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IVF

Dr. H. R. Muharam, SPOG (K)

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Introduction

• In vitro fertilization (IVF) is a process by which egg cells are fertilised by sperm outside of the womb, in vitro.

• IVF is one method of assisted reproductive technology

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2%

36%

17%

16%

5%

5%

19%

No cause

More than one

Endometriosis

Dysovulation

Unexplained

Tubal factor

Male factor

Figure 1 The causes of infertility in a large observational multicenter study in the UK, 2003

McVeigh,ASRM, 2004

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Table 32.1. IVF indication list of the Dutch Society of Obstetrics and Gynaecology.

1.Tubal pathology– if tubal surgery is not a realistic option, IVF is the method of choice.– In case of impaired tubal function but no occlusion present, or after tubal surgery, IVF is the method of choice after an infertility

duration of 2 years or longer. Depending on the women’s age IVF can be done after a shorter duration of infertility

2.Unexplained infertility (Idiopathic)*– In case of idiopathic infertility IVF is indicated if the duration is 3 years or longer. If the woman is older than 36 years, IVF may be considered earlier.

3. Male infertility– Total motile sperm count (TMC) <1 million: first treatment of choice is ICSI– TMC >1 and <10 million: IVF can be performed if infertility duration is 2 years or longer*– TMC >10 million: treat as unexplained infertility

4. Endometriosis – In case of mild or moderate endometriosis treat as unexplained infertility – In case of severe endometriosis treat as tubal pathology

5. Cervical factor/immunological infertility*– After an infertility duration of 2 years, IVF is indicated. This may be considered sooner if the woman is over 36 years of age.

6. Hormonal disturbances*– Anovulatory cycle abnormalities are an indication for IVF if 12 cycles of treatment with ovulation induction have been unsuccesful

* In these situations intrauterine insemination treatment merits consideration before proceeding to IVF

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Table 32.2. Indications for ICSI

• Total motile sperm count (TMC) <1 million

• No or poor fertilization in the first IVF cycle when TMC <10 million

• No or poor fertilization in two IVF cycles when TMC >10 million

• Epididymal or testicular spermatozoa

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Introduction

• The first IVF baby in the world (Louise Brown) was born in July of 1978 in England.

• Louise Brown was 28 when she delivered her own baby in 2006. Her baby was conceived without IVF. Hundreds of thousands of children are now born annually as a result of the IVF technique

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• The process involves :– Hormonally controlling the ovulatory process– Removing ova (eggs) from the woman's

ovaries – Letting sperm fertilise them in a fluid medium. – The fertilised egg (zygote) is then transferred

to the patient's uterus with the intent to establish a successful pregnancy

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• Problems of the fallopian tube, but it turned out that it was successful in many other infertility situations as well.

• The introduction of intracytoplasmic sperm injection (ICSI) addresses the problem of male infertility to a large extent.

• This means that IVF can be used for females who have already gone through menopause.

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Indication1. An anatomic problem with the uterus, such as severe intrauterine

adhesions1. Blocked fallopian tubes or pelvic adhesions 2. tubal reversal surgery 3. vasectomy reversal surgery  4. Male factor infertility (low sperm count or low motility).

1. ICSI is an IVF procedure that can fertilize eggs even with poor sperm quality.

1. Failed 2-4 cycles of ovarian stimulation with intrauterine insemination 

2. Advanced female age - over about 38 years of age. 3. Severe endometriosis 1. Unexplained infertility when inseminations have failed - unexplained

infertility means standard fertility tests have not found the cause of the fertility issue

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MethodOvarian stimulation• Started on the third day of menstruation and consist of a

regimen of fertility medications to stimulate the development of multiple follicles of the ovaries

• Monitoring – Estradiol– USG, follicular growth. Typically approximately 10 days of

injections will be necessary. • Spontanenous ovulation during the cycle is prevented by

the use of GnRH agonists or GnRH antagonists, which block the natural surge of luteinising hormone (LH).

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Stimulation protocolThree types of drugs:1. GnRH-agonist (gonadotropin releasing hormone agonist) or a

GnRH-antagonist (e.g. Ganirelix) to suppress the LH surge and ovulation until the follicles are mature

2. FSH product (follicle stimulating hormone) to stimulate development of multiple follicles

3. HCG (human chorionic gonadotropin) to cause final maturation of the eggs in the follicles

• The purpose of the GnRH-agonist (or antagonist) is to suppress release of LH (luteinizing hormone) from the woman's pituitary gland during the ovarian stimulation process. LH surges would cause premature ovulation (release) of the eggs.

• The purpose of the FSH product is to stimulate development of multiple follicles (structures that contain eggs) in the ovaries.

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Ovarian Stimulation Protocols Using GnRH-agonists

1. "Long protocols", also called "luteal Lupron", or "down regulation" protocols

2. "Flare" protocols, also sometimes called "short" protocols

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• Long Protocol IVF

Har

i pert

ama h

aid la

por

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Pemeriksaan USG vag

Hormonal

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Buserelin nasal3 kali setiap hari

± 2 mg 36 jam 2 hari 14 hari

Suntikan gonadotropin

Usg vagdarah

Ovum Pick

upTran

sfer e

mbrio

Tes urin

hCG mala

m

Suami siap

Tiap hari

± 2 mg

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Egg retrieval

• When follicular maturation is judged to be adequate, • human chorionic gonadotropin (β-hCG) is given.

