Infertility treatment related to PCOS

1. INFERTILITY TREATMENT RELATED TO PCOS
The Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group, 2008
Prof Aboubakr Elnashar
Benha university Hospital, Egypt

2. Treatment modalities
Lifestyle Modifications
Clomiphene Citrate
Insulin Sensitizing Agents
Gonadotrophins
Laparoscopic Ovarian Drilling
IVF
Ovulation Induction and IUI
Aboubakr Elnashar

3. Lifestyle Modifications
Obesity:
adversely affects reproduction {anovulation, pregnancy loss and late-pregnancy complications}.
within PCOS: failure of infertility tt.
Weight loss:
prior to infertility tt
improves ovulation rates
limited data that it improves fecundity or lowers pregnancy complications.
Aboubakr Elnashar

4. lifestyle modifications: 1st line tt of obesity in PCOS.
Caloric restriction
increased physical activity
•The ideal amount of weight loss: unknown 5% decrease of B W
Aboubakr Elnashar

5. Clomiphene Citrate
first choice for induction of ovulation in most anovulatory women with PCOS.
Selection of patients for CC:
body weight/BMI
female age
other infertility factors.
The starting dose: 50 mg/d (for 5 days) maximum dose: 150 mg/d.
Aboubakr Elnashar

6. Monitoring:
US or P is not mandatory to ensure good outcome.
Conception rate:
up to 22%/cycle in those women ovulating on CC.
Aboubakr Elnashar

7. Aromatase inhibitors
Further studies to demonstrate efficacy & safety
Mechanism
1. Release the pituitary/hypothalamic axis from the estrogenic negative feedback, increase Gnt secretion, stimulate ovarian follicle development
2. locally in the ovary: increase the follicular sensitivity to FSH
Aboubakr Elnashar

8. Insulin Sensitizing Agents Metformin
Restricted to those with glucose intolerance.
Alone: less effective than CC
Added to CC: no advantage
Aboubakr Elnashar

9. DIAGNOSIS OF INSULIN RESISTANCE
1.BMI: > 30 K/m2 is almost always IR 2. Waist to hip ratio: >0.85. 3. Waist cir.: >100 cm 4. Acanthosis nigricans (grey-brown velvety discoloration on neck, axilla or groin). 5. Numerous achrochordons (skin tags) 6. Fasting insulin: normal levels are variable 10-20 u/ml. 7. Fasting glucose insulin ratio < 4.5.
Aboubakr Elnashar

10. Continuing during pregnancy: should be left to obstetricians& based on a careful evaluation of risks& benefits.
Recommended 2nd -line TT should CC fail to result in pregnancy: Gnt or LOD.
Aboubakr Elnashar

11. Gonadotrophins:
Chronic low-dose
•Starting dose: 37.5 IU
•Duration of starting dose:14 d
•The weekly dose increment: reduced from 100% to 50% or 37.5 IU
:Marked dec in OHSS.
The duration: should not exceed 6 ovulatory cycles.
Aboubakr Elnashar

12. 0
14
21
28
35
75 iu
112.5 iu
150 iu
187.5 iu
225 iu
Days
7
37.5 iu
½ Amp.
One Amp.
42
49
2 Amp.
3 Amp.
White et al. J Clin Endocrinol Metab 1996;81:3821–4
Aboubakr Elnashar

13. Monitoring
I. US
-Baseline:
-Serial
Documentation of all follicles >10 mm {predict the risk of multiple pregnancies}.
Cycle cancellation
>3 follicles ≥16 mm
>2 follicles ≥16 mm or
>1 follicle ≥16 mm& 2 additional follicles ≥14 mm (ASRM, ESGRE, 2008)
Aboubakr Elnashar

14. II. E2 levels:
•Used to cancel cycles (due to over- or under-response) adjust the dose of Gnt
•Caution: rapidly rising or >2500 pg/ml (ASRM, 2006). <1000 pg/ml
Aboubakr Elnashar

15. Overall, ovulation induction (representing the CC, Gnt paradigm) is reported to be highly effective with a cumulative singleton live birth rate of 72%.
Aboubakr Elnashar

16. Laparoscopic Ovarian drilling
An alternative to Gnt for CC-RPCOS.
1. No risk of OHSS or
high-order multiples.
2. Intensive monitoring is not required
3. Single tt using existing equipment
Not be offered for non-fertility indications.
Aboubakr Elnashar

17. Risks: 1. risk of laparoscopy 2. adhesion 3. destruction of normal ovarian tissue.
 To decrease risk: 1. Minimal damage to the ovaries. 2. Irrigation 3. trained personnel.
LOD is usually effective in <50% of women and additional ovulation induction is required under those circumstances.
Aboubakr Elnashar

18. IVF Recommended 3rd-line treatment {effective in women with PCOS}.
IVF is a reasonable option, {number of multiple pregnancies can be kept to a minimum by transferring small numbers of embryos}.
The optimal stimulation protocol is still under debate: further RCTs comparing FSH stimulation protocols with use of GnRHa Vs. GnRHant are required
PR in women with& without PCOS are similar: implantation is not compromised in PCOS.
The increase in the cycle cancellation rate in women with PCOS:
1.absent or limited ovarian response or
2.increased OHSS.
Aboubakr Elnashar

19. Ovulation Induction and IUI
Indicated:
1.Male factor
2.PCOS who failed to conceive despite successful induction of ovulation.
Aboubakr Elnashar

20. Overall Conclusions
Evaluation of women with presumed PCOS desiring pregnancy should exclude any other health issues in the woman or infertility problems in the couple.
Before any intervention is initiated, preconceptional counselling should be provided emphasizing the importance of life style, especially weight reduction and exercise in overweight women, smoking and alcohol consumption.
The recommended first-line treatment for ovulation induction remains the anti-estrogen CC.
Aboubakr Elnashar

21. •Recommended second-line intervention should CC fail to result in pregnancy is either exogenous Gnt or LOD.
•Both have distinct advantages and drawbacks. Choice should be made on an individual basis.
•The use of exogenous gonadotrophins is associated with increased chances for multiple pregnancy and intense monitoring of ovarian response is therefore required.
•LOD is usually effective in <50% of women and additional ovulation induction is required under those circumstances.
Aboubakr Elnashar

22. •Overall, ovulation induction (representing the CC, gonadotrophin paradigm) is reported to be highly effective with a cumulative singleton live birth rate of 72%.
•Recommended third-line treatment is IVF, because this treatment is effective in women with PCOS. Data concerning the use of single ET in (young) women with PCOS undergoing IVF, significantly reducing chances of multiple pregnancies, are awaited.
Aboubakr Elnashar

23. •More patient-tailored approaches should be developed for ovulation induction based on initial screening characteristics of women with PCOS.
•Such approaches may result in deviation from the above mentioned first-, second- or third-line ovulation strategies in well- defined subsets of patients.
Aboubakr Elnashar

24. •Metformin use in PCOS should be restricted to women with glucose intolerance. Based on recent data available in the literature, the routine use of this drug in ovulation induction is not recommended.
•Insufficient evidence is currently available to recommend the clinical use of aromatase inhibitors for routine ovulation induction.
•Even singleton pregnancies in PCOS are associated with increased health risk for both the mother and the fetus.
Aboubakr Elnashar

25. GnRHa
with Gnt: not justified:
1. The significantly higher OHSS
2. Risk of multiple pregnancies
3. Inconvenience
4. Cost
5. Absence of documented increases in pregnancy success
Aboubakr Elnashar

26. Thank you
Aboubakr Elnashar
elnashar53@hotmail.com
Aboubakr Elnashar