Men’s sperm quality has fallen drastically in high-income countries in the past 50 years. Intensive research is therefore underway to find ways to revitalize these lethargic sperm. Now, Danish researchers have measurably increased the chances of men with low sperm quality becoming fathers through vitamin D pills, even though the sperm quality did not seem to improve. The researchers believe that giving vitamin D pills to women may improve the chances of an egg being fertilized by a high-quality sperm, thereby improving the chances of pregnancy.
Involuntary childlessness has been a growing problem in high-income countries since the 1980s. A study in the United Kingdom revealed that 1 in 7 couples could not achieve pregnancy naturally. A study in Sweden demonstrated that the quality of men’s sperm was a reason for infertility among two thirds of couples. Research has shown that vitamin D deficiency may be part of the reason and that vitamin D supplements have improved sperm quality in animals. This is the first time that researchers have directly investigated how vitamin D supplements affect men with reduced fertility.
“Men who were totally vitamin D deficient increased sperm production if we gave them vitamin D pills. However, the sperm quality of men with a slightly reduced level of vitamin D did not improve. Nevertheless, men with low sperm counts fathered twice as many children as those who did not get vitamin D supplements. We do not yet understand why, but one of our theories is that vitamin D plays an important role in the communication between a woman’s egg and a man’s sperm,” explains Martin Blomberg Jensen, Department of Growth and Reproduction, Rigshospitalet.
The study included 330 men with a low level of vitamin D who had difficulty in fathering children because of poor sperm quality. Half the men received a high dose of vitamin D – and the other half a placebo. The researchers then monitored the sperm quality and the number of pregnancies during the following 150 days.
“The results were conclusive. Vitamin D supplementation benefited sperm production in the group of infertile men who were vitamin D deficient. For men with reduced sperm production, this appeared to significantly improve their chances of becoming a father. And this is good news for men with poor sperm quality, because vitamin D is an inexpensive and harmless contribution to fertility treatment for men severely deficient in vitamin D.”
More natural pregnancies
According to the researchers, people who are vitamin D deficient and have reduced fertility can benefit from taking 25–35 micrograms (1000–1400 IU) of vitamin D daily during the winter. The researchers had naturally hoped to see an equally beneficial effect for men with a slightly reduced level of vitamin D, but the evidence is also clear there. These men had no measurable improvement in their sperm quality or their reproductive hormones after 5 months of taking the supplement.
“This shows that these types of studies are needed because they can show causal connections. But Rome wasn’t built in a day. Simply taking large quantities of vitamin D does not lead to fantastic sperm quality. It is just not that simple.”
Thus, the study concludes that men who are severely deficient in vitamin D can benefit from taking vitamin D. For other men, however, vitamin D is apparently not the solution – or perhaps it is anyway?
“We also looked at the main problem for infertile couples: pregnancies and live births. Here we actually saw a trend that taking supplementary vitamin D increased the chances of getting pregnant naturally and that men with reduced sperm production actually had twice as great a chance of becoming a father compared with the men who received the placebo therapy. So perhaps there is something in the sperm function we do not fully understand, although the results need to be reproduced by others before they can be used as clinical recommendations.”
Long journey without vitamin D
Just as this new study provides new answers, it raises the crucial question of how more women got pregnant naturally even though sperm quality did not improve measurably. Because a man’s sperm quality is largely determined at the fetal stage, male infertility often results from undescended testicles before birth, and vitamin D is important in producing sperm cells in the testicles. But the sperm cells go on a long journey before they again meet vitamin D.
“We know that sperm cells must learn to swim when they leave the tube in the testicles – the epididymis. And they remain there until they are released and mixed with seminal fluid from the prostate. The interesting thing is that there is actually a long delay between when sperm cells are produced in the testicles, during which time they are not affected by the level of vitamin D level, and when they are transferred to a woman.”
Women’s concentration of active vitamin D follows a cycle, meaning that it totally depends on her menstrual cycle. The level is low during menstruation but is high at ovulation – not just in her blood but also in the fluid surrounding the egg.
“We have previously shown by labelling a man’s sperm as to whether they can respond to vitamin D and convert it that only the very best sperm cells can do this. So vitamin D may be a signal from a woman’s egg to a man’s sperm cells. This may therefore be one way that a woman’s egg can choose the best sperm cells for fertilization.”
More than 1000 different genes
The role of vitamin D in fertility therefore appears to be much more complex than initially thought. If the researchers’ theory that the egg’s vitamin D level helps to select the sperm cells that respond to vitamin D can be confirmed, this may explain why the men in the study were associated with more pregnancies without any apparent improvement in their sperm quality.
“We can consider whether we have actually given vitamin D to the wrong sex. Maybe women should also be given vitamin D and not just the men. So we hope others will investigate whether increasing the vitamin D levels of women can help to increase the chances of fertility for infertile couples.”
Additional research is thus required before researchers can conclude whether both men and women can benefit from vitamin D supplementation. Above all, the researchers would like to understand exactly how vitamin D works, but this has proved to be more complex than initially thought because vitamin D regulates more than 1000 genes.
“We have previously shown beneficial local effects of vitamin D, but increasing the level of vitamin D in the body does not simply affect the bones and testicles. It also affects all the organs, and other organ functions affected by vitamin D supplementation could reduce fertility. We would therefore really like to pinpoint the genes that vitamin D regulates so that, instead of giving people a substance that influences many functions, we can find one that is more specific,” concludes Martin Blomberg Jensen.
“Effects of vitamin D supplementation on semen quality, reproductive hormones and live birth rate: a randomized clinical trial” has been published in the Journal of Clinical Endocrinology and Metabolism. The Novo Nordisk Foundation awarded a grant in 2017 to Martin Blomberg Jensen, Senior Researcher and Group Leader at Rigshospitalet, for the project RANKL and Male Fertility, which focuses on a gene regulated by vitamin D and how it affects male reproduction.
