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Natural process
• In order to understand what happens in an IVF cycle, it is important to understand what happens in a normal menstrual cycle first.
• A gland in the brain releases the ‘Follicle Stimulating Hormone’ (FSH) which causes the follicle (the sac containing the egg) to grow until
eventually it can be seen as a black circle on an ultrasound scan
• In a normal cycle only one follicle and one egg develops
• When the follicle becomes mature, a second hormone called ‘Luteinizing Hormone’ (LH) is released from the gland in the brain
• This hormone triggers the egg to be released from the follicle and this is called ‘Ovulation’
• The follicle produces a hormone called ‘oestrogen’ which develops the lining of the womb which is called the ‘endometrium’
• After ovulation the follicle is called the ‘corpus luteum’.
• This produces another hormone called ‘progesterone’ which further develops the lining of the womb for implantation
• The tube picks up the egg and if sexual intercourse has occurred the sperm will swim up through the neck of the womb called the ’cervix’ and
through the uterus into the fallopian tubes to fertilise the egg
• The embryo will then travel to the uterus and implant if it has a good potential for development
Female reproductive system
What is IVF(Assisted Reproductive Technology
(ART)?

• In vitro fertilisation (IVF) literally means ‘fertilisation in glass’ giving
us the familiar term ‘test tube baby’.
• During the IVF process, eggs are removed from the ovaries and
fertilised with sperm in the laboratory. The fertilised egg (embryo) is
later placed in the woman’s womb.
IVF: History
• In vitro fertilization (IVF) is a fertility procedure which first
succeeded as recently as 1978 by Dr. Edwards ( an embryologist) and
Dr. Steptoe ( a gynecologist) in England. Since then the technology
has been further refined and developed by physicians and
embryologists, with over 20,000 babies born worldwide.
Reason for infertility
•
•
•
•
•
•

Tubes are blocked or damaged
Sperm do not swim well
Sperm are too few in number
The lining of the womb is affected
Ovaries do not produce eggs
Quality of eggs is compromised
Basic Principle of IVF

Hormonal
treatment
Female
Harvest
the ovum
Mature Ova

Mix in a test tube

Keep to
develop
embryo

Motile sperms
Collect semen

Natural
ejaculation

Male

Transfer
to mother
Modifications in an IVF or ICSI cycle
• Why do we need to make changes?
•
•
•
•
•

We need more than one egg in the cycle
Not all eggs fertilise or grow
Not all embryos have a good potential for development
We want to transfer 1-3 embryos for a good success rate
We do not want the gland in the brain to become confused in treatment
IVF CYCLE PROTOCOL
6 PHASES
1.

Suppression of the natural cycle
To switch off the gland in the brain so that it does not interfere in treatment

2.

Stimulation
Hormone injections to produce multiple eggs

3.

Ovulation trigger or HCG injection

4.

Egg collection

5.

Embryo transfer

6.

Hormonal support after the embryo transfer
Stage 1:Suppression of the natural cycle
Oral Contraceptive Pill
Prostap once a month injection
OR

Buserelin daily injection
OR

Nafarelin three times a day nasal spray
Side effects
headaches, hot flushes, night sweats, mood-swings, prolonged
period or second bleeding
Stage 2: Stimulation of the Ovary
Dose of stimulation is adjusted for:
Reserve of eggs in the Ovary (hormone levels and scan findings)
Age
Weight or Body Mass Index
Past history (infections, cyst removal)
Presence or absence of PCOS
Types:Menopur, Merional, Puregon,Gonal-F, Fostimon
All are subcutaneous injections
Stage 3: Ovulation Trigger
HCG injection
Pregnyl (commonest)
Ovitrelle
Recombinant LH
Timed 36 hours prior to egg collection
Stage 4: Egg Collection
Performed under ultrasound guidance
Fast acting sedation & analgesia
Duration 20 - 45 minutes
Egg Collection
Events after Egg Collection
 Sperm production
 Insemination of Eggs or Sperm injection into the
eggs

 Fertilisation check
 Observation of growth
 Selection of embryos for transfer
Stage 5: Intracytoplasmic Sperm
Injection
• During the process of ICSI, an embryologist isolates a
sperm cell, draws it up into a microscopic needle and
injects it inside an egg using a high power microscope.
Fertilization
• Once mature eggs have been retrieved, the sperm and eggs are
placed together in the laboratory and incubated in a
meticulously prepared culture medium at a temperature
identical to that of the woman’s body.
Embryonic Development
2 cells

