Aile Hekiminiz

The available evidence from epidemiologic studies and clinical trials presents a mixed picture regarding the health benefits and potential risks of fish consumption and omega-3 fatty acid supplementation for pregnant women, the fetus and young children. For virtually all of the outcomes we considered where research is available – length of gestation and risk of prematurity, birthweight, hypertension and preeclampsia, depression in pregnancy and postpartum depression, fetal brain development and early childhood IQ, allergy and asthma in children – there is evidence suggestive of benefit for fish intake or omega-3 supplementation; however, there are also many studies showing no benefit, or, in a few instances, possible harmful effects. Evidence from the available randomized, controlled trials is most suggestive of benefit for the outcome of preterm birth before 34 weeks, particularly among women with a prior preterm birth. Results of clinical trials of omega-3 fatty acid supplementation are summarized in Table 2.

In assessing their findings of no impact or negative effect, investigators raised a number of issues, including noncompliance to study protocol requirements on the part of participants,[36] the type of fish products consumed,[49] the possible role of industrial contamination,[41] and the timing of intervention.[56,58,67] It is also worth noting in considering inconsistent findings that data collection methodology varies across studies with use of food frequency questionnaires, surveys, measurement of acid levels and other approaches, making consistent cross-study comparisons difficult. For some outcomes, such as childhood neurodevelopment, the few intervention studies that are available vary in terms of time points used for assessment (i.e., age of children studied), the specific subtests that are considered (e.g., mental processing, intelligence, verbal skills, visual acuity, problem solving, quantitative skills, communication abilities, presocial behavior and attention), and the tools used to evaluate these aspects of behavior. Appropriately powered, randomized, controlled trials are needed that can address these and other issues. Using the highly purified omega-3 fatty acid supplements now available, future trials should benefit from improved participant compliance, which should allow for better determination of true treatment effects. We feel that more investigation is needed to clarify the possible benefits of omega-3 fatty acid supplementation in perinatal depression, early childhood cognitive functioning (including IQ, attention and behavior), and risk for allergic diseases. Current evidence does not support a role for omega-3 fatty acid supplementation for prevention of preeclampsia, pregnancy-induced hypertension, or intrauterine growth restriction. More needs to be learned regarding whether the effects of omega-3 supplements differ between singleton and twin gestation, or between high- and low-risk pregnancies. More research needs to be carried out on the differential effects of eating fish versus taking supplements, and the optimal dosage of omega-3 supplements need to be established.

In the available randomized, controlled trials, doses of omega-3 fatty acids up to 6 g/day have been used. In the USA, the FDA has designated omega-3 fatty acid doses up to 3 g/day as “generally regarded as safe”.[203] In our review of the available studies of fish oil supplementation for high-risk pregnancies, a dose of approximately 1000 mg of DHA appeared to be the most frequently used beneficial dose. Doses of EPA in these studies varied widely between 1300 and 3000 mg, so no optimal dose has been established.[46] Most trials have commenced fatty acid supplementation in the second or third trimester of pregnancy. After reviewing the available evidence, a recent EU-supported Perinatal Lipid Intake Working Group has recommended that all pregnant and lactating women achieve a dietary intake of DHA of at least 200 mg daily. The authors note that DHA intakes of up to 1000 mg/day and total omega-3 LC-PUFA intake up to 2.7 g/day have been used in randomized trials without significant adverse effects.[5]

Lifestyle Management Before Infertility Treatment
Peter Kovacs, MD, PhD

Peter Kovacs, MD
Clinical Reproductive Endocrinologist, Research and Scientific Coordinator, The Kaali Institute-IVF Center, Budapest, Hungary

It is well known that women who are under- or overweight have difficulty with reproduction. Obese women are at risk for miscarriage, gestational diabetes, gestational hypertension, preterm delivery, macrosomia, low birth weight, stillbirth, delivery via operative route, and postoperative complications. Underweight women are also at risk for miscarriage, low birth weight, preterm delivery, and stillbirth. Therefore, preconceptional counseling about weight and lifestyle management is very important.

