Thyroid disorders can significantly impact fertility in both females and males. Hypothyroidism is associated with menstrual irregularities and anovulatory cycles in females which can lead to infertility. It may also cause delayed puberty. In males, untreated hypothyroidism from a young age can damage testicular development. The document discusses the prevalence of thyroid disorders like hypothyroidism and thyroid autoimmunity in infertile populations. It recommends evaluating thyroid levels through TSH tests for all women with infertility and treating any thyroid abnormalities. Treatment of hypothyroidism is important to improve fertility outcomes and IVF success rates.

1. Thyroid disorders and
Infertility
Dr. Jyoti Agarwal
Dr Sharda Jain

2. Over 350 ppts are available on
slideshare.net for use of public/Doctors
www.slideshare.net / Lifecarecentre

3. Thyroid and Infertilty
Endocrine & immunological factor play a
significant role in reproduction
Assisted reproductive technology has led to
tremendous change in perspective of
infertility
Endocrine Factors
Have To Be Taken Care Of First

4. 4
•Increased prolactin Level
•Delay in onset of puberty with
anovulatory cycle
•Recurrent miscarriage
•Amenorrhea, oligomenorrhea,
galactorrhea – due to high
prolactin level
•Incidence of infertility and PCOD
•Increased estrogen
production.
•Defective
spermatogenesis.
•Low sperm count with
•sperm motility defect.
Thyroid and Infertility
FEMALES MALES

5. Thyroid Hormones Act On Nearly
Every Cell In The Body
• Have profound effects on oestrogen and androgen
metabolism , menstrual function and fertility
• May cause delayed onset of puberty , anovulatory
cycles , miscarriages and infertility
Undiagnosed & Untreated
Thyroid Disease Can Adversely Affect Fertility

6. Evaluation of serum
thyroid stimulating
hormone (TSH) is
recommended for all
women seeking care
for infertility
Normal TSH levels is pre-requisite
requirement for fertilization

7. Hypothyroidism
Hyperthyroidism
Thyroid Disorders

8. Thyroid Disorders and
Infertility

9. Hypothyroidism : Types
• Elevated serum TSH and low FT4
• Symptomatic thyroid hormone
deficiency
Overt
hypothyroidism
• Elevated serum TSH and normal
FT4
• Biochemical thyroid hormone
deficiency
Subclinical
hypothyroidism

10. 3 Clinical Scenarios
• Clinical overt hypothyroidism (3.3%)
• Subclinical hypothyroidism (0.7 - 43%)
• Autoimmune thyroid disease (5 – 20 %)
Wide range of prevalence is due to the differences in sensitivity of TSH measurement

11. Impact Of Thyroid Hormones
• One third of subfertile patients have thyroid disease
• Over 50 -70 % of hypothyroid patients have
menstrual irregularities
• 46 % of infertile patients with hypothyroidism have
hyperprolactinaemia
• 10 % have Inadequate corpus luteum & luteal phase
defects

12. Menstrual Disturbances & Hypothyroidism
92%
8%
Euthyroid Controls
(n =214 )
Regular menses
Irregular Menses
77%
23%
Hypothyroid females
(n = 171 )
Regular Menses
Irregular Menses

13. Probably through an impact on the ovaries and
indirectly by SHBG, PRL and GnRH secretion and
coagulation factors
Ovulatory
disturbance
Defects in
hemostasis
Altered peripheral
estrogen
metabolism
Disturbances in GnRH
secretion: an abnormal
pulsatile release of LH
High TRH
Hyper-
prolactinemia
↑ Ovarian Vol
↑ Stromal
DepotsAnovulation

14. These disturbances disappear after T4
administration
LT4 treatment is
recommended for all
infertile women with
overt hypothroidism
who desire pregnancy

15. Infertility & Sub Clinical Hypothyroidism (SCH)
• SCH may remain latent, asymptomatic, or even
undiagnosed for a long – long time
• No RCT’s; few observational studies
• Different SCH definitions used
• Results have been inconsistent

16. Data is insufficient to conclude that SCH is
clearly associated with infertility
Study Main Observation
Poppe et al
Prospective study
(2002)
•No increased rates of SCH among infertile women
•However, there was slight increase in median serum TSH
Abalovich et al
Retrospective study
(2007)
•Higher incidence of SCH in infertile women
compared to fertile controls (13.9% vs 3.9%)
Yoshioka et al
Retrospective study
(2015)
•84.1% of infertile women with SCH (TSH> 3 mIU/L)
conceived after LT4 therapy
•Infertility duration was shortened in SCH women
receiving LT4 (p<0.001)

17. 84.1% of infertile women with SCH (TSH> 3
mIU/L) conceived after LT4 therapy
0.00% 20.00% 40.00% 60.00% 80.00%
6 wk to 3 mths
3 mths to 1 yr
62.50%
37.50%
Women Conceived
Women Conceived
Yoshioka et al Retrospective study (2015)

