1. Introduction

Infertility is defined the failure to conceive after at least one year of unprotected coitus ^[1]. The number of couples affected by infertility has increased from 42.0 million in 1990 to 48.5 million in 2010 ^[2]. Obesity is defined as the accumulation of adipose tissue to excess ^[3]. The global prevalence of obesity has nearly doubled from 6.4% in 1980 to 12.0% in 2008 ^[4]. The prevalence of obesity has steadily increased in Turkey. According to Turkey Nutrition and Health Survey data, for example, 41.0% of all Turkish women are obese ^[5].

Obesity has long been observed to affect fertility adversely. A previous study concluded that various menstrual problems, recurrent miscarriage, and infertility affect 43.0% of all overweight and obese women ^[6]. The potential adverse effects of obesity on fertility in women include irregular cycles, oligo/amenorrhoea, chronic anovulation, increased risk of miscarriage, decreased conception rates after assisted reproductive technologies, increased morbidity in pregnant women, poorer outcomes of preterm deliveries, and polycystic ovary syndrome (PCOS) ^{[7, 8]}. Obesity has also been associated with reduced fecundity, while weight loss has been observed to increase fecundity ^{[9, 10]}.

Studies report that even a slight weight loss in obese infertile women improves reproductive function; a 5%–10% reduction in body weight, for example, has been shown to be effective in reducing insulin and androgen levels ^{[11, 12, 13]}.

The reproductive axis in women is controlled by a complex series of anterior pituitary gland hormones, gonadal sex steroid hormones, neurotransmitter systems, hypothalamic releasing factors, and various growth factors ^[14]. Disruption of the normal secretion of luteinizing hormone (LH) and follicular stimulating hormone (FSH) is evidenced in a number of reproductive disorders in women ^[15]. Thyroid hormones seem to play an important role in controlling the reproductive cycle. Hyperthyroidism and hypothyroidism exert adverse effects on female reproduction and cause menstrual disturbances. Hyperthyroidism is associated with increased sex hormone binding globulin, total estradiol, testosterone; hypothyroidism is associated with oligomenorrhea. In women, hyperprolactinemia leads to infertility ^{[16, 17, 18]}. Hyperprolactinemia usually presents as menstrual abnormalities, such as amenorrhea or oligomenorrhea, and luteal-phase issues ^[19].

Unhealthy eating habits, such as excessive intake of foods with high carbohydrate and fat contents, are the main factors promoting the development of nutritional problems ^[20]. A low-fat diet is traditionally believed to aid weight loss and improve reproductive dysfunction ^[21]. To boost reproductive health, a diet that includes fruits, vegetables, and whole grains and is low in saturated fats, cholesterol, refined grains, and sweets is recommended ^{[22, 23]}.

The purpose of this study was to evaluate the association of anthropometric measurements, hormone profiles, and daily energy and macronutrient intakes in both primary and secondary infertility.

2. Materials

This study was carried out at the Department of Obstetrics and Gynecology of the Maternity and Child Health Hospital in Diyarbakır, Turkey. All the women underwent a preliminary clinical examination in the gynecology department and those without any history of any medical illness in either partner were included. A total of 100 women aged 20–42 years were included in this study, and all subjects gave informed consent to take part in this research after being provided verbal and written explanations. All studies were conducted according to the guidelines laid down in the Declaration of Helsinki, and all procedures involving human subjects were approved by the Ethics Committee of Ankara University (Ethics approval code 2014/1269). In this work, 65 women presented with primary infertility while 35 presented with secondary infertility. All of the women’s general characteristics and their 24-h food consumption records were collected by face to face interviews using a standard questionnaire. Anthropometric measurements were taken by the researcher. Fasting blood samples were collected between 8:00 am and 11:00 am. Five millilitre fasting venous blood sample was drawn from the subject on day 3 of menstrual cycle using standard venipuncture techniques. FSH, LH, prolactin and TSH levels were measured using a electrochemiluminescence immunoassay on a COBAS 6000 system E601 (Elecsys module) and immunoassay analyzers (Roche Diagnostics GmbH, Mannheim, Germany). Couple that has never conceived despite exposure to the risk of pregnancy for a period of 1 year were defined primary infertility and couples who fail to conceive following a previous pregnancy despite cohabitation and exposure to the risk of pregnancy (in the absence of contraception, breastfeeding or postpartum amenorrhea) for 1 year were defined secondary infertility.

