an ivf cycle typically includes the
TRANSCRIPT
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An IVF cycle typically includes the following steps or procedures:
Medications to grow multiple eggs Retrieval of eggs from the ovary or ovaries Insemination of eggs with sperm Culture of any resulting fertilized eggs (embryos) Placement (“transfer”) of one or more embryo(s)
into the uterus Support of the uterine lining with hormones to
permit and sustain pregnancy
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Medications for IVF Treatment
The success of IVF largely depends on growing multiple eggs at once
Injections of the natural hormones FSH and/or LH (gonadotropins) are used for this purpose
Additional medications are used to prevent premature ovulation
An overly vigorous ovarian response can occur, or conversely an inadequate response
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Gonadotropins
Menopur
Bravelle
Follistim Gonal-F
FSH/LH
r FSH
hp FSH
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Gonadotropin Side Effects Breast fullness/tenderness Pelvic discomfort Headache Ovarian cyst formation Nausea Intermenstrual bleeding Diarrhea Flatulence Changes in libido Emotional lability
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Premature Luteinization In Ovulation Induction
Early secretion of progesterone prior to ovulation
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Medications Used In IVF Ovarian Stimulation To Block Premature Progesterone Release
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Ovarian Stimulation -GnRH Antagonist
1 2 3 4 5 6 7 8 9 Cont. hCG +2 Ret. + 3 Ret. + 5 Cont.
Gonadotropins hCG Ret. Embry
o trans.
OR Blast. Trans.
Antagonist
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Use Of GnRh Antagonist To Cause Down Regulation Of
LH/FSH Prior To Stimulation
Lupron Gonadotropins
Progesterone
hCG Retrieval
Transfer
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Use Of Lupron Flare For Poor Responders
Gonadotropins Progesterone
hCG Retrieval
Transfer
Lupron
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Human Chorionic Gonadotropin (hCG)
Placental Luteinizing Hormone-like protein
10x stronger than LH Effects:
– Matures eggs (meiosis) – Stimulates progesterone secretion – Causes follicle release ~38-40 hours
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Preparations of Human chorionic gonadotropin (hCG):
Profasi® Novarel® Pregnyl® Ovidrel®
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hCG Side Effects (in ~15 – 25 %)
Breast Tenderness/Fullness Mood Changes Water
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Other Medications Possibly Used During The Cycle
Oral contraceptive pills Other medications Antibiotics Low dose aspirin Medrol (glucocorticoid) Metformin Progesterone
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Monitoring Ovarian Stimulation
Transvaginal ultrasound scanning: - No. & size of follicles - Pattern & thickness of endometrium Estrogen blood level
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Complications: Ovarian Hyperstimulation Syndrome (OHSS) Mild: < 5% (50% of pregnancy
cycles) Ovaries <5 cm
Moderate: 1-2% <10 cm
Severe: << 1% >10 cm
Risk Factors Treatment
Interstitial fluid accumulation
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Severe Ovarian Hyperstimulation Syndrome
(OHSS)
Prevention High protein diet Hydration Medications(e.g cabergoline)
Treatment Cryopreservation of all
embryos Coasting Lupron Trigger Cancellation of IVF Cycle
Interstitial fluid accumulation
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In Vitro Procedures
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Transvaginal Egg Retrieval Eggs are removed from the ovary with a
needle under ultrasound guidance Anesthesia is provided to make this
comfortable Injury and infection are rare but possible Bleeding Tissue damage/trauma Anesthesia complications Failure to recover eggs
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In Vitro Fertilization and Embryo Culture
Sperm and eggs are placed together in specialized conditions (culture media, controlled temperature, humidity and light) in hopes of fertilization
Culture medium is designed to permit normal fertilization and early embryo development
Embryo development in the lab helps distinguish embryos with more potential from those with less or none
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Semen Preparation
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Lab staff analyzing
sperm
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Micromanipulation
Intracytoplasmic Sperm Injection (ICSI)
Assisted Hatching
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Intracytoplasmic Sperm Injection (ICSI)
ICSI is used to increase the chance of fertilization when fertilization rates are anticipated to be lower than normal
Overall fertilization rates with ICSI of mature eggs are higher than for standard IVF insemination
ICSI will not improve oocyte defects
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1.4% increase in inherited abnormalities – related to severity of sperm factor
