Clinical trial NCT03050944: Association of the Mediterranean Diet With Fertility Outcomes
Official title: Association of the Mediterranean Diet With Fertility Outcomes: a Study Among Couples Undergoing in Vitro Fertilization Treatment
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Infertility
Keywords: Fertility
Infertility
Dietary Patterns
Mediterranean diet
Adiponectin
Follistatin
Assisted Reproduction
In Vitro Fertilization
Semen quality
Diet
IVF
Lead sponsor: Harokopio University
Sponsor class: OTHER
Collaborators: name: Embryogenesis Assisted Conception Unit
First posted: 2017-02-13
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subfertile couples undergoing IVF treatment at a Fertility Clinic in Athens

Brief summary: Infertility affects one of every six couples and one out of ten couples may seek fertility treatment such as ovulation induction and assisted reproductive technologies. With respect to diet, several dietary factors, i.e. micro-, macro-nutrients and individual food groups, have been associated with the risk of subfertility; however, more information is needed on the role of dietary factors in reproductive functions. However, evidence concerning the association between dietary patterns, such as the Mediterranean diet (MD) pattern, and fertility is scarce. The aim of this study is to investigate the relationship between preconception dietary patterns, especially the MD pattern, and in vitro fertilization (IVF) outcomes, as well as adiponectin and follistatin concentrations in the plasma and follicular fluid of women undergoing IVF treatment. Blood and follicular fluid adiponectin and follistatin concentrations will be measured on each day of the ovarian stimulation protocol. Main IVF treatment outcomes are fertilization rate, oocyte and embryo quality, implantation, clinical pregnancy and live birth rates.

Detailed description: Infertility affects one of every six couples and one out of ten couples may seek fertility treatment such as ovulation induction and assisted reproductive technologies. There are multiple causes of infertility, including ovulatory disorders, endometriosis and sperm factors, or even psychological problems, among others. Modifiable lifestyle factors, such as diet, smoking and physical activity, may also affect fertility. With respect to diet, several dietary factors, i.e. micro-, macro-nutrients and individual food groups, have been associated with the risk of subfertility; however, more information is needed on the role of dietary factors in reproductive functions. A more comprehensive approach to investigate the associations between dietary factors and health outcomes is to assess the impact of the overall diet rather than separate foods or nutrients. However, evidence concerning the association between dietary patterns, such as the Mediterranean diet (MD) pattern, and fertility is scarce. The benefits of the MD on health have been well-publicized; it is associated with a significant reduction of overall mortality, cardiovascular disease and cancer. Adherence to the MD also seems to reduce the risk of weight gain and diabetes, conditions that raise insulin resistance and may thus lead to ovulatory infertility. Recently, adherence to MD was also associated with an increase in circulating adiponectin levels, a hormone produced by the adipose tissue that acts to reduce insulin resistance. Interestingly, adiponectin has been shown to exert actions in the female reproductive system, including the hypothalamic-pituitary ovarian axis and endometrium, and thus, it can be hypothesized that MD may exert a beneficial effect on reproductive functions through a raising effect on adiponectin levels. The aim of this study is to investigate the relationship between preconception dietary patterns, especially the MD pattern, and in vitro fertilization (IVF) outcomes, as well as adiponectin and follistatin concentrations in the plasma and follicular fluid of women undergoing IVF treatment.

Two-hundred subfertile couples undergoing IVF treatment at a Fertility Clinic in Athens (www.embryogenesis.gr/) will be invited to participate. Participants will fill out the following questionnaires: a general questionnaire to record the baseline characteristics of the subjects (age, educational level, annual income, medical history, body mass index, smoking, etc), a semi-quantitative 77-item food frequency questionnaire to assess habitual dietary intakes, and a 40-item state-trait anxiety inventory instrument to measure anxiety symptoms. Dietary patterns will be evaluated using principal component analysis and factor analysis. Adherence to the MD will be assessed with a MD-score that incorporates the inherent characteristics of this traditional diet, that is, high intake of plant foods and olive oil, low intake of meat and dairy products, and moderate intake of alcohol. Blood and follicular fluid adiponectin and follistatin concentrations will be measured on each day of the ovarian stimulation protocol. Main IVF treatment outcomes are fertilization rate, embryo quality, implantation, clinical pregnancy and live birth.

Associations between dietary patterns, adiponectin and follistatin concentrations and the IVF treatment outcomes will be tested using linear and logistic regression analyses, adjusting for potential confounders (e.g. age, smoking, anxiety symptoms, etc). The findings of the study could contribute in the development of guidelines to prevent infertility or to nutritional management associated to infertility treatments to improve reproductive performance. Furthermore, the elucidation of the role of adiponectin and follistatin in female reproductive functions and its association with dietary variables and the IVF outcomes could lead to the use of adiponectin or follistatin as therapeutic targets in novel treatment strategies of infertility disorders.

Eligibility criteria: Inclusion Criteria:

* Presence of subfertility (male or female origin)

Exclusion Criteria:

* Women's age \<41.
* Previous IVF attempt or pregnancy.
* Female obesity (BMI\>30 kgr/m2).
* Endometriosis
* Oocyte donation.
* Adherence to a hypocaloric diet for weight loss or changes in dietary habits during the last six months.
* Presence of female diabetes mellitus, cardiovascular disease, hypertension, neoplasm, hypothyroidism or psychiatric disorders.
* Previous ovarian surgery.
* Natural cycle IVF.
* Couples whose male partner shows an abnormality of the male genital tractus : Varicocele, undescended testis, testicular volume \< 12ml

Primary outcomes:
measure: Live Birth
timeFrame: 9 months
Secondary outcomes:
measure: Hormonal profile
timeFrame: 3 months
measure: Oocyte number.
timeFrame: 3 months
measure: Oocyte quality.
timeFrame: 3 months
measure: Embryo number.
timeFrame: 3 months
measure: Embryo quality.
timeFrame: 3 months
measure: Semen volume.
timeFrame: 1 month.
measure: Semen concentration.
timeFrame: 1 month.
measure: Semen morphology.
timeFrame: 1 month.
measure: Semen Motility.
timeFrame: 1 month.
measure: Fertilization rate
timeFrame: 3 months
measure: Serum Adiponectin
timeFrame: 6 months
measure: Follicular Fluid Adiponectin
timeFrame: 6 months
measure: Follicular Fluid Follistatin,
timeFrame: 6 months
measure: Clinical Pregnancy
timeFrame: 6 months
Other outcomes:
Locations:
city: Athens
country: Greece
facility: Harokopio University
state: Attiki
Study officials:
affiliation: Associate Professor of Physiology
name: Nikolaos Yiannakouris, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Karayiannis D, Kontogianni MD, Mendorou C, Douka L, Mastrominas M, Yiannakouris N. Association between adherence to the Mediterranean diet and semen quality parameters in male partners of couples attempting fertility. Hum Reprod. 2017 Jan;32(1):215-222. doi: 10.1093/humrep/dew288. Epub 2016 Nov 14.
citation: Karayiannis D, Kontogianni MD, Mendorou C, Mastrominas M, Yiannakouris N. Adherence to the Mediterranean diet and IVF success rate among non-obese women attempting fertility. Hum Reprod. 2018 Mar 1;33(3):494-502. doi: 10.1093/humrep/dey003.