This document discusses embryo development and factors that influence IVF outcomes. It summarizes key stages of embryo development from fertilization through blastocyst formation. It identifies the woman's age, controlled ovarian stimulation protocol, and embryology laboratory as factors governing embryo aneuploidy and IVF success. The document provides details on different ovarian stimulation protocols and considerations for individual patient factors like ovarian reserve, previous response, and risk of over or underresponse.

1. GEOFFREY SHER M.D.

2. Submit additional questions
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Or my blog:
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4. THE MOST IMPORTANT
DETERMINANT OF IVF OUTCOME:

5. Embryo Development
Fisch et al., 2001
16-18 Hrs. Post Fertilization
Day 2 - Cleaved Embryo
Day 3 - 8-Cell Embryo
Day 5-6: Expanded Blastocyst

6. Embryo “Competence”

7. Embryo “Competence”

10. MATURE EGG (M-2)

11. Meiosis
Meiosis

13. Blastocysts (Hatching)

15. No embryology laboratory can
yield “competent” quality
embryos out of “aneuploid”
eggs!

16. Factors in IVF that Govern
Embryo Aneuploidy
 Woman’s age
 Protocol for controlled ovarian stimulation
(COS)
 Embryology Laboratory

17. Determining the Best Protocol for
Controlled Ovarian Stimulation
1. Age
2. Ovarian Reserve (FSH/AMH/inhibin-B)
3. Previous Response to COS

18. Orchestration of Follicle/Egg Development
 IN THE STROMA:
 LH promotes production by stroma/theca of male hormone
(androgen)
 IN THE FOLLICLE:
 FSH converts testosterone to estradiol
 THE EGG IS THE CONDUCTOR OF FOLLICLE EVENTS

19. Ovary
Stroma/Theca
(Produces Androgen)
Follicle
Egg
Granulosa Cells
(Produce Estrogen)

20. Role of Ovarian Male Hormones (Androgens)
A small amount testosterone is essential for
follicle and egg development
Excessive testosterone is a cause of poor
follicle and egg development.

21. Who is Most Vulnerable
to Excessive Androgens?
 Older Women
 Women with ovarian Lesions (cysts,
endometriomas & tumors)
 Women with polycystic Ovarian Syndrome
(PCOS)

22. Effects of Excessive Androgens
 Poor-follicle development (premature luteinization,
“empty” follicles)
 Poor- egg/embryo quality (increased aneuploidy)
 Poor- endometrial development
 Poor-endometrial development and implantation rate
 Poor -IVF Success

23. What leads to Increased Exposure to
Androgens?
 HIGH LH
 Age
 Ovarian resistance / failure
 PCOS
 INAPPROPRIATE OVARIAN
STIMULATION PROTOCOLS
 “Flare protocols”
 Clomiphene
 Menotropins
 OVARIAN LESIONS
 Endometriomas
 Functional cysts
 Tumors
 ANDROGEN ADMINISTRATION
 Testosterone
 DHEA?

24. How to Limit Exposure to Androgens
 Limit exposure to exogenous LH
Use purified FSH
 Treat ovarian lesions pre-COS
 Endometriomas
 Cysts
 Suppress endogenous LH pre-COS
 Use “long” GnRH agonist / antagonist protocols (esp.
in DOR and PCOS)
 Avoid “flare” protocols (esp. in DOR & PCOS)
 Avoid Clomid/Femara


25. Drugs Used for Ovarian Stimulation

Clomid/Femara

Gonadotropins (Folistim, Puregon, Gonal-F ,Bravelle, Menopur)

Agonists (Lupron, Superfact)

Antagonists (Ganirelix, Cetrotide, Orgalutron)

hCG (Pregnyl, Profasi, Novarel, Ovidrel)

Estrogen (I.M. estradiol valerate, estrogen skin patches, oral
estrace)

26. Long Pituitary Agonist-Down-Regulation
Protocol
Agonist (Lupron/
Buserelin)
FSH(Follistim/
Gonal-F/
Puregon)
10 days +
Menses
5-10 days
Menses
7-14(+) days
hCG 10,000U
Ovidrel 500mcg

