HOW TO OPTIMIZE ART OUTCOME
- 1. Prof. Rokeya Begum Director Surgiscope fertility center & Honorary Adviser USTC Bangladesh. HOW TO OPTIMIZE ART OUTCOME
- 3. Selection of Patient Age Nutritional status Lifestyle Psychological factor Medical H/O Reproduction H/O Family history Risk variable
- 4. Fertility is decreased by half in woman in their late 30s compared with woman in their early 20s. IVF cannot reverse the effect of age on fertility . Age Live birth rate following IVF diminish by 2% for each year of female age.
- 5. Maternal age is a strong independent factor for increase in outcome of IVF.
- 6. Decline in male fertility Increase risk of genetic mutation Autism related disorder after age of 45-50 years. Advanced Paternal Age
- 7. Life style Weight Obesity -BMI 30kg/m2 under weight -BMI 18kg/m2 Both obesity and under weight are associated with decline fertility through chronic anovulation. Why Reduced responsiveness to stimulation protocol. Higher cycle cancellation rate. Embyo quality. Impaired embyo implantation rate. Particularly abdominal adiposity.
- 8. Pregnancy rate decreases by 30% per cycle for each 0.1 increase in waist/hip ratio. In men obesity • Abnormal sperm count.>35kg/m2 • Higher DNA fragmentation.
- 9. Pathogenic mechanisms - Increase testicular temp due to fat deposition. - Decrease in circulatory testosterone due to sleep apnea. - Hyper insulinaemia. - Dysregulation of HPO by increased oestrogen.
- 10. Smoking All couples should be counsel to avoid smoking and to eliminate exposure to passive smoking.
- 11. Alcohol All woman should be assessed for alcohol use and advised of the risks to fertility and to the fetus. Woman should be informed that there is no safe level of alcohol exposure in pregnancy. Alcohol Causes : - Anovulation - Impaired implantation - Reduced libido - Impotency - Abnormal sperm parameter
- 12. Psychosocial stress In Women - 1. Lower number of oocyte retrieval 2. Lower implantation 3. Lower pregnancy rate In Men – Stress - testosterone spermatogenesis
- 13. Immunization The assessment of the woman’s vaccinations history is strongest recommended before beginning the treatment of infertility.
- 14. Autosomal recessive disease – carriers are asymptomatic. Thalassemia - use of donor gametes - pre implantation genetic diagnosis Genetic counseling
- 15. Adverse outcomes in previous pregnancies – 1. Counsel regarding recurrence of another event . 2. Preventive strategies – Repeat miscarriages, still birth or preterm delivery necessitate work up to identifies the cause. Reproduction history
- 16. Chronic medical conditions Maternal fetal medicine specialized involved to care these woman in pre conceptional stage. For majority of chronic disease optimal control prior to ART for favorable maternal and neonatal outcome.
- 17. High risk for pregnancy pulmonary HTN Eisenmenger’s syndrome Marfans syndrome, with aortic involvement. Severe renal insufficiently.
- 19. Men are active partners in ART Undergo medical evaluation before ART in order to detect and modify high risk behaviors and poorly controlled diseases.
- 20. Pelvic pathology is detrimental to IVF outcome.
- 21. Uterine fibroids Uterine fibroids occur in upto 30% of reproduction age women. (Verkaut 1992)
- 22. 1.Submucous fibroid is essential to remove before IVF. 2. Sub serious fibroid should be ignored. 3. There are no studies to confirm the value of removing intramural fibroids. However there is evidence to suggest a benefit after removing them. Treatment Fibroid
- 23. Hydrosalpinx which are visualized by USG reduced IVF outcome and should be removed. As an alternative cornual ligation could be done. Hydrosalpinx
- 24. Surgical management of endometriomas has no significant effect on IVF pregnancy rates and ovarian response to stimulation. Endometrioma Fewer oocytes were retrieved. Endometrioma effect oocyte number but not embryo quality or pregnancy outcome, irrespective of the presence of an ovarian endometrioma.
- 25. . Uterine septum Removed of uterine septum may improve the IVF outcome
- 26. Sharam et al (1997) recommended that all couples with elevated titers of chlamedia trachomatis IgG antibodies be treated with Doxycycline prior to IVF. Pelvic infection before IVF
- 27. IVF patient with bacterial vaginosis have decreased conception rates and increased rate of early pregnancy loss.
