New studies continue to fail to confirm a clear relationship between low vitamin D levels and a reduced likelihood of pregnancy by in vitro fertilization (IVF). However, they do corroborate a lower rate of live newborns in those patients with vitamin D levels below 20ng/ml. Two new meta-analyses published in 2018 reopen research in this area.
What is vitamin D and how does it relate to pregnancy?
Vitamin D is a steroid hormone involved in calcium, phosphorus homeostasis and bone metabolism. It also acts in autoimmune processes, insulin and cardiovascular diseases.
The main source of vitamin D is sunlight (95%) and a small part is obtained through a healthy diet, mainly from foods such as whole milk, mushrooms, salmon, fish oil, red meat, liver or egg yolk. That is why during the winter months it becomes more complicated to get sufficient levels of this vitamin.
As far as fertility is concerned, vitamin D can play an important role in both men and women. Animal studies suggest that vitamin D deficiency may affect the process of spermatogenesis, and in the case of women, an association between vitamin D and ovarian hormone production, polycystic ovary and endometriosis has been demonstrated.
Vitamin D receptors have also been found in the endometrium and this aspect could influence its capacity to intervene and make implantation possible.
Several studies link vitamin D deficiency during pregnancy with weak placentation, something that could lead to problems of arterial hypertension, preeclampsia, gestational diabetes, low fetal growth and, in turn, increases the probability of cesarean delivery. According to the Spanish Society of Endocrinology, the above-mentioned links still need to be confirmed, as the studies have been carried out on a small number of patients.
Vitamin D values: ideal, insufficient and deficient
Vitamin D can be measured in serum (by a blood test) and its levels indicate fairly closely the values that can be found in the ovaries, specifically in the follicular fluid.
However, this is not always the case for other important fertility parameters that can help in the study of its role in the ovaries.
As for normal vitamin D values, the ideal is considered to be between 30 and 50 ng/ml, since this facilitates adequate bone health and, in general, favors human health.
When the levels are between 20 and 30 ng/ml we speak of vitamin D insufficiency and when they are below 20 ng/ml a deficiency of this vitamin is found.
Many studies warn about vitamin D deficiency in the general population, since worldwide it is estimated that 12% achieve optimal vitamin D levels, while the remaining 88% are between insufficiency and deficiency (44%). The Spanish Society of Endocrinology warns that the figures in Spain are similar to the above.
Age, body mass index (BMI) and skin pigmentation, keys to understanding vitamin D levels.
It is known that there is an inverse association between blood levels of vitamin D and the degree of skin pigmentation, as well as body mass index (BMI) and age. Thus, people with darker skin, who are overweight and of advanced age are more likely to have low vitamin D levels.
Because vitamin D levels are generally low in the population, the validity of the ideal values is questioned and the possibility of re-evaluating them is raised.
In fact, most of the studies on vitamin D and fertility take into account values above 20 ng/ml to be considered normal.
Diversity of opinion in studies on vitamin D, IVF pregnancies and oocyte donation
Women starting IVF treatment show a pattern of vitamin D levels similar to the rest of the population.
According to the meta-analysis by Chu et al (2019), which included 2700 patients, only 26% of individuals were recorded with optimal vit D levels, 45% with insufficient levels (20-30ng/ml) and 34% with vitamin D deficiency (
The pioneer team in the study of the impact of vitamin D levels in IVF was Ozkan et al. in 2010. On a total of 84 patients, they found a significant positive correlation between vitamin D levels and implantation rate and pregnancy probability. Since then, different investigations have been performed and the results are controversial.
Rudick et al. in 2014 conducted a study with 99 oocyte donation patients and found a lower pregnancy rate in recipients with vitamin D insufficiency (
Three recent meta-analyses (Lv et al. 2016, Chu et al. 2018 and Zhao et al. 2018) compile data from IVF cycles, ovodonation and cryotransfers from up to 134 previous studies, but only one of them notes a significant association between vitamin D deficiency (below 15ng/ml) and lower pregnancy rates.
However, all three meta-analyses point to an association between vitamin D deficiency (below 20ng/ml) and a lower rate of live newborns.
However, none of them establish a relationship between the number of miscarriages and vitamin D levels. Even so, it is possible to state possible adverse effects during pregnancy associated with low vitamin D levels, but not necessarily at the time of IVF treatment or embryo implantation.
What should we do in routine clinical practice?
The determination of vitamin D is simple and inexpensive. In fact, at URH GarcÃa del Real we think that it is worth studying in patients who are going to undergo fertility treatments.
Finding a mild vitamin D insufficiency does not mean running out to buy vitamin D supplements, since an overdose can be accompanied by an exaggerated increase of calcium in the body which, consequently, could cause damage to the bones, heart and kidneys.
For those women who are seeking pregnancy with IVF or other treatment and whose vitamin D level is insufficient (20-30 ng/ml), we recommend that they take a vitamin complex that includes this vitamin and improve their lifestyle.
It is also advisable to increase the time of daily sun exposure for 20 minutes and without using sunscreen and to make dietary changes. Only in those cases in which we find a clear vitamin D deficit (