NEW OvInd - Sum 1 Mar08

SAMSULHADI
DEPT. OF OBSTETRIC & GYNECOLOGY,

FAC. OF MEDICINE AIRLANGGA UNIVERSITY.
DR. SOETOMO HOSPITAL
SURABAYA
SAMSULHADI. DEPT. OF OBSTETRIC & GYNECOLOGY, FAC. OF MEDICINE AIRLANGGA UNIVERSITY. DR. SOETOMO HOSPITAL SURABAYA MARCH 2008
OVULATION INDUCTION ( SUMMARY )
OBJECTIVE
I.  INTRODUCTION
A. Physiology of ovulation
B. Causes, WHO Classification & diagnosis of anovulation
C. Treatment
 The General Factors affecting ovulation – induction
II. REGIMENS
A. Anti Estrogens
B. Insulin sensitizing agent (ISA)
C. Ovarian Drilling
D. Gonadotropin
III. ART (Clinical Implementation)
A. COH – IUI
B. COH –IVF –ET
C. OHSS
OLIGO / AN OVUL WHO Class MENS. DISTURB.
PHYSIOLOGY
CENTRAL :
HYPOTHAL HYPOTHAL HYPOG- IV
I AMENORRHEA
HYPOG
PITUITARY PITUITARY
III
IV
OVUL.
DYSFUNC / Normo • DUB
(ABNORMALITY gonadotrophic
II • Oligomenorrhea
OF F.B. Normo
estrogenic • Amenorrhea
MECHANISM)
HYPER- AMENORRHEA
OVARY PERIPHERY III II
HYPOG
OOGENESIS
FOLICULOGEN. OVULATION
STEROIDOGEN
Causes and
AMENORRHEA
UTERINE
(ENDOMET) Diagnosis of -ABN. OF DEVELOP
-INFECTION
I
MENS. Anovulation COMPAR-
TEMENT
CAUSES – CLASSIFICATION & DIAGNOSIS OF ANOVULATION
DIAGNOSIS
Menstrual Cycles TVS

(DUB, Oligo / Amenorrhea)
• History –
Physical Exam. Diagnosis TREATMENT
FSH –PRL
• R/O Pregnant
• Endometrial • Monitoring
Thickness • Predict. of
FSH  or ↔ • Follicle / PCO Ovulation
• Other anatomy Time
• (PCOs) PRL ↑ Problems
• Hypothal. Prolac FSH ↑
I tinoma
Ovarian FSH ↔
IV Failure
Anatomic
III Defect
II
CAUSES – DIAGNOSIS & TREATMENT OF ANOVULATION ( OI & COH)
TREATMENT
OI COH
Anovulation • Regular ovulation

• Oligo / anovulation
WHO I Hypog-Hypog Gonadotropin
WHO II Normo gonad CC + Aromatase IUI or IVF
Normo estrogen Inhibitor
CC
Metformin (ISA)
Ovarian Drilling CC + Gonadotropin
Gonadotropin Gonadotropin
WHO III Hyper-Hypog  (Donor oocyte) Others
WHO IV Hyper-prolactin Bromocryptin
Multiple
Ovulation Ovulation
GENERAL FACTORS AFFECTING OI / COH
AGE Ovarian Reserved /

Others Pathology Cases
 Serum FSH, E2 Basal
 AFC, TVS
 Genetic, Immunology Factors
 Inhibin B
 Pelvic Surgery
 AMH
 Others Pathol. Cases
- PCOs
Ovarian Response
- Obesity
- Insulin Resistance
Poor Normal High - Endometriosis, etc.
Responder
Strategy of
OI / COH
HIGH RESPONDER
(PCOs)
Dx
• Serum – FSH / E2 / Inhibin B Basal ?

• AFC
REDUCED OVARIAN RESERVE
DOCUMENTED POOR RESPONSE TO AGGRESSIVE OVULATION INDUCTION
TREATMENT OPTIONS
FSH 10 – 19 mIU / ml FSH > 20 mIU / ml
Aggressive ovulation
Induction with
Intrauterine
Inseminations
Adequate response Poor response Counseling for other options

