ALBU D. 1,2,5, ALBU Alice 1,3,5, POP Anca Lucia1, VARLAS Valentin1,4
1 1. U.M.F. Carol Davila, Romania
- Medlife, Reproductive medicine departament, Romania
- Elias Hospital, Romania
- Filantropia Hospital, Romania
- ARTHOPE, Romania
Subfertility is an increasing problem in the industrialized countries, is accentuated by the unhealthy lifestyle such as: smoking, alcohol use, nutrition alteration either obesity or malnutrition . Worldwide 15-25% of couples encounter fertility problems during their reproductive life . Men’s problems such as azoospermia, oligoasthenospermia, or other sperm analysis abnormalities represent half of the situations . Obesity became an epidemic in some countries, almost 50% of reproductive age women being obese or overweight , malnutrition is a problem in developing countries, the reproductive axis being strongly related to nutritional status . Many experts sustain the importance of weight loss before IVF in women that are overweight or obese . There are clinicians and authorities that refuse to treat patients whose body mass index (BMI) is not under a cut-off value. Periconceptional nutritional status of mother and father is important not only for achieving pregnancy but also for early pregnancy development, fetal wellbeing, and long-term health of the offspring . However, there is little scientific evidence that diet variations like vegetarian diets, low-fat diets, antioxidants, high vitamin diets, herbal remedies improve fertility, but there are some data that certain components of the diet influence reproductive health outcome .
Keywords: nutrition, in vitro fertilization, Mediterranean diet
The effect of obesity over reproductive function is well known from antiquity, Hippocrates writing this in his Essay to the Scythians: ‘The girls get amazingly flabby and podgy … People of such a constitution cannot be prolific … fatness and flabbiness are to blame. The womb is unable to receive the semen, and they menstruate infrequently and little’ .
Obesity is an important problem for reproduction and pregnancy. This problem is affecting more and more women. One of the lifestyle modifications recommended before IVF is weight loss. Bariatric surgery is used in extreme cases, and the results of IVF are better . The increasing popularity of bariatric surgery in reproductive age women determines clinicians to be more aware of its impact on fertility problems .
One characteristic of the diet which was taken into consideration regarding sperm parameters and IVF outcome was meat intake in men. Poultry ingestion seems to have a positive impact; in the meantime, other processed meat has a negative impact . Several studies in the past decades showed a progressive alteration in sperm quality in men, which could determine men’s subfertility. Strong adherence to healthy dietary patterns goes to improve semen tests, especially in men with poor semen previous results . Anorexia nervosa and bulimia nervosa affect 5% of women, which will present amenorrhea, infertility, and in those who manage to conceive an increased risk of miscarriage .
Pregnancy in obese women has an increased risk of diabetes, hypertension, large for gestational age babies, cesarean section and also high perinatal morbidity and mortality . The worst obesity is a particularly abdominal phenotype. An important role in reproductive disturbances is related to hyperandrogenism and hyperinsulinaemia that accompanies the insulin-resistant status . These are the mechanisms through which obesity determines resistance to clomiphene and gonadotropin induction of ovulation and decrease IVF/ICSI outcomes.
Obesity, anovulation, and hyperandrogenism are typical characteristics of polycystic ovarian syndrome (PCOS). Weight loss in obese anovulatory women increases ovulation and conception rate . Increase abdominal fat mass is a component of metabolic syndrome (MBS), which includes hypertension, hypertriglyceridemia, elevated fasting blood glucose, high-density lipoprotein (HDL) low cholesterol. In these situations, lipids are accumulating in non-adipose cells (lipotoxicity). When energy intake exceeds the capacity of adipose tissue to store fat, fatty acids are deposited in the liver and muscles. In these tissues, there is an increase in oxidative stress on reticulum endoplasmic, which is linked to inflammation and insulin resistance .
However, two recent studies looking at reproductive outcomes, show no benefit of lifestyle modifications in comparison with starting IVF immediately . Overweight and obese women need a higher dose of medications, whether it is oral or injectable. The dropout rate of lifestyle modifications is high in obese and overweight women. Physicians who are dealing with such situations should consider informing the patients about the benefits of losing weight, but they should proceed with IVF treatment if they see that women are not progressed in such direction.
Obesity seems to affect oocytes morphology, fertilization rate in some studies but not in all, and embryos quality in women less than 35 years old . The oocytes from women with BMI>25kg/m2 are smaller, and the embryos arrested before blastulation are less likely to form a good quality blastocyst. The blastocysts obtained from these women are smaller and contain higher triglycerides and have lower glucose consumption (Fig.1).
