Researchers at Lund University in Sweden have made a groundbreaking discovery, establishing a connection between specific defects in sperm DNA and the risk of pregnancy complications as well as adverse outcomes for newborns. The study reveals that a higher proportion of spermatozoa with DNA strand breaks is associated with a doubled risk of preeclampsia in women who conceive through in vitro fertilization (IVF). Additionally, this DNA damage increases the likelihood of premature births.
As infertility rates continue to rise, the demand for IVF procedures has surged. Previous research has indicated that women undergoing assisted reproductive technologies face a heightened risk of complications, including preeclampsia, recurrent miscarriages, and the birth of underweight or premature babies. However, the underlying causes of these risks have remained unclear.
“Prior to a planned IVF procedure, a man’s sperm is evaluated for concentration, motility, and morphology. Yet, some men who exhibit normal results in these tests still experience reduced fertility,” explains Amelie Stenqvist, a lecturer at Lund University and a specialist in gynecology and obstetrics at Skåne University Hospital in Malmö.
The study found that approximately 20-30% of babies conceived through IVF have fathers with significant DNA damage in their sperm, as indicated by elevated levels of DNA fragmentation. The DNA fragmentation index (DFI) measures the extent of DNA strand breaks and provides critical insights into male fertility. While sperm with DNA damage can still achieve fertilization, the likelihood diminishes, particularly when the DFI exceeds 30%, at which point natural conception becomes nearly impossible.
Despite advancements in assisted reproduction techniques allowing men with high DFI levels to father children, the implications of DNA fragmentation on pregnancy and newborn health have not been well understood. Research in this area has been hampered by the absence of DFI measurement in standard fertility assessments at Swedish clinics, alongside the challenges of accessing large study populations and national medical registries.
“Since half of the placenta’s DNA is inherited from the father and proper placental development is crucial for preventing preeclampsia, we aimed to explore how a high percentage of DNA damage in sperm affects the risk of this condition,” says Aleksander Giwercman, professor of reproductive medicine at Lund University and consultant at Skåne University Hospital.
Giwercman led a significant study involving 1,660 children conceived through IVF and intracytoplasmic sperm injection (ICSI) at the Reproductive Medicine Centre in Malmö from 2007 to 2018. The results indicated that in the 841 couples who underwent IVF, a DFI exceeding 20% doubled the likelihood of preeclampsia (10.5% risk) and also increased the chances of premature birth. In contrast, couples with a DFI below 20% experienced a 4.8% risk of preeclampsia, comparable to naturally conceived pregnancies. No association was found between DFI and preeclampsia in couples undergoing ICSI.
Currently, DFI analysis is only standard at select fertility clinics in Sweden. Giwercman advocates for its broader implementation across all clinics, asserting that it can provide couples with insights into infertility and guide the choice of assisted reproductive methods. Furthermore, he emphasizes that DFI analysis could play a vital role in identifying high-risk pregnancies.
What adds another layer of significance to this study is the potential treatability of sperm DNA fragmentation, which is often linked to the father’s overall health. Oxidative stress, an imbalance between damaging molecules and protective antioxidants, is a primary cause of DNA damage. Other contributing factors include the father’s age, smoking habits, obesity, and infections.
“The next step is to determine which groups of men are most likely to benefit from interventions aimed at preventing and treating sperm DNA damage, as well as testing these methods to mitigate pregnancy complications,” concludes Amelie Stenqvist.
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