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Understanding the Impact of Sperm DNA Damage on IVF Pregnancy Risks

by Ella

Lund, Sweden — In a groundbreaking study from Lund University, researchers have established a link between specific defects in sperm and increased risks of pregnancy complications, including preeclampsia and premature birth in babies conceived through in vitro fertilization (IVF). The study reveals that a high percentage of spermatozoa with DNA strand breaks in fathers is associated with a doubled risk of preeclampsia among women who become pregnant via IVF.

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Infertility rates are rising, leading to a surge in IVF procedures. Women utilizing assisted reproductive technologies are already known to face higher risks of complications such as preeclampsia, recurrent miscarriages, and low birth weight infants. However, the underlying causes of these risks have remained largely unclear.

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“Current analyses of sperm samples focus on concentration, motility, and morphology, yet some men may have normal sperm according to these criteria but still experience reduced fertility,” explains Amelie Stenqvist, a lecturer at Lund University and specialist in gynecology and obstetrics at Skåne University Hospital in Malmö.

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Approximately 20 to 30 percent of babies conceived through IVF have fathers with damaged DNA in their sperm, as indicated by elevated DNA fragmentation levels. The DNA fragmentation index (DFI) measures the extent of DNA strand breaks and offers crucial insights into male fertility. While sperm with DNA damage can still achieve fertilization, the likelihood decreases significantly; if the DFI exceeds 30 percent, the chances of natural conception drop to nearly zero.

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Despite advances in reproductive technologies allowing men with high DFI to become fathers, little has been understood about the implications of DNA fragmentation for pregnancy outcomes and infant health. Research has been hampered by the absence of DFI evaluations in standard fertility clinic protocols in Sweden, as well as the necessity for large population studies and access to national medical registries.

“Given that half of the placenta’s DNA is inherited from the father and that placental health is critical to the development of preeclampsia, we aimed to determine whether elevated sperm DNA damage correlates with preeclampsia risk,” states Aleksander Giwercman, professor of reproductive medicine at Lund University and consultant at Skåne University Hospital. Giwercman led the research study encompassing 1,660 children conceived through IVF and intracytoplasmic sperm injection (ICSI) at Malmö’s Reproductive Medicine Centre between 2007 and 2018.

The findings indicated that among 841 couples undergoing IVF, a DFI exceeding 20 percent was linked to a doubling of the risk of preeclampsia, which affected 10.5 percent of these women. This high DFI also correlated with an increased risk of premature birth. In contrast, couples with a DFI below 20 percent showed a preeclampsia risk of just 4.8 percent, comparable to naturally conceived pregnancies. No such association was found in couples undergoing ICSI.

Currently, DFI testing is only conducted at select fertility clinics in Sweden, but researchers advocate for its standardization across all clinics. This testing could provide critical answers for couples struggling with infertility and help inform their assisted reproductive options. Furthermore, the latest findings suggest that DFI analysis could identify high-risk pregnancies.

Giwercman notes, “High DNA fragmentation in sperm is associated with the father’s overall health and is potentially treatable. Most DNA damage stems from oxidative stress—an imbalance between damaging molecules and protective antioxidants. Other contributing factors include the father’s age, smoking habits, obesity, and infections.”

The researchers plan to further investigate which groups of men are most responsive to interventions aimed at preventing and treating sperm DNA damage, ultimately seeking methods to mitigate pregnancy complications.

This study sheds light on the intricate relationship between sperm health and reproductive outcomes, opening new avenues for improving assisted reproductive techniques and enhancing the health of mothers and infants alike.

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