Swedish study links vitamin D deficiency to infertility duration in women

The association between vitamin D and human reproduction is supported by studies linking it to polycystic ovary syndrome​ and endometriosis​, which can lead to infertility.

However, according to the authors of this study, from University of Gothenburg, Sweden, the relationship between 25(OH)D status and outcomes of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) remains unclear.

A potential mechanism through which vitamin D insufficiency may impact in vitro fertilization IVF/ICSI outcomes is by exerting a negative effect on endometrial function​.

Studies have demonstrated that vitamin D can up-regulate the expression of HOXA10, a crucial protein involved in embryo implantation and fertility. HOXA10 expression increases significantly during the implantation period, and it has been shown that vitamin D binds to the vitamin D receptor in human endometrial stromal cells​, thereby potentially influencing the expression of HOXA10.

What's more, the enzyme 1-alpha-hydroxylase, responsible for the conversion of calcidiol into calcitriol, the bioactive form of vitamin D, is up-regulated in the human endometrial stromal cells during early pregnancy​. Therefore, it is plausible that vitamin D levels may indirectly affect implantation rates in infertile women undergoing IVF/ICSI through its influence on endometrial receptivity.

A recent meta-analysis​ of 15 cohort studies indicated a higher live birth rate among women with sufficient 25(OH)D status than among those with deficient status [25].

However, since both 25(OH)D status and IVF treatment success are influenced by various parameters, such as age, underlying infertility cause, skin phototypes, country of origin, and body mass index, the authors of this study felt the independent effect of vitamin D on IVF outcomes needs to be fully elucidated.

The current study aimed to address the dearth of literature on the status of 25(OH)D in women with infertility seeking IVF treatment in Nordic countries. The primary aim was to examine the prevalence of 25(OH)D insufficiency, both overall and seasonally, and to identify the determinants associated with this insufficiency in this population.

In this prospective cohort study, it was observed that three out of ten women with infertility had 25(OH)D insufficiency, with a higher incidence in the winter season. Notably, women with 25(OH)D insufficiency exhibited a longer duration of infertility as they initiated treatment later than women with sufficiency. 

This study represents the first investigation into the serum 25(OH)D status of infertile women residing at northern latitudes.

The authors conclude: "The study findings have important clinical implications, suggesting that addressing vitamin D insufficiency should be considered in the management of infertility, particularly among non-Nordic women. Strategies, such as vitamin D supplementation and tailored sunlight exposure, may improve vitamin D status and potentially influence IVF outcomes.

"However, further research is warranted to explore targeted interventions and elucidate the underlying mechanisms connecting vitamin D insufficiency and impaired fertility, enabling the development of novel therapeutic approaches."

The vitamin D gap

Vitamin D is a liposoluble steroid hormone that plays crucial roles in various physiological processes. Its endocrine effects are mainly related to the regulation of calcium and phosphorus metabolism, which are essential for bone and skeletal health. Several studies have also suggested that vitamin D is involved in pathological conditions, such as neurological and cardiovascular diseases, as well as cancer.

The primary source of vitamin D is cutaneous synthesis, which occurs when the skin is exposed to ultraviolet B (UVB) radiation from sunlight. It can also be obtained from natural (cod liver oil, egg, fatty fish) and fortified (milk, yogurt, cereals) dietary sources and supplements.

The European Food Safety Authority Panel on Dietetic Products, Nutrition and Allergies and the Institute of Medicine recommend a serum 25- hydroxyvitamin D (25(OH)D) concentration of at least 50 nmol/L (obtained from both cutaneous synthesis and dietary sources) to ensure good musculoskeletal health and reduce adverse pregnancy-related outcomes.

Previous studies have shown that the prevalence of 25(OH)D insufficiency (serum 25(OH)D concentration < 50 nmol/L) in Northern Europe ranges from 7% to 34%. Since sunlight exposure is lower at higher latitudes, the generally adequate vitamin D status in Nordic countries is mainly due to vitamin supplements and dietary fortification. However, vitamin D status among immigrants in Northern Europe is still poor​, mainly due to lower consumption of fatty fish, vitamin supplements, and clothing habits that reduce sunlight exposure.

The study

The current study was conducted between September 2020 and August 2021 in the Department of Obstetrics and Gynecology, Reproductive Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden. All women aged 18–38 years, who were scheduled for IVF/ICSI treatment during the study period, were invited to participate via mail within a couple of weeks prior to their planned visit to the clinics, and the recruitment of the participants was conducted continuously.

All invited women received a questionnaire validated for the dietary assessment of vitamin D intake, together with an invitation to participate in the study.

Blood samples for the measurement of serum 25(OH)D concentration were collected in connection with participants’ first visit to the clinics upon consenting to participate.

Clinical data, including the woman’s age and BMI, smoking/snuffing habits, previous parity, antral follicle count, cause, and length of infertility, were obtained from the Reproductive Medicine electronic database. Data on country of origin, education level, skin phototype, UVB exposure (sun vacations, sun exposure habits), and dietary and supplemental intake of vitamin D were obtained from the questionnaires.

The resulting data indicates that overall prevalence of 25(OH)D insufficiency was 27.2%, with a range of 7.4% in summer and 32.5% in winter. Women with 25(OH)D insufficiency had a significantly longer duration of infertility than those with sufficiency (median: 36 months vs. 24 months). Moreover, the prevalence of 25(OH)D insufficiency varied significantly depending on the participants’ country of origin. Specifically, women originating from Nordic countries had the lowest prevalence, whereas those from nonNordic European, Middle Eastern, and Asian countries had a higher prevalence.

Regarding limitations of the study, the authors note the questionnaire used did not contain inquiries regarding sun protection factor use during sun exposure, which could be a potential limitation of our stud.

Source: Nutrients

https://doi.org/10.3390/nu15122820 (registering DOI)

"Prevalence of Vitamin D Insufficiency and Its Determinants among Women Undergoing In Vitro Fertilization Treatment for Infertility in Sweden"

Maaherra Armstrong, P.; Augustin, H.; Bärebring, L.; Osmancevic, A.; Bullarbo, M.; Thurin-Kjellberg, A.; Tsiartas, P.