 Egg donation
Try 3 cycles  Adoption
then IVF
Steven R. Bayer, Michael M. Alper, Alan S. penzias : The Boston IVF Handbook of Infertility, Practical guide for
practioners who care for infertile couples. The Parthenon publishing Group. Massachusetts. 2002. 67 - 74
OBJECTIVE
I.  INTRODUCTION
B. Caused – WHO Classification & diagnosis of anovulation
C. Treatment
II. REGIMENS
A. Anti Estrogens
C. Ovarian Drilling
D. Gonadotropin
A. COH – IUI
B. COH –IVF –ET
C. OHSS
A. ANTI ESTROGEN
 CLOMIPHEN CITRATE
 AROMATASE INHIBITOR
CLOMIPHENE CITRATE
TREATMENT
OI COH
Anovulation • Regular ovulation

• Oligo / anovulation
WHO I Hypog-Hypog Gonadotropin
WHO II Normo gonad CC + Aromatase IUI or IVF
Normo estrogen Inhibitor
CC
Metformin (ISA)
Ovarian Drilling CC + Gonadotropin
Gonadotropin Gonadotropin
WHO III Hyper-Hypog  (Donor oocyte) Others
WHO IV Hyper-prolactin Bromocryptin
Multiple
Ovulation Ovulation
DOSES CC
DOSES OVULATION NOTE

(mg) (%)
50 52
F.D.A Recommendation
100 22 in US
150 12
200 7 High dose success in

several women
250 5
Speroff Leon (2005) ; Clinical Gynecolgic Endocrinology and Infertility, ed VIIth.

Lippincott Williams & Wilkins. Page : 1170 - 1189
OVULATION INDUCTION
7.1 Antioestrogens
Women with WHO Group II ovulation disorders (hypothalamic pituitary dysfunction)
such as polycystic ovary syndrome should be offered treatment with clomifene citrate A
(or Tamoxifen) as the first line of treatment for up to 12 months because it is likely to
induce ovulation.
Women should be informed of the risk of multiple pregnancies associated with both
clomifene citrate and tamoxifen. B
Women with unexplained fertility problems should be informed that clomifene citrate
treatment increases the chance of pregnacy, but that this needs to be balanced by the A
possible risks of treatment, especially multiple pregnancy
Women undergoing treatment with clomifene citrate should be offered ultrasound
monitoring during at least the first cycle of treatment to ensure that they receive a GPP
dose that minimizes the risk of multiple pregnancy.
RCOG Fertility : Assessment and treatment for people with fertility problems. RCOG Press. London (2004)
ANTI ESTROGEN
 CLOMIPHEN CITRATE
 AROMATASE INHIBITOR
ANTI ESTROGEN
CC AROMATASE INHIBITOR
- LETROZOLE
- ANASTROZOLE
Hypothalamic Level Periphery

Mode of Action
(Blocked/depletion ER) (Androgen E)
Half Life Longer Shorter ( + 2 days)
Multiple Ovulation Higher Less
Deleterious effect
on C.M &  
endometrium
Day 3-7 3-7
Treatment
Strategy Dose /
50 – 150 mg 2.5 – 5 mg ( ? )
day
B. Insulin Sensitizing Agent (ISA)
METFORMIN
7.2 Metformin
Anovulatory women with polycystic ovary syndrome who have not responded to
clomifene citrate and who have a body mass index of more than 25 should be offered A
metformin combined with clomifene citrate because this increases ovulation and
pregnancy rates
Women prescribing metformin should be informed of the side effects associated with
its use (such as nausea, vomiting and other gastrointestinal disturbances). GPP
CLOMIFEN CITRATE + METFORMIN
Check Screening Labs
Initiate Metformin and
Titrate dose to 1000 mg Initiate clomiphene and titrate
b.i.d. for 2 – 6 months Up to 150 mg / dose
Ovulation ? Yes
No Ovulation
Continue metformin Yes

No
Or initiate metformin as above for 5 weeks
And start clomiphene 50 mg Continue clomiphene
with titration to 150 mg For total of 6 cycles
Ovulation ? Yes If predictable ovulation occurs,

No Continue current regimen.
Consider alternate treatment
If conception occurs, stop all
(e.g. FSH + Metformin)
therapies
Fertility & Sterility . 2002 ; Vol. 77 ; 209 - 215
C. OVARIAN DRILLING
7.3 Ovarian Drilling
Women with polycystic ovary syndrome who have not responded to clomifene citrate
should be offered laparoscopic ovarian drilling because it is as effective as A
gonadotrophin treatment and is not associated with an increased risk of multiple
pregnancy
INDICATION OF L.O.D
A. CC THERAPY RESISTANT
B. LH ↑↑
C. Impossible to intensive monitoring

