Uterine factors in recurrent

pregnancy losses
Marie Carbonnel, M.D., Paul Pirtea, M.D., Dominique de Ziegler, M.D., and Jean Marc Ayoubi, M.D., Ph.D.

de Me
Department of Obstetrics and Gynecology and Reproductive Medicine, Hopital Foch, Faculte
decine Paris Ouest,
Suresnes, France

Congenital and acquired uterine anomalies are associated with recurrent pregnancy loss (RPL). Relevant congenital M€ ullerian tract
anomalies include unicornuate, bicornuate septate, and arcuate uterus. Recurrent pregnancy loss has also been associated with acquired
uterine abnormalities that distort the uterine cavity such as, notably, intrauterine adhesions, polyps, and submucosal myomas. Initial
evaluation of women with RPLs should include an assessment of the uterine anatomy. Even if proof of efficacy of surgical management
of certain uterine anomalies is often lacking for managing RPLs, surgery should be encouraged in certain circumstances for improving
subsequent pregnancy outcome. Uterine anomalies such as uterine septa, endometrial polyps, intrauterine adhesions, and submucosal
myomas are the primary surgical indications for managing RPLs. (Fertil SterilÒ 2021;115:538–45. Ó2020 by American Society for
Reproductive Medicine.)
Key Words: Recurrent pregnancy loss (RPL), miscarriage, congenital, uterine, myoma, adhesion, endometrial polyp

Discuss: You can discuss this article with its authors and other readers at https://www.fertstertdialog.com/posts/31673

T
here is no general consensus for
defining recurrent pregnancy
loss (RPL) and its management
(1). Classically, RPL is defined by the
occurrence of three or more miscar-
riages—consecutive or not—occurring
before 20 weeks of gestation, that is,
before fetal viability (2). In spite of
this commonly accepted idea, it has
been recently suggested that it is appro-
priate to start investigating infertile
women—particularly if they are
young—after two miscarriages (3, 4).
The American Society for Reproductive
Medicine (ASRM) does not mention a
threshold number of miscarriages in
the context of RPL (5).
It is generally accepted that RPL
occurs in 1%–3% of couples who try
to conceive (3). The prevalence of
anatomical uterine anomalies in
women experiencing RPL varies from
15% to 42% according to different
studies (6–10). Congenital uterine
anomalies are associated with 7%–
28% of RPL (6–10). These mainly
include septate uteri and more rarely
arcuate or bicorporeal uteri. Acquired
uterine anomalies are associated with
6%–15% of RPL (6–10). These include
submucosal myomas, intrauterine
adhesions (IUAs), and endometrial
polyps. Endometrial polyps are
commonly found in both fertile and
infertile women. Therefore, it must be
acknowledged that their mere
presence observed on uterine imaging
or during hysteroscopies does not
necessarily imply a specific negative
impact on fertility. Because clinicians
may not know when these findings
negatively impact early pregnancy
development, endometrial polyps are
commonly removed when identified.
To determine which of the above-
mentioned entities are likely to impair
pregnancy development and which
are just innocent bystanders unrelated
to RPL, clinicians must perform a
thorough uterine assessment in
concordance with the international
guidelines. Yet the investigations
recommended slightly vary according
to the different published guidelines
(Table 1). The Royal College of Obstetri-
cians and Gynaecologists recommends
first performing a classical two-
dimensional (2D) pelvic ultrasound.
When uterine anomalies are suspected
on regular ultrasound, further explora-
tions are then recommended, including
three-dimensional (3D) pelvic ultra-
sound, hysteroscopy, sonohysterogra-
phy (SHG), and laparoscopy (11).
However, the European Society of Hu-
man Reproduction and Embryology
(ESHRE) recommends first performing
transvaginal 3D ultrasound as the pri-
mary examination of uterine anatomy
(3). In contrast, the ASRM guidelines
recommend performing SHG or hyster-
oscopy (12). The French College Na-
tional des Gyn
ecologues et
Obst
etriciens recommends performing
2D or 3D ultrasound, magnetic reso-
nance imaging (MRI), hysteroscopy,
and/or SHG depending on the diag-
nostic measures available (13).

