CURRICULUM VITAE

dr. Inu Mulyantoro, Sp.O.G., Subsp. FER, DMAS

RIWAYAT PENDIDIKAN :

❖ S1 Kedokteran Umum FK UNDIP Semarang

❖ Pendidikan Dokter Spesialis Obstetri & Ginekologi FK UNDIP Semarang
❖ Diploma in Minimal Acces Surgery, Laparoscopy Hospital, New Delhi, India
❖ Pendidikan Subspesialis Fertilitas, Endokrinologi, Reproduksi FK UNDIP Semarang
❖ S3 Pendidikan Doktor Ilmu Kedokteran dan Kesehatan FK UNDIP Semarang

RIWAYAT PEKERJAAN :

❖ Staf Divisi Fertilitas Endokrinologi dan Reproduksi Bagian Obsgin FK UNDIP-RSUP Dr. Kariadi Semarang tahun 2009 -
sekarang.
❖ Dokter Obsgin RSI Sultan Agung Semarang 2011 – sekarang.
❖ Kepala Instalasi Kutilang RSUP Dr. Kariadi Semarang tahun 2018 – 2022.
❖ Kepala Instalasi Kls III dan Unit Stroke Rajawali RSUP Dr. Kariadi Semarang tahun 2022.
❖ Ketua Kelompok Staf Medik Obstetri –Ginekologi RSUP Dr. Kariadi tahun 2022 – 2025

ORGANISASI PROFESI :
❖ Pengurus HIFERI Cabang Semarang
❖ Anggota Tim Pengembangan Pelayanan Infertilitas RSUP Dr. Kariadi
❖ Anggota IDI
❖ Anggota ESHRE
❖ Pengurus POGI Cabang Semarang
❖ Ketua komisariat RSUP Dr. Kariadi dan RSND POGI Cab. 2018-sekarang
❖ Anggota IGES
❖ Anggota PERFITRI
 Medical Managemen For
Adenomyosis: Pain, AUB, Infertility
Inu Mulyantoro
Divisi FER FK UNDIP RSUP Dr. Karisdi Semarang
 ADENOMYOSIS
• Adenomyosis is defined as the presence of ectopic endometrial
glands and stroma surrounded by hyperplastic smooth muscle
within the myometrium.

J.A. Abbott / Best Practice & Research Clinical Obstetrics and Gynaecology 40 (2017) 68e81
ADENOMIOSIS

• The clinical symptoms of pain, abnormal uterine bleeding, and

subfertility are the primary presentations of adenomyosis
• Dysmenorrhoea and dyspareunia are the most common
symptoms; however, the clinical presentation of adenomyosis is
often mixed and occasionally it may even be asymptomatic
(Farquhar and Brosens, 2006).
• No international guidelines
• Like endometriosis, uterine adenomyosis is another enigmatic
disease and remains a source of controversy. Two main theories
may explain its pathogenesis:

- adenomyosis may arise from invagination of the

myometrial basalis into the myometrium
- an alternative theory maintains that it may result from
metaplasia of displaced embryonic pluripotent
mullerian remants or differentiation of adult stem cells.

• Uterine adenomyosis is responsible for pelvic pain, abnormal

bleeding, and infertility.
 ADENOMIOSIS
- abnormal gene expression
- increased angiogenesis and
- proliferation
- decreased apoptosis
- impaired cytokine expression
- local estrogen production
- resistance to progesterone
- increased nerve density
- immunologicalstress Schematic representation of direct and indirect Morphological Uterus
Sonographic Assessment (MUSA) features of uterine adenomyosis (not
- oxidative stress endometriosis), according to modified Delphi procedure. Adapted from
Van den Bosch et al

Ultrasound Obstet Gynecol 2022; 60: 118–131

García-Solares. Origin and pathogenesis of adenomyosis. Fertil Steril 2018.
García-Solares. Origin and pathogenesis of adenomyosis. Fertil Steril 2018.
García-Solares. Origin and pathogenesis of adenomyosis. Fertil Steril 2018.
REPRODUCTIVEBIOMEDICINEONLINE35(2017)592–601
Munro. Uterine factors in embryo implantation failure. Fertil Steril
2019.
Medical Therapy
• Ovulation, menstruation, and estrogens play a major role in
endometriosis and adenomyosis development.
• For this reason, suppression of ovulation and menstruation, and
reduction of estradiol to postmenopausal levels through
hormone modulating therapies, are therapeutic means of
controlling the disease and its associated symptoms in women
not seeking pregnancy.
• ASRM : a long-life management plan, with the goal of
maximizing use of medical therapy and avoiding repeated
surgical procedures.
• GnRH Agonis
• direct antiproliferative effect within the myometrium
through the action on the GnRH receptors expressed by
adenomyotic lesions, together with a systemic and local
hypoestrogenic effect through a central downregulation
and a deep suppression of gonadotropin secretion.
• inducing apoptosis in adenomyotic tissues, reducing
inflammation and angiogenesis
• Goserelin, leuprolide and nafarelin are commonly used in
clinical practice causing uterine size reduction and an
improvement in pelvic pain and bleeding
• associated with hypoestrogenic side effects, including
vasomotor syndrome, reduced bone mineral density,
genital atrophy, and mood instability.
• Therefore, an add-back therapy should be used to
minimizeside effects
• Vercellini et al. :
clearly established that the value of treatment is a balance
between potential benefits, possible harm, and cost of care.

