Recurrent Pregnancy Loss: What Genetics Can and Can’t Tell Us

Miscarriage is far more common than most people realize, and it is rarely talked about. At least 1 in 10 known pregnancies ends in early pregnancy loss.¹ For some people, it happens more than once. The American Society for Reproductive Medicine (ASRM) defines recurrent pregnancy loss (RPL) as two or more pregnancy losses, including very early losses detected only by a pregnancy test.²

If you have experienced this, it’s natural to question why it happened, or even whether you did something to cause it. According to the American College of Obstetricians and Gynecologists, exercising, typical work environments, having sex, and past birth control pill use typically do not cause miscarriage.^3–6

This guide covers what research tells us about the causes of pregnancy loss and where genetics fit in.

Chromosomes are the most common cause

About half of first-trimester miscarriages are associated with a chromosomal difference in the embryo, such as a missing or extra chromosome.⁷ These changes usually happen by chance as the embryo forms, and nothing a person did caused them. The largest factor that raises the chance of a chromosomal difference is the age of the egg.⁸

This is why testing the tissue from a miscarriage is often one of the first steps after a loss, if possible.² It can show whether a chromosomal difference was present.

Is there any testing available for the parents?

Yes. If a couple has experienced recurrent pregnancy loss (RPL), a karyotype is recommended for both partners. This blood test looks at a person’s chromosomes and can show whether a parent carries a balanced translocation, meaning pieces of two chromosomes have swapped places.

People with a balanced translocation are usually healthy, because all of their genetic material is still present. However, their embryos can inherit an unbalanced amount of genetic material, which can lead to failed implantation or miscarriage.

If a translocation is found, one option is to screen embryos during IVF, before pregnancy, using preimplantation genetic testing for structural rearrangements (PGT-SR).

Chromosomes don’t explain every loss

Even when an embryo has the expected number of chromosomes (called euploid), it can still fail to implant or be lost. Other well-documented contributors include:²

• Uterine structural differences (e.g., septum, fibroids, polyps)
• Endocrine factors (e.g., thyroid disease, diabetes)
• Antiphospholipid syndrome and other immune factors
• Chronic endometritis and other infection-related factors

In many cases, no clear cause is found, even after a complete evaluation.

Other genetic causes

In some individuals with pregnancy loss, some specific changes in single genes can:

• Affect implantation, making it harder for an embryo with the expected number of chromosomes to implant⁹
• Disrupt early development in ways that can lead to miscarriage¹⁰
• Cause severe genetic syndromes, serious enough that a continuing pregnancy would likely lead to stillbirth or death shortly after birth⁹

This is an active area of research, and the list of genes linked to pregnancy loss continues to grow.

What genetics can’t tell us yet

Genetic screening can’t explain every loss, and it can’t guarantee a healthy pregnancy. Many factors that contribute to failed implantation and miscarriage, both genetic and non-genetic, are still unknown to science. Screening is one part of a larger picture that also includes your medical history, your evaluation, and the care your doctor recommends.

How Orchid can help

For families going through IVF, Orchid’s whole genome embryo screening (PGT-WGS) looks at chromosomes and single genes using the same biopsy.

• Chromosomes. Orchid screens embryos for missing or extra chromosomes. It also screens for smaller chromosomal changes and differences that traditional PGT-A may miss.
• Translocations. If a parent carries a balanced translocation, PGT-SR can be added to screen embryos for unbalanced rearrangements.
• Single genes. Orchid’s failed implantation, miscarriage, and stillbirth panel screens embryos for 130+ genes, each supported by published evidence linking it to these outcomes.

This information can help you and your care team prioritize embryos for transfer. PGT is a screen. It doesn’t replace care recommended during pregnancy, including ultrasound and diagnostic testing such as amniocentesis.

References

1. American College of Obstetricians and Gynecologists. Early Pregnancy Loss. acog.org/womens-health/faqs/early-pregnancy-loss
2. Practice Committee of the American Society for Reproductive Medicine. Recurrent pregnancy loss: a committee opinion. Fertil Steril. 2026;125(6):1023–1041. doi:10.1016/j.fertnstert.2026.03.001
3. American College of Obstetricians and Gynecologists. Early Pregnancy Loss. acog.org/womens-health/faqs/early-pregnancy-loss
4. Barakat R, et al. The influence of physical activity during pregnancy on miscarriage: systematic review and meta-analysis. J Clin Med. 2023;12(16):5393. doi:10.3390/jcm12165393
5. Niles KM. Sex in the first trimester. In: Farine D, González PT, eds. Sex and Pregnancy: From Evidence-Based Medicine to Dr Google. Cambridge University Press; 2022:70–76. doi:10.1017/9781009025034.012
6. Yland JJ, et al. Preconception contraceptive use and miscarriage: prospective cohort study. BMJ Med. 2023;2(1):e000569. doi:10.1136/bmjmed-2023-000569
7. Pylyp LY, et al. Chromosomal abnormalities in products of conception of first-trimester miscarriages detected by conventional cytogenetic analysis. J Assist Reprod Genet. 2018;35(2):265–271. doi:10.1007/s10815-017-1069-1
8. Elmerdahl Frederiksen L, et al. Maternal age and the risk of fetal aneuploidy. Acta Obstet Gynecol Scand. 2024;103(2):351–359. doi:10.1111/aogs.14713
9. Hyde KJ, Schust DJ. Genetic considerations in recurrent pregnancy loss. Cold Spring Harb Perspect Med. 2015;5(3):a023119. doi:10.1101/cshperspect.a023119
10. Quintero-Ronderos P, et al. Potential genetic causes of miscarriage in euploid pregnancies: a systematic review. Hum Reprod Update. 2019;25(4):452–472. doi:10.1093/humupd/dmz015

This material is for general educational purposes and is not a substitute for medical advice, genetic counseling, or diagnostic testing.