Received October 20, 2020; revised November 15, 2020; accepted December 2, 2020.
M.C. has nothing to disclose. P.P. has nothing to disclose. D.d.Z. has nothing to disclose. J.M.A. has
nothing to disclose. CONGENITAL
Reprint requests: Dominique de Ziegler, M.D., Department of Obstetrics and Gynecology and Repro-
ductive Medicine, Hopital Foch, Suresnes 92150 France (E-mail: dom@deziegler.com). MALFORMATIONS AND RPL
The risk of RPL is increased in women
Fertility and Sterility® Vol. 115, No. 3, March 2021 0015-0282/$36.00
Copyright ©2020 American Society for Reproductive Medicine, Published by Elsevier Inc.
with congenital uterine malforma-
https://doi.org/10.1016/j.fertnstert.2020.12.003 tions (14). The two most widely used

538 VOL. 115 NO. 3 / MARCH 2021

 Fertility and Sterility®

TABLE 1

Comparison of the recurrent pregnancy loss guidelines.

ESHRE (3) ASRM (5, 12) RCOG (11) CNGOF (13)
Year of publication 2017 2012–13 2011 2016
Anatomical 2D ultrasound SHG, hysteroscopy Pelvic ultrasound first. If suspected 2D or 3D ultrasound, SHG,
assessment anomalies: hysteroscopy, hysteroscopy, or MRI depending
laparoscopy or 3D pelvic on availability
ultrasound
Congenital anomalies Insufficient evidence; Section of uterine Insufficient evidence Section of uterine septum
section of uterine septum
septum in trials
Acquired anomalies Insufficient evidence Insufficient evidence Insufficient evidence Resection of endometrial polyps,
submucosal myomas Section of
IUAs
2D ¼ two-dimensional; 3D ¼ three-dimensional; ASRM ¼ American Society for Reproductive Medicine; CNGOF ¼ College National des Gyn
ecologues et Obst

etriciens Français; ESHRE ¼ European
Society of Human Reproduction and Embryology; IUAs ¼ intrauterine adhesions; MRI ¼ magnetic resonance imaging; RPL ¼ recurrent pregnancy loss; RCOG ¼ Royal College of Obstetricians and
Gynaecologists; SHG ¼ sonohysterography.
Carbonnel. Uterine factors in recurrent pregnancy losses. Fertil Steril 2020.

classifications are provided by ASRM (15) and ESHRE/Euro-
pean Society for Gynecological Endoscopy. The latter clas-
sification system of female genital tract congenital
anomalies—used in the present article—is illustrated in
Figure 1 (16). The septate uterus is the congenital malforma-
tion most commonly associated with RPL, being found in
6%–16% of cases (6, 7, 9). Septate uteri (class U2) result
from partial or complete failure of resorption of the medial
septum between the two M€ ullerian ducts during fetal life.
The degree of indentation of the protruding medial portion
defines the two conditions known as septate and arcuate
uterus, with different cutoffs ranging from 10 to 15 mm

FIGURE 1

The European Society of Human Reproduction and Embryology/European Society for Gynecological Endoscopy classification system for female
genital congenital anomalies (16).
Carbonnel. Uterine factors in recurrent pregnancy losses. Fertil Steril 2020.

