Document Type : Original Article
Authors
1 Nursing and Midwifery Care Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
2 4Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
3 Department of Midwifery and Reproductive Health, Woman's Health Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
Abstract
Keywords
Infertility is defined as the inability to conceive a clinical
pregnancy after 12 months of unprotected intercourse
(
According to the Society for Assisted reproductive
technology (ART), of 39,573 assisted reproductive
cycles performed in the United States clinics among
women younger than the age of 35 in 2014, only 37.1%
of fresh nondonor ART cycles have resulted in live
births (
However, animal studies have shown that deficiencies or excesses in a range of macro- and micronutrients during pre-conception period can lead to impairments in fertility and fetal development and affect the long-term offspring health (
There are many studies that examine the impact of micro- and macronutrients on reproductive health and pregnancy outcomes (
The aim of the present study was to assess the relation between dietary patterns and reproductive outcomes in women with primary infertility seeking ART.
The present study was a prospective cohort study that was performed at Isfahan Fertility and Infertility center, Isfahan, Iran. A simple sampling design was used. The following formula was used for calculating the sample size:
Z1=1.6
Z2=0.84
P=40% (an estimate of pregnancy rate in fresh nondonor
IVF cycles in each tertile (
d=0.6P
The sample size for each tertile was estimated to be 65 women plus a 10% sample dropping. So 217 participants were included in the study.
Between August 2015 and January 2016, 217 women with primary infertility aged between 20-45 years who were undergoing suppression protocol for IVF/ICSI, were invited to participate in this study. The inclusion criteria were having female infertility (idiopathic or ovarian infertility), not having significant changes in diet during the last 3 months or having a specific diet, not consuming alcohol and not smoking, not having a history of diseases affecting metabolism including diabetes, galactosemia, maple syrup urine disease (MSUD), phenylketonuria (PKU), inflammatory bowel disease, celiac disease, chronic pancreatitis, nephrotic syndrome, acute and chronic kidney failure, dialysis, hypothyroidism and hyperthyroidism (
All participants filled out the 168-item food frequency questionnaire (FFQ) and the short form of international physical activity questionnaire (IPAQ). Also their demographic characteristics were recorded. Body mass index (BMI) was calculated as weight in kg divided by the square of height in meters (kg/m2). The waist circumference was measured with a non-stretch tape to the nearest 0.1 cm between the lowest rib margin and the iliac crest with minimal clothing (
In the laboratory, the researcher recorded the total number of retrieved oocytes and the number of Metaphase II oocytes. Then IVF/ICSI procedure was conducted based on the standard protocols using G-V series media form VitroLife (
The 168-item FFQ was validated in a previous study (
In this study, suppression protocol was used. On the second day of the last menstrual period, when no ovarian cyst was observed in a transvaginal ultrasound scan, ovarian stimulation was commenced with Gonal-F (Serono, Switzerland) in combination with Menogon (Ferring, Germany). Serial ultrasound scans were carried out and when the dominant follicle reached the size of 13-14 mm, gonadotropin-releasing hormone (GnRH) antagonist was administered daily. Ovulation was triggered with 10,000 IU hCG, when the size of dominant follicles reached 17-18 mm. After 36 hours, transvaginal oocyte retrieval was carried out.
All participants were informed of the details of the study and were allowed to leave the study at any time. Informed consent was obtained from all the women who agreed to participate in the study. The study was approved by the Ethics Committee of the Isfahan University of Medical Sciences.
To identify major dietary patterns, factor analysis was used with oblique transformation. Factors were retained using the Scree test, if their eigenvalues were >1.5. Three factors were selected as major dietary patterns based on the Scree test and eigenvalues. Dietary patterns were labeled based on the previous knowledge about nutrition and according to the food groups with highest factor loading (
To perform all the statistical analyses, SPSS software version 20.0 (Armonk, NY: IBM Corp) was used. P<0.05 was considered significant.
A total of 217 infertile women participated in this study. Because of discontinuing the treatment due to ovarian hyperstimulation syndrome, unwillingness to continue the study, and diagnosing male factor infertility in the next steps of research, 77 cases were excluded from the study.
