Thyroid Axis Dysregulation During <i>In Vitro</i> Fertilization in Hypothyroid-Treated Patients

Busnelli, Andrea; Somigliana, Edgardo; Benaglia, Laura; Sarais, Veronica; Ragni, G.; Fedele, Luigi

doi:10.1089/thy.2014.0088

Cited by 37 publications

(27 citation statements)

References 21 publications

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“…In fact, in a recent study, Lv et al (23) observed, during the first trimester, a higher level of estrogens in pregnancies achieved through IVF than in natural pregnancies. Noteworthy, there is consistent evidence showing a TSH rise during IVF in euthyroid women, and this increase appears to be more evident in women with treated hypothyroidism (10,14). This modification mainly occurs during gonadotropin treatment (i.e., prior to hCG administration).…”

Section: Clinical Study a Busnelli And Others Levothyroxine Adjustmenmentioning

confidence: 93%

“…The magnitude of the TSH increase seems to be particularly pronounced among hypothyroid women. In a previous study, we observed that during COH, serum TSH exceeded the recommend threshold of 2.5 mIU/l in up to two-thirds of adequately treated hypothyroid patients, and this increase tends to persist after the end of COH (14). Considering such a considerable impairment of the thyroid function during COH, one could speculate that hypothyroid women who become pregnant after IVF may require, especially in early gestation, a different L-T 4 dose adjustment.…”

Section: Introductionmentioning

confidence: 89%

“…In our series, we also observed a trend for higher serum estrogens at the time of hCG administration in women requiring early adjustment of L-T 4 . On the other hand, data from studies in women undergoing IVF failed to show a pivotal role of estrogens in IVF-related serum TSH modifications (10,11,14). Overall, even if estrogens may play a role, it is likely that other, yet obscure mechanisms are also involved.…”

Section: Clinical Study a Busnelli And Others Levothyroxine Adjustmenmentioning

confidence: 99%

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Levothyroxine dose adjustment in hypothyroid women achieving pregnancy through IVF

Busnelli

Vannucchi

Paffoni

et al. 2015

European Journal of Endocrinology

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Objective: About one out of two women with primary hypothyroidism has to increase the dosage of exogenous levothyroxine (L-T 4 ) during pregnancy. Considering the detrimental impact of IVF on thyroid function, it has been claimed but not demonstrated that L-T 4 dose adjustment may be more significant in hypothyroid women who become pregnant after IVF. Design: Retrospective cohort study. Methods: Hypothyroid-treated women who achieved a live birth through IVF were reviewed. Women could be included if thyroid function was well compensated with L-T 4 before the IVF cycle (i.e., serum TSH !2.5 mIU/l and serum free T 4 within the normal range). Serum TSH and dose adjustment were evaluated at five time points during pregnancy. The trimester ranges for serum TSH considered as reference to adjust L-T 4 therapy were 0.1-2.5 mIU/l for the first trimester, 0.2-3.0 mIU/l for the second trimester, and 0.3-3.0 mIU/l for the third trimester. Results: Thirty-eight women were selected. During the whole pregnancy 32 women (84%; 95% CI: 72-96%) required an increase in the dose of L-T 4 . In most cases (nZ28), this occured within the first 5-7 weeks of gestation (74%, 95% CI: 58-85%). At 5-7 weeks of gestation, the median (interquartile range) increase of L-T 4 dose for the whole cohort was 26% (0-50%). At 30-32 weeks, it was 33% (14-68%). In order to identify predictive factors of dose adjustment, we compared women who did (nZ28) and did not (nZ10) adjust L-T 4 dosage at 5-7 weeks' gestation. Significant differences emerged for thyroid autoimmunity prevalence and for the distribution of hypothyroidism aetiology. Conclusions: The vast majority of hypothyroid-treated women who achieve pregnancy through IVF need an increase in the L-T 4 dose during gestation. This requirement tends to occur very early during gestation.

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Section: Clinical Study a Busnelli And Others Levothyroxine Adjustmenmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 89%

Section: Clinical Study a Busnelli And Others Levothyroxine Adjustmenmentioning

confidence: 99%

See 1 more Smart Citation

Levothyroxine dose adjustment in hypothyroid women achieving pregnancy through IVF

Busnelli

Vannucchi

Paffoni

et al. 2015

European Journal of Endocrinology

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“…During the procedure, a TSH elevation is observed in hypothyroid patients on LT4, particularly 1 week after hCG administration, and 84% of women on replacement treatment and a prefertilization TSH < 2.5 mIU/L require an LT4 increase [36,37]. In such cases it seems reasonable to obtain a TSH concentration < 2.5 mIU/L through this approach, and possibly < 1.5 mIU/L, and to start treatment with LT4 in women positive for thyroid antibodies with a prestimulation TSH > 2.5 mIU/L [38].…”