VOL. 115 NO. 3 / MARCH 2021 539

VIEWS AND REVIEWS
reported in the literature (15, 17). While the pathophysi-
ology by which this disorder interferes with early pregnancy
development is not entirely known, hypotheses have been
formulated. Miscarriages in case of septate uteri likely result
from inadequate implantation of the embryo on a poorly
vascularized septum. Furthermore, the septum could alter
the pre- and postovulatory changes of the endometrium un-
der the influence of estradiol and progesterone, uterine
contractibility, and/or disruption of the physiology of endo-
metrial factors such as, notably, vascular endothelial
growth factor (18). Other congenital disorders, in particular,
unicornuate (class U4), arcuate (class U2), and bicornuate
uteri (class U3), are reported in only 0.5%–2% of cases of
RPL (6, 7).
The presence of congenital malformations can be sus-
pected with traditional 2D transvaginal ultrasounds. The
sensitivity of 2D ultrasounds is, however, low (60%–80%)
for detecting uterine malformations. Conversely, 3D trans-
vaginal ultrasounds have the highest overall diagnostic
sensitivity and accuracy (19), especially for distinguishing
between septate and bicornuate uteri (20). The coronal—
frontal view—of the uterus is ideal for diagnosing congenital
uterine anomalies (Fig. 1A and 1B). The uterine cavity can be
further explored with SHG and/or hysteroscopy. In contrast,
hysterosalpingography is not very effective for assessing
uterine malformations. Hysteroscopy only offers mediocre
accuracy for distinguishing septate from arcuate uteri with
poor interobserver agreement on final diagnosis. Hence,
hysteroscopy per se is insufficient as a single tool for appro-
priately diagnosing uterine malformations and deciding on
the appropriate treatment, notably, the need for resection—
metroplasty—of septate uteri (21).
Combining both hysteroscopy and laparoscopy remains
the gold standard for diagnosing uterine malformations
because it offers a simultaneous internal and external view
of the uterus. Yet this dual approach is invasive. This has
led researchers to seek simpler approaches using 2D or 3D
SHG, which ultimately have great value for diagnosing the
most commonly encountered congenital uterine anomalies.
In particular, SHG allows the delineation of the internal
contours of the uterine cavity as well as the surface of the
uterus (22).
Pelvic MRI may be helpful in complicated cases associ-
ated with complex anatomical defects like rudimentary cav-
ities but is not routinely necessary (3, 19). When class U3
and U5 malformations are diagnosed, it is recommended to
investigate the kidneys and urinary tract as well for possible
associated malformations (3).
CONGENITAL MALFORMATION
MANAGEMENT
Hysteroscopic metroplasty is the most commonly preferred
approach for resecting the uterine septum. A 15 French gauge
(FR) hysteroscope with a 5 FR operative channel allows the
use of instruments (including bipolar and monopolar electrodes
and cold scissors). Alternatively, a 15–26 FR resectoscope (hys-
teroscope with cauterization loop) equipped with bipolar or mo-
nopolar cautery or laser can be used with comparable results
540
(23). This procedure has been determined to be safe and effec-
tive, although this determination was based on nonrandomized
and mainly retrospective trials only (14). Observational studies
report important improvements in pregnancy chances
when comparing before and after septum resection in
observational studies, which are highly susceptible to various
biases (24–27). First among the possible biases is the fact that
participants with RPL treated by hysteroscopic metroplasty
have commonly served as their own controls. A meta-
analysis showed that hysteroscopic removal of a septum was
associated with reduced probability of spontaneous abortion
(28). The ASRM and French guidelines recommend septum
resection in case of septate uteri associated with RPL (12, 13).
However, the Royal College of Obstetricians and Gynaecologists
concludes that there is insufficient evidence for justifying sur-
gical correction of septate uteri (11). Likewise, the ESHRE guide-
lines conclude that the net value of septum resection should be
evaluated in randomized controlled trials (RCTs) (16). In fact, an
international RCT (the TRUST trial) comparing septum resection
versus no resection in women with a history of RPL is currently
in progress (29).
Some investigators have proposed additional morpho-
logic criteria beyond those proposed by the American Fertility
Society for better characterizing the differences between
septate and arcuate uteri (30). These investigators also define
the role played by the angle existing at the tip of the septum
protruding in the cavity. Following this approach, a closed
angle between the two uterine horns is characteristic of the
arcuate configuration (31). Furthermore, emphasis is put on
the length of the septum, which in the case of arcuate uterus
ranges between 10 and 15 mm (32). The lack of a universally
accepted standard definition of septate uterus may add vari-
ability in diagnostic classifications and affect the actual inci-
dence of surgical metroplasties (33).
Surgical and obstetrical complications of hysteroscopic
metroplasty have been described. These include perforation
of the uterus, postoperative IUAs, cervical laceration (34),
and an increased rate of cesarean sections due to dystocic
obstetrical presentations (35). Some cases of uterine rupture
during subsequent pregnancies have also been reported
(35, 36). Abdominal ultrasound guidance during surgery,
the use of barrier gels, and postoperative hysteroscopies are
options aimed at reducing postoperative complications (37).
However, no evidence of a benefit of surgical treatment
for arcuate, bicornuate, or unicornuate uterus has been shown
(25). Data about uterine enlargement metroplasty for
dysmorphic uteri (class U1) are controversial in the case of
RPL (38–40). No RCT and case control studies are available.
The risk of uterine perforation and IUAs is increased. To
date, international guidelines do not recommend treating
dysmorphic uteri (3, 11).
ACQUIRED UTERINE ANOMALIES AND RPL
Leiomyomas/Fibroids/Myomas
The prevalence of fibroids in RPL varies from 0.5% to 1.3%,
depending on the study (6, 7, 9). Fibroids are also associated
with infertility due to implantation failure. There are
three cell populations in leiomyomas: well-differentiated,
VOL. 115 NO. 3 / MARCH 2021

