Management of early pregnancy in ART (ectopic pregnancy & miscarriage) 奇美醫院 蔡永杰 TSRM

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1 Management of early pregnancy in ART (ectopic pregnancy & miscarriage) 奇美醫院 蔡永杰 TSRM

2 Contents Pregnancy of unknown location Ectopic pregnancy is a potentially life-threatening condition. While surgical approaches are the mainstay of treatment, advances in early diagnosis facilitated the introduction of medical therapy with methotrexate. Management of miscarriage Miscarriage is a common complication of early pregnancy that can have both medical and psychological consequences

3 Schematic diagram summarizing the potential factors contributing to the development of tubal ectopic pregnancy Human Reprod Update, 2010

4 Risk factors of ectopic pregnancy Chlamydia trachomatis Cigarette smoking In vitro fertilization: IVF (approximately 2 5%) Spontaneous pregnancy (approximately 1 2%) technique of embryo transfer number of embryos that are transferred altered endocrine environment tubal factor infertility embryo factor:the cell adhesion protein, E-cadherin Human Reprod Update, 2010

5 Schematic diagram summarizing the potential factors contributing to the development of tubal ectopic pregnancy Human Reprod Update, 2010

6 DIAGNOSIS The diagnosis is usually made clinically, based upon results of the imaging studies (ultrasound) and laboratory tests (hcg) Progesterone Curretage Doppler Laparoscopy Culdocentesis Magnetic resonance imaging

7 Discriminatory zone The discriminatory zone is based upon the correlation between visibility of the gestational sac and the hcg concentration. It is defined as the serum hcg level above which a gestational sac should be visualized by ultrasound examination if an intrauterine pregnancy is present. In most institutions, this serum hcg level is 1500 or 2000 IU/L with TVS Obstet Gynecol 1981; 58:156

8 Pregnancy of Unknown Location (PUL) A negative ultrasound examination at hcg levels below the discriminatory zone is consistent with an early viable intrauterine pregnancy or an ectopic pregnancy or nonviable intrauterine pregnancy. 8 to 40 percent are ultimately diagnosed as ectopic pregnancies Ultrasound Obstet Gynecol 2005; 26:770.

9 Fertil Steril 1998:70(5): Serum human chorionic gonadotropin measurement in the diagnosis of ectopic pregnancy when transvaginal sonography is inconclusive A cutoff level of 1,500 IU/L is recommended for patients with an ectopic mass or fluid in the pouch of Douglas. In patients without these findings, the cutoff level should be at least 2,000 IU/L.

10 HCG above the discriminatory zone If TVS does not reveal an intrauterine pregnancy and shows a complex adnexal mass, an extrauterine pregnancy is almost certain. Repeat the TVS examination and hcg concentration two days later. If an intrauterine pregnancy is still not observed on TVS, then the pregnancy is abnormal. An ectopic pregnancy can be diagnosed if the serum hcg concentration is increasing or plateaued. A falling hcg concentration is most consistent with a failed pregnancy (eg, arrested pregnancy, blighted ovum, tubal abortion, spontaneously resolving ectopic pregnancy

11 HCG below the discriminatory zone A serum hcg concentration less than 1500 IU/L should be followed by repetition of hcg in three days to follow the rate of rise. HCG concentrations usually double every 1.4 to two days A normally rising hcg concentration should be evaluated with TVS when the hcg reaches the discriminatory zone. At that time, an intrauterine pregnancy or an ectopic pregnancy can be diagnosed.

12 Progesterone A meta-analysis of 26 studies on the performance of a single serum progesterone measurement in the diagnosis of ectopic pregnancy found that a level less than 5 ng/ml (15.9 nmol/l) was highly unlikely to be associated with a viable pregnancy: only 5 of 1615 patients (0.3 percent) with a viable intrauterine pregnancy had a serum progesterone below this value Progesterone level greater than 20 ng/ml (63.6 mmol/l) reasonably excluded an ectopic pregnancy: only 29 of 1107 patients (2.6 percent) with ectopic pregnancies had a progesterone level above this value. Hum Reprod 1998; 13(11):3220-7

13 Serum P4 Con. Gp A1 pts who conceived after COH for IVF or IUI; Gp 2 pts who conceived after OI ; Gp A3 pts who conceived spontaneously; Gp B spontaneously pregnant ER pts who presented with pain or bleeding. SA spontaneous abortion; VIUP viable intrauterine pregnancy Fertil Steril 2000; 73:499

14 Comparison of serum progesterone as an indicator of pregnancy nonviability in spontaneously pregnant emergency room and infertility clinic patient populations The predictive value of a low serum progesterone for identifying nonviable pregnancies varies with the patient population. The sensitivity and specificity of a low serum progesterone concentration for predicting a nonviable pregnancy in spontaneously pregnant patients are different from those in infertile patients who have undergone controlled ovarian hyperstimulation for IVF or intrauterine insemination Fertil Steril 2000; 73:499

