Recurrent Pregnancy Loss (RPL) Testing

       Pregnancy loss alone is devastating. Not knowing why it occurs even once is heartbreaking. To continue to experience loss after loss causes anxiety, depression and fear. Recurrent pregnancy loss is typically defined as 3+ consecutive losses, while some practitioners may Dx RPL as 2 consecutive losses.
       One thing I ran into personally, was I had two early miscarriages and then an ectopic- some doctors may not consider this RPL because ectopics are either flukes or caused by tubal factors, not necessarily in the same department as another type of loss. My old OB did not feel as though I need RPL testing, whereas my current OB and RE did.  Depending on the types of losses you’ve had, your doctor may order a couple, a handful or all of the testing listed below.
       Bottom line is you need to advocate for what you feel is right. RPL testing can be very expensive (I’ve listed prices my insurance was billed FYI, but obviously prices and benefits will vary), emotionally exhausting and may still not provide you with answers. Below are some tests you may request or discuss with your medical practitioner. I decided not to include normal lab values because one lab’s ‘normal’ may be another lab’s ‘abnormal’.

  • Hormonal Factors Tests (prices may vary from $50-300 per test): This includes prolactin, thyroid and progesterone. Other hormones that may be checked (as part of an IF work-up, some tests may be cycle day sensitive) are estradiol, testosterone, LH and FSH. 
    •  An imbalance with one or more hormone may warrant treatment depending on the Dx. Depending on hormonal imbalance an ultrasound may also be ordered to make a firm Dx (PCOS, DOR)  
  • Blood Clotting Disorders- typically treated with some type of blood thinner (baby aspirin, heparin, lovenox)
    • homocysteine/MTHFR
    • Prothrombin gene
    • Protein C&S
    • Antithrombin III
    • Factor V Leiden
    • Fibrinogen
    • PT/PTT (INR)
  • Structural Factors Tests: These tests are conducted to determine the size and shape of your uterus as well as checking the uterine wall in hopes it is free of scarring, polyps, fibroids or a septum- all of which can affect implantation. Tests to check the integrity of your tubes may also be ordered if one or more of your losses were ectopic, or if you are at higher risk for one. 
    • SHG (sonohysterogram) ($300-ish): This test is conducted by inserting a catheter through your cervix to push saline into the uterine cavity. Simultaneously, your doctor will also be performing a transvaginal ultrasound to get a visual of your uterus. This test can identify if there’s abnormalities in your uterus (listed above). If there are concerns about the uterus, a hysteroscopy or laparoscopy may be performed to fix and further Dx the issue.
    • HSG (hysterosalpingogram) ($500-ish): This test is typically performed in your local hospital’s X-ray lab by an X-ray tech, and sometimes your doctor depending on how their practice handles this procedure. Similar to an SHG, a catheter is inserted through your cervix, except this test requires dye to get an adequate picture of your tubes. Sometimes, simply performing this test may unblock tubes if there’s a blockage while other situations may require surgery. 
  •  Uterine Lining Test/ Endometrial Biopsy: While this test is considered obsolete by some in the medical community (results may vary from tech to tech reading doing the biopsy, which may not give accurate results), it can still be an important piece of the puzzle, especially if you’re dealing with possible luteal phase defect (LPD) or spotting for more than a couple days during your LP. 
    •  This test is typically performed in the office after CD 21 (be SURE you have ovulated, as this test is checking your uterine lining for implantation). To get an accurate and reliable reading, it is typically recommended for this test to be performed two cycles for comparison to make a firm Dx. 
    •  If the uterine lining is ‘out of phase’ (2+ days… meaning you’re 7dpo and your biopsy is showing 9dpo, your body may not be adequately using hormones to build your uterine lining) treatments of clomid/femara, hCG trigger and/or booster and progesterone supplementation may be used for Tx. 
    •  I do want to mention that if the endo biopsy does leave you with a LPD Dx, to ask your doctor about what type of defect it is. Click HERE to read more about the different types and causes.  LPD is a controversial Dx in the medical community, about 50/50- if you are concerned about your LP and your doctor does not believe it’s an issue, seek a second opinion.
  •  Tests for Chromosomal Causes
    • Pathology from D&C/D&E ($480- pathology only): this will show if the cause of your loss was from a chromosomal abnormality or not. Most chromosomal abnormalities found are not typical to repeat in the future. 
    • Genetic testing (saliva testing $960 for MH and I) on one or both partners- This may consist of blood or saliva tests. Some cultural groups may be at higher risk/genetic carriers for certain chromosomal defects. 
    • Karyotyping ($2300 for MH and I): Blood test to be performed on you and your partner to check for translocations (normal number of genes, but are joined together abnormally) Tests for 
  • Immunologic Causes: This is one area that seems to not have as much research on all areas of testing, some are controversial and some are routine- and that I admittedly do not know much about. If you have more information I can add to this section, please feel free to leave a comment, message me on the bump or page me on TTCAL
    •  Anti cardiolipin antibodies (ACA) 
    • Anti-nuclear antibodies (ANA) 
    • Anti-thyroid antibodies (ATA) 
    • Anti-Ovarian Antibodies (AOA) 
    • Anti-Sperm Antibodies (ASA) 
    • Anti-phospholipid antibodies (APA) 
    • Leukocyte Antibody Detection (LAD) 
    • Lupus anticoagulant (LAC) 
    • Embryo Toxic Factor (ETF) 
    • NK activation assay (NKa) 
    • reproductive immuno-phenotype (RIP)
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"Genes for Pre-Eclampsia Discovered"

BBC Article

Scientists say they have identified genetic errors that appear to increase a pregnant woman’s chance of getting the potentially life-threatening condition called pre-eclampsia.

