Defective sperm doubles pre-eclampsia risk in IVF patients

Swedish and Danish researchers have linked specific frequent defects in sperm to risk of pregnancy complications and negative impacts on the health of the baby, showing that a high proportion of the father’s spermatozoa possessing DNA strand breaks is associated with doubled risk of pre-eclampsia in women who become pregnant by IVF. This also increases the risk of the baby being born prematurely.

It is already known that women who become pregnant by assisted reproduction techniques such as in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) have an increased risk of pre-eclampsia, repeated miscarriages and the baby being born prematurely and with a lower birth weight, yet the reasons behind this have not been fully understood. As noted by Lund University’s Dr Amelie Stenqvist, a lecturer at Lund, “Before a planned in vitro fertilisation, the man’s sperm sample is analysed for concentration, motility and morphology. But there are men who, according to this analysis, have normal sperm, but still have reduced fertility.”

Around 20–30% of babies born through IVF have fathers with damaged DNA in their sperm, as shown by elevated levels of DNA fragmentation. The DNA fragmentation index (DFI) is a measure of the amount of strand breaks in the DNA and is used to provide important new information about male fertility. Sperm with DNA damage may still be fertile, but the chances of fertilisation are lower and if the percentage of DFI exceeds 30%, the chances of natural conception are close to zero.

Until now, little has been known about the impact of DNA fragmentation on pregnancy and the health of the baby. Furthermore, it has been difficult to research the topic because the DFI value is not included in the standard measurements currently taken by Sweden’s fertility clinics. Seeking to rectify this, Lund’s Professor Aleksander Giwercman led a research study that included 1660 children conceived through IVF and ICSI at the Reproductive Medicine Centre in Malmö from 2007–2018.

The study results, published in Fertility and Sterility, showed that in the 841 couples who underwent IVF, a DFI of over 20% doubled the risk of the woman developing pre-eclampsia (10.5%) and also increased the risk of premature birth. In the IVF group with a DFI below 20%, there was a 4.8% risk of pre-eclampsia, which is comparable to pregnancies that occur naturally. For couples undergoing ICSI, there was no association with pre-eclampsia.

“Today DFI analysis is only performed at some fertility clinics in Sweden, but we think that it should be introduced as standard at all clinics,” Giwercman said. “It can give couples answers as to why they are not getting pregnant and can influence the chosen method of assisted fertilisation. Not only that, our latest results show that a DFI analysis could be used to identify high-risk pregnancies.”

What makes this finding interesting is that high DNA fragmentation in sperm is linked to the overall health of the father and is potentially treatable. Most DNA damage is caused by oxidative stress, which is an imbalance between harmful molecules and the antioxidants that protect cells. Other factors that increase DNA fragmentation include the man’s age, smoking, obesity and infections.

“The next step is to identify which group of men respond best to methods to prevent and treat sperm DNA damage, and to test these methods to prevent pregnancy complications,” Stenqvist concluded.

Image credit: iStock.com/Rasi Bhadramani