IVF - what everyone needs to know about IVF

Dr Aniruddha Malpani, MDwww.DrMalpani.com

Egg plus sperm = baby !

Traditional approachImportant and urgent for the patient

However, most doctors take a “wait and watch “ approach

Often , patients get fed up and frustrated and drop out of treatment

This is a shame !

Need to change !Patients are getting married at an older age

Time is running out as the biological clock ticks on

We now have effective technology to help them !

IVF cycle 4 basic steps

1. Superovulation2. Egg collection3. In vitro fertilisation4. Embryo transfer

Only 6 visits to the clinicDay care basis – no hospitalisation needed

IVF cycle1. Superovulation 1. With HMG ( gonadotropins)Natural hormonesNewer recombinant preparations much more

expensive, but no better2. Downregulation with Buserelin ( GnRH)3. GnRH antagonists to prevent LH surge4. Low cost – clomiphene plus HMG

IVF cycle SuperovulationMonitor follicular growth ( ovarian response)Vaginal ultrasound scans – Day 3, 10, 12, 14Rarely need to measure blood estradiol levels !

IVF cycle 2. Egg collection

Vaginal ultrasound guidance

Non-surgical

IVF cycle3. InseminationSperm added to egg in the incubatorKept in vitro in conditions which mimic in

vivo conditionsThe incubator is the heart of the IVF lab

IVF cycle 4. Embryo transfer

Non-surgicalNumber of embryos ?When to transfer ? Day 2 or 3 or 5

IVF cycle No need for bed rest – you cannot cough the embryo out !

Still a matter of luck !Not the patient’s “fault” if she doesn’t conceive

She cannot “reject” the embryo !

Risks of IVF 1.No pregnancy2.Multiple pregnancy3.Ectopic pregnancy4.OHSS – ovarian

hyperstimulation syndrome. Managed conservatively

Limitations of IVFFew medical risksMajor risks are

FinancialEmotional

Advanced fertilisation techniquesIntracytoplasmic Sperm Injection(ICSI)

Assisted HatchingBlastocyst transferPreimplantation Genetic Diagnosis (PGD)

ICSIMicroinjection ( Intracytoplasmic sperm injection)

One egg + one sperm = one embryo !

Can use testicular sperm even from men with testicular failure ( with high FSH levels and small testes)

Blastocyst transferCulture in vitro to Day 5 allows improved

selection of viable embryos

Advantage of blastocyst transfer is that the number of embryos transferred can be reduced without risking a decline in pregnancy rates . This helps to reduce the risk of multiple pregnancy .

Freezing - cryopreservation

VitrificationCan store and preserve

SpermEmbryosEggsOvarian tissue

The promise of ART We can help any couple to have a baby, no matter what their medical problem !

Third party reproductionEmbryo adoptionDonor eggsSurrogate uterus

PGD – the newest ARTPGD marries genetic technology and IVF

technology The newest patient is the embryo !

Procedure for preimplantation genetic diagnosis1. IVF cycle2. 8-cell embryo at Day 33. Biopsy embryo ( micromanipulator)4. Fix blastomere5. Study genetic composition of blastomere

using genetic probes ( FISH)6. Transfer selected embryos into uterus

Signal interpretationEvaluate slides with a fluorescence microscope.Locate nucleus using DAPI filter Interpret signalsProbe will bind to specific chromosome onlyPink = Y ( Spectrum Orange)Green = X ( Spectrum Green)

Normal blastomere

Trisomy 21

Comparative Genomic Hybridisation

PCR

Indications for preimplantation genetic diagnosis1. Sex linked genetic disorders

HemophiliaDuchenne muscular dystrophy

2. Chromosomal disordersDown’s syndrome ( Trisomy 21)

Indications for preimplantation genetic diagnosis3. Single gene diseases ( using PCR)

Thalassemia4. Older women doing IVF

Screen embryos for aneuploidy5. Recurrent pregnancy loss because of

chromosomal anomalies

CloningReproductive cloningTherapeutic cloning

Embryonic stem cellsCan change the face of medicineVery promising futureLots of research still needs to be done

Indian can be a leading center in this field

Collaboration between IVF clinics and basic research labs

We’ve come a long way, baby !

