Prior authorization request form Form

Recurrent Pregnancy Loss

Last Review Date: March 13, 2026 
Number: MG.MM.ME.52cC4

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Definitions Recurrent pregnancy loss (RPL) — aka recurrent spontaneous abortion (RSA) (or miscarriage) — refers to the occurrence of two or more losses of consecutive pregnancies prior to the 20th week of gestation (excluding ectopic, molar or biochemical pregnancies). The loss may be primary (in women has never carried to viability) or secondary (after a previous live birth). Causative factors include anatomic, chromosomal, hormonal or immunological abnormalities, as well as thrombolytic disorders, or underlying factors of unknown etiology.

Guideline Members are eligible for coverage of the evaluation and treatment of RPL (≥ 2 lost spontaneous miscarriages in < 20 weeks) per the table below. Medically necessary diagnostic tests/procedures

1. Assessment of thyroid function:  Thyroid antibodies
    Thyroid stimulating hormone (TSH)
2. Detection of anatomic abnormalities (e.g., ovaries, uterus, uterine cavity):
    Hysteroscopy/hysterosalpingography  Sonohysteroscopy/sonohysterography
    Pelvic ultrasound
3. Detection of chromosomal abnormalities:
    Karyotype serology

 Karyotype of abortus tissue (when ≥ 2 RPL occurrences)  Molecular cytogenetic probe (e.g., FISH) DNA analysis when karyotyping above is not possible (e.g., poor culture, insufficient tissue sample)

4. Detection of antiphospholipid syndrome (APSS) using standard assays:
    Anticardiolipin antibody detection (IgG, IgM),  Anti-β2-glycoprotein I (IgG or IgM) antibodies  Lupus anticoagulant (LA) antibodies
5. Prenatal genetic diagnosis:
    Couples in which 1 partner has a balanced translocation or inversion Medically necessary treatment
6. Low-dose heparin and aspirin for antiphospholipid syndrome
7. Antenatal transvaginal cervical cerclage
8. Antenatal transabdominal cervical cerclage (if prior transvaginal cerclage is contraindicated or previously failed)

9. Surgical correction of structural uterine abnormalities

   Limitations/Exclusions A. The following evaluative tests are not considered medically necessary for RPL, as clinical utility has not been established:

10. Angiotensin converting enzyme (ACE) and plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms testing
11. Antibodies to phosphatidylserine, phosphatidylethanolamine or phospholipids (except anti- cardiolipin and lupus anticoagulant, as depicted in table above)
12. Cytokine polymorphisms analysis (Th1/Th2 intra-cellular cytokine ratio)
13. Embryo toxicity assay (ETA)
14. Genetic association studies of inflammatory cytokine polymorphisms
15. Inter-α trypsin inhibitor-heavy chain 4 (ITI-H4) (as a biomarker for recurrent pregnancy loss)
16. Maternal antiparental antibodies
17. Methylenetetrahydrofolate reductase (MTHFR) testing
18. Molecular cytogenetic testing (serological or on products of conception) using comparative genomic hybridization (CGH)
19. Molecular genetic testing for highly skewed X-inactivation patterns
20. Natural killer (NK) testing to determinat circulating-cell % or status of NK-like cells through luteal phase biopsy
21. Parental human leukocyte antigen (HLA) status
22. Pre-implantation genetic screening (PGS) (See Infertility Services to determine whether members pursuing assisted reproductive technology services meet PGS criteria)
23. Reproductive immunophenotype (CD3+, CD4+, CD5+, CD8+, CD16+, CD19+, CD56+)
24. Routine preimplantation embryo aneuploidy screening
25. Tests for embryotoxic factor
26. Tests for inherited thrombophilic disorders: factor V Leiden (genetic testing), prothrombin G20210A mutation, serum homocysteine, and deficiencies of the anticoagulants protein C, protein S, and antithrombin II
27. Tests for maternal antileukocytic antibodies to paternal leukocytes
28. Tests for serum “blocking factor”

20. X-chromosome inactivation study

    B. The following medical procedures are not considered medically necessary for the prevention/treatment of RPL due to insufficient evidence of therapeutic value:

21. Donor leukocytes/ infusion
22. Immunoglobulin (IVIG) therapy
23. Intralipid therapy
24. Low-molecular-weight heparin (unless thrombophilic disorder is present and member is undergoing active treatment for venous thromboembolism
25. Paternal leukocyte immunization

26. Trophoblast membrane infusion

    Revision History Mar. 11, 2022 Removed tissue analysis for luteal phase defect as a medically necessary procedure Mar. 12, 2021 Updated recurrent pregnancy loss definition — changed “three “or more consecutive pregnancy losses to “two” or more

