IRON INTAKE AND RISK OF OVULATORY INFERTILITY: A JOURNAL REPORT Clerk Maria Karla L. Guinto

Infertility  Results in important emotional distress among those affected  Identification of modifiable risk factors could lead to effective interventions for prevention

Iron deficiency and infertility  Women with iron and other micronutrient deficiency have delayed menarche, early menopause and infertility of unknown cause  Resumption of fertility in women with low body iron stores receiving iron supplements  Iron-containing supplement given to women who had unsuccessfully tried to be pregnant documented a higher pregnancy rate

General objective  To evaluate whether iron supplement use or greater intake of total, heme, and nonheme iron is associated with lower risk of ovulatory infertility

Methodology  Duration of the study: 8 years  Inclusion criteria:  Female, 24 to 42 years old  Married  With available dietary information  Without a history of infertility  Tried to become pregnant or became pregnant between 1991 and 1999  Nondiabetic

 Dietary information was collected in 1991 and 1995 using a semiquantitative food frequency questionnaire  How often they consumed each of the foods and beverages included in the questionnaire  Use of multivitamins and other nutrient supplements  Daily dose of iron intake

 18,555 subjects  Divided into users and nonusers of iron supplements  Users further divided into:  Using a supplement with low iron content (<51 mg/d for 1991 questionnaire, <41 mg/d for 1995)  With high iron content (≥51 mg/d for 1991, ≥41 mg/d for 1995)

 Relative risk of ovulatory infertility according to categories of iron intake and iron supplement use was estimated  Potential confounders: BMI, parity, smoking history, physical activity, history of contraceptive use, dietary factors, intakes of alcohol, coffee, multivitamins, retinol, a-carotene, vitamin C

Results  Use of iron supplements was associated with approximately one half the risk of developing ovulatory infertility compared with non-use of these supplements  Women consuming iron supplements with low iron content had similar risk of ovulatory infertility as nonusers  Consumption of supplements with high iron content was associated with a 70% lower risk of ovulatory infertility (95% confidence interval)

 Heme iron intake was associated with an increased risk of ovulatory infertility  Total and nonheme iron intakes were inversely related  Women with highest intake of heme iron has a 31% greater risk of ovulatory infertility (95% CI)  Those with the highest category of nonheme intake had 40% lower risk of ovulatory infertility when compared with those in the lowest category

 No evidence of interaction of Vitamin C intake with iron supplement use, heme iron intake or nonheme iron intake  No interactions between intake of these kinds of iron and menstrual cycle length or history of contraceptive use  Not associated with age, BMI or parity

Discussion  Iron deficiency is the most prevalent nutritional deficiency worldwide.  Women of child bearing age are at increased risk of this condition.  Iron supplements have been associated with lower prevalence of iron deficiency among women of reproductive age.

 Granulosa cells can synthesize transferrin, which may be translocated to the oocytes  Transferrin and its receptor may be redundant in the ovary or do not play an important role in local iron metabolism. However, these proteins are essential for ovum development and are required to support the increasing iron demand of the developing follicle.

Limitations of the study  Not a cohort of women known to be planning a pregnancy  Included only married women whose pregnancies are more likely to be intentional than those of umarried women

Conclusion  Use of iron supplements with high iron content was associated with a reduced risk of ovulatory infertility  Inverse relationship between nonheme iron intake and risk of ovulatory infertility due to the use of supplements containing iron  Women planning to be pregnant should consider using iron supplements because these may help them prevent iron deficiency and improve fertility

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