The Role of Vitamin D in Reproductive Health—A Trojan Horse or the Golden Fleece?

Abstract

In the last decade, vitamin D was in the spotlight in many fields of research. Despite numerous publications, its influence on reproductive health remains ambiguous. This paper presents an up-to-date review of current knowledge concerning the role of cholecalciferol in human reproduction. It covers various infertility issues, such as polycystic ovary syndrome, endometriosis, myoma-induced infertility, male infertility, premature ovary failure and in vitro fertilization techniques. Vitamin D deficiency, defined as serum concentration of 25-hydroxycalciferol of less than 50 nmol/L, is commonly noted more frequently than only in fertility clinic patients. It is a global trend that is observed in all age groups. The results of original publications dated up to 2015 have been summarized and discussed in a critical manner. Most experts agree that vitamin D supplementation is a necessity, particularly in women suffering from obesity, insulin resistance or small ovarian reserve, as well as in men with oligo- and asthenozoospermia if serum concentration should fall below 50 nmol/L (normal range up to 125 nmol/L). High concentration of vitamin D and its metabolites in decidua during the 1st trimester suggests its important role in the implantation process and a local immunological embryo-protection. On the other hand, evidence-based research did not prove a significant difference so far in ovulation stimulation or embryo development depending on vitamin D level. In one of the publications, it was also found that vitamin D binding protein (VDBP) has a molecular similarity to anti-sperm antibodies, and another one concluded that both low (<50 nmol/L) and high (>125 nmol/L) concentration of vitamin D are associated with decreased number and quality of spermatozoa in semen. Vitamin D is definitely not a Trojan Horse in reproductive health, since there were no adverse effects reported for vitamin D intake of up to 10,000 IU/day, but to proclaim it the Golden Fleece, more evidence is needed.

1,25‐Dihydroxy‐vitamin D3 regulates NK‐cell cytotoxicity, cytokine secretion, and degranulation in women with recurrent pregnancy losses

“…Low vitamin D level has been linked to major common health problems in populations, particularly inflammatory conditions such as cardiovascular disease, cancers, diabetes, autoimmune diseases including multiple sclerosis, rheumatoid arthritis, and others [3]. In addition, vitamin D deficiency is a predisposing factor for various female diseases such as osteoporosis, uterine fibroids, endometriosis, and breast cancer and a risk factor for obstetrical complications such as gestational diabetes and preeclampsia [4,5]. Recently, we have reported that 47.4% of women with recurrent pregnancy losses (RPL) have vitamin D deficiency [6].…”

“…In addition, vitamin D deficiency is a predisposing factor for various female diseases such as osteoporosis, uterine fibroids, endometriosis, and breast cancer and a risk factor for obstetrical complications such as gestational diabetes and preeclampsia [4,5]. Recently, we have reported that 47.4% of women with recurrent pregnancy losses (RPL) have vitamin D deficiency [6].…”

Assessment of the Possible Role of Vitamin D Defificiency with the Relevant Mechanisms in Gynecological Disorders

“…7,16,[17][18][19] [20][21][22] Genel olarak PCOS'ta vitamin D eksikliğinin obeziteyle birlikte insülin reseptör ekspresyonunu azaltarak ya da insülin üretimini/direncini artıra-rak glukoz transportunu bozup metabolizmasını değiştirdiği düşünülmektedir (Şekil 1). 7,11 Vitamin D, IR ile ilişkili insülin salımının dü-zenlenmesi, insülin reseptör ekspresyonunun uyarılması, insülin duyarlılığının değişimi ve inflamatuar sitokinlerin baskılanması gibi çeşitli doğru-dan ve dolaylı etkileriyle glukoz metabolizmasında görev almaktadır. 4,24 İnsülinsalımı üzerindeki doğru-dan etkisini pankreatik β-hücrelerinde eksprese olan VDR'nin aktivasyonu aracılığıyla göstermektedir.…”

“…13 Obezite, vitamin D'nin adipoz dokuda birikmesi ve hirsutizm nedeniyle güneşlenmekten kaçınma gibi durumların etkisiyle PCOS'lu kadınların %67-85'sinde vitamin D eksikliği (<20 ng/ml) görül-mektedir. 7,11,13 Literatürde vitamin D eksikliğinin, obezite, IR, menstrüel disfonksiyon, kardiyovaskü-ler olumsuzluklar, infertilite gibi PCOS ile ilişkili durumlara katkısı olabileceğini ileri süren çok sayıda çalışma mevcuttur. 4,6,7,11,[20][21][22]30,36,[38][39][40][41] Ancak PCOS'lu kadınların vitamin D düzeylerinin değiş-mediği, düşük ya da yüksek bulunduğu çalışmalar da mevcuttur.…”

Vitamin D: the tricky hormone

“…(8) and also by others (9) did not show lower levels compared to controls. The literature in the field is ambiguous, showing both the importance of its adequate level and the lack of effect in infertility issues, such as polycystic ovary syndrome, endometriosis, myoma-induced infertility, male infertility, premature ovary failure and in vitro fertilization techniques (10,11). Interestingly, however, Lopes and cols.…”