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Danhof.

Hum Reprod Update, 2020

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Danhof. Hum Reprod Update, 2020

#berjuangbersama

Danhof. Hum Reprod Update, 2020

#berjuangbersama
Danhof. Hum Reprod Update, 2020

#berjuangbersama

Gonadotropin dosis rendah kronik

Normal women

Conceptualized model of
granulosa cell responses to a
range of follicle stimulating
hormone (FSH) doses
administered during
ovulation induction

PCOS women Yen and Jaffe. Reproductive Endocrinology, 2014

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NOMOGRAMS FOR PREDICTION OF
INDIVIDUAL FSH THRESHOLD
DOSE
a. Amenorrhea
b. Oligomenorrhea
c. Anovulatory cycles with cycle
length 21–35 days

Andersen et al. Hum Reprod, 2008

Chronic low dose gonadotropin


FSH AM
H

Gently increasing the serum FSH level reduces the AMH excess, thus relieving the
inhibition from the latter on aromatase expression by selectable follicles and allowing the
emergence of a dominant follicle

Jonard et al. J Clin Endocrinol Metab, 2007

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Fertilisasi In Vitro Penunjang fase luteal

Stimulasi ovarium terkendali banyaknya korpora lutea

Penekanan kadar LH endogen

Petik oosit

Sel granulosa terambil

Penyuntikan hCG
Korpus luteum tidak
sempurna

Insufisiensi fase luteal

Fatemi, 2009
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JENDELA DAN BATAS AMAN KADAR


PROGESTERON

transisi hCG
dari kehamilan
Kadar progesteron
27 ng/mL

Waktu: 4 hari

Connel dkk. Fertil Steril,


2015

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KAPAN PEMBERIAN PROGESTERON
SEBAGAI PENUNJANG FASE LUTEAL PADA FIV ?

Connel dkk. Fertil Steril,


2015

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EFEK AKSELERASI ENDOMETRIUM TERHADAP


KEHAMILAN
“ akselerasi = insufisiensi fase luteal

Akselerasi
No Studi Tahun Protokol p
≤ 3 hari > 3 hari

Kehamilan biokimia

1 Ubaldi dkk 1997 hMG-agonist 13/32 0/7 0.0


4

Kolibianakis dkk 2002 rFSH- 14/49 0/6 0.1


antagonist 3

Kehamilan klinis

2 Ubaldi dkk 1997 hMG-agonist 10/32 0/7 0.0


9

Kolibianakis dkk 2002 rFSH- 11/49 0/6 0.1


antagonist 9
Kolibianakis et al. Fertil Steril,
2005 Kehamilan lanjut

3 Ubaldi dkk 1997 hMG-agonist 10/32 0/7 0.0


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9
PENUNJANG FASE LUTEAL
1 Menyelamatkan korpus luteum

LH / hCG
eksogen

Progestogen eksogen

2 Suplementasi hasil korpus luteum

Estrogen eksogen

Frozen embryo transfer


surrogacy

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PENUNJANG FASE
LUTEAL

Didrogesteron Suntik progesteron Progesteron hCG


oral / vaginal / rectal
3 x 10 mg / day progesterone in oil 1500 IU 2x /
50 – 100 mg / hari micronized progesterone minggu
3 x 200 mg / hari

PROGESTOGEN PAINFU TINGKAT RISIKO


SINTETIK L TOLERANSI OHSS
(stabil dan ketersediaan- (menjadi isu utama)
hayati tinggi)

“ live birth were not different “

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Bedah minimal invasif

Kapan LAPAROSK ?
HIDROSALPING
OPI

OKLUSI TUBA BILATERAL

KISTA ENDOMETRIOSIS

MIOMA UTERI SUBMUKOSUM

MIOMA UTERI INTRA MURAL MENDESAK


KAVUM UTERI

SALPINGOSTOMI

#berjuangbersama

Second surgery for recurrent endometriomas is more harmful to healthy


ovarian tissue and ovarian reserve than first surgery

Muzii et al. Fertil Steril,


2015

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Second surgery for recurrent endometriomas is more harmful to healthy
ovarian tissue and ovarian reserve than first surgery

Muzii et al. Fertil Steril,


2015

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MANAGEMENT OF
ENDOMETRIOSIS

5
ESHRE Guidelines,
2013

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MANAGEMENT OF
ENDOMETRIOSIS

9
ESHRE Guidelines,
2013

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Hiperprolaktinemia Cek WHO GRUP


