Adherence to the Mediterranean diet and IVF success rate among non-obese women attempting fertility.

STUDY QUESTION: Is adherence to the Mediterranean diet (MedDiet) associated with better IVF performance in women attempting fertility? SUMMARY ANSWER: Greater adherence to the MedDiet, defined using the validated Mediterranean diet score (MedDietScore), was associated with a higher likelihood of achieving clinical pregnancy and live birth among non-obese women <35 years of age. WHAT IS KNOWN ALREADY: Diet impacts fertility and certain nutrients and food groups appear to have a greater effect on reproductive health, but there are relatively few published data on the role of dietary patterns, and the MedDiet in particular, on assisted reproductive performance. STUDY DESIGN, SIZE, DURATION: This prospective cohort study included 244 non-obese women (22-41 years of age; BMI < 30 kg/m2) who underwent a first IVF treatment in an Assisted Conception Unit in Athens, Greece, between November 2013 and September 2016. The study was designed to evaluate the influence of habitual dietary intake and lifestyle on fertility outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS: Diet was assessed before the IVF treatment via a validated food-frequency questionnaire. Adherence to the MedDiet was assessed through the MedDietScore (range: 0-55), with higher scores indicating greater adherence. Intermediate outcomes (oocyte yield, fertilization rate and embryo quality measures) and clinical endpoints (implantation, clinical pregnancy and live birth) were abstracted from electronic medical records. Associations between MedDietScore and IVF outcomes were analysed using generalized linear models adjusting for age, ovarian stimulation protocol, BMI, physical activity, anxiety levels, infertility diagnosis, caloric intake and supplements use. MAIN RESULTS AND THE ROLE OF CHANCE: No association of MedDietScore with any of the intermediate outcomes or with implantation was found. However, compared with women in the highest tertile of the MedDietScore (≥36, n = 86), women in the lowest tertile (≤30, n = 79) had significantly lower rates of clinical pregnancy (29.1 vs 50.0%, P = 0.01) and live birth (26.6 vs 48.8%, P = 0.01). The multivariable-adjusted relative risk (95% CI) for clinical pregnancy comparing women in the lowest with women in the highest tertile of the MedDietScore was 0.35 (0.16-0.78; P-trend=0.01), and for live birth it was 0.32 (0.14-0.71; P-trend = 0.01). These associations were significantly modified by women's age (P-interaction <0.01 for both outcomes). MedDietScore was positively related to clinical pregnancy and live birth among women <35 years old (P ≤ 0.01) but not among women ≥35 years. Among women <35 years, a beneficial 5-point increase in the MedDietScore was associated with ~2.7 times higher likelihood of achieving clinical pregnancy and live birth. LIMITATIONS, REASONS FOR CAUTION: Our finding cannot be generalized to the whole reproductive population nor to obese women nor to women attending infertility clinics around the world. In addition, due to the observational study design, causal inference is limited. WIDER IMPLICATIONS OF THE FINDINGS: The results suggest that diet modifications and greater compliance to the Mediterranean diet may help increase the chances of a successful pregnancy and delivering a live baby for women undergoing IVF treatment. STUDY FUNDING/COMPETING INTEREST(S): This work was partially supported by a grand from Harokopio University (KE321). All authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: NCT03050944.

Association between adherence to the Mediterranean diet and semen quality parameters in male partners of couples attempting fertility.

