Vitamin D3 Fails to Improve IVF Outcomes

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Vitamin D3 fails to improve IVF outcomes

Single oral dose of vitamin D3 supplementation prior to in vitro fertilization and embryo transfer in normal weight women: the SUNDRO randomized controlled trial

A two-center randomized double-blind placebo controlled trial was conducted to test the effect of vitamin D3 supplementation on the chances of clinical pregnancy in women with insufficient levels undergoing IVF.

Participants were initially recruited from the infertility units of the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico and IRCCS San Raffaele Scientific Institute in Italy outside the summer periods (November to July) to minimise change in sun exposure levels.

Included women were aged 18-39 years, with a BMI 18-25kg/m2, having preserved ovarian reserve (AMH > 0.5ng/ml) and 2 or less previous IVF cycles, who were scheduled for controlled ovarian stimulation and fresh embryo transfer.

Women using frozen oocytes or embryos, surgically retrieved spermatozoa, serum calcium < 10.6mg/dl or vitamin D > 30ng/ml, already taking vitamin D3 or featuring contra-indications to vitamin D3 supplementation were excluded from the trial.

Supplementation of vitamin D3 was given as a single dose of 600,000 IU diluted in Olive oil, previously shown to maintain peripheral levels of vitamin D above 30ng/ml for approximately 3 months. Participating women were then required to commence their IVF cycle within 3 months of vitamin D3 (or placebo) administration.

IVF cycles were carried out according to standard center procedures and patient characteristics with peripheral levels of vitamin D measured on the day of oocyte retrieval.

Primary study outcome was clinical pregnancy rate per randomized woman given the effect from a single dose of vitamin D3 is limited to about 3 months. Clinical pregnancy itself was defined by the presence of at least one intrauterine gestational sac with a viable fetus.

However to identify other effects: total dose of gonadotrophins, oocytes retrieved, fertilization rate, top quality embryos, time to pregnancy, miscarriage rate, termination of pregnancy, stillbirth, live birth, gestational age, birth weight and neonatal health were also recorded during the trial.

After assessment of initial women, 630 met the inclusion exclusion criteria. Following randomization 308 women were administered 600,000 IU of vitamin D (cholecalciferol) and 322 women a like-for-like placebo. Median levels of vitamin D prior to trial was 20.0ng/ml and 19.9ng/ml, for both treatment and control groups respectively.

Following treatment/placebo administration, a further 57 women dropped out of the study, leaving 285 women in the treatment group and 288 controls to undergo oocyte retrieval. Initial analysis of data prior to embryo transfer showed no significant difference in the total dose of gonadotrophins, number of developed follicles, oocytes retrieved, suitable oocytes, fertilisation rate, number of embryos or top quality embryos. However vitamin D levels at the time of oocyte retrieval was 52.2ng/ml and 19.8ng/ml, for the treatment and control groups respectively. Fresh embryo transfer was then carried out in 328 women (Treatment = 169, Control = 159) with the number of embryos transferred per cycle similar across both groups (P > 0.3).

Post-transfer results showed no significant difference in either primary or secondary outcomes, with clinical pregnancy rates of 32% and 33%, for both treatment and control groups respectively. Of those successful pregnancies, live birth rate was 85% (Treatment) and 92% (Control) respectively.

Further subgroup analysis of vitamin D supplementation across BMI, age, IVF indication, ovarian reserve, drug to cycle intervals and vitamin D basal levels failed to identify any particular subgroup that may benefit from vitamin D supplementation undergoing IVF.


SUMMARY: VITAMIN D AND IVF

In this largest study to date, vitamin D supplementation prior to IVF, in women with insufficient levels (< 20ng/ml), BMI 18-25 and preserved ovarian reserve, failed to cause an increase in the fertilization, clinical pregnancy or live birth rates, versus the placebo controlled group (P > 0.3).


Limitations

  1. Free vitamin D levels not measured
  2. Vitamin D3 supplementation does not cover the entire period of folliculogenesis (~6 months)


Similar studies

Cai S, et al. (2020). Impact of vitamin D on human embryo implantation-a prospective cohort study in women undergoing fresh embryo transfer. https://doi.org/10.1016/j.fertnstert.2020.09.005

Espinola M S B, et al. (2020). Positive effect of a new supplementation of vitamin D3 with myo-inositol, folic acid and melatonin on IVF outcomes: a prospective randomized and controlled pilot study. https://doi.org/10.1080/09513590.2020.1760820

Abedi s, et al. (2019). Effect of Vitamin D Supplementation on Intracytoplasmic Sperm Injection Outcomes: A Randomized Double-Blind Placebo-Controlled Trial. https://doi.org/10.22074/ijfs.2019.5470

Fatemi F, et al. (2017). Role of vitamin E and D3 supplementation in Intra-Cytoplasmic Sperm Injection outcomes of women with polycystic ovarian syndrome: A double blinded randomized placebo-controlled trial. https://doi.org/10.1016/j.clnesp.2017.01.002

Aflatoonian A, et al. (2014). Effect of vitamin D insufficiency treatment on fertility outcomes in frozen-thawed embryo transfer cycles: A randomized clinical trial. http://www.ncbi.nlm.nih.gov/pmc/articles/pmc4248143/


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