Impact of Different Ovarian Stimulation Protocols on Thyroid Hormone Levels: A Prospective Cohort Study
Dampak dari Protokol Stimulasi Ovarium yang Berbeda terhadap Kadar Hormon Tiroid: Sebuah Studi Kohort Prospektif
Keywords:
Ovarian Stimulation, Clomiphene Citrate, Pergonal, Thyroid hormones, InfertilityAbstract
Background: Ovarian stimulation is pivotal in assisted reproductive technologies, yet its systemic hormonal effects—particularly on thyroid function—remain underexplored. Specific Background: Estrogen-induced increases in thyroxine-binding globulin and the structural mimicry between hCG and TSH suggest a complex thyroid-ovarian interaction. Knowledge Gap: Prior studies yield conflicting evidence on thyroid hormone alterations during stimulation, with limited attention to regimen-specific effects and longitudinal dynamics in thyroid-naïve women. Aim: This study investigates the temporal impact of distinct ovarian stimulation protocols—Clomid, Pergonal, and their combination—on thyroid hormone levels in euthyroid infertile women. Results: A significant elevation in TSH and reduction in T3/T4 was observed as early as month one in the combination group, month two in the Pergonal group, and month three in the Clomid group (P<0.05). Novelty: This study delineates protocol- and time-dependent thyroid disturbances, offering mechanistic clarity on drug-specific endocrine crosstalk. Implications: Findings support tailored thyroid monitoring during ART and propose a stratified approach based on stimulation regimen and exposure duration to prevent potential subclinical hypothyroidism and optimize fertility outcomes.
Highlights:
-
Combination therapy (Clomid + Pergonal) caused the earliest and most significant thyroid disruption-elevated TSH and decreased T3/T4 from Month 1.
-
Thyroid dysfunction varied by stimulation protocol: Clomid-only showed delayed effects (Month 3), while Pergonal-only effects began in Month 2.
-
Clinical recommendation: Thyroid monitoring is crucial during ovarian stimulation, especially with combination regimens.
Keywords: Ovarian Stimulation, Clomiphene Citrate, Pergonal, Thyroid hormones, Infertility
References
[1] A. Pacchiarotti, H. Selman, C. Valeri, S. Napoletano, M. Sbracia, G. Antonini, G. Biagiotti, and A. Pacchiarotti, "Ovarian Stimulation Protocol in IVF: An Up-To-Date Review of the Literature," Current Pharmaceutical Biotechnology, vol. 17, no. 4, pp. 303–315, Mar. 2016.
[2] A. F. Muller, A. Verhoeff, M. J. Mantel, F. H. De Jong, and A. Berghout, "Decrease of Free Thyroxine Levels After Controlled Ovarian Hyperstimulation," The Journal of Clinical Endocrinology & Metabolism, vol. 85, no. 2, pp. 545–548, Feb. 2000.
[3] K. Poppe, D. Glinoer, H. Tournaye, J. Schiettecatte, P. Devroey, A. Van Steirteghem, P. Haentjens, and B. Velkeniers, "Impact of Ovarian Hyperstimulation on Thyroid Function in Women With and Without Thyroid Autoimmunity," The Journal of Clinical Endocrinology & Metabolism, vol. 89, no. 8, pp. 3808–3812, Aug. 2004.
[4] S. Mariotti and P. Beck-Peccoz, "Physiology of the Hypothalamic-Pituitary-Thyroid Axis," in Endotext [Online]. South Dartmouth (MA): MDText.com, Inc., Apr. 20, 2021. [Online]. Available: https://www.ncbi.nlm.nih.gov/books/NBK285570/
[5] J. Zhang, Y. Wang, X. Mao, Q. Chen, Q. Hong, R. Cai, S. Zhang, and Y. Kuang, "Dual Trigger of Final Oocyte Maturation in Poor Ovarian Responders Undergoing IVF/ICSI Cycles," Reproductive Biomedicine Online, vol. 35, no. 6, pp. 701–707, Dec. 2017.
[6] Y. J. Du, X. Xin, N. Cui, L. Jiang, A. M. Yang, G. M. Hao, and B. L. Gao, "Effects of Controlled Ovarian Stimulation on Thyroid Stimulating Hormone in Infertile Women," European Journal of Obstetrics & Gynecology and Reproductive Biology, vol. 234, pp. 207–212, Mar. 2019.
[7] A. Reh, S. Chaudhry, F. Mendelsohn, S. Im, L. Rolnitzky, A. Amarosa, M. Levitz, S. Srinivasa, L. Krey, A. S. Berkeley, and J. A. Grifo, "Effect of Autoimmune Thyroid Disease in Older Euthyroid Infertile Women During the First 35 Days of an IVF Cycle," Fertility and Sterility, vol. 95, no. 3, pp. 1178–1181, Mar. 2011.
[8] A. Busnelli, E. Somigliana, S. Ferrari, F. Filippi, G. Vannucchi, L. Fugazzola, and L. Fedele, "The Long-Term Impact of Controlled Ovarian Hyperstimulation on Thyroid Function," Endocrine Practice, vol. 22, no. 4, pp. 389–395, Apr. 2016.
[9] C. R. Gracia, C. B. Morse, G. Chan, S. Schilling, M. Prewitt, M. D. Sammel, and S. J. Mandel, "Thyroid Function During Controlled Ovarian Hyperstimulation as Part of In Vitro Fertilization," Fertility and Sterility, vol. 97, no. 3, pp. 585–591, Mar. 2012.
[10] W. M. Henawi and M. O. Aljahdali, "Effect of Clomiphene Citrate on Thyroid Hormones T3, T4 and TSH Levels in Mice Offspring," Endocrinology & Diabetes Research, vol. 4, pp. 1–4, 2018.
[11] M. A. Krassas, G. Poppe, and K. Glinoer, "Thyroid Function and Human Reproductive Health," Endocrine Reviews, vol. 31, no. 5, pp. 702–755, Oct. 2010.
[12] T. A. van den Boogaard, M. E. Vissenberg, E. J. Land, E. van Wely, A. M. van der Post, F. J. Goddijn, and J. B. Bisschop, "Significance of (Sub)clinical Thyroid Dysfunction and Thyroid Autoimmunity Before Conception and in Early Pregnancy: A Systematic Review," Human Reproduction Update, vol. 17, no. 5, pp. 605–619, Sep.–Oct. 2011.
[13] P. Negro, E. Formoso, D. Mangieri, G. Pezzarossa, G. Dazzi, and A. Hassan, "Levothyroxine Treatment in Euthyroid Pregnant Women With Autoimmune Thyroid Disease: Effects on Obstetrical Complications," The Journal of Clinical Endocrinology & Metabolism, vol. 91, no. 7, pp. 2587–2591, Jul. 2006.
[14] N. Andersen, M. Laurberg, C. Wu, and J. J. Andersen, "Thyroid Function Changes in Early Pregnancy and Development of Subclinical Hypothyroidism: A Longitudinal Study," The Journal of Clinical Endocrinology & Metabolism, vol. 98, no. 7, pp. 2655–2664, Jul. 2013.
[15] L. E. Alexander, D. Pearce, G. Brent, E. Brown, A. Chen, J. Dosiou, D. Grobman, J. Laurberg, and E. Lazarus, "2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum," Thyroid, vol. 27, no. 3, pp. 315–389, Mar. 2017.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Buthainah Al-Azzawi

This work is licensed under a Creative Commons Attribution 4.0 International License.