Senior Consultant, Medical Genetics, Artemis Hospitals, Gurgaon, India
Part 10 of 12 in Finding Answers in Recurrent Pregnancy Loss
What to Test For: A Practical Investigation Framework by Trimester
June 7, 2026
Dr. Singh's framework starts with one question: did the losses happen in the first or second trimester? First-trimester losses point toward genetic and chromosomal causes, antiphospholipid antibody syndrome, endocrine factors and uterine structure; second-trimester losses point toward cervical incompetence, intrauterine adhesions, endometriosis, bacterial vaginosis, genitourinary anomalies, and (if there's a recurring ultrasound finding) a single-gene cause. Every patient should be tested for product-of-conception chromosomal microarray, uterine cavity evaluation (3D ultrasound, HSG or saline sonography), antiphospholipid antibodies (ideally 6 weeks post-loss), thyroid profile, HbA1c and PCOS screening.
Selected patients, where first-line workup is normal, may need couple karyotype (only if tissue testing wasn't possible), sperm DNA fragmentation, chronic endometritis screening, fasting prolactin, inherited thrombophilia testing, or the autoimmune markers described above. Key history points include the number and timing of losses, any autoimmune illness, occupational exposures, family history of loss or birth defects, and a history of PCOS, diabetes or DVT.
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 first question to ask when investigating recurrent pregnancy loss?▼
Whether the losses happened in the first or second trimester, since this shapes the entire investigation pathway.
What tests should every patient with recurrent pregnancy loss receive?▼
Product-of-conception chromosomal microarray, uterine cavity evaluation (3D ultrasound, HSG, or saline sonography), antiphospholipid antibodies ideally 6 weeks post-loss, thyroid profile, HbA1c, and PCOS screening.
When is couple karyotype testing recommended?▼
Only if product-of-conception tissue testing wasn't possible.
Which causes should be investigated for second-trimester losses?▼
Cervical incompetence, intrauterine adhesions, endometriosis, bacterial vaginosis, genitourinary anomalies, and a single-gene cause if there's a recurring ultrasound finding.
What key history points should be gathered from a couple with recurrent loss?▼
The number and timing of losses, any autoimmune illness, occupational exposures, family history of loss or birth defects, and a history of PCOS, diabetes, or DVT.
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