    Applicable Procedure Codes 58100 Endometrial sampling (biopsy) with or without endocervical sampling (biopsy), without cervical dilation, any method (separate procedure) 58340 Catheterization and introduction of saline or contrast material for saline infusion sonohysterography (SIS) or hysterosalpingography 58555 Hysteroscopy, diagnostic (separate procedure) 58558 Hysteroscopy, surgical; with sampling (biopsy) of endometrium and/or polypectomy, with or without D & C 58559 Hysteroscopy, surgical; with lysis of intrauterine adhesions (any method) 58560 Hysteroscopy, surgical; with division or resection of intrauterine septum (any method) 58561 Hysteroscopy, surgical; with removal of leiomyomata 58562 Hysteroscopy, surgical; with removal of impacted foreign body 58563 Hysteroscopy, surgical; with endometrial ablation (eg, endometrial resection, electrosurgical ablation, thermoablation) 58565 Hysteroscopy, surgical; with bilateral fallopian tube cannulation to induce occlusion by placement of permanent implants 59320 Cerclage of cervix, during pregnancy; vaginal 59325 Cerclage of cervix, during pregnancy; abdominal 74740 Hysterosalpingography, radiological supervision and interpretation 76831 Saline infusion sonohysterography (SIS), including color flow Doppler, when performed 76856 Ultrasound, pelvic (nonobstetric), real time with image documentation; complete 81403 Molecular pathology procedure, Level 4 (eg, analysis of single exon by DNA sequence analysis, analysis of 10 amplicons using multiplex PCR in 2 or more independent reactions, mutation scanning or duplication/deletion variants of 2-5 exons
    81404 Molecular pathology procedure, Level 5 (eg, analysis of 2-5 exons by DNA sequence analysis, mutation scanning or duplication/ deletion variants of 6-10 exons, or characterization of a dynamic mutation disorder/triplet repeat by Southern blot analysis

81405 Molecular pathology procedure, Level 6 (eg, analysis of 6-10 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of 11-25 exons, regionally targeted cytogenomic array analysis) CPOX (coproporphyrinogen oxidase) (eg, hereditary coproporphyria), full gene sequence CTRC (chymotrypsin C) (eg, hereditary pancreatitis), full gene sequence PKLR (pyruvate kinase, liver and RBC) (eg, pyruvate kinase deficiency), full gene sequence
81406 Molecular pathology procedure, Level 7 (eg, analysis of 11-25 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of 26-50 exons, cytogenomic array analysis for neoplasia) ANOS1 (anosmin-1) (eg, Kallmann syndrome 1), full gene sequence HMBS (hydroxymethylbilane synthase) (eg, acute intermittent porphyria), full gene sequence PPOX (protoporphyrinogen oxidase) (eg, variegate porphyria), full gene sequence
81407 Molecular pathology procedure, Level 8 (eg, analysis of 26-50 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of >50 exons, sequence analysis of multiple genes on one platform) 81408 Molecular pathology procedure, Level 9 (eg, analysis of >50 exons in a single gene by DNA sequence analysis) 84443 Thyroid stimulating hormone (TSH) 85307 Activated Protein C (APC) resistance assay 85335 Factor inhibitor test
85337 Thrombomodulin
85705 Thromboblastin inhibition, tissue
86146 Beta 2 Glycoprotein I antibody, each[IgG or IgM]
86147 Cardiolipin (phospholipid) antibody, each Ig class
86800 Thyroglobulin antibody 88230 Tissue culture for non-neoplastic disorders; lymphocyte 88233 Tissue culture for non-neoplastic disorders; skin or other solid tissue biopsy 88235 Tissue culture for non-neoplastic disorders; amniotic fluid or chorionic villus cells 88237 Tissue culture for neoplastic disorders; bone marrow, blood cells 88239 Tissue culture for neoplastic disorders; solid tumor 88245 Chromosome analysis for breakage syndromes; baseline Sister Chromatid Exchange (SCE), 20-25 cells 88248 Chromosome analysis for breakage syndromes; baseline breakage, score 50-100 cells, count 20 cells, 2 karyotypes (eg, for ataxia telangiectasia, Fanconi anemia, fragile X) 88249 Chromosome analysis for breakage syndromes; score 100 cells, clastogen stress (eg, diepoxybutane, mitomycin C, ionizing radiation, UV radiation) 88261 Chromosome analysis; count 5 cells, 1 karyotype, with banding 88262 Chromosome analysis; count 15-20 cells, 2 karyotypes, with banding 88263 Chromosome analysis; count 45 cells for mosaicism, 2 karyotypes, with banding 88264 Chromosome analysis; analyze 20-25 cells 88267 Chromosome analysis, amniotic fluid or chorionic villus, count 15 cells, 1 karyotype, with banding 88269 Chromosome analysis, in situ for amniotic fluid cells, count cells from 6-12 colonies, 1 karyotype, with banding 88271 Molecular cytogenetics; DNA probe, each (eg, FISH) 88272 Molecular cytogenetics; chromosomal in situ hybridization, analyze 3-5 cells (eg, for derivatives and markers) 88273 Molecular cytogenetics; chromosomal in situ hybridization, analyze 10-30 cells (eg, for microdeletions) 88274 Molecular cytogenetics; interphase in situ hybridization, analyze 25-99 cells 88275 Molecular cytogenetics; interphase in situ hybridization, analyze 100-300 cells

