Why IVF Cycles Fail by Dr. Abayomi Ajayi

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WHY IVF CYCLES
FAIL
DR ABAYOMI AJAYI MD.
Nordica Fertility Centre

SYNOPSIS
•Introduction
•Basic requirements for a
successful cycle
•Success rates
•Why cycles fail
•Reducing failure/Improving
success rates
•Conclusion
•Questions?

INTRODUCTION
•Failure of an IVF cycle can
be frustrating to both the
couple and the doctor.
•Anger, disappointment,
dashed hopes, blame
•Money, time, injections,
emotionally tasking
•2week wait (2ww) a
difficult period

INTRODUCTION
Difficult for patients to
understand why after all
apparently went well the
cycle fails
One of most difficult part of
the practice of IVF is to
counsel patients after a
failed cycle.

INTRODUCTION
FAQs
 Why did even one of the embryos not stick?
 Is there something wrong with my womb?
 Do I need to change my womb (surrogacy) or get another source of
eggs or sperms (donor egg/sperm)?
 Should we change hospital or doctor?
 We were told embryos were grade A and beautiful so why didn’t it
work?
 We were told the eggs had successfully fertilized does that not mean
pregnancy has started?
 Is there a guarantee that if I try again it will work?
 What will you do differently if I repeat the cycle?

BASIC REQUIREMENTS
FOR A SUCCESSFUL
CYCLEPlanting (implantation) a
seed(embryo) in the
soil(womb lining)

BASIC REQUIREMENTS
FOR A SUCCESSFUL
CYCLE

BASIC REQUIREMENTS
FOR A SUCCESSFUL
CYCLEGood quality egg

BASIC REQUIREMENTS
FOR A SUCCESSFUL
CYCLEGood quality sperm

BASIC REQUIREMENTS
FOR A SUCCESSFUL
CYCLEProper union of sperm and
egg (fertilization)

BASIC REQUIREMENTS
FOR A SUCCESSFUL
CYCLEGood quality, genetically
normal embryo

BASIC REQUIREMENTS
FOR A SUCCESSFUL
CYCLEGood uterine cavity and
lining

BASIC REQUIREMENTS
FOR A SUCCESSFUL
CYCLEA good, smooth transfer

BASIC REQUIREMENTS
FOR A SUCCESSFUL
CYCLEImplantation of
Embryo(attachment to wall
of the womb)

SUCCESS RATES
Not every woman gets pregnant every time she has
intercourse during her ovulation.
What is the chance of pregnancy monthly?
 Average of 20% (1 in 5 Couples), the others try again next month
Human reproduction is one of the most inefficient
processes in life.

SUCCESS RATES
IVF has a better success rate than natural conception
Averagely 40-50% (1 in 2 or 3 women <35yrs per cycle)

WHY IVF CYCLES FAIL
Egg Quality
 First and most important factor
in analysis of a failed cycle
 The egg contributes most
(80%) of the ingredients for a
good embryo
 Age is a key factor here
 Egg quality and quantity
decline from 30yrs, more
rapidly from 35yrs and by 40yrs
only about 10% of the woman’s
eggs are normal
 Leading to poorer embryos
 More chances of failure
 E.g
 <35yrs 40-50% success rate
 >40yrs with own eggs <10% success
rate
 but with donor eggs 50% success
rate

WHY IVF CYCLES FAIL
Egg quality
 Improper administration of
stimulation drugs
 Improper storage of stimulation
drugs
 Improper timing and
administration of HCG which
matures the eggs

WHY IVF CYCLES FAIL
Sperm Quality
 Abnormal sperms can
contribute to failure
 May appear normal but sperm
DNA(genetic material) may be
damaged
 Eg by exposure to chemicals, tobacco
 If an abnormal sperm fertilizes
an egg, abnormal embryo may
result
 Leading to increased chance of
failure
 Some selection processes like
IMSI, PICSI etc can help

WHY IVF CYCLES FAIL
Embryo Quality
 Important factor in success or
failure
 Good quality embryos better
chance of success
 Poor quality eggs and sperms
can lead to poor quality
embryos
 Lab environment must be
optimal
 Embryos may look beautiful but
be genetically abnormal
 PGD and others can help
select genetically normal
embryos

WHY IVF CYCLES FAIL
Stimulation protocol
 Wrong protocol may lead to
poor response
 Must be individualized
 Age
 Ovarian reserve
 BMI (body weight and height)
 Occasionally we are only wiser
after one stimulation
 Warranting a change in
protocol, drug, dose, technique
of IVF

WHY IVF CYCLES FAIL
Lining of the womb
(Endometrium)
 Very important factor
 If abnormal even with good
embryos failure may occur
 Because implantation
(attachment) of embryo is
disturbed
 Drugs given to thicken lining
 Measure the lining
 If not thick and lush enough cycle may
fail

WHY IVF CYCLES FAIL
 The space inside the womb is
checked beforehand
Sono

WHY IVF CYCLES FAIL
Checking the womb
Hysteroscopy

WHY IVF CYCLES FAIL
Implantation failure
 Sometimes even the best
embryos still fail to attach to the
womb and grow
 Attachment to the womb
(implantation) is not under
doctors’ direct control
 Must occur naturally
 Drugs given to make the womb
ready to receive and maintain
the embryo
 There may be no obvious
reasons identified
 Rejection of embryo?