(Gonadotropin Therapy)
In Infertility – PCOs cases

who
Need Laparoscopic assessment to explore

her pelvic organs
LOD : Laparoscopic Ovarian Drilling

L.O.D - PCOs
OUT COME
DEPEND ON
Not Pre-treatment characteristics
High Basal LH level > 10 IU / L *

 Testosterone level
> 8 IU / L **
 B.M.I. High Responder
 Ovarian volume
• Unilateral L.O.D restored bilateral activity (untreated ovary often being the first ovulate)
Balen Adam H. et.al. Polycystic ovary syndrome a guide to clinical management. Ed.Ist Taylor & Francis Group.
London 2005. p : 169 - 192
* Amer S.A.K. Ovulation induction using LODin women with PCOs : predictors of success, Human reproduction, vol.
19. no. 8 . 2004
** Hayashi Hiroshi, Preoperative LH Level predict the ovary response to LOD in patients with CC resistant PCOs, Gynecol
Endocrinol. 21. no. 6 . 2005
C. OVARIAN DRILLING
ADVANTAGES & DISADVATAGES
• Lowers the overall cost of treatment • Need for surgery and anesthesia
• Single treatment cycle can result in
multiple ovulatory cycles • Non-permanent ovulatory effect
• No need intensive monitoring as
gonadotropin treatment • Possibility of post operative
adhesions
• High ovulation and pregnancy rate
• P.O.F (Rare)
• Eliminates risk of OHSS and
multiple pregnancy
• Abortion rate 
PCOs
CC
OVULATION
 
Other LH
Infertility < 10 IU/L > 10 IU/L
Factors
Metformin LOD
+ CC
 Ovulation 
Gonadotropin
Gonadotropin Regimens
URINE DNA Recombinant

Techniques
 h MG (FSH + LH) r FSH

 p FSH
 FSH - HP
SAMSULHADI. DEP. OF OBSTETRIC & GYNECOLOGY, FAC. OF MEDICINE AIRLANGGA UNIVERSITY. DR. SOETOMO HOSPITAL SURABAYA
D. GONADOTROPIN
7.4 Gonadotrophin use in ovulation induction therapy for ovulatory disorders
Women with WHO Group II ovulation disorders such as polycystic ovary syndrome
who do not ovulate with clomifene citrate (or tamoxifen) can be offered treatment with
gonadotrophins. Human menopausal gonadotrophin, urinary follicle-stimulating A
hormone and recombinant follicle-stimulating hormone are equally effective in
achieving pregnancy and consideration should be given to minimising cost when
prescribing
Women with WHO Group III ovulation disorders such as polycystic ovary syndrome
who ovulate with clomifene citrate but have not become pregnant after 6 months of A
treatment should be offered clomifene citrate stimulated intrauterine insemination
7.5. Gonadotrophin use during in vitro fertilization treatment
Human menopausal gonadotrophin, urinary follicle-stimulatig hormone and
recombinant follicle-stimulating hormone are equally effective in achieving a live birth A
when used following pituitary downregulation as part of in vitro fertilization treatment.
Consideration should be given to minimising cost when prescribing
OPTIMAL REQUIREMENT OF LH LEVEL
IN COH
SERUM LH LEVEL
(BASAL)
1,2 < IU / L < 5
ASRM, Fertil Steril 2005, 83 : 1043 - 1046

D. GONADOTROPIN
TRADE MARK OF uFSH & rFSH
FSH IU
• Pergonal Merck-Serono
• Humegon Organon
u • Gestyl Organon
75
• Metrodin Merck-Serono
• Gonal F Merck -Serono

r • Puregon Organon 75
OBJECTIVE
I.  INTRODUCTION
B. Caused – WHO Classification & diagnosis of anovulation
C. Treatment
II. REGIMENS
A. Anti Estrogens
C. Ovarian Drilling
D. Gonadotropin
A. COH – IUI
B. COH –IVF –ET
C. OHSS
A.R.T
IUI IVF - ET
• Unexplained Inf. • Severe Abnormality

• Mild Endometriosis Indication • Failure of previous Treat.
• Oligo zoopspermia • Multiple Factors
• Ovarian Factor • Unexplained Inf.
• Etc.
There is Requirement There is

• Sperm • Sperm
• Oocyte (Legal Couple) • Oocyte
• Uterus • Uterus
Normal Tube
- Poor ov. Reserve - Poor ov. Reserve

