Fibroids and Reproduction - 1st Edition
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Contents
Preface...................................................................................................................................................... vii
Contributors............................................................................................................................................... ix
1 Fibroids and Reproduction: A Bird’s-Eye View............................................................................. 1
Botros R.M.B. Rizk, Candice P. Holliday, and Yakoub Khalaf
2 Fibroids and Assisted Reproduction Technology.........................................................................11
Eman A. Elgindy
3 Fibroids and Endometrial Receptivity/Embryo Implantation................................................... 23
Kamaria C. Cayton Vaught, Maria Facadio Antero, Jacqueline Y. Maher, and Chantel I. Cross
4 Uterine Fibroids and Recurrent Pregnancy Loss........................................................................ 33
Natasha K. Simula and Mohamed A. Bedaiwy
5 Fibroids in Pregnancy..................................................................................................................... 45
Magdi Hanafi
6 Medical Options for Uterine Fibroids in the Context of Reproduction..................................... 55
Hoda Elkafas, Mona Al Helou, Qiwei Yang, and Ayman Al-Hendy
7 Fibroid Preoperative Imaging: Ultrasound.................................................................................. 71
Nicole Catherine Michel, Shima Albasha, and Botros R.M.B. Rizk
8 Fibroid Preoperative Imaging: Magnetic Resonance Imaging.................................................. 85
Linda C. Chu, Mounes Aliyari Ghasabeh, and Ihab R. Kamel
9 Interventional Procedures.............................................................................................................. 95
Kristin Patzkowsky
10 Hysteroscopic Myomectomy......................................................................................................... 103
Anja Frost and Mostafa A. Borahay
11 Laparoscopic and Robotic-Assisted Myomectomy.....................................................................113
Harold Wu, Anja Frost, and Mostafa A. Borahay
Index....................................................................................................................................................... 125
v
Preface
Dear Reader,
We put in your hands a book that covers all aspects of clinical evaluation and management of uterine
fibroids. We put in a lot of effort to get it in the best possible form to help you help your patients. We hope
you enjoy it, as we enjoyed putting it together.
Our deepest appreciation to our families. Without their support and dedication, we could not have
completed it.
We would also like to acknowledge our dearest friends and colleagues who shared the journey with
us and thank Drs. Mohamed Aboulghar, Gamal Serour, Hossam Abdalla, Shawky Badawy, and Fouad
Sattar for decades of friendship and cooperation. We would also like to thank Robert Peden and the staff
who worked on this book.
Botros R.M.B. Rizk
Yakoub Khalaf
Mostafa A. Borahay
vii
Contributors
Shima Albasha Eman A. Elgindy
Reproductive Endocrinology and Infertility Department of Obstetrics and Gynecology
Department of Obstetrics and Gynecology University of Zagazig
Hamad Medical Corporation Zagazig, Egypt
Doha, Qatar
Hoda Elkafas
Mona Al Helou Department of Pharmacology
Makassed General Hospital and Toxicology
American University of Beirut University Hospital National Organization for Drug Control
Beirut, Lebanon and Research (NODCAR)
Cairo, Egypt
Ayman Al-Hendy
Department of Surgery and
University of Illinois at Chicago
Chicago, Illinois Department of Surgery
University of Illinois at Chicago
Maria Facadio Antero Chicago, Illinois
Division of Reproductive Endocrinology and
Infertility Anja Frost
Department of Gynecology and Obstetrics Department of Gynecology and Obstetrics
Johns Hopkins University Johns Hopkins University
Baltimore, Maryland Baltimore, Maryland
Mohamed A. Bedaiwy
Division of Reproductive Endocrinology Mounes Aliyari Ghasabeh
and Infertility Russell H. Morgan Department
Department of Obstetrics and Gynecology of Radiology and Radiological Science
University of British Columbia Johns Hopkins University
Vancouver, British Columbia, Canada Baltimore, Maryland
Mostafa A. Borahay Magdi Hanafi
Department of Gynecology and Obstetrics Gynecology Department
Johns Hopkins Bayview Medical Center Emory Saint Joseph’s Hospital
Johns Hopkins University Atlanta, Georgia
Baltimore, Maryland
Candice P. Holliday
Linda C. Chu
