For the first time, researchers have linked certain common defects in sperm with the risk of pregnancy complications and negative effects on the health of the baby. The study by the University of Lund in Sweden shows that a high proportion of the father’s sperm with DNA strand breaks is associated with a twofold risk of preeclampsia in women who have become pregnant through IVF. This also increases the risk of premature birth.
In Vitro Fertilization and Male Sperm
Infertility is a growing problem and the number of in vitro fertilizations is increasing rapidly. It is already known that women who become pregnant through assisted reproductive techniques have an increased risk of preeclampsia, recurrent miscarriage and premature birth with lower birth weight. However, the reasons for this are not yet fully understood.
“Before in vitro fertilization is planned, the man’s sperm sample is examined for concentration, motility and morphology. However, there are men who, according to this analysis, have normal sperm but still have reduced fertility,” says Amelie Stenqvist, a lecturer at Lund University. She completed her doctorate in Lund and now works as a specialist in gynecology and obstetrics at the University Hospital of Skåne in Malmö. In about 20-30 percent of babies born through in vitro fertilization, the fathers have DNA damage in their sperm, as indicated by increased DNA fragmentation levels. The DNA Fragmentation Index (DFI) is a measure of the number of strand breaks in the DNA and is being used to provide important new information about male fertility. Sperm with DNA damage can still be fertile, but the chances of fertilization are lower, and if the DFI percentage exceeds 30 percent, the chances of natural conception are almost nil.
Sperm DNA Damage And the Risk of Preeclampsia
Although men with high DFI can become fathers thanks to today’s in vitro techniques, little was previously known about the effects of DNA fragmentation on pregnancy and the health of the baby. Research on this topic was difficult because the DFI value is not included in the standard measurements currently performed in Swedish fertility clinics. Furthermore, a large study population and access to national medical registers are required.
“Since half of the placenta’s DNA comes from the father and the development and function of the placenta play a central role in preeclampsia, we wanted to investigate whether a high percentage of DNA damage in the sperm affects the risk of preeclampsia,” says Aleksander Giwercman. He is a professor of reproductive medicine at Lund University, a consultant at Skåne University Hospital in Malmö and one of the researchers behind ReproUnion. Aleksander Giwercman also led a research study involving 1,660 children conceived through IVF and ICSI at the Center for Reproductive Medicine in Malmö during the period 2007–2018.
The results showed that among the 841 couples who underwent IVF, a DFI of over 20 percent doubled the risk of preeclampsia in the woman (10.5 percent) and also increased the risk of preterm birth. In the IVF group with a DFI below 20 percent, the risk of preeclampsia was 4.8 percent, which is comparable to pregnancies that occur naturally. No link with preeclampsia was found in couples who underwent ICSI.
Preventing Pregnancy Complications
Today, DFI analysis is only performed in some fertility clinics in Sweden, but researchers believe that it should be introduced as standard in all clinics. It can provide couples with answers as to why they are unable to conceive and influence their choice of assisted reproduction method. Furthermore, these latest results show that DFI analysis could be used to identify high-risk pregnancies.
This finding is all the more interesting given that high levels of DNA fragmentation in semen are associated with the father’s overall health and are potentially treatable. Most DNA damage is caused by oxidative stress, i.e. an imbalance between damaging molecules and the cell-protecting antioxidants. Other factors that increase DNA fragmentation include a man’s age, smoking, obesity and infectious diseases. The next step is to identify which group of men will respond best to methods of preventing and treating sperm DNA damage, and to test these methods to prevent pregnancy complications.