Recurrent Miscarriage (Fetal Wastage) by olliegoblue31

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     Recurrent Miscarriage                               Abortion: termination of pregnancy before
                                                         20 wks gestation calculated from the LMP
        (Fetal Wastage)                                    Early: prior to 12 wks
                                                           Late: between 12 and 20 wks
         By: Christina Hitchcock, MD
           Tacoma Family Medicine
                  April 2006

                Definitions                                          Definitions
Complete AB: spontaneous expulsion of all fetal and
placental tissue from uterine cavity
                                                         Threatened AB: uterine bleeding without
                                                         cervical change
Incomplete AB: passage of some but not all of the        Recurrent SAB: the loss of three or more
fetal or placental tissue                                pregnancies before 20 wks gestation
                                                         Septic AB: any type of abortion that is
Inevitable AB: uterine bleeding with cervical dilation
but without expulsion of any fetal or placental tissue   accompanied by uterine infection

Missed AB: fetal death without expulsion of any fetal
or maternal tissue for 8 wks thereafter

                                                    15-20% of all known pregnancies terminate in
                                                    clinically recognized abortions (sporadic)
                                                    Reproductive Hx is most important factor
                                                       Abortion rate 5% in women with prior h/o
                                                       successful pregnancy
                                                       Abortion rate 25% in women with prior h/o
                                                       abortions (50% with prior >4 abortions)
                                                    80% abortions occur in 1st trimester

              Incidence                             Incidence of Pregnancy Loss
Incidence of loss is 2-3% when fetal cardiac
activity seen; 15% loss with fetal cardiac                       Live Births    25%
activity and uterine bleeding
                                                                                        Clinical Pregnancies
Increases with maternal age                                 Miscarriage        12-15%
  Under age 30: 7-15%
  Ages 30-34: 8-21%                            Early Pregnancy Loss             30%

  Ages 35-39: 17-28%                                                                          Pre-Clinical loss
                                               Failure of Implantation          30%
  Age 40 & older: 34-52%

    Risk of Early Pregnancy Loss in
             Young Women
                      # prior SAB         %Risk of SAB next pregnancy   Genetic
 Women who had at least        0                     12 %
 one live born infant          1                     24 %               Immunologic
                               2                     26%
                               3                     32 %               Endocrinopathies
                               4                     26 %
                               6                     53 %               Alloimmunopathology
                                                                        Inherited thrombophilias
Women who have not had at     2 or more              40-45%
least one live born infant:                                             Environmental exposures

                              Genetics                                                Genetics
   Major cause for abortion
     50% of 1st trimester losses, 30% of 2nd trimester                  Types of Anomalies in descending order:
     and only 3% of stillbirths
   Newer analyses not dependant on cell culture (i.e,                     Autosomal trisomy (13-16, 21 or 22): 50%
   FISH) suggest 75% of miscarriages have abnormal                        Monosomy, 45 X most common
   90% are numerical: aneuploidy/polyploidy                               Triploidy: 15%
   Remainder are structural abnormalities

        Anatomic Factors                       Anatomic: Congenital Anomalies

Congenital malformations                       Unicornuate uterus
                                                  50% of clinical recognized pregnancies fail
Uterine leiomyomas
                                               Uterine Didelphys
Uterine synechiae                                 40% pregnancies miscarry
                                               Bicornuate uterus
                                                  30-40% pregnancies miscarry
                                               Septate Uterus
                                                  Incomplete resorption of medial septum
                                                  Most common uterine developmental anomaly, 80—

       Congenital Defects
DES exposure
  Stopped in 1971, most women are beyond
  reproductive years
  Caused T shaped uterus most commonly
  Constriction rings and hypoplastic uterus
  also seen
  Two-fold higher risk of SAB, 9 fold higher
  risk of ectopic pregnancy
Cervical Incompetence

                                                        Acquired Anatomic Defects
                                                           May be some benefit to removal of subserosal
                                                           fibroids in those with recurrent loss
                                                        Intrauterine Adhesions (Asherman’s syndrome)
                                                           Filling defects on HSG
                                                           Treatment: hysteroscopic LOA, placement of
                                                           foreign body (IUD), high dose estrogen (CEE 2.5
                                                           mg po BID) followed by provera withdrawal in 60d
                                                           Abortion rate 40-80% and approx 25% preterm
                                                           deliveries before surgical correction
                                                           50-90% complete term delivery, 7-23% end in

