Uterine fibroids are noncancerous growths of the uterus that often appear during childbearing years. Also called leiomyomas (lie-o-my-O-muhs) or myomas, uterine fibroids aren't associated with an increased risk of uterine cancer and almost never develop into cancer. Fibroids range in size from seedlings, undetectable by the human eye, to bulky masses that can distort and enlarge the uterus. You can have a single fibroid or multiple ones. In extreme cases, multiple fibroids can expand the uterus so much that it reaches the rib cage and can add weight. Symptoms: Many women who have fibroids don't have any symptoms. In those that do, symptoms can be influenced by the location, size and number of fibroids. In women who have symptoms, the most common signs and symptoms of uterine fibroids include: Heavy menstrual bleeding Menstrual periods lasting more than a week Pelvic pressure or pain Frequent urination Difficulty emptying the bladder Constipation Backache or leg pains

1. • President ‐ Association of Private Gynecologist of Lucknow
• Vice President – ISPAT U.P. Chapter
• Vice Chairman ‐ ISAR U.P. Chapter
• Past Secretary ‐ ISAR U.P. Chapter
• Director ‐ Javitri Hospital & Test Tube Baby Centre, Lucknow.
• Javitri Institute of Para Medical Sciences
• Board member Endometriosis Committee, FOGSI (2017‐2019)
• Board member Bayer Zydus
• Borad member mankind
• Secretary ‐ I.H.R.F.
• Member organising committee – AICOG 2020. ,IAGE 2019
• Organising chairperson –ISPAT Biennial conference 2022 Lucknow
• Organising chairperson –ISAR (U.P. chapter)
International Infertility Training :
• Vitrification & Laser Hatching ‐ Thomson Medical Center Malaysia, University Collage London
• I.V.F. & I.C.S.I. ‐ Cleave land, U.S.A.
• Embryology ‐ Brusselss, Belgium & Damansara, Fertility Center Malaysia & TMC
• Clinical Infertility ‐ Bourn Hall – England
• Embryo Biopsy ‐ Barcelona ‐ Spain
• Stem Cell ‐ Miami ‐ Florida
Special Awards and Recognition :
(1) NARI Award 2014
(2) Istri Shakti Puraskar Award 2015
(3) Aspiring Gynecologist & IVF Specialist of India award 2019
(4) Isar Champion Award 2020.
(5) Corona warrior Award 2021
(6) Nari Award 2021
(7) Women Achievers award 2022 by Governor of UP

2. Fibroid & Fertility
Let’s together
Help Her
“PRESERVE THE UTERUS

3. Uterine Fibroids- Introduction
A benign tumour of muscular and fibrous tissues, typically
developing in the wall of the uterus
Up to 40% women over the age of 40 have Uterine
Fibroids
A benign tumour of muscular and fibrous tissues, typically
developing in the wall of the uterus
Up to 40% women over the age of 40 have Uterine
Fibroids
Nearly 20-30% Indian women in reproductive age group
have fibroid uterus3
At any given time, nearly 15-25 million Indian women
have fibroid fibroid uterus3
Nearly 20-30% Indian women in reproductive age group
have fibroid uterus3
At any given time, nearly 15-25 million Indian women
have fibroid fibroid uterus3
5‐10% of infertile females suffered with Fibroid
2‐3% ‐‐single cause of infertility
5‐10% of infertile females suffered with Fibroid
2‐3% ‐‐single cause of infertility

4. • ‐ ve impact on fertilization
• Anatomic distortion of the cervix
• Enlargement & deformity of uterine
cavity
• Uterine contractility and peristalsis
• Distortion or obstruction of tubal
ostia
• ‐ ve impact on Implantation
• Alteration of endometrial contour
• Focal endometrial vascular
disturbance
• Endometrial inflammation
• Secretion of vasoactive substances
• Disturbance of junctional
myometrial zone
• Enhanced endometrial androgen
environment
Impact of Fibroid on fertility

5. • Type of Fibroid
Submucus ‐‐Most detrimental
Intramural fibroid ‐‐‐Modest impact
‐Ve impact on fertility
• Size of Fibroid >4cm
• Number of Fibroids >3
• Distance from the Endometrium < 5mm: No effect
Impact of Fibroid on fertility outcome

