Dr. Anuradha Katragadda
ANU TEST TUBE BABY CENTER
Over 2 decades and still sailing : Anu Test Tube Baby Centre
Training in MFS
Over 2 decades and still sailing : Anu Test Tube Baby Centre
Search for „would – be – embryologist‟
Dr. Prasad, “a gift”
Slaughter house – for sheep ovaries
Hands on training at MFS
Visit to other IVF centres
Over 2 decades and still sailing : Anu Test Tube Baby Centre
The „Night mares‟
Fertilization checks – night outs
Procuring / bringing over;
Drugs
Ham‟s – F 10 powder
Cleaning solutions
„In – house‟ prepar-ations-
Culture medias
Flushing medias etc.
Present „scenario‟
Conferences, work-shops, courses, fellow ships
Companies setting up labs, equipment,
Availability of prepared culture medias
Flying physicians & embryologists
Visit by Mr. Andy Walker,
Sue Barlow
Self-analysis / Quality-check
The most awaited event
Over 2 decades and still sailing : Anu Test Tube Baby Centre
The „I - IVF Baby‟ (early days of IVF)
Birth of Louis Brown – July, 1978
„Steptoe & Edwards‟, the pioneers
of In-Vitro-Fertilization (IVF)
Result of a single oocyte
retrieved in a natural cycle laparoscopically
Performed for tubal factor
Time-line of major Mile Stones
Initial experience with unstimulated cycles
- Yielded on average 0.7 Oocytes / retrieval
- Overall PR of 6 % / initiated cycle
Stimulated IVF cycles with HMG
- Extensively studied at Jone‟s Institute (1982)
- 1980 – 83;
- Recovery of 2.1 – 2.6 Oocytes / retrieval
- PR 23.5 – 30 %
Conventional IVF (GnRH –
analogue cycles)
Prevalent problem
- 20 % of IVF cycles cancelled;
- Premature LH surge & ovulation
Pituitary desensitization
- Administration of GnRH-a (1984)
- Incidence of premature ovulation 2 %
- However, raise in incidence of potentially „life-
threatening‟ OHSS (Nugent et al, 2000)
GnRH – antagonist (1990‟s)
-More friendly protocol
Over 2 decades and still sailing : Anu Test Tube Baby Centre
Stimulation Regimens – „What
Terminolgy‟
„International society for mild approaches in
Assisted Reproduction‟(ISMAAR)
COS - Complications
Multiple Pregnancy
Increased incidence of heterotopic
pregnancies
OHSS
Ectopic & Heterotopic Pregnancies
Incidence of ectopic – 1.5 - 2 %
 With Ovulation Induction - 3 %
 With ART - 5 %
Incidence of Heterotopic Pregnancies –
1 in 30,000
 With Ovulation Induction & ART – 1 %
Surgical treatment – viable option
 1/3rd spontaneous miscarriages
A high index of suspicion required
Over 2 decades and still sailing : Anu Test Tube Baby Centre
OHSS
‘ Loss of control over COH ’
 Only after overstimulated ovaries
‘ exposed to hCG inj ’
C U L P R I T
HMG HCG
Ovarian Hyperstimulation
An iatrogenic complication
Significant increase globally
Incidence of moderate cases ≈ 5 %
Incidence of cases requiring admission
hospitalization ≈ 2 %
Devastating consequence of OHSS is a serious
threat to life –
3 maternal deaths 100,000
OHSS - FUTURE
Design individualized treatment
protocols
In-Vitro maturation of oocytes
Artificial ovary
„ Mild ‟ stimulation for IVF
Single embryo transfer (SET)
An OHSS – Free Clinic
Segmentation –
of –
IVF treatment
Segmentation of IVF
OHSS can be „erased‟ by applying ovarian stimulation
using a combination of GnRH-antagonist with
GnRH-agonist trigger
- freeze all
Agonist - Trigger
Possibility of luteal phase defect
Reduced pregnancy rates
1. Rescue of luteal phase
2. „Freeze all‟ – a safe alternative
The Patient-friendly Protocol
Segmentation of IVF –
- Freeze-all &
Frozen embryo cycle
„The balance between the desire for
pregnancy
and patient‟s safety is a top priority‟.
Over 2 decades and still sailing : Anu Test Tube Baby Centre
Is antagon protocol-
a universal protocol
No-one-size Fits All
Over 2 decades and still sailing : Anu Test Tube Baby Centre
HMG
GnRH ant.