TSH KonsensusIV
HIFERI,
TSH tinggi TSH normal2010
(hipotiroid)

Penanganan hipotiroid MR
I

Normal Mikroadenoma Makroadenoma Stalk effect tumour

Bromokriptin Penekanan chiasma opticum


Mulai 2.5-7.5
mg
Pembedahan
Compliance Compliance buruk
baik Tidak respon
Prolaktin > 25 ng /
ml
Evaluasi Cabergoline 0.25 mg/minggu
Siklus haid
Prolaktin: 6 bulan
MRI: 1 tahun
Makroadenoma: bila hamil, agonis dopamin
Anovulas Ovulas Konseps dilanjutkan
i i i
Penghentian agonis dopamin :
1. Setelah 2-3 tahun pengobatan, kadar prolaktin normal, dosis agonis dopamin bisa diturunkan perlahan
2. Bila selama 1 tahun kadar prolaktin normal dengan dosis agonis dopamin yang telah diturunkan, pengobatan bisa
dihentikan
Amenorea sekunder
KLASIFIKASI ANOVULASI WHO

Hipogonadotropin-hipogonadism
1
FSH dan E2 rendah

Normogonadotropin-
2
normogonadism
FSH dan E2 normal SOPK

Hipergonadotropin-hipogonadism
3
FSH tinggi dan E2 rendah

4 Hiperprolaktinemia
PRL tinggi

Dhont M. Int Cong Ser, 2005

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4 Amenorea sekunder
FSH
WHO
rendah
3 I
E2 rendah
Estrogen endogen rendah UJI
+ P
ve
- +
FSH tinggi ve ve
2 E2 rendah
UJI
WHO EP •Tidak ada obstruksi saluran
III
reproduksi
•Proliferasi endometrium
1 - adekuat
Asherman ve •Estrogen endogen cukup
Endometritis •Poros hipotalamus-hipofisis-
ovarium baik
KOMPARTEME
N
ANOVUL WHO II
ASI WHO
IV
DIMINISHED OVARIAN HIPERPROLAKTINE SOP
RESERVED MIA K
PEMERIKSAAN
LANJUTAN
No Kinis Uji P Uji EP AMH Prolaktin Diagnosis
1 (+) Tinggi Normal WHO II
SOPK
2 (+) Normal Tinggi WHO IV
Hiperprolaktinemia
3 Amenorea (-) (+) Normal WHO I
atau Hipogonadotropin
oligomenorea hipogonadisme
4 (-) (+) Rendah WHO III
Insufisiensi ovarium
primer
5 (-) (-) Amenorea uteriner

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Primary amenorrhea

Secondary sexual characteristic

N Ye
o s
Uterus Uterus

Uterus absent Uterus present Uterus absent Uterus present

Karyotyp FS Karyotyp Outflow obstruction


e H e

Lo Hig X X Hymen
X imperforata
w h X Y
Y
Karyotyp
PAIS Rokitansk CAIS
e y
X X
X O
CAH HH Turner
Histeroskopi dan infertilitas

Hysteroscopic surgery is a clinical tool used in women with


1. Abnormal uterine bleeding (AUB)
2. Infertility or recurrent pregnancy loss due to several uterine pathologies such as
uterine septa, adhesions, myomas and polyps

Ambrosini et al. Eur J of Obstet Gynecol and Reprod Biol, 2008 ; 139 : 210–
214

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Results of 2500 office hysteroscopy prior to


IVF
Finding Number %
Normal 1927 77.1
Abnormal
• Endometrial polyps 192 7.7
• Mullerian anomalies (septum) 130 5.2
• Myoma 96 3.8
• Mullerian anomalies(bicornu uterus) 28 1.1
• Polypoid endometrium 31 1.2
• Adhesion 27 1.1
• Endometrial hyperplasia 22 0.9
• T-shaped uterus 18 0.7
• Endometritis 13 0.5
• Cervical polyps 13 0.5
Karayalcin et al. RBM Online,
• Cervical stenosis 3 0.1 2010

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Prevalence of unsuspected uterine cavity abnormalities diagnosed by office
hysteroscopy prior to in vitro fertilization
H.M. Fatemi, J.C. Kasius, A. Timmermans, J. van Disseldorp,
B.C. Fauser, P. Devroey, and F.J. Broekmans

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RESULTS OF 1000 OFFICE HYSTEROSCOPY