Three major dietary patterns were identified among 140 women. The first dietary pattern was named the “healthy diet” and included high consumption of fruits, nuts, vegetables, red and white meat, dairy, green olive, cream, and legume. The second dietary pattern was labeled as the “western diet” and was comprised of high consumption of sweet drinks, sweets, caffeinated drinks, potatoes, fast foods, whole grains, refined grains, liquid oils, and salt. The third dietary pattern was called the “unhealthy diet” and contained high consumption of mayonnaise, butter, egg, junk foods and solid oils (
Factor loading for food groups of the three dietary patterns identified from food frequency questionnaire (FFQ) in 140 infertile women
Food groups | Healthy | Western | Unhealthy |
---|---|---|---|
dietary pattern | |||
Fruits | 0.750 | - | - |
Nuts | 0.672 | - | - |
Vegetables | 0.597 | - | - |
Meat | 0.535 | - | - |
Dairy | 0.418 | - | - |
Green olive | 0.443 | - | - |
Cream | 0.272 | - | - |
Legume | 0.142 | - | - |
Sweet drinks | - | 0.782 | - |
Sweets | - | 0.519 | - |
Caffeinated drinks | - | 0.480 | - |
Potato | - | 0.416 | - |
Fast foods | - | 0.344 | - |
Whole grain | - | -0.334 | - |
Refined grain | - | 0.303 | - |
Liquid oil | - | 0.298 | - |
Salt | - | 0.237 | - |
Mayonnaise sauce | - | - | 0.777 |
Butter | - | - | 0.738 |
Egg | - | - | 0.509 |
Junk foods | - | - | 0.320 |
Solid oil | - | - | 0.279 |
Variance explained (%) | 12.679 | 8.892 | 7.133 |
Demographic characteristics by tertiles of the dietary patterns
Characteristic | n=140 | Tertile of healthy pattern | Tertile of western pattern | Tertile of unhealthy pattern | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
T1 | T2 | T3 | P valuea | T1 | T2 | T3 | P value | T1 | T2 | T3 | P value | ||
n=46 | n=47 | n=47 | n=46 | n=47 | n=47 | n=46 | n=47 | n=47 | |||||
Age (Y), mean ± SD | 32.4 ± 5.2 | 32.4 ± 5.6 | 33.2 ± 5.2 | 31.6 ± 4.7 | 0.294 | 31.3 ± 5 | 33.6 ± 5 | 32.3 ± 5.4 | 0.106 | 32.7 ± 4.7 | 33 ± 5.3 | 31.5 ± 5.6 | 0.324 |
BMI (kg/m2), mean ± SD | 28.1 ± 4.9 | 28.6 ± 5.5 | 28.3 ± 4.4 | 27.2 ± 4.6 | 0.338 | 28.2 ± 5.2 | 28.1 ± 4.5 | 27.9 ± 4.9 | 0.969 | 28.2 ± 5 | 28.2 ± 4 | 27.7 ± 5.6 | 0.875 |
Waist circumference (cm), mean ± SD | 83.4 ± 10.4 | 84.3 ± 11.7 | 83.6 ± 9.2 | 82.3 ± 10.1 | 0.642 | 84 ± 10 | 83.5 ± 10 | 82.7 ± 11.3 | 0.842 | 84.1 ± 10.1 | 82.5 ± 7.9 | 83.6 ± 12.8 | 0.747 |
