fertility options: ivf overview
DESCRIPTION
Mark Perloe, MD Atlanta, 404-843-2229 Learn about the factors that can adversely affect fertility and the tests that can help pinpoint problems. Fertility treatment options including IVF and other high tech options are presented.TRANSCRIPT
Fertility Options
Mark Perloe, M.D.Georgia Reproductive
Specialists
Objectives
• Discuss general fertility factors
• Describe basic evaluation and treatment
• Describe Assisted Reproductive Technology (ART) at GRS
• Understand fertility preservation options
Fertility Preservation
• Indications– Chemotherapy, radiation therapy, surgery– On-hold for career– Haven’t found partner
• Criteria: Age, Antral follicle count, AMH
• Success: 2-5% chance for each stored oocyte
• Cost: – Cryopreservation cycles: ~$9-$21,000 (1-3x)– Thaw, culture & transfer: $5,000
Infertility….
• Inability to conceive after an interval of unprotected intercourse
• One year for women under 35• Six months for women over 35
• Medical history and physical findings may dictate earlier evaluation and treatment
Scope
• At any given time, 10% of reproductive age couples seeking conception are unable to do so6.1 million women and their partners
• 15% of all reproductive age women have an infertility-related office visit each year
• Half of couples experiencing fertility problems never seek treatment
Fertility Factors
• Ovulation factors 25%
• Male factor 40%
• Tubal/anatomic factors 35%
• Endometriosis 35% or more
• Multiple factors 25%
• Unexplained 30%
0
20
40
60
80
100
1 3 5 7 9 11Months
% women pregnant
Cumulative frequency of pregnancy in couples
trying to conceive
Let’s look first at how easy, or difficult, it is to get pregnant…
Fecundity
Oocyte
Membrana granulosa
Theca interna
Basement membrane
Graafian follicle
Antrum
-50 -4 +10-9 +1-180
Time (days)
0
Very little atresia
Ovulation
Corpusluteum
Large antral
Recruited
Growing
50 - 80% atresia
Primordial SmallAntral
Pre-ovulatory
Possible time of action of nutrition on folliculogenesis
Selecte
d
The cleavage divisions produce cells called blastomeres.
Embryo Cleavage
Fertilization occurs in the ampulla of the oviduct, implantation in the uterus.
Motile systems are important: cilia and smooth muscle.
The Fallopian tube produces secretions which control and provide a vehicle for transport.
Control over embryo transport may also operate at the ampullary isthmic junction and at the utero-tubal junction.
Implantation at the blastocyst stage
Fertilization
Embryo enters uterus after about 4-5 days
Embryo transport
Hatching from zona
The zona pellucida must be lost before the embryo can contact the uterine epithelium.
Observations in vitro suggests that the blastocyst squeezes out of fractures in the zona (“hatches”).
Identical twins may be produced if the embryo breaks into two during this process.
Empty zona
Zona free blastocysts
The syncytiotrophoblast proliferates and invades the extracellular matrix of the stroma.
Cytotrophoblast cells migrate between the syncytia, followed by fetal stroma - leading to placental villi.
Implantation
Ovulation Factors
• Insulin resistance– PCOS, hyperandrogenism
• Hypothalamic dysfunction– Exercise induced, eating
disorders, stress
• Pituitary disorders– hyperprolactinemia
• Ovarian Failure– Chemotherapy, Age, Surgery
Polycystic Ovary Syndrome
• Low glycemic diet
• Metformin, TZD, GLP-1
• Exercise
• Ovarian drilling
• Clomiphene/letrozole
• Injectable gonadotropins– OHSS risk– High multiple birth rate
• IVF or IVM
PCOS Ovarian Drilling
65-85% success
not effective in smokers
1/3 require ovulation meds
requires surgery
adhesion formation
Endometriosis
• Presence of uterine lining in locations outside the uterus
• 35-55% of infertile women demonstrate endometriosis at laparoscopy
• Not all women with endometriosis have infertility
• Surgical treatment and Lupron do not enhance success rates
Age related infertility
Reduced pregnancy rates
Increased miscarriage rates
Increased risk fetal anomalies
Pregnancy, Live Birth, and Singleton Live Birth by Age,* 2001
0
10
20
30
40
50
Age (years)
Perc
enta
ge
Pregnancy rate Live birth rate Singleton live birth rate
*For consistency, all rates are based on cycles started.*For consistency, all rates are based on cycles started.
