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Association of Thyroid Function and Autoimmunity with Ovarian Reserve in Women Seeking Infertility Care.

ABSTRACT: BACKGROUND:While overt thyroid disease is a well known risk factor for infertility, the potential consequences of mild thyroid dysfunction or thyroid autoimmunity remain unknown. Experimental studies suggest a considerable role for thyroid hormone in the physiological mechanisms of ovarian reserve, but translation of such findings to human studies remains rare. A potential role for thyroid function in female reproduction could be especially relevant when the cause of infertility remains unknown, such as in women with diminished ovarian reserve (DOR) or unexplained infertility. The aims of this study were to investigate the association of thyroid function and autoimmunity with markers of ovarian reserve day 3 follicle-stimulating hormone (FSH) concentrations and antral follicle count (AFC), and to investigate whether thyroid function or autoimmunity may have different effects in women with DOR or unexplained infertility. METHODS:Thyrotropin, free thyroxine, thyroxine, free triiodothyronine (fT3), triiodothyronine, thyroid peroxidase antibodies (TPOAbs), and thyroglobulin antibodies (TgAbs), as well as AFC and the day 3 FSH concentration, were measured among women seeking fertility treatment at the Massachusetts General Hospital Fertility Center. Multiple linear or mixed regression models were used to study the association of thyroid function or autoimmunity with AFC or day 3 FSH. RESULTS:In the total study population (436 women, 530 AFC measurements), there was no association of thyroid function or TPOAb positivity with AFC. However, TgAb positivity was associated with a higher AFC (mean difference?=?3.4 [95% confidence interval (CI) 1.8-5.1], p?

SUBMITTER: Korevaar TIM

PROVIDER: S-EPMC6157366 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Association of Thyroid Function and Autoimmunity with Ovarian Reserve in Women Seeking Infertility Care.

Korevaar Tim I M TIM Mínguez-Alarcón Lidia L Messerlian Carmen C de Poortere Ralph A RA Williams Paige L PL Broeren Maarten A MA Hauser Russ R Souter Irene C IC

Thyroid : official journal of the American Thyroid Association 20180814 10

<h4>Background</h4>While overt thyroid disease is a well known risk factor for infertility, the potential consequences of mild thyroid dysfunction or thyroid autoimmunity remain unknown. Experimental studies suggest a considerable role for thyroid hormone in the physiological mechanisms of ovarian reserve, but translation of such findings to human studies remains rare. A potential role for thyroid function in female reproduction could be especially relevant when the cause of infertility remains ...[more]

PMID: 29943679

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Project description:Study questionAre urinary phthalate metabolites associated with reduced antral follicle growth among women in an infertility setting?Summary answerHigher urinary concentrations of di(2-ethylhexyl) phthalate (DEHP) metabolites were associated with significant decreases in antral follicle count (AFC) among women seeking infertility care.What is known alreadyExperimental animal studies show that DEHP accelerates primordial follicle recruitment and inhibits antral follicle growth. Whether phthalates also reduce the growing antral follicle pool in humans remains unknown.Study design, size, durationWe examined the association between urinary phthalate metabolites and AFC using prospective data from 215 females recruited between 2004 and 2012 in the Environment and Reproductive Health (EARTH) study.Participants/materials, setting, methodsWe quantified the urinary concentrations of 11 phthalate metabolites. We estimated the geometric mean for all urine samples provided prior to unstimulated day 3 AFC assessment for each woman. We evaluated the association of AFC with ∑DEHP (molar sum of four DEHP metabolites) and individual phthalate metabolites using Poisson regression, adjusting for age, BMI and smoking.Main results and the role of chanceWe observed significant decreases in mean AFC for all higher quartiles of ∑DEHP as compared with the lowest quartile. Compared with women in the first quartile of ∑DEHP, women in the second, third and fourth quartiles had a -24% (95% confidence interval (CI): -32%, -16%), -19% (95% CI: -27%, -9%), and -14% (95% CI: -23%, -5%) decrease in mean AFC. The absolute mean AFC in the first quartile was 14.2 follicles (95% CI: 13.2, 15.2) compared with 10.7 follicles (95% CI: 9.9, 11.6) in the second quartile. We observed similar trends among the four individual DEHP metabolites. There was no consistent change in AFC among the remaining phthalate metabolite concentrations evaluated.Limitations, reasons for cautionWe demonstrated a negative association between DEHP and a well-established marker of ovarian reserve among a subfertile population. However these findings may not be generalizable to women without fertility concerns, and we cannot rule out co-exposure to other chemicals.Wider implications of the findingsEnvironmental chemicals that inhibit the size of the growing antral follicle pool can impair fertility and reduce fecundity. This study suggests evidence in need of further investigation on the impact of phthalates on the human oocyte and follicular development.Study funding/competing interestsWork supported by grants ES009718, ES022955, ES000002, and T32ES007069 from the National Institute of Environmental Health Sciences (NIEHS) and grant T32 DK007703-16 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). C.M. was supported by a post-doctoral training award from the Canadian Institutes of Health Research. There are no competing interests to declare.