Education, count (%) | 0.003 | 0.357 | 0.864 | ||||||||||
Under diploma | 37 (26.4) | 21 (45.7) | 11 (23.4) | 5 (10.6) | - | 14 (30.4) | 9 (19.1) | 14 (29.8) | - | 10 (21.7) | 15 (31.9) | 12 (25.5) | - |
Diploma | 45 (32.1) | 13 (28.3) | 16 (34) | 16 (34) | - | 11 (23.9) | 20 (42.6) | 14 (29.8) | - | 16 (34.8) | 14 (29.8) | 15 (31.9) | - |
Academic | 58 (41.4) | 12 (26.1) | 20 (42.6) | 26 (55.3) | - | 21 (45.7) | 18 (38.3) | 19 (40.4) | - | 20 (43.5) | 18 (38.3) | 20 (42.6) | - |
Employment status, count (%) | 0.033 | 0.207 | 0.423 | ||||||||||
Housewife | 110 (78.6) | 42 (91.3) | 35 (74.5) | 33 (70.2) | - | 39 (84.8) | 38 (80.9) | 33 (70.2) | - | 37 (80.4) | 34 (72.3) | 39 (83) | - |
Employed | 30 (21.4) | 4 (8.7) | 12 (25.5) | 14 (29.8) | - | 7 (15.2) | 9 (19.1) | 14 (29.8) | - | 9 (19.6) | 13 (27.7) | 8 (17) | - |
The cause of infertility, count (%) | 0.523 | 0.111 | 0.482 | ||||||||||
Ovarian | 105 (75) | 33 (71.7) | 38 (80.9) | 34 (72.3) | - | 39 (84.8) | 35 (74.5) | 31 (66) | - | 34 (73.9) | 33 (70.2) | 38 (80.9) | - |
Idiopathic | 35 (25) | 13 (28.3) | 9 (19.1) | 13 (27.7) | - | 7 (15.2) | 12 (25.5) | 16 (34) | - | 12 (26.1) | 14 (29.8) | 9 (19.1) | - |
a; P value from One-way analysis of variance for continuous quantitative variables and from Chi-square test for categorical variables.
Comparison of the assisted reproductive technology outcomes by tertiles of the dietary patterns in infertile women
Variables | Helthy pattern | Western pattern | Unhelthy pattern | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
T1 | T2 | T3 | P valuec | T1 | T2 | T3 | P value | T1 | T2 | T3 | P value | |
The average number of total oocyte | ||||||||||||
Model1a (mean ± SD) | 7.1 ± 6.1 | 10.6 ± 8.6 | 12.2 ± 9 | 0.009 | 12 ± 9.3 | 8.7 ± 6.7 | 9.2 ± 8.3 | 0.119 | 9.8 ± 7.9 | 9.8 ± 8.8 | 10.4 ± 8.1 | 0.929 |
Model2b (mean ± SE) | 7.4 ± 1.2 | 11.1 ± 1.2 | 11.4 ± 1.3 | 0.053 | 12.1 ± 1.2 | 9.5 ± 1.1 | 8.4 ± 1.2 | 0.088 | 9.8 ± 1.2 | 10.5 ± 1.2 | 9.6 ± 1.2 | 0.837 |
The average number of metaphase II oocyte | ||||||||||||
Model1 (mean ± SD) | 6.1 ± 5.3 | 8.6 ± 6.8 | 10.6 ± 7.9 | 0.006 | 10 ± 7.4 | 7.5 ± 6.3 | 7.9 ± 7.1 | 0.184 | 8.6 ± 7 | 8.2 ± 7.6 | 8.6 ± 6.4 | 0.956 |