intermediate-differentiated, and fibroid stem cells. Their
growth and impact on fertility may vary depending on the
cell proportions, with faster growth when there exists a higher
proportion of fibroid stem cells. A number of potential mecha-
nisms that could explain how leiomyomas may adversely
affect pregnancy development have been described. These
include altered uterine contractility and disturbances in endo-
metrial cytokine expression, as well as abnormal vasculariza-
tion and chronic endometrial inflammation. In addition,
some investigators have suggested that mechanical stretch of
the endometrium and/or myometrium can alter varying gene
expressions (41–43). HOXA-10 levels have been reported to
be reduced in the endometrium of women with submucous
leiomyomas, not only in the tissue around the leiomyomas
themselves but also in the endometrium elsewhere in the endo-
metrial cavity (44). Although there may be changes in some
endometrial genes, the expressions related to receptivity were
not altered in a large retrospective study that also looked at as-
sisted reproductive technology (ART) success rates. The latter
did not vary regardless of leiomyoma size or number (45).
Classically, fibroids were classified according to their po-
sition in the uterus, being submucosal, intramural, or subser-
osal. Today, the more precise classification proposed by the
International Federation of Obstetricians and Gynecologists
(FIGO) is preferred. As illustrated in Figure 2, fibroids altering
the anatomy of the uterine cavity (FIGO 0–2) are susceptible
of causing RPL through chronic endometrial inflammation,
abnormal vascularization, increased uterine contractibility,
and abnormal local endocrine patterns (46, 47). Submucosal
fibroids (FIGO 0–2) have the strongest association with lower
ongoing pregnancy rates and miscarriages, but according to
certain reports, a correlation also exists between intramural
fibroids and low fertility outcomes (46, 48–50). Intramural
leiomyomas have a questionable impact on fertility and
early pregnancy development, which may due to differences
FIGURE 2
Leiomyoma classification according to the International Federation of Obstetricians and Gynecologists (47).
Carbonnel. Uterine factors in recurrent pregnancy losses. Fertil Steril 2020.
VOL. 115 NO. 3 / MARCH 2021
Fertility and Sterility®
related to their size. Indeed, the size of intramural myomas
can augment the risk of RPL, especially when myomas are
>4 cm, a point of view that remains controversial
according with certain researchers (50). The presence of
multiple fibroids is a significant predictor of miscarriage
and RPL (51). Subserosal myomas are not associated with
miscarriages and/or poor fertility outcomes (49, 50).
The first-line tool for diagnosing uterine fibroids is ul-
trasound (52). Hysteroscopy is the gold standard for diag-
nosing intrauterine anomalies, fibroids protruding into the
endometrial cavity (FIGO 0–2), and endometrial polyps
(Fig. 3). Sonohysterography can also delineate submucosal
myomas, and in the case of totally or partially intramural
myomas (FIGO 3–5), it can indicate the proximity of intra-
mural myomas to the endometrial cavity with high accuracy
(52). Magnetic resonance imaging can at times provides ex-
tra information, particularly on the number of myomas,
size, and relationship with the serosal surface, but it is an
expensive diagnostic tool (52). Magnetic resonance imaging
can be used as a second diagnostic test when ultrasounds are
not sufficiently informative. The distance between myomas
and the subserosal surface has to be measured before per-
forming operative hysteroscopy to reduce the risk of uterine
perforation during surgery.
Management of Leiomyomas/Fibroids/Myomas
Most studies on the effects of myomectomy on RPL were
small case report series without controls, which were subject
to various methodologic limitations. Myomectomy improves
the chances of pregnancies in case of submucosal myomas,
but the data are insufficient to support a true decrease of preg-
nancy losses and even less for the possible cure of RPL (50).
No clear benefit of surgery has been demonstrated for intra-
mural myomas with no impact on the uterine cavity (50).
541
VIEWS AND REVIEWS
FIGURE 3
Office hysteroscopy of intrauterine acquired anomalies. (A) Endometrial polyp; (B) submucocal myoma type 0; (C) severe intrauterine adhesions.
Carbonnel. Uterine factors in recurrent pregnancy losses. Fertil Steril 2020.
Hysteroscopic resection of submucosal myomas is performed
routinely on outpatient bases for type 0 and 1 myomas <2 cm
in diameter (47, 52). It is also possible in the case of larger my-
omas to schedule a two-step procedure (52). ‘‘Classic’’ 22–26
FR resectoscope with a U-shaped cutting loop is commonly
used, but the hysteroscopic tissue removal system without en-
ergy through the progressive slicing and morcellation of the
myoma has shown good results (53). The risk of complications
increases for myomas having a diameter >3 cm (52). Intra-
uterine hyaluronic-based barrier gels and postoperative diag-
nostic hysteroscopy at 4–6 weeks decrease the risk of
adhesions after myomectomies (37). Other types and multiple
myomas need an abdominal approach to the myomectomy
(54). Abdominal myomectomies carry a higher morbidity
and, moreover, carry a risk of complications that far exceeds
hysteroscopic approaches. Indeed, abdominal approaches
often mandate future cesarean sections and a postsurgical
delay before attempting to conceive because of the potential
risk of uterine rupture, which is estimated at around 1%
(52). Furthermore, abdominal myomectomies are more likely
to generate pelvic adhesions that could cause subsequent
542
infertility issues (55). The risk-benefit ratio has to be taken
into account, and all options have to be discussed with the pa-
tient before surgery. Surgeons should adopt a routine adhe-
sion reduction strategy and good surgical techniques (56).
Randomized controlled trials have provided clinical evidence
supporting the safety and efficacy of barrier gels for the
reduction of postsurgical adhesions after myomectomies
(57). Minimally invasive abdominal myomectomies reduce
the risk of adhesions and improve postoperative recovery
and cosmetic results (58), but they are not possible in all cases
especially when multiple fibroids are present and/or their size
is >10 cm (58). The possible benefit of robotic surgery has not
been yet demonstrated for such procedures and still needs to
be investigated (59).
Against common wisdom, ESHRE guidelines surprisingly
conclude that there is insufficient evidence supporting the
hysteroscopic removal of submucosal fibroids in women
with RPL (3, 50, 60). Despite the lack of consensus,
surgery for submucosal fibroids is conducted by most practi-
tioners to improve fertility outcome—notably, in case of
RPL (46, 48, 50, 61). Myomectomy through hysteroscopy is
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a safe and effective method for removing submucosal my-

