Hypothyroidism and Infertility

Hypothyroidism &
Infertility
Dr Amandeep K Anand,
Consultant Gynecologist
J&K Health Services
MD, FICOG
Overview
Introduction
Problem statement
Hypothyroidism & ovulatory dysfunction
ART and Hypothyroidism
Subclinical hypothyroidism and infertility
AITD and pregnancy outcome
Summary
Introduction
Normal fertility involves spatio-temporally
regulated endocrine cellular and molecular
events.
Before ovulation, oocyte maturation demands a
favourable endocrine environment including
normal levels of thyroid hormones.
A close interplay between thyroid hormones and
normal steroid action and secretion exists for
normal ovarian function and thus fertility.
Problem Statement
Infertility is defined as the inability to conceive after 1
year of regular intercourse without contraception.
The prevalence of infertility is estimated to range
between 10% and 15% and has remained stable over
recent decades.
The causes of infertility subdivided into :
Female infertility (35%),

Male infertility (30%),
Combination of both (20%),
Unexplained or idiopathic infertility (15%).
Poppe, K., Velkeniers, B. and Glinoer, D. (2007), Thyroid disease and female reproduction. Clinical Endocrinology, 66:
309321.
Problem Statement (contd.)

Prevalence of hypothyroidism in women in the
reproduction age group (20-40 yrs) varies
between 2-4%
Commonest cause: Autoimmune thyroid disease
(AITD) in this age group.
In infertile women, the prevalence of AITD is
significantly higher as compared to parous age
matched women especially in case of
endometriosis and PCOS.
Problem Statement (contd.)

TH screening & Rx is strongly recommended as
part of workup of infertility because:
Increased prevalence of AITD in infertile women.
Beneficial effects of L-Thyroxine treatment in hypothyroidism on
menstrual cycle, LH pulsatility and hyperprolactinemia.
It has been recommended that in the presence of raised TSH
along with raised PRL levels, the treatment should be first to
correct the hypothyroidism before evaluating further causes of
hyperprolactinemia.
Prevention of evolution to overt Thyroid dysfunction after COH
in women with AITD.

Severe hypothyroidism is commonly associated with
ovulatory dysfunction due to numerous interactions of
TH with the female reproductive system.
Both hyperprolactinaemia, due to increased TRH
production, and altered GnRH pulsatile secretion,
leading to a delay in LH response and inadequate corpus
luteum, have been reported.
Thyroid responsivity by the ovaries could be explained
by the presence of TH receptors in human oocytes.

Advisable to measure thyroid function and detect AITD in
infertile women before ART
Follow-up these parameters after COH and during pregnancy
when AITD was initially present.
Women with thyroid dysfunction at early gestation stages should
be treated with thyroxine to avoid pregnancy complications.
Whether TH should be given prior to or during pregnancy in
euthyroid women with AITD remains controversial.
There is a lack of well-designed randomized clinical trials to
elucidate this controversy
309321.

TH also synergize with the FSH-mediated LH/hCG
receptor to exert direct stimulatory effects on granulosa
cell function (progesterone production).
Hypothyroidism may impact fertility by:
Altering the peripheral metabolism of estrogen and by decreasing
SHBG production.
An abnormal feedback at the pituitary level.
Independently of hormonal changes, hypothyroidism can also
lead to menorrhagia by altered production of coagulation factors
(decreased levels of factors VII, VIII, IX and XI).
Studies on the incidence of infertility in hypothyroid

patients are scarce.
10
Advantages of Hypothyroidism Rx
In the case of hypothyroidism, thyroxine should be
administered
Euthyroidism
Normalizes PRL and LH levels
Reverses menstrual abnormalities
Increases spontaneous fertility.
Given the potential implications of hypothyroidism on

ovulatory function, screening for thyroid insufficiency is
certainly indicated in women with ovulatory dysfunction.
11
ART & Hypothyroidism

When ovulation induction and IUI fail to treat infertility,
ART is the ultimate tool.
The period before and immediately after the ART procedure
may significantly alter thyroid hormone distribution and
kinetics due to marked changes in estradiol levels.
Medical preparation for ART involves COH.
At the end of this COH procedure, supraphysiological
estradiol levels are obtained, comparable to values in the
second trimester of pregnancy (40006000 ng/ml).
It is clear that ART, even in the presence of a normal thyroid,
involves a rapid increase in plasma estradiol concentrations
and therefore induces an additional strain on the
hypothalamicpituitarythyroid axis.
12
ART & Hypothyroidism (contd.)