Miscarriage Rates by Age, 2001
0
10
20
30
40
50
60
Age (years)
Per
cent
age
Male Factor Infertility
• Causes– varicocele– infection– smoking– genetic– cancer, radiation, chemorx– hot tub– bicycle riding– medications
• Testing– Semen analysis– SCSA/SDFA: DNA
fragmentation
Sperm Chromatin Structure Assay
SCSA®/SDFA test is a good predictor, relative to other sperm measures, for the clinical diagnosis of male infertility
Uterine Evaluation
Uterine Fibroids
5. Analyze ResultsReal-time continuous monitoring with 3D dose accumulation and thermometry determines whether treatment can proceed as planned or has to be changed.
This interactive process continues until the entire region of treatment has been ablated.
Congenital Uterine Anomalies
Bicornuate
Vs
Septate
Uterus
Hydrosalpinx
Abnormal Hysterosalpingogram
Pelvic Adhesions
Hydrosalpinx
What do we know about pregnancy losses??
6 20 40
Weeks gestation
100
50
%
Pregnancies can easily berecognized clinically by 6 wks.
Ovulation rates are high!
So probably are fertilization rates!
Early human embryos may show a high incidence of developmental abnormalities.
10-15% of of all clinically recognised
pregnancies are lost in the 1st trimester; 2-3%
are lost later.
50% of these losses have cytogenetic
abnormalities.
1/3 of all pregnancies are lost soon after implantation - before they are clinically recognised.
Unexplained InfertilityUnexplained Infertility
Letrozole or Clomid/IUI
Letrozole/HMG/IUIIVF
Injectable Gonadotropins
Assisted Reproductive
Technology (ART)
• In vivo = inside the body• In vitro = in glass = outside the body• IVF = in vitro fertilization
• ART involves both the sperm and the egg in the laboratory
• Fertilization and early embryo development usually achieved in vivo accomplished in vitro
In vitro fertilizationScreening
Optimize reproductive health
Psychological counseling
Financial counseling
Nursing education
Ovarian hyperstimulation
Egg retrieval
Embryo culture
Embryo transfer
Cryopreservation
The wait!
Lifestyle
• Smoking– Up to 13% of infertility problems may be
attributable to smoking– Conception delay– Egg depletion and diminished quality– Higher miscarriage rates, ectopic pregnancies– Passive smoking equivalent to active smoking– Possibly lower IVF delivery rates– Male smoking may pose greater risk
Emotional Support
• Psychological counseling requirement prior to cycle initiation; continued referral as necessary
• Patient support groups, AFA, INCIID, RESOLVE
• “Mind, Body…Baby” Program– Acupuncture– Massage– Exercise– Support
Financial Support
• Assisted Reproductive Technology Financial Options– “Making IVF Affordable Plan”
• Includes all Frozen Embryo Transfers• No “Hidden Fees” for extra visits or ICSI• FREE second IVF treatment cycle
– Shared Risk Program Refund IVF– Global Fee IVF– Global Frozen Embryo Transfer– IVF PLUS– Advanced Reproductive Care (ARC) financing
• 60% of patients have some degree of insurance coverage
IVF Overview
• Stimulation phase ~ 8-12 days– Over-ride usual ovulation status– Intentionally hyperstimulate ovaries with
injectable hormones– Monitor closely with vaginal ultrasound and
blood hormone levels– Anticipate 4-6 clinic visits
IVF Overview
• Retrieval ~ 20 minutes– Outpatient minor surgery under IV sedation– Vaginal ultrasound guided oocyte retrieval– All visible follicles entered and aspirated– Recovery ~ 1 hour in clinic, remainder of day
