Fibroid occur commonly in female of reproductive age. They are a common variant in Sub-fertility practice. "To treat" or "To Not treat" is a clinical dilemma in vast majority of cases. Here, i describe the pertinent literature so that you can make a informed decision on management of fibroids.

1. PRE ART MANAGEMENT
OF FIBROIDS
Dr Tejas Gundewar
Dept of Reproductive Medicine & Surgery
SRIHER, Chennai

3. Incidence
■ Uterine myomas are present in approximately one third of women of reproductive age.
■ It is estimated to occur in 20–50% of women with increased frequency during the late reproductive years
(Verkauf,1992).
■ In 2009, Laughlin et al.reported a similar prevalence of 10.7% in 4217 women undergoing ultrasound
screening in the first trimester of pregnancy.
■ Uterine fibroids are detected in about 5–10% of women with infertility.
■ Furthermore, in 1–2.4% of women affected with infertility, fibroids are the only abnormality detected.
(TheImpactof Uterine LeiomyomasonReproductiveOutcomes,2010) .

4. Postulated mechanism of Infertility
■ Mechanism is not monocausal.
■ Mechanical :
I. Greater distance for sperm to travel
II. Encroachment on tubal ostium /occlusion
III. Distortion of uterine cavity
IV. ⇧ Uterine contractility : cytokines, growth factors,
neurotensin, neuropeptides, enkephalin & oxytocin
modulators

5. ■ Caveolae in host myometrium & fibromyomata are decreased
compared to normal myometra.
■ Affect calcium metabolism by causing a decrease in defect
calcium extrusion and thus raising the intracellular calcium
■ Increased intracellular calcium produces myometrial irritability
and hyperactivity, resulting in disruption of the rhythmical
contraction process of the JZ.

6. ■ Effect on Implantation :
I. altered uterine vascular perfusion,
II. Myometrial / endometrial gene expression
III. Submucosal fibroids : ⇩ ⇩ IL-10 & Glycodelin (support the
implantation and early embryonic development)
IV. TGF - 𝛽 reduces BMP 1 & 2 receptors
V. Affects endometrial receptivity – expression of HOXA 10, 11, LIF,
BTEB 1
VI. Chronic Inflammatory state
VII. Alteration of JZ zone : ⇩ ⇩ Macrophages & NK cells (contribute to
the endometrial decidualisation during implantation).

8. ■ Leiomyoma-derived TGF- 𝛽 impairs BMP 1 and 2 receptors that are essential for endometrial receptivity. [DohertyL,
TaylorHS.Leiomyoma-derivedTGF-bimpairsBMP-2mediatedendometrialreceptivity. FertilSteril2015;103:845–52]
■ Large fibroids produce more TGF- 𝛽 and those closest to the uterine cavity allow more TGF to reach endometrial cells.
■ TGF- 𝛽 production ∝ Size of Fibroid
■ Amount of TGF- 𝛽 reaching the cavity ∝ 1/ Square of distance from the cavity
■ TGF- 𝛽 : ⇩ ⇩ PAI-1, AT III & Thrombomodulin in the endometrium. These alterations in endometrial haemostatic
mechanisms contribute to menorrhagia.
■ As endometrial receptivity and endometrial anti- coagulant expression are both altered by the same signalling
molecules, it is likely that those fibroids that affect bleeding also simultaneously affect endometrial receptivity.

9. WHY IS IT SO DIFFICULT TO ANALYSE
EFFECT OF FIBROIDS ON FERTILITY?
■ Data evaluating reproductive outcomes related to myomas are
derived primarily from observational studies
■ Studies are prone to selection bias and confounding variables
(For example, women with myomas tend to be older, compared with
women without myomas)
■ Heterogeneous patient populations
■ Inconsistent myoma characterization (in terms of location,
size, and number of myomas)
■ No comprehensive evaluation of clinically relevant reproductive
outcomes such as time to pregnancy, clinical pregnancy rate,
live-birth rate, and miscarriage rate

10. TYPES OF FIBROIDS

12. In women with otherwise unexplained
infertility, submucosal fibroids should be
removed in order to improve conception
and pregnancy rates . (II-2A)
■ There is fair evidence that hysteroscopic myomectomy
for submucosal fibroids improves clinical pregnancy
rates. (Grade B)
■ There is insufficient evidence to conclude that
hysteroscopic myomectomy reduces the likelihood of
early pregnancy loss in women with infertility and a
submucous fibroid. (Grade C)

15. Conclusions : The present evidence suggests that noncavity-
distorting intramural fibroids would significantly reduce the IR,
and significantly increase the MR after IVF treatment, but it
significantly increase the ePR.

17. ■ Prospective evaluation of 193 women. All evaluated with USG, HSG or Hysteroscopy
■ 1-5 fibroids, with at least one >5 cm in diameter, and no submucosal fibroids.
■ Patients were given the choice of myomectomy or no surgery prior to IVF. In the myomectomy group, IVF cycles were
performed at least 3 months following surgery.
■ Women who underwent myomectomy prior to IVF had higher CPR (34 vs. 15%) and LBR (25% vs. 12%) compared to
women who did not elect surgery.
■ Lack of randomization - limitation of this study.