PRIOR TO IVF
Finding Number %
Normal 618 62
Abnormal
• Endometrial polyps 323 32
• Submucous fibroids 27 3
• Intrauterine adhesions 25 3
• Polypoid endometrium 9 0.9
• Septum 5 0.5
• Bicornuate uterus 3 0.3
• Retained products of conception 3 0.3

Hinckley et al. JSLS,


2004

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Endometrial polyps are identified by hysteroscopy in 16.5-
26.5% of women with unexplained infertility

Pregnancy Rate after IUI


Hysteroscopy polypectomy vs control: 63.4% vs 28.2%

Pregnancy Rate in Infertile Women

(+) Polypectomy Normal uterine cavity

Varasteh et al 78.3% 42.1%

Shokeir et al 50%

Spiewankiewicz et al 76%

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Chronic endometritis: correlation among hysteroscopic, histologic, and bacteriologic


findings in a prospective trial with 2190 consecutive office hysteroscopies

Micropoly
p

Cicinelli et al. Fertil Steril,


2008

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Chronic endometritis: correlation among hysteroscopic, histologic, and
bacteriologic findings in a prospective trial with 2190 consecutive office
hysteroscopies

Cicinelli et al. Fertil Steril,


2008

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Outpatient hysteroscopy and


subsequent IVF cycle outcome: a
systematic review and meta- analysis

Toukhy. RBM Online,


2008

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Results of office hysteroscopy prior to IVF in
RSCM
Findings No. %
Normal 37 25.5
Chronic endometritis 26 17.9
Endometrial polyp 54 37.2
Endometrial polipoid 8 5.5
Bicornu uterus 1 0.6
Endometrial hyperplasia 6 4.1
Fibroid 1 0.6
Cervical polyp 5 3.5
Cervical stenosis 3 2
Adhesion / septum intra uterine 4 2.8
TOTAL 145 100 Wiweko et al. Klinik Yasmin,
2010

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Future Applications of Office


Hysteroscopy
No Application
1 Study of endometrial surface changes in various phases of menstrual cycle
2 Study of intratubal milieu, biochemistry of tubal secretions, tubal motility with open-
ended catheters
3 New methods of tubal occlusion
4 Intratubal insemination, GIFT or ZIFT
5 Study of endometrium to assess adequate maturity
6 Chorionic villus sampling
7 Embryoscopy-fetoscopy

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Kontrasepsi dan fertilitas

3 PERTANYA
AN

1. Bagaimana kesuburan dapat kembali


pasca kontrasepsi hormonal ?
2. Berapa lama kesuburan dapat kembali
pasca kontrasepsi hormonal ?
3. Apa pilihan kontrasepsi hormonal
yang cepat mengembalikan kesuburan ?

#berjuangbersama

KONTRASEPSI
Sunti HORMONAL
Pi
k
l

MANFAAT KONTRASEPSI
MENCEGAH, MENUNDA atau
MENJARANGKAN kehamilan

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FAKTOR YANG MEMPENGARUHI KESUBURAN
PASCA KONTRASEPSI
USIA
PARIT
AS

kebiasaan merokok obesitas lingkungan

Sperma NORM
Saluran telur AL
D. Mansour et al. / Contraception 84 (2011) 465–477

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Terdeposit dalam GnR


jaringan lemak
H

Keseimbangan FSH dan LH


terganggu
Sulit
hamil??

#berjuangbersama
KESUBURAN PASCA KONTRASEPSI
HORMONAL
Metode Lama Usia pasca Kehamilan 1 Waktu yang
Kontrasepsi pemakaian kontrasepsi tahun pasca dibutuhkan
(tahun) (tahun) kontrasepsi untuk hamil
(%)
Kontrasepsi Oral 1.7-7.2 26.8-28.1 79.4-95 2.5-3 siklus
Implan 2.4-4.7 25.8-29.7 37.5-85.6 2.9-7.7 bulan
Suntik 0.6-1 24.5-25.6 72.5-82.9 4.5-5 bulan

D. Mansour et al. / Contraception 84 (2011) 465–477

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Laju kehamilan pasca pil kontrasepsi berkisar 72%–94%, sebanding dengan pasca AKDR
(71%–92%), pil progestin(70%–95%), kondom (91%), and KB alamiah (92%)

Barnhart et al. Fertil Steril, 2009

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when is it safe to switch ?
ULTRA LOW DOSE ESTROGEN OCP HORMONAL
THERAPY

childbearing age perimenopause menopause

natural estrogen = estradiol valerate OC


Safety
P
• Impact of hormone
• Ovarian function

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Intra cytoplasmic morphologically selected sperm injection

