Recurrent Pregnancy Loss by sammyc2007

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									Recurrent Pregnancy Loss
         Deepthi Foxhall
         August 3, 2005
       UCSF Family Practice
Case Presentation
   31 yo female, G3PO
       CC: questions regarding future pregnancies
       PMH: depression, chronic pelvic pain, and s/p
        breast cyst surgery
       Meds: PNV, prn Naproxen
       All: NKDA
       FH: No hypercoagulability, pregnancy probs
       SH: Married, stress d/t pregnancy losses
31 yo G3P0 with RPL
   Gynecologic History
       Menarche 15, Irregular menses q 4-6 weeks
       1998:       6 wk SAb, El Salvador
       1999:       12 wk SAb, El Salvador
       Brief OCP use, condoms for contraception
       2004:       11 wk SAb, SFGH
                    by U/S, CRL c/w 7 wk gestation,
                    Pathology with decidualized tissue, clot only
       Same partner; partner has prior children
       No infections, PID, surgery, instrumentation
31 yo G3P0 with RPL
   Exam
       119/70, 84, Wt 140 lbs
       Mildly anxious, no hirsutism
       HEENT, CV, Resp, Neuro, MSK WNL
       Abd: mild central obesity, TTP suprapubic
       Pelvic: Nl external, cervical appearance, no
        adnexal masses, tenderness, nl uterus size
        Pap pending, - GC, - CT, - UA
Recurrent Pregnancy Loss
   Definition
       3 or more consecutive pregnancy losses prior
        to 20 weeks
       not including ectopic, molar, biochemical
   Subclassification
       Primary vs. Secondary
       Pre-embryonic (<4), Embryonic (5-9), and
        Fetal (>10)
 50% of all conceptions fail (most
 13-15% of recognized pregnancies are
  lost, 90 % of these before 12-14 weeks
 10-20% of pregnant women have 1
  sporadic spontaneous abortion
 2% have 2 consecutive SAb
 0.4-1% have 3 consecutive SAb
Uterine Pathology
   10-50% of RPL via abnormal implantation and
    uterine distention
       Evaluation: Sonohysterography or
        Hysterosalpingogram; 2nd line tests include
        hysteroscopy, laparoscopy, transvaginal U/S or MRI
   Mullerian anomalies of septate, bicornuate,
    didelphic uteri (not arcuate)
       Hysteroscopic or transfundal surgery
   Submucous leimyoma >>intramural or subserous
       Hysteroscopic or abdominal myomectomy
   Intrauterine synechiae (Asherman’s)
       Hysteroscopic lysis of adhesions
   Cervical incompetence - midtrimester
       Cervical cerclage
Hypercoagulable States
   Antiphospholipid syndrome
       5-15 % of RPL, as well as late fetal death
       History of thromboembolism or pregnancy
        complication with high titers of anti-cardiolipin
        antibody and/or lupus anticoagulant
       Evaluate with IgG and IgM ACA and APTT, PTT-
        LAC, or Russell’s viper venom time; tests may
        need to be repeated after 6-8 weeks
       Treat with heparin (5,OOO-10,000 units BID)
        and aspirin (81 mg)
Hypercoagulable States
   Other Thrombophilias
       More often cause fetal death or at least > 10
        weeks, but may play a role in RPL
       Factor V Leiden > prothrombin mutations,
        protein S deficiency >> protein C deficiency,
        antithrombin deficiency, hyperhomocystinemia
        from MTHFR mutation
       Treatment: no good evidence, consider ASA
        depending on the defect and risk/benefit
Endocrine Disorders
   15-60 % of RPL
   Poorly controlled diabetes with HgA1c > 8
       Routine eval and management, esp metformin
   Insulin resistance +/- PCOS
       History or GTT and metformin off-label use
       Few, small studies of metformin show no obvious SE on
        fetus, and some evidence of benefit in fertility, RPL, and
        gestation DM
   PCOS via insulin resistance, high LH or
       Metformin trial, but some authors argue that main
        problem is infertility not pregnancy loss and poor data
Endocrine Disorders
   Ovarian reserve for women of any age
       Day 3 FSH and estradiol
   Poorly controlled thyroid disease and potentially
    subclinical hypothyroidism
       TSH screening and management
   High antithyroid peroxidase Ab
       But not treatable, so not part of routine screen
   Hyperprolactinemia
       History with prolactin level and Bromocriptine
   Historically luteal phase defects
       Diagnosis in question and suggested treatments not
        effective, but source of progesterone trial
Immunologic Factors
 Alloimmune reaction of mother to
  “foreign” tissue of embryo
 HLA-mediated factors
 Poorly understood mechanisms, but areas
  of increasing research
       Evaluation: no specific tests
       Treatment: historically several treatments,
        but recent meta-analyses show no significant
        benefit to any of these
Chromosomal Factors
   2-4% of RPL with chromosomal rearrangement:
        ½ balanced translocation; ¼ Robertsonian
        translocation; other sporadic mutations, inversions
       Evaluation: Parental karyotype and karyotype of
        abortus if possible
       Treatment: Genetic counseling; IVF with
        preimplantation screening of embryos or gamete
   Even when normal parental genotype:
       Risk of subsequent chromosomally abnormal SAb
        increases when prior abnormal SAb
       Possibly due only to increased maternal age
Environmental Factors
 No good evidence for recurrent SAb
 Sporadic pregnancy loss affected by
       Smoking, alcohol, anesthetic gases, caffeine >
        300mg/day, obesity, NSAID use
       Evaluation: history
       Treatment: weight loss and avoidance as few
        risks, adverse effects
Evaluation Basics
   H&P
       Gestational age and characteristics of SAb
       Gyn infections or instrumentation
       Galactorrhea, obestiy, hirsutism, irreg menses
       Venous Thrombosis or FH of VTE/preg loss
       Environmental exposures
       Consanguinity, FH of birth defects
       Standard vaginal exam
Evaluation Basics
   Testing
       Hysterosalpingogram/sonohysterography
       Anticardiolipin, lupus anticoagulant, factor V
        Leiden, (prothrombin, activated protein C
        resistance, protein S deficiency)
       TSH, Day 3 FSH and estradiol concentrations
       Possibly luteal phase endometrial biopsy
       Parental karyotype (if other tests wnl)
       Other specific tests if suggested by H & P
   Etiology discovered in only 50% of cases
Management Basics
   Treatment based on + workup, if possible
   If multifactorial, can discuss with patient to treat
    all factors at same time or in stepwise manner
   When unexplained RPL:
       Counseling: 50% successful pregnancy, but recurrence
        risk rises with each subsequent loss
       Eliminate tobacco, caffeine, alcohol; Weight loss
       ?Progesterone 50-100 mg vaginally BID
       ?Metformin 500 mg TID/Clomid 50 mg on D 5-9
       IVF with preimplantation genetic dx or oocyte donation
   In pregnancy, greatest risk is prior to dates of
    previous miscarriage, but also some increase in
    fetal growth restriction, preterm delivery and
    perinatal loss.
31 yo G3P0 with RPL
   Studies
       Anticardiolipin Abs                        Negative X 2
       Russel Viper Venom for Lupus Anticoagulant Negative X 2
       Factor V Leiden                            Negative
       MTHFR                                      Homozygous
       Prothrombin                                Negative

