OVARIAN STIMULATION: WHEN DOES LESS ACHIEVE MORE? Milton K.H. Leong, M.D. IVF Centre Hong Kong...
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Transcript of OVARIAN STIMULATION: WHEN DOES LESS ACHIEVE MORE? Milton K.H. Leong, M.D. IVF Centre Hong Kong...
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OVARIAN STIMULATION:WHEN DOES LESS ACHIEVE MORE?
Milton K.H. Leong, M.D.
IVF Centre
Hong Kong Sanatorium & Hospital, China
Overview and Introduction
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LEARNING OBJECTIVESAt the conclusion of this presentation, participants
should be able to:
1. Explain the developmental steps in human IVF
2. Outline the disadvantages of conventional IVF approaches
3. Describe the strategies to overcome the disadvantages of conventional IVF treatments
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DISCLOSURE
Milton K.H. Leong, M.D.
None
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History
• 1890s - Walter Heape; transferred embryos from one mother to another in rabbits
• 1959 – Chang; successful IVF in rabbits
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History;The first pregnancy achieved following in-vitro human fertilisation of a human oocyte
• De kretzer D et al. Transfer of a Human Zygote. Lancet. 1973; ii: 728-729
• a biochemical pregnancy
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First test-tube baby
• natural cycle
• laparoscopic oocyte retrieval
• one mature oocyte
• IVF
• born in July 25, 1978
Steptoe PC, Edwards RG (1978). "Birth after the reimplantation of a human embryo". Lancet 2 (8085): 366
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Candice Reed born in Melbourne in 1980
• It was the subsequent use of stimulated cycles with clomiphene citrate and the use of human chorionic gonadotrophin (hCG) to control and time oocyte maturation, thus controlling the time of collection.
Trounson AO, Leeton JF, Wood C, Webb J, Wood J. Pregnancies inhumans by fertilization in vitro and embryo transfer in the controlledovulatory cycle. Science. 1981;212:681-2
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Controlled Ovarian Stimulation
• The Jones team in Norfolk, Virginia, further improved stimulated cycles by incorporating the use of a follicle stimulating hormone (uHMG).
• Then became known as controlled ovarian hyperstimulation (COH)
Jones HW Jr. et al. The program for in vitro fertilization at Norfolk Fertil Steril.1982;38:14-21
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Later steps in human IVF
• Transvaginal oocyte retrieval
• Gn Agonist
• Gn antagonist
• Embryo cryopreservation
• ICSI
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0
10
20
30
40
50
60
0 1 3 5 6
20-24
25-29
30-34
35-39
40-45
N
% c
um
ula
tive
co
nce
pti
on
rat
e
Number of cycles/months
Age-Specific Cumulative Conception Rates
Tan et al, Lancet, 1990; 229Tan et al, Lancet, 1992; 1390-1394
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Conventional IVF
• pregnancy and livebirth rates are higher with IVF than following natural conception in fertile couples
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Pregnancy is more likely with multiple embryos transferred
Cochrane
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Desire for pregnancy
Transfer of Multiple embryos
Ovarian stimulation
Increased chance of pregnancy
More oocytes retrieved
More embryos available Freeze the surplus embryos
Risk of OHSS
Medication side effectsCost of medication
Multiple pregnancy risk
Conventional IVF
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Conventional IVF;concerns
• high success rates achieved at the expense of OHSS and multiple pregnancy
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Multiple Pregnancies• Multiple pregnancies(MP) have increase
during the last 30 years.
• Main reason ART
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Noted trends in multiple births in USA
For twin (upper) and triplet or higher order (lower) multiple births.