88280 Chromosome analysis; additional karyotypes, each study 88283 Chromosome analysis; additional specialized banding technique (eg, NOR, C-banding) 88285 Chromosome analysis; additional cells counted, each study 88289 Chromosome analysis; additional high resolution study 88291 Cytogenetics and molecular cytogenetics, interpretation and report [not covered for preimplantation genetic screening] 89325 Sperm antibodies
J1644 Injection, Heparin sodium, per 1000 units

Applicable ICD-10 Diagnosis Codes N96 Recurrent pregnancy loss O03.9 Complete or unspecified spontaneous abortion without complication O09.291 Supervision of pregnancy with other poor reproductive or obstetric history, first trimester O09.292 Supervision of pregnancy with other poor reproductive or obstetric history, second trimester O09.293 Supervision of pregnancy with other poor reproductive or obstetric history, third trimester O09.299 Supervision of pregnancy with other poor reproductive or obstetric history, unspecified trimester O26.20 Pregnancy care for patient with recurrent pregnancy loss, unspecified trimester Z31.441 Encounter for testing of male partner of patient with recurrent pregnancy loss

References American Congress of Obstetricians and Gynecologists (ACOG). ACOG Committee Opinion No. 430: Preimplantation genetic screening for Aneuploidy. Obstet Gynecol. 2009 Mar;113(3):766-7.
American Congress of Obstetricians and Gynecologists (ACOG). Antiphospholipid syndrome. ACOG Practice Bulletin No.

118. Washington, DC: ACOG; January 2011.
     American Congress of Obstetricians and Gynecologists (ACOG). Cervical Insufficiency. Practice Bulletin No. 48. American College of Obstetricians and Gynecologists. August 2003, reaffirmed 2008.
     American Congress of Obstetricians and Gynecologists (ACOG). Inherited thrombophilias in pregnancy. Practice Bulletin No. 124 American College of Obstetricians and Gynecologists. Obstet Gynecol 2011;118:730-40.
     American Congress of Obstetricians and Gynecologists (ACOG). Management of recurrent early pregnancy loss. ACOG practice bulletin no. 24. Washington, DC: American College of Obstetricians and Gynecologists (ACOG); 2001 Feb 12.
     American Congress of Obstetricians and Gynecologists (ACOG)/The Society for Maternal-Fetal Medicine. ACOG Committee Opinion 581: The use of chromosomal microarray analysis in prenatal diagnosis. December 2013.
     American Society of Reproductive Medicine (ASRM). Practice Committee Report. Definitions of infertility and recurrent pregnancy loss. 2020 http://www.fertstert.org/article/S0015-0282(12)02242-X/pdf. Accessed March 24, 2026.
     American Society of Reproductive Medicine (ASRM). Practice Committee. Intravenous immunoglobulin (IVIG) and recurrent spontaneous pregnancy loss. 2006. http://www.fertstert.org/article/S0015-0282(06)03297-3/fulltext. Accessed March 24, 2026. American Society of Reproductive Medicine. Evaluation and treatment of recurrent pregnancy loss: a committee opinion.
119. http://www.fertstert.org/article/S0015-0282(12)00701-7/fulltext. Accessed March 24, 2026. Martini AE, Jasulaitis S, Fogg LF, Uhler ML, Hirshfeld-Cytron JE. Evaluating the Utility of Intralipid Infusion to Improve Live Birth Rates in Patients with Recurrent Pregnancy Loss or Recurrent Implantation Failure. J Hum Reprod Sci. 2018;11(3):261–268. doi:10.4103/jhrs.JHRS2818. Recurrent Spontaneous Miscarriage: a Comparison of International Guidelines. Vomstein K, Aulitzky A, Strobel L, Bohlmann M, Feil K, Rudnik-Schöneborn S, Zschocke J, Toth B. Geburtshilfe Frauenheilkd. 2021 Jul;81(7):769-779. Specialty-matched clinical peer review.