During this counseling, one should evaluate the patient’s diet, frequency and intensity of exercise, toxic habits, and use of drugs that affect body weight. The best way to assess weight is to calculate the body mass index (BMI) using the following equation: weight (kg)/height2 (m2).

A BMI between 18.5 and 24.9 kg/m2 is considered normal. Women with a BMI < 18.5 kg/m2 are underweight, whereas women with a BMI > 25 kg/m2 are overweight, and those with a BMI > 30 kg/m2 are obese.

Underweight women should be screened for eating disorders and thyroid dysfunction. In some cases, it may be appropriate to work together with a nutritionist and a psychologist. Low body weight is associated with ovulatory dysfunction. Usually, minimal weight gain (3 to 5 kg) is sufficient to restore ovulation and to improve the outcome of a subsequent pregnancy.

Overweight women also need to undergo a throrough endocrinologic evaluation (thyroid function, Cushing’s syndrome, polycystic ovary syndrome [PCOS]). They should be screened for diabetes, lipid abnormalities, and hypertension and should be advised about a lower-calorie diet with approriate nutrients. Women with PCOS may benefit from a diet that is low in saturated fat and high in low-glycemic-index-carbohydrate. Besides adhering to a healthy diet, regular exercise is needed to burn excess calories and to help to maintain a lower weight. Daily moderate exercise for about 30 minutes is recommended. Very often ovarian activity is restored by losing 5% to 10% of weight, even without reaching the ideal range.

Drugs that improve insulin resistance also improve reproductive outcome among women with PCOS. They should not be used alone, however, but rather should be combined with a healthy diet and regular exercise.

Adequate folic acid intake is essential for reproductive-age women, as it can reduce the incidence of fetal neural tube defects and cardiac anomalies.

Weight control is very important for those women who enter an assisted reproductive technology (ART) program. Treatment outcome is clearly worse among obsese patients. Aside from the lower pregnancy rates and higher miscarriage rates and other obstetric complications, they are at higher risk during the entire process. Obesity can limit the accuracy of ultrasound monitoring. Obese patients are at higher risk during the procedures (eg, oocyte collection), especially when anesthesia is provided. Thin women are also at increased risk during ART; for example, ovarian hyperstimulation occurs more commonly among thin women.

Toxic habits not only adversely affect the developing fetus but also compromise gonad function. In men, smoking has been associated with lower sperm number and motility, and in women, smoking has toxic ovarian effects. Drug use may also affect gonadal activity by altering the stimulatory pathways of the central nervous system. Consumption of alcohol and caffeine adversely affects fertility, and their intake needs to be limited before attempting pregnancy.

Whether stress can cause infertility is a question commonly asked during pretreatment counseling. It is not easy to answer this question, as it is rather difficult to measure the degree of stress objectively. Although at least one small prospective longitudinal study has found no evidence that psychological stress influenced the outcome of in vitro fertilization (IVF) in women undergoing their first IVF treatment (the number of good-quality embryos transferred was the only variable that was independently associated with pregnancy), many experts believe stress can affect the outcome of infertility treatment. Infertility itself, with its family-related and social consequences, the evaluation and treatment (especially when repetitive), and the lack of success can have a major impact on a patient’s psychological well-being. Thoroughly explaining the steps and process of treatment and providing the patient with a plan if the first few attempts are not successful may reduce the psychological burden. It is also important to explain to the patient what she may reasonably expect. A patient with irrational expectations will have even greater difficulty accepting a treatment failure.

In summary, patients who lead a healthy lifestyle before initiating infertility treatment are optimizing the potential for a good outcome. Those who are not need to be encouraged and supported to alter their habits and counseled about the associated risks to which they and their fetus will be exposed. Finally, it is very important to have medical staff who are able to provide medical and psychological information and support during the course of infertility treatment.

