ART: Factors affecting success


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Factors affecting

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ART: Factors affecting success

  1. 1. Benha University Hospital, Egypt Aboubakr Elnashar
  2. 2. •IVF specialist 1. Identification of the successful techniques 2. Valid comparison between the results of different centers •General gynecologist who make most of referrals. 1. Treatment of the factors decreasing success before ART 2. Proper counseling regarding the factors that can not •Infertile couple who should be involved in decision making. Importance of definition of these factors Aboubakr Elnashar
  3. 3. Aboubakr Elnashar
  4. 4. ART success rates: are expressed in several ways The 2 most common 1. Pregnancy rate (PR) 2. live birth: more relevant. Pregnancy or live birth can be calculated as a percentage of cycle starts, retrievals, or transfers. In Egypt (2000): PR/retrieval: 28.9% for ICSI (The Egyptian IVF registry; Mansour,2003) Aboubakr Elnashar
  5. 5. Couple 1. Age 2. Ovarian reserve 3. Number of previous treatment cycles 4. Duration of infertility 5. Type of infertility 6. Cause of infertility 7. Body weight 8. Smoking, alcohol, caffeine consumption Technique I. Stimulation protocol II. Oocyte retrieval III. Laboratory IV. Embryo transfer V. Luteal phase support Aboubakr Elnashar
  6. 6. Aboubakr Elnashar
  7. 7. I. Age A woman’ ability to become pregnant declines with age both naturally & with treatment (Templeton et al, 1996). Age (years) Live birth/ treatment cycle (%) 23-35 36-38 39 40 or older >20 15 10 6Aboubakr Elnashar
  8. 8. II. Ovarian reserve Women with decreased ovarian reserve respond poorly to COH & have poor clinical outcome in IVF (Sharif et al,1998). • Ovarian reserve: Basal FSH: >15 Inhibin B: <45 Ovarian volume Antral follicle count: <5 Anti-mullerian hormone: <1ng/ml Aboubakr Elnashar
  9. 9. III. Number of previous treatment cycles The delivery rate for cycles: 1: 27% 2: 27.4% 3: 23% 4: 16% >4: 15% (Meldrum et al,1998) Aboubakr Elnashar
  10. 10. IV. Type of infertility ART is more effective in women who have previously been pregnant &/or had live birth (NICE,2004) Aboubakr Elnashar
  11. 11. V. Duration of infertility A significant decrease in PR with increasing duration of infertility (HEFA data base,1996). 1-3Y: 15% 4-6Y: 14% 7-9Y: 13% 10-12Y: 12% > 12Y: 9% Aboubakr Elnashar
  12. 12. VI. Cause of infertility Live birth rates were 27% for male factor, 26% for endometriosis, 25% for tubal factor, 25% for unexplained infertility 23% for ovulatory dysfunction (Templeton et al, 1996). In Egypt (2000): Female factor represented 16.6% of the cycles Male factor represented 56% of the cycles (The Egyptian IVF registry; Mansour,2003)Aboubakr Elnashar
  13. 13. Hydrosalpinx: Hydrosalpinx had a negative effect on PR, IR, early pregnancy loss & live delivery rate. {The fluid of hydrosalpinx may constitute a mechanical barrier to implantation by causing the embryo to float Hydrosalpinx fluid is deficient to support the developing embryo Hydrosalpinx is toxic to the developing embryo}. Salpingectomy resulted in improvement of outcomes (NICE, 2004) Aboubakr Elnashar
  14. 14. Male factor: In IVF: poor success rates due to poor fertilization rate In ICSI: dramatic improvement in the outcome. Aboubakr Elnashar
  15. 15. Endometriosis: • Minimal & mild: No effect (Vrtovec et al,2000) • Moderate & severe: The fertilization rate, PR per transfer, & birth rates were significantly lower (Azim et al,1999; Garrido et al, 2000). On other hand, HFEA database (2000) did not show lower PR in endometriosis, but it did not take into account the stage of endometriosis. • Aboubakr Elnashar
  16. 16. Fibroid: Fibroids not causing deformity of the uterine cavity & <7 cm did not affect the implantation or miscarriage rate in ART (Ramzy et al,1998). Aboubakr Elnashar