- > 40 yrs of old Contra - > 40 yrs of old
- C.I. to be Pregn. Indication - C.I. to be Pregn.
IUI
Depend on :
• Age
• Diagnose of infertility
NATURAL STIMULATED
CYCLE CYCLE
Where intrauterine insemination is used to manage male factor fertility problems,

ovarian stimulation should not be offered because it is no more clinically effective A
than unstimulated intrauterine insemination and it carries a risk of multiple pregnancy
IUI – NATURAL CYCLE
(UNSTIMULATION)
Progesterone
14 10 17-OHP
Ng/mL
PHISIOLOGY MENSTRUATION
- -
L
24 12 10
H
ho ho 9
Progesteron
ur ur L
8 FSH H e
s s
7 FS FSH
Estradi
H ol
6
L LH
5
H
L 4
Estradi
H 3
Estradiol ol 17-OH
17-OH Progesterone
E 2
Progesterone Progesterone
2 4 6 8 10 12 14 16 18 20 22 24 26 28
2 1
Ov.
IUI
- 16
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28
36 hrs
• Ur. LH
• TVS • ≥  18 mm
• > 9 mm endom.
IUI – COH
• ≥  18 mm hCG *
• > 9 mm endom.
TVS CC 50 – 100 mg/day TVS
36 hrs
CC 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28
IUI
Ur. LH
TVS
≥  12 mm  18 mm hCG *
TVS ≥  15 mm  18 mm
CC +
FSH 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28
CC
50 – 100 mg/day <  15 mm
<  12 mm  18 mm
TVS TVS • ≥  18 mm hCG *

• > 9 mm endom.
CC +
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28
FSH
Ur. LH
* IUI after 36 hours post hCG
IUI – COH
TVS
2-3 day
TVS
>  18 mm hCG *
TVS >  15 mm
FSH 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28
<  12 mm
<  15 mm  USG
* IUI after 36 hours post hCG
STEP-UP
↑ 75 IU
↑ 75 IU Every 3 days
75 IU
7 days
LOW-DOSE STEP-UP
↑ ½ dose
½ dose
14 days
PCO
STEP-DOWN
150 IU
3 days ↓ 75 IU
Start Low dose
37,5 IU
7 DAYS
PCO
USG A B C D
NO 1 follicles 1-4 follicles ≥ > 4 follicles
RESPON ≥ 10 mm 14 mm ≥ 14 mm
1st cycle : = Dose 4 days = Dose Dose ↓

= dose 7days C-D 2 days USG in 2days
B-C-D 1-4 follicles ≥ D

No change 15 mm
↑ Dose = Dose 2 days
No change
Stop
NO CHANGE / 1-2 follicle ≥ 18mm >2 follicle ≥ 18mm

↓ 1-3 follicle ≥ 14mm >4 follicle ≥ 14mm
= Dose 2 days
hCG CANCEL
Balen AH, 2003
 Indication
 Requirement
SPERM hCG or
 Contra Indication PREPARATION Progesterone P
R
E
INSEMI LUTEAL G
SCREENING
NATION SUPPORT N
A
N
Ovarian  Superovulation T
Reserve
 Monitoring ?
 hCG
COH - IUI
10
Menstruation Ovulation
Tx CC / IUI : 2 – 3 oocytes
r FSH IVF – ET : > 4 oocytes
 Indication S P E R M
 Requirement AZOOSP OLIGO “N”
 Contra Indication ICSI

PESA / TESE
Patient O F Embryo E Luteal P

Selection P E or blastocyst T Supp. R
R E
U T Selection
G
I N
Ovarian  GnRHa or GnRH L A
I PGD N
Reserve Antagonist Z
A C
 Gonadotropin Y
T
 Monitoring I
O
 hCG N
Mechanisme of Action of GnRH analogs Antagonists vs Agonists
INACTIVATION
1) ACTIVATION 2) DESENSITIZATION
0 10 20 days 0 2 4 8 12 24 hours
GnRH Agonist GnRH Antagonist
Chabbert – Buffet Nathalie, Clinical Obstetrics and Gynecology : GnRH Antagonists.