From Human Reproduction
A Prospective Study of Dietary Fat Consumption and Endometriosis Risk
Stacey A. Missmer; Jorge E. Chavarro; Susan Malspeis; Elizabeth R. Bertone-Johnson; Mark D. Hornstein; Donna Spiegelman; Robert L. Barbieri; Walter C. Willett; Susan E. Hankinson

Abstract
Background: Endometriosis is a prevalent but enigmatic gynecologic disorder for which few modifiable risk factors have been identified. Fish oil consumption has been associated with symptom improvement in studies of women with primary dysmenorrhea and with decreased endometriosis risk in autotransplantation animal studies.
Methods: To investigate the relation between dietary fat intake and the risk of endometriosis, we analyzed 12 years of prospective data from the Nurses’ Health Study II that began in 1989. Dietary fat was assessed via food frequency questionnaire in 1991, 1995 and 1999. We used Cox proportional hazards models adjusted for total energy intake, parity, race and body mass index at age 18, and assessed cumulatively averaged fat intake across the three diet questionnaires.
Results: During the 586 153 person-years of follow-up, 1199 cases of laparoscopically confirmed endometriosis were reported. Although total fat consumption was not associated with endometriosis risk, those women in the highest fifth of long-chain omega-3 fatty acid consumption were 22% less likely to be diagnosed with endometriosis compared with those with the lowest fifth of intake [95% confidence interval (CI) = 0.62–0.99; P-value, test for linear trend (Pt) = 0.03]. In addition, those in the highest quintile of trans-unsaturated fat intake were 48% more likely to be diagnosed with endometriosis (95% CI = 1.17–1.88; Pt = 0.001).
Conclusion: These data suggest that specific types of dietary fat are associated with the incidence of laparoscopically confirmed endometriosis, and that these relations may indicate modifiable risk. This evidence additionally provides another disease association that supports efforts to remove trans fat from hydrogenated oils from the food supply.

Stressful Life Events are Associated with a Poor In-vitro Fertilization (IVF) Outcome: A Prospective Study
S.M.S. Ebbesen; R. Zachariae; M.Y. Mehlsen; D. Thomsen; A. Højgaard; L. Ottosen; T. Petersen; H.J. Ingerslev
From Human Reproduction

Abstract
Background: There is preliminary evidence to suggest an impact of stress on chances of achieving a pregnancy with in-vitro fertilization (IVF). The majority of the available research has focused on stress related to infertility and going through IVF-treatment, and it is still unclear whether non-fertility-related, naturally occurring stressors may influence IVF pregnancy chances. Our aim was to explore the association between IVF-outcome and negative, i.e. stressful, life-events during the previous 12 months.
Methods: Prior to IVF, 809 women (mean age: 31.2 years) completed the List of Recent Events (LRE) and questionnaires measuring perceived stress and depressive symptoms.
Results: Women who became pregnant reported fewer non-fertility-related negative life-events prior to IVF (Mean: 2.5; SD: 2.5) than women who did not obtain a pregnancy (Mean: 3.0; SD: 3.0) (t(465.28) = 2.390, P = 0.017). Logistic regression analyses revealed that the number of negative life-events remained a significant predictor of pregnancy (OR: 0.889; P = 0.02), when controlling for age, total number of life-events, perceived stress within the previous month, depressive symptoms, and relevant medical factors related to the patient or treatment procedure, including duration of infertility, number of oocytes retrieved and infertility etiology. Mediation analyses indicated that the association between negative life events and IVF pregnancy was partly mediated by the number of oocytes harvested during oocyte retrieval.
Conclusion: A large number of life-events perceived as having a negative impact on quality of life may indicate chronic stress, and the results of our study indicate that stress may reduce the chances of a successful outcome following IVF, possibly through psychobiological mechanisms affecting medical end-points such as oocyte retrieval outcome.