Health Rounds: Increasing sperm mutations in older fathers may affect offspring

Audio By Carbonatix

Enlarge

(This is an excerpt of the Health Rounds newsletter, where we present latest medical studies on Tuesdays and Thursdays.)

By Nancy Lapid

(Reuters) -The age of the father plays a role in pregnancy outcomes, with harmful genetic changes in sperm being substantially more common in older men, new research shows.

Along with a steady build-up of random changes in DNA as men got older, the researchers also discovered the increase in mutations is due to a subtle form of natural selection, with some mutations having a competitive edge during sperm production in the testes, according to a report in Nature.

In 81 healthy volunteers, researchers found that approximately 2% of sperm from men in their early 30s carried disease-causing mutations, compared to 3% to 5% of sperm from men ages 43 to 74, and 4.5% of sperm from 75-year-olds.

Some of the mutations have been previously linked to cell growth and development, while others are associated with severe neurodevelopmental disorders in children and inherited cancer risk, the researchers noted.

Others may impair fertilization, embryo development, or result in pregnancy loss, they said.

“Some changes in DNA not only survive but thrive within the testes, meaning that fathers who conceive later in life may unknowingly have a higher risk of passing on a harmful mutation to their children,” Professor Matt Hurles of the Wellcome Sanger Institute in Hinxton, England, said in a statement.

In a complementary study involving over 54,000 parent–child trios and 800,000 healthy individuals, also published in Nature, some of the same researchers analyzed mutations already passed on to children, rather than those measured directly in sperm.

They identified more than 30 genes where mutations give sperm cells a competitive edge via natural selection, again including many linked to rare developmental disorders and cancer. Many such mutations overlap the set of genes observed directly in sperm.

The work highlights how natural selection within sperm can be directly observed in the DNA of children, influencing their chances of inheriting certain genetic disorders, the researchers said.

“Our findings reveal a hidden genetic risk that increases with paternal age,” Hurles, who co-authored both studies, said.

POPULAR PAIN MEDICINE FAILS TO KILL PAIN

The opioid painkiller tramadol is not very effective for easing the chronic pain for which it is widely prescribed, and it likely increases the risk of serious side effects, a new study found.

Researchers who pooled data from 19 previous trials involving 6,506 volunteers with chronic pain concluded that the potential harms of tramadol probably outweigh its benefits.

Five of the trials looked at the impact of tramadol on nerve-related pain; nine focused on osteoarthritis; four looked at chronic lower back pain; and one focused on fibromyalgia.

The average age of the trial participants was 58 and length of treatment ranged from 2 to 16 weeks.

The risk of harms associated with tramadol was twice the risk of placebo in the trials, mainly driven by a higher proportion of cardiac events such as chest pain, coronary artery disease, and congestive heart failure, according to a report in BMJ Evidence-Based Medicine.

Milder side effects included nausea, dizziness, constipation, and sleepiness.

Tramadol was also associated with a heightened risk of some cancers, although the follow-up period was short, making this finding “questionable,” the researchers said.

Until now, doctors have thought tramadol has a lower risk of side effects and is safer and less addictive than other opioid painkillers.

“Given the limited analgesic benefits and increased risk of harm, tramadol use for chronic pain should be reconsidered,” the researchers concluded.

AT-HOME MEDICAL ABORTION BEFORE 12 WEEKS IS SAFE

At-home early medical abortions before 12 weeks of pregnancy were just as safe and effective as those performed in a hospital, a small study from Scotland found.

Researchers analyzed five years of data from a single health center on 258 at-home medical abortions and 113 medical abortions done in hospital, all performed between 10 weeks and just under 12 weeks of pregnancy. There was a 97% success rate in completing the abortion in both groups, according to a report in BMJ Sexual & Reproductive Health.

Patients in both groups received the same medication regimen: an initial dose of 800 micrograms of misoprostol (administered orally or vaginally), followed by up to three 400-microgram doses at 4-hour intervals if needed. They also took 5 tablets of 30 mg dihydrocodeine for pain and 3 tablets of 50 mg cyclizine for nausea.

There were no statistically significant differences between the two groups in incomplete abortion rates, with 1.6% in the at-home group and 2.6% in the hospital group, or in ongoing pregnancy rates, which were 1.2% versus 0%.

For the hospital group, completion was confirmed by a healthcare professional witnessing the passage of the products of conception. For the home group, it was confirmed using a self-performed urinary pregnancy test two weeks after the procedure.

Although follow-up visits were low in both groups, the at-home group had higher rates than the hospital group, at 7% versus 2%, and also received telephone advice more often, 11% compared with 4%.

Additionally, patients in the at-home group were also more likely to make unscheduled contact with the hospital or abortion clinic (23% vs 9%).

“While patients receive written and verbal information on what to expect, some will also want verbal reassurance from a clinician,” said lead author Dr. Jacqueline Quinn from the University of Edinburgh Medical Research Council Centre for Reproductive Health.

Only four serious complications were reported, all in the at-home group. They were one hemorrhage a month after the procedure that the researchers say was unlikely to have been prevented by an in-hospital abortion, and three infections treated with IV antibiotics.

Since 2020, British law has allowed women to take abortion medication at home. In England and Wales, this is limited to pregnancies up to 10 weeks, while Scotland allows early medical abortion at home up to 12 weeks.

“This study demonstrates that policy in England/Wales and other parts of Europe which preclude early medical abortion at home (after) 10 weeks should be changed to allow women more choice,” Quinn said.

(To receive the full newsletter in your inbox for free sign up here)

(Reporting by Nancy Lapid; Editing by Bill Berkrot)