Lippincott Williams & Wilkins,46: 2. 2003
10
GnRHa Treatment
9
in IVF -ET
8
OC
Long Luteal Protocol FSH
Agonist
Cycle day 15 17 19 21 23 25 27 M 3 5 7 9 11
hCG
Short / Flare-up Protocol FSH
Agonist
15 17 19 21 23 25 27 M 3 5 7 9 11
hCG
GnRH Antag.
Treatment in IVF - ET
Single dose Protocol FSH

Antagonist
15 17 19 21 23 25 27 M 3 5 7 9 11
3 mg hCG
Multiple dose Protocol FSH

Antagonist
15 17 19 21 23 25 27 M 3 5 7 9 11
hCG
0,25 mg / day
(0,125 mg /day)
Semin Reprod Med. 2002. Thieme Medical Publishers
10
9
L
8 H
FS
7 H
FSH
6 Estrad
iol
5
L
4 H
2 Estr
adio 17-OH
1 l Progestero Proge
ne steron
e
Single dose Protocol FSH

Antagonist
15 17 19 21 23 25 27 M 3 5 7 9 11
hCG
Multiple dose Protocol FSH
Antagonist
15 17 19 21 23 25 27 M 3 5 7 9 11
hCG
TRADE MARK OF GnRHa, GnRHantag & rLH
GnRH agonist (Depot)
• Tapros Takeda 3,75 mg
• Zoladex Zeneca
• Endrolin Kalbe Farma
GnRH agonist (Daily)
• Suprefact Hoechst AG 0,3 – 0,5 cc

• Lucrine / Lupron 0,1 cc
GnRH antagonist
• Cetrotide Merck-Serono 0,125 – 0,25 mg Multiple
THE SIMPLIFIED IVF PROTOCOL EMPLOYED BY A FERTILITY CLINIC
10
9
L
H
8 FS
H
7 FSH
Estradiol
6
LH
5
3 Est
rad 17-OH
iol Progester Prog
2 one ester
one
1
Month 1 Month 2 Egg and Sperm Pregnancy *

GnRH Collection Test
Antagonist
Embryo Transfer
hCG
OCP r- hFSH **
Luteal Support
5 26 2 4 6 8 10 12 14 16 18 20 22 24 26 28
* Life Issue. 12 . March 2005
** titration Doses
OHSS
CAUSED
 E2
• OI
• COH  IL – 6 hCG
 
 Renin - Angiotensin II
Mild Stronger  VEGF
2–3 5 – 15  Vasodilatation
Fol. Fol.  Capillary hyper permeability
IUI IVF -ET

Homburg Roy, Neiman Emma. Ovulation Induction and Controlled Ovarian Stimulation. A Practical Guide.
Taylor Francis. London. 2005.
CLASSIFICATION OF OVARIAN HYPERSTIMULATION SYNDROME
 Mild Abdominal Bloating and discomfort
Ovarian enlargment up to 8 cm
 Moderate Criteria for mild plus
Nausea, vomiting or diarrhea
Ultrasound evidence of ascites
Ovarian enlargement up to 12 cm
 Severe Criteria for moderate plus
Oliguria < 500 ml/24h
Serum creatinine 1.0 – 1.5 mg/dl
Hematocrit > 45 %, leukocytosis > 15.000 / ml
Clinically evident ascites with or without pleural effusion
 Critical Tense ascites with pleural and / or pericardial effusions
Hematocrit > 55%, leukocytosis > 25.000 / ml
Oliguria with serum creatinine > 1.5 ml/dl
Renal failure, liver dysfunction
Thromboembolic phenomena
RISK FACTORS FOR OVARIAN HYPERSTIMULATION SYNDROME (OHSS)
 Before Starting Treatment  Age < 30 years

 Lean
 Polycycstic ovaries
 Previous OHSS
 During Treatment  Rapidly rising estradiol concentrations
 Very high estradiol concentrations
 Large number of developing follicles
 Luteal support with human chorionic gonadotropin
 Pregnancy particularly multiple pregnancy
OHSS
PREVENTION
 Cases with risk factors
● use - Smaller starting dose
- small incremental dose rises
 OHSS Imminent
- With holding hCG
- Cancel cycle
- Coasting
- Rescue – IVF
- Embryo cryopreservation
- Avoid luteal support by hCG
PROGESTERONE
hCG INJECTION
TREATMENT
FORFOR
LUTEAL
LUTEAL
SUPPORT
SUPPORT
Stimulating Cycles Egg retrieval
Progesterone
Optional Start timing
-14 -12 - 10 - 8 -6 -4 -2 0 2 4 6 8 10 12 14
hCG hCG hCG