6. • TVS
Confirm diagnosis
Locate the myomas
• TAS:
Uterus >12w
• SIS Vs office hysteroscopy
easier
Less uncomfortable
Less expensive
• MRI
When the number of lesions >5 precise mapping[0x
Patient Evaluation

7. Progesterone Receptor binding is three times higher in fibroid as in myometrium
The future of medical therapy
Traditionally the dominant
thought was that fibroid growth was fueled
by estrogen
• It has been discovered that
progesterone and PRs are
required for cellular proliferation
and fibroid growth
• Fibroids express elevated levels
of both types of PR: PR‐A and
PR‐B
Pathophysiology
Progesterone
plays a vital role in promoting uterine fibroid growth
Uterine fibroids is progesterone‐dependent disease

8. Progesterone
a physiological regulators of Uterine Fibroid growth
BCL-2
Expression in
fibroid cells
EGF
Expression in
fibroid cells
TNF-
Expression in
fibroid cells
Inhibit
Apoptosis
↑Angiogenesis
↑Proliferation
P
R
O
G
E
S
T
E
R
O
N
E

9. Surgical Medical
Treatment for Fibroids
Myomectomy
(Removal of fibroid)
Hysteroscopic
myomectomy
Harmonal
NonHarmonal
Age & parity
Child bearing expectation
Extent & Severity of Symptoms
Size,number & location of Myomas
Risk of Malignancy
Other Modalities
MRgFUS
UAE
Laproscopic
myomectomy
Minilap
myomectomy

10. Medical therapies for Uterine fibroid Management
Symptomatic bleeding & pain
Tranexamic acid
NSAIDs
OCPs & Progesterogens
• Etiologic Management
GnRHa
SPRMs
Mifepristone
Ulipristal acetate
Raloxifen

11. Drawbacks of Medical Treatment
.
GnRH agonists:
Leuprolide,Triptorelin
 Incompliance: Monthly IM injections
 Recurrence: Myoma usually return to
the pre‐therapy size within a few
months of discontinuation
 Hypoestrogenic side effects:
 67% patients report Hot flashes
 Vaginal dryness, mood swing
 Reduced BMD: Risk of osteoporosis
 Can reduce fibroid size by up to 50%
 Can not be used for extended
period
NSAIDs
 Lack of supportive evidence
from clinical trials
 GI side effects
 Risk of gastric ulceration
Anti‐fibrinolytics (T.A)
 Use to treat Menorrhagia &
Dysmenorrhea
 Can increase the size of
myoma
Danazol Androgenic S/E
and liver dysfunction
OCPs
 Break through bleeding
 Do not affect fibroid size
 May increase the size of myoma
LNG IUD ‐ more Irregular bleeding
Aromatase inhibitors
 Causes hypoestrogenic side effects
 Insufficient evidence to support use of
for treatment of uterine fibroid
Progestins
 Use to treat Menorrhagia &
Dysmenorrhea
 Breakthrough bleeding
 Can increase size of myoma

12. SPRMs – The future of Uterine fibroid therapy
Selective progesterone receptor modulators (SPRMs) are designed to compete at the PR binding site in
a tissue‐specific manner
A mix of agonistic and antagonistic effects
Unlike GnRH agonists, which only affect the pituitary gland, SPRMs have direct effects on the pituitary gland
the fibroid, and the endometrium
SPRMs produce a reduction in the fibroids by inhibiting the cell proliferation and by inducing apoptosis
Mifepristone ULIPRISTAL
To Erase Fibroids with Ease

13. Mifepristone
10/25mg
Mifepristone bind with
high affinity to
progesterone receptors on
targeted tissues with
limited side effects
Pituitary gland
Endometrium Fibroid
Mifepristone
Targeted action to Erase Uterine Fibroids
Inhibit Ovulation thus
inducing Amenorrhea
Reduces Uterine Blood flow;
Helps to shrink the fibroids
endometrium vasculaturization
stromal VEGF menstrual blood loss
3 2 1
BCL-2
Expression in
fibroid cells
Induces
Apoptosis
EGF
Expression in
fibroid cells
↓Angiogenesis
TNF-
Expression in fibroid
cells
↓Proliferation
Decreases Fibroid Size & Volume
1
2
3

