Senior Consultant, Medical Genetics, Artemis Hospitals, Gurgaon, India
Part 2 of 12 in Finding Answers in Recurrent Pregnancy Loss
Fetal Chromosomal Abnormalities: The Leading Cause of First-Trimester Loss
June 7, 2026
Chromosomal abnormality in the fetus is the single most common cause of first-trimester pregnancy loss, accounting for roughly 50% of losses overall and as much as 50-90% the earlier the loss occurs, a figure that falls to just 6-12% by the second trimester. The abnormalities range from aneuploidy (an abnormal chromosome count, with trisomies 16 and 22 among the most common found in recurrent loss tissue) to triploidy, where all chromosomes are present in three copies instead of two, to mosaicism and more complex structural rearrangements.
Parental age matters here: women above 35 and men above 40 have a greater tendency to produce eggs or sperm carrying an abnormal chromosome count, with the effect roughly twice as likely to originate from the mother. When a pregnancy loss occurs (particularly if tissue is retrieved surgically), Dr. Singh recommends chromosomal microarray over traditional karyotype testing, since microarray has a much higher diagnostic yield; a maternal blood sample must be sent alongside the tissue to rule out maternal cell contamination skewing the result.
This guide is based on a live Jivo Masterclass — Dr. Kanika Singh taught doctors across Africa on June 7, 2026.
FROM THE LIVE Q&A
Dr. Agbogus Stanley
For patients with PCOS, how long should metformin be taken before conception and after conception?
Dr. Kanika Singh
Metformin should be started at least 2 to 3 months before conception. It is safe to continue in pregnancy and is generally continued through the first trimester and sometimes beyond. It should be monitored with GTT as well as regular HbA1c and blood sugar checks throughout.
Frequently Asked Questions
My question is about sperm collection. In my clinic I often see couples where the male is over 50 years old. What are the chances of getting good quality sperm, and what are the implications for implantation?▼
I will not be able to give you details about specific sperm selection procedures, as in our hospital this is a multidisciplinary process involving the IVF specialist and the andrology laboratory. But in terms of the genetic implications: above the age of 50, there is a high chance that sperm quality is reduced, and the sperm DNA fragmentation index is likely to be elevated. Unless we specifically test for it, we do not know the exact level, but even without testing, there is a significant chance that sperm DNA quality is impaired, which can result in recurrent pregnancy loss or implantation failure. Testing the sperm DNA fragmentation index in men above 50 with a history of recurrent pregnancy loss or implantation failure would be worthwhile.
For patients with PCOS, how long should metformin be taken before conception and after conception?▼
Metformin should be started at least 2 to 3 months before conception. It is safe to continue in pregnancy and is generally continued through the first trimester and sometimes beyond. It should be monitored with GTT as well as regular HbA1c and blood sugar checks throughout.
What is the most common cause of first-trimester pregnancy loss?▼
Chromosomal abnormality in the fetus, accounting for roughly 50% of losses overall and as much as 50-90% the earlier the loss occurs, falling to just 6-12% by the second trimester.
Which chromosomal abnormalities are most often found in recurrent pregnancy loss tissue?▼
Trisomies 16 and 22 are among the most common, alongside triploidy (all chromosomes present in three copies), mosaicism, and more complex structural rearrangements.
Does parental age increase the risk of chromosomal abnormality in pregnancy loss?▼
Yes. Women above 35 and men above 40 have a greater tendency to produce eggs or sperm carrying an abnormal chromosome count, with the effect roughly twice as likely to originate from the mother.
Why is chromosomal microarray recommended over karyotype testing after a pregnancy loss?▼
Microarray has a much higher diagnostic yield than traditional karyotype testing when analysing tissue retrieved after a loss.
Why is a maternal blood sample needed alongside the tissue sample for microarray testing?▼
A maternal blood sample must be sent alongside the tissue to rule out maternal cell contamination skewing the result.
In This Series: Finding Answers in Recurrent Pregnancy Loss
- 1.Finding Answers in Recurrent Pregnancy Loss
- 2.Fetal Chromosomal Abnormalities: The Leading Cause of First-Trimester Loss
- 3.Balanced Translocation: When a Genetically Normal Parent Passes on Recurrent Loss
- 4.Single-Gene Causes: Why Second-Trimester Losses Need a Different Genetic Workup
- 5.Anatomical Causes: Uterine Septum, Fibroids, and Cervical Incompetence
- 6.Antiphospholipid Antibody Syndrome: Diagnosis and Treatment
- 7.Endocrine Causes: Thyroid, PCOS, and Diabetes in Recurrent Pregnancy Loss
- 8.Sperm DNA Fragmentation: The Male Factor in Recurrent Pregnancy Loss
- 9.The Immunological Debate: NK Cells, TNF-Alpha, and IVIG Therapy
- 10.What to Test For: A Practical Investigation Framework by Trimester
- 11.Pre-Implantation Genetic Testing: PGT-A, PGT-M, PGT-SR and PGT-HLA Explained
- 12.Prognosis After Recurrent Pregnancy Loss: Why the Outlook Is Better Than Most Couples Expect