CC
Mild IVF
0 7 14
Days
3
OR
HCG
F – 14 mm
„ This method is likely to increase and possibly even
replace the current conventional protocol in future‟.
Over 2 decades and still sailing : Anu Test Tube Baby Centre
Refinements in O.I drugs
The initial regimens:
Clomiphene citrate.
Urinary gonadotropins
Highly purified urinary Gonadotrophins
In the late 1980s- early 1990s:
addition of a GnRH agonist to achieve pituitary modulation.
1990s-
Development of Recombinant Gonadotrophins, GnRH
antagonists.
Refinements in techniques
Moving away from operating room;
Improvements in U/S
Catalyzed evolution of modern oocyte-pick up
Transabdominal / Transvosical (1982)
Transvaginal U/S guided follicular aspiration (1987)
Follicular aspiration –
Using double lumen needle
and follicular flushing
Single lumen needle
Refinements in techniques
Embryo Transfer
Blind technique
Under Trans-abdominal U/S guidance
3-D U/S guided
Single Embryo Transfer
Addressing the needs of
Infertile men
Development of techniques to overcome
fertilization problems
PZD (Ist technique)
SUZI
ICSI (Ist pregnancy reported in 1992)
Increasingly applied
Created a new possibility for azoospermic
men; MESA/PESA/TESE
Nov, 1998
Cryopreservation
Sperms
Oocytes
Young women with cancer, before chemo or
radiotherapy
To circumvent advancing age (social egg freezing
– oocyte banking)
(ASRM declared egg freezing - „no longer
experimental‟, 2012)
Embryos
Ist reported pregnancy, 1983
Cryopreservation Techniques
• Slow freezing
• Vitrification
‘Embryonomics’-
(Science of handling frozen accounts)
- For storage problems
IVF – advanced techniques of
Genetic analysis
PGD / PGS – performed at DNA / chromosome level
- PCR – Ist technique to detect single-gene-mutations
chromosomal imbalances & mitochondrial mutations
- FISH – to screen aneuploidy & chromosomal translocation
- Both have high false Positives or Negatives
Newer diagnostic methods –
Improved clinical efficiency outcome
a- CGH
Karyomapping
NGS
Non-Invasive technology
- „Time-lapse-imaging‟
Oocyte / Embryo Donation
Gamete donation
- The first sperm donor insemination-Philadelphia, in 1884
- First oocyte donation- Monash IVF centre, 1983
- Over last 2 decades, predominant indication for oocyte
donation has shifted
„Cross –Border Reproductive care‟.
- gametes & embryos moving across borders
- individuals travelling to different countries
Over 2 decades and still sailing : Anu Test Tube Baby Centre
The End Of Donor Anonymity
Genetic testing
Direct-to-consumer (DTC)
Formation of large international genetic geneology
databases
DTC genetic testing- (commercial co.)
„Family tree DNA‟-
Offers Y-DNA matching database
„The 23 and Me‟-
Autosomal DNA test for males & females
-to solve unknown parentage cases
End Of Donor Anonymity
„uncovering secrets‟
Donor anonymity not guaranteed
May drive gamete donation out of business
Change in the approach
Increase in medico legal problems
Video counselling
Increased expectations
Frills / website
Patient – client
Practice - Business
Fast- track treatment
Changes which made greater impact
on treatments
Choosing safer O.I protocols
Aiming for single follicle in O.I
IVF - Antagon cycle with Agonist trigger and freeze all
OHSS free clinic
Individualising treatment protocols
Improvement in OR, ET & lab. Techniques
Blastocyst transfer, use of emb. glue
Reducing no. of embryos transferred
Increase in no. of frozen embryo cycles
Availability of HP & recombinant drugs
Refinements in fertility enhancing surgeries
Robotic surgeries
Use of versa point for hysteroscopic procedures
Increasing incidence of
PCO, endometriosis
Low ovarian reserve
Male infertility
Academics
Over 2 decades and still sailing : Anu Test Tube Baby Centre
Robert Edward – (Nov, 2002)
James Catt – 2010
Robert Shaw – 2012
Dr. Fukuda - 2013
Other celebrity visitors
Knowledge Sharing
Ways fertility treatments could
change in the near, and far, future
HLA – typing for stem cell donation
Approaches to obtain stem cell from siblings
„Designer – Babies‟
- Genetic make up has been artificially selected by
genetic engineering combined with IVF (to
ensure absence or presence of
particular gene or characteristics)
- British scientists granted permission by HFEA; Feb,
2016
Egg freezing
-More women will freeze their eggs
„Three-parent‟ embryos –
To prevent passing on mitochondrial diseases
Over 2 decades and still sailing : Anu Test Tube Baby Centre

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Over 2 decades and still sailing : Anu Test Tube Baby Centre

  • 1. Dr. Anuradha Katragadda ANU TEST TUBE BABY CENTER
  • 5. Search for „would – be – embryologist‟ Dr. Prasad, “a gift” Slaughter house – for sheep ovaries Hands on training at MFS Visit to other IVF centres
  • 7. The „Night mares‟ Fertilization checks – night outs Procuring / bringing over; Drugs Ham‟s – F 10 powder Cleaning solutions „In – house‟ prepar-ations- Culture medias Flushing medias etc.