18. 0 1 2 3
After LT4 trearment
Before LT4 treatment
0.9
2.8
Estimated Duration of Infertility years
Estimated Duration of
Infertility years
Infertility duration was shortened in SCH
women receiving LT4 (p<0.001)
Yoshioka et al Retrospective study (2015)

19. ATA & AACE (2017) Recommends
• Administration of L-thyroxine may be considered in
subclinically hypothyroid, women who are
attempting natural conception
• With a presumption to prevent progression to more
significant hypothyroidism once pregnancy is
achieved
• Further low dose LT4 therapy (25 to 50 microgm )
carries minimal risk

20. Subclinically hypothyroid women undergoing IVF - ICSI
has significantly lower fertilization , lower
implantation & significantly higher pregnancy loss
rates compared to euthyroid women

21. ATA 2017 Recommends
Subclinically hypothyroid women undergoing IVF or
ICSI should be treated with LT4 to improve IVF – ICSI
results
Goal of treatment is to achieve a TSH < 2.5 mU/L

22. Major Outcomes are Not Different
Treated Hypothyroidism vs Controls in IVF-ICSI
Pregnancy rate, implantation rate, and delivery rate
were similar in Cases versus controls
Anti-thyroid antibodies made no difference, Nor did
Overt vs Subclinical Hypothyroidism
Authors Conclude-
IVF-ICSI outcome is not hampered in women with
adequately treated hypothyroidism

23. Thyroid autoimmunity & subfertility
• Numerous studies have been done
• Pooling the results of these studies suggests
• TAI is significantly more prevalent in women with subfertility
than in controls,
• With an overall estimated relative risk of 2.1
Infertility Control Reference
65% 7% Roussev etal.(1996)
81% 10% Kaider et al (1999)
41% 15% Reimand et al.(2001)

24. These antibodies interfere with
Folliculogenesis Spermatogenesis Fertilization Embryogenesis
Pathogenesis of subfertility in women with
TAI is not fully understood
Proposed mechanisms involve
• Abnormal cellular and humoral immunity
• Vitamin D deficiency
• Cross-reactivity of thyroid antibodies with extrathyroid sites

25. AITD has also been found to be
associated with increase incidence of
Premature
ovarian
failure
Endomet
riosis
PCOS

26. Thyroid Antibody Testing Is Not Routinely Done
AACE - one might consider testing anti-TPO
• Repeatedly TSH values > 2.5 mIU/L
• When there is history of miscarriage as well as SCH
TSH (2.5 – 4) mIU/L

27. Treatment strategies
• Intravenous immunoglobulins
• Treatment with L-thyroxine must
• Steroids not be used
• ICSI : to avoid fertilization failure

28. 0
5
10
15
20
25
Frequency(%)
Miscarriage Pre-term delivery
TPOAb+
TPOAb+ LT4
Control
*P<0.05 vs. others
*
*
The only study with L-thyroxine Rx in women with + ab
who became pregnant through ART was published by
Negro et al (2006)
115 pregnant TPO Ab+ women, TSH <3, randomized to LT4 Rx or placebo
Miscarriage rate was reduced to 33% in the treated group,
compared to 52% in controls

29. COH places an Additional Strain
On The Thyroid Gland
• COH involves a rapid increase in plasma estradiol
concentrations
• Hence impact of controlled ovarian hyperstimulation
becomes more severe
• Need to increase the dose of L-thyroxine earlier and to a
greater extent in these women than in natural pregnancies
• In case she is not pregnant following controlled ovarian
stimulation, serum TSH measurements should be repeated
in 2–4 weeks because levels may normalize

30. TSH level ≥ 2.5 mIU/L in an oocyte donor may negatively
impact implantation & clinical pregnancy in recipients

31. Hyperthyroidism & infertility
• Exact impact of hyperthyroidism on fertility remains
ill-defined
• Moreover studies are limited , uncontrolled & small
in size
• Prevalence 0.9% to 5.8%

32. In males , infertility starts in
childhood
• Thyroid failure in the
pre-pubertal period is
associated with
testicular enlargement
and alterations in sexual
hormones
• There is macro
orchidism without
virilization
• Longer the
hypothyroidism
persists, greater is the
degree of damage to
the testes
• If adequately treated
these boys progress
through puberty
normally

33. Impact On Male Infertility
HYPO
Morphology
EDS
HYPER
Motility
SHBG>,>Estrogen

34. Evaluation of serum TSH for all women
seeking care for infertility
Overt
Hypothyroidism
LT4 Therapy
Subclinical
Hyothyroidism
TPO Ab
- ve
LT4 Therapy
TPO Ab
+ve
LT4 Therapy
IVF or ICSI
LT4 Therapy

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