In patients undergoing IVF, a serum vitamin D level of 20 ng/mL or more was associated with a significantly greater chance of obtaining 3 or more high-quality embryos and with successful embryo implantation and clinical pregnancy compared with lower levels, researchers report write in an article published online August 14 in the Journal of Clinical Endocrinology and Metabolism.
"Our work is the largest study to date to examine how vitamin D affects fertility in women who are undergoing IVF," lead author Alessio Paffoni, MSc, said in a news release.
Vitamin D is known to be essential for animal reproduction, but its role in human fertility has been less well-studied, Paffoni, from the Ospedale Maggiore Policlinico, Milan, Italy, and coauthors note. "We deem it important to definitely clarify whether vitamin D deficiency negatively affects clinical pregnancy rate, as this may potentially open new therapeutic scenarios for women scheduled for IVF and, more in general, to all women with infertility."
They evaluated pregnancy outcomes in 335 women attending a fertility clinic in Milan between January and December 2012. Serum vitamin D levels were assessed by measuring 25-hydroxy-vitamin D [25(OH)D] no more than 90 days before embryo transfer. Overall, 154 women had vitamin D deficiency, defined as serum 25(OH)D levels lower than 20 ng/mL. The mean 25(OH)D level in the vitamin D-deficient group was 14.1 (standard deviation [SD], ±3.8) ng/mL. The remaining 181 women had serum 25(OH)D levels of 20 ng/mL or more, with a mean of 29.1 ± 8.3 ng/mL (P = .001). A level of at least 30 ng/mL is considered sufficient.
Women with higher 25(OH)D levels were more likely to be white (P = .02). They had a mean body mass index of 20.4 ± 2.0 kg/m2 vs a mean of 21.1 ± 2.0 kg/m2 among women with lower vitamin D levels (P = .004). The mean duration of infertility was 4.0 ± 2.5 years and 4.6 ± 2.5 years in the high and low groups, respectively (P = .03). There were no other significant differences between the groups. Ovarian responsiveness, oocyte competence, and embryo development also were similar between the groups.
Each group had similar numbers of embryos transferred, but 29 women with higher 25(OH)D levels (16%) obtained 3 or more top-quality embryos compared with 9 women (6%) in the deficient 25(OH)D group (P = .003). A "top-quality" embryo was defined as a 4-celled embryo at day 2 or an 8-celled embryo at day 3, with a relative degree of fragmentation of less than 10%.
The number of implanted embryos for women with higher vitamin D levels was 70, for an implantation rate of 21%, compared with 37 implanted embryos and an implantation rate of 13% among women with lower levels of vitamin D (P = .006). The rates of clinical pregnancies were 56 (31%) and 30 (20%), respectively (P = .02).
The chances of successful implantation and clinical pregnancy increased with increasing levels of 25(OH)D. Women with levels exceeding 30 ng/mL had an odds ratio for implantation of 2.2 (95% confidence interval, 1.3 - 3.8) compared with women who had lower vitamin D levels (P = .004) and an odds ratio for clinical pregnancy of 2.1 (95% confidence interval, 1.1 - 4.0; P = .03). These analyses were adjusted for age, ethnicity, parity, body mass index, fertility duration, number of retrieved oocytes, number of transferred embryos, study period, and presence of at least a single top-quality embryo.
"[W]e believe that it can be concluded that vitamin D insufficiency negatively affects clinical pregnancy rate in women undergoing IVF," the authors write. However, they warn that a causal relationship between low vitamin D and infertility cannot yet be established. For that, randomized, controlled trials would be "required to definitely support a role for vitamin D in influencing the chances of pregnancy."
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