Hold On To Your Dreams

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1 Hold On To Your Dreams Dr. Michael Kettel Dr. Sandy Chuan

2 1. THE BASICS OF IVF & EMBRYO DEVELOPMENT 2. IVF ADD-ONS - MYTH VS. SCIENCE

3 IN VITRO FERTILIZATION 1. Ovarian Stimulation 2. Egg Retrieval 3. Create Embryos 4. Transfer Embryos

4 Conventional Fertilization ICSI: Intracytoplasmic Sperm Injection Fertilization DAY 1 EMBRYO

5 STAGES OF EMBRYO DEVELOPMENT Day 1: Zygote Day 3: Multi-celluar Day 3-4: Compacting Day 4-5: Morula Blastocyst Hatching Blastocyst

6 IVF ADD-ONS Ovarian Stimulation: improving egg quantity/quality Embryo Transfer: Improving implantation Embryo Selection: Choosing the best embryo

7 Ovarian Stimulation Decline in Egg Quality with Time Androgenic Steroids Growth Hormone

8 Ovarian Stimulation Maximizing Egg Quantity & Quality Androgenic Steroids: Testosterone DHEA Increases response to FSH Growth Hormone Effects on Granulosa Cells

9 Embryo Transfer Improving Implantation Embryo Glue Endometrial Scratch New Uterine Eval Assays

10 EMBRYO GLUE Hyaluronan (HA) supplementation of culture medium was introduced to improve implantation and pregnancy rate in IVF-ET cycles.[3] HA is present in the oviduct and uterine fluid and increases at the time of implantation. EmbryoGlue is a human ET medium, which contains high concentration of HA (0.5 mg/ml) and low concentration of recombinant human albumin (rha = 2.5 mg/ml) STUDIES SHOW SOME BENEFIT IN RECURRENT IVF FAILURE RCT NEEDED TO DETERMINE THE DEGREE OF IMPROVEMENT IN PREGNANCY SUCCESS

11 ENDOMETRIAL SCRATCH Procedure to disrupt the endometrium prior to transfer May improve uterine environment and aid in implantation Benefit from 1 month to 7 days prior to embryo transfer when done in the luteal phase

12 ENDOMETRIAL SCRATCH Implantation is a complex process NINE RANDOMIZED CONTROLLED TRIALS MOST STUDIES SHOWED SOME BENEFIT IN PATIENTS WITH UNEXPLAINED INFERTILITY MAY BENEFIT A SUBSET OF PATIENTS WITH IMPLANTATION FAILURE ONGOING DUTCH RANDOMIZED STUDY OF 900 PATIENTS

13 Uterine Evaluation Assays Endometrial Receptivity Assay (ERA) Receptiva

14 Endometrium: Window of Implantation - Endometrium is a complex part of the reproductive endocrine system - Cross talk from the embryo to the endometrium directs implantation - To achieve successful implantation, an embryo must be at the correct developmental stage when the uterus is prepared to accept it. - Window of Implantation - WOI is affected by amount of time endometrium is exposed to progestesterone

15 Endometrial Receptivity Assay Personalized Embryo Transfer NGS analysis of the expression of 236 genes involved in endometrial receptivity

16 Endometrial Receptivity Assay Initial published studies are small in size - 25% of women with repeat implantation failure were nonreceptive - 50% of women who underwent pet became pregnant Awaiting outcomes of larger cohort studies Universal testing prior to all transfers is premature Who should be tested: - Repeat implantation failure : 2-3 transfers : one transfer with good quality egg donor embryo

17 Receptiva Assay Endometrial Biopsy in luteal phase Detects: - BCL-6: Chronic inflammation due to endometriosis/hydrosalpiges - CD138: Chronic endometritis Recommended for women with unexplained infertility, unexplained recurrent pregnancy loss. repeat implantation failure Treatment: Lupron, laparoscopy Pregnancy rate Lessey et all, in women with unexplained infertility, abnormal BCL-6 expression had significantly lower pregnancy rates Almquist et all, if left untreated patients with abnormal BCL-6 had significantly lower pregnancy rates. Awaiting large cohort studies on outcome after treatment

18 Embryo Selection for Transfer Morphological Grading Embryos can be graded on their appearance. Embryos with the best grade are more likely to implant than those with lesser grades. Blastocysts Many critical features of an embryo cannot be seen and are therefore not considered when grading the embryo. Among the invisible features are the chromosomes.

19 CHROMOSOMES

20 GENES There are about 25,000 genes on all 46 human chromosomes, combined

21 Embryo Selection for Transfer Preimplantation Genetic Testing - PGT- A (aneuploidy) 23 PAIRS OF CHROMOSOMES? GENDER XX OR XY Blastocyst Biopsy - PGT-SR (structure rearrangement) - PGT-M (monogenic/single gene defect)

22 Blastocyst Biopsy

23 Who can benefit from PGT? PGT- A (aneuploidy) Embryo selection to increase IVF success rates % of embryos from women years old have abnormal number of chromosomes. Rate increases with female age. 37yo =70% aneuploidy 39yo =90% aneuploidy Family balancing (gender selection). PGT-SR (structure rearrangement) Chromosome translocation PGT-M (monogenic/single gene defect) Carrier of single gene mutations

24 % of normal embryos Incidence of Genetically Normal Embryos by Age % 20 21% 13% 0 Donor Egg < >42 Munne 2012 Years of Age

25 Percent Live Birth in IVF with and without PGS in Women >40 years old Untested Schoolcraft ASRM 2013 PGS

26 Limitations of PGT-A Sometimes the collected cells do not represent the entire embryo ( mosaicism ). Potential harm to embryo. Delay to await results. Require embryo freezing. However, success rates with thawed embryos are similar to fresh transfers at many centers. Little or no improvement in success rates with genetic screening when there is low aneuploidy risk: Young egg source (Age <35). Good quality sperm. Typical egg donation cycles

27 Study by David Barad et al Retrospective National U.S. Study Data from Conclusions: PGS in donor egg cycles has not been associated with improved odds of live birth or reduction in miscarriage rates.

28 Take Home Message IVF treatment is complex The field is ever changing & innovative Still much regarding reproductive physiology we don t understand Takes a long time to accumulate significant data to justify treatments EVERY patient is UNIQUE Our bodies are DYNAMIC Key is to INDIVIDUALIZE care

29 Hold On To Your Dreams Steps to Success El Camino Real San Diego, CA Phone:

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