Early day 2

4 cells

8 cells

Late day 2

Day 3

Morula

Blastocyst

Day 4

Day 5
Stage 6: Embryo Transfer
• Embryo transfer is not a painful
procedure and can be performed
without sedation.
• Usually up to three embryos are
placed together in a catheter ( a
tubular instrument) and
transferred, via the vagina, into
the uterus.
Success rate of IVF
• Varies from programme to programme.
• It is dependent upon correct diagnosis of patient, and age.
• Pregnancy rate is in the range of 25-30% per oocyte retrieval.
• The take home is about 15-20% per procedure.
Factors
• Increased risk of abortion.
• Multiple pregnancy.
• Ectopic pregnancy.
• Low birth weigh baby.
• Premature delivery.
Limitation of IVF
• Genetic defect in oocytes.
• Genetic defect in fertilizing sperm.
• Environmental mutagenesis.
• Inadequate supply of nutrients and hormones.
• Exposure to toxic agents and free radicals.
Understanding the Natural and IVF Fertilization Process

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Understanding the Natural and IVF Fertilization Process

  • 1.
  • 2. Natural process • In order to understand what happens in an IVF cycle, it is important to understand what happens in a normal menstrual cycle first. • A gland in the brain releases the ‘Follicle Stimulating Hormone’ (FSH) which causes the follicle (the sac containing the egg) to grow until eventually it can be seen as a black circle on an ultrasound scan • In a normal cycle only one follicle and one egg develops • When the follicle becomes mature, a second hormone called ‘Luteinizing Hormone’ (LH) is released from the gland in the brain • This hormone triggers the egg to be released from the follicle and this is called ‘Ovulation’ • The follicle produces a hormone called ‘oestrogen’ which develops the lining of the womb which is called the ‘endometrium’ • After ovulation the follicle is called the ‘corpus luteum’. • This produces another hormone called ‘progesterone’ which further develops the lining of the womb for implantation • The tube picks up the egg and if sexual intercourse has occurred the sperm will swim up through the neck of the womb called the ’cervix’ and through the uterus into the fallopian tubes to fertilise the egg • The embryo will then travel to the uterus and implant if it has a good potential for development
  • 4.
  • 5.
  • 6. What is IVF(Assisted Reproductive Technology (ART)? • In vitro fertilisation (IVF) literally means ‘fertilisation in glass’ giving us the familiar term ‘test tube baby’. • During the IVF process, eggs are removed from the ovaries and fertilised with sperm in the laboratory. The fertilised egg (embryo) is later placed in the woman’s womb.
  • 7. IVF: History • In vitro fertilization (IVF) is a fertility procedure which first succeeded as recently as 1978 by Dr. Edwards ( an embryologist) and Dr. Steptoe ( a gynecologist) in England. Since then the technology has been further refined and developed by physicians and embryologists, with over 20,000 babies born worldwide.
  • 8. Reason for infertility • • • • • • Tubes are blocked or damaged Sperm do not swim well Sperm are too few in number The lining of the womb is affected Ovaries do not produce eggs Quality of eggs is compromised
  • 9. Basic Principle of IVF Hormonal treatment Female Harvest the ovum Mature Ova Mix in a test tube Keep to develop embryo Motile sperms Collect semen Natural ejaculation Male Transfer to mother
  • 10. Modifications in an IVF or ICSI cycle • Why do we need to make changes? • • • • • We need more than one egg in the cycle Not all eggs fertilise or grow Not all embryos have a good potential for development We want to transfer 1-3 embryos for a good success rate We do not want the gland in the brain to become confused in treatment
  • 11. IVF CYCLE PROTOCOL 6 PHASES 1. Suppression of the natural cycle To switch off the gland in the brain so that it does not interfere in treatment 2. Stimulation Hormone injections to produce multiple eggs 3. Ovulation trigger or HCG injection 4. Egg collection 5. Embryo transfer 6. Hormonal support after the embryo transfer
  • 12. Stage 1:Suppression of the natural cycle Oral Contraceptive Pill Prostap once a month injection OR Buserelin daily injection OR Nafarelin three times a day nasal spray Side effects headaches, hot flushes, night sweats, mood-swings, prolonged period or second bleeding
  • 13. Stage 2: Stimulation of the Ovary Dose of stimulation is adjusted for: Reserve of eggs in the Ovary (hormone levels and scan findings) Age Weight or Body Mass Index Past history (infections, cyst removal) Presence or absence of PCOS Types:Menopur, Merional, Puregon,Gonal-F, Fostimon All are subcutaneous injections
  • 14. Stage 3: Ovulation Trigger HCG injection Pregnyl (commonest) Ovitrelle Recombinant LH Timed 36 hours prior to egg collection
  • 15. Stage 4: Egg Collection Performed under ultrasound guidance Fast acting sedation & analgesia Duration 20 - 45 minutes
  • 17. Events after Egg Collection  Sperm production  Insemination of Eggs or Sperm injection into the eggs  Fertilisation check  Observation of growth  Selection of embryos for transfer
  • 18. Stage 5: Intracytoplasmic Sperm Injection • During the process of ICSI, an embryologist isolates a sperm cell, draws it up into a microscopic needle and injects it inside an egg using a high power microscope.
  • 19. Fertilization • Once mature eggs have been retrieved, the sperm and eggs are placed together in the laboratory and incubated in a meticulously prepared culture medium at a temperature identical to that of the woman’s body.
  • 20. Embryonic Development 2 cells Early day 2 4 cells 8 cells Late day 2 Day 3 Morula Blastocyst Day 4 Day 5
  • 21. Stage 6: Embryo Transfer • Embryo transfer is not a painful procedure and can be performed without sedation. • Usually up to three embryos are placed together in a catheter ( a tubular instrument) and transferred, via the vagina, into the uterus.
  • 22.
  • 23. Success rate of IVF • Varies from programme to programme. • It is dependent upon correct diagnosis of patient, and age. • Pregnancy rate is in the range of 25-30% per oocyte retrieval. • The take home is about 15-20% per procedure.
  • 24. Factors • Increased risk of abortion. • Multiple pregnancy. • Ectopic pregnancy. • Low birth weigh baby. • Premature delivery.
  • 25. Limitation of IVF • Genetic defect in oocytes. • Genetic defect in fertilizing sperm. • Environmental mutagenesis. • Inadequate supply of nutrients and hormones. • Exposure to toxic agents and free radicals.