at home– Goal: multiple eggs to work with in the
laboratory
IVF Overview
• Laboratory ~ 3-5 days– Provide semen specimen– Combine sperm and eggs at appropriate
intervals– Inject sperm into eggs as required– Incubate and allow to grow for 3-5 days– Embryologists update patients regarding
progress
IVF Overview
• Transfer– Plan transfer for Day 3 or 5 after retrieval– Abdominal ultrasound visualization requires a
FULL bladder; Valium available– Transfer catheter containing embryos
threaded though cervix– Embryos gently injected into uterus– Normal activity after transfer
IVF Overview
• Number of embryos transferred based on patient age and embryo quality– General for Day 3:
• < 35 years: 2-3 embryos• 35-37: 3 embryos• 38-40: 3-4 embryos• >40: 4-5 embryos
– Blastocysts (Day 5): 2 embryos up to age 40
Embryos
• Day 3 • Day 5
IVF Overview
• 14 days after retrieval…– Check pregnancy test
• Progesterone supplementation from just after retrieval until outcome known– Intramuscular progesterone– Continues through the 10th week of pregnancy
Special Issues
• ICSI • PGD
2007 GRS IVF Statistics
Age <35 35-37 38-40 >40 Donor
# cycles 105 63 39 12 28
birth/cycle 33.3% 27.0% 28.2% 2/12 60.7%
Avg # ET
%Twins
%FET del
2.3
29.2
30.8
2.4
29.2
33.2
2.9
7.6
42.8
3.3
-
-
2.0
-
36.8
Success Rates: What do they mean?
32.8
27.0
31.433.4
20.2 21.4
0
10
20
30
40
50
Per
cen
tag
e
PregnanciesPregnanciesper cycleper cycle
Live birthsLive birthsper retrievalper retrieval
Live birthsLive birthsper cycleper cycle
Live birthsLive birthsper transferper transfer
Singleton Singleton live births live births per transferper transfer
Singleton Singleton live births live births per cycleper cycle
Live Births per Transfer and % Multiple Births in Women <35 by Number of Embryos Transferred, 2001
0
10
20
30
40
50
60
1 2 3 4 5 +
Number of embryos transferred
Live
birt
hs p
er tr
ansf
er
(per
cent
)
Singletons Twins Triplets or more
(100.0)*(100.0)* (59.3)*(59.3)*
(39.6)*(39.6)*
(53.4)*(53.4)*
(38.8)*(38.8)*
(7.8)*(7.8)*
(49.1)*(49.1)*
(41.3)*(41.3)*
(9.6)*(9.6)*
(43.3)*(43.3)*
(46.8)*(46.8)*
(9.9)*(9.9)*
*Percentages of live births that were singletons, twins, and triplets or more are in parentheses. *Percentages of live births that were singletons, twins, and triplets or more are in parentheses. Note: In rare cases a single embryo may divide and thus produce twins. For this reason a smallNote: In rare cases a single embryo may divide and thus produce twins. For this reason a smallpercentage of triplets resulted when two embryos were transferred.percentage of triplets resulted when two embryos were transferred.
30.030.0
51.751.746.946.9
42.942.9 43.143.1(1.2)*(1.2)*
Live Births per Transfer Using Fresh Embryos From Own and Donor Eggs,
by ART Patient’s Age, 2001
0.0
10.0
20.0
30.0
40.0
50.0
60.0
25 27 29 31 33 35 37 39 41 43 45
Age (years)
Per
cen
tag
e
Live births per transfer (Donor Eggs)
Live births per transfer (Own Eggs)
Success Rates vs. Multiple Births
Type of ARTType of ART
Embryo Evaluation “omics”• GENomics
– FISH– CGH– SNPs
• TRANSCIPTomics– Gene transcription
• PROTEomics– Proteins– Secretomics
• METABOLomics– Metabolites– Amino Acids
GRS
• Meridian Mark– Drs. Perloe, Kaplan and
Singleton
• Alpharetta– Dr. Conway
• DeKalb Medical Center– Dr. Kaplan
Please join us for a complimentary 20 minute visit….Please join us for a complimentary 20 minute visit….