Model2 (mean ± SE) | 6.2 ± 1 | 8.9 ± 1 | 10.2 ± 1.1 | 0.034 | 9.9 ± 1 | 8.1 ± 1 | 7.4 ± 1 | 0.225 | 8.6 ± 1 | 8.8 ± 1 | 7.9 ± 1 | 0.824 |
The fertilization rate | ||||||||||||
Model1 (mean ± SD) | 0.61 ± 0.4 | 0.7 ± 0.3 | 0.7 ± 0.2 | 0.168 | 0.7 ± 0.3 | 0.7 ± 0.3 | 0.7 ± 0.3 | 0.776 | 0.7 ± 0.3 | 0.7 ± 0.3 | 0.6 ± 0.3 | 0.649 |
Model2 (mean ± SE) | 0.6 ± 0.05 | 0.7 ± 0.05 | 0.7 ± 0.05 | 0.310 | 0.7 ± 0.05 | 0.7 ± 0.05 | 0.7 ± 0.05 | 0.545 | 0.7 ± 0.05 | 0.7 ± 0.05 | 0.6 ± 0.05 | 0.536 |
The ratio of good quality embryo | ||||||||||||
Model1 (mean ± SD) | 0.2 ± 0.3 | 0.2 ± 0.2 | 0.2 ± 0.3 | 0.705 | 0.2 ± 0.3 | 0.2 ± 0.3 | 0.2 ± 0.3 | 0.870 | 0.2 ± 0.3 | 0.2 ± 0.3 | 0.2 ± 0.3 | 0.433 |
Model2 (mean ± SE) | 0.2 ± 0.05 | 0.2 ± 0.04 | 0. 2 ± 0.05 | 0.874 | 0.2 ± 0.04 | 0.2 ± 0.04 | 0.2 ± 0.04 | 0.656 | 0.2 ± 0.04 | 0.2 ± 0.04 | 0.2 ± 0.04 | 0.352 |
The ratio of bad quality embryo | ||||||||||||
Model1 (mean ± SD) | 0.2 ± 0.3 | 0.4 ± 0.3 | 0.3 ± 0.3 | 0.159 | 0.3 ± 0.3 | 0.3 ± 0.3 | 0.3 ± 0.3 | 0.559 | 0.3 ± 0.3 | 0.3 ± 0.3 | 0.3 ± 0.3 | 0.733 |
Model2 (mean ± SE) | 0.3 ± 0.05 | 0.4 ± 0.05 | 0.3 ± 0.05 | 0.425 | 0.3 ± 0.05 | 0.3 ± 0.05 | 0.4 ± 0.05 | 0.653 | 0.3 ± 0.05 | 0.3 ± 0.05 | 0.3 ± 0.05 | 0.923 |
The biochemical pregnancy [OR (IC)]d | ||||||||||||
Model1 (mean ± SD) | 1 | 1.5 (0.4-5.3) | 1.1 (0.3-4.2) | 0.816 | 1 | 1.4 (0.3-5.5) | 1.4 (0.4-5.1) | 0.858 | 1 | 0.14 (0.3-0.7) | 0.72 (0.2-2.6) | 0.036 |
Model2 (mean ± SE) | 1 | 1.3 (0.3-5.8) | 1.3 (0.3-6.7) | 0.914 | 1 | 1.8 (0.3-9.4) | 1.1 (0.2-5.9) | 0.749 | 1 | 0.09 (0.01-0.6) | 0.9 (0.1-5.9) | 0.022 |
The clinical pregnancy[OR (IC)] | ||||||||||||
Model1 (mean ± SD) | 1 | 1.5(0.4-5.3) | 1.1(0.3-4.2) | 0.816 | 1 | 1.4(0.3-5.5) | 1.4(0.4-5.1) | 0.858 | 1 | 0.14 (0.3-0.7) | 0.72(0.2-2.6) | 0.036 |
Model2 (mean ± SE) | 1 | 1.3(0.3-5.8) | 1.3(0.3-6.7) | 0.914 | 1 | 1.8(0.3-9.4) | 1.1(0.2-5.9) | 0.749 | 1 | 0.09 (0.01-0.6) | 0.9(0.1-5.9) | 0.022 |
Model1a; Crude, Model2b; Adjusted for age, marriage age, BMI, waist circumference, physical activity, total energy intake, supplement consumption, duration of metformin consumption, c; P trends from ANOVA analysis for model1 and from ANCOVA analysis for model2 in quantitative variables and p trends from logistic regression analysis for qualitative variables, and d; OR (CI): Odds ratio and 95% interval confidence calculated by logistic regression analysis.