15 Pregnancy of Unknown Location (PUL) Prediction of spontaneous resolution Progesterone < 20 nmol/l Daily hcg decrease > -5% Sensitivity 73% Specificity 97% Positive predictive value 97% Hum Reprod 1995; 10:1223-7

16 Interventions for tubal ectopic pregnancy (Review) Petra J Hajenius 1, Femke Mol 2, BenWillem J Mol 3, Patrick MM Bossuyt 4, Willem M Ankum 5, Fulco Van der Veen 6 1 Academic Medical Centre, Obs Gyn, University of Amsterdam, Amsterdam, Netherlands. 2 Obs Gyn,Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands. 3 Obs Gyn, Máxima Medical Center, Veldhoven, Netherlands. 4 Depart Clinical Epide Bios, Academic Medical Center, University ofamsterdam, Amsterdam, Netherlands. 5 Depart Obs Gyn Academie Medical Center, Amsterdam, Netherlands. 6 Center for Reprod Med, Depart Obs Gyn, Academic Medical Center, Amsterdam,Netherlands 2009, Issue 1

17 Interventions for tubal ectopic pregnancy (Review) Search strategy Cochrane Menstrual Disorders and Subfertility Group s Specialised Register, Cochrane Controlled Trials Register Current Controlled Trials Register MEDLINE Selection criteria Randomized controlled trials (RCTs) comparing treatments in women with tubal ectopic pregnancy. Main results Thirty five studies have been analyzed on the treatment of tubal ectopic pregnancy, describing 25 different comparisons 2009, Issue 1

18 Comparison laparoscopic salpingostomy versus salpingostomy by open surgery, primary treatment success 2009, Issue 1

19 Comparison laparoscopic salpingostomy versus salpingostomy by open surgery, persistent trophoblast 2009, Issue 1

20 Comparison laparoscopic salpingostomy versus salpingostomy by open surgery, tubal patency. 2009, Issue 1

21 Comparison laparoscopic salpingostomy versus salpingostomy by open surgery, subsequent intrauterine pregnancy 2009, Issue 1

22 Comparison 1 laparoscopic salpingostomy versus salpingostomy by open surgery, repeat ectopic pregnancy 2009, Issue 1

23 Comparison salpingostomy without tubal suturing versus salpingostomy with tubal suturing,primary treatment success 2009, Issue 1

24 Comparison salpingostomy without tubal suturing versus salpingostomy with tubal suturing, tubal patency rate 2009, Issue 1

25 Comparison salpingostomy alone versus combined with medical treatment, primary treatment success 2009, Issue 1

26 Comparison salpingostomy alone versus combined with medical treatment, tubal patency 2009, Issue 1

27 Comparison Systemic MTX versus laparoscopic salpingostomy, primary treatment success. Favor surgery Favor MTX 2009, Issue 1

28 Comparison Systemic MTX versus laparoscopic salpingostomy, Outcome tubal preservation 2009, Issue 1

29 Comparison Systemic MTX versus laparoscopic salpingostomy, Outcome tubal patency 2009, Issue 1

30 Comparison Systemic MTX versus laparoscopic salpingostomy, Outcome subsequent intra uterine pregnancy 2009, Issue 1

31 Comparison Systemic MTX versus laparoscopic salpingostomy, Outcome repeat ectopic pregnancy. 2009, Issue 1

32 Comparison local MTX versus laparoscopic salpingostomy, Outcome primary treatment success 2009, Issue 1

33 Comparison local MTX versus laparoscopic salpingostomy, Outcome tubal preservation 2009, Issue 1

34 Comparison local MTX versus laparoscopic salpingostomy, Outcome tubal patency 2009, Issue 1

35 Comparison local MTX versus laparoscopic salpingostomy, Outcome subsequent intra uterine pregnancy 2009, Issue 1

36 Comparison local MTX versus laparoscopic salpingostomy, Outcome repeat ectopic pregnancy. 2009, Issue 1

37 Comparison MTX transvaginally under sonographic guidance versus MTX under laparoscopic guidance, Outcome primary treatment success 2009, Issue 1

38 Comparison MTX transvaginally under sonographic guidance versus systemic single dose MTX im, Outcome primary treatment success 2009, Issue 1

39 Comparison single dose MTX versus fixed multiple dose MTX both im, Outcome primary treatment success. 2009, Issue 1

40 Comparison expectant management versus medical treatment, Outcome primary treatment success. 2009, Issue 1

41 Interventions for tubal ectopic pregnancy Authors conclusions In the surgical treatment of tubal ectopic pregnancy laparoscopic surgery is a cost effective treatment. An alternative non surgical treatment option in selected patients is medical treatment with systemic methotrexate. Expectant management can not be adequately evaluated yet. 2009, Issue 1

