This document summarizes the relationship between thyroid function and female fertility and assisted reproductive technology (ART). It discusses how thyroid disorders like hyperthyroidism and hypothyroidism can impact female fertility through hormonal changes and menstrual disturbances. It also reviews how thyroid autoimmunity without overt thyroid disease is associated with infertility, polycystic ovary syndrome, and recurrent miscarriage. The document recommends screening women for thyroid dysfunction before fertility treatments like ovarian hyperstimulation. Proper treatment with levothyroxine is important to optimize fertility outcomes and prevent complications during ART.

1. Thyroid function:
Female fertility &
ART
Aboubakr Elnashar
Benha university Hospital, EGYPT
elnashar53@hotmail.com
ABOUBAKR ELNASHAR

2. A. Thyroid Function and
female fertility
ABOUBAKR ELNASHAR

3. I. Thyrotoxicosis
a. Hormonal changes.
 Estrogen levels: 2- to 3-fold higher
{SHBG changes or
increase in free estrogen levels}
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4. b. Menstrual disturbances.
 Hypomenorrhea earliest clinical changes
Amenorrhea, Oligomenorrhea, anovulation.
{Biochemical and hormonal abnormalities
nutritional disturbances
emotional upheavals}
Less than early studies: 3 times more than in
control
{better medical care and public awareness,
thyroid disturbances are diagnosed much earlier when the symptoms
are still mild}
Related to: Total T4 levels not to total T3
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5. c. Fertility
Reduced fertility
although most thyrotoxic women remain
ovulatory
(Sturgis et al,1952).
Infertility: 5.8%
(Joshi et al., 1993)
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6. d. R-I131 and reproduction.
Hyperthyroidism:
10 mCi (370 MBq): negligible genetic risk: no
significant detrimental effect on gonads
Cancer:
10–20 times higher:
Avoid conception at least 6 months
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7. II. Hypothyroidism
 Prevalence:
 Increasing with advancing age.
 Most cases
•Chronic autoimmune thyroiditis (3.5/1000
women/y), followed by
•Destructive TT for thyrotoxicosis (0.6/ 1000
women/y).
 Risk factors for progression from SCH to overt
hypothyroidism (OH):
thyroid antibodies
already elevated TSH.
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8. Screening:
/5 yrs beginning at 35y
/2 yrs beginning at 60y, or
any symptoms suggesting hypothyroidism
(Sperof et al, 2010)
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9. a.Hormonal changes.
Gn levels: normal.
However, blunted or delayed LH response to GnRH
PRL
± increased
{hypothalamic TRH increasing both TSH and PRL }:
±Galactorrhea
These disturbances disappear after T4 administration.
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10. b. Menstrual disturbances.
Oligomenorrhea: most common
amenorrhea, polymenorrhea, and menorrhagia
{1. Estrogen breakthrough bleeding secondary to anovulation.
2. Defects in hemostasis factors e.g. decreased
levels of factors VII, VIII, IX, and XI) that occur in hypothyroidism}
Not related to: thyroid antibodies
lower in recent studies: 3 times greater than in the
normal population.
{delayed diagnosis in the earlier studies: more severe clinical picture}
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11. c. Fertility in SCH
Definition
TSH or
TRH test: TSH response above 15 mIU/liter.
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12. SCH and infertility
TSH:
significantly higher compared with the
controls.
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13. AITD
No significant difference between infertile women
and controls.
Screening:
No {low incidence}
(Zollenar et al, 2001)
LT4 treatment
Of SCH: pregnancy success rate of 44%.
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14. SCH and miscarriage
TSH: high
More frequent miscarriages, irrespective of
the presence of AITD.
Screening
in recurrent pregnancy loss.
Am Ass of endocrinology, 2013
Up Todate, 2013
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15. SCH and OD:
OD:
SCH: 6.3%
SCH
precocious ovarian failure: 40%
OD: 15%
(Abalovich et al. 2007).
Screening
In OD
(Lincoln et al.1999; Poppe et al, 2007).
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16. SCH and fertilization failure
Both Gn and T4 necessary to achieve
maximum fertilization rates and blastocyst
development
(Cramer et al. 2003)
Serum TSH levels are a significant
predictor of fertilization failure in women
undergoing IVF.
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17. c. Fertility in OH.
Infertile females
SCH: 4%
OH: 3.3%
(Arojoki et al. ,2000)
Myxedema
Anovulation
inadequate corpus luteum (10%).
menstrual irregularities 70%
(Goldsmith et al., 1952).
Myxedema: associated with hypothyroidism; the facial changes are distinctive, with
swollen lips and thickened nose. myxedematous
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18. High frequency of infertility in hypothyroidism
1. Altered peripheral estrogen metabolism
2. Hyperprolactinemia
3. Defects in hemostasis
4. Disturbances in GnRH secretion: an abnormal
pulsatile release of LH
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19. Treatment with LT4:
normalize PRL levels
normal LH responses to LHRH
reduce menstrual disturbances
increase the chances of spontaneous fertility
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20. d. Thyroid autoimmunity and fertility.
 AITD
Prevalence:
5 and 15%:
most common endocrine disorders in women of
reproductive age.
often undiagnosed
{No overt thyroid dysfunction for several years}
(Poppe et al, 2007).
Formal names
Thyroid Peroxidase Antibody : TPO-Ab
Thyroglobulin Antibody: Tg-Ab
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21. AITD and infertility
Most studies:
increased prevalence of AITD
(Kaprara et al, 2007, Krassas et al, 2008).
ReferenceControlInfertility
Roussev etal.(1996)7%65%
Kaider et al (1999)10%81%
Reimand et al.(2001)15%41%
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22. Some studies:
no significant difference
(Wilson et al.1975, Abalovich et al. ,2007)
Pooling together all the studies:
Significantly increased incidence of AITD in female
infertility.
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23. Mechanisms
Adequate levels of circulating TH are important for
normal reproductive function.
T3 modulates FSH and LH action on steroid
biosynthesis, and multiple T3 binding sites have
been identified in granulosa and stromal cells, and
human oocytes
(Cecconi et al, 1999)
Any impairment of T3 locally (as in AITD): disruption
of reproductive function.
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24. AITD and PCOS:
AITD in PCOS: 3-fold greater than controls.
(Janssen et al. , 2004)
1. Thyroid Peroxidase Antibody
2. Thyroglobulin Antibody
3. US hypoechoic areas characteristic of AITD,
ControlPCOS
8%27%Elevated TPO-Ab1 and TG-Ab2
6.5%42%US thyroid hypoechoic areas3
2%11%Elevated serum TSH
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25. AITD and Endometriosis:
No association
(Petta et al, 2007).
Increased prevalence of AITD in endometriosis
(Poppe et al, 2002).
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26. AITD and recurrent miscarriage:
TPOAb measurement should be considered when
evaluating patients with recurren
miscarriage Grade A
Am Ass of endocrinology, 2013
TSH and thyroid peroxidase antibodies
Up To date, 2013
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27. Screening
Over 35y:
1. Risk of progression to OH in women with SCH
2. Morbidity-associated hypercholesterolemia
frequently seen in such patients
3. Reversal of potentially unrecognized symptoms
associated with mild TH deficiency
(Dancase et al,1997).
Endometriosis or OD is the cause of infertility
For thyroid dysfunction and autoimmunity
(Poppe et al. 2008)
RPL
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28. B. Thyroid Function and
ART
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29. I. Background
 E2 levels become very high
(1470–2203 pmol/liter or 4000–6000 ng/liter):
depends on the type and duration of COH.
: strain on the hypothalamic-pituitary-thyroid axis:
impair TH distribution and kinetics.
: increase in serum T4- binding globulin (TBG).
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30. COH and OHSS:
marked increase of E2 and TBG: more
severe thyroid function changes than
observed with spontaneous pregnancy.
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31. COH: Significant increase in TSH
compared with baseline values
{rapid 10-fold E2 increase after COH (3492 vs. 359
pmol/liter}
ReferenceAfter
COH
Before
COH
Poppe et al, 2004, 20053.31.8TSH mIU/L
Muller et al., 20003.22.3
Poppe et al, 2004, 200513.212.4FT4 ng/L
Muller et al., 200012.914.4
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32. In hypothyroid-treated women:
Rapid increase (already after 4–6 wk gestation) in
T4 is required to maintain euthyroidism.
The timing of such increased requirement is
more rapid and pronounced when conception had
been achieved after ART
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33. II. Clinical management
Screening for thyroid disorders
1. Universal screening is not recommended for patients who
are planning pregnancy, including ART.
Am Ass of endocrinology, 2013
2. Endometriosis and OD {increased prevalence of
AITD which is risk factor for the development of
hypothyroidism}.
3. Menstrual irregularities, hyperprolactinemia {LT4
therapy has beneficial effect}.
4. Before COH {severe changes in serum TSH and
FT4 may occur}
(Poope et al, 2008).
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34.  ART could be postponed
When hypothyroidism is treated and normal menses
restored {avoiding medical and psychological
burden of ART}
(Poppe et al, 2007).
LT4 administration on ART:
no beneficial impact
(Negro et al, 2005).
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35. Treatment with L-thyroxine
in women with normal serum TSH levels when they
are planning a pregnancy, including ART in the
immediate future, if they have
1. Positive TPOAb, particularly when there is a
history of miscarriage or past history of
hypothyroidism.
2. TSH is greater than 2.5 mIU/L
Am Ass of endocrinology, 2013, Grade B
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36. LT4 dosage should be increased
To obtain TSH < 2.5 mIU/liter before COH
{latter procedure increases TH demands}.
AITD treated with LT4 who underwent COH
developed OHSS
{E2 increase sharply and markedly:
severe hypothyroidism (TSH, 42 mIU/liter)
{association between OHSS and AITD}.
:increase daily LT4 dosage 4 wk before starting the
COH
(Poppe et al, 2008)
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37. Spontanous pregnancy:
by 30%
Pregnancy after COH treatment with Gn
stimulation or oral medications:
by 32%
(Davis et al., 2007)
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38. Thank you
ABOUBAKR ELNASHAR