18. ■ Only women with IM fibroids of ≤ 5 cm in size (n = 106)
■ PR, IR & OPR were significantly reduced: 23.3, 11.9 and 15.1 respectively compared with 34.1, 20.2 and
28.3% in the control group (P = 0.016, P = 0.018 and P = 0.003).
■ Mean size of the largest fibroids was 2.3 cm (90% range 2.1–2.5 cm).
■ Logistic regression analysis demonstrated that the presence of intramural fibroids was one of the
significant variables affecting the chance of an ongoing pregnancy, even after controlling for the number
of embryos available for replacement and increasing age, particularly age > 40 years, odds ratio 0.46 (CI
0.24–0.88; P = 0.019).

20. Results :
■ Our study demonstrates that the presence of non-cavity- distorting fibroids appears to negatively affect
CPR (odds ratio, OR 0.62; 95% confidence interval, 95% CI 0.41–0.94) and LBR (OR 0.58; 95% CI 0.48–0.78)
in patients undergoing their first IVF/ICSI cycle, when matched with controls of the same age, starting
dose of FSH, stimulation protocol, number of embryos, and day of embryo transfer.
■ Deleterious effect of fibroids on LBR was significant in women with two or more fibroids (OR 0.47; 95% CI
0.26–0.83) and in women with fibroids of ≥30 mm in diameter (OR 0.41; 95% CI 0.19–0.89).
■ The negative impact of non-cavity-distorting fibroids was also present in women with an embryo transfer
on day 5 (OR 0.58; 95% CI 0.35– 0.94).
■ Conversely, in women with single fibroids of <30 mm in diameter, no difference in pregnancy outcomes
was identified.

21. Compared with the corresponding control subjects,
patients with type 3 fibroids with a single fibroid diameter
(SD) or total reported fibroid diameter (TD) >2.0 cm also
had significantly lower rates of live birth, clinical pregnancy,
and implantation. Type 3 fibroids with SD or TD ≤2.0 cm
had no significant difference in IVF-ICSI outcomes
compared with corresponding control subjects.
AUC – 0.585 for LBR & SD > 2cm

22. ■ There is insufficient evidence that removal of subserosal fibroids improves fertility.
(Grade C)
■ There is fair evidence that myomectomy does not impair reproductive outcomes
(clinical pregnancy rates, live- birth rates) following ART. (Grade B)
■ There is insufficient evidence that myomectomy (laparo- scopic or open) reduces
miscarriage rates. (Grade C).

23. ■ There is fair evidence to recommend against myomectomy in women with intramural
fibroids (hysteroscopically confirmed intact endometrium) and otherwise unexplained
infertility, regardless of the size of the fibroids. (II-2D)
■ If the patient has no other options, the benefits of myomectomy should be weighed
against the risks, and management of intramural fibroids should be individualized. (III-C)

24. ■ Avoid surgery in the presence of fibroids <5 cm when the uterine cavity is regular.
■ offer surgery first to women with intramural fibroids ≥7 cm.
■ Proceed with IVF treatment without surgery in the presence of fibroids of 5-6 cm in the
first IVF attempt. We usually offer surgery for fibroids of 5-6 cm if the woman had one
or two failed IVF attempts. This approach aims to keep the NNT as low as possible per
additional pregnancy achieved.

26. LASMAR PRE SURGICAL
CLASSIFICATION OR STEP-W
CLASSIFICATION

27. ■ GnRH agonist for 2-3 months when the fibroid is ≥4 cm to reduce the likelihood of two-stage
procedures.
■ Single type II submucosal fibroids <4 cm hysteroscopically; some 3-4 cm type II fibroids require a
two- stage approach.
■ Type II fibroids of ≥4 cm, we give serious consideration to abdominal myomectomy
(laparoscopic when possible, open in the presence of numerous fibroids).
■ We pay special attention to reducing the risk of intrauterine adhesions in the presence of
multiple submucosal fibroids, including removal of fibroids on opposing walls in different
sessions.

28. ROLE OF
MEDICAL
MANAGEMENT
IN FIBROIDS
IN
INFERTILITY
Various medical modalities
shown to cause shrinkage in
size of myoma
• GnRH analogs
• Mifepristone
• Danazol
• Gestrinone
• Ulipristal acetate
None of these are
recommended for infertility
as :
• They do not improve fertility
• Can lead to a delay in more
effective treatments for infertility

29. The only indication for medical management may be –
use of GnRH analogues to decrease size of fibroids before
myomectomy
There is no role for medical therapy as a stand-alone
treatment for fibroids in infertile population
Kaur H. Fibroids and infertility. International Journal of Infertility and
Fetal Medicine, January-April 2014;5(1):1-7

31. Conclusions
■ Submucosal fibroids – should be removed
■ Sub-Serosal – leave alone
■ Non Cavity distorting Intramural fibroids :
I. Decreased CPR/LBR
II. Insufficient evidence that removal improves the outcomes.
■ Medical Mx : No stand alone role. Can be used for reducing myoma size prior
to surgery.
■ Open or Laparoscopic Myomectomy – similar cumulative pregnancy rates.

32. tejasgundewar87@gmail.com
+91-9970054337
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