42 Management of Miscarriage

43 Miscarriage Definition: A pregnancy that ends before the fetus is able to live outside the uterus. Miscarriage rate: 10 to 20 % of pregnant women before 20 weeks 80 % of these occur in the first 12 weeks. Clin Obstet Gynaecol 2000; 14:839 By hormone level detection, early pregnancy found a total miscarriage rate of 31 percent. N Engl J Med 1988; 319:189

44 MISCARRIAGE RISK FACTORS Age Previous miscarriage Smoking : 10 cigarettes/day Alcohol :No amount of alcohol is known to be safe Fever Trauma Caffeine: > 500 mg/day Other causes infections medications radiation physical stresses environmental chemicals

45 Previous miscarriage Previous miscarriage Having a miscarriage in the past may increase the risk for a future miscarriage. 1 miscarriage future miscarriage is about 20 percent 2 miscarriage future miscarriage is about 28 percent 3 miscarriage future miscarriage is about 43 percent By comparison, only 5 percent of women whose previous pregnancy was successful miscarried in the next pregnancy.

46 Various types of miscarriage Threatened miscarriage vaginal bleeding early in pregnancy without other problems. The cervix is closed. Inevitable miscarriage The cervix is open, bleeding is heavy or increasing, and abdominal cramping is present. Incomplete miscarriage passed much of the pregnancy tissue, but some remains in the uterus Complete miscarriage passes all of the pregnancy tissue, common in miscarriages before 12 weeks Septic miscarriage miscarriage develop an infection in the uterus

47 Maternal age and fetal loss: population based register linkage study Anne-Marie Nybo Andersen, Jan Wohlfahrt, Peter Christens, Jørn Olsen, Mads Melbye British Medical Journal 2000;320:

48 Pregnancy outcomes by maternal age at conception in women in Denmark, BMJ VOLUME JUNE 2000

49 Fig 1 Risk of fetal loss from spontaneous abortion, ectopic pregnancy, and stillbirth according to maternal age at conception BMJ VOLUME JUNE 2000

50 Fig 2 Risk of spontaneous abortion according to maternal age at conception, stratified according to calendar period BMJ VOLUME JUNE 2000

51 Fig 3 Risk of spontaneous abortion in nulliparous and parous women according to maternal age at conception and number of spontaneous abortions in preceding 10 years BMJ VOLUME JUNE 2000

52 Fig 4 Risk of ectopic pregnancy according to maternal age at conception BMJ VOLUME JUNE 2000

53 Fig 5 Risk of stillbirth according to maternal age at conception BMJ VOLUME JUNE 2000

54 MISCARRIAGE DIAGNOSIS Ultrasound Yolk Sac Pseudo Sac

55 MISCARRIAGE TREATMENT OPTIONS Observation Medical treatment Surgical treatment

56 Expectant care versus surgical treatment for miscarriage(review) Kavita Nanda 1, Alessandra Peloggia 2, David A Grimes 1, Laureen M Lopez 1, Geeta Nanda 3 1 Behavior Biomed Research, Fam Heal International, Research Triangle Park, North Carolina, USA; 2 Campinas, Brazil;; 3 C/o Cochrane Pregnancy and Childbirth Group, School of Reprod Develop Med, Division of Perinatal and Reprod Med, The University of Liverpool, Liverpool, UK 2010, Issue 2

57 Search strategy Cochrane Pregnancy and Childbirth Group s Trials Register Cochrane Central Register of Controlled Trials PubMed POPLINE LILACS reference lists of reviews. 2010, Issue 2

58 Types of interventions Expectant management Excluded any surgical or medical treatment for miscarriage, but allowed bedrest, ultrasound examination,and antibiotics. Surgical management Such as manual vacuum aspiration,suction curettage, and sharp curettage (with or without dilation). 2010, Issue 2

59 Comparison Expectant care versus surgical treatment for miscarriage, Miscarriage not complete (up to 6 weeks) 2010, Issue 2

60 Comparison Expectant care versus surgical treatment for miscarriage, Needed (additional) surgical evacuation. 2010, Issue 2

61 Comparison Expectant care versus surgical treatment for miscarriage, Had surgery (clinical need or woman s preference). 2010, Issue 2

62 Comparison Expectant care versus surgical treatment for miscarriage, Localized pelvic infection. 2010, Issue 2

63 Comparison Expectant care versus surgical treatment for miscarriage, Mean (standard deviation) days of bleeding. 2010, Issue 2

64 Comparison Expectant care versus surgical treatment for miscarriage, Bleeding with need for transfusion 2010, Issue 2

65 Comparison Expectant care versus surgical treatment for miscarriage, Participant satisfaction with management 2010, Issue 2

66 Comparison Expectant care versus surgical treatment for miscarriage, Subsequent conception

67 Expectant care versus surgical treatment for miscarriage Authors conclusions Expectant management led to a higher risk of incomplete miscarriage, need for surgical emptying of the uterus, and bleeding. None of these were serious. In contrast, surgical evacuation was associated with a significantly higher risk of infection. Given the lack of clear superiority of either approach, the woman s preference should play a dominant role in decision making 2010, Issue 2

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