  • 8. Present „scenario‟ Conferences, work-shops, courses, fellow ships Companies setting up labs, equipment, Availability of prepared culture medias Flying physicians & embryologists
  • 9. Visit by Mr. Andy Walker, Sue Barlow Self-analysis / Quality-check
  • 12. The „I - IVF Baby‟ (early days of IVF) Birth of Louis Brown – July, 1978 „Steptoe & Edwards‟, the pioneers of In-Vitro-Fertilization (IVF) Result of a single oocyte retrieved in a natural cycle laparoscopically Performed for tubal factor
  • 13. Time-line of major Mile Stones Initial experience with unstimulated cycles - Yielded on average 0.7 Oocytes / retrieval - Overall PR of 6 % / initiated cycle Stimulated IVF cycles with HMG - Extensively studied at Jone‟s Institute (1982) - 1980 – 83; - Recovery of 2.1 – 2.6 Oocytes / retrieval - PR 23.5 – 30 %
  • 14. Conventional IVF (GnRH – analogue cycles) Prevalent problem - 20 % of IVF cycles cancelled; - Premature LH surge & ovulation Pituitary desensitization - Administration of GnRH-a (1984) - Incidence of premature ovulation 2 % - However, raise in incidence of potentially „life- threatening‟ OHSS (Nugent et al, 2000) GnRH – antagonist (1990‟s) -More friendly protocol
  • 16. Stimulation Regimens – „What Terminolgy‟ „International society for mild approaches in Assisted Reproduction‟(ISMAAR)
  • 17. COS - Complications Multiple Pregnancy Increased incidence of heterotopic pregnancies OHSS
  • 18. Ectopic & Heterotopic Pregnancies Incidence of ectopic – 1.5 - 2 %  With Ovulation Induction - 3 %  With ART - 5 % Incidence of Heterotopic Pregnancies – 1 in 30,000  With Ovulation Induction & ART – 1 % Surgical treatment – viable option  1/3rd spontaneous miscarriages A high index of suspicion required
  • 20. OHSS ‘ Loss of control over COH ’  Only after overstimulated ovaries ‘ exposed to hCG inj ’ C U L P R I T HMG HCG
  • 21. Ovarian Hyperstimulation An iatrogenic complication Significant increase globally Incidence of moderate cases ≈ 5 % Incidence of cases requiring admission hospitalization ≈ 2 % Devastating consequence of OHSS is a serious threat to life – 3 maternal deaths 100,000
  • 22. OHSS - FUTURE Design individualized treatment protocols In-Vitro maturation of oocytes Artificial ovary „ Mild ‟ stimulation for IVF Single embryo transfer (SET)
  • 23. An OHSS – Free Clinic Segmentation – of – IVF treatment
  • 24. Segmentation of IVF OHSS can be „erased‟ by applying ovarian stimulation using a combination of GnRH-antagonist with GnRH-agonist trigger - freeze all
  • 25. Agonist - Trigger Possibility of luteal phase defect Reduced pregnancy rates 1. Rescue of luteal phase 2. „Freeze all‟ – a safe alternative
  • 26. The Patient-friendly Protocol Segmentation of IVF – - Freeze-all & Frozen embryo cycle „The balance between the desire for pregnancy and patient‟s safety is a top priority‟.
