Diagnostic criteria
Two or more pregnancy losses
First, second or third trimester
Do NOT need to be consecutive
Including biochemical pregnancies
Excluding molar and ectopic pregnancies
Confirmed by urine, blood hCG, or ultrasound
If you are a PCP: Refer to OB/Gyn
Diagnostic workup
Loss 1ASRM 2026 RPL Guideline recommends no action taken unless clinically indicated. A proactive approach could include standard tests for hypothyroidism, diabetes, and anemia to rule out common and easily addressed factors.
Loss 2+Chromosome testing of pregnancy or fetal tissue (POC)* + RPL evaluation
* Recommend microarray analysis vs karyotype
RPL evaluation
Parental karyotypes (to evaluate for balanced translocations and chromosomal abnormalities)
Uterine cavity evaluation (hysterosalpingogram, hysterosonogram, hysteroscopy, or MRI)
APS panel after 3 consecutive losses or 1 loss at/after 10 weeks (testing not indicated if all losses are known to be aneuploid)
TSH, HbA1c
For consideration:
Endometrial biopsy (EMB) stained for CD138 (syndecan-1), a marker of plasma cells to detect chronic endometritis
Semen analysis
Sperm DNA fragmentation
Urology evaluation
APS panel after 2 euploid losses
Important considerations
45%
of patients will have at least one abnormal test result
65%
will have an abnormal POC result
Other considerations
Most patients with RPL will go on to have a live birth regardless of whether an explanation is found
RPL is often multifactorial
Optimizing preconception physical and emotional health of both parents is the cornerstone of proven treatments of RPL
RPL patients experience high rates of anxiety, depression, and PTSD in subsequent pregnancies. Offer more frequent monitoring, assess mental health, refer to psych as indicated.
RPL can cause intense grief and feelings of shame. Alleviate the burden of guilt: “This is not your fault.”
OB/Gyn: Consider referral to REI