Obstetrics & GynaecologyDr. Soma SinghInfertility & IVF

Associate Director, IVF & Infertility, Max Super Speciality Hospital, Noida

Part 5 of 9 in Recent Advances in the Management of an Infertile Couple

Sperm DNA Fragmentation and the Evaluation of Male Infertility

December 21, 2025

A standard semen analysis does not tell the whole story. Many men with a normal semen analysis still have unexplained infertility, which is why sperm function tests such as the DNA fragmentation index, or DFI, have become an important additional marker.

What drives DNA fragmentation

Sperm DNA damage is caused by an imbalance between reactive oxygen species, free radicals normally produced during oxygen metabolism, and the body's antioxidant defences. Infections, smoking, pollution, radiation, varicocele and chronic illnesses such as diabetes all increase reactive oxygen species and raise the risk of sperm DNA damage. A DFI below 15% suggests good fertility potential, 15 to 25% suggests reduced potential, and above 25% suggests poor fertility potential.

When DFI testing is used, and a real case

DFI testing is reserved for selected situations: advanced male age, obesity, diabetes, smoking, varicocele, prior chemotherapy or radiation, unexplained infertility, or a male partner whose new partner cannot conceive despite a previously fertile history. In one case Dr. Singh presented, a couple had tried for four years with three unsuccessful IUI cycles elsewhere; the female partner's workup was entirely normal, but the male partner, a smoker with an otherwise normal semen analysis, had a DFI of 42%. Based on this finding they were counselled toward ICSI rather than further IUI attempts, and the woman conceived after her first embryo transfer.

This article is based on a Jivo Masterclass session conducted by Dr. Soma Singh, Associate Director, IVF & Infertility, Max Super Speciality Hospital, Noida. The article has been summarised with the assistance of an AI tool from the original masterclass recording. Watch the full Masterclass recording

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This guide is based on a live Jivo Masterclass — Dr. Soma Singh taught doctors across Africa on December 21, 2025.

FROM THE LIVE Q&A

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Host (Varun, Jivo Healthcare)

Given that couples are increasingly delaying pregnancy, how should a woman in her late 30s or 40s think about her real chances, and what can medically be done for her?

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Dr. Soma Singh

Ovarian reserve varies a great deal between individuals at the same age, so egg number is not always the limiting factor after 35 or 40; egg quality is. As age advances, errors in the meiotic spindle mechanism increase, making chromosomally abnormal eggs and embryos more likely, which raises both implantation failure and miscarriage risk: roughly 12 to 15% up to age 35, rising toward 20% between 35 and 38, 25% between 38 and 41, and around 50% after 42. For a woman who wants to use her own eggs, pre-implantation genetic testing can screen embryos before transfer, provided she has enough reserve to reach a day-five blastocyst. Endometrial receptivity also declines with age, independent of egg quality, which is why even donor-egg pregnancies become harder to sustain after 44. Ovarian rejuvenation therapy using platelet-rich plasma is being tried and shows promise for some women, though the evidence is still accumulating.

See all 7 questions from this masterclass →

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Frequently Asked Questions

What are the complications and risks of embryo transfer?

The procedure itself is not risky, but the implantation rate is only around 30 to 40%, which is why IVF success rates are not higher. Transferring more than one embryo to improve the pregnancy rate raises the chance of a multiple pregnancy, such as twins or triplets, well above the rate seen in natural conception. Placement technique also matters: pushing too much volume or placing an embryo too close to the fallopian tube raises the risk of an ectopic pregnancy, and in rare cases a heterotopic pregnancy can occur, where one embryo implants in the uterus and another develops in the tube, a complication seen almost exclusively with IVF.

Can IVF be used for women in menopause who still want to conceive, and do they have any extractable eggs at that stage?

A menopausal woman has no retrievable eggs of her own, but she can still conceive using a donor egg, which is a common and well-established approach even at a young age. After menopause the ovary is no longer producing estrogen, so hormones are given from outside to prepare the uterine lining, a donor egg is used, and the pregnancy proceeds and can be carried to delivery without issue.

What is the importance of haemoglobin electrophoresis in evaluating infertility?

It is used as a screening tool before starting any infertility treatment, whether ovulation induction, IUI or IVF, to know whether the woman carries an abnormal haemoglobin such as haemoglobin S or C, or is a thalassaemia carrier. If she is found to be a carrier, the male partner needs to be evaluated too, because of the inheritance risk: if both partners are thalassaemia minor carriers, for example, there is a 25% chance of a child being thalassaemia major. Couples in this situation may need genetic counselling or pre-implantation genetic testing, screening embryos for these conditions before transfer.

A married 28-year-old man reported two years of painless issues with sperm appearing in his urine, mostly at the start of urination, with no history of conception. How should this be managed?

Sperm found in urine points to retrograde ejaculation, which usually follows a pelvic, perineal or urological surgery, or occasionally occurs in diabetes. Natural conception is not possible in this situation. The approach is to give the male partner an alkalinizing agent, then collect a urine sample immediately after ejaculation, centrifuge it and separate the sperm. Depending on the concentration recovered, those sperm can then be used for IUI or for IVF with ICSI. Any underlying epididymitis should be treated with antibiotics first, and the infection cleared, before using the sperm collected this way.

What is the principle behind managing oligospermia, and is there a therapy for congenital azoospermia?

For oligospermia, the approach depends on how low the concentration is: a genetic evaluation including karyotyping and Y-chromosome microdeletion testing is warranted, alongside correcting modifiable lifestyle factors such as smoking and alcohol, and giving antioxidants. Because sperm production takes about 90 days from formation to transport, semen analysis should be repeated after 8 to 12 weeks. If genetics are normal and the count improves, IUI is reasonable; if not, assisted reproduction is the next step. For azoospermia, a full hormonal evaluation is needed to distinguish hypergonadotropic from hypogonadotropic causes. A hypogonadotropic pattern can often be managed medically with gonadotropins. A hypergonadotropic pattern means the testes themselves have failed, and the approach then is surgical sperm retrieval, such as TESA or micro-TESE, followed by ICSI.

What is the DNA fragmentation index (DFI) and why does it matter?

DFI measures the extent of DNA damage inside sperm. A result below 15% suggests good fertility potential, 15 to 25% suggests reduced potential, and above 25% suggests poor fertility potential, and it can explain infertility even when a standard semen analysis looks normal.

Who should be tested for sperm DNA fragmentation?

Testing is reserved for selected cases: advanced male age, obesity, diabetes, smoking, varicocele, prior chemotherapy or radiation, unexplained infertility, or recurrent pregnancy loss.

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