Case Report:

Adenomyosis excision followed by successful live birth after three

consecutive IVF
I Made Purnama Adimerta1, I B Putra Adnyana1,2, Anom Suardika1,2
1. Departement of Obstetrics and Gynecology, Medical Faculty Udayana University –
Sanglah General Hospital
2. Royal IVF clinic, Bali Royal Hospital (BROS)

Background:
Adenomyosis has been established as a cause of infertility and impact the result of IVF. The
presence of endometrial tissue (glands and stroma) within the myometrium; heterotopic
endometrial tissue foci are associated with a variable degree of smooth muscle cell
hyperplasia is the definition of adenomyosis.1 Conservative surgery alone or combined with
GnRH agonist could be the modality to preserve future fertility. However, the proper time to
start IVF, the best stimulation protocol and its impact to the outcome still not established yet.
Clinical case:
A 38‐year women attending fertility clinic with primary infertility. This patient complained
severe menstrual pain and heavy menstrual bleeding which were typical for adenomyosis.
The couple were married for 18 months and no pregnancy had been achieved.
Gynecologic examination found an enlarged uterus with no adnexal masses palpable.
Initial Ultrasound scan showed enlarged globular shaped uterus with thick posterior wall
showed heterogeneous echo structure. CT scan imaging were reporting a 6.1 cm x 7.5 cm
solitaire nodule in the posterior uterine wall concluded as uterine fibroid which was
conflicted with our diagnostic.
Laparoscopic was performed as diagnostic and treatment procedure, it was found that
the uterine was enlarged with 20 cm x 15 cm size, with mild adhesions. The ovarium size and
shape were normal. The fallopian tubes were bilaterally obstructed.
Initially the laparoscopic excision was planned but due to its large size and technical
difficulties for complete excision, laparotomy was performed followed by Osada’s triple flap
suture technique. Antibiotic and analgesic were administered following the procedure and the
patient discharged after two days without surgical complication.

.
figure 1: The enlarged uterus with mild adhesion from laparoscopic view
 .
figure 3: The uterus exteroriated from abdominal cavity.

The histopathologic result was completed next day, confirming several gland and endometrial
tissues within the myometrium which was a sign of adenomyosis.
After surgery patient received GnRH agonist treatment immediately after the surgery.
Leuprolide acetate (Tapros; Takeda, Japan) 3.5 mg were administrated intramuscularly every
4 weeks for three months. After the treatment patient experienced significant improvement in
menstrual pain and the menstrual blood volume were normal.
Six months after surgery the couple attend our clinic to start the IVF-ICSI procedure.
At the 2nd menstrual day basal hormones examinations were performed and the results were
LH 1.98 mIU/mL (1.5-8.0 mIU/mL), FSH 5.53 mIU/mL (3.9-12.0), Prolactin 26.35 ng/mL
(0.5-20), E2 18.55 pg/mL (18-147), and the AMH level were 3.06 ng/mL. Short protocol
controlled ovarian stimulation were start with 225 IU rFSH (Gonal F), at day 13th oocytes
retrieval yielding total 11 oocytes followed by ICSI and three fresh embryos were transfer on
day 3. Clinical pregnancy was achieved, but unfortunately complicated with anembryonic
pregnancy which was found at 7 weeks pregnancy and curettage was performed to end the
pregnancy.
Due to the failure, the patient attended another clinic to get second opinion and
underwent second IVF procedure. This second attempt was also unsuccessful and failed to
established a clinical pregnancy.
Eighteen months after previous conservative treatment, patient come to our clinic and
prepared for the third IVF-ICSI procedure. Ultrasound scan found the uterus size was 5.8 cm
x 3.2 cm x 3,0 cm and endometrial thickness was 0.67 cm, the ovarium shown total 9 antral
follicles. Blood tests for basal hormones profile were normal. A short protocol stimulation
was performed with starting dose 225 IU of rFSH (Gonal-F; Merck-Serono), after hCG
(ovidrelle; Merck Serono) injection, oocyte retrieval was done at day 15, yielding 10 oocytes.
Following ICSI three top quality embryos were transferred. At the 5th week following embryo
transfer intra uterine gestational sac was found and fetal heart beat were confirmed at 8 weeks
gestational age. Fetal morphologic scanning and amniocentesis was conducted at 16 weeks
pregnancy, reporting a normal 46 XY baby with no major morphologic anomaly. Both
normal fetal growth and normal routine laboratory results were observed during antenatal
care. However, at 34w4d gestational age, this pregnancy was complicated with PPROM,
immediate prophylactic antibiotic was administered and emergency cesarean section was
performed, delivering a healthy 2000 g male baby, and both discharged without any serious
complication.