FIGURE 4
omas < 3 cm. This should be promoted to optimize fertility
outcomes in patients of reproductive age with RPL and sub-
mucosal fibroids (FIGO 0–2), while waiting for definitive
data (13, 60). Surgical removal of intramural fibroids is not
recommended by international guidelines (3).

Endometrial Polyps
The prevalence of endometrial polyps related to RPL varies
from 1.6% to 6% (6, 7, 9). Their association with infertility
has long been suspected, but there is no clear evidence
showing an association with RPLs (62). Endometrial polyps
are localized endothelial tumors that include endometrial
glands, stroma, blood vessels, and, typically, fibrous tissue.
Their morphology varies considerably, from millimeters to
centimeters in largest dimension, sessile or pedunculated in
shape, and single or multiple in number. When followed for
a year, spontaneous resolution may occur in up to 27% of
cases. The presence of endometrial polyps can adversely Three-dimensional ultrasound image of a uterus septum.
impact fertility by both mechanical interference and the Carbonnel. Uterine factors in recurrent pregnancy losses. Fertil Steril 2020.
release of molecules with relevant evidence of increased levels
of glycodelin (63), aromatase (64), inflammatory markers (65),
and reduced levels of HOXA-10 and -11 messenger RNA. So
far, no studies compared these expressions before and after opposing walls of the uterine cavity or cervix that alter the
polypectomy. Ultrasound is an efficient means for diagnosing quality of the endometrial mucosa. Characteristically, these
endometrial polyps. Sonohysterography or office hysterosco- alterations are encountered after uterine curettages, infec-
py has found 20%–30% cases of endometrial abnormalities tions, and intrauterine surgery or postobstetrical complica-
that had been missed on ultrasound (66) (Fig. 3). tions such as, notably, retained fragments of placenta.
Intrauterine adhesions are also frequent complications of
Management of Endometrial Polyps hysteroscopic surgery for polypectomy, myomectomy, and
lysis of adhesions (10%–30%) (37). The prevalence of IUAs
According to ESHRE and ASRM, there is insufficient evidence
in RPL varies from 1.3% to 9.6%, depending on the study
to recommend hysteroscopic removal of polyps to reduce the
(6, 7, 9). Intrauterine adhesions are encountered in one in
risk of RPL (3, 11, 12, 62). Yet case report studies indicate that
five women (20%) after miscarriage, with 42% of cases being
hysteroscopic polypectomy improves fertility outcome after
rated as moderate to severe (10). Recurrent miscarriage and
intrauterine insemination and/or ART (62, 67). Therefore, it
dilatation and curettage procedures are also identified as
remains the fact that endometrial polypectomies ought to be
risk factors for IUA formation. A meta-analysis reported by
recommended in patients seeking to conceive. Surgical
Hooker et al. (10) showed that, relative to women who only
removal of polyps is performed mainly using a 15–26 FR re-
had one miscarriage, women who had two or more miscar-
sectoscope or 5 FR hysteroscope with an operative channel
riages showed an increased risk of IUAs. There were no studies
(bipolar electrodes, scissors) under general anesthesia or dur-
assessing IUAs as a cause—or a consequence—of RPL. Howev-
ing ‘‘see-and-treat’’ approaches using office hysteroscopy
er, the presence of moderate to severe IUAs may greatly affect
(62, 68). This procedure—very safe—has a low rate of compli-
fertility and predisposes to pregnancy and obstetrical compli-
