Dr Aniruddha Malpani, MD www.DrMalpani.com

Egg plus sperm = baby !

Traditional approach Important 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 !

Important 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 !

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. Superovulation 2. Egg collection 3. In vitro fertilisation 4. Embryo transfer Only 6 visits to the clinic Day care basis – no hospitalisation needed

4 basic steps

1. Superovulation

2. Egg collection

3. In vitro fertilisation

4. Embryo transfer

Only 6 visits to the clinic

Day care basis – no hospitalisation needed

IVF cycle 1. Superovulation 1. With HMG ( gonadotropins) Natural hormones Newer recombinant preparations much more expensive, but no better 2. Downregulation with Buserelin ( GnRH) 3. GnRH antagonists to prevent LH surge 4. Low cost – clomiphene plus HMG

1. With HMG ( gonadotropins)

Natural hormones

Newer recombinant preparations much more expensive, but no better

2. Downregulation with Buserelin ( GnRH)

3. GnRH antagonists to prevent LH surge

4. Low cost – clomiphene plus HMG

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

Monitor follicular growth ( ovarian response)

Vaginal ultrasound scans

– Day 3, 10, 12, 14

Rarely need to measure blood estradiol

levels !

IVF cycle 2. Egg collection Vaginal ultrasound guidance Non-surgical

2. Egg collection

Vaginal ultrasound guidance

Non-surgical

IVF cycle 3. Insemination Sperm added to egg in the incubator Kept in vitro in conditions which mimic in vivo conditions The incubator is the heart of the IVF lab

3. Insemination

Sperm added to egg in the incubator

Kept in vitro in conditions which mimic in vivo conditions

The incubator is the heart of the IVF lab

IVF cycle 4. Embryo transfer Non-surgical Number of embryos ? When to transfer ? Day 2 or 3 or 5

4. Embryo transfer

Non-surgical

Number 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 !

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 No pregnancy Multiple pregnancy Ectopic pregnancy OHSS – ovarian hyperstimulation syndrome. Managed conservatively

No pregnancy

Multiple pregnancy

Ectopic pregnancy

OHSS – ovarian hyperstimulation syndrome. Managed conservatively

Limitations of IVF Few medical risks Major risks are Financial Emotional

Few medical risks

Major risks are

Financial

Emotional

Advanced fertilisation techniques Intracytoplasmic Sperm Injection(ICSI) Assisted Hatching Blastocyst transfer Preimplantation Genetic Diagnosis (PGD)

Intracytoplasmic Sperm Injection(ICSI)

Assisted Hatching

Blastocyst transfer

Preimplantation Genetic Diagnosis (PGD)

ICSI Microinjection ( 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)

Microinjection ( 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 transfer Culture in vitro to Day 5 allows improved selection of viable embryos

Culture 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 .

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

Vitrification Can store and preserve Sperm Embryos Eggs Ovarian tissue

Can store and preserve

Sperm

Embryos

Eggs

Ovarian tissue

The promise of ART We can help any couple to have a baby, no matter what their medical problem ! Third party reproduction Embryo adoption Donor eggs Surrogate uterus

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

Third party reproduction

Embryo adoption

Donor eggs

Surrogate uterus

PGD – the newest ART PGD marries genetic technology and IVF technology The newest patient is the embryo !

PGD marries genetic technology and IVF technology

The newest patient is the embryo !

Procedure for preimplantation genetic diagnosis 1. IVF cycle 2. 8-cell embryo at Day 3 3. Biopsy embryo ( micromanipulator) 4. Fix blastomere 5. Study genetic composition of blastomere using genetic probes ( FISH) 6. Transfer selected embryos into uterus

1. IVF cycle

2. 8-cell embryo at Day 3

3. Biopsy embryo ( micromanipulator)

4. Fix blastomere

5. Study genetic composition of blastomere using genetic probes ( FISH)

6. Transfer selected embryos into uterus

Signal interpretation Evaluate slides with a fluorescence microscope. Locate nucleus using DAPI filter Interpret signals Probe will bind to specific chromosome only Pink = Y ( Spectrum Orange) Green = X ( Spectrum Green)

Evaluate slides with a fluorescence microscope.