Weight was measured by electronic scales to the nearest 0.1 kg and height was measured to the nearest 0.1 cm a wall-mounted stadiometer while participants were wearing light clothing and no shoes. Body mass index (BMI) (kg/m²) was evaluated according to World Health Organization (WHO) standards. Underweight was diagnosed when the BMI was less than 18.5 kg/m²; normal weight when the BMI was between 18.5–24.9 kg/m²; whereas overweight was diagnosed when the BMI was between 25.0–29.9 kg/m²; and when BMI exceeded 29.9 kg/m², then participants were classified as obese ^[24]. Waist-hip-ratio (WHR) refers to the relationship between the waist circumference and the hip circumference. WHR is calculated by dividing the waist circumference by the hip (or gluteal) circumference. A WHR of more than 0.80 in women indicates central body distribution (android obesity), while a ratio of less than 0.80 indicates gynoid obesity ^[25].

Macronutrient intake was assessed by 24 hours recall dietary records maintained for one day by using a photographic atlas of food portion sizes ^[26]. The average energy (kcal), dietary fat (%), saturated fatty acids (%), dietary carbohydrate (%), dietary protein (%) and dietary fiber (g) intake analysis was carried out using a computerized system ^[27]. The number of women whose diet contained higher amounts than the maximum recommended intake for macronutrient as defined by Food and Nutrition Guideline for Turkey (FNGT) was calculated and reported in the tables ^[28].

Statistical analysis was performed using SPSS 21.0 version for Windows. The results were given as mean ± Standard error of mean (SEM). Kolmogrov–Smirnov and Shapiro Wilk tests were used to assess the normality of the data. The difference between various anthropometric measurements, hormone levels, daily energy and macronutrient intakes between the primary and secondary infertility groups was determined by Mann Whitney U. Correlations were evaluated using the Pearson’s correlation test. For all statistical comparisons, the level of significance was set at p<0.05.

3. Results

The ages and anthropometric measurements of women included in both groups were compared. The secondary infertility group had significantly higher BMIs, waist circumferences, hip circumferences, and waist-hip ratios than the primary infertility group (Table 1). The average duration of infertility in the primary infertility group was 1.71 ± 1.32 years and that in the secondary infertility was 2.72 ± 2.35 years (p = 0.019).

Table 1. Age and Anthopometric Parameters of Women with Primary and Secondary Infertility

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The primary and secondary infertility groups showed similar LH and FSH levels, but women with primary infertility revealed slightly higher mean levels of prolactin than women with secondary infertility. This difference was not statistically significant. Thyroid stimulating hormone (TSH) levels were slightly higher in the secondary infertility group than in the primary infertility group, but differences observed were statistically insignificant. No significant difference in LH/FSH ratio was observed between the groups (Table 2).

Table 2. Comparison of Hormone Profile of Women with Primary and Secondary Infertility

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In the primary infertility group, no significant correlation was observed between hormonal factors and anthropometric measurements. By contrast, in the secondary infertility group, prolactin levels demonstrated significant positive correlations with body weight, and BMI (Table 3).

Table 3. Correlation of Hormonal Factors with Anthropometric Measurements in Primary and Secondary Infertility

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Daily mean energy and macronutrient intakes and comparisons with the FNGTs are presented in Table 4. The percentages of dietary fat and saturated fatty acid intakes were high in both groups, and dietary carbohydrate intakes were below the FNGT value.

Table 4. Daily Energy and Nutrient Intakes and Comparisons with the FNGT in Primary and Secondary Infertility Patients

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4. Discussion

Most of the women recruited for this study presented with primary infertility. Several studies have similarly found that primary infertility is more common among women than secondary infertility ^{[29, 30, 31, 32]}. The prevalence of primary infertility, however, is relatively low throughout sub-Saharan Africa ^[33].

Increasing age in women is an acknowledged factor negatively influencing time to pregnancy (ESHRE, 2005. In our study, women with primary infertility (25.30 ± 4.99 years) were significantly younger than women with secondary infertility (31.27 ± 5.36 years). Several studies have shown that fertility declines with increasing age ^{[34, 35]}.

