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Folate, Hormones and Infertility: Different factors affecting IVF pregnancy outcome
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Various hormones have been studied as regards prediction of pregnancy outcome after infertility treatment, but no ideal candidate has been found. Folate and genetic variations in folate metabolism have also been associated with infertility, but it remains unclear how these factors affect IVF pregnancy outcome. It is known that infertility is associated with active folic acid supplement use, but the effect of socioeconomic and lifestyle factors on folic acid supplement use in infertile women has not been well investigated. The overall aim of this work was to obtain information on the prediction of live birth, and to study factors affecting the role of folate and folic acid intake in relation to IVF pregnancy outcome. Infertile women with various infertility diagnoses were studied. Healthy, fertile non-pregnant women were used as controls in three of the studies. Blood samples were taken for assay of eight different hormones, folate and homocysteine, and for genomic DNA extraction. A questionnaire was used to assess background data and use of folic acid supplements. Twenty-four-hour recall interviews were performed for validation of the questionnaire. The studied hormones were not good predictors of live birth. The best predictor was age of the women, together with ovulatory menstrual cycles, and thyroid-stimulating hormone and anti-Müllerian hormone (AMH) status. Well-educated women, high-status employed women, and married and infertile women used the most folic acid supplements. Infertile women had better folate status than fertile women. However, pregnancy outcome after infertility treatment was not dependent on folic acid intake, folate status, genetic variation of 5,10-methylenetetrahydrofolate reductase or socioeconomic status. In conclusion, AMH levels vary less than those of other hormones during the menstrual cycle, and AMH could be used as a predictive marker of live birth together with age and ovulation. Folate might play a minor role in IVF pregnancy outcome, but the importance of folate as regards other health perspectives should not be forgotten.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2014. , 57 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 987
Keyword [en]
Folate, folic acid supplement, homocysteine, hormones, infertility, IVF, lifestyle factor, MTHFR, predictive value, socioeconomic factor, women
National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Obstetrics and Gynaecology
Identifiers
URN: urn:nbn:se:uu:diva-220476ISBN: 978-91-554-8919-9 (print)OAI: oai:DiVA.org:uu-220476DiVA: diva2:707736
Public defence
2014-05-22, Gustavianum, Auditorium Minus, Akademigatan 3, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2014-04-29 Created: 2014-03-15 Last updated: 2014-06-30
List of papers
1. Predictive value of hormonal parameters for live birth in women with unexplained infertility and male infertility
Open this publication in new window or tab >>Predictive value of hormonal parameters for live birth in women with unexplained infertility and male infertility
2013 (English)In: Reproductive Biology and Endocrinology, ISSN 1477-7827, E-ISSN 1477-7827, Vol. 11, 61- p.Article in journal (Refereed) Published
Abstract [en]

Background: Infertile women might get pregnant sometime after fertility treatment, but today, there is no prediction model on who will eventually have children. The objective of the present study was to characterize hormone levels in an arbitrary menstrual cycle in women with unexplained infertility and male infertility, and to determine the predictive value for long-term possibility of live birth. Methods: In this cross-sectional study, with 71 infertile women with diagnosis unexplained infertility and male infertility, blood samples were obtained during the proliferative and secretory phases of an arbitrary menstrual cycle. Serum concentrations of FSH, LH, AMH, inhibin B, estradiol, progesterone, PRL and TSH were determined. The predictive value of ovulation and hormonal analysis was determined by identifying the proportion of women with at least one live birth. Mann Whitney U test, chi2 test and Spearman's correlation were used for statistical analysis. A value of p < 0.05 was considered statistically significant. Results: There were no differences in hormone values and live birth rates between women with unexplained infertility and male infertility. The best sole predictors of live birth were age of the women, followed by ovulatory cycle, defined as serum progesterone concentration of greater than or equal to 32 nmol/L, and a serum TSH concentration of less than or equal to 2.5 mIU/L. Combining the age with the ovulatory cycle and serum TSH less than or equal to 2.5 mIU/L or serum AMH greater than or equal to 10 pmol/L the predictive value was close to 90%. Conclusions: Age in combination with the presence of an ovulatory cycle and serum TSH or serum AMH is predictive for long-term live birth. The advantage of serum AMH compared with serum TSH is the very little variation throughout the menstrual cycle, which makes it a useful tool in infertility diagnosis.

Keyword
AMH, FSH, Inhibin B, LH, Oestrogen, Progesterone, Prolactin, TSH
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-204858 (URN)10.1186/1477-7827-11-61 (DOI)000321740200001 ()
Available from: 2013-08-12 Created: 2013-08-12 Last updated: 2017-12-06Bibliographically approved
2. Folic acid supplementation and IVF pregnancy outcome in women with unexplained infertility
Open this publication in new window or tab >>Folic acid supplementation and IVF pregnancy outcome in women with unexplained infertility
Show others...
2014 (English)In: Reproductive Biomedicine Online, ISSN 1472-6483, E-ISSN 1472-6491, Vol. 28, no 6, 766-772 p.Article in journal (Refereed) Published
Abstract [en]

Folic acid supplements are commonly used by infertile women and lead to a positive folate status. However, the effect of folic acid supplements on pregnancy outcome in women with unexplained infertility has not been well investigated. This study evaluated folic acid supplement use and folate status in women with unexplained infertility in relation to pregnancy outcome. In addition, use of folic acid supplements and folate status were compared between women with unexplained infertility and fertile, nonpregnant control women. Women with unexplained infertility used significantly more folic acid supplements and had higher median total folic acid intake from supplements compared with fertile control women (both P < 0.001). Women with unexplained infertility also had significantly higher median plasma folate and lower median plasma homocysteine concentrations than fertile women (both P < 0.001), but folic acid supplementation or folate status were not related to pregnancy outcome in women with unexplained infertility. In conclusion, folic acid supplementation or good folate status did not have a positive effect on pregnancy outcome following infertility treatment in women with unexplained infertility.

