I am sharing current thoughts on how the thyroid and Hashimoto’s thyroiditis can affect fertility and my take on this. You can just read from the key points to the references, and/ or you can read deeper into my blog after the references for more of a sense of the current research.
Key points and Findings:
1) Women With high TSH (subclinical hypothyroid or hypothyroid) and/or Hashimoto’s thyroiditis (+ TPO-Abs) can have decreased fertility. Women who have high BMI or are of Asian origin and present with subfertility are more likely to have thyroid dysfunction.
2) Patients with Hashimoto’s have higher risk of infertility and miscarriages. Reasons for this include: 1) They can have a lower ovarian follicle reserve and this may contribute to infertility and lower quality embryos if doing IVF. 2) Cells in the thyroid glands of women with Hashimoto’s have had inflammatory damage, and thus they may not respond appropriately to the stimulating message from the pregnancy hormone HCG to increase the production of more thyroid hormone when its needed as pregnancy progresses. 3) TPO antibodies may affect directly the ovary by altering function of granulose cells at ovarian follicles. 4) Women who are > age 35 or have Hashimoto’s thyroiditis are also more vulnerable to having further decreases of their ovarian reserve after they receive radioactive iodine treatment for thyroid cancer.
Current recommendations: Endocrine Society and American Thyroid Association suggestions on how to treat thyroid dysfunction depends on thyroid levels, and the clinical history of infertility and/or past miscarriage(s). Most would treat women with Hashimoto’s if TSH is > 4-10 mIU/L. Most would not treat women without Hashimoto’s if TSH is in the normal range of 2.5-4.0 mIU/L unless is part of infertility treatment or IVF. In this group there is clear benefit in decrease in miscarriage rate. Most would not treat women with Hashimoto’s or TPO-Ab, who have TSH < 4.0 (upper pregnancy range). This is because two large prospective studies have not shown benefit or alterations in rate of miscarriages or live births in these women, and a retrospective study has shown that while there may be a lower miscarriage rate there is also higher risk of pre-term labor, gestational diabetes, and preeclamsia.
To be clear most studies are not perfect, so I would hope that most would treat women with Hashimoto’s if TSH >2.5 mIU/L and have a history of subfertility, prior miscarriages, age >35, prior I131 treatment, or thyroidectomy being aware of benefits and risks. This is because In 2021 we do not know apriori how to identify which women with “normal“ thyroid tests and positive TPO-AB whose thyroids are not responding to hCG appropriately, have follicle dysfunction, and who could benefit from thyroid treatment prior to manifesting infertility and miscarriages.
There are no current specific recommendation in conventional medicine on how to address or reverse the autoimmune problem even though this likely a large part of the solution.
My integrative endocrinology take on all this: While in the past we saw thyroid antibodies as innocent bystanders this view can no longer be maintained. We endocrinologists, as a group, have tended to treat Hashimoto’s thyroiditis with observation and added thyroid hormone when the thyroid hormone test become abnormal. We have not treated it as an inflammatory, toxic and potentially reversible condition. My current thoughts, based on the research, is that autoimmunity needs to be stopped and reversed when possible. Autoimmunity is often a combination of variable degree of genetic tendency, whereas its manifestation is largely affected by environmental factors such as viral infections, big hormone shifts like pregnancy, treatments that damage our self-knowing immune mechanism, our microbiome, and others. I think it is about time that we actively pursue and address environmental factors that initiate and fuel autoimmunity, perhaps we need to be more proactive with antioxidants to limit inflammatory damage to the gland In addition, we need to be very mindful of evaluating and treating women with TPO-Ab’s to promote healthy pregnancies and births. Women should assess their fertility potential as part of the process of their treatment for thyroid cancer if it is likely to involve radioactive iodine.
References:
- Dosiou Chrysoula. Thyroid and Fertility: recount advances. Thyroid 30(4):479-486, 2020.
- Dhillon-Smith RK et al. The prevalence of thyroid dysfunction and autoimmunity in women with a history of miscarriage and subfertility. J of Clinical Endocrinology and Metabolism., 105(8):2667-2677, 2020.
Most of this report below is based on reference 1, a review by Dr. Chrysoula Dosiou of recent literature that has been regarding fertility and thyroid. There have been some enlightening new discoveries that actually alter ideas on how to treat patients. I specifically want to share this information with my patients who either have Hashimoto’s thyroiditis and/or have received radioactive iodine for thyroid cancer treatment.
