Hypothyroidism and Menstruation, Repeated miscarriage, Infertility, ART

1. Hypothyroidism
and
Menstruation,
Repeated miscarriage,
Infertility,
ART
Aboubakr Elnashar
Benha university Hospital, EGYPT
ABOUBAKR ELNASHAR

2. CONTENTS
I. CLINICAL HYPOTHYROIDISM
II. SUBCLINICAL HYPOTHYROIDISM
III. AUTOIMMUNE THYROID DISEASE
 CONCLUSION
ABOUBAKR ELNASHAR

3. I. CLINICAL (overt)HYPOTHYROIDISM
Prevalence
Increasing with advancing age.
Causes
.
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4. Definition
Symptomatic patient
Elevated TSH level
low levels of FT4 and FT3.
Screening
1. /5 yrs beginning at 35y
2. /2 yrs beginning at 60y, or
3. any symptoms suggesting hypothyroidism
(Sperof et al, 2010)
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5. 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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6. Menstrual disturbances
3 times greater than in the normal population.
Oligomenorrhea: most common
Amenorrhea
Polymenorrhea
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
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7. Infertility
Incidence:
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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8. Causes of infertility
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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9. Treatment :
Thyroxin
normalize PRL levels
normal LH responses to LHRH
reduce menstrual disturbances
increase the chances of spontaneous fertility
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10. ART
Screening before ART
not recommended
(Am Ass of endocrinology, 2013)
Recommended:
(Poope et al, 2008).
{severe changes in serum TSH and FT4 may occur}
 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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11. Effect of COS on hypothyroidism
COS: very high E2 levels
(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).
OHSS:
marked increase of E2 and TBG: more severe
thyroid function changes than observed with
spontaneous pregnancy.
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12. 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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13. 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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14. 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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15. Spontanous pregnancy:
by 30%
Pregnancy after COH treatment with Gn
stimulation or oral medications:
by 32%
(Davis et al., 2007)
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16. II. SUBCLINICAL HYPTHYROIDISM
(SCH)
Definition
Asymptomatic patient.
Elevated TSH
Normal FT4 and FT3
TRH test: TSH response above 15 mIU/liter.
Risk factors for progression from SCH to OH
thyroid antibodies
already elevated TSH
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17. Infertility
TSH:
significantly higher compared with the controls.
Screening:
No {low incidence}
(Zollenar et al, 2001)
LT4 treatment
Of SCH: pregnancy success rate of 44%.
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18. Miscarriage
TSH: high
More frequent miscarriages, irrespective of the
presence of AITD.
Screening
in recurrent pregnancy loss.
(ASRM, 2012, Am Ass of endocrinology, 2013, Up Todate, 2013)
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19. Ovarian dysfunction
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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20. 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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21. III. AUTOIMMUNE THYROID DISEASE
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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22. 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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23. Some studies:
no significant difference
(Wilson et al.1975, Abalovich et al. ,2007)
AITD
No significant difference between infertile women
and controls.
Pooling together all the studies:
Significantly increased incidence of AITD in female
infertility.
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24. 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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25. 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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26. Endometriosis
No association
(Petta et al, 2007).
Increased prevalence of AITD in endometriosis
(Poppe et al, 2002).
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27. Repeated miscarriage
TPOAb
should be considered when evaluating patients
with recurrent miscarriage
(Am Ass of endocrinology, 2013, Up To date, 2013)
Not required
(ASRM, 2012)
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28. 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
OD
For thyroid dysfunction and autoimmunity
(Poppe et al. 2008)
RPL
controversial
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29. Treatment with L-thyroxine
Positive TPOAb
1. Normal serum TSH +planning
pregnancy or
ART
particularly with history of miscarriage or
hypothyroidism.
2. TSH ≥2.5 mIU/L
Am Ass of endocrinology, 2013, Grade B
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30. CONCLUSION
1. Screening for thyroid disorders
1. Endometriosis
2. Ovarian dysfunction
{increased prevalence of aitd which is risk factor for
the development of hypothyroidism}.
3. Menstrual irregularities
4. Hyperprolactinemia
{LT4 therapy has beneficial effect}.
5. Repeated miscaraige
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31. 2. Management of hypothyroidism in fertility
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32. Thank you
ABOUBAKR ELNASHAR