  • 28. Is antagon protocol- a universal protocol No-one-size Fits All
  • 30. HMG GnRH ant. CC Mild IVF 0 7 14 Days 3 OR HCG F – 14 mm „ This method is likely to increase and possibly even replace the current conventional protocol in future‟.
  • 32. Refinements in O.I drugs The initial regimens: Clomiphene citrate. Urinary gonadotropins Highly purified urinary Gonadotrophins In the late 1980s- early 1990s: addition of a GnRH agonist to achieve pituitary modulation. 1990s- Development of Recombinant Gonadotrophins, GnRH antagonists.
  • 33. Refinements in techniques Moving away from operating room; Improvements in U/S Catalyzed evolution of modern oocyte-pick up Transabdominal / Transvosical (1982) Transvaginal U/S guided follicular aspiration (1987) Follicular aspiration – Using double lumen needle and follicular flushing Single lumen needle
  • 34. Refinements in techniques Embryo Transfer Blind technique Under Trans-abdominal U/S guidance 3-D U/S guided Single Embryo Transfer
  • 35. Addressing the needs of Infertile men Development of techniques to overcome fertilization problems PZD (Ist technique) SUZI ICSI (Ist pregnancy reported in 1992) Increasingly applied Created a new possibility for azoospermic men; MESA/PESA/TESE Nov, 1998
  • 36. Cryopreservation Sperms Oocytes Young women with cancer, before chemo or radiotherapy To circumvent advancing age (social egg freezing – oocyte banking) (ASRM declared egg freezing - „no longer experimental‟, 2012) Embryos Ist reported pregnancy, 1983
  • 37. Cryopreservation Techniques • Slow freezing • Vitrification ‘Embryonomics’- (Science of handling frozen accounts) - For storage problems
  • 38. IVF – advanced techniques of Genetic analysis PGD / PGS – performed at DNA / chromosome level - PCR – Ist technique to detect single-gene-mutations chromosomal imbalances & mitochondrial mutations - FISH – to screen aneuploidy & chromosomal translocation - Both have high false Positives or Negatives Newer diagnostic methods – Improved clinical efficiency outcome a- CGH Karyomapping NGS Non-Invasive technology - „Time-lapse-imaging‟
  • 39. Oocyte / Embryo Donation Gamete donation - The first sperm donor insemination-Philadelphia, in 1884 - First oocyte donation- Monash IVF centre, 1983 - Over last 2 decades, predominant indication for oocyte donation has shifted „Cross –Border Reproductive care‟. - gametes & embryos moving across borders - individuals travelling to different countries
  • 41. The End Of Donor Anonymity Genetic testing Direct-to-consumer (DTC) Formation of large international genetic geneology databases DTC genetic testing- (commercial co.) „Family tree DNA‟- Offers Y-DNA matching database „The 23 and Me‟- Autosomal DNA test for males & females -to solve unknown parentage cases
  • 42. End Of Donor Anonymity „uncovering secrets‟ Donor anonymity not guaranteed May drive gamete donation out of business
  • 43. Change in the approach Increase in medico legal problems Video counselling Increased expectations Frills / website Patient – client Practice - Business Fast- track treatment
  • 44. Changes which made greater impact on treatments Choosing safer O.I protocols Aiming for single follicle in O.I IVF - Antagon cycle with Agonist trigger and freeze all OHSS free clinic Individualising treatment protocols Improvement in OR, ET & lab. Techniques Blastocyst transfer, use of emb. glue Reducing no. of embryos transferred Increase in no. of frozen embryo cycles Availability of HP & recombinant drugs Refinements in fertility enhancing surgeries Robotic surgeries Use of versa point for hysteroscopic procedures Increasing incidence of PCO, endometriosis Low ovarian reserve Male infertility
  • 47. Robert Edward – (Nov, 2002) James Catt – 2010 Robert Shaw – 2012 Dr. Fukuda - 2013 Other celebrity visitors Knowledge Sharing
  • 48. Ways fertility treatments could change in the near, and far, future HLA – typing for stem cell donation Approaches to obtain stem cell from siblings „Designer – Babies‟ - Genetic make up has been artificially selected by genetic engineering combined with IVF (to ensure absence or presence of particular gene or characteristics) - British scientists granted permission by HFEA; Feb, 2016 Egg freezing -More women will freeze their eggs „Three-parent‟ embryos – To prevent passing on mitochondrial diseases