Section: Discussionmentioning

confidence: 99%

A 2018 Italian and Romanian Survey on Subclinical Hypothyroidism in Pregnancy

et al. 2018

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Objectives: Pregnancy induces changes in thyroid function, and thyroid dysfunction during gestation is associated with adverse outcomes. We examined the management of subclinical hypothyroidism and chronic autoimmune thyroiditis in pregnancy among Italian and Romanian endocrinologists. Methods: Members of the Associazione Medici Endocrinologi (AME) and Romanian Society of Endocrinology (RSE) were invited to participate in a web-based survey investigating the topic. Results: A total of 902 individuals participated in the survey, 759 of whom completed all sections. Among the respondents, 85.1% were aware of the 2017 American Thyroid Association guidelines about thyroid disease and pregnancy, and 82.9% declared that thyroid-stimulating hormone (TSH) screening at the beginning of pregnancy should be warranted. In a patient negative for peroxidase antibodies, 53.6% considered 2.5 mIU/L and 26.2% considered 4.0 mIU/L as the upper normal limit of TSH, and 50% would treat a patient with TSH 3.5 mIU/L with levothyroxine. About 20% did not suggest iodine supplementation. Isolated hypothyroxinemia detected in the first trimester would be treated by 40.8%. In patients undergoing ovarian stimulation, a TSH < 2.5 mIU/L would be targeted by 70%. Conclusions: Respondents globally appeared well informed about the management of thyroid autoimmunity and subclinical hypothyroidism in pregnancy. A more aggressive attitude in implementing iodine supplementation would be desirable. Most endocrinologists were convinced about an evident association between mild thyroid impairment and adverse outcomes in pregnancy, thus using a TSH value of 2.5 mIU/L as the threshold for diagnosing hypothyroidism and starting levothyroxine in pregnant women.

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“…If serum progesterone was unremarkable, the women initiated ovarian hyper-stimulation the same day. Cycle monitoring, oocytes retrieval and embryo transfer modalities were performed in a standardized manner as described in details elsewhere [10] . Cancelled cycles were excluded because the detrimental impact of elevated basal progesterone on embryo implantation could not be assessed.…”

Section: Methodsmentioning

confidence: 99%

Clinical Value of Basal Serum Progesterone Prior to Initiate Ovarian Hyper-Stimulation with GnRH Antagonists: A Retrospective Cohort Study

Faulisi

Reschini

Borroni

et al. 2016

Gynecol Obstet Invest

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Background: The routine assessment of day 3 serum progesterone prior to initiation of ovarian hyper-stimulation with the use of GnRH antagonists is under debate. In this study, we evaluated the clinical utility of this policy. Methods: Retrospective cohort study of women undergoing in vitro fertilization (IVF) with the use of GnRH antagonists aimed at determining the frequency of cases with progesterone levels exceeding the recommended threshold of 1,660 pg/ml and at evaluating whether this assessment may be predictive of pregnancy. Results: Serum progesterone exceeded the recommended threshold in one case (0.3%, 95% CI 0.01-1.5). The median (interquartile range) basal progesterone in women who did (n = 95) and did not (n = 217) become pregnant were 351 (234-476) and 380 (237-531) pg/ml, respectively (p = 0.28). The 90th percentile of the basal progesterone distribution in women who became pregnant was 660 pg/ml. Cases with serum progesterone exceeding this threshold in successful and unsuccessful cycles were 10 (10%) and 30 (14%), respectively (p = 0.47). The capacity of basal progesterone to predict pregnancy was evaluated using receiver operating characteristic curve (area under the curve = 0.54, 95% CI 0.47-0.61, p = 0.28). No graphically evident threshold emerged. Conclusion: Routine day 3 serum progesterone assessment in IVF cycles with the use of GnRH antagonists is not justified. Further evidence is warranted prior to claiming its systematic use.

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Thyroid Axis Dysregulation During In Vitro Fertilization in Hypothyroid-Treated Patients

Cited by 37 publications

References 21 publications

Levothyroxine dose adjustment in hypothyroid women achieving pregnancy through IVF

Levothyroxine dose adjustment in hypothyroid women achieving pregnancy through IVF

A 2018 Italian and Romanian Survey on Subclinical Hypothyroidism in Pregnancy

Clinical Value of Basal Serum Progesterone Prior to Initiate Ovarian Hyper-Stimulation with GnRH Antagonists: A Retrospective Cohort Study

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