WHY IVF CYCLES FAIL
Unknown factors
 Seen in multiple IVF failures
 Sometimes all done properly
 May still fail
 A couple of repeat attempts
may then succeed
 Chance of success same in the
first 3 attempts/cycles
 Majority of patients will
conceive after 3 attempts
 In natural conception, try again
and try again for up to 6
months or a year
 Difference here
drugs/injections, costs

REDUCING
FAILURE/IMPROVING
SUCCESS RATESEGG
 Age/patient selection
 Source of eggs
 Donor eggs
 Own preserved eggs
 Less aggressive Stimulation
 DHEAS
 Femara
 Estrogen priming protocol
 LAH

REDUCING
FAILURE/IMPROVING
SUCCESS RATESSPERM
 Selection
 IMSI
 PICSI
 SAT(SPERM ANEUPLOIDY
TESTING)
 *DNA FRAGMENTATION TEST

IMSI IMAGES

REDUCING
FAILURE/IMPROVING
SUCCESS RATES SPERM
 SAT (13,18, 21, X, Y)
 DNA fragmentation test
 Older men
 Exposure to chemicals etc

REDUCING
FAILURE/IMPROVING
SUCCESS RATES: SAT

REDUCING
FAILURE/IMPROVING
SUCCESS RATESEMBRYO
Aneuploidy is the most common reason why IVF cycles
fail
70% of natural or IVF embryos are lost before birth
A major cause of embryo loss and miscarriage is
aneuploidy
 Loss or gain of single chromosome
 Complex abnormalities

REDUCING
FAILURE/IMPROVING
SUCCESS RATESEMBRYO
 Selection/PGS

REDUCING
FAILURE/IMPROVING
SUCCESS RATES:
GENETICSPGS
 Trophectoderm Biopsy
(blastocyst)
 More tissue available
 No Inner cell mass so less risk to
embryo

REDUCING
FAILURE/IMPROVING
SUCCESS RATES: TIME LAPSE
EMBRYO
IMAGING/PHOTOGRAPHY
Embryologists in routine IVF cannot differentiate between
genetically normal and abnormal embryos using the
standard method
We may end up inevitably transferring abnormal embryos

REDUCING
FAILURE/IMPROVING
SUCCESS RATES: TIME LAPSE
EMBRYO
IMAGING/PHOTOGRAPHY

TIME LAPSE EMBRYO
IMAGING/PHOTOGRAPH
Y

TIME LAPSE EMBRYO
IMAGING/PHOTOGRAPHY

TIME LAPSE EMBRYO
IMAGING/PHOTOGRAPHY:
STUDY BY CARE FERTILITY UK
 April 2011-Dec 2012 among 69 couples
 88 embryos (33 low risk, 51 medium risk, 4 high risk)
 Single transfers only, observed/no intervention
 Overall CPR 42%
 LR 33, 73%, MR 51, 25.5%, HR 4, 0%
 Delivery Data available for 46 embryos (Overall LBR 39%)
 LR 18, 61%, MR 26. 19%, HR 2, 0%

TIME LAPSE EMBRYO
IMAGING/PHOTOGRAPH
YTime lapse vs Standard
method
 More images
 Morphokinetics vs Static
imaging
 No disturbance to embryos
 Non invasive (vs PGD)- i.e No
biopsy
 Improved success rates (early
days yet)
Video

REDUCING
FAILURE/IMPROVING
SUCCESS RATESEMBRYO TRANSFER
 Dummy
 USS guided
 Echogenic Catheter


REDUCING
FAILURE/IMPROVING
SUCCESS RATESIMPLANTATION
 ERA/ WOI/pET
 Embryo glue
 Less aggressive stimulation
better for lining
 Endometrial scratching
 Acupuncture
 Freeze all

REDUCING
FAILURE/IMPROVING
SUCCESS RATES: ERA

REDUCING
FAILURE/IMPROVING
SUCCESS RATES:
WOI/PET

REDUCING
FAILURE/IMPROVING
SUCCESS RATES:
GENETICS

REDUCING
FAILURE/IMPROVING
SUCCESS RATES:
MISCARRIAGES
POC Analysis
 2 or more repeated miscarriages
 50-60% of first trimester miscarriages chromosomal
 PGS can then help if diagnosed to increase take home baby rate

REDUCING
FAILURE/IMPROVING
SUCCESS RATESEMBRYO GLUE
8% Increase in live
births
Adherence compounds in embryo transfer
media for assisted reproductive technologies
Stephan Bontekoe1,
Neil Johnson2,
Deborah Blake3,*
Evidence suggests improved clinical pregnancy
and live birth rates with the use of functional
concentrations of HA as an adherence compound
in ART cycles. However, the evidence obtained is
of moderate quality. The increase in multiple
pregnancy rate may be the result of use of a
combination of an adherence compound and a
policy of transferring more than one embryo.
Further studies of adherence compounds with
single embryo transfer need to be undertaken.

REDUCING
FAILURE/IMPROVING
SUCCESS RATES:
ENDOMETRIAL SCRATCHING

REDUCING
FAILURE/IMPROVING
SUCCESS RATES:
ACUPUNCTURE

REDUCING
FAILURE/IMPROVING
SUCCESS RATES:
GENERAL ISSUESLifestyle eg Alcohol, smoking esp in women (Stop 3
months to IVF)
Diet (Refined foods)
Exposure to radiations IT Age
Weight issues: loose at least 5% of weight
Stress? No effect.

CONCLUSION
We must be reminded that
although IVF can facilitate
the union of sperm and
egg, it cannot guarantee
the miracle that is life.
As science continues to
look for ways to eliminate
IVF failures, we must
continue to give hope to
women who have suffered
IVF failures as with
perseverance, patience
and more research we
shall fashion out the
weapon against IVF failure
in due course.

QUESTIONS??????

Why IVF Cycles Fail by Dr. Abayomi Ajayi

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