Martin Dunitz, Textbook of Assisted Reproductive Techniques. Laboratory and clinical Perspectives.
The Livery House. London 2001. 515-525
hCG IU
•Serono
Profasi 5000 IU / amp
u Organon
• Pregnyl ( 5000 – 10.000)
r • Ovidrel 6500
Serono
MANAGEMENT GUIDELINES FOR THE OVARIAN HYPERSTIMULATION SYNDROME (OHSS) 1
Ovarian stimulation
PATIENT INSTRUCTION
Ovulatory hCG administration • Alarm Signals
• Telephone number treatment team
LUTEAL PHASE • Weight daily from ovulatory hCG
• Abdominal pain
ALARM SIGNALS administration
• Increasing girth
• Nausea, vormiting
OUTPATIENT DIAGNOSIS • Weight increase > 2.5 kg
1. Ultrasound from ovulatory hCG
2. Lab. Hematocrite administration
PARAMETER FOR POSSIBLE ACTION

1. Multicystic ovaries > 12 cm max, diameter
2. Ascites
3. Hematocrite > 45%
1 Parameter  > 2 Parameter 
MANAGEMENT GUIDELINES FOR THE OVARIAN HYPERSTIMULATION SYNDROME (OHSS) 2
1 Parameter  > 2 Parameter 
OHSS
OUTPATIENT OBSERVATION
CLINICAL DIAGNOSIS
Repeat every 1-2 days 1. Fluid Balance
OUTPATIENT DIAGNOSIS Hospitalization 2. Daily Weighting
3. Ultrasound follow-up
4. Lab : Hematocrite (Hct)
Thrombocytes
Improvement Electrolytes
Ureum
Total protein
Albumin
Liver Function
END OF
OBSERVATION THERAPY
Trauma Nausea / Hypovolaemia
Pain Dyspnoea
Prevention vomiting Hct > 45 %
Bed Rest PG- Synthetase Glucose – salt
Antiemetric Poss. X-ray Thorax
inhibitor Heparinization Poss. Ascites / pleura
Albumin, Dextran Puncture
PPPS (Past Plasma
CAUTION hypovolaemia Protein solution)
Poss. CVP monitoring
ART IN INFERTILITY
MANAGEMENT INFERTILITY MANAGEMENT
FEMALE MALE
 Age > 37 Years
and or Sperm An.
OVULATION FACTOR TUBAL FACTORS
 Multiple Factors Normal Abnormal
of Infertility
Irregular Cycles Regular  Age > 30 yrs  Age < 30 yrs

(WHO) cycles  Infertility  Infertility
duration > 3 yrs duration < 3 yrs Tx  Tx 
There are Risk No Risk Factors

I II III IV  
Factors of PID / of PID /

Endometriosis Endometriosis Succeed Failed
Gona  CC / Bromo
dotro HRT criptin HSG / SIS Normal
 CC + ISA LAPAROSCOPY
pin
 Ov. Drilling
 CC Abnormal • 6 Months
 Gonadotro
Gonado Abnormal Normal • “N” Others F.
pin 
tropin 6 months
Un-ope Operable - 1 years
6 months rable Included
? - 1 years 2 years IUI 3 – 6 x
Included Included
IUI 3 – 6 x IUI 3 – 6 x
No Pregnancy
IVF –ET /
ICSI
ART IN INFERTILITY
MANAGEMENT INFERTILITY MANAGEMENT
FEMALE MALE
 Age > 37 Years
and or Sperm An.
OVULATION FACTOR TUBAL FACTORS
 Multiple Factors Normal Abnormal
of Infertility
Irregular Cycles Regular  Age > 30 yrs  Age < 30 yrs

(WHO) cycles  Infertility  Infertility
duration > 3 yrs duration < 3 yrs Tx  Tx 
There are Risk No Risk Factors

I II III IV  
Factors of PID / of PID /

Endometriosis Endometriosis Succeed Failed
Gona  CC / Bromo
dotro HRT criptin HSG / SIS Normal
 CC + ISA LAPAROSCOPY
pin
 Ov. Drilling
 CC Abnormal • 6 Months
 Gonadotro
Gonado Abnormal Normal • “N” Others F.
pin 
tropin 6 months
Un-ope Operable - 1 years
6 months rable Included
? - 1 years 2 years IUI 3 – 6 x
Included Included
IUI 3 – 6 x IUI 3 – 6 x
No Pregnancy
IVF –ET /
ICSI
“SURABAYA” INFERTILITY SCORE
SCORE 1 2 3
Wife Age (Year) < 30 30 - 35 > 35
Marital duration /
1-2 >2 > 3
Length of Infertility ( Year)
Menstrual Cycle Regular Oligo / DUB Amenorrhea
Pain (Pelvic) * 1 Type > 2 Type of Pain
Neg
of Pain or Pelvic Mass
History of **
Neg 1 Time / IUD > 2 Times
PID / Pelvic Surgery
Sperm Analysis
Consentration : 20 million / ml Normal 1 abnormality > 2 abnormality
Motility ( a + b) : 50 % value of major parameter of major parameter
Normal Morphology : 30 %
If there is score 3 one of the infertility factors the total score directly to > 12 (red code)
** • IUD Score 6
* - Dysmenorrhea • STD
- Dyspareunia • Pelvic Surgery Score 7 - 12
- Spontaneous pelvic pain
Score > 12
Services :
A. Infertility
B. Reconstruction Surgery
C. Andrology - Sexology
D. IVF - ET
E. Endocrinology Reprod.
F. Menopause
G. Genetics
COMPREHENSIVE FERTILITY CLINIC