There was a significant increase in the average number of total oocytes (P-trend=0.009) and metaphase II oocytes (P-trend=0.006) in the third tertile of “healthy diet” compared to the first tertile. After adjusting for confounding variables, these relations remained significant for the average number of total oocytes (P-trend=0.053) and metaphase II oocytes (P-trend=0.034). But the “western diet” and the “unhealthy diet” were not associated with the average number of total and metaphase II oocytes. Women with high adherence to the second tertile of “unhealthy diet” compared to the first tertile, had a significantly lower chance of getting pregnant (chemical and clinical pregnancy) (model1: OR: 0.14, 95% CI: 0.3-0.7, model2: OR: 0.09, 95% CI: 0.01-0.6). None of these dietary patterns were associated with the fertilization rate and the ratio of good and bad quality embryo (
The present study assessed the relation between dietary patterns and outcome of ART in infertile women undergoing IVF/ICSI procedure. The first dietary pattern included high consumption of fruits, nuts, vegetables, red and white meat, dairy, green olive, cream, and legume. Intake of fruits, nuts, and vegetables was outstanding. So this dietary pattern was called as the “healthy diet” (
Based on the results, women with the highest “healthy diet” score had a higher educational level and were employed. So higher education and being employed were predictors of a healthy diet. This relation has been seen in previous studies too (
Present findings showed that dietary patterns were related to some ART outcomes. The average number of total and metaphase II oocytes was increased significantly in women with high adherence to the “healthy diet”. These relations were significant even after taking confounding variables into account.
A randomized clinical trial showed that having a healthy diet rich in fruits and vegetable, like dietary approach for stopping hypertension (DASH), can have a positive effect on total antioxidant capacity (TAC). In this study, 60 women with polycystic ovary syndrome (PCOS) were equally randomized into DASH diet (being rich in fruits, vegetables, whole grains and low-fat dairy products, as well as low in saturated fats, cholesterol, refined grains and sweets) and control groups. After a 12-week follow-up, the DASH diet group had an increase in TAC (
In this study, the “healthy diet” was richer in vegetable, fruits, and nuts. These food groups contained a high level of antioxidants (
No relation was observed between fertilization rate and all three dietary patterns. Despite the fact that male factor infertility had been excluded in this study, environmental factors such as nutrition and job might affect the sperm quality and fertilization.
In the present study, the chance of getting pregnant was decreased significantly in women who had more adherence to the “unhealthy diet”. This diet contained foods high in saturated fatty acids like mayonnaise sauce, butter, and solid oils. A previous study reported that dietary fatty acid content reflects in the fatty acid profile of follicular fluid (
No relation was found between the healthy and western diets and the chance for getting pregnant.
A prospective cohort study in the Netherlands on 161 subfertile couples undergoing IVF/ICSI treatment showed that the Mediterranean diet, as a healthy diet, has a 40% increased probability of achieving pregnancy after IVF/ICSI treatments (
Some limitations in the present study might cause these null findings. Although male factor infertility was excluded, environmental factors like nutrition were uncontrollable and could affect fertilization and establishment of pregnancy. Also we could not distinguish chromosomally abnormal embryos from normal. These abnormal embryos might fail to implant and be less affected by the diet (
One strength of the present study was its prospective cohort design so multiple assisted reproductive outcomes could have been evaluated. Also, the current study is the first follow-up study that was performed in countries undergoing nutrition transition. For assessing dietary intakes, a validated FFQ which reflects Iranian food consumption was used and filled out by an experienced interviewer. Also, many confounder variables such as age, marriage age, BMI, waist circumference, physical activity, total energy intake, supplement consumption and duration of metformin consumption were adjusted.
Since the number of questions was too much, it is probable that some of the participants had not answered the food frequency questionnaire accurately and this was one of the limitations of the present study. Although a validated FFQ was used and filled out by an experienced interviewer, measurement bias was unavoidable and might underestimate or overestimate dietary intakes.
Results of the present study suggested that the average number of total and metaphase II oocytes were significantly higher in women with high adherence to “healthy diet” than the others, with low adherence. Also having “unhealthy diet” decreased the chance of getting pregnant after IVF or ICSI procedure.
The present study showed that having a “healthy diet” had a positive effect and could cause an increase in the average number of total and metaphase II oocytes and an “unhealthy diet” could decrease the chance of getting pregnant. The fertilization rate and the ratio of good and bad quality embryo were not affected by any of the dietary patterns. The results showed that nutrition status could affect infertility treatment outcomes. So nutritional interventions before attempting the infertility treatments could improve outcomes, reduce costs, and increase the mental and fertility health in couples. Considering the small number of conducted studies, it is suggested to perform more investigations on this issue to elucidate this relation and evaluate nutritional effects on reproductive health especially in infertile women.