         Endocrine Causes                                        Endocrine Causes
Progesterone Deficiency                                 Thyroid Disorders
   CL makes progesterone for 7 wks to support             No definitive evidence that hypothyroidism
   endometrium                                            causes SAB
   HCG dependent progesterone production by               Antithyroid antibodies are risk markers for
   trophoblasts                                           miscarriage but euthyroid women may also
   DX made if mid luteal (D21) level < 10ng/ml or EMB     have these
   is discrepant of >3days for 2 cycles
   RX: progesterone vaginal suppository (25mg BID),
   IM at 12.5mg/d starting 3 d after ovulation
                                                          Increased risk of SAB with uncontrolled
                                                          DM, elevated blood glucose and
   Meta-analysis shows no benefit of progesterone in
                                                          glycosylated hemoglobin levels
   those with 2 or more losses

        Endocrine Factors                                    Immunologic Factors
PCOS                                                   Antiphospholipid Syndrome:
  LH hypersecretion induces hyperandrogenism             Usually 1st tri loss but can occur in 2nd tri
  Hyperinsulinemia and increased levels of PAI
  activity increase pregnancy loss (30-50%)
                                                         Lupus anticoagulant
  Metformin an insulin sensitizing drug helps induce     Anti-cardiolipin antibody, IgM & IgG types
  ovulation and decrease PAI levels                      Antibodies inhibit prostacyclin production
  Losses: 26% treated vs. 62% untreated group            from endothelial tissue, resulting in a
  In those with recurrent losses: Miscarriage at 11%     relative excess of thromboxane
  treated vs. 58% not treated with metformin             thrombosis
  Metformin category B

      Immunologic Factors                                     Infectious Factors
Antiphospholipid antibodies:                           Ureoplasma
  15% of women with recurrent abortion of              Mycoplasma
  undetermined etiology have antibodies
                                                       Toxoplasma gondii
  DX: Need 2 levels at least 2 months apart
                                                       Listeria monocytogenes
  RX: ASA (81 mg) + heparin (5000 SQ BID)
  Live Birth rate 70-80% compared to those
  on ASA or no treatment (20-40%)                      Herpes
  Pregnancy complications: PTL, PROM, IUGR,            Cytomegalovirus
  fetal demise, preeclampsia and placental

        Infectious Factors                                     Infectious Factors
HSV                                                    Bacterial vaginosis
  Infection in 1st half of pregnancy results in          In one study, BV at 1st prenatal visit before
  abortion rate of 34%                                   14 wks gestation was associated with 5-fold
  Infection within 18 months prior to                    increased abortion
  conception results in abortion rate of 55%
                                                         In another study where IVF used in
Ureoplasma ureolyticum                                   infertile women: no difference between
  Endometrial colonization up to 30% in                  conception rates in women with and without
  recurrent abortion                                     BV but those had a 2 fold increase risk of
  RX: tetracycline x 10 d reduces subsequent             loss
  abortion rate

     Environmental Factors                               Inherited Thrombophilias
                                                       Coagulation factors:
Alcohol                                                  Favor clotting when increased
   Exceeding 2 drinks/d doubled risk of loss                Fibrinogen
   Known teratogen                                          Factors VII, VIII, X
Smoking                                                  Favor clotting when decreased
   Dose dependent, Even as few as 10 cigs/d                 Antithrombin III
                                                            Protein S
   MOA: vasoconstrictive, antiembolic lead to
                                                            Protein C
   placental insufficiency
                                                       Fibrinolysis factors:
   Increase loss of chromosomal normal abortuses
                                                          Favor clotting when increased: Plasminogen,
                                                          plasminogen activator inhibitor
   Consumption greater than 300 mg/d (3 cups of
                                                          Favor clotting when decreased: Antiplasmin
   coffee) associated with modest risk (less than 2-
   fold) increase in loss