Project description:Importance:Despite lack of evidence of their utility, biomarkers of ovarian reserve are being promoted as potential markers of reproductive potential. Objective:To determine the associations between biomarkers of ovarian reserve and reproductive potential among women of late reproductive age. Design, Setting, and Participants:Prospective time-to-pregnancy cohort study (2008 to date of last follow-up in March 2016) of women (N?=?981) aged 30 to 44 years without a history of infertility who had been trying to conceive for 3 months or less, recruited from the community in the Raleigh-Durham, North Carolina, area. Exposures:Early-follicular-phase serum level of antimüllerian hormone (AMH), follicle-stimulating hormone (FSH), and inhibin B and urinary level of FSH. Main Outcomes and Measures:The primary outcomes were the cumulative probability of conception by 6 and 12 cycles of attempt and relative fecundability (probability of conception in a given menstrual cycle). Conception was defined as a positive pregnancy test result. Results:A total of 750 women (mean age, 33.3 [SD, 3.2] years; 77% white; 36% overweight or obese) provided a blood and urine sample and were included in the analysis. After adjusting for age, body mass index, race, current smoking status, and recent hormonal contraceptive use, women with low AMH values (<0.7 ng/mL [n?=?84]) did not have a significantly different predicted probability of conceiving by 6 cycles of attempt (65%; 95% CI, 50%-75%) compared with women (n?=?579) with normal values (62%; 95% CI, 57%-66%) or by 12 cycles of attempt (84% [95% CI, 70%-91%] vs 75% [95% CI, 70%-79%], respectively). Women with high serum FSH values (>10 mIU/mL [n?=?83]) did not have a significantly different predicted probability of conceiving after 6 cycles of attempt (63%; 95% CI, 50%-73%) compared with women (n?=?654) with normal values (62%; 95% CI, 57%-66%) or after 12 cycles of attempt (82% [95% CI, 70%-89%] vs 75% [95% CI, 70%-78%], respectively). Women with high urinary FSH values (>11.5 mIU/mg creatinine [n?=?69]) did not have a significantly different predicted probability of conceiving after 6 cycles of attempt (61%; 95% CI, 46%-74%) compared with women (n = 660) with normal values (62%; 95% CI, 58%-66%) or after 12 cycles of attempt (70% [95% CI, 54%-80%] vs 76% [95% CI, 72%-80%], respectively). Inhibin B levels (n?=?737) were not associated with the probability of conceiving in a given cycle (hazard ratio per 1-pg/mL increase, 0.999; 95% CI, 0.997-1.001). Conclusions and Relevance:Among women aged 30 to 44 years without a history of infertility who had been trying to conceive for 3 months or less, biomarkers indicating diminished ovarian reserve compared with normal ovarian reserve were not associated with reduced fertility. These findings do not support the use of urinary or blood follicle-stimulating hormone tests or antimüllerian hormone levels to assess natural fertility for women with these characteristics.

Project description:ImportanceMaternal hypothyroidism and hyperthyroidism are risk factors for preterm birth. Milder thyroid function test abnormalities and thyroid autoimmunity are more prevalent, but it remains controversial if these are associated with preterm birth.ObjectiveTo study if maternal thyroid function test abnormalities and thyroid autoimmunity are risk factors for preterm birth.Data sources and study selectionStudies were identified through a search of the Ovid MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar databases from inception to March 18, 2018, and by publishing open invitations in relevant journals. Data sets from published and unpublished prospective cohort studies with data on thyroid function tests (thyrotropin [often referred to as thyroid-stimulating hormone or TSH] and free thyroxine [FT4] concentrations) or thyroid peroxidase (TPO) antibody measurements and gestational age at birth were screened for eligibility by 2 independent reviewers. Studies in which participants received treatment based on abnormal thyroid function tests were excluded.Data extraction and synthesisThe primary authors provided individual participant data that were analyzed using mixed-effects models.Main outcomes and measuresThe primary outcome was preterm birth (<37 weeks' gestational age).ResultsFrom 2526 published reports, 35 cohorts were invited to participate. After the addition of 5 unpublished data sets, a total of 19 cohorts were included. The study population included 47 045 pregnant women (mean age, 29 years; median gestational age at blood sampling, 12.9 weeks), of whom 1234 (3.1%) had subclinical hypothyroidism (increased thyrotropin concentration with normal FT4 concentration), 904 (2.2%) had isolated hypothyroxinemia (decreased FT4 concentration with normal thyrotropin concentration), and 3043 (7.5%) were TPO antibody positive; 2357 (5.0%) had a preterm birth. The risk of preterm birth was higher for women with subclinical hypothyroidism than euthyroid women (6.1% vs 5.0%, respectively; absolute risk difference, 1.4% [95% CI, 0%-3.2%]; odds ratio [OR], 1.29 [95% CI, 1.01-1.64]). Among women with isolated hypothyroxinemia, the risk of preterm birth was 7.1% vs 5.0% in euthyroid women (absolute risk difference, 2.3% [95% CI, 0.6%-4.5%]; OR, 1.46 [95% CI, 1.12-1.90]). In continuous analyses, each 1-SD higher maternal thyrotropin concentration was associated with a higher risk of preterm birth (absolute risk difference, 0.2% [95% CI, 0%-0.4%] per 1 SD; OR, 1.04 [95% CI, 1.00-1.09] per 1 SD). Thyroid peroxidase antibody-positive women had a higher risk of preterm birth vs TPO antibody-negative women (6.6% vs 4.9%, respectively; absolute risk difference, 1.6% [95% CI, 0.7%-2.8%]; OR, 1.33 [95% CI, 1.15-1.56]).Conclusions and relevanceAmong pregnant women without overt thyroid disease, subclinical hypothyroidism, isolated hypothyroxinemia, and TPO antibody positivity were significantly associated with higher risk of preterm birth. These results provide insights toward optimizing clinical decision-making strategies that should consider the potential harms and benefits of screening programs and levothyroxine treatment during pregnancy.

Dataset Information

Association of Thyroid Function and Autoimmunity with Ovarian Reserve in Women Seeking Infertility Care.

Publications

Association of Thyroid Function and Autoimmunity with Ovarian Reserve in Women Seeking Infertility Care.

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