GRAHA AMERTA
DEPT. OG. MEDICAL FAC. AIRLANGGA UNIVERSITY
DR. SOETOMO GENERAL HOSPITAL SURABAYA
Telp. 031 – 70906307 Fax. 031-5501704 e-mail:batabsby@yahoo.com

SAMSULHADI. DEPT. OF OBSTETRIC & GYNECOLOGY, FAC. OF MEDICINE AIRLANGGA UNIVERSITY. DR. SOETOMO HOSPITAL SURABAYA
MARCH 2008
GENERAL FACTORS AFFECTING OI / COH
AGING AND REPRODUCTION IN WOMEN
% of maximum fertility Miscarriage rate (%)
% of maximum fertility 50
100
Miscarriage rate (%)
80 40
60 30
40 20
20 10
0 0
20-24 25-29 30-34 35-39 40-44
Leon Speroff and Frits marc A. Clinical Gynecologic Endocrinology and Infertility. Ed. VII TH. Lippincott
Williams & Wilknis Philadelphia (2005) p : 1013 - 1056
B. Insulin Sensitizing Agent (ISA)
Screening Lab. Test
METFORMIN CC (TITRATION)
( TITRATION ) ? - 150 mg/ days
- 1000 mg BID
(2 – 6 Months)
- OVULATION
OVULATION
5 WEEKS METFORMIN +
Following by Combination
CC 50 - 150 mg
6 Cycles
+ OVULATION -
NOTE : IF Pregnant
all Tx STOP METFORMIN
* NESTLER JOHN E (2002): STRATEGIES FOR THE USE OF INSULIN – SENSITIZING DRUGS TO TREAT & FSH
INFERTILITY WOMEN WITH PCOS. FERTIL STERIL 2002, 77 : 209 - 215
THE MODERN USE OF CLOMIFENE CITRATE
80
70
60
Pregnancy rate (%)
50
40
30
20
10
0 1 2 3 4 5 6 >6
Cycles
CLOMIPHENE CLOMIPHENE + GONADOTROPHINS
Day 2 Day 11
FSH 150 IU 150 IU
TVS TVS TVS TVS
Day
Clomiphene Clomiphene 2&9
100 mg /daily 100 mg /daily
Menses Menses
2 6 2 6
5 7 9
Alternate Day GONADOTROPHINS Daily GONADOTROPHINS
FSH FSH
150 IU 150 IU 150 IU 150 / 75 IU alternately X 6
TVS TVS Day TVS TVS Day

2, 8 2, 8
Menses Menses
2 4 6 8 2 7
COH – PCOs
Start with 37.5 – 75 IU

Starting dose 75 IU Do not increase for 14 days (1st cycle)
increase by 75 IU after / days or 7 days (subsequent cycles)
and then ever3-5 days until response Increments of 25 – 37.5 IU every 7 days threshold
(a) Conventional Step Up (b) low-dose step up
Dominant follicle becomes more sensitive to

Lower concentration of FSH
• Step up
Decrease when follicle is recruited may • Low –dose step up

decrease again 3 days later until day of hCG,
sometimes requires an increase to maintain • Step down
response
(c) Step down
Balen Adam H. et.al. Polycystic ovary syndrome a guide to clinical management. Ed.I st Taylor & Francis Group.
London 2005. p : 169 - 192
PATIENT C.O.H MONITORING SPERM I.U.I OUTCOME
SELECTION PREPARATION
- Age ♀  CC & (hCG) TVS Methode ? - Single

