Sperm fragmentation a risk factor for pregnancy complications

High sperm deoxyribonucleic acid fragmentation index (DFI) level appears to negatively affect the outcome of pregnancies achieved with assisted reproductive technology (ART), being linked to increased risks of complications such as preterm birth and pre-eclampsia in a new research.

In a cohort of 1,594 infertile couples who underwent in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment and their 1,660 children in Sweden, DFI analysis by Sperm Chromatin Structure Assay showed that a DFI level of ≥20 percent was associated with increased odds of preterm birth (odds ratio [OR], 1.4, 95 percent confidence interval [CI], 1.0–2.0), with a DFI level of <20 percent as reference. [Fertil Steril 2024;doi:10.1016/j.fertnstert.2024.08.316]

In the IVF subgroup (n=841) specifically, a DFI level of ≥20 percent raised the odds of pre-eclampsia by twofold (OR, 2.2, 95 percent CI, 1.1–4.4). When a DFI level of <10 percent was used as reference, the odds of pre-eclampsia successively increased at higher DFI levels: ≥10 percent to <20 percent (OR, 2.0, 95 percent CI, 0.95–4.3), ≥20 percent to <30 percent (OR, 2.9, 95 percent CI, 1.1–7.9), ≥30 percent to <40 percent (OR, 3.5, 95 percent CI, 0.89–14), and ≥40 percent (OR, 13.7, 95 percent CI, 2.2–86). This association was not observed in the ICSI subgroup (n=741).

“A potential explanation for why we see this association in the IVF group and not in the ICSI group could be that a spermatozoon with normal morphology is chosen by the embryologists for fertilization in ICSI cycles. This active selection may lead to fertilization with a spermatozoon with less DNA damage,” the investigators said. [Biol Reprod 2019;101:1076-1082]

“In IVF, the oocyte is coincubated with spermatozoa, which makes it at higher risk of being exposed to increased levels of reactive oxygen species, metabolic end-products, and microbes. Because the reactive oxygen species levels increase with a high DFI level, a hypothesis is that these elevated levels of harmful products affect the oocyte and that this could be a contributing factor in the development of the placenta and, thereby, increasing the risk of pre-eclampsia and preterm birth,” they explained. [Hum Reprod 2004;19:129-138]

DFI testing warranted

“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. It can give couples answers as to why they are not getting pregnant and can influence the chosen method of assisted fertilization. Our latest results [also] show that a DFI analysis could be used to identify high-risk pregnancies,” said senior investigator Dr Aleksander Giwercman from Skåne University Hospital in Malmö, Sweden.

Giwercman emphasized that implementing a DFI-based risk assessment and screening program can enable personalized risk evaluation and targeted interventions to minimize the likelihood of pre-eclampsia. For example, in couples with a DFI level above 10–20 percent, ICSI may be performed instead of IVF. Additionally, prophylactic acetylsalicylic acid use during pregnancy can help reduce pre-eclampsia risk in certain high-risk ART patients.

The next step in the study is to investigate which groups of men are most likely to benefit from sperm DNA damage prevention and treatment methods. This information will help develop tailored strategies for preventing pregnancy complications, according to Giwercman and colleagues.