14. Benefit of Mifipristone in uterine Fibroid
Increases
Hb level
Reduces duration
of surgery
Shrink Fibroid
size & Volume
Correction of Patient Anemia
Reduction of Intraoperative
Blood loss
Facilitation of Myomectomy
instead of Hysterectomy
Ideal Dosage of Mifepristone
DOSAGE: 10‐25mg daily minimum for 3 months.
For best results better to starts from day 1‐7 of the menses.
It can be safely given to young patients above 20 years of age.
Up to 6‐12 months safety is proven in clinical trials
 No risk of decrease in BMD & Osteoporosis.

15. Ulipristal Acetate Effects
 A first‐in‐class, effective, well‐tolerated SPRM specifically designed for uterine fibroids
 Reversible blockage of progesterone receptors binds progesterone receptors, but not estrogen receptors
 No affinity on mineralocorticoid receptors
Inhibition of progesterone activity
Reduced FSH release
Maintains physiological mid follicular
estrogen levels of 60-150pg/ml
Inhibits cell proliferation &
Stimulates apoptosis
Significant & sustained
fibroid volume reduction
Rapid control of
Heavy bleeding
Increase Haemoglobin levels
Contributes to controlled bleeding
and amenorrhea

16. PEARL Studies (European studies)
PEARL I
(UPA vs placebo for 13
weeks)
N= 237; 3-10 cm fibroid
 Control of uterine bleeding in 91% of patients
 21% reduction in total fibroid volumemj
PEARL II
 Amenorrhea induced in 7 days (UPA) & 21 days
(Leuprolide)
 No significant re-growth till 6 months (UPA group).
Regrowth in Leupolide started within 1-3 months after
stopping
 Hot flushes significantly less in UPA group
(UPA vs Leuprolide acetate
for 3 months
N=307; 3-10 cm fibroid)
PEARL III +
extension
 79% women with amenorrhea in first course & 90%
women with amenorrhea in fourth course
 Fibroid volume change was -45% in first course & -
72% in fourth course
Long-term efficacy: up to
four 3-month course
N=209;
PEARL IV
 Patients achieving controlled bleeding during two
treatment courses were >80%
 Menstruation resumed after each treatment course
 Pain and QoL improved
Efficacy & safety of two 12-
week courses
N=451; 3-12 cm fibroid

17. • Multicenter retrospective cohort study
• Women aged 18–55 years, who received pharmacologic
therapy with UPA 5mg orally once a day
• 57.0% women treated with UPA did not undergo
surgery
• Surgical treatment occurred in 70, 23, 32, and 8% of the
women who received one course, two courses, three
courses, or four courses, of UPA treatment
The effectiveness and safety of repeated UPA treatment courses in reducing
number of women requiring surgery is confirmed by real-world data
Gynecol Endocrinol. 2020 Feb;36(2):171-174.

18. Ulipristal acetate Dosage & Administration
Indications
• Management of symptomatic uterine fibroids
• Pre/Post‐operatively for Large/ Seedling Fibroids
Dosage‐‐‐‐‐ 5 mg once daily
Do LFT before starting UPA
• However, ulipristal does not belong to drug classes commonly associated with
Drug‐induced liver injury (DILI)
• Thus, this may be a type of idiosyncratic DILI
• European Medicines Agency issued recommendations for ensuring liver safety
Ulipristal acetate does not belong to DILI
Class

19. Surgery
Type 0 myomas
If type 0 myomas are present,
cutting the pedicle by hysteroscopy
is indicated
Type 1 Myoma
Hysteroscopic myomectomy
<3 cm in size
>3 cm, or if the patient presents with anemia.
pre‐hysteroscopic medical therapy
(SPRMs or GnRH agonist)
It should be pointed out that in some cases, myomas
regress so much that surgery may be avoided.