Adipose tissue is essential for the normal development of female reproductive functions. The association between obesity and hyperinsulinaemia, hyperandrogenism, and abnormal secretion of other hormones, such as leptin, underlies the many reproductive disorders observed among infertile women ^{[8, 36, 37]}. In this study, 42% of the women recruited had a normal BMI, 38% were overweight, and 20.0% were either obese or grossly obese. Mean body weights, BMIs, waist circumferences, hip circumferences, and waist/hip ratios were found to be significantly higher in women with secondary infertility than in women with primary infertility. Higher anthropometric measurements observed in the secondary infertility group are generally attributed to the accumulation of fat with age as a result of previous pregnancies and nutritional and lifestyle changes ^{[38, 39]}.

Infertility is often caused by an insufficiency or imbalance of hormones. Hormonal imbalances can be determined by blood tests of reproductive hormone levels. Measurement of FSH, LH, prolactin, and TSH at day 2 or 21 can indicate whether or not the hormonal state is compatible with pregnancy. Ovulatory disorders are often characterized by low serum concentrations of FSH and LH and high serum concentrations of prolactin ^{[40, 41, 42]}. Elevated serum LH concentrations and LH/FSH ratios are characteristic of women with PCOS ^[43]. While the LH/FSH ratio is a controversial criterion for identifying a sub-group of infertile women, high LH/FSH ratios have been associated with infertility ^[44]. In the present study, serum FSH, prolactin, and TSH levels were within the normal range but serum LH levels and LH/FSH ratios were above the reference range. All hormone levels were similar between both groups, and differences observed were not significant.

The primary role of LH is to regulate androgen production in the theca interna, while the primary role of FSH is to regulate the growth and maturation of ovarian follicles and stimulate the aromatization of androgens to estrogens ^[45]. High LH/FSH ratios (LH/FSH ratio of >2) have been associated with obesity ^[44]. Additionally, undiagnosed and untreated thyroid diseases can cause infertility ^[46]. While several studies report that reproductive hormonal parameters did not differ between slim and obese women ^{[36, 47, 48, 49]}, other studies reveal that these parameters differed significantly ^{[50, 51, 52]}. In the present study, no significant associations among serum FSH, LH, TSH levels, and LH/FSH ratio with anthropometric measurements were found in both study groups.

Serum concentrations of prolactin increase physiologically in pregnancy and during lactation. Hyperprolactinemia induced by other reasons is a common cause of secondary amenorrhoea in reproductive women ^{[53, 54]}. A high prevalence of obesity has been significantly associated with hyperprolactinaemia ^[55], and an association between hyperprolactinemia and increased body weight has been demonstrated ^{[56, 57, 58]}. A previous work found that serum prolactin levels in infertile women are higher than those in their fertile counterparts ^[59]. In this work, the secondary infertility group revealed a significant positive correlation between prolactin levels and body weight and BMI.

Inappropriate diets, insufficient exercise, and obesity are often associated with infertility ^[60]. The quantity, proportion, and type of carbohydrates, proteins, and lipids consumed by women may exert important impacts on their fertility ^[61]. While our study revealed similar energy intakes and macronutrient consumption between both groups, all of the patients consumed more fat and saturated fat than recommended for healthy women. Limited data on the diet history of women with infertility are available. A study found that high saturated fatty acid levels in follicular fluid are inversely associated with the number of mature oocytes during assisted reproduction ^[62]. Similarly, in previous dietary studies, women with PCOS tended to consume diets with high dietary fat and saturated fat levels ^{[63, 64]}.

This study presents several limitations. First, the small patient sample recruited for this research prevents us from drawing definitive conclusions and our exploratory findings must be confirmed in larger populations. Another limitation is that there was no control group with which to compare the anthropometric measurements, hormone profile, daily energy and macronutrient intakes.

5. Conclusion

In our study; the secondary infertility group had significantly higher BMIs, waist circumferences, hip circumferences, and waist-hip ratios than the primary infertility group. The primary and secondary infertility groups showed similar hormone levels. In the primary infertility group, no significant correlation was observed between hormonal factors and anthropometric measurements. By contrast, in the secondary infertility group, prolactin levels demonstrated significant positive correlations with body weight, and BMI. The percentages of dietary fat and saturated fatty acid intakes were high in both groups.

Healthy body weights may increase the chance of infertile women to succeed in trying to get pregnant naturally so we recommend that women of reproductive age adjust their lifestyles accordingly and make efforts to control their weight.

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