Division of Reproductive Endocrinology and
Russell H. Morgan Department of Radiology and
Infertility
Radiological Science
Department of Obstetrics and Gynecology
Johns Hopkins University
University of South Alabama
Baltimore, Maryland
Mobile, Alabama
Chantel I. Cross
Division of Reproductive Endocrinology Ihab R. Kamel
and Infertility Russell H. Morgan Department of Radiology and
Department of Gynecology and Obstetrics Radiological Science
Johns Hopkins University Johns Hopkins University
Baltimore, Maryland Baltimore, Maryland
ix
x Contributors
Yakoub Khalaf Natasha K. Simula
Reproductive Medicine and Surgery Department of Obstetrics and Gynecology
Guy’s and St Thomas’ Hospital and King’s University of British Columbia
College London Vancouver, British Columbia, Canada
and
Centre for Pre-Implantation Genetic Diagnosis Kamaria C. Cayton Vaught
Guy’s and St Thomas’ Hospital Division of Reproductive Endocrinology
London, United Kingdom and Infertility
Department of Gynecology and Obstetrics
Jacqueline Y. Maher Johns Hopkins University
Division of Reproductive Endocrinology Baltimore, Maryland
and Infertility
Department of Gynecology and Obstetrics Harold Wu
Johns Hopkins University Division of Minimally Invasive Gynecologic
Baltimore, Maryland Surgery
Department of Gynecology and Obstetrics
Nicole Catherine Michel Johns Hopkins University School of Medicine
Alabama College of Osteopathic Medicine Baltimore, Maryland
Dothan, Alabama
Qiwei Yang
Kristin Patzkowsky Department of Surgery
Department of Gynecology and Obstetrics University of Illinois at Chicago
Johns Hopkins University Chicago, Illinois
Baltimore, Maryland
Botros R.M.B. Rizk
Elite IVF
Houston, Texas
and
Advanced Fertility Centers
Odessa, Texas
1
Fibroids and Reproduction: A Bird’s-Eye View
Botros R.M.B. Rizk, Candice P. Holliday, and Yakoub Khalaf
CONTENTS
Introduction................................................................................................................................................. 1
Classification............................................................................................................................................... 1
Diagnosis..................................................................................................................................................... 4
Fertility........................................................................................................................................................ 7
Conception.................................................................................................................................................. 7
Miscarriage................................................................................................................................................. 7
In Vitro Fertilization Outcome.................................................................................................................... 9
References................................................................................................................................................... 9
Introduction
A fibroid (or leiomyoma) is a benign, monoclonal, smooth muscle tumor of the uterus, which usually presents
as multiple lesions (Figure 1.1) but can occur as a single lesion (Figure 1.2). Fibroids are diagnosed in 20%–
40% of women, generally after age 30 years, with a stable increase in incidence with increasing age [1]. This
age-related increase in incidence of fibroids should be considered when looking into the relationship between
fibroids and reproductive dysfunction (subfertility or miscarriage), as both are intimately age related.
Although it is biologically plausible and clinically evident that fibroids are associated with reproductive
dysfunction (see Chapter 2), a cause-effect relationship has not been established.
Most symptomatic fibroids can be diagnosed clinically, but crucial clinical information can be obtained
by one imaging modality or another.
Ultrasound is a noninvasive imaging modality that is well tolerated by patients, and it is a rather
inexpensive way to obtain a relatively accurate assessment of fibroids within the pelvis (see Chapter 8).
Assessing fibroid size and location can be beneficial for planning surgery or for monitoring changes in
fibroids over time (Figures 1.3–1.5).
In some complex cases (multiple fibroids, previous surgery, and associated morbidities), magnetic
resonance imaging (MRI) can provide additional valuable information that could help in planning surgery
or guide the choice of alternative therapeutic approaches, such as the use of uterine artery embolization
(UAE) or MRI-guided focused ultrasound (see Chapter 7).
