Information for Non-IVF Providers

Biopsy Information
Understanding Results
Provider FAQs

About ReceptivaDx

ReceptivaDx is an immunohistochemistry test that detects inflammatory conditions of the endometrium most often associated with endometriosis. ReceptivaDx identifies BCL6, a protein biomarker associated with inflammation. BCL6 is dramatically overexpressed in women with endometriosis.

The Power of ReceptivaDx

The first test for endometriosis with high sensitivity (93%) and specificity (96%)

Intended for patients looking for answers to unexplained infertility, recurrent pregnancy loss, and pelvic pain or associated symptoms of endometriosis

ReceptivaDx is the only test capable of identifying all major forms of uterine inflammation in a single biopsy.

Combined with a complete pathology analysis, women’s healthcare providers in any clinical setting can now access powerful information that can expedite fertility treatment decisions and/or uncover conditions such as endometriosis that have historically taken 7-10 years to diagnose properly.

For patients with unexplained infertility & recurrent pregnancy loss

ReceptivaDx provides enhanced screening for all stages of endometriosis and other conditions that interfere with implantation and endometrial receptivity. This is vital because, despite advances in imaging, ultrasound and MRI often miss superficial endometriosis. These lesions are known to significantly impair fertility.

BCL6 is overexpressed in more than 50% of women with unexplained infertility. Endometriosis is associated with impaired implantation and recurrent pregnancy loss. This includes silent endometriosis, which occurs without typical symptoms, often going undetected until infertility issues arise. 

Every test includes a pathology review that assesses tissue adequacy/architecture and detects polyps, hyperplasia, and other abnormalities.

The CD138 marker can be added to screen for endometritis, a chronic infection that is also associated with infertility and recurrent pregnancy loss. 

For patients with undiagnosed pain/suspected endometriosis

For patients with undiagnosed pelvic or abdominal pain or other symptoms suggestive of endometriosis, ReceptivaDx provides a non-surgical way to identify if endometriosis is the likely source. 

By providing objective data during a routine office visit, the test allows clinicians to develop an immediate action plan, which may include medical or surgical interventions or an expedited referral to an endometriosis specialist.

A negative BCL6 result reduces the likelihood of uterine lining inflammation and the presence of endometriosis.

Studies show that women testing negative have less than a 7% chance of endometriosis on diagnostic laparoscopy.

Cicero Diagnostics has performed more than 50,000 tests and continues to collect and publish results on outcomes.

Download our physician brochure

When to use ReceptivaDx

ReceptivaDxTM testing is suggested for the following:

Women with unexplained infertility

  • Rule out uterine inflammation usually caused by endometriosis (BCL6) or endometritis (CD138)
  • Establish chances of success or failure before beginning advanced fertility treatment options.

Women with recurrent pregnancy loss

  • Rule out uterine inflammation, most frequently caused by endometriosis (BCL6)
  • Rule out uterine inflammation, usually caused by endometritis (CD138)
  • Rule out progesterone resistance, shown to be correlated with recurrent pregnancy loss.

Women with pelvic pain or symptoms associated with endometriosis

  • In conjunction with imaging, ReceptivaDx can help identify endometriosis as a cause of pain and help guide potential treatment or management pathways

Biopsy and Sample Collection for BCL6 and CD138

Biopsy Procedure

  • Procedure timing: Must be collected 7-10 days after ovulation in a natural cycle (Collect using standard pipelle) 
  • Place in 10% formalin vial only (provided in ReceptivaDx collection kit)
  • One pass/half pipelle is sufficient for analysis
    NOTE: Floating sample in vial indicates more mucosa than endometrial tissue therefore 2nd pass is recommended

Contraindications:

Biopsies should not be performed in cycles that involve other invasive procedures, such as hysteroscopies. These procedures generate temporary inflammation and can influence results. It is highly recommended to wait at least one cycle before taking the biopsy. Patients coming off birth control should wait for at least one period before scheduling a biopsy.

Non-ovulatory patients:

Our medical advisory board recommends using Clomid to induce ovulation. BCL6 biopsy results should only be interpreted within the luteal phase. Every ReceptivaDx report includes a full pathology analysis with histological dating.