- Systemic Abn.  CC + Gonadot. - Multiple
TVS + E2
Obesity,  Gonadotropin -Combined
DM-2, Thyroid,  Others : Color Dopler
Pelvic. Surg. - Metformin
- Etc. - Bromocryptin -  Follicle
- Etc. - Fol. discription
• Infertility Fac. - Endometrium
• Ginecol. Pathol. - Other abnormality
• Social - Economy
• Education Blood supply of
Endom. + Fol.
CONTINUED PROFESSIONALS DEVELOPMENT
FERTILITY AND REPRODUCTIVE ENDOCRINOLOGY IV
“ PENATALAKSANAAN INFERTILITAS
SECARA PARIPURNA DAN TERPADU”
SURABAYA : 15 – 17 MEI 2008
Termasuk
Hands on
Laparoscopy
DIVISI FERTILITAS DAN ENDOKRINOLOGI-REPRODUKSI

Informasi lebih lanjut hubungi : DEPT. / SMF OBSTETRI & GINEKOLOGI
Yanti : 031-5501474 FK UNAIR / RSU DR SOETOMO SURABAYA
Irawan : 031-70576450
IUI – NATURAL CYCLE
(UNSTIMULATION)
Progesterone
17-OHP
Ng/mL
10
9
8 LH L Progesteron
FSH H e
7 FSH L
H FSH
6 FSH Estradi
ol
5 LH
4
3 Estradiol
2 Estradiol 17-OH Progesterone

17-OH Progesterone
17-OH
Progesterone Progesterone

1 Progesterone
2 4 6 8 10 12 14 16 18 20 22 24 26 28
16 days M
USG LH
12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28
IUI

NEW OvInd - Sum 1 Mar08

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SAMSULHADI

DEPT. OF OBSTETRIC & GYNECOLOGY,

Menstrual Cycles TVS

Anovulation • Regular ovulation

AGE Ovarian Reserved /

• Serum – FSH / E2 / Inhibin B Basal ?

Adequate response Poor response Counseling for other options

Anovulation • Regular ovulation

DOSES OVULATION NOTE

200 7 High dose success in

Speroff Leon (2005) ; Clinical Gynecolgic Endocrinology and Infertility, ed VIIth.

Hypothalamic Level Periphery

Half Life Longer Shorter ( + 2 days)

Multiple Ovulation Higher Less

Continue metformin Yes

Ovulation ? Yes If predictable ovulation occurs,

C. Impossible to intensive monitoring

In Infertility – PCOs cases

Need Laparoscopic assessment to explore

LOD : Laparoscopic Ovarian Drilling

High Basal LH level > 10 IU / L *

ADVANTAGES & DISADVATAGES

URINE DNA Recombinant

 h MG (FSH + LH) r FSH

1,2 < IU / L < 5

ASRM, Fertil Steril 2005, 83 : 1043 - 1046

• Gonal F Merck -Serono

• Unexplained Inf. • Severe Abnormality

There is Requirement There is

- Poor ov. Reserve - Poor ov. Reserve

Where intrauterine insemination is used to manage male factor fertility problems,

TVS TVS • ≥  18 mm hCG *

* IUI after 36 hours post hCG

1st cycle : = Dose 4 days = Dose Dose ↓

B-C-D 1-4 follicles ≥ D

NO CHANGE / 1-2 follicle ≥ 18mm >2 follicle ≥ 18mm

 Contra Indication ICSI

Patient O F Embryo E Luteal P

GnRH Agonist GnRH Antagonist

Chabbert – Buffet Nathalie, Clinical Obstetrics and Gynecology : GnRH Antagonists.

Single dose Protocol FSH

Multiple dose Protocol FSH

Semin Reprod Med. 2002. Thieme Medical Publishers

Single dose Protocol FSH

• Endrolin Kalbe Farma

GnRH agonist (Daily)

• Suprefact Hoechst AG 0,3 – 0,5 cc

Month 1 Month 2 Egg and Sperm Pregnancy *

IUI IVF -ET

 Before Starting Treatment  Age < 30 years

Stimulating Cycles Egg retrieval

hCG hCG hCG

PARAMETER FOR POSSIBLE ACTION

1 Parameter  > 2 Parameter 

Irregular Cycles Regular  Age > 30 yrs  Age < 30 yrs

There are Risk No Risk Factors

Factors of PID / of PID /

Irregular Cycles Regular  Age > 30 yrs  Age < 30 yrs

There are Risk No Risk Factors

Factors of PID / of PID /

COMPREHENSIVE FERTILITY CLINIC

Telp. 031 – 70906307 Fax. 031-5501704 e-mail:batabsby@yahoo.com

Alternate Day GONADOTROPHINS Daily GONADOTROPHINS