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Clinical Aspects of HyFoSy as Tubal Patency Test in Subfertility Workup

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Background: Tubal patency testing is an essential part of female subfertility evaluation. Traditionally, hysterosalpingography (HSG) was the first step to evaluate tubal patency. However, during the past decade Hysterosalpingo-Contrast Sonography (HyCoSy) was introduced in order to avoid radiation exposure and Hysterosalpingo-Foam Sonography (HyFoSy) has been developed as a safe and less painful alternative. Objectives and rationale: The aim of this narrative review is to provide an overview of the currently available HyFoSy literature and related clinical aspects. Search methods: A literature search was conducted using PubMed and Embase from the introduction of HyFoSy to March 2019. Unfortunately, a meta-analysis was not possible due to a too small number of studies, being mutually incomparable for the various subjects of clinical aspects, even for the reliability as a test for tubal patency. Outcomes: Nine small studies concluded that the accuracy and effectiveness as a test for tubal patency of 2D- and 3D-HyFoSy are comparable or even better than HSG or HyCoSy. With or without using Doppler techniques, 3D-HyFoSy does not seem to offer benefits above real-time 2D-HyFoSy. Five studies reported on pain and discomfort during HyFoSy, concluding that HyFoSy is a well-tolerated, less painful procedure compared to HSG, without a need for the use of analgesics. There are suggestions about an increased pregnancy rate in the first three cycles after the procedure but in no studies pregnancy outcome after HyFoSy was compared with other or no intervention. Wider implications: HyFoSy is a promising and safe alternative for HSG with regard to accuracy and effectiveness. HyFoSy lacks radiation and iodine exposure and is a well-tolerated and less painful procedure than HSG, without the need for analgesics. However more research is needed to make clear statements regarding a therapeutic effect of HyFoSy.
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Review Article
Clinical Aspects of HyFoSy as Tubal Patency Test
in Subfertility Workup
Niek Exalto 1and Mark Hans Emanuel2,3
1Division of Obstetrics and Prenatal Medicine, Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre,
Rotterdam, Netherlands
2Division of Woman and Baby, Department of Gynaecology and Reproductive Medicine, University Medical Centre,
Utrecht, Netherlands
3Department of (Uro)gynaecology, University Hospital, Ghent, Belgium
Correspondence should be addressed to Niek Exalto; n.exalto@erasmusmc.nl
Received 31 March 2019; