What is Recurrent Pregnancy Loss ?
![Recurrent Pregnancy Loss](https://diagnostics.medgenome.com/wp-content/uploads/2019/12/recurrent-pregnancy-loss-banner.png)
Recurrent Pregnancy Loss (RPL) is defined as three consecutive pregnancy losses occuring prior to 20 weeks from the last menstrual period1
Prevalence
- RPL is reported in approximately 1% to 2% of pregnant women
- Current techniques can identify up to 50% of couples suffering from RPL2
- Genetic causes account for about 2% to 5% of RPL1
- [1] Ford HB, Schust DJ. Recurrent pregnancy loss: etiology, diagnosis, and therapy. Rev Obstet Gynecol 2009;2: 76-83.
- [2] Jaslow CR, Carney JL, KuttehWH. Diagnostic factors identified in 1020 women with two versus three or more recurrent pregnancy losses. Fertil Steril. 2010;93(4):1234–43.
![Recurrent Pregnancy Loss](https://diagnostics.medgenome.com/wp-content/uploads/2019/12/recurrent-pregnancy-loss-banner.png)
What are the genetic causes of RPL?
![recurrent miscarriage testing](https://diagnostics.medgenome.com/wp-content/uploads/2019/12/What-are-the-genetic-causes-of-RPL.jpg)
- 30% to 50% of all miscarriages are due to cytogenetic reasons3
- 2% to 4% of RPL is associated with a parental balanced structural chromosome rearrangement, most commonly balanced reciprocal or Robertsonian translocations1
- Other reasons include chromosomal inversions, insertions, and mosaicism1
- [3] Ogasawara M, Aoki K, Okada S, et al. Embryonic karyotype of abortuses in relation to the number of previous miscarriages. Fertil Steril. 2000;73: 300–304
Why do you need the test?
![rpl in pregnancy](https://diagnostics.medgenome.com/wp-content/uploads/2019/12/recurrent-pregnancy-loss-left.jpg)
Abortion has multiple causes and may involve endocrine, anatomic, immunological, infectious, environmental, and genetic factors. RPL testing can:
- Detect if the pregnancy loss was due to an abnormal chromosome number (aneuploidy)
- Provide information that can be helpful for patients and physicians to understand the cause of the pregnancy loss
- Develop a plan to support a successful pregnancy in the future
When do you need to get tested?
![rpl testing](https://diagnostics.medgenome.com/wp-content/uploads/2019/12/recurrent-pregnancy-loss-right2.jpg)
When a couple experiences a second pregnancy loss they can consider getting a RPL test done. This involves testing the products of conception (POC). In addition, parental karyotyping can be done along with an appropriate pre and post-test genetic counselling.
How is the test done?
![](https://diagnostics.medgenome.com/wp-content/uploads/2019/08/rpl-ttesting.png)
RPL testing is done by taking a small sample of the POC and checking for chromosomal abnormalities using standard techniques such as Karyotyping and Fluorescence In Situ Hybridization (FISH).
![](https://diagnostics.medgenome.com/wp-content/uploads/2019/08/rpl-ttesting2.png)
More advanced methods such as Chromosomal Microarrays(CMA) offer an in-depth analysis of the defect going into microdeletions and microduplications that could have caused the miscarriage.
Advantages of CMA
- Needs no cell culture
- Detects chromosomal deletion/duplications by use of the highly sensitive platform with >99% sensitivity
- Increased whole-genome coverage targeting 396 relevant regions for prenatal analysis (18,018 CNV and 148,450 SNP)
- Increased coverage density (25 markers/100 kb) in 396 empirically selected regions relevant for prenatal research
- Detects low levels of mosaicism in the sample
- Offers a minimum resolution of 1Mb for losses, 2Mb for gains, and 5Mb for LOH/AOH (Loss/Absence of Heterozygosity)
Parental Karyotyping
![recurrent pregnancy loss testing](https://diagnostics.medgenome.com/wp-content/uploads/2019/12/Parental-Karyotyping.jpg)
About 5% of couples with RPL are known to carry Robertsonian translocations and balanced reciprocal translocations. Both the specific chromosome(s) affected, and the types of rearrangement influence the probability of a future live birth. Conventional karyotyping can be used in such cases. This standard method can detect most chromosomal abnormalities. Pre and post-test genetic counselling are essential.4
- [4] Regan L, Backos M, Rai R. 2011. Green-top GuidelineNo 17. The investigation and treatment of couples with recurrent first-trimester and second-trimester miscarriage. Royal College of Obstetricians and Gynaecologists (RCOG), London.
Who needs to get tested?
Couples who have:
- Pregnancy loss with fetal abnormalities
- Recurrent pregnancy loss
- Repeated miscarriages while undergoing IVF
RPL workflow
![](https://diagnostics.medgenome.com/wp-content/uploads/2019/08/RPL_Claria02.png)
Test Sample Requirement for CMA
![](https://diagnostics.medgenome.com/wp-content/uploads/2019/08/test-sample01.png)
Minimum 100 mg of Product of Conception (POC)
![](https://diagnostics.medgenome.com/wp-content/uploads/2019/08/test-sample02.png)
Taken in a sterile 15ml falcon tube either in a saline solution + 1% antibiotic or RPM1640 + 10%fbs + 1% antibiotic (Formalin fixed or degraded samples will not be accepted)
![](https://diagnostics.medgenome.com/wp-content/uploads/2019/08/test-sample03.png)
Also provide 3ml of maternal whole blood in a EDTA vacutainer for Maternal Cell Contamination check.