  17. 17. VII. Body weight BMI should ideally be in the range 19-30 before commencing ART. The BMI outside this range is likely to reduce the success of ART(NICE,2004). On other hand Wass et al (1997) revealed that BMI has no effect on PR but that the android body fat distribution WHR >0.8: PR is 16% 0.7-0.79: PR is 30%. {Excessive androgen levels have a negative effect on oocyte development resulting in poor quality embryo} Aboubakr Elnashar
  18. 18. VIII. Smoking, alcohol, Caffeine consumption • PR amongst smokers (maternal or paternal)were significantly lower than non- smokers after IVF.(14% Vs 21%) (Feichtinger et al,1997) • Consumption of more than one unit (12 g) of alcohol per day reduces the effectiveness of ART, including IVF (NICE,2004) Aboubakr Elnashar
  19. 19. • Caffeine consumption (over 2-50 mg/d Vs 0-2 mg/d; 100 mg caffeine in one cup of coffee) during lifetime & during the week of initial visit for infertility has adverse effects on the success rates of ART including IVF (Kohen et al, 2002). Aboubakr Elnashar
  20. 20. Aboubakr Elnashar
  21. 21. The success rate of IVF & ICSI vary from one center to another ranging from 4% to 36% per cycle started, in UK (HEFA,2000). 1. Some clinics are better than the others: in their clinical & embryology practices. 2. Patient selection: Some centers decline to treat patients with poor prognostic factors 3. Success rates are reported differently. No reporting of cancelled cycles. Success rate per number of cycles started, oocyte retrieval, embryo transfer. Aboubakr Elnashar
  22. 22. I. Ovarian Stimulation COH leads to the creation of numerous embryos, which could be available for transfer or cryopreservation, thus increasing the chance of pregnancy (Wang et al,1994). Aboubakr Elnashar
  23. 23. 1. GnRH agonist Vs HMG: • The use of GnRH agonist in down regulation protocols improves the IVF outcome • Clinical PR increases compared to the use of HMG alone (Hughes et al, 1992). {Allow many follicles to reach maturity thereby increasing the number of oocytes collected & reducing the cancellation rate. Prevent premature LH surge & consequently spontaneous ovulation, making cycle monitoring much easier} (Wang et al,1994). Spontaneous abortion was similar. • However, GnRHa was associated with a slight, but insignificant increase in the incidence of OHSS & multiple pregnancy Aboubakr Elnashar
  24. 24. 2. Long Vs short protocols: Long stimulation protocols are superior to short & ultrashort protocols in terms of clinical pregnancies (Daya, Cochrane library, 2002). 3. GnRH agonist Vs antagonist: The clinical PR was significantly lower in the antagonist group (Al-Inany & Aboulghar, Cochrane library, 2002) Aboubakr Elnashar
  25. 25. 4. Urinary FSH Vs HMG: CPR was higher when uFSH was used compared to HMG (Daya, Cochrane library, 2002). 5. Rec FSH Vs uFSH: No statistically significant difference in PR/started cycle between rec FSH & uFSH (Al-Inany et al, 2003) Aboubakr Elnashar
  26. 26. II. Oocyte retrieval 1. Vaginal disinfection with povidine iodine: PR was significantly higher in the normal saline group (17.2% Vs 30.3%) 2. The number of oocytes retrieved: < 4 oocytes: reduced fertilization, CPR, & live birth (Victory et al, 2004). >4 oocytes: Similar chances of success for all Aboubakr Elnashar
  27. 27. III. Laboratory 1. ICSI Vs IVF: In couples with borderline semen, ICSI results in higher fertilization rates (van Rumsteke et al, Cochrane library, 2002) In couples with normal semen, ICSI results in higher fertilization rates per oocyte injected but not per oocyte retrieved compared to conventional IVF. Aboubakr Elnashar
  28. 28. Tubal factor infertility: IVF should be the initial treatment of choice (Aboulghar et al,1996; Bukulmez et al,2000). {No significant difference in PR or take-home baby}. Unexplained infertility: ICSI should be the first option (Sertac et al,2000). {Complete fertilization failure was higher in conventional IVF (34.3%) than ICSI (10.3%)} (Jaroudi et al,2003). Aboubakr Elnashar