• They concluded that estroprogestins should be used as first-line

treatment in low- and intermediate-risk cases, with progestin-only
therapy reserved for high-risk women (those with deep
endometriosis), or those with contraindications or intolerance to
estroprogestins.
• Casper :
strongly asserts that progestin-only pills constitute a better first-
line approach than estroprogestins, considering that the dose of
ethinylestradiol in a low-dose oral contraceptive pill is equivalent
to 4 to 6 times the physiological dose of estrogen, which may
promote attachment of endometrial cells deposited in the pelvis.
COMBINED ORAL CONTRACEPTIVES

• induced decidualization and subsequent

atrophy of the endometrium, reducing
pain and AUB
• Patients with dysmenorrhea and
menorrhagia in fact may benefit from
the resulting amenorrhea, which may
provide relief of symptoms .
• COCs suppress aromatase expression in
the eutopic endometrium and in
adenomyotic foci
 PROGESTINS
Norethindrone Acetate (NETA)
• Inhibit estradiol-induced vascular
endothelial growth factor and stromal cell-
derived factor 1 in human endometrial
stromal cell
• may act on the progesterone resistance
observed in ectopic and eutopic
endometrium, but also in the inner and
outer layers of the myometrium
adenomyosis
---------Improvement of both dysmenorrhea
and bleeding after treatment
(5 mg/d dose) norethindrone acetate
• NETA may be considered an effective,
welltolerated and inexpensive medical
treatment for adenomyosis, with few and
mild side effects.
Dienogest

• shosignificant decrease of pain score

and visual analogue scale.
• A greater reduction of uterine volume
• well-tolerated, although a high
irregular uterine bleeding
• safety and efficacy of long-term
administration of DNG (52 weeks).
Dienoges
• DNG resulted effective in reducing
t
pain score scale for dysmenorrhea and
pelvic pain and in
Levonorgestrel-releasing Intrauterine
System
• effective in reducing menstrual bleeding.
• effect of levonorgestrel on adenomyosis foci
with decidualization and increase in apoptosis
in endometrial glands and stroma
• caused atrophy and shrinkage of adenomyotic
lesions through a downregulation of estrogen
receptors.
• effective and simple alternative method for
the treatment of chronic pelvic pain.
• cost effective, reversible, and long-term
treatment for women with pelvic pain
associated with adenomyosis, especially mild
and moderately severe.
Danazol
• an isoxazole derivative of 12 aloha-ethinyl
testosterone, has strong antigonadotropic
properties, lowering the mid-cycle
luteinizing hormone surge and increasing
serum free testosterone levels.
• The androgenic and hypoestrogenic milieu
cause both a direct effect on adenomyotic
lesions and an indirect effect on symtoms
• has a direct effect on cell proliferation, by
inhibiting DNA synthesis and inducing
apoptosis.
• effective in reducing the size of the uterus Danazol capsules for oral administration
and pregnancy was achieved in 66.6% contain 50 mg, 100 mg or 200 mg danazol
cases
 NON-STEROIDAL ANTI-INFLAMMATORY DRUGS

• Selective Progesterone Receptor Modulators

• Valproic Acid
• GnRH Antagonists
• Anti-platelet Therapy
Partial suppression of estradiol
An improvement in symptoms, mainly pain resulting from inflammatory endometriotic
lesions, should be the main goal of long-term treatment.

By inducing amenorrhea and halting menstrual bleeding (and reflux), or even simply
lessening its severity, the number of regurgitated erythrocytes in the pelvis can be
significantly reduced.
This serves to diminish pelvic oxidative stress, which is the main source of inflammation,
caused by an excess of free iron and heme in the peritoneal cavity .
Barbieri : the ideal solution would be to lower estradiol enough to induce amenorrhea and treat
symptoms, while maintaining sufficient levels to mitigate severe side effects, such as vasomotor
symptoms and bone mineral density loss. Partial suppression of estradiol within the 20-60 mg/ml
range could be the optimal compromise between efficacy, tolerance and safety.
Percentage of patients showing different estradiol levels in the OBE2109 trial at 12
weeks.
Donnez. Inklings. Fertil Steril 2017.
Advantages and drawbacks of the main drug groups used against adenomyosis
symptoms.

J. Clin. Med. 2021, 10, 4878.

Expected estradiol (E2) levels during the menstrual cycle, under GnRH agonist and under
GnRH antagonist therapy without and with add-back therapy (ABT).

J. Clin. Med. 2021, 10, 1085

GnRH antagonist mechanism of action
Efficacy and side effect of different doses of GnRH antagonist at 24
weeks.

J. Clin. Med. 2021, 10, 1085

Efficacy and side effects of different doses of GnRH antagonist at 52
weeks

J. Clin. Med. 2021, 10, 1085

Thank you