Men with very low sperm count (< 5 million) are at
higher risk of carrying genetic abnormalities that could be passed on to offspring
In some cases male offspring at risk for low sperm
count/infertility – Y chromosome microdeletion
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Assisted Hatching
Assisted Hatching involves making a hole in the outer shell (zona pellucida) that surrounds the embryo
Hatching may make it easier for embryos to escape from the shell (egg wall) which surrounds them
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Embryo Development
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A Fertilized Egg (2PN Stage or
2 Pro Nuclear Stage)
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2 Cell Embryo
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4 Cell Embryo (typically day 2 post retrieval)
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8 Cell Embryo (typically day 3)
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A Blastocyst (day 5 or day 6)
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Potential Embryo Problems
Laboratory problems Natural disaster Hurricanes Floods Power outage
No fertilization Abnormal fertilization/failure to grow
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Testing an embryo when inherited risk is known
Biopsy at the blastocyst stage Cells subjected to the genetic test Identifies which embryo(s) to transfer
Types of test:
CGH for whole chromosome analysis Blastocyst must be frozen after biopsy with
embryo transferred in subsequent cycle 1% chance of error
PGD (Pre-implantation Genetic Diagnosis)
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PGS (Pre-implantation Genetic Screening)
No pre-existing known abnormality in the parents
Screening for chromosome copy number
Benefit most notable in women of advanced maternal age, recurrent pregnancy loss and unexplained IVF failures
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Embryo Transfer After a few days of development, the best appearing
embryos are selected for transfer The number chosen influences the pregnancy rate and the
multiple pregnancy rate A woman’s age and the appearance of the developing
embryo have the greatest influences on pregnancy outcome Embryos are placed in the uterine cavity with a thin tube Excess embryos of sufficient quality that are not transferred
can be frozen
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Blastocyst Transfer
Highly specialized sequential culture media which supports embryonic growth after 72 hours in tissue culture
These nutrients are required for continued development in vitro
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Blastocyst Transfer
Allows for self selection of “robust” embryos in extended culture and optimal in patients under the age of 38 years.
Reduced number blastocyst transfer with higher implantation rate
Theoretically more mature blastocyst for cryopreservation (but decreased number)
Some risk as ~5% will not continue to grow Increased cost – time/media
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Is Blastocyst Culture For Everyone?
Blastocyst Culture is optimal for those under the age of 38.
In patients over the age of 38 or with diminished ovarian reserve, transfer may be performed on Day #3 as embryos from these patients may not tolerate extended culture conditions.
We have noted an improvement in pregnancy outcomes for patients in this category.
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High quality blastocyst embryos available Almost guarantees a singleton pregnancy Lower risk of maternal complications in pregnancy Lower risk of premature delivery Allows other embryos to be frozen and used in the future
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Hormonal Support of Uterine Lining
Successful attachment of embryo(s) to the uterine lining depends on adequate hormonal support
Progesterone, given by intramuscular or vaginal route, is routinely given for this purpose
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Potential Risks of Transfer
Infection
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Indications for Cryopreservation To reduce the risks of multiple gestation To preserve fertility potential in the face of certain
necessary medical procedures (e.g., cancer treatment)
To increase the chance of having one or more pregnancies from a single cycle of ovarian stimulation
If the risks for OHSS or other stimulation related complication are high, then all embryos may be frozen to be used safely in the future
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Cryopreservation of Embryos
Slow freeze Rapid freeze Vitrification
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Embryo Storage Dewar
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IVF Outcome Data
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Do IVF Success Rates Differ by Age?
0.0%
10.0%
20.0%
30.0%
40.0%
50.0%
<35 35-37 38-40 41-42 >42
Live Birth Rates for ART Cycles Fresh vs Frozen Embryos by Age of Woman
Fresh Embryos Thawed Embryos
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How Do Miscarriage Rates Vary Among IVF Patients Of Different Ages?
