Getting to the Truth: Vitamin D Status, Reproductive Outcomes, and Challenges in the Current Evidence - Samantha Butts
As a fertility specialist, my goal is to educate the role of vitamin D in female reproductive functioning and its physiological impact. I aim to review the existing evidence linking vitamin D deficiency to both natural fertility and outcomes of infertility treatments. Furthermore, utilizing the research findings on how vitamin D deficiency relates to the success of ovarian stimulation cycles. Lastly, I will explore the challenges we face in this field and the potential opportunities for future research to better understand the influence of vitamin D status on reproductive outcomes.
Vitamin D deficiency affects around 1 billion people worldwide. Risk factors include obesity, dark skin, geography, poor sun exposure, and sunscreen use. Dark-skinned individuals require more UVB exposure to produce vitamin D. In northern regions, a significant number of African American mothers (83–92%) and White mothers (42–47%) are deficient or insufficient. Prenatal vitamin compliance is high among those with deficiency. Addressing vitamin D insufficiency is important, especially for vulnerable populations like pregnant women.
In my work within the fertility field, I have observed the widespread presence of vitamin D receptors in various reproductive tissues and cells. For instance, vitamin D receptors are found in granulosa cells in the ovaries, the myometrium, endometrium, and decidua in the uterus, as well as in the fallopian tubes and sperm cells. Through my research, I have discovered that vitamin D plays a crucial role in follicle development. In experiments conducted on rhesus macaque follicles, the addition of vitamin D to the culture media significantly improved the growth and survival of preantral follicles compared to unsupplemented media.
Furthermore, vitamin D is involved in regulating genes related to decidualization, implantation, trophoblast invasion, and placental functioning. The human placenta possesses a functional vitamin D endocrine system, enabling local activation, catabolism, and response to vitamin D. Notably, vitamin D plays a role in upregulating the expression of a critical transcription factor involved in embryo-endometrial communication and implantation.
In vitro studies using trophoblast cells derived from human placentas have also demonstrated that vitamin D influences the expression and secretion of human chorionic gonadotropin, estrogen, and progesterone. These findings highlight the significant impact of vitamin D on various aspects of reproductive processes, emphasizing its importance in fertility and pregnancy.
In my research within the fertility field, I investigated the impact of vitamin D deficiency on live birth rates in women undergoing ovarian stimulation. The primary aim of my study is to determine the association between vitamin D deficiency and treatment outcomes in women with unexplained infertility or anovulatory infertility caused by polycystic ovary syndrome (PCOS). I have formulated two hypotheses for my research. Firstly, I hypothesize that vitamin D deficiency is linked to reduced ovulation during treatment cycles for PCOS. Secondly, I propose that vitamin D deficiency is associated with a lower likelihood of achieving a live birth in ovarian stimulation cycles for women with unexplained infertility and anovulatory infertility due to PCOS.
In conclusion, the role of vitamin D deficiency in reproductive outcomes is complex and variable, particularly in women with and without infertility. Our research indicates a specific association between vitamin D deficiency prior to ovarian stimulation and subsequent live birth, which is particularly relevant in women with polycystic ovary syndrome (PCOS) due to shared metabolic dysfunction. Factors such as income level and duration of infertility play a significant role in treatment success for women with unexplained infertility, while race, BMI, and AMH levels do not show consistent associations. Studies examining vitamin D status and spontaneous conception suggest a higher risk in women with a history of prior spontaneous abortions, although sample size limitations exist. There is mixed and varying quality of data regarding IVF outcomes, but pooled evidence suggests more favorable outcomes in individuals with sufficient vitamin D levels. The specific impact of vitamin D deficiency on endometrial receptivity, egg/embryo quality, or a combination thereof remains unclear and requires further investigation.
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Samantha Butts, MD MSCE, is a reproductive endocrinologist and sought-after thought leader in FemTech. She specializes in treating individuals and couples who require fertility treatments to achieve pregnancy. Currently, Sam serves as a professor of obstetrics and gynecology and chief of the Division of Reproductive Endocrinology and Infertility at Penn State Health. She is devoted to building the next generation of medical leaders, who will lead the way in health tech, patient education, and reproductive health equity.