20. Type 2 Myoma
• Type 0 myomas
• If type 0 myomas are present, cutting the pedicle by hysteroscopy
• is indicated
• Type 0 myomas
• If type 0 myomas are present, cutting the pedicle by hysteroscopy
• is indicated

22. Conclusion
Available treatments for uterine fibroids include medical therapies, surgery, and newer
options such as UAE and MRI‐guided focused ultrasound (MRgFUS).
The proper treatment for each individual patient will depend on the patient's age and desire
to retain her uterus and/or future fertility
Current evidence supports that myomectomy is still the better choice for women who desire
to have a child.
Treatment selection will also be dictated by the location, size, and number of fi‐ broid(s).
Submucous myoma ‐‐‐myomectomy should be performed before ART
Intramural fibroid
>5cm operate
< 5cm ‐no differ rences and significant decreased cumulative pregnancy rates?
evaluation related to distance to and/or involvement of junctional zone?

23. THANKYOU
THANKYOU
Team of Javitri IVF

24. Other medical therapies
Pros:
• Symptomatic relief (causes amenorrhea)
Cons:
Drug Des Devel Ther. 2014 Feb 20;8:285-92. Int J Endocrinol. 2012;2012:436174
OCPs/Progesterone
Medication Limitations
Progestins  Weight gain, Acne
 Breakthrough bleeding
 Can increase size of myoma
COC Breakthrough bleeding
Not safe for long term use
Can increase size of myoma

25. Newer Research
Progesterone Receptor binding is three times higher in fibroid as in myometrium
ER expression on uterine cells is inhibited by the PR pathway
PROGESTERONE plays Vital role in promoting Uterine Fibroid Growth

26. Other Medical therapies
Pros:
• Approved therapy
• Effectively reduces fibroid size and volume
Cons:
Drug Des Devel Ther. 2014 Feb 20;8:285-92. Int J Endocrinol. 2012;2012:436174
GnRHa
Medication Limitations
GnRHa  IM injections thus requires supervision (not possible
during COVID-19 situation)
 Effects are transient & myoma usually return to pre-
therapy size after treatment discontinuation
 Causes hypoestrogenism – Hot flushes, Bone loss
 Needs add-back therapy

27. VENUS I & II
(US Studies)
• One course of
treatment in
VENUS I,
• 2 courses in
VENUS II
US Study
Obstet Gynecol 2019;133:869–78
VENUS I VENUS II
 Shorter time to
amenorrhea with
ulipristal than placebo
 Improved quality of life
Significant improvement in
quality of life

28. Points to note for Ulipristal Acetate use
1. Ulipristal must not be used in women with known liver problems
2. A liver function test should be performed before starting each treatment
course and treatment must not be started if liver enzyme levels are more than
2 times the upper limit of normal
3. Keep a watch on symptoms related to jaundice. If needed do a Liver function
test. If the test is abnormal (liver enzyme levels more than 3 times the upper
limit of normal), the doctor should stop treatment and closely monitor the
patient.
4. SPRM-associated endometrial changes are benign, are not related to
cancer and are not pre cancerous.
Biomed Res Int. 2018 Jun 24;2018:1374821.

29. • 4 studies were considered eligible for analysis
Results:
 UPA does not worsen the overall
technical difficulty of hysteroscopic
myomectomy
It may increase the chance of complete
primary myomectomy in complex
hysteroscopic procedures
Obstet Gynecol Surv. 2020 Feb;75(2):127-135.
Feb 2020 Study

30. Six RCTs (1121 participants)
5 mg for 3 months
UFS-QOL symptom severity
Amenorrhea outcome
Compared with placebo, oral Ulipristal acetate significantly induces amenorrhea,
reduces heavy menses, and improves quality-of-life in women with uterine fibroids
Int J Gynecol Obstet 2019; 146: 141–148

31. 2017
Author’s conclusions:
• Short-term use of SPRMs resulted in improved quality of life, reduced
menstrual bleeding and higher rates of amenorrhoea than were seen with
placebo
• SPRMs may provide effective treatment for women with symptomatic
fibroids
• SPRM-associated endometrial changes are benign (PAEC), are not related
to cancer and are not precancerous.
Cochrane Database of Systematic Reviews 2017, Issue 4. Art. No.: CD010770
PAEC: Progesterone associated endometrial changes