27. Agonist/ Antagonist Conversion Protocol
(A/ACP)
BCP
Agonist
(Lupron/
Buserelin)
10 days +
Menses
5-10 days
Menses
Antagonist
(Ganirelix/Cetrotide/Orgalutron)
FSH
(Follistim)
FSH
+HMG
(Menopu)
7-14 (+) days
hCG 10.000U
Ovidrel 500mcg

28. Short Agonist (Micro) “Flare” Protocol
Agonist (Lupron/
Buserelin)
7-14(+) days
Spontaneous
Menstruation
FSH(Follistim/
Gonal-F/
Puregon)
hCG 10,000U
Ovidrel 500mcg

29. Short Antagonist Protocol
Antagonist
(Ganirelix/’Cetrotide/Orgalutron)
FSH(Follistim/
Gonal-F/
Puregon)
Day 6-8
Menses
hCG 10,000U
Ovidrel 500mcg

30. Mini-IVF / EZ-IVF
Clomiphene/
Femara
Day 2
Menses
Day5
(Menotropin)
+/7-10 (+) days
hCG 10.000U
Ovidrel 500mcg

31. Natural Cycle IVF
(Monitoring)
US/ blood LH
Day 1
Menses
Day 10
+/-hCG 10.000U
Ovidrel 500mcg

32. Additional Considerations
1. Under-response
A/ACP+E2V
 Human Growth hormone
 DHEA
 Egg Donor
Over-response (Hyperstimulation - OHSS)
 “Prolonged Coasting”
Thin Uterine Lining
 Viagra
Premature Luteinization (“Premature LH Surge”)
“Empty Follicle” Syndrome

2.
3.
4.
5.

33. Under-Response

A/ACP + E2V

Human Growth Hormone (HGH)?

DHEA??

Egg Donor

34. Agonist/ Antagonist Conversion with
Estrogen Priming (A/ACP+ E2V)
BCP
Agonist
(Lupron/
Buserelin)
Antagonist
(Ganirelix/Cetrotide/Orgalutron)
Estrogen
(E2V)
FSH
(Follistim)
Priming
10 days+
Menses
5-10 days
7-10 days
Menses
5 days
FSH +
Menotropin
(Menopur)
4-14 days
hCG

35. Who Can Benefit from A/ACP + E2V?
1. Advanced Maternal Age: (41+)
2. Women With Decreased Ovarian Reserve:
(AFC/AMH/FSH)

36. Over-Response/Hyperstimulation (OHSS)
“Prolonged Coasting”

37. Preventing Severe Ovarian Hyperstimulation
Syndrome (OHSS) through “Prolonged Coasting”
Agonist
FSH
>25 follicles
(50%=14MM+)
E2 = >2500pg/ml
7-10 days
36 hrs
E2=<2500pg/ml
2-5days
STOP FSH!!
Initiate “coasting”
Stop
ER
“coast”
+
hCG-10,000U

38. A THIN UTERINE LINING & VIAGRA
1.
2.
3.
4.
5.
6.
Endometritis
Surgical
Clomiphene
DES
PCOS
Reduced uterine blood flow

Age

Adenomyosis

fibroids

39. Endometrial Lining (Pre-Viagra)

40. Endometrial Lining (Post-Viagra)

41. Triggering Ovulation 36 Hrs. Prior to ER
 hCGu 10,000 IU (Pregnyl/Profasi/Novarel)
 hCGr (Ovidrel), if used ideally should be 500mcg.
 Criteria:
 2 lead follicles at least 18mm in diameter
 1/2 of total number of follicle at least 15mm in
diameter
 Endometrial lining at least >9mm with trilaminar
pattern

42. Thank You!
If you would like to schedule a
consultation with Dr. Sher,
please call 1-800-780-7437
Read Dr. Sher’s Blog at:
www.IVFauthority.com
SIRM Website: www.haveababy.com