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) Incidence 50% of all conceptions fail (most unrecognized) 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 testosterone 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 donation 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) References 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.
Pages to are hidden for
"Recurrent Pregnancy Loss"Please download to view full document