Playing God ?When does life begin? What are the rights of an embryo? Can human embryos be used for harvesting embryonic stem cell lines ? Should cloning be allowed ?

Vexed issues – and since they deal with creating human life, these debates generate more heat than light !

Should embryo research be banned ?Banning research ends up stopping scientific progress

We are not mad scientists trying to play God

We are doctors trying to do the best for our patients

ART is a medical success story !However, advances in IVF have come with government guidelines and laws

The purpose of these guidelines is to ensure that these technologies are used safely and responsibly

How well do these guidelines work ? What purpose do really serve ?

Human Fertilisation and Embryology Authority (HFEA) Act, UKProtect the “welfare of the child” Theory - It should be the parent(s) of the

child who should be empowered to make the best decisions for their child

Practice - An impersonal government body without a heart or a soul makes these decisions, claiming that they are acting in the interests of the child.

UK v/s US Interestingly, the US has not found it necessary to pass a federal law to regulate IVF

And they are doing fine – thank you very much !

Doctors v/s politiciansIs it better to allow doctors to make medical decisions ( as is done in the USA) ?

Or to have legal hurdles, as is the practice in many European countries ?

Who can we trust ?

Global pictureWhat is remarkable about the regulations which govern ART in each country is that they vary so widely!

Guidelines are arbitrary and often designed to fulfill prevailing political pressures, rather than being based on scientific principles.

Law of unintended consequencesIn Spain, it is legal to put embryos in frozen

storage, but it is illegal to destroy embryos or to donate them to research

There are currently 50,000 embryos sitting unused in frozen storage in Spain - some beyond the five-year storage limit.

Sad mockery . The law which was designed to protect embryos on paper , ends up destroying them in practice !

IVF laws and doctorsBy forcing doctors to practice medicine as laid down in a mindless statue drafted by bureaucrats, rather than by applying their own judgment, we are ending up harming our patients.

Doctors are trusted professionalsOur freedom to do what is best for our patients will be curtailed by bureaucrats , activists and politicians.

If doctors can be trusted to make life and death decisions in the ICU, then why can’t we be trusted to make decisions about IVF responsibly ?

Useful regulationMost doctors would agree that there is a

need to regulate the practice of IVF, so that all IVF clinics meet certain basic standards.

Need to protect infertile patients, who are emotionally vulnerable, and can get cheated easily by unscrupulous doctors

In real lifeBureaucrats only understand paperworkOverburdened doctors end up spending more

time filling up forms rather than talking to patients !

Good doctors don’t need to bemonitored; and monitoring bad doctors does not help !

Real life problem - How many embryos to transfer ?Ideal would be one. However, the technology

is still not perfect The law is blind – limit of 2 for everyone !Why ? Makes sense for the NHS !Does this make sense for a 43 year old

woman doing her 5th IVF cycle ?Let the couple decide for themselves – weigh

the pros and cons

SurrogacyOne of the thorniest issues !Who has the rights ?What happens when something goes wrong ?Will India become the surrogacy outsourcing

capital of the world ?Are we exploiting poor women by “hiring

their wombs” ?

The fact that rules vary so much from country to country means that there are no right answers.

Rather than apply rules blindly, isn’t it better to allow doctors the freedom to select what is best for their patients ?

Solution ?Let patients decide for themselves – after all,

it’s their life – and their baby !A democracy empowers people to make their

own choices – and they should be allowed to use the technology to fulfill their personal reproductive desires, as long as they don’t harm anyone else !

It’s unethical to interfere in their personal family-building plans !

Going too far ?

3 principles of medical ethicsAutonomyBeneficenceNon-maleficence

Simplifying IVF to make it affordableLow cost IVFYoung couples ( get married young)

Cannot afford expensive treatmentMistake – have copied the West blindly so far

Need to adapt IVF for India !

Low cost innovationsMinimal stimulation IVF

( gentle IVF)Transport IVF – eggs and sperm transported to central IVF lab

Satellite IVF

Intravaginal CultureUse the patient’s vagina as an incubator !No need for expensive incubator or electric

supplyStepped care IVF – can be made available in

government hospitals in district townsShould be part of each teaching hospital in

India

What society can doInfertility treatment should be a part of the

Family Planning and Family Welfare servicesShould be covered by medical insurance

because infertility is a disease and needs medical treatment