How science is advancing
- 1. How Science is advancing!!
- 2. N-acetylaysteine (NAC) Mucolytic Recently reported to have insulin senitizing properties Accordingly we used it with C.C to avoid the anti-oestrogenic effect on cervical mucous
- 3. Observation Improved ovarian response with development of more than one follicle
- 4. Idea NAC can be a novel combination to CC
- 5. Clinical Trial The best candidates to this idea are CC resistant cases
- 6. Keeping in mind NAC has been used safely since long time (Borgstrom et al 1986).
- 7. Objective to evaluate the effect of NAC adjuvant therapy in women with PCOS resistant to CC.
- 8. Design prospective RCT, placebo-controlled, double blind Allocation was done using opaque sealed envelopes
- 9. Patients and Methods Patients: 150 cases diagnosed as CC-resistant PCOS were recruited. Inclusion criteria 1-Normal semen parameters 2-Clomiphene citrate resistant PCOS 3-Normal HSG . 4- No treatment was taken during last 3 ms prior to recruitment.
- 10. Intervention Participants assigned randomly to receive either NAC 600 mg / twice daily ( group I ) with CC 50 mg / twice daily or placebo ( group II ) with CC 50 mg / twice daily for 5 days starting at day 3 of the cycle . Allocation was done using opaque sealed envelopes
- 11. Monitoring of the cycle Transvaginal determination of the mean follicular diameter. Measurement of serum E2 levels at time of HCG adminstration. 3. Monitoring intervals were determined by patient response.
- 12. Then Human chorionic gonadotropin was administered when at least one follicle measured 18 mm Timed intercourse was advised 24-36 hours after hCG injection
- 13. Success was monitored by A serum progesterone level was checked 6-8 days after the administration of hCG. A serum hCG level was determined 14 days after hCG injection if menses had not yet occurred. Pregnancy was defined as a rise in the serum hCG level on serial determinations at least 2 days apart.
- 14. Outcomes Primary: Ovulation rate Secondary: pregnancy rate Tolerability
- 15. Results 150 women with PCO resistant to CC were randomized to CC +NAC: n = 75 (GroupI) CC + placebo: n = 75 (GroupII)
- 16. Demographics NS 28.5 ± 5.7 30.5 ± 2.6 BMI NS 99.2 ± 12.3 101.3 ± 12.4 B WT (Kg) NS 4.4 ± 2.6 5.0 ± 2.9 Duration (Ys) NS 28.4 ± 5.7 28.9 ± 4.7 Age (Ys) P value Group II Group I Variable
- 17. Hormonal profile NS 85.9 ± 14.1 81.9 ± 12 Fasting Glucose (mg/dL) NS 17.2 ± 4.4 18.8 ± 4.7 Fasting insulin (U/mL) NS 2.1 2.2 LH/FSH ratio P value Group II Group I Variable
- 18. Clinical outcomes of both groups
- 19. Pregnancy rates in patients who received NAC according to their insulin
- 20. How To Explain Antiapoptotic Odetti et al., 03 . Antioxidant De Mattia et al., 98. Insulin sensitizing effect Fulghesu et al 02.
- 21. Potential biological activities of NAC Reduces testosterone levels and free androgen index values. Fulghesu et al 02. A safe mucolytic drug.
- 22. Side effects NAC is generally safe & well tolerated The most common side effects were : 1-Nausea & vomiting. 2-Diarrhea. It is contraindicated in active peptic ulcer disease.
- 23. Conclusions NAC is a a novel adjuvant treatment for PCOS patients. It is a simple, well tolerated and inexpensive agent. Accepted for publication in Fertil & Steril 2005 Feb
- 24. STEP II A feasible approach to friendly IVF
- 25. PILOT STUDY The objective of this study was to examine the use of NAC with clomiphene citrate for ovarian stimulation in assisted conception as a model for “Friendly IVF”
- 26. Intervention Patients were offered NAC, 1,200 mg/day from day 3-7 of the menstrual cycle with CC (100 mg /day) starting on day 3-7. HCG (10,000 IU) was given when leading follicle(s) were 18mm followed by ICSI
- 27. RESULTS Twenty women were enrolled in this pilot study with a mean age of 27.3 ± 1.9 and mean BMI of 28.1 ± 0.8.
- 28. The mean number of follicles >18 mm on the day of HCG injection was 4.8 ± 1.6. The mean number of oocytes retrieved was 3.6±1.2 . Four women got pregnant (20%) [all were single ton pregnancy). The implantation rate was 14.3%. No miscarriages were reported till now.
- 29. cost of medications the number of NAC sachets used was 6 per day for 5 days making a total of 30 costing 27 E.P plus an average of two fillings of clomid = 18 EP, thus the total cost of medications in NAC-CC / ICSI cycle = 45 E.P (7$) which is considerably less than the average cost of medications in the long protocol of ICSI cycle (about 2000EP) (~450$).
- 30. CONCLUSION II a simple NAC-CC protocol is compatible with the concept of `friendly IVF', yielding a reasonable pregnancy rate per cycle started. The results of this study should be substantiated in a larger cohort of patients .
- 31. Thank you