Figure 1. Blastocyst image obtained by time-lapse technology in our IVF laboratory from an obese patient.
The negative effect of obesity on reproductive function is also on implantation being detrimental for endometrium . The source of complications related to obesity is inflammation. Inflammation determines dysregulating genes in endometrium around the window of implantation. Dietary interventions could improve inflammation, which is associated with PCOS and obesity.
Bariatric surgery is recommended for women with BMI >40 kg/m2 or >35 kg/m2 and sleep apnea, cardiovascular problems, or diabetes. Extreme obese determines the alteration of hypothalamus function and alter gonadotropin release hormone pulsatile secretion provoking decreasing reproductive hormones secretion and deficiency in the function of corpus luteus. The most common bariatric surgeries are laparoscopic gastric bands or Roux-en-Y gastric bypass. Gastric bands reduce intake by reducing gastric reservoir and delaying emptying, Roux-en-Y gastric bypass reduces small intestine absorption and also reduce gastric reservoir . These gastric surgeries could lead to malabsorption and deficiency in iron, folate vitamin B12, calcium, and vitamin D. These deficiencies should be corrected before IVF procedures because they could determine growth restriction, hypocalcemia, and neural tube defects in children . Antimullerian hormone (AMH) is lower in obese women and remain lower after bariatric surgery. The risk of miscarriage is reduced or remain unmodified after bariatric surgery. Clinicians, when counseling patients regarding bariatric surgery, could say that this could improve fertility status, hormone secretion, sexuality but seems to produce more oral contraceptives failures. Malnutrition affects implantation, ovulatory function, and ovarian response to stimulation and assisted reproductive technology and could determine health problems in pregnancy and newborns.
The discovery of adipokines and enterokines increases the capability to analyze the relationship between obesity, weight loss, and reproductive function. Animal and human data showed that these are the mediators of obesity action on reproduction function. Some adipokine such us adiponectin has a beneficial effect on insulin activity other such as TNF- a has a negative effect.
Emerging data from epidemiological studies showed that dietary polyphenols prevent cancer, diabetes, neurodegenerative disorders, and cardiovascular diseases . Polyphenols are the most abundant dietary antioxidants and are very common constituents of food plant sources such as fruits, vegetables, coffee, chocolate, wine, and tea. The bioactivity of each polyphenol is different and depends on its antioxidant activity, but also on its absorption, metabolized, and excretion from the body.
Mediterranean diet base on health conscious-low processed dietary pattern consisting on fruits, vegetables, fish, legumes and whole grains and low intake of snacks are associated with high red blood cells folate, high vitamin B6 in blood and follicular fluid increasing the probability of pregnancy in both ICSI and IVF (1). An unbalanced diet with a low intake of vitamins and minerals is correlated with poor pregnancy outcomes.
The effect of vitamin D as a determinant of embryo development is unclear at this moment, even so, there are data showing that it is a key factor in fertilization, sperm-egg binding, and inactivation of acrosine which is involved in digesting zona pellucida (6). The increase in vitamin D in follicular fluid is associated with poor oocyte and embryo morphology. In our study , we found no correlation between serum vitamin D level and pregnancy rate in IVF patients (Fig.2).
Figure 2. Eight cells embryo obtained in our IVF laboratory from a woman with low-level vitamin D
Long-chain polyunsaturated fatty acids (LC-PUFAs)
High intake of eicosapentaenoic acid and docosahexaenoic acid determine to reduce the level of oestradiol during ovarian stimulation and the low number of follicles . Long-chain polyunsaturated fatty acids (LC-PUFAs) are an important component of the cell membrane; they are activated by hormones and growth factors and are implicated in mediating immune response. Omega 3 and omega 6, which improve embryos morphology and reproductive outcomes, are found in fish and green vegetables. Preconceptionally diet with omega-three polyunsaturated fatty acids improves embryo’s morphology .
Diet and men infertility
Studies in men’s infertility had shown that the poultry intake is associated with a higher fertilization rate and processed meat intake with a low fertilization rate during IVF or ICSI. Also, a diet with low fully fat and sweets and higher folate-rich sources determine the improvement of sperm parameters . Healthy nutrition based on fruits, vegetables, fish, and whole grains determines lower DNA damage in sperm. The use of acid, folic, and zinc increases the sperm count in subfertile men.
Obesity is a cause of fertility struggles in men and women, through a complex mechanism, and lower the success rate of IVF. Fortunately it is a modifiable risk factor for infertility, and are evidences that a healthy weight can boost fertility. Nutritional intervention for a healthy eating and an appropriate weight improves fertility.
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