During 8 years of follow-up, 26,971 eligible pregnancies and pregnancy attempts were accrued among 18,555 women. Of these events, 3,430 (12.7% of all events) were incident reports of infertility, of which 2,165 were of women who underwent medical investigation for infertility and 438 (1.6% of all events, 20.2% of investigated infertility cases) were incident reports of ovulatory infertility. Ovulatory infertility cases were more likely to report manifestations of PCOS (menstrual cycles >40 days or clinical signs of excess androgens) than women reporting infertility due to other causes (OR [95% CI] = 4.00 [2.87 – 5.57]) or women who became pregnant during follow-up (OR [95% CI] = 4. 41 [3. 33 –5.83]).
At baseline, women who consumed more animal protein, also consumed more saturated fat, less alcohol and coffee, and were slightly younger, heavier, less physically active and more likely to be parous (). Women who consumed more vegetable protein consumed more coffee and less saturated, monounsaturated and trans fat, were slightly older, leaner and more physically active, were less likely to smoke, be recent users of oral contraceptives or experience long menstrual cycles and more likely to be nulliparous. Protein intake was unrelated to use of multivitamins.
Baseline* characteristics of the study population by quintiles of animal and vegetable protein intake.
Total protein intake, as well was the intakes of animal and vegetable protein were unrelated to ovulatory infertility in age and energy-adjusted analyses (). After adjusting for potential confounders (particularly for intake of specific fatty acids, parity and BMI) women in the highest quintile of total protein intake had a 41% greater risk of ovulatory infertility than women in the lowest quintile of intake (95% CI: 4% – 91%). The association between animal protein intake and ovulatory infertility closely resembled the association for total protein intake. Conversely, there was a suggestion of an inverse association between vegetable protein intake and ovulatory infertility (P, trend = 0.07).
Relative risks and 95% confidence intervals for ovulatory infertility by quintiles of cumulative averaged protein intake.
We then examined the association between specific protein-rich foods and ovulatory infertility (). In multivariate-adjusted analyses, meat intake was positively associated with ovulatory infertility. Adding one serving of meat (red meats, chicken, turkey, processed meats and fish) per day, while holding calories, constant was associated with a 32% greater risk of ovulatory infertility (p = 0.01). This increased risk was due mostly to intake of chicken and turkey, the most important protein source in this population, and to a lesser extent to the intake of red meats. Intakes of processed meats, fish and eggs were unrelated to ovulatory infertility. Consuming foods rich in vegetable protein was related to modest decreases in the risk of ovulatory infertility, but none of these associations reached statistical significance.
Relative risks (95% CIs) of ovulatory infertility associated with increasing the intake of specific protein-rich foods by 1 serving/day.
Next, we estimated the effect that consuming protein instead of other energy sources would have on the risk of developing ovulatory infertility (). Consuming 5% of total energy intake as animal protein instead of as carbohydrates was associated with 19% greater risk of ovulatory infertility (p = 0.03). In contrast, consuming 5% of energy as vegetable protein rather than as carbohydrates was associated with a 43% lower risk of ovulatory infertility (p = 0.05). Furthermore, consuming 5% of energy as vegetable protein as opposed to as animal protein was associated with a more than 50% lower risk of ovulatory infertility (RR [95% CI; p] = 0.48 [0.28 – 0.81; 0.007]). When these analyses were repeated excluding women who used oral contraceptives within two years of the event, the results were essentially the same for animal protein and stronger for vegetable protein. The multivariate-adjusted relative risk (95% CI) of ovulatory infertility associated with increasing protein intake by 5% at the expense of carbohydrates was 1.18 (1.00 – 1.39) for animal protein and 0.50 (0.27 – 0.92) for vegetable protein. The corresponding RR (95% CI) for increasing vegetable protein intake by 5% at the expense of animal protein was 0.42 (0.24 – 0.76).
Relative risks (RRs) of ovulatory infertility associated with the specified isocaloric substitution of protein
Lastly, we assessed the possibility that the association between protein intake and ovulatory infertility could differ according to levels of personal characteristics including age, BMI, parity and menstrual cycle length. The associations between animal and vegetable protein intake did not differ according to menstrual cycle length (p, interaction = 0.14 and 0.99, respectively), BMI (p, interaction = 0.30 and 0.22) or parity (p, interaction = 0.39 and 0.78). However, the association between vegetable protein intake and ovulatory infertility was different according to age levels (p, interaction = 0.05). For women 32 years of age or younger consuming 5% of energy as vegetable protein rather than as carbohydrates was unrelated to ovulatory infertility whereas for women over 32 years this nutrient substitution was associated a more than 50% lower risk of ovulatory infertility (RR [95% CI; p] = 0.48 [0.27 – 0.86; 0.01). Similarly, consuming 5% of energy as vegetable protein instead of as animal protein was associated with a lower risk among women above 32 years (RR [95% CI; p] = 0.27 [0.14 – 0.51; <0.001]) but not among younger women (RR [95% CI; p] = 0.95 [0.50 – 1.78; 0.87]).