Obesity, SLE, Thyroid disease and ICSI

1. Obesity
SLE
Thyroid disease
and
ICSI
Aboubakr Elnashar
Benha university Hospital,
Egypt
ABOUBAKR ELNASHAR

2. Obesity and ICSI
ABOUBAKR ELNASHAR

3. ART: OB or OW had significantly
lower CPR
Lower live birth rates
Higher miscarriage rate .
Longer duration of Gnt stimulation
Higher dose of Gnt stimulation
(Rittenberg et al, 2011)
33 studies including 47,967 tt cycles
ABOUBAKR ELNASHAR

4.  Mechanism of the poor outcome
1. Hyperandrogenaemia
(Brewer and Balen, 2010)
2. Insulin resistance
(Dumesic et al., 2008)
3. Abnormal leptin concentrations and LH
hypersecretion
(Qiao and Feng, 2011).
4. Alterations in serum concentrations of insulin-
like growth factors
involved in cell proliferation and differentiation, and
their binding proteins could influence
folliculogenesis, oocyte maturation and embryo
development
(Wang et al., 2006; Fowke et al., 2010).
ABOUBAKR ELNASHAR

5. 5. BMI correlates with endometrial and intra-
follicular concentrations of the inflammatory
markers, interleukin 6 and tumor necrosis factor:
poor oocyte quality
impaired implantation
increased risk of miscarriage
(Lee and Loke, 2000; Gosman et al., 2006; Ma et al., 2010; Dimitriadis
et al., 2010).
6. Difficult ET:
{difficulty to see the air-bubble of the catheter and
tendency for blood in the catheter tip}
[Martinuzzi et al, 2008]
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6. Should overweight or obese women be
denied access to ART?
• In New Zealand (2000): BMI> 32 kg/m2
• BFS (2007): BMI≥35kg/m2 or BMI ≥ 30 kg/m2 in
young women with good ovarian reserve
• NICE (2013): BMI ≥ 29 kg/m2
{uncertainties about underlying data
different weighing of benefits, risks
and costs}.
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7. Age stronger negative effect on oocyte number,
number of mature and fertilized oocytes, CPR and
live birth rates
(Sneed et al., 2008).
In older women
tt rather than unsuccessful attempts to lose weight
should be the priority.
Recognise the medical risks associated with
obesity
Counsel patients in an unbiased manner about
problems that may be encountered during IVF
treatment and in pregnancy
Avoiding blame and maintaining their dignity
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8.  Informed consent that they wish to proceed
under these circumstances
 Refusal of treatment may be deemed unethical.
 Denying access to funded ART simply because
the female partner is overweight: violation of
Articles 12 (the right to marry and found a
family) and
Article 14 (prohibition of discrimination) of the
Human Rights Act.
ABOUBAKR ELNASHAR

9. Management options
Wt loss
1.Dietary and life style changes
 10 % loss in B wt : rapid improvement of in H
profile and chances of conceptions
 Insufficient evidence to recommend one specfic
diet over another
 Risk of anovulatory infertility dropped by 5% with
each h/w of vigrous physical activity
(Edwards et al, 2002)
ABOUBAKR ELNASHAR

10. 2. Pharmacologic agents for wt loss
 Considered when failure to lose at least 10% of B
wt despite life style changes and diet control
(Mathys, 2005)
 Orlistat: Lipase inhibitor
 Advantages
1. Minimal risk to the fetus should a pregnancy
occur bec of its low systemic absorption
2. Effective in restoring ov and normalization of
hormonal profile
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11. 3. Bariatric surgery:
 Indications: (NICE, 2013)
1. Morbid obese failed to lose wt by other means
2. Moderate obesity with significant co-morbid
condition that could be improved by wt loss
 Most suitable technique:
laparoscopic adjustable gastric band
{tightness of the band can be adjusted to
accommodate for increased demands of
pregnancy}
ABOUBAKR ELNASHAR

12. 4. Increasing doses of Gnt for ov induction and
superovulation
Obese patient with PCOS may suffer from OHSS
ABOUBAKR ELNASHAR

13. SLE and ICSI
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14. How to promote and safeguard fertility
In SLE
1. CYC
Lowest effective dose
Shortest duration
Gonadal protection if risk of therapy-induced POF.
use a different disease-modifying and steroid-sparing
therapy e.g. Mycophenolate mofetil MMF (Cellcept)
Fertility is more likely to be preserved if
Age ≤ 30 ys
IV pulse course of CYC lasts ≤ 6 months
Cumulative dose ≤ 7 g
No changes in the menstrual cycle during tt
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15. 2. Prevention of POF
a. GnRha: leuprolide.
protective against POF when administered
10-14 d before each CYC pulse.
Leuprolide: reduction in E and P levels
:reduce the risk of POF from 30 to 5%
[Somers et al,2005].
ABOUBAKR ELNASHAR