STUDY QUESTION: Is adherence to the Mediterranean diet (MedDiet) associated with better semen quality in men of subfertile couples attempting fertility? SUMMARY ANSWER: Greater adherence to the MedDiet, as assessed through the validated Mediterranean diet score (MedDietScore), was significantly associated with higher sperm concentration, total sperm count and sperm motility. WHAT IS KNOWN ALREADY: A-posteriori dietary pattern approaches have revealed that dietary patterns characterized by high intakes of fruits, vegetables, whole grains, fish and low intake of meat are associated with better semen quality. Yet, whether adherence to the MedDiet is associated with better semen profile remains largely unexplored. STUDY DESIGN, SIZE, AND DURATION: This was a cross-sectional study of 225 men from couples attending a fertility clinic in Athens, Greece, recruited between November 2013 and May 2016. The study was designed to evaluate the influence of habitual dietary intake and lifestyle on fertility outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS: Men aged 26-55 years, 51.1% overweight or obese, 20.9% smokers, with complete dietary data were analyzed. Diet was assessed via a food-frequency questionnaire and adherence to the MedDiet was assessed through the MedDietScore (range: 0-55; higher scores indicating greater adherence to MedDiet). Semen quality was evaluated according to World Health Organization 2010 guidelines. Multiple logistic regression analysis was used to evaluate associations between tertiles of the MedDietScore and the likelihood of having abnormal semen parameters, after adjusting for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: Compared to men in the highest tertile of the MedDietScore (≥37, N = 66), a higher percentage of men in the lowest tertile of the score (≤30, N = 76) exhibited below the WHO reference values for sperm concentration (47.4% vs 16.7%, P < 0.001), total sperm count (55.3% vs 22.7%, P < 0.001), total motility (65.8% vs 31.8%, P < 0.001), progressive motility (84.2 vs 62.1%, P = 0.011) and sperm morphology (50.0 vs 28.8%, P = 0.023). In the multivariable adjusted models, men in the lowest tertile of the MedDietScore had ~2.6 times higher likelihood of having abnormal sperm concentration, total sperm count and motility, compared to men in the highest tertile of the score. LIMITATIONS, REASONS FOR CAUTION: The main limitation of the study stems from its cross-sectional nature, limiting our ability to determine causality. WIDER IMPLICATIONS OF THE FINDINGS: The results suggest that greater compliance to the MedDiet may help improve semen quality. Whether this translates into differences in male fertility remains to be elucidated. Our findings are consistent with previous studies showing that dietary patterns with some of the characteristics of the MedDiet, i.e. rich in fruit, vegetables, legumes and whole grains, are associated with better measures of semen quality. STUDY FUNDING/COMPETING INTERESTS: No funding was obtained. The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: n/a.

High affinity 17alpha-substituted estradiol derivatives: synthesis and evaluation of estrogen receptor agonist activity.

We synthesized four derivatives of 17beta-estradiol (E2) with an azide substitution on a 17alpha-side chain of varying length, namely 17alpha-(azidopropargyl)-3,17beta-estradiol (5), its 17beta-azido derivative (diazide 7), 17alpha-(5-azido-pent-1-ynyl)-3,17beta-estradiol (6) and 17alpha-(azidopentyn-2-yl)-3,17beta-estradiol (10). While most of the derivatives had low (7) or marginal (6 and 10) relative binding affinity (RBA) for both types of estrogen receptor (ERalpha and ERbeta), the RBAalpha and RBAbeta of 5 were practically identical to those of E2. The estrogenic activity of the derivatives was assessed using estrogen-responsive breast (MCF-7) and endometrial cancer (Ishikawa) cells. While 5 was a potent and effective inducer of alkaline phosphatase in Ishikawa cells and 7 was less potent but as effective as 5, 6 was marginally active and 10 was totally inactive in this respect. In the presence of 0.1 nM E2, however, 6 exhibited some ER antagonist activity at the highest concentration tested (1 microM). Similar results were obtained as regards the potency and efficacy of stimulation of MCF-7 cell proliferation and induction of luciferase gene expression in MCF-7:D5L cells, a clone stably transfected with an estrogen-responsive form of the gene. These data suggest that, while 5, 6, 7 and 10 interact with either type of ER in isolation, only 5 and 7 exhibit substantial ER agonist activity in the different estrogen-target cells examined, which could provide for photoaffinity labelling of the receptor in the cell as well as in isolation.