  29. 29. 2. Co-culture & group culture: The value of Co- culture in improving PR has not been established (Veiga et al,1999) RCTs failed to prove that culturing the embryos in groups improve the CPR (Spyropoulou et al,1999). 3. Embryo selection: The clinical value of embryo selection based on scoring systems has not been established by RCTs (Sallam,2003). Aboubakr Elnashar
  30. 30. 4. Assisted hatching: The results of RCTs have been controversial & there is a need for a large RCT (Sallam, 2003). 5. Embryo cryopreservation: The main aim is to increase the chances of achieving a live birth from a single COH cycle. The average CPR in frozen embryo replacement cycles are 15% (HEFA,2000). Cryopreservation increased the PR by 11% (Wang et al, 1994) Aboubakr Elnashar
  31. 31. IV. Embryo transfer 1. Trial (dummy, mock) transfer: Clinical P & IR are significantly increased (Mansour et al, 1990). Trial ET: determines the most suitable catheter & avoids unexpected difficult & failed ET. Aboubakr Elnashar
  32. 32. 2. The best day for embryo transfer: Day 2 Vs day 3: Although an increase in CPR with D3 ET, there is no sufficient good quality evidence to suggest an improvement in live birth (Oatway et al, 2004, Chocrane library). Day 2 or 3 (early) Vs day 5 or 6 (late): Day 5 ET has no advantages over day 3 (Sallam et al, 2003; meta-analysis). Little difference in the major outcome parameters between early ET & blastocyst culture (Blake et al, 2004, Chocrane library). Aboubakr Elnashar
  33. 33. 3. Type of ET catheter: PR was significantly higher in soft catheter (van Weering,2002). PR was increased by 50% when the soft double lumen catheter rather than the single lumen catheter was used (McDonald & Norman ,2002). Aboubakr Elnashar
  34. 34. 4. Ultrasound-guided ET: is associated with an increase in the CPR & IR (Salam & Saad-eldin ,2002; Buckett 2003 ,meta-analysis) Value of UGET: - confirm that the embryos are properly deposited - to follow the embryo-associated air bubble - increases the frequency of easy ET. - decrease cervical & uterine trauma Aboubakr Elnashar
  35. 35. 5. Site of embryo deposition IR was significantly higher when the embryos were deposited 2 cm below the uterine fundus (Coroleu et al ,2002). Aboubakr Elnashar
  36. 36. 6. Number of embryo transferred • To balance the chance of a live birth & the risk of multiple pregnancy, no more than 2 embryos should be transferred (NICE, 2004; HEFA, 2000) Aboubakr Elnashar
  37. 37. Age (ys) Favorable conditions No favorable conditions < 35 35-37 38-40 > 40 1 2 3 5 2 3 4 5 • ASRM (2004) Most favorable conditions. 1. The first cycle of IVF 2. Previous success of IVF 3. Good Quality embryos 4. Excess of embryos of sufficient quality to warrant cryopreservation Aboubakr Elnashar
  38. 38. V. Luteal phase support 1. IM Vs oral: IM P conferred the most benefit compared with oral P (meta-analysis, Prittis & Atwood, 2002) 2. Vaginal Vs oral: • The C & OPR were significantly lower with the oral formulation (Pouly et al, 1996; Frieder et al, 1999, Sucedo et al, 2000). Aboubakr Elnashar
  39. 39. 3. Addition of E To P: 1. No advantage (Lewin et al, 1994; Smitz et al,1993;Tay & Lenton, 2003; Rashidi et al,2004). 2. Beneficial effect on IR & PR (Farhi et al,2000; Gorkemli et al,2003). 3. Beneficial effect on PR in patients with profound E2 decline (E2 on day of HCG/ E2 of ET >50%) (Lakkis et al,2002; Gleicher et al,2000). Aboubakr Elnashar
  40. 40. 4. Progesterone plus Prednisolone & Low dose aspirin No benefit on PR , but it may reduce the rate of spontaneous pregnancy loss (Mollo et al,2003) Progesterone plus ascorbic acid No benefit (Griesinger et al, 2002) Aboubakr Elnashar
  41. 41. Benha University Hospital, Egypt Email: Aboubakr Elnashar