Nikolaos P Polyzos1, Evangelos Sakkas2, Alberto Vaiarelli2, Kris Poppe3, Michel Camus2, Herman Tournaye2. 1. Center for Reproductive Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium Department of Clinical Medicine, Faculty of Health, University of Aarhus, Incuba/Skejby, bld. 2, Palle Juul-Jensens Boulevard 82, 8200 Aarhus N, Aarhus, Denmark n.polyzos@gmail.com nikolaos.polyzos@uzbrussel.be. 2. Center for Reproductive Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium. 3. Endocrine Unit, University Hospital St-Pierre, Blvd. de Waterloo 129, 1000 Brussels, Belgium.
Abstract
STUDY QUESTION: Is there any association between thyroid autoimmunity (TAI) and diminished ovarian reserve (DOR)? SUMMARY ANSWER: TAI and hypothyroidism are not associated with low ovarian reserve. WHAT IS KNOWN ALREADY: TAI is a common co-existent endocrinopathy in women with primary ovarian insufficiency. Several studies support a potential link between TAI and the reduction in ovarian reserve. However, robust evidence regarding its prevalence in women with DOR is lacking. STUDY DESIGN, SIZE, DURATION: This study is a large cross-sectional analysis of retrospective data from the Centre for Reproductive Medicine/University Hospital of Brussels. Serum measurements were taken for anti-Mullerian hormone (AMH), free thyroxine (FT4), thyroid-stimulating hormone (TSH) and anti-thyroperoxidase (anti-TPO). PARTICIPANTS/MATERIALS, SETTING, METHODS: Among 5076 consecutive women, 4894 women had their AMH, FT4, TSH and anti-TPO levels measured on the same day. AMH levels were plotted in relation to age for the whole patients' cohort and age-specific AMH values (per year) were considered in order to categorize women according to the AMH levels of ovarian reserve. There were 3929 women who demonstrated normal reserve, 487 women who had low ovarian reserve and 478 women who demonstrated high ovarian reserve. MAIN RESULTS AND THE ROLE OF CHANCE: Serum FT4 and TSH levels were comparable between different ovarian reserve categories (P = 0.611 and 0.811, respectively). No significant differences were observed in the prevalence of positive anti-TPO antibodies among women with low (12.1%), normal (10.3%) and high (9.8%) ovarian reserve (P = 0.423). Finally, the prevalence of overt or subclinical hypothyroidism was comparable between the groups (4.1% in low, 4.6% in normal and 3.8% in high ovarian reserve women, P = 0.645).Analysis according to the exact cause of low ovarian reserve demonstrated that women with a genetic cause of low ovarian reserve had a significantly higher prevalence of overt hypothyroidism and subclinical hypothyroidism compared with women with unexplained low ovarian reserve for their age (25 versus 3.2%, P = 0.002 and 18.8 versus 1.6%, P = 0.004, respectively). On the contrary, no significant differences were observed in the prevalence of hypothyroidism between genetic causes and iatrogenic causes (P = 0.316) and between iatrogenic and unexplained causes (P = 0.219) of low ovarian reserve. LIMITATIONS, REASONS FOR CAUTION: This is a cross-sectional analysis based on retrospective data collection. Due to the retrospective design of this study, the presence of biases related to such a study design cannot be excluded. Furthermore, this study assessed only the association of TAI, and not autoimmunity in general, with ovarian reserve. WIDER IMPLICATIONS OF THE FINDINGS: TAI and hypothyroidism are not associated with low ovarian reserve. Future research should focus on examining underlying mechanisms, other than TAI, which may have an effect on ovarian reserve. STUDY FUNDING/COMPETING INTERESTS: No external funding was used for this study. No conflicts of interest are declared.
STUDY QUESTION: Is there any association between thyroid autoimmunity (TAI) and diminished ovarian reserve (DOR)? SUMMARY ANSWER: TAI and hypothyroidism are not associated with low ovarian reserve. WHAT IS KNOWN ALREADY: TAI is a common co-existent endocrinopathy in women with primary ovarian insufficiency. Several studies support a potential link between TAI and the reduction in ovarian reserve. However, robust evidence regarding its prevalence in women with DOR is lacking. STUDY DESIGN, SIZE, DURATION: This study is a large cross-sectional analysis of retrospective data from the Centre for Reproductive Medicine/University Hospital of Brussels. Serum measurements were taken for anti-Mullerian hormone (AMH), free thyroxine (FT4), thyroid-stimulating hormone (TSH) and anti-thyroperoxidase (anti-TPO). PARTICIPANTS/MATERIALS, SETTING, METHODS: Among 5076 consecutive women, 4894 women had their AMH, FT4, TSH and anti-TPO levels measured on the same day. AMH levels were plotted in relation to age for the whole patients' cohort and age-specific AMH values (per year) were considered in order to categorize women according to the AMH levels of ovarian reserve. There were 3929 women who demonstrated normal reserve, 487 women who had low ovarian reserve and 478 women who demonstrated high ovarian reserve. MAIN RESULTS AND THE ROLE OF CHANCE: Serum FT4 and TSH levels were comparable between different ovarian reserve categories (P = 0.611 and 0.811, respectively). No significant differences were observed in the prevalence of positive anti-TPO antibodies among women with low (12.1%), normal (10.3%) and high (9.8%) ovarian reserve (P = 0.423). Finally, the prevalence of overt or subclinical hypothyroidism was comparable between the groups (4.1% in low, 4.6% in normal and 3.8% in high ovarian reserve women, P = 0.645).Analysis according to the exact cause of low ovarian reserve demonstrated that women with a genetic cause of low ovarian reserve had a significantly higher prevalence of overt hypothyroidism and subclinical hypothyroidism compared with women with unexplained low ovarian reserve for their age (25 versus 3.2%, P = 0.002 and 18.8 versus 1.6%, P = 0.004, respectively). On the contrary, no significant differences were observed in the prevalence of hypothyroidism between genetic causes and iatrogenic causes (P = 0.316) and between iatrogenic and unexplained causes (P = 0.219) of low ovarian reserve. LIMITATIONS, REASONS FOR CAUTION: This is a cross-sectional analysis based on retrospective data collection. Due to the retrospective design of this study, the presence of biases related to such a study design cannot be excluded. Furthermore, this study assessed only the association of TAI, and not autoimmunity in general, with ovarian reserve. WIDER IMPLICATIONS OF THE FINDINGS: TAI and hypothyroidism are not associated with low ovarian reserve. Future research should focus on examining underlying mechanisms, other than TAI, which may have an effect on ovarian reserve. STUDY FUNDING/COMPETING INTERESTS: No external funding was used for this study. No conflicts of interest are declared.
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