- 28. Ovarian stimulation There is a strong association between the number of oocytes retrieved and live birth rates in IVF.
- 29. The optimum number of oocytes needed to maximize IVF outcomes seems to be about 15. COS should be tailored to individualized. Maximum – for poor responder Fine tuning for – Hyper responder
- 30. Young and older patients Polycystic ovaries/PCOS High basal FSH/small ovaries Previous OHSS/poor response Easily Recognized Who is Who in ART
- 31. AMH and AFC are currently the best tools to predict ovarian response . BIOMARKERS of Ovarian Response
- 34. Rec hFSH has greater potency compared to both HMG and HP HMG.
- 35. Protein content Specific activity (IU/mg protein) Injected protein per 75 IU (mcg) hMG < 5% ~100 ~750 hMG-HP < 70% 2,000–2,500 ~33 rec-hFSH* > 99% 13,645 6.1 Size Exclusion High Performance Liquid Chromatograph y (SE- HPLC) Protein content in solution bymass (FbM)
- 36. Higher FSH bioactivity, which is related to the way the drug is made, filled and delivered.
- 37. Accurate dose delivery Adjustments by small increments Self-administration 25% Folitropin alfa prefilled ready-to- use pen Needle-free reconstitution, conventional syringe Easy of use 58% Dosing mechanism 43% Less chance of error 26% 75%
- 38. GnRh Antagonist in High Responders LH Trigger with GnRH agonist in high responders.
- 39. GnRH Antagonists in High Responders 9 RCT; 966 PCOS women GnRH Antagonist X Agonist Weight Mean Difference (WMD)1; Relative Risk (RR)2 Duration of stimulation -0.74 (95% CI: -1.12; -0.36)1 Gonadotropin dose -0.28 (95% CI: -0.43; -0.13)1 Oocytes retrieved 0.01 (95% CI: -0.24; 0.26)1 20% vs 32% Risk of OHSS (Moderate & Severe) 0.59 (95% CI: 0.45-0.76)2 Clinical PR 1.01 (95% CI: 0.88; 1.15)2 Miscarriage rate 0.79 (95% CI: 0.49; 1.28)2
- 40. LH Trigger with GnRH agonist in high responders.
- 41. Intervention Outcome Evidence Ovarian biomarkers Identify who are at risk 1a Recombinant rather than urinary gonadotropins Oocyte yield 1a Biomarkers + low starting doses of rec- hFSH FbM Fine-tune COS + oocyte yield 1b GnRH Antagonists OHSS 1a GnRH Agonist for LH Triggering OHSS 1a Two-step IVF OHSS 1b Evidence-based Strategies to Optimize COS in High Responders
- 42. Impaired Oocyte Quality Reduced Fertilization Rate Reduced Embryo Quality Increased Miscarriage Rates Ovarian Aging
- 43. Intervention Outcome Evidence Ovarian biomarkers Identify who are at risk 1a Recombinant rather than urinary gonadotropin Oocyte yield 1a Adjuvant therapy Pregnancy rate 1a GnRH antagonist protocol Duration of stimulation 1a LH supplementation Pregnancy rate 1a Biomarkers + rec-LH Oocyte yield/cancellation/PR 2a LH supplementation with rec-LH rather than hMG Pregnancy rate 2a Evidence-based Strategies to Optimize COS in Poor Responders
- 45. Culture media Sequential – where embryos are moved part way through the culture period to a medium with a different composition. Single step – Embryo are held in the same dish throughout and culture medium is not replenished any point.
- 46. Single step media – is advantageous when used in conjunction with continuous embryo monitoring system. This minimizes – stress to embryo change in PH Light Temp outside the incubator
- 47. Continuous embryo monitoring through time- lapse technology by use of single step culture.
- 48. Cryopreservation Cryopreservation which is mostly used to preserve surplus embryos and cryopreserve donoted gamates or embryo for future cycles.
- 50. Vitrification achieves higher survival rates than slow cooling.