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Risks of multiple pregnancy
• Obstetric– Miscarriage– Fetal reduction– Pregnancy complications
• Anemia• Pre-eclampsia• Gestational diabetes• Growth retardation
– C/S– Post-partum hemorrhage– Mortality
• Postnatal– Infection– Bleeding– Isolation, stress, depression– Bonding with child or children
Perinatal Prematurity Low birth weight Mortality, morbidity Malformations
Long-term Cerebral palsy Disability Learning difficulties Infant mortality Adult health risks
Maternal Child Family Single-survivor
Guilt Blamed by parents
Sibling Attention deficit Delayed
development Parents
Stress Isolation, depression Divorce
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Multiple pregnancy – preterm delivery
Blickstein I. Does assisted reproduction technology, per se, increase the risk of preterm birth? BJOG 2006;113(Suppl. 3):68–71. Based on data Martin JA et al. Births: final data for 2003. Natl Vital Stat Rep 2005;54:1–116.
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Conventional IVF;Concerns
• 40% of children born as a result of IVF/ICSI are twins.
• These babies had a 7,4-fold increase in delivery before 32 weeks compared to singletons.
• Also, significant increases in stillbirth, C/S and admission to the NICU.
Pinborg A et al., 2004. Neonatal outcome in a Danish national cohort of 8602 children born after in vitro fertilization or intracytoplasmic sperm injection: the role of twin pregnancy. Acta Obstet et Gynecol Scandinavica 83, 1009-
1011.
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Conventional IVF;Concerns
• Maternal well being in IVF/ICSI twin pregnancies was compromised with a significant increase in sick leave and hospitalization compared with singleton IVF/ICSI pregnancies.
Pinborg A et at. 2004 Maternal risk and perinatal outcome in a Danish national cohort of 1005 twin pregnancies:the role of in-vitro fertilization. Acta Obstet et Gynecol Scan 83, 75-84.
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Conventional IVF;Concerns
• The cost to the healthcare budget of multiple births is considerable.
• average hospital cost per multiple gestation delivery is greater than the average cost of IVF and ICSI cycles
European Society for Human Reproduction and Embryology Capri Workshop, 2000.
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OHSS• incidence of severe OHSS 0.6 to 1.9% but may
be as high as 6% in high-risk groups; e.g., young women with PCO
• although there are a number of strategies to predict and prevent this potentially life-threatening complication, none is universally successful
• only reliable way is to avoid ovarian stimulation
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Other disadvantages of conventional IVF
• Cost of medication• Immediate side effects of the stimulation
hormones• Long-term health implications of the
gonadotropins– The long-term effects of conventionally stimulated
cycles have thrown up the possibility of an increased risk of endometrial cancer but not of ovarian cancer (Brinton, 2004; Althuis et al., 2005)
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Conventional IVF;Concerns
• endometrial receptivity may be adversely affected by ovulation induction therapy.
• This may be due to advanced endometrial maturation and dysfunctional progesterone receptor activity.
•Basir GS et al., 2001 Morphometric analysis of peri-implantation endometrium in patients having excessively high-oestradiol concentrations after ovarian stimulation. Human Reprod 6,435.•Devroey P et al., BCJM 2004 Reproductive biology and IVF: ovarian stimulation and endometrial receptivity. Trends in Endocrinology and Metabolism15, 84-90.
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Conventional IVF;Concerns
• ovulation induction may induce oocyte abnormalities.
• The reduced viability of in-vitro matured oocytes from stimulated cycles could be related to a significantly higher proportion of chromosomal abnormalities
Magli MC et al. 2006 First meiosis errors in immature oocytes generated by stimulated cycles. Fertiliand Steril 86, 629-635.
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• OHSS None / minimal ovarian
stimulation
• Multiple pregnancy SET
Reduce cost
Dilemma: These measures will result in lower pregnancy rate ?
Strategies to overcome the disadvantages
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Some countries changed policy to decrease multiple pregnancy rates
Kallen B et al., Temporal trends in multiple births after in vitro fertilisation in Sweden, 1982-2001: a register study. BMJ 2005;331;382-383.
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Twinning rates have dropped without significant decrease in overall PR-Belgium
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Less embryos to transfer
• Need of less oocytes
• Less stimulation
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Less aggressive approaches
• Natural cycle IVF
• Minimal stimulation IVF
• IVM
• Natural cycle IVF/IVM
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Opposition from patients
• Cost of treatment
• Insurance
• Patient education
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Acknolwedge
Dr. Ezgi Demirtas
Reproductive Centre
McGill University