Classification
When fibroids develop from the uterine wall but distort the uterine cavity, it is helpful to detail the
degree of uterine cavity impingement (see Chapter 7) with the Wamsteker and de Blok classification [2].
Following are the types of fibroids:
• 0: 100% of the fibroid is pedunculated into the uterine cavity
• I: Greater than 50% of the fibroid is within the uterine cavity
• II: Less than 50% of the fibroid is within the uterine cavity (i.e., greater than 50% of the fibroid
is within the myometrium)
1
2 Fibroids and Reproduction
FIGURE 1.1 (a) Varying fibroid locations within the uterus; (b) multiple fibroids—intramural, subserosal, and submucosal;
(c) uterus enlarged with intramural fibroids.
FIGURE 1.2 Solitary large fibroid.
Fibroids and Reproduction: A Bird’s-Eye View 3
FIGURE 1.3 (a–c) Intramural fibroids.
FIGURE 1.4 (a–c) Submucosal fibroids.
4 Fibroids and Reproduction
FIGURE 1.5 (a) Subserosal fibroid; (b) pedunculated fibroid; (c) Doppler scan showing feeder vessels of pedunculated fibroid.
It can be difficult to assess on two-dimensional (2D) ultrasound scan what type of fibroid a patient has.
Three-dimensional (3D) ultrasound and saline infusion sonohysterography are often used to obtain that
information (Figures 1.6–1.8). A diagnosis that is accurate is critical to determine presurgical treatment,
what type of surgery would be best, and what sort of prognosis a patient can expect [2]. A comparable
classification system has been suggested for intramural and subserosal fibroids in order to describe what
degree of myometrial involvement exists (see Chapter 2 for the detailed classification system). Three-
dimensional ultrasound is becoming an increasingly valuable imaging tool to map out the relationship
between the fibroid and the endometrial cavity.
Diagnosis
Two-dimensional ultrasound is the traditional manner of imaging fibroids, although other imaging
modalities exist. For ideal visualization of fibroids, especially of their outline, the best technique uses
a transvaginal scan (TVS) (see Figures 1.3–1.5). With a transvaginal approach, the ultrasound probe is
closer to the uterus, which allows a higher frequency to be used. This higher frequency provides better
definition of the tissues. A patient should empty her bladder first before a TVS is done. The TVS transducer
is curvilinear, multifrequency, and endocavity, with a central frequency that is usually 6.5 MHz. The
ultrasound beam can be highly attenuated by fibroids due to fibroids’ dense and mixed tissue composition.
Thus, poor through transmission and shadowing may result. As a result of this attenuation, sometimes a
lower frequency is used to achieve better penetration of the fibroid in order to see the posterior outline.
When a uterus is significantly burdened by fibroids, a TVS can fail to visualize the entire uterus, and a
transabdominal ultrasound (TAS) is warranted as well.
Fibroids and Reproduction: A Bird’s-Eye View 5
FIGURE 1.6 Three-dimensional ultrasound showing fundal intramural fibroid.
FIGURE 1.7 SIS showing intramural fibroid protruding in the cavity.
6 Fibroids and Reproduction
FIGURE 1.8 Submucosal fibroid in three-dimensional (3D) view: (a) transverse section; (b) coronal section; (c) rendered
3D ultrasound.
TAS uses a curvilinear, multihertz abdominal transducer that has a central frequency of 3.5 MHz.
The transabdominal approach gives a larger visual perspective to allow for adequate visualization of an
enlarged uterus. The abdominal transducer also can use lower frequencies to achieve better penetration of
tissue. Additionally, harmonic selection as well as higher power settings can improve the visualization of
fibroids on ultrasound. The TAS usually requires a full bladder to see pelvic organs, but such techniques
may be unnecessary when the uterus is significantly enlarged with fibroids. This difference is often
because the bowel loops that often obscure pelvic organs have been displaced by the large fibroid uterus.