Sample Submission

  • Samples are collected in formalin only (provided in the collection kit)
    NOTE: Do not use vial provided by other companies. Many are not formalin
  • Make sure the vial cap is secured (the cap clicking indicates the sample is secure)
  • Place the vial in the hazard/safety bag (provided in the collection kit)
  • Verify the two patient identifiers on the vial match the information on the test request form
  • Verify the test request form is complete, including payment information and patient email
  • Place the bag and test request form in the ReceptivaDx collection box
  • Place collection box in FedEx Clinical Pak
  • Attach the prepaid billable stamp
  • Arrange for FedEx pick-up

Preferred shipment days are Monday–Friday FedEx overnight. Friday shipments will arrive on Monday.
NOTE: The sample is stable at room temperature for up to 14 days.

Results will be available within 10 business days from the date received by the lab.

Results can only be faxed to the fax number provided on the test request form. Online access to the results is available. Please call 800-795-5385 to register your center.

Understanding Results

Both biomarkers BCL6 and CD138 are assessed via immunohistochemistry staining. 

BCL6 is a protein marker highly associated with endometriosis. Results are reported as an H-score value between 0-4. Positive results were established using a value of 1.4 or above and validated against laparoscopy-confirmed endometriosis patients. The H-score is calculated as the sum of the percentage of staining multiplied by an ordinal value corresponding to the intensity level and reported as (0 = none, 1 = weak, 2 = moderate, 3 = strong 4= very strong). Please note that the H-Score value is not an indicator of endometriosis disease stage.

CD138 is an antigen specific to plasma cells and used to detect chronic endometritis. The results are calculated and reported based on presence of clusters of plasma cells. While rare stromal cells will be indicated, they are not considered consistent with a diagnosis of endometritis.

View Sample Report

BCL6 Results

  • Positive results indicate inflammation of the uterine lining most likely caused by the body’s immune response to endometriosis. The test has been validated to be 93% sensitive and 96% specific for the presence of endometriosis. This inflammatory condition is associated with severe pelvic pain (especially during periods/sex), extreme fatigue, and gastrointestinal issues in addition to unexplained infertility. It has proven to impact implantation and/or cause early pregnancy loss. 
  • A negative result indicates uterine lining is likely to be receptive. Less than 7% chance of endometriosis found via laparoscopy.

CD138 Results

  • Negative for endometritis: No cells staining positive for CD138
  • Negative for endometritis: Some singular plasma cells are seen but insufficient for positive diagnosis.
  • Positive for chronic endometritis: Multiple or clusters of cells seen staining positive.

Left untreated, studies show patients with a positive BCL6 have a significantly reduced chance of a successful pregnancy and live birth.

Treatment Strategies for a Positive BCL6 Test Result

Current published studies recommend the following treatments:

Positive BCL6 Result

Indicates uterine inflammation, often associated with endometriosis.

Proven treatment pathways include medical management comprising hormone therapy, pain management, and complementary therapies like pelvic floor physical therapy, acupuncture, and nutritional support. For some patients, surgical intervention may be recommended.

Ultimately, a positive result facilitates shared decision-making regarding fertility preservation and allows for a treatment plan tailored to the patient’s specific reproductive and lifestyle goals.

Negative BCL6 Result

Reduces the likelihood of uterine lining inflammation and the presence of endometriosis.

Studies have shown that women testing negative have less than a 7% chance of endometriosis on diagnostic laparoscopy.

Treatment Strategies for a Positive CD138 Test Result

A combination regimen of ampicillin, gentamicin, and metronidazole provides coverage against most of the organisms encountered in chronic endometritis. Doxycycline should be used if chlamydia is the cause of endometritis. Ampicllin sulbactam can be used as a monotherapy.

Learn more about endometriosis medication

Clinical Data

Cicero Diagnostics is a data driven company

We are dedicated to providing relevant and updated published clinical data to support the use of the ReceptivaDx test in the patient setting. As evidenced by the dozens of current independent studies as well as our own NIH supported research, Cicero Diagnostics provides more proven data than any other endometrial biopsy based test in the fertility sector.