Keyword
dietary supplement, folate, folic acid, homocysteine, infertility, pregnancy
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-220114 (URN)10.1016/j.rbmo.2014.01.017 (DOI)000338862000014 ()
Available from: 2014-03-11 Created: 2014-03-11 Last updated: 2017-12-05Bibliographically approved
3. Folic acid supplementation and methylenetetrahydrofolate reductase (MTHFR)gene variations in relation to IVF pregnancy outcome
Open this publication in new window or tab >>Folic acid supplementation and methylenetetrahydrofolate reductase (MTHFR)gene variations in relation to IVF pregnancy outcome
Show others...
2015 (English)In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 94, no 1, 65-71 p.Article in journal (Refereed) Published
Abstract [en]

Objective:

To study folic acid intake, folate status and pregnancy outcome afterinfertility treatment in women with different infertility diagnoses in relation tomethylenetetrahydrofolate reductase (MTHFR) 677C>T, 1298A>C and 1793G>A genevariations. Also the use of folic acid supplements, folate status and the frequency ofdifferent gene variations were studied in women undergoing infertility treatment andfertile women.

Design:

Observational study. Setting: University hospital. Population:Women undergoing infertility treatment and healthy, fertile, non-pregnant women.

Methods:

A questionnaire was used to assess general background data and use ofdietary supplements. Blood samples were taken to determine plasma folate andhomocysteine levels, and for genomic DNA extraction. A meta-analysis of four studieswas performed to assess pregnancy outcome in relation to MTHFR 677 TT vs. CC, and1298 CC vs. AA polymorphisms.

Main outcome measures:

Folic acid supplementintake, and plasma folate, homocysteine and genomic assays.

Results:

Women in theinfertility group used significantly more folic acid supplements and had better folatestatus than fertile women, but pregnancy outcome after fertility treatment was notdependent on folic acid intake, folate status or MTHFR gene variations. However, ameta-analysis demonstrated that MTHFR 1298AA polymorphism was related topregnancy outcome.

Conclusion:

Folic acid supplementation seems to play only a minorrole in the context of pregnancy outcome after in vitro fertilisation, and other variablesin folate metabolism are of more importance. In particular, MTHFR 1298AA genevariation appears to have a positive association with the success of fertility treatment

Keyword
Folate, folic acid, homocysteine, infertility, MTHFR, pregnancy outcome
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-220246 (URN)10.1111/aogs.12522 (DOI)000346704100012 ()25283235 (PubMedID)
Available from: 2014-03-12 Created: 2014-03-12 Last updated: 2017-12-05Bibliographically approved
4. Socioeconomic and lifestyle factors in relation to folic acid supplement use in infertile and fertile Swedish women
Open this publication in new window or tab >>Socioeconomic and lifestyle factors in relation to folic acid supplement use in infertile and fertile Swedish women
Show others...
(English)Manuscript (preprint) (Other academic)
Abstract [sv]

Background: Socioeconomic and lifestyle factors are considered to be associated with folic acid supplement use and intake in the general population, but studies on infertile women are lacking. When investigating dietary supplement intake, the validity of the assessment of reported supplement use and actual intake is crucial. The objective of the study was to investigate socioeconomic, lifestyle and dietary factors in relation to folic acid supplement use and folate status in infertile and fertile women. In addition, a sub-analysis was performed to validate the used questionnaire. Methods: In this observational study, 340 infertile women and 188 fertile women were investigated. A questionnaire was used to assess lifestyle and dietary habits and use of dietary supplements. Blood samples were obtained for analyses of plasma folate and homocysteine levels. 24-hour recall interviews were performed to validate the questionnaire. Results: Folic acid supplement use was related to marital status, educational level and employment status. Infertile women had significantly higher mean folic acid daily intake and better folate status. However, folate status did not correlate with socioeconomic or lifestyle factors. The infertile women were physically more active, smoked less and had better employment status, but they were also more obese than fertile women. Socioeconomic and lifestyle factors were not related to in vitro fertilization outcome. Dietary data from the questionnaires showed good validity compared with the data from the 24-hour recall interviews, but data regarding folic acid supplement use showed only fair agreement between these methods. Conclusions: Highly educated, employed, married and infertile women were most prone to using folic acid supplements. Only a few socioeconomic and lifestyle factors differed between infertile and fertile women, and these were not related to folate status or IVF outcome. Methods other than a questionnaire are recommended when investigating folic acid supplement use.

 

Keyword
Folic acid supplement, infertility, socioeconomic status, lifestyle, dietary
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-220409 (URN)
Available from: 2014-03-15 Created: 2014-03-13 Last updated: 2014-04-29

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