Discussion
In present case, the patient was met the clinical criteria for adenomyosis. The clinical
triad of uterine adenomyosis includes abnormal uterine bleeding (nearly 50%), secondary
dysmenorrhea (nearly 30%) and an enlarged, tender uterus.2
 Infertility was another problem of this patient. The patient had attempt to conceived
for 18 months but had not succeed. Bilateral fallopian tube obstruction was found as the
cause of infertility, this may be related to adenomyoma that distorts the uterine cavity and
obstruct the tubal ostia and interfere with sperm migration and embryo transport. 3
Adenomyosis could impact the reproductive outcome, decreased clinical pregnancy rate and
increased abortion rate were related to adenomyosis. The increased rate of spontaneous
abortion in women with adenomyosis were related to the uterine junctional zone dysfunction,
3
implantation failure was found to be higher when JZ was greater than 7 mm. Endometrial
environment also altered by adenomyosis. Women with adenomyosis had more accumulation
of macrophages which may secrete cytokines such as TNF alpha, IL-1 and reactive oxygen
and nitrogen species which were hostile for embryo implantation.4
This patient had a large adenomyosis at the posterior uterine wall and we performed
adenomyosis excision followed by the triple flap suturing method (Osada procedure). The
triple-flap method offers some advantages. First, it permits the excision of the affected tissues
more widely and thoroughly than the conventional wedge resection, resulting improvement in
dysmenorrhoea and hypermenorrhoea. Secondly, the large defects created by the wide
excision of the lesion can be reconstructed with adequate thickness by the three layers of
myometrium in the reconstructed wall, which was important for sustaining a normal
5
pregnancy without the risk of uterine rupture. In a recent review the authors found that
surgical approach could provide significant improvement in symptom (> 81% dysmenorrhea
control and 50% menorrhagia control) of women with adenomyosis and/or adenomyoma.
Pregnancy rates appeared to be > 46% in women treated with Type II conservative
cytoreductive surgery, and 60% in women treated with Type I adenomyomectomy surgery;
two-thirds of the women treated with Type II surgery and more than four-fifths of the women
treated with Type I surgery had a successful delivery.1
After the surgery, we treat the patient with GnRH agonist injection to maximize the
chance of successful IVF. The effects of GnRHa treatment before IVF in women with
adenomyosis were evaluated in two studies. The results showed that pretreatment with
GnRHa appears to be beneficial to the pregnancy rate. 6,8 The use of GnRHa seems to have
beneficial effects in the results of surgery and ART, probably because of its effects on
reducing adenomyosis foci in the uterus.8 First IVF were done six months after the treatment,
resulting a clinical pregnancy but failed due to anembryonic pregnancy, the second IVF also
failed even to achieve a clinical pregnancy. Adenomyosis appeared to have a detrimental
impact on IVF/ICSIoutcome in terms of reduction in clinical pregnancy rate and increasein
miscarriage risk, although the potential confounding effect of endo metriosis could not be
adequately assessed.9 There are various hypotheses concerning the effects of adenomyosis on
implantation, including impaired endometrium-myometrium interface, altered uterine
peristaltic activity, altered endometrial-myometrial vascular growth, increased levels of
prostaglandins in the ectopic endometrial epithelium, higher expression of aromatase
cytochrome P450 in the eutopic endometrium, decreased integrin b3, osteopontin, and
leukemia-inhibiting factor, and impaired HOXA-10 gene function during the implantation
window.6,9 In vitro fertilization result also altered by the presence of adenomyosis. The rates
of implantation, clinical pregnancy per-cycle, clinical pregnancy per embryo transfer,
ongoing pregnancy, and live birth were significantly lower among women with adenomyosis
underwent IVF.6
The Third IVF were done 18 months after the treatment, resulting a single livebirth
without a serious complication. We assumed the result might related to the healing process of
the uterus, in Osada’s procedure the results of the post-operative examination using contrast-
enhanced MRI or a transvaginal ultrasonography with color Doppler imaging showed that the
blood flow in the operated area had returned to normal within 6 months in almost all cases
(99/104, 95.2%). However, in a few cases (5/104, 4.8%) the blood flow took nearly a year to
return to normal.5 Spontaneous pregnancy might occur to 36 months after complete
conservative surgery, suggesting that the therapeutic effect of conservative surgery might
maintain longer than that of medical treatment. Taken together, conservative surgery might
be an alternative if subfertile women with adenomyosis fail to become pregnant after an
active treatment, including a long protocol GnRH agonist treatment and IVF/ ICSI.2 As the
common surgical wound healing process, the event of Injury, inflammation, proliferation,
repair and finally remodeling of the wound occurs immediately after injury and completed up
to one year.10
Adenomyosis treatment both surgical and medical may increase the chance of having
a successful pregnancy. However, determine a proper evaluation tools and proper time to
start an IVF after conservative surgery still need further research.

Conclusion: In present case, adenomyosis excision and GnRH agonist treatment improve the
outcome of IVF, 18 months after the procedure.

Reference
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