Higher serum TSH levels: A significant predictor of
failure of IVF
Hypothyroidism: Production of oocytes which failed
to fertilize
Low maternal FT4 levels> disruption of local
availability of T3 in fetal tissues > interference with
normal neuro and placental development
However, these effects are more pronounced in
women with AITD.
In women without AITD, changes in thyroid
hormones after COH do not influence the outcome of
ART.
13
Subclinical hypothyroidism (SCH) and infertility

Subclinical hypothyroidism (SCH) has recently been challenged as
data have indicated that physiological free T4 (FT4) variations are
narrower in one individual than those observed within the
reference range of a population.
An abnormally low FT4 value for patients who present a mildly
increased serum TSH.
Some authors have proposed restricting the upper normality limit

of serum TSH to 25 mU/l.
No agreement among endocrinologists about the most appropriate
upper limit of normality for serum TSH.
Overall, the studies investigating the association between SCH and
infertility were poorly controlled.
Considering the largest cohorts published, the prevalence of SCH in
infertile women ranged from 1% to 4% and most cases with SCH
were associated with ovulatory dysfunction.
309321.
14

The particular association between AITD and altered
pregnancy outcome was first described by Stagnaro-Green et
al.
AITD (without overt thyroid dysfunction) was significantly
associated with a three- to fivefold increase in overall
miscarriage rate.
The presence of AITD seems to be an independent risk factor
for miscarriage in spontaneous pregnant women, even in the
absence of anti-nuclear or anti-cardiolipin antibodies.
309321.

15
Miscarriage is not directly related to the presence of

AITD
AITD represents a marker of a more generalized
autoimmune imbalance responsible for a greater
rejection rate of the foetal graft.
Supported by the observation that women with
recurrent abortions have an increased number of
CD5/20-positive B cells compared to women with no
or only one abortion.
An abnormal T-cell function has also been reported.
Stagnaro-Green, A. & Glinoer, D. (2004) Thyroid autoimmunity and the risk of miscarriage. Best Practice and
Research. Clinical Endocrinology and Metabolism, 18, 167181.

16
The second hypothesis postulates that, despite euthyroidism

during pregnancy, the presence of AITD could be associated
with a subtle deficiency in thyroid hormones or an inadequate
response of the thyroid to adapt to the changes associated
with increased estrogen levels, such as ovarian
hyperstimulation or pregnancy.
In women with threatened abortion, significantly lower
thyroid hormone levels were observed in those who
subsequently did have a miscarriage compared with those who
delivered successfully.
Maruo, T., Katayama, K., Matuso, H., Anwar, M. & Mochizuki, M. (1992) The role of maternal thyroid hormones in
maintaining early pregnancy in threatened abortion. Acta Endocrinologica, 127, 118122.
Algorithm for the screening of thyroid dysfunction and autoimmunity in infertile women.
17
Poppe, K. & Velkeniers, B. (2004) Female infertility and the thyroid. Best Practice and Research. Clinical
Endocrinology and Metabolism, 18, 153165.
18
Summary
Thyroid hormones play an important role in normal
reproductive function
Thyroid dysfunction can lead to (reversible) menstrual
irregularities and infertility.
Women with infertility should be screened for thyroid
dysfunction, particularly because endometriosis and the
PCOS are more prone to be associated with AITD, which is
the most common cause of thyroid dysfunction.
When thyroid dysfunction is detected, l-thyroxine treatment
is able to restore normal fertility.
Women with AITD carry an increased risk for miscarriage
after ART.
Controlled ovarian hyperstimulation leads to an additional
strain on the thyroid, especially in women with AITD.
19
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How does hypothyroidism affect fertility?

How does hypothyroidism affect fertility?

What are the effects of autoimmune thyroid disease on pregnancy outcomes?

What are the effects of autoimmune thyroid disease on pregnancy outcomes?

Hypothyroidism &

Female infertility (35%),

Problem Statement (contd.)

Problem Statement (contd.)

Hypothyroidism & ovulatory dysfunction

Hypothyroidism & ovulatory dysfunction

Hypothyroidism & ovulatory dysfunction

Studies on the incidence of infertility in hypothyroid

Given the potential implications of hypothyroidism on

ART & Hypothyroidism

ART & Hypothyroidism (contd.)

Subclinical hypothyroidism (SCH) and infertility

Some authors have proposed restricting the upper normality limit

AITD and pregnancy outcome

AITD and pregnancy outcome

Miscarriage is not directly related to the presence of

AITD and pregnancy outcome

The second hypothesis postulates that, despite euthyroidism

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