Denny Sakkas. Post Graduate Course, ASRM annual meeting -


2014

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Regular (ICSI) Versus Ultra-High Magnification (IMSI) Sperm Selection for Assisted
Reproduction

Danielle M Teixeira, Andre Hadyme Miyague, Mariana Ap Barbosa, Paula A Navarro, Nick Raine-
Fenning, Carolina O Nastri, Wellington P Martins

The updated search retrieved 535 records; we included 13 parallel-designed RCTs comparing
IMSI and ICSI (four studies were added since the previous version), comprising 2775 couples
(IMSI = 1256; ICSI = 1519)

The current evidence from randomised controlled trials does not support or refute the clinical use
of intracytoplasmic morphologically selected sperm injection (IMSI)

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Quality Control Laboratorium


Embriologi

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THE RESPONSIBILITIES OF THE EMBRYOLOGY LABORATORY


DIRECTOR
No Description
1 Providing accessibility for on-site, telephone, or electronic consultations as needed.
2 Ensuring that the physical plant (space, facilities, and equipment) and environmental conditions of
the laboratory are appropriate and safe.
3 Maintaining aseptic conditions in the laboratory
4 Ensuring that patient confidentiality is maintained throughout the laboratory ART process
5 Providing an approved procedural manual to all laboratory personnel and establishing and
maintaining a laboratory quality assurance program
6 Providing consultation to physicians and others, as appropriate, regarding laboratory aspects of
treatment.
7 Employing a sufficient number of qualified laboratory personnel to perform the quality laboratory
procedures.
There should be a backup plan in case of emergency.
8 Ensuring that all personnel receive appropriate training for the ART laboratory procedures to be
performed, obtain the required number of annual continuing education hours, and demonstrate
continued competence for the ART laboratory procedures performed.
Practice Committee of American Society for Reproductive M. Revised minimum standards for practices offering assisted reproductive
technologies. Fertil Steril, 2014

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CODE OF PRACTICE FOR ASSISTED REPRODUCTIVE
TECHNOLOGY UNITS
INTERNATIONAL EDITION

Fertility Society of Australia


Reproductive Technology Accreditation Committee

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PRA IMPLANTATION GENETIC


TESTING (PGT)

Carlos Simon. Post Graduate Course, ASRM annual meeting -


2014

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Carlos Simon. Post Graduate Course, ASRM annual meeting -
2014

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Carlos Simon. Post Graduate Course, ASRM annual meeting -


2014

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Correlation between embryo morphology and
development and chromosomal complement
Vy Phan, Eva Littman, Dee Harris, Antoine
La

Objective: To analyze the correlation between embryo morphology and the


chromosomal status using the array comparative genomic hybridization [array
comparative genomic hybridization (a-CGH)] technique for screening 23
chromosome pairs in a single blastomere biopsy from Day 3 embryos

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1257 cleavage-stage embryos were biopsied and analyzed for aneuploid.


A total of 783/1257 (62.3%) were aneuploidy and 474/1257 (37.7%) were euploid.

slow developed embryos that have 4-6 cells have significantly higher aneuploidy rate of 83.1%

Phan et al. As Pac J Reprod,


2014

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Embryos with fast development also have aneuploidy rate nearly 1.2 times higher than
embryos which have 7-9 embryos (RR= 65.7/56.3= 1.167; P<0.001).

Figure 1. Chromosome abnormalities and cellular stage.

Phan et al. As Pac J Reprod,


2014

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Table 2. Chromosomal abnormalities and percentage of fragmentation

The embryos with a lot of fragmentation 16%- 30% have the highest aneuploidy rate
(75.1%)

Phan et al. As Pac J Reprod,


2014

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Uneven blastomeres have 1.8 times higher aneuploidy rate compared to embryos
with even blastomeres
(RR=81.6/44.1=1.85; P < 0.001)

Phan et al. As Pac J Reprod,


2014

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Methods:

Blastocysts from 437 patients underwent trophectoderm biopsy followed by array


comparative genomic hybridization.

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A greater number of euploid blastocysts in a given cohort predicts
excellent outcomes in single embryo transfer cycles

The number of euploid blastocysts produced in a given cohort following CCS is predictive of
improved clinical pregnancy rate.
Morin et al. J Assist Reprod Genet,
2014

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PERTANYAAN DAN
DISKUSI

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