Publications

FAQs for Patients Not Undergoing IVF

Unfortunately, the BCL6 marker was not validated during egg retrieval cycles and should not be obtained in that same cycle. Biopsy at the time of egg retrieval, while convenient for the provider and patient, occurs too early in the cycle to detect the presence of BCL6. Medications used during the egg retrieval cycle could impact results and do not represent an accurate portrayal of the uterine lining during an embryo transfer or natural cycle. It is suggested to wait until the next cycle after the egg retrieval cycle to obtain an optimal biopsy.

Positive BCL6 Result: Indicates uterine inflammation, often associated with endometriosis. Proven treatment pathways include medical management comprising hormone therapy, pain management, and complementary therapies like pelvic floor physical therapy, acupuncture, and nutritional support. For some, surgical intervention may be recommended. Ultimately, a positive result facilitates shared decision-making regarding fertility preservation and allows for a treatment plan tailored to the patient’s specific reproductive and lifestyle goals.

Results are reported as an H-score between 1 and 4. The H-score is calculated as the sum of the percentage of staining multiplied by an ordinal value corresponding to the intensity level and reported as (0 = none, 1 = weak, 2 = moderate, 3 = strong 4= very strong). Please note that the H-Score value is not an indicator of endometriosis disease stage.

The use of the test specific to infertility has been validated against laparoscopy-confirmed endometriosis patients using a cutoff value of 1.4. Any results above 1.4 should be considered positive and treated according to the guidelines under treatment. For clinical purposes, a value of 1.5 vs 4 will not affect protocols.

View here for a short review of cutoff values and interpretation

Patients with:

  • Family history of endometriosis
  • Undiagnosed pelvic or abdominal pain
  • Pain during and after sex 
  • Recurrent bladder or bowel pain
  • High Body Mass Index (BMI)

The ReceptivaDx test is performed on an endometrial biopsy sample using immunohistochemistry and sent to one of our accredited pathology labs. Results are faxed back to the referring office within 10 business days.

ReceptivaDx must be collected 7–10 days after ovulation in a natural cycle

Samples are stable at room temperature during the entire shipping process and can be collected any day of the week. Biopsy timing information is provided below. Our ReceptivaDx collection kit comes complete with everything necessary to properly collect and submit a sample.

Yes. For a natural cycle, the biopsy should occur 7-10 days after ovulation. Samples are sent overnight to one of our testing facilities and results are available within 10 business days.

The price of ReceptivaDx testing (BCL6 and full pathology report) is $690. This includes overnight shipping costs via FedEx to our nearest licensed testing center. 

CD138, a marker that identifies endometritis, can be ordered for an additional $145.

Payment is required via credit card at the time of sample submission. Patients may call our offices to make the payment in advance if preferred. Cicero Diagnostics provides a receipt that can be used for reimbursement from insurance or healthcare spending accounts. To receive this detailed receipt, please provide an email address on the test request form. International customers should contact us at 1-714-951-9245 or email us at info@receptivadx.com for complete international shipping instructions.

Wait a full cycle after any invasive procedures involving the uterus before  scheduling the biospy. These procedures generate temporary inflammation and can influence results. 

Patients coming off birth control should wait for at least one period before scheduling a biopsy.

Our medical advisory board recommends using Clomid to induce ovulation. BCL6 biopsy results should only be interpreted within the luteal phase. Every Receptiva report includes a full path analysis with histological dating.

Cicero Diagnostics, Inc. is a diagnostics company dedicated to the advancement of women’s healthcare. Cicero Diagnostics has exclusive rights to BCL6 analysis on endometrial tissue. As such, Cicero Diagnostics is the only licensed provider in the US for the detection of BCL6 as a marker in endometrial biopsy samples.

Our company maintains and collaborates with key academic research centers on various research studies. We are dedicated to developing new testing modalities for endometriosis and unexplained infertility. Cicero Diagnostics maintains two laboratory locations in the US. Both of these testing sites are fully licensed and operate under CLIA-established guidelines for the best laboratory practices.

Please feel free to contact us at 800-795-5385 for further information. International clients can email us at info@cicerodx.com or call us at 1-714-951-9245

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Call us at 800-795-5385 or send us an email at info@receptivadx.com for more information.