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Donor Egg IVF
Age of egg donor determines outcome
Pregnancy rates at CRM are between 60-
70% per cycle
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0
10
20
30
40
50
60
25 27 29 31 33 35 37 39 41 43 45
Own EggsDonor Eggs
Age
Live
birt
hs p
er tr
ansf
er (%
)
Live Births per Transfer for Fresh Embryos From Own & Donor Eggs
Donor Oocytes
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Embryo Disposition Freezing extra healthy embryos provides additional
chances for pregnancy without stimulation/egg retrieval required (bonus babies)
Frozen embryos do not always survive the process of freezing and thawing
Freezing of eggs before fertilization is currently much less successful than freezing of fertilized eggs (embryos)
Ethical and legal dilemmas can arise when couples separate or divorce; disposition agreements are essential
It is the responsibility of each couple with frozen embryos to remain in contact with the clinic on an annual basis
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Storage – Options
Thawed and transferred in future Donated Donated to research (not currently
available) Discarded Must be transferred to a commercial
storage facility if not used within two years
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Risks to the Woman with IVF
Ovarian Hyperstimulation Syndrome (OHSS) ~1%
Risks of Pregnancy-related complications
No scientific evidence supporting risk for cancer caused by ovarian stimulation
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Absolute Risk (%) in IVF-conceived Pregnancies
Relative Risk (vs. non IVF-conceived Pregnancies)
Pre-ecclampsia 10.3% 1.6 (1.20 – 2.0)
Placenta previa 2.4% 2.9 (1.5 – 5.4)
Placental abruption 2.2% 2.4 (1.1 – 5.2)
Gestational diabetes
6.8% 2.0 (1.4 – 3.0)
Cesarean delivery 26.7% 2.1 (1.7 – 2.6)
Potential Risks in Singleton IVF Pregnancies
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Absolute Risk (%) in IVF Pregnancies
Relative Risk (vs. non-IVF Pregnancies)
Preterm birth 11.5% 2.0 (1.7 – 2.2)
Low birth weight (< 2500g) 9.5% 1.8 (1.4 – 2.2)
Very low birth weight (< 1500g) 2.5% 2.7 (2.3 – 3.1)
Small for gestational age 14.6% 1.6 (1.3 – 2.0
NICU admission 17.8% 1.6 (1.3 – 2.0)
Stillbirth 1.2% 2.6 (1.8 – 3.6)
Neonatal mortality 0.6% 2.0 (1.2 – 3.4)
Cerebral palsy 0.4% 2.8 (1.3 – 5.8)
Genetic risks
-imprinting disorder 0.03% 17.8 (1.8 – 432.9)
-major birth defect 4.3% (1.5 (1.3 – 1.8)
-chromosomal abnormalities (after ICSI):
-of a sex chromosome 0.6% 3.0
-of another chromosome 4.6% 5.7
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Multiple Gestation Risks Obstetrical Risks
Preterm labor and delivery
Intrauterine Growth Retardation
Pregnancy-induced hypertension
Gestational Diabetes
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Multiple Pregnancy Complications Singleton Twin Triplet Av. Wks at Birth 39 wks 36 wks 32 wks % Very Premature 1.7% 14% 41% Av. Birth Weight (lbs) 7.4 5.3 3.8 % Severe Handicap 1.9% 3.4% 5.7% % Infant Mortality 1.1% 6.6% 19%
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IVF babies may be at a slight increased risk for birth defects
The risk for a multiple pregnancy is significantly higher for patients undergoing IVF, even when only one embryo is transferred
Multiple pregnancies are the greatest risk for babies following IVF
Some risk may also stem from the underlying infertile state, or from the IVF techniques, or both
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Studies reassuring Possible slight increase in hospitalization
and Genito-Urinary surgery (males) No increase in Cancer risk No increase in Neurologic dysfunction
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20 fold increase in twins with ART No difference in risks compared with
spontaneously occurring twins But twins are at higher perinatal risks than
singletons Vanishing twins pose a higher risk for the
surviving fetus(es) than if the pregnancy had started as a singleton (or twin)
Reduced twin pregnancies at higher risk than nonreduced twin pregnancies
Adverse Outcomes Of ART Twins
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Optimizing Natural Fertility
Weight Obesity—increases time to pregnancy
two fold Underweight—increases time to
pregnancy four fold Toxins—decreases fertility
Smoking Alcohol (>2 servings a day) Caffeine (greater than 250 mg/day)
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BMI Severe obesity—defined as a BMI >35 Decreased fertility and implantation Six fold increase in miscarriages Increases the risk of obstetrics and neonatal
complications Obesity in men: Abnormal seminal parameters and
adversely affect male fertility. For the female patient with a BMI of greater than 40
undergoing IVF, the egg retrieval is at the hospital.
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Indications: Any condition that will compromise your future fertility (e.g. cancer, premature menopause, genetic concerns)
Cryopreservation Sperm Oocyte Embryo
Falcone et al, 2007
Fertility Preservation
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Additional Resources
American Society of Reproductive Medicine . www.asrm.org
American Congress of Obstetrics and Gynecology . www.acog.org
Resolve – National Infertility Association . www.resolve.org
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Please Print/Sign the next page and
submit to your nurse.
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Certificate of Completion
In-Vitro Patient Education
We(I) acknowledge reading and understanding the In-Vitro Fertilization process and risks information outlined in the presentation.
______________________________________ __________________________________ Patient Signature Date ______________________________________ Patient Name
______________________________________ __________________________________ Spouse/Partner Signature Date ______________________________________ Spouse/Partner Name