fertility options: ivf overview

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….