16. b. Oocyte storage.
Cryopreservation of gametes before gonadotoxic tt
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17. 3. IVF.
Ovarian stimulation using GnRHa:
1. increase levels of oestrogens: increase the risk
of thrombosis
Thrombosis often occurs in the context of overt
OHSS
2. Flare
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18. Avoid ART
{high risk of complications for mother and fetus during
pregnancy & puerperium}
1. SLE manifested in acute flares
2. Badly controlled arterial hypertension, pulmonary
hypertension
3. Advanced renal disease
4. Severe heart disease and major previous
thrombotic events
 Before ART:
1. Disease has been silent for at least 6 months
2. BP
3. Urine analysis
4. RFT
5. Pulmonary hypertension to be ruled out
ABOUBAKR ELNASHAR

19. During ART:
1. Ovarian stimulation
 Aggressive should be avoided
 low effective Gnt dose
 Mild ovarian stimulation {avoid high E2}.
Anti-oestrogens (CC or aromatase inhibitors)
 Avoidance of OHSS & multiple pregnancy
2. OR:
If Heparin: to be stopped 12-24 h prior to OR & restarted
6-12 h after
3. ET:
Single
4. Luteal phase support:
Natural P through a non-oral route
{avoid OHSS and first passage effect in liver}
(Huong et al. 2002; Askanase and Buyon 2002; Bellver , 2012)
ABOUBAKR ELNASHAR

20. APA, Hx of thrombosis
APA, No Hx of
thrombosis
SLE, No APA
1. Warfarin is switched to
heparin therapeutic dose
before ov stim.
2. Heparin to be stopped 12-24
h prior to OR & restarted 6-
12 after
3. Heparin to be continued till
day of preg test & if pregnant
to continue during
pregnancy
4. Aspirin low dose to be added
, but to be interrupted 5-7 d
before OT
1.Heparin:
prophylactic dose
from day of ET
2. Aspirin:
unproven
1. Anti coagulation is not
recommended
2. Anti-inflammatory
(Corticosteroids or
immunosuppressant) to
be introduced or
increased
5. Prophylactic therapy
 Anticoagulant: for thrombosis
 Corticosteroids or immunosuppressant: for lupus
activity) during and after ovarian stimulation
(Huong et al, 2002)
ABOUBAKR ELNASHAR

21. Thyroid disease and ICSI
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22. COS and thyroid function
E2 levels become very high:
increase in serum T4- binding globulin (TBG):
Significant increase in TSH
OHSS and thyroid function
Marked increase of E2 and TBG:
Significant increase in TSH
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23. Severe untreated thyrotoxicosis:
inhibition of ovulatian: infertility.
Infertility: 5.8% (Joshi et al., 1993)
 Miscarriage, IUGR, PTL and perinatal mortality,
congestive heart failure, PET.
 Control before conception
 Carbimazole or methimazole: PTU
 Monitor/4w: FT4 at upper 1/3 of normal range
PTU (b.d)
Carbimazole (o.d)
50 mg
10 mg
150 mg
30 mg
300 mg
60 mg
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24. COS in hyperthyroid-treated women:
PTU may need to be reduced
{ increased thyroxine requirements}
TFT should be checked during COS
once PT is +ve
/2-4 w
FT4: upper 1/3 of normal range
ABOUBAKR ELNASHAR

25. COS in hypothyroid-treated women:
Rapid increase (already after 4–6 wk gestation) in
T4 required to maintain euthyroidism.
When conception had been achieved:
The timing of such increased requirement is
more rapid and pronounced
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26. 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 IVF.
ABOUBAKR ELNASHAR

27. Recommendation
 Screening for thyroid disorders
Universal screening:
not recommended
Am Ass of endocrinology, 2013
1. RM
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 COS
{severe changes in serum TSH and FT4 may occur}
(Poope et al, 2008).
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28.  ART should be postponed
 First treat hypothyroidism or hyperthyroidism
 Normal menses restored
(Poppe et al, 2007).
 Carbimazole or methimazole: PTU
 Monitor/4w: FT4 at upper 1/3 of normal range
 Empirical LT4 administration on ART:
Not beneficial
(Negro et al, 2005).
ABOUBAKR ELNASHAR

29. Treatment with L-thyroxine in Normal TSH
planning pregnancy, (including ART) in the
immediate future, if they have
1. Positive TPOAb, particularly when there is a
history of miscarriage or hypothyroidism.
2. TSH is greater than 2.5 mIU/L
Am Ass of endocrinology, 2013, Grade B
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30. LT4 dosage should be increased
1. To obtain TSH < 2.5 mIU/L before COS
{latter procedure increases TH demands}.
2. AITD treated with LT4 and developed OHSS
{E2 increase sharply and markedly:
severe hypothyroidism (TSH, 42 mIU/L)
{Association between OHSS and AITD}.
:increase daily LT4 dosage 4 wk before starting the COH
(Poppe et al, 2008)
3. Pregnancy:
Spontaneous: 30%
After COS: 32%
(Davis et al., 2007)
ABOUBAKR ELNASHAR

31. Thank you
ABOUBAKR ELNASHAR