32. Other medical therapies
Pros:
• Very few Indian clinical evidences available
Cons:
• Not yet approved by DCGI
• Globally No Trial
Drug Des Devel Ther. 2014 Feb 20;8:285-92. Int J Endocrinol. 2012;2012:436174
Mifepristone

33.  In CTs, Mifepristone in a dose up to 50mg/d reported Safe & Well
tolerated in Uterine Fibroid.
 It can be safely given to young patients above 20 years of age.
 No significant atypical hyperplasia is noted with Mifepristone.
 Repeat endometrial-histopathology did not reveal any complex
hyperplasia or atypia in 10mg/d & 25mg/d Mifepristone treatment in INDIAN
women with Uterine fibroid.
 Endometrial biopsies showed no premalignant changes with 50mg/d
Mifepristone for 3 months.
Up to 6-12 months safety is proven in clinical trials
 No risk of decrease in BMD & Osteoporosis.
 May increase endometrial hyperplasia which is reversible.
Safety of Mifepristone
Erase fibroids with ease
Hum Reprod. 2009 Aug;24(8):1870-9; Fertil Steril.1995;64(1):187-90;
Indian J Med Res.2013 ;137(6):1154-62.

34. Ideal Dosage of
Mifepristone
To Erase Fibroids with ease
DOSAGE: 10-25mg daily minimum for 3 months. For best results
better to starts from day 1-7 of the menses.
INDICATIONS:
 Management of symptomatic uterine fibroids
 Pre-operatively to reduce the size & symptoms of fibroids
 Pre-operative treatment for severely anemic uterine fibroid patients
 Perimenopausal women with Symptomatic fibroids
Mifepristone 300mg is FDA approved in Cushing ‘s Syndrome
so low dose Mifepristone is well tolerated

35. Ulipristal Acetate & Gene Transcription
SPRMs interact with coactivators and corepressors
In this way, the gene transcription is either inhibited or activated
Biomed Res Int. 2018 Jun 24;2018:1374821.

36. Comparison of different drug therapies
Gestagens Leuprolide Ulipristal acetate
Drug group
Progesterone receptor
agonist
GnRH analogs
Selective progesterone
receptor modulator
Remark on studies
Small number of
participants
High‐quality
Study
High quality of studies
Fibroid volume
reduction
Marginal
53%
after 3 months
36–59.8%
after 3 months
Improvement in
symptoms
Yes. especially with
intrauterine
administration
89%
of patients
90–98%
of patients
Unwanted drug effects
Few vasomotor
complaints
Vasomotor
Complaints, BMD loss
Headache,
abdominal pain
Dtsch Arztebl Int 2014 Dec; 111(51-52): 877–183.

37. Take Home Messages
• Small – Medium Size fibroids can be managed with UPA
• Treatment option for the Patients desiring Pregnancy
• Post surgeries to manage seedling fibroids
• Temporary withdrawal on UPA has been lifted across the globe & widely
available in 80 countries
• LFT is must for all the patients undergoing UPA therapy
• Ulipristal acetate is widely accepted, available & approved medical
therapy for UF

38. Scientific Studies

39. PEARL Studies Important Points
• A median time to amenorrhoea of 3.5 days (generally
before 10 days)
• After treatment cessation, return of menstruation
usually occurs within 4–5 weeks but fibroid volume
reduction can be sustained for up to 6 months
• Thickening of the endometrium occurs with ulipristal, but
the changes reverse after the drug is stopped and there is
a return to menstruation

41. Progesterone
Selective progesterone receptor modulators (SPRM)
would be needed to manage uterine fibroids
Uterine Fibroid
growth
A physiological
regulator
Progesterone
pathway needs
to be modulated
BCL2, TNF‐α, EGF
Steroids 2000;65:585‐92; Curr Opin Obstet Gynecol 2009;21:318‐24; Drug Des Devel Ther. 2014 Feb 20;8:285‐92; N Engl J Med. 2012 Feb 2;366(5):409‐20
Recent Prog Horm Res 1999;54:291‐313; Eur J Obstet Gynecol Reprod Biol 2012 Aug 14

43. Many International & National
studies on UPA

44. Thank You!