HLA Class-I & Class-II molecules -EVT only express HLA class-I & No HLA class-II molecules .

20. Miscellaneous Environmental chemicals & stress Anesthetic gases (nitrous oxide), formaldehyde, pesticides, lead, mercury Personal habits  Obesity, smoking, alcohol, and caffeine Male factor Abnormal sperm

21. Time of evaluation of RPL Detected FHR in previous pregnancies. Maternal age >35. Infertility. . MANAGEMENT

22. History Characteristics of prior pregnancy losses History of S ubfertility or infertility Menstrual history Prior or current gynecologic or obstetric infections Sings or symptoms of thyroid, prolactin , glucose tolerance , hyperandrogenic disorders (PCOS) Personal or familial thrombotic history

23. Features associated with the antiphospholipid syndrome (thrombosis, false-positive test results for syphilis) H/o a utomimune disorder Medication Environmental exposures, illicit and common drug use (Caffeine /Alcohol/ Cigarettes/ DES ) Previous diagnostic tests and treatments

24. Physical examination a) Preconceptional - Obesity - Hirsutism and acanthosis - Thyroid examination - Breast examination and galactorrhea - Pelvic examination A natomy Infection Trauma(CI) Estrogenization (DES)

25. Investigations Complete blood count with platelets Thyroid-stimulating hormone level, Serum prolactin level, if indicated Anticardiolipin antibody level Lupus anticoagulant Parental peripheral blood karyotype Screening for Bacterial vaginosis Urine C/S

26. MRI/Pelvic USG TORCH Luteal -Phase endometrial biopsy HSG, followed by hysteroscopy or laparoscopy, if indicated

27. b) Postconception Evaluation C lose monitoring : confirm intrauterine pregnancy and its viability Serum levels of beta- hCG S erum   beta- hCG levels should be serially monitored from the time of a missed menstrual period until the level is about 1500 mIU / mL , at which time an ultrasonographic scan is performed and blood sampling is discontinued

28. USG examination Ultrasonographic assessment is then performed every 2weeks until the gestational age at which previous pregnancies were aborted CVS : 10-14 weeks ( transcervical / transabdominal ) Amniocentesis: 16-18 wks, fetal K aryotype after the pregnancy has progressed past the time of prior losses (Maternal serum for AFP)

29. Therapy Genetic abnormalities Anatomic Anomalies Endocrine Abnormalities Infection Immunologic Factors Antithrombotic Therapy Psychological Support

30. Genetic abnormalities A ntithrombotic therapy : I nherited thrombophilias ART, including PGD the removal of a single cell from an in vitro-matured embryo Genetic testing can be performed on this cell to rule out gross chromosomal abnormalities or the presence of specific genetic diseases genetically normal would be considered appropriate for transfer into the uterus . U se of either donor oocyte or donor sperm depending on the affected partner

31. Anatomic Anomalies Placement of a cervical cerclage for patients with a history of loss secondary to cervical incompetence performed early in the second trimester Hysteroscopic resection submucous leiomyomas , intrauterine adhesions, intrauterine septa, patients with DES exposure, hypoplastic uteri, complicating septal anomalies in the operating room, general anesthesia USG Guided transcervical metroplasty safe and effective, ambulatory, office-based procedures

32. Endocrine Abnormalities LPD: Stimulating folliculogenesis with ovulation induction and luteal -phase support with progesterone PCOS, hyperandrogenism , hyperinsullinemia Insulin-sensitizing agents Overt diabetes mellitus Pre pregnancy glycemic control H ypothyroidism thyroid hormone replacement with synthroid

33. Infection A n infectious organism has to be identified A ppropriate antibiotics should be administered to both partners Post treatment culture

34. Immunosuppressive Therapies To antiphospholipid antibodies and to inappropriate cellular immunity toward the implanting fetus Intravenous immunoglobulin Progesterone

35. IV immunoglobulin Mechanism decreased autoantibody production and increased autoantibody clearance D isadvantage expensive, invasive, and time-consuming, requiring multiple intravenous infusions over the course of pregnancy Side effects nausea, headache, myalgias , hypotension, anaphylaxis

36. P rogesterone Administered intramuscularly intravaginally

37. Antithrombotic Therapy Combined use of low-dose aspirin (75-80mg/dl) and subcutaneous unfractionated heparin ( 5000 unit twice daily) : APLA A spirin (75mg every day) beginning A fter pregnancy : 5000 IU Heparin is administered SC twice daily, throughout gestation. an aPTT should be obtained weekly I ncreased risk for preterm labor, PROM, IUGR,IUD, and preeclampsia. Gastric bleeding, O steopenia , and A bruptio placenta. LMWH

38. Psychological Support Guilty among patients with recurrent losses Major depression is increased greater than two fold among women with spontaneous pregnancy loss Caring and empathetic attitude is prerequisite to all healing. Prognosis Depends upon underlying cause of pregnancy loss the number of prior losses.

39. Chance of a viable birth even after four prior losses : 60% cytogenetic etiology : 20%-80% corrected anatomic anomalies : 60%-90% corrected endocrinologic abnormalities : higher than 90% women receiving therapy for antiphospholipid antibodies : 70% - 90%

40. Life style modification – high BMI Diet Exercise Pharmacological agents

41. UNEXPLAINED RPL  Lifestyle modification   Eliminating use of tobacco, alcohol, and caffeine & reduction in BMI (for obese women). Progesterone : w idely used emperically Human menopausal gonadotropin Correcting LPD or creating thicker endometrium IVF +/- PGD : Mixed results but Promising Prognosis : 30-40% risk of repeated Abortion .

42. Cervical Incompetence “Inability of uterine cervix to retain a pregnancy in the absence of contractions or labor” / “Painless cervical dilation” Normal : 25mm at 25 wks Not helpful to measure before 14 weeks Abnormal : CL <25mm between 14-24wk Shorter CL, the highest risk for PTB Dilatation of internal OS with herniation of membrane: Diagnostic

43. Cervical Insufficiency H/o of > 2 second-trimester pregnancy losses Hx of painless cervical dilation up to 4 cm Hx of cervical trauma caused by: D & C/D & E Cone Biopsy Intrapartum Cervical Lacerations Amputation of Cervix

44. Investigations Interval - Passage of no-8 hegars dilator beyond OS without resistance -HSG showing funneling of Cx Pregnancy -Cervical length <2.5 cm between 14-25 wks(TVS) -Width of int. OS > 1.5 cm with or without bulging membrane

45. Role of TVS in Cervical Insufficiency

46. Types McDonald Shirodkar Transabdominal Tocolytics Antibiotics Success rate : 80%

47. Prior : Anomaly to be ruled out & fetal growth is to be assessed Time : 14 wks or at least 2 wks earlier than lowest period of previous loss Advice on discharge Bed rest for 2-3 days Avoidance of intercourse Avoid journey Report if vaginal bleeding/abdominal pain occurs Follow up USG for fetal growth & condition of cervix

48. Contraindications Intrauterine infections Ruptured membranes H/o vaginal bleeding Severe uterine irritability Cervical dilatation > 4 cm Removal : 38wk or earlier if labor pain starts/features of abortion appear

49. Thank u