Locate nucleus using DAPI filter

Interpret signals

Probe will bind to specific chromosome only

Pink = Y ( Spectrum Orange)

Green = X ( Spectrum Green)

Normal blastomere

Trisomy 21

Comparative Genomic Hybridisation

PCR

Indications for preimplantation genetic diagnosis 1. Sex linked genetic disorders Hemophilia Duchenne muscular dystrophy 2. Chromosomal disorders Down’s syndrome ( Trisomy 21)

1. Sex linked genetic disorders Hemophilia Duchenne muscular dystrophy

2. Chromosomal disorders Down’s syndrome ( Trisomy 21)

Indications for preimplantation genetic diagnosis 3. Single gene diseases ( using PCR) Thalassemia 4. Older women doing IVF Screen embryos for aneuploidy 5. Recurrent pregnancy loss because of chromosomal anomalies

3. Single gene diseases ( using PCR) Thalassemia

4. Older women doing IVF Screen embryos for aneuploidy

5. Recurrent pregnancy loss because of chromosomal anomalies

Cloning Reproductive cloning Therapeutic cloning

Reproductive cloning

Therapeutic cloning

Embryonic stem cells Can change the face of medicine Very promising future Lots of research still needs to be done Indian can be a leading center in this field Collaboration between IVF clinics and basic research labs

Can change the face of medicine

Very promising future

Lots 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 !

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

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 ?

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, UK Protect 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.

Protect 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 !

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 politicians Is 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 ?

Is 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 picture What 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.

What 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 consequences In 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 !

In 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 doctors By 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.

By 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 professionals Our 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 ?

Our 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 regulation Most 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

Most 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 life Bureaucrats only understand paperwork Overburdened doctors end up spending more time filling up forms rather than talking to patients ! Good doctors don’t need to be monitored; and monitoring bad doctors does not help !

Bureaucrats only understand paperwork

Overburdened doctors end up spending more time filling up forms rather than talking to patients !

Good doctors don’t need to be

monitored; 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 5 th IVF cycle ? Let the couple decide for themselves – weigh the pros and cons

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 5 th IVF cycle ?

Let the couple decide for themselves – weigh the pros and cons

Surrogacy One 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” ?

One 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 ?

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 !

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 ethics Autonomy Beneficence Non-maleficence

Autonomy

Beneficence

Non-maleficence

Simplifying IVF to make it affordable Low cost IVF Young couples ( get married young) Cannot afford expensive treatment Mistake – have copied the West blindly so far Need to adapt IVF for India !

Low cost IVF

Young couples ( get married young)

Cannot afford expensive treatment

Mistake – have copied the West blindly so far

Need to adapt IVF for India !

Low cost innovations Minimal stimulation IVF ( gentle IVF) Transport IVF – eggs and sperm transported to central IVF lab Satellite IVF

Minimal stimulation IVF ( gentle IVF)

Transport IVF – eggs and sperm transported to central IVF lab

Satellite IVF

Intravaginal Culture Use the patient’s vagina as an incubator ! No need for expensive incubator or electric supply Stepped care IVF – can be made available in government hospitals in district towns Should be part of each teaching hospital in India

Use the patient’s vagina as an incubator !

No need for expensive incubator or electric supply

Stepped care IVF – can be made available in government hospitals in district towns

Should be part of each teaching hospital in India

What society can do Infertility treatment should be a part of the Family Planning and Family Welfare services Should be covered by medical insurance because infertility is a disease and needs medical treatment

Infertility treatment should be a part of the Family Planning and Family Welfare services

Should be covered by medical insurance because infertility is a disease and needs medical treatment