For the purpose of this discussion the review defines fertility as the ability to produce a live baby. This requires a healthy conception and no miscarriages.
First let’s start with the impact of being hypothyroid and fertility. The data shows that treatment with levothyroxine of women that have a TSH greater than 4 miU/L improves the outcome of pregnancies by lowering rates of miscarriages however treatment might be a little bit of an increase in preeclampsia.
For women who have Hashimoto’s thyroiditis and positive TPO antibodies the presence of TPO-AB autoimmunity is indeed associated with a higher miscarriage rate. In addition to a higher miscarriage rate autoimmunity with TPO antibodies is also associated with lower ovarian (follicles) reserve. For example in women with history of unexplained infertility up to 30 % have TPO positive antibodies. The way that they measure ovarian reserve is to measure anti-müllerian hormone. While anti-mullerian hormone levels decrease over time as we get older. However patients with Hashimoto’s thyroiditis seem to have a lower ovarian reserve relative to similar aged control patients.
Another finding is that women that have thyroid autoimmunity also have a decrease in the percentage of good quality embryos during IVF and they also have a Higher percentage of fair quality or poor quality embryos in comparison to women who do not have Hashimoto’s thyroiditis. For these reasons we enhance fertility and decrease miscarriage rates by giving thyroid hormone replacement to women with history of infertility and TPO AB with TSH greater than 2.5 miU/L
While we now have the knowledge that Hashimoto’s is indeed associated with a higher risk of infertility and lower ovarian reserve in a subset of women, a controversial issue in the Endocrine world has been whether or not to treat with thyroid hormone women with TPO antibodies who have normal thyroid tests (TSH less than 4.5 MIU/L) to alter rate of miscarriage or live births. Two recent large placebo controlled trials have not shown a benefit of treating women with Hashimoto’s and TPO positive antibodies because it does not improve the rates of miscarriage or live births.
To reconcile differences of how it is that thyroid replacement may help some women but not others scientist have looked at how thyroid hormones affect the physiology of pregnancy. Thyroid hormones are extremely important through the whole process of pregnancy in addition it has been found the TPO enzyme is actually present in the granulosa cells of the ovary what this means is that possibly women that have antibodies to the TPO enzyme may be attacking their ovaries by attacking directly that TPO enzyme and this may have an impact early in the course of the pregnancy. Later on, after pregnancy ensues, levels of the hormone human chorionic hormone, or HCG, increase and this normally stimulates an increase in the synthesis and release of more thyroid hormone by the thyroid gland to ascertain that mama, the baby have enough thyroid hormone, and that the whole apparatus of the uterus is working correctly to deliver a life birth. Women who have Hashimoto’s thyroiditis appear to have a problem responding to the hCG stimulus to their thyroid to produce extra thyroid hormone. As a result there may be less thyroid hormone than is necessary, this may lead to miscarriage or early pregnancy loss. In 2021 We do not know apriori how to identify which women with “normal thyroid tests and positive TPO-AB are not responding to hCG appropriately, and who could benefit from thyroid treatment.
Effects of thyroid cancer treatment on fertility to be aware of:
For women who do not have Hashimoto’s thyroiditis but have received radioactive iodine for treatment of thyroid cancer, in general the long-term outcomes are very similar to women who have not received radioactive iodine – there is no increase in stillbirths. However a history of thyroid cancer is associated with more obstetrical complications such as postpartum hemorrhage or a higher risk of multiple gestation’s at the time of pregnancy.
Radioactive iodine treatment can decrease the ovarian reserve whether or not there are TPO-Abs at three months and 12 months after the radioactive iodine treatment, this is particularly impactful for women who are older than 35 years of age in comparison to younger women. Women who have TPO positive antibodies are the most vulnerable to the impact of receiving radioactive iodine for their thyroid cancer. For them their ovarian reserve is markedly decreased and this is particularly amplified if the woman is older.
These effects on ovarian follicle reserve are not seen with the smaller doses < 13 millicuries of radioactive iodine used for the treatment of Graves’ disease.
Some new information on men who have received radioactive iodine for thyroid cancer shows that after radioactive iodine the sperm counts drop at three months but recover at 13 months however the new finding is that there are a number of chromosomal sperm abnormalities that may remain.
Nuclear medicine guidelines recommended that men and women wait 6 months after radioactive iodine treatment to attempt conception