Editor's Notes

  1. There are 6 phases in the LONG CYCLE that are listed above.Each of these points will now be discussed in detail further on in this presentation.
  2. THE LONG PROTOCOLAs explained before, we need to suppress your pituitary gland from becoming confused and sending inappropriate signals during the course of the development of multiple eggs. We usually do this by combining the pill with once a month injection (Prostap) that lasts for 4-5 weeks. A daily injection of Buserelin or the Naferelin nasal spray is sometimes used. These drugs are may also be used to supplement Prostap, if the suppression phase becomes prolonged for any reason. The side effects are due to a fall in your natural oestrogen levels but this affect will soon disappear as soon as stimulation of the ovary takes effect and your oestrogen levels rise.
  3. Everybody varies in how they will respond to the stimulating drugs.Usually we consider age, weight, cause of infertility, past response etc in deciding the dose to prescribe. Usually older and overweight women respond less wellWomen with Polycystic ovaries often produce a lot of follicles, sometimes too many which then gives them a risk of ‘Ovarian hyperstimulation’.We try to adjust the dose from the outset and sometimes need to further increase or lower the dose during treatment in a ‘Step-Down or Step-up’ manner.There are several preparations of the hormones that we use which are listed in the slides above.They vary in the way they are prepared, and what they contain. We choose the most suitable one for your clinical situation.Their cost may also be differ slightly.
  4. This is also an injectionIt is given when the follicles have grown to a mature size This will help the eggs to enter a stage of maturation so that they are ready for fertilisationThis injection is known as the “late night injection” because it is usually administered late in the nightWe commonly use Pregnyl but there are others also as listed aboveThis injection is usually given approximately 35 hours before the time we plan your egg collection. Doing so gives us a 4-5 hours window in which to collect eggs, make a preparation of the sperm for IVF or ICSI.It is absolutely vital that this injection is taken at the time you are advised to takeWhen in doubt, please check!
  5. The egg collection is also performed with the help of ultrasound scanIt is important to be as relaxed as possible for the EC and we will give you a pain killer and sedative into your vein.It does not take long.It is out-patient based so you should be able to go home after a couple of hoursPrepare yourself for some discomfort because your ovaries are considerably larger than normal at this stageDue to the sedative drugs, you should not drive or operate machinery on this dayYou are advised to have someone be with you for the dayYour husband needs to provide a sperm sample on this day, unless we have a previously frozen sampleIf you think that there may be a problem in giving a sample on demand, please do not take a risk and opt for sperm freezing beforehand.
  6. This diagram illustrates the Egg Collection procedureWe have a user friendly approach:Dim lightMusic for relaxation (you may bring your iPod with you, if you wish)
  7. Shortly before or after the egg collection the male partner will be asked to give a sperm sample (Unless a sperm sample has been stored beforehand) Later on the eggs will either be inseminated as in the IVF procedure or injected into the egg as in the ICSI procedure. Please refer to the booklets.Fertilisation check is performed the next day approximately 18 hours after sperm injection or insemination of the eggs.The fertilised eggs are now called “embryos”The embryologist will call you on the day after the egg collection and discuss fertilisation details. They will also provisionally indicate when the embryo transfer procedure is likely to be and may give you a date or time for this. Usually this is 2 or 3 days after the day of egg collection.On the morning of the embryo transfer the embryologist will look at the embryos again. If there a good number of appropriately growing embryos with a satisfactory appearance of their cells, after consultation with the consultant, the embryologist may call you again and postpone the embryo transfer to day 5. All decisions regarding when and how many embryos to transfer are taken in consultation with the consultant in charge of the unit on that day.Please refer to the next slide for the embryo transfer procedure.