The specific appearance of a fibroid’s outline can be well demonstrated on TVS, even of very small
fibroids, because of the fibroid’s pseudocapsule. The fibroid has a mixed tissue composition such that
a heterogenous echo pattern develops on ultrasound. This echo can be highly attenuating for some
fibroids. A fibroid should have a definite outline because heterogenous myometrium without a defined
margin could be adenomyosis instead. Fibroids are typically hypoechoic when compared to neighboring
myometrium, but then sometimes they can be isoechoic (or even hyperechoic if fatty or fibrous changes
have occurred). Cystic degeneration of fibroids can be visualized on ultrasound as a central anechoic
area that can contain internal echoes or fluid/fluid levels [3] (Figure 1.9). When fibroid tissue has been
replaced with fibrous tissue, there is a total increase in reflectivity on ultrasound. Calcification of
fibroids can also occur and is seen as echogenic foci or a bright outer rim that causes posterior acoustic
shadowing on ultrasound.
FIGURE 1.9 (a,b) Degenerating fibroids.
Fibroids and Reproduction: A Bird’s-Eye View 7
FIGURE 1.10 (a,b) Myomectomy showing removal of intramural fibroid.
Fertility
How fibroids affect fertility is of great importance to reproductive medicine practitioners
(see Chapter 3), and many uncertainties remain. Fibroids become symptomatic usually after the age
of 35 years, which is the age when fertility starts to decline. However, it is beneficial to first examine
how fibroids may affect fertility and then specifically examine the effects of fibroids on in vitro
fertilization (IVF) outcomes.
Conception
The fact that delayed conception is more frequent in women with fibroids had been highlighted many
years ago. In a retrospective study of women with uterine fibroids who presented in labor, 43% of women
had at least a 2-year history of infertility [4]. More importantly, the spontaneous conception and live
birth rates that follow removal of fibroids (Figure 1.10) may provide indirect evidence that fibroids may
have played an important role in impeding pregnancy and contributed to subfertility. In one study, it was
reported that the cumulative live birth rate following myomectomy was 50% after 1 year of surgery, with
more pregnancies occurring in the second year but at a lower frequency and hardly any beyond 24 months
of observation [5] (Figure 1.11). The cumulative chance of pregnancy was obviously affected by age, as
reported in another study [6] (Figure 1.12).
Miscarriage
• Many studies looking at the relationship between fibroids and miscarriage examine intramural
fibroids, rather than submucosal fibroids [7]. In several studies, intramural fibroids were
associated with an increase in miscarriage rate (see Chapter 4) from 8% to 15% [7]. Additionally,
multiple fibroids, as opposed to a single fibroid, are a significant risk factor for miscarriage
[8]. In one review, miscarriage rates dropped from 41% to 19% after myomectomy for patients
with symptomatic fibroids [9]. However, a recent study reported that the hazard ratio (HR)
for miscarriage is increased in the presence of uterine fibroids (HR = 1.29%, 95% [CI]: 1.02,
1.64), but after adjusting for the confounding variables—maternal age, race/ethnicity, alcohol
use, prior termination of pregnancy, and parity—this increased risk disappeared when adjusted
(HR = 0.83%, 95% CI: 0.63, 1.08) [10].
8 Fibroids and Reproduction
FIGURE 1.11 Cumulative probability of spontaneous intrauterine pregnancy after myomectomy using the Kaplan and
Meier method (time 0 is the date of the myomectomy). (From Fauconnier A et al. Hum Reprod. 2000;15:1751–7. With
permission.)
100
90
80
Probability of pregnancy (%)
70
60
50
40
30
20
10
0
0 6 12 18 24
No. of months
FIGURE 1.12 Cumulative 24-month probability of pregnancy in 138 women who underwent myomectomy, 32 of whom
were younger than 30 years of age (-------------), 69 of whom were 30 to 35 years of age (………), and 38 of whom were older
than 35 years of age (- - - - - -) (log rank test, χ22 = 12.05, P = .0024). (From Vercellini P et al. Fertil Steril. 1999;72:109–14.
With permission.)
