Differentials

Common

Idiopathic recurrent miscarriage

History

3 or more consecutive miscarriages where no cause is found

Exam

no specific abnormalities

1st investigation
  • FBC:

    normal

  • blood group and antibodies:

    no antibodies

  • antiphospholipid antibody screen:

    normal

    More
  • cytogenetic analysis for the karyotype of products of conception:

    normal

  • pelvic ultrasound scan (transabdominal or transvaginal, ideally 3-dimensional):

    normal

    More
Other investigations
  • sperm DNA fragmentation:

    increased

    More
  • thrombophilia screen:

    normal

    More

Fetal chromosomal abnormality

History

no specific features

Exam

no specific abnormalities

1st investigation
  • cytogenetic analysis for the karyotype of products of conception:

    chromosomal abnormalities detected

    More
  • FBC:

    normal

  • blood group and antibodies:

    no antibodies

  • antiphospholipid antibody screen:

    normal

    More
  • cytogenetic analysis of blood for the karyotype of both partners:

    normal

  • pelvic ultrasound scan (transabdominal or transvaginal, ideally 3-dimensional):

    normal

    More
Other investigations
  • thrombophilia screen:

    normal

    More

Chronic endometritis

History

often asymptomatic; non-specific symptoms include pelvic pain, vaginal discharge, dyspareunia and abnormal vaginal bleeding

Exam

suprapubic and uterine tenderness

1st investigation
  • endometrial biopsy:

    histologic appearance of endometritis with or without CD138 staining

Other investigations

    Uncommon

    Parental chromosomal abnormality

    History

    may be a family history of recurrent miscarriage or congenital abnormalities

    Exam

    no specific abnormalities

    1st investigation
    • cytogenetic analysis of blood for the karyotype of both partners:

      chromosomal abnormality detected

      More
    • FBC:

      normal

    • blood group and antibodies:

      no antibodies

    • antiphospholipid antibody screen:

      normal

      More
    • cytogenetic analysis for the karyotype of products of conception:

      occasionally normal

    • pelvic ultrasound scan (transabdominal or transvaginal, ideally 3-dimensional):

      normal

      More
    Other investigations
    • thrombophilia screen:

      normal

      More

    Antiphospholipid syndrome

    History

    previous history of thrombotic event, thrombotic event in family member, autoimmune disease

    Exam

    no specific abnormalities

    1st investigation
    • antiphospholipid antibody screen:

      ELISA for IgG and/or IgM anticardiolipin (aCL) antibodies: medium or high titres (>99th percentile) in 2 or more tests at least 12 weeks apart; activated partial thromboplastin time (lupus APTT): prolonged in 2 or more tests at least 12 weeks apart if lupus anticoagulant present; dilute Russell viper venom time (DRVVT): increased in 2 or more tests at least 12 weeks apart if lupus anticoagulant present; kaolin clotting time (KCT): increased test-control ratio in 2 or more tests at least 12 weeks apart if lupus anticoagulant present; ELISA for IgG and/or IgM anti-beta-2 glycoprotein-1 antibodies: medium or high titres (>99th percentile) in 2 or more tests at least 12 weeks apart

      More
    • FBC:

      normal

    • blood group and antibodies:

      no antibodies

    • cytogenetic analysis for the karyotype of products of conception:

      normal

    • pelvic ultrasound scan (transabdominal or transvaginal, ideally 3-dimensional):

      normal

      More
    Other investigations
    • thrombophilia screen:

      normal

      More

    Cervical incompetence

    History

    history of painless dilatation of the cervix or spontaneous rupture of membranes followed by a second-trimester miscarriage

    Exam

    no specific abnormalities

    1st investigation
    • pelvic ultrasound scan (transabdominal or transvaginal, ideally 3-dimensional):

      normal; measurement of cervix may be performed but is not diagnostic

      More
    • FBC:

      normal

    • blood group and antibodies:

      no antibodies

    • serum antiphospholipid antibody screen:

      normal

      More
    • cytogenetic analysis for the karyotype of products of conception:

      normal

    Other investigations
    • thrombophilia screen:

      normal

      More

    Uncontrolled diabetes mellitus

    History

    polyuria, polydipsia, blurred vision, paraesthesia, fatigue or lethargy, weight loss; may be a family history of diabetes mellitus; diabetic ketoacidosis (nausea, vomiting, abdominal pain); prior history of type 1 or type 2 diabetes mellitus

    Exam

    tachypnoea, signs of skin infection

    1st investigation
    • random blood glucose:

      ≥11.1 mmol/L (≥200 mg/dL)

      More
    • FBC:

      normal

    • blood group and antibodies:

      no antibodies

    • serum antiphospholipid antibody screen:

      normal

      More
    • cytogenetic analysis for the karyotype of products of conception:

      normal

    • pelvic ultrasound scan (transabdominal or transvaginal, ideally 3-dimensional):

      normal

      More
    Other investigations
    • fasting blood glucose:

      >6.94 mmol/L (125 mg/dL)

      More
    • 75 g oral glucose tolerance test:

      2-hour postload glucose 11.1 mmol/L or greater (≥200 mg/dL)

      More
    • thrombophilia screen:

      normal

      More

    Uncontrolled thyroid dysfunction

    History

    hypothyroidism: cold sensitivity, dry skin, fatigue, weight gain, constipation, menstrual irregularity; hyperthyroidism: heat intolerance, palpitations, sweating, weight loss, tremor, irritability, menstrual irregularity

    Exam

    hypothyroidism: dry skin, bradycardia, facial oedema, goitre; hyperthyroidism: tachycardia, chemosis, proptosis, lid retraction, tremor, goitre

    1st investigation
    • serum thyroid-stimulating hormone (TSH):

      primary hypothyroidism: elevated; hyperthyroidism: suppressed

      More
    • serum free thyroxine:

      hypothyroidism: below normal range; hyperthyroidism: above normal range

      More
    • FBC:

      normal

    • blood group and antibodies:

      no antibodies

    • serum antiphospholipid antibody screen:

      normal

      More
    • cytogenetic analysis for the karyotype of products of conception:

      normal

    • pelvic ultrasound scan (transabdominal or transvaginal, ideally 3-dimensional):

      normal

      More
    Other investigations
    • thrombophilia screen:

      normal

      More

    Thrombophilias

    History

    previous history of thrombosis; thrombotic event in first- or second-degree relatives

    Exam

    no specific abnormalities

    1st investigation
    • thrombophilia screen:

      factor V Leiden (FVL) gene mutation: heterozygous or homozygous; activated protein C (APC) resistance assay: resistance ratio >1.2; prothrombin G20210A gene mutation: present; protein S assay: <70%; protein C assay: <50%; antithrombin III activity: <80%

      More
    • FBC:

      normal

    • blood group and antibodies:

      no antibodies

    • serum antiphospholipid antibody screen: ELISA for IgG and/or IgM anticardiolipin (aCL) antibodies:

      normal range

    • serum antiphospholipid antibody screen:

      normal

      More
    • cytogenetic analysis for the karyotype of products of conception:

      normal

    • pelvic ultrasound scan (transabdominal or transvaginal, ideally 3-dimensional):

      normal

      More
    Other investigations

      Uterine abnormalities (e.g., bicornuate, septate, or arcuate uterus)

      History

      no specific features

      Exam

      no specific abnormalities

      1st investigation
      • pelvic ultrasound scan (transabdominal or transvaginal, ideally 3-dimensional):

        structural abnormality seen

      • FBC:

        normal

      • blood group and antibodies:

        no antibodies

      • serum antiphospholipid antibody screen:

        normal

        More
      • cytogenetic analysis for the karyotype of products of conception:

        normal

      Other investigations
      • hysteroscopy:

        structural abnormality seen

        More
      • thrombophilia screen:

        normal

        More

      Bacterial vaginosis

      History

      history of previous second-trimester miscarriage

      Exam

      fishy-smelling vaginal discharge

      1st investigation
      • FBC:

        normal

      • blood group and antibodies:

        no antibodies

      • serum antiphospholipid antibody screen:

        normal

        More
      • cytogenetic analysis for the karyotype of products of conception:

        normal

      • pelvic ultrasound scan (transabdominal or transvaginal, ideally 3-dimensional):

        normal

      Other investigations
      • high vaginal swab for wet mount microscopy, pH, Gram stain, and culture:

        wet mount microscopy: clue cells present, the numbers of lactobacilli are decreased, and WBCs are absent; vaginal pH: increased (usually >4.5); Gram stain: reduced or absent lactobacilli; culture: increased Gardnerella vaginalis, Mycoplasma hominis, and gram-negative anaerobes

        More
      • thrombophilia screen:

        normal

        More

      Polycystic ovarian syndrome (PCOS)

      History

      menstrual irregularities, acne, hirsutism, subfertility

      Exam

      commonly, elevated BMI

      1st investigation
      • serum testosterone:

        elevated

      • pelvic ultrasound scan:

        enlarged ovaries with at least 20 follicles in each ovary measuring 2-9 mm in diameter and/or increased ovarian volume (>10 mL)

      • FBC:

        normal

      • blood group and antibodies:

        no antibodies

      • random blood glucose:

        may be elevated

        More
      • serum antiphospholipid antibody screen:

        normal

        More
      • cytogenetic analysis for the karyotype of products of conception:

        normal

      Other investigations
      • day 1-3 follicle-stimulating hormone:

        normal

        More
      • serum estradiol:

        normal

        More
      • serum LH:

        elevated

      • thrombophilia screen:

        normal

        More

      Smoking, caffeine intake

      History

      history of smoking and caffeine ingestion

      Exam

      no specific abnormalities

      1st investigation
      • FBC:

        normal

      • blood group and antibodies:

        no antibodies

      • serum antiphospholipid antibody screen:

        normal

        More
      • cytogenetic analysis for the karyotype of products of conception:

        normal

      • pelvic ultrasound scan (transabdominal or transvaginal, ideally 3-dimensional):

        normal

        More
      Other investigations
      • thrombophilia screen:

        normal

        More

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