- 51. 1. Avoid the formation of ice crystals during the freezing process. 2. Intracelluler crystal formations creates lethal factors through unwanted physical and chemical events that may injure the cell during the cryopreservation process. The most important principle of cryopreserving oocytes and embryos
- 52. 1. No mechanical injury 2. Less osmotic stress to cells. 3. No intracellular crystal formation. 4. Less labor in laboratory daily work. 5. Simple protocol. 6. Useful for oocytes and blastocyst which have less success with slow freezing. 7. No need for expensive devices. Why do to prefer the Vitrification procedure now ?
- 53. Fresh embryo transfers can be replaced by cryopreserved – thawed embryo transfers in ART cycles. COH has been shown to advance endometrial maturation and adversely affects implantation in ART. There is a better embryo- endometrium synchrony in frozen-Thawed embryo transfer cycles than fresh embryo transfer cycles.
- 54. Freeze all cycle – safer approach to eliminate risk of hyper stimulation with at least equivalent results and better obstetric and perinatal outcome versus fresh embryo prefer.
- 55. Embryo grading has been proposed as the most appropriate system for selecting the best embryo. Assessment of morphological characteristics is an easy and non invasive way. Selection of embryo
- 56. Preimplantation genetic screening (PGS). Age more than 40 yrs - - Risk of trisomy - Risk of miscarriage RIF (Repeated Implantation Failure). Recurrent Miscarriage Male Infertility Technique to assess embryo quality
- 57. PROS - Time to pregnancy decrease - Decreased risk of miscarriage CONS - More RCTs required - Embryo may be autocorrect - Mosaicsm : confusing the issue of transfer
- 58. No of embryo transfer Single embryo transfer VS Multiple embryo.
- 59. Faced with the prospect of never giving birth, women were willing to accept a significantly greater risk of experiencing the worst perinatal outcome. Perinatal death was valued significantly lower than treatment failure (P values < 0.001) . All disability outcome were valued significantly higher than the no birth outcome (all P values < 0.001).
- 60. Techniques and technology for Embryo transfer Parameters affecting ET outcomes 1. Anatomy - Uterine position - Utero cervical angle - Bacterial inoculation - Uterine contraction 2.Technique - catheter guidance - catheter tip location - injection mode
- 61. 3. Catheter - Soft versus firm - Internal diameter - Tip shape 4.Transfer medium - Medium/Air volume - Viscosity - Adherence compounds
- 62. ET practices with supported proof benefit Use of soft embryo catheters Ultrasound guidance
- 63. 1. Mid uterine position of catheter tip. 2. Mechanical closure of the cervical canal following ET. 3. Acupuncture during ET 4. Use of hyaluronic acid during ET 5. Shortening of the loading discharging interval time of embryos. ET practices with Limited proof benefit
- 64. 1. Use of mock transfer. 2. Full bladder during ET. 3. Use of cervical tenaculum. 4. Removal or flushing of cervical mucus. 5. Antibiotic administration during ET. 6 .Bed rest following ET. 7 Use of fibrin sealants during ET. ET practices with no proof benefit
- 65. Human endometrium –The last challenge
- 66. Strategies for improving endometrial receptivity To develop ovarian stimulation protocols- minimal reduction of receptivity or increase it. To avoid the endometrium during stimulated cycle- Freezing the embryo and replacing in subsequent natural cycles. To increase uterine vascularity- Low dose aspirin, L-arginine, Sildenafil. To treat the uterine pathology. 5.Local injury stimulates the endometrium.
- 67. Luteal phase support Corpus luteum A major source of steroid hormone and secretes progesterone upto 40mg/day. LPS is definitely indicated in IVF treatment cycle.
- 68. When to start progesterone Day of OPU How long Debatable 1. Upto 8weeks or 12 weeks 2. Upto 1st ultrasound scan 3.Upto establishing pregnancy
- 69. What is the route 1.Oral-micronised 600-800mg/day in a divided dose. 2.Vaginal/ Rectal- micronised 600-800mg/day in a divided dose. 3. I/M 50-100mg/day 4. S/C Aqueous 25mg/day 5. Dydrogesterone-10mg twice daily 6. Gel 8%-90 mg once daily
- 70. No evidence favoring a specific route or duration of administration of progesterone.
- 71. Maximize Beneficial Effects Minimize Complications and Risks Cycle Cancellation Multiple Pregnancy OHSS Failure Singleton live birth at term
- 72. Cumulative pregnancy is a key strategy to optimize success in ART.
- 73. Prof. Syeda Nurjahan Bhuiyan