– Acts as an analogue of luteinising hormone• The eggs are retrieved from the patient using a

transvaginal technique involving an ultrasound-guided needle piercing the vaginal wall to reach the ovaries.

• The retrieval procedure takes about 20 minutes and is usually done under conscious sedation or general anesthesia

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Ovum Pick Up• Aspirasi folikel• Pencarian sel telur

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Fertilisation• Eggs are stripped of surrounding cells and prepared for fertilisation., • Semen is prepared for fertilisation by removing inactive cells and

seminal fluid. • The sperm and the egg are incubated together (at a ratio of about

75,000:1) in the culture media for about 18 hours.

• By that time fertilisation should have taken place

• The fertilised egg would show two pronuclei.

• In situations where the sperm count is low, a single sperm is injected directly into the egg using intracytoplasmic sperm injection (ICSI).

• The fertilised egg is passed to a special growth medium and left for about 48 hours until the egg has reached the 6-8 cell stage.

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ICSI

Intracytoplasmic Sperm Injection

diperlukan hanya 1 sperma

motil saja untuk disuntikkan

kedalam ooplasma

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Perkembangan Embrio

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Perkembangan Embrio

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Perkembangan embrio

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Perkembangan Embrio

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Simpan Beku• Sperma• Embrio

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Selection

• Laboratories have developed grading methods to judge oocyte and embryo quality

• Typically, embryos that have reached the 6-8 cell stage are transferred three days after retrieval or embryos are placed into an extended culture system with a transfer done at the blastocyst stage, especially if many good-quality day-3 embryos are available.

• Blastocyst stage transfers have been shown to result in higher pregnancy rates.[1]. In Europe, transfers after 2 days are common.

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Sperma Suami• Persiapan sperma

suami

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ICSI Intra Cytoplasmic Sperm injection

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Pengelolaan embrioKonvensional

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Embryo Transfer• Embryos are graded by the embryologist based on the

number of cells, evenness of growth and degree of fragmentation.

• The number to be transferred depends on the number available.

• In the UK and according to HFEA regulations– > 40 may have up to three embryos transferred,– Younger women may have many embryos transferred based on

individual fertility diagnosis. – Most clinics and country regulatory bodies seek to minimise the

risk of pregnancies carrying multiples. • The embryos judged to be the "best" are transferred to the

patient's uterus through a thin, plastic catheter, which goes through her vagina and cervix.

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Transfer embrio

• Penentuan hari transfer

• Persiapan transfer embrio

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Transfer Embrio

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Complications• The major complication of IVF is the risk of

multiple births.[2] – Increased risk of pregnancy loss, – obstetrical complications, prematurity, and – neonatal morbidity with the potential for long term

damage – Spontaneous splitting of embryos in the womb

after transfer can occur, but • Ovarian stimulation is the development of

ovarian hyperstimulation syndrome.

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Monitoring Pasca Transfer Embrio

• Luteal suppport• USG• Monitoring sampai

12 minggu

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Komplikasi

• Ovarium hiperstimulasi • Kehamilan ektopik• Perdarahan

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Cause of infertility

Number of cycles

Livebirth rate (%) (95% CI)

Pretreatment cycle

Per egg collection

Per embryo transfer

Tubal disease 19096 13.6 (13.0 to 14.0)

15.0 (14.5 to 15.6)

16.5 (15.9 to 17.1)

Endometriosis 4117 14.2 (13.2 to 15.3)

15.9 (14.7 to 17.0)

17.9 (16.6 to 19.3)

Unexplained 12340 13.4 (12.9 to 14.1)

15.2 (14.6 to 15.9)

19.7 (18.8 to 20.5)

Cervical 4232 14.2 (13.2 to 15.3)

16.2 (15.1 to 17.4)

18.8 (17.5 to 20.2)

Table 32.3. Impact of cause of infertility on livebirth rate from IVF.

Templeton AA, et.al, Lancet 1996

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Pregnancy Rate on indication Yasmin 2007

Indication Clinical PR (%)

Ongoing PR (%)

Tuba (4) 50 25

Endometriosis (5) 20 20

Male Factor (18) 56 39

Idiopatic (5) 20 0

Disfungsion ovulation (1) 0 0

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Correlation between female age and pregnancy rate

Age(year)

Number of cycles (n(%))

Pregnancies(n(%))

<35 842 (59 %) 316 (37.5 %)

35-40 412 (28.9 %) 129 (31.3 %)

>40 173 (12.1%) 33 (19.1%)

Total 1427 (100% 478 (33.5%)

1427 IVF cycles in UK in 2003

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Pregnancy Rate on Diff. AgeYasmin IVF 2007

Age (year)

Clinical Pregnancy rate

(%)

Ongoing Pregnancy rate

(%)25-30 50 50

31-35 50 43

36-38 43 14

39-42 40 0

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