Around four in every 100 women develops this problem of high blood pressure and leaky kidneys during pregnancy.

Now researchers have found faulty DNA may be to blame in some cases, PLoS Medicine journal reports.

The discovery could lead to new ways to spot and treat those at risk, they say.

The US researchers from the Washington University School of Medicine in St. Louis analysed DNA from over 300 pregnant women.

Sixty of these were otherwise healthy women who were hospitalised because they developed severe pre-eclampsia.

The remaining 250 were women who were being monitored for other health complications. Forty of these also went on to develop pre-eclampsia.

DNA analysis revealed a few genetic errors shared by five of the 60 otherwise healthy women and seven of the 40 “higher-risk pregnancy” women who developed pre-eclampsia.

The genes on which the errors were identified (MCP factor I and factor H) play a role in regulating immune response and the researchers believe this could explain their possible link to pre-eclampsia.

Scientists have suspected that problems with the immune system provoke many cases of pre-eclampsia because women with lupus and certain other autoimmune diseases – like 250 of the women in the study – have an increased risk of the disorder.

The researchers now plan to study more pregnant women and other genes to further their understanding.

Professor Basky Thilaganathan, spokesman for the Royal College of Obstetricians and Gynaecologists, said: “This work shows an association.

“At best genes like these might identify 10-15% of pre-eclampsia, so it’s relative importance may not be sensational. But it may allow us to study new treatments to prevent or delay the onset of pre-eclampsia and to know which women need closer surveillance.”

He said that currently the only real way to halt the condition was to deliver the baby. This can be relatively risk free if the pregnancy is nearing its natural end anyway, but can be risky if the baby is premature.

RPL- Testing and General Information

What is RPL?

RPL means Repeat/Recurrant Pregnancy Loss. Generally when a woman has had two or more losses confirmed by an OB, they are sent for RPL testing. Many doctors have varying views on when a woman should receive RPL testing. Some may say after “x” many weeks, three losses, or even after a certain age and a certain number of losses. Only your doctor will have the correct answer for you and your situation. If you ever question your doctors decision, it is best to seek a second, professional, opinion.
What will they test for?

Genetic testing

Studies have concluded that about half of all first trimester miscarriages are the result of chromosomal abnormalities. These generally occur on a sporadic basis, meaning that they are random occurrences. They are, however, related to the age of the woman and are more likely to occur with advancing maternal age.

Research suggests that after a couple has had 2 or more unexplained miscarriages, there is a 2-5% risk that one member of the couple is a carrier of a balanced chromosome rearrangement. Chromosomal analysis of the products of conception (the miscarried fetal tissue) and of the woman and her partner may provide additional important information that will affect future reproductive decisions and additional testing recommendations.

Hormonal testing

There are several hormonal imbalances that can contribute to miscarriage rates. These can be evaluated with simple blood tests and treated if present. The recommended hormonal testing will depend up on the symptoms experienced, but may include thyroid, prolactin, follicle stimulating hormone, fasting glucose and insulin levels.

Hematologic and Immunologic Testing

Several blood disorders have been implicated in recurrent miscarriages. Women with abnormal blood clotting may be predisposed to early or late miscarriage and women with high risk personal or family histories should be tested. Women with these disorders have a high success rate when properly treated. Testing and treatment of low risk patients continues to be debated among physicians, however even in these cases, the most common abnormalities should be ruled out.

Uterine Abnormalities.

Distortion of the uterine cavity may be found in approximately 10% to 15% of women with recurrent pregnancy losses.

There are some great online resources to finding out how much testing will cost, a breakdown of each area of testing and what they all mean. Once you get tested and talk to your doctor, you can then move forward. Never start your own treatment based on what is found online. Only your doctor will know the best way to treat you and help you achieve a healthy pregnancy.

(RPL information)http://www.stanfordivf.com/recurrent-pregnancy-loss.html

(RPL Overview) http://emedicine.medscape.com/article/260495-overview

(Should you ask for Genetic Testing?) https://www.dnadirect.com/web/article/testing-for-genetic-disorders/recurrent-pregnancy-loss/50/who-should-consider-testing

(Information on testing cost and breakdown) http://www.fertilityplus.org/faq/miscarriage/rpl.html

Check back for information on Infertility information and testing information and some of the common factors into fertility difficulties.

Feel free to add any questions or comments in the comments section below or in this thread on TTCAL- RPL Blog Post- Link and Discussion/Questions