cations (69). Evidence linking hysteroscopic polypectomy to
cations (71). Intrauterine adhesions may lead to pregnancy
ART success rates remains conflicting, but investigations
loss due to insufficient endometrium development for sup-
regarding ET after polypectomy exist (70). In a nonrandom-
porting the fetoplacental growth (72).
ized retrospective study on 487 patients, no differences
Office hysteroscopy is the gold standard for IUAs diag-
were seen between embryo transfer performed after one,
nosis (Fig. 4). Conversely, ultrasound is a poor tool for detect-
two to three, or more than three subsequent cycles with
ing IUAs when used without SHG. No consensus exists about
similar implantation (42.4%, 41.2%, 42.1%), clinical preg-
the proper management of IUAs. Similar pregnancy outcomes
nancy (48.5%, 48.3%, 48.6%), and live birth rates (44.0%,
were reported after conservative, medical, or surgical treat-
43.6%, 44.6%) or spontaneous pregnancy loss (4.56%,
ment of IUAs (10). There is no consensus regarding the surgi-
4.65%, 4.05%) (70). No universally accepted recommenda-
cal method, instruments, or use physical barriers—intrauterine
tions have been accepted to guide polyp management.
device, Foley catheters, and so on—for preventing recurrence.
Mild avascular adhesions can be treated during the course of
Intrauterine Adhesions office hysteroscopy, whereas lysis of severe adhesions re-
Intrauterine adhesions, also referred as Asherman syndrome, quires general anesthesia. Hysteroscopic adhesiolysis is best
are characterized by fibrotic tissue developing from the performed with cold scissors or bipolar/monopolar energy,

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VIEWS AND REVIEWS
which is effective in the case of mild to moderate IUAs (72).
The initial severity of the adhesions appears to strongly corre-
late with reproductive outcome, severe adhesions having the
highest rate of recurrence (72). Precautions must also be taken
to prevent such recurrences after hysteroscopic resections of
IUAs (60). These precautions include, notably, practicing
second-look office hysteroscopy for identifying and easily
removing newly formed IUAs approximately 4 weeks after
surgery. This practice should be recommended for all women
undergoing hysteroscopic surgery with a risk of IUA recur-
rence (resection for myomas, polyps, or IUAs) (37). Contrary
to the clinical practice at our intuition, the ESHRE and
ASRM guidelines conclude that there is insufficient evidence
of a benefit for surgical removal of IUAs in women with RPL
(3, 12). However, treatment of mild and moderate adhesions
has a positive impact on subsequent fertility (72).
CONCLUSIONS
Significant progress has been made in understanding many of
the endometrial factors that might interfere with pregnancy
success. Uterine anatomical factors—congenital and ac-
quired—are involved in RPLs. Given the relatively easy access
to hysteroscopy, MRI, and high-resolution ultrasound tech-
niques, we should perform complete uterine assessment in
all women who present with a history of RPL. Even if the tools
for assessing the uterus are present, much work remains to be
done to better understand the clinical process of RPL and
identify the molecular mechanism underlying it. Data on sur-
gical indications in case of congenital and acquired uterine
anomalies are still conflicting. In spite of this, we believe
that resection of uterine septa, IUAs, submucosal myomas,
and endometrial polyps is indicated in women with RPL.
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