  Inherited Thrombophilias                         Inherited Thrombophilias
Maternal villous blood flow does not develop     Available evidence suggests that
to any degree before 8 wks: thrombosis           thrombophilias predispose to a higher risk of
related to a thrombophilia is less likely to     loss.
explain early pregnancy loss                     Evidence also demonstrates reproductive
In a prospective study, live birth rate in       performance is entirely normal for many
untreated women with recurrent loss and          women who carry thrombophilia
heterozygous for Factor V Leiden (38%) was       At present time, it cannot be established who
substantially lower than among women with        among women with recurrent pregnancy loss
similar reproductive histories having a normal   that carry a thrombophilia is truly at
Factor V genotype (69%)                          increased risk for pregnancy loss

              Evaluation                                         Evaluation
Anembryonic heart activity observed before       H&P exam, especially obstetrical history, cervical
any earlier pregnancy loss
Normal karyotype on products of conception       TSH
from an earlier loss                             D21 LH
Female partner age over 35                       D21 Progesterone
Infertility                                      Homocysteine levels
                                                 Antithyroid antibodies
2 or more consecutive losses                     Lupus Anticoagulant
Do after one 2nd trimester loss                  Anticardiolipin antibody
                                                 Activated protein C resistance

If blood work is normal, evaluate for
  HSG, sonohysterogram or hysteroscopy
  Karyotype of couple
30-40% of couples with idiopathic recurrent
Psychological support during early pregnancy
improves live birth rate (50% vs. 80%)

              Treatment                                     Treatment
Threatened AB:                                 Inevitable AB and Incomplete AB:
  No evidence that bed rest improves             Usually between 8-14 wks
  outcomes                                       Usually presents with vaginal bleeding and
  If anembryonic gestation of intrauterine       pain
  fetal death, may offer prostaglandin tx        Suction D&C with IV sedation and
  (misprostol 200 mcg PO q 4h x4 doses) or       paracervical block safest
  surgery                                        Methergine 0.2mg PO q4-6 hr x1-2 d
                                                 Rhogam for Rh negative patients

Septic AB:
  Fatality rate 0.4-0.6 per 100,000 SAB’s
  Order CBC, UA, CMP, culture of uterine
  discharge, gram stain
  DIC panel, CXR, and blood cultures in ill
  appearing patients
  Broad spectrum antibiotics
  D&C after adequate blood levels of
  antibiotics are obtained (usually within 2

                                                Medical Termination of Pregnancy

                                                 Provider requirements
                                                   Make an accurate assessment if gestational
                                                   Diagnose ectopic pregnancy
                                                   Provide surgical intervention or make
                                                   provision to provide such care when needed
                                                   Assure patient access to medical facilities
                                                   equipped to perform blood transfusions and
                                                   resuscitation when needed

                                                             Question #1
  Medical Termination cont
Side effects:                                    A 21 yr old married Hispanic female who is
                                                 using no method of contraception presents to
   Excessive bleeding
   GI discomfort (nausea, vomiting, diarrhea)    your office for evaluation of vaginal spotting
   Headache                                      six wks after her last menstrual period. Her
   Dizziness                                     periods have previously been regular. She has
   Back Pain                                     had one previous episode of pelvic
   Fever                                         inflammatory disease. A home pregnancy test
                                                 is positive.
Efficacy 92-98% prior to 49 days gestation

Which one of the following is
                                                             Question #2
A) Serum HCG levels should double every 2-3      A 22 yr old G2P1 presents to your office with
days if the pregnancy is viable                  a 1 day history of vaginal bleeding and
B) Painless bleeding excludes the diagnosis of   abdominal pain. Her LMP was 10 wks ago, and
ectopic pregnancy                                she had a positive home pregnancy test 6 wks
C) Laparoscopy should be performed to            ago. She denies any passage of clots. On
exclude ectopic pregnancy                        pelvic examination, you note blood in the
                                                 vaginal vault. The internal cervical os is open.
D) A serum progesterone level >25 ng/ml
indicates that ectopic pregnancy is likely

Which one of the following
best describes the patient’s
     current condition?
A) Inevitable abortion
B) Completed abortion
C) Threatened abortion
D) Incomplete abortion
E) Missed abortion


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