Examinations for Recurrent Pregnancy Loss

creening for recurrent miscarriage was proposed by the Subcommittee of the Recurrent Endocrinology Committee of the Japan Society of Obstetrics and Gynecology from 2003 to 2004, "Investigation of clinical conditions for human reproductive loss (habitual miscarriage, etc.)" However, some items of measurement were ultimately omitted due to burden on the patient and lack of effective treatment options. Useful tests are listed here.

 

Uterine Morphology Test

The presence and location of uterine malformations, endometrial polyps, and fibroids are confirmed by hysterosalpingography, transvaginal ultrasound, and sonohysterography. An MRI scan may be done. Uterine morphological abnormalities are found in 7.8% of recurrent miscarriage patients.

 

Endocrine Function (Blood Test)

Thyroid function FT3, FT4, TSH
Diabetes test HbA1c
Hypothyroidism is found in 6.8% of patients.

 

Antiphospholipid antibody (blood test)

Antiphospholipid antibodies are autoantibodies that react with plasma proteins bound to phospholipids on the surface of all cell membranes in the human body. They are present in the blood of healthy people in trace amounts, but when excessive amounts are produced, this is called antiphospholipid-antibody-positive. This causes blood clots in the uterus and prevents angiogenesis. Since this test is not highly accurate, if it continues to be positive at intervals of 12 weeks or more, it should be managed as antiphospholipid antibody syndrome to be safe. The positive rate accounts for about 10% of recurrent miscarriage, but antiphospholipid antibody syndrome is said to be 4% (Rai RS, et al., Hum Reprod. 1995 Dec; 10 (12). ): 3301-4.).

Except for antiphospholipid antibodies caused by infectious diseases, there are measurement methods for thrombosis-causing antibodies.

  • Anti-cardiolipin β2 glycoprotein I complex antibody (anti-CLβ2GP I antibody)
  • Anti-cardiolipin antibody IgG (anti-CL antibody IgG) 
  • Lupus Anticoagulant Qualitative (LAC)

According to the antiphospholipid antibody syndrome diagnostic criteria advocated by the International Society for Antiphospholipid Antibodies, testing is indicated in the case of: 
(A) One or more intrauterine fetal deaths without fetal malformations after 10 weeks gestation
(B) Recurrent miscarriage of unknown cause three or more times in a row at less than 10 weeks gestation
(C) One or more pre-34 weeks gestation due to preeclampsia or placental insufficiency
Premature birth is also a pregnancy complication. False positives may occur, so sometimes you must test positive again after 12 weeks or more, in order to be diagnosed with antiphospholipid antibody syndrome.

■Antinuclear Antibody
Antinuclear antibody positive rates are also frequently seen in patients with recurrent miscarriage, but if antiphospholipid antibody is negative, there may be no significant difference in the miscarriage rate of the next pregnancy between positive and negative antinuclear antibodies. So, this is an adjunct test.

 

Coagulation Test

Blood coagulation factor (factor Ⅻ)
Among blood coagulation factors, a decrease in factor Ⅻ has been found to be a risk factor for miscarriage (Gris JC, et al., Thromb Haemost. 1997; 77 (6): 1096-103.). This may account for about 15% of recurrent miscarriage cases, and while 80% of the cases with decline have miscarriage, the miscarriage rate decreases to 12.5% after treatment.

 

Chromosome Test

Chromosomal abnormalities that do not affect normal health may cause repeated miscarriages (Hirshfeld-Cytron J, et al. Semin Reprod Med. 2011 Nov; 29 (6): 470-81.) However, there are many cases in which the ultimate rate of childbirth is high even without treatment. Diagnosis is made by blood tests of both husband and wife. Sufficient genetic counseling is required before the test is performed.