       FSH     5.7 (wnl)             Estradiol      25 (wnl)

       HSG with anteverted uterus, nl anatomy, nl fallopians
31 yo G3P0 with RPL
   Plan
       Reassurance that 50% of women go on to
        have live birth even without treatment
       Further testing: TSH, parental karyotype
       Since pt also has anovulatory/infertility
        component, Clomid  Metformin + Clomid
       MHTFR homozygosity  ASA 81 mg
       Consider progesterone trial (less likely)
       IVF/oocyte donation (cost problems)
   Al-Fozan H, Tulandi T. Incidence and etiology of recurrent
    pregnancy loss. UpToDate v 13.2, May 2005.
   Barbieri, RL, Ehrmann DA. Metformin for treatment of the
    polycystic ovary syndrome. UpToDate v 13.2, April 2005.
   Christiansen OB, Nybo Anderson AM Bosch E, Dava S,
    Delves PJ, Hviid, TV, Kutten WH, Laird SM, Li TC, van der
    Ven K. Management of recurrent pregnancy loss. Fertility
    and Sterility. Vol 83 (4), April 2005: 821-839.
   Porter TF, Scott JR. Evidence-based care of recurrent
    miscarriage. Best Practice and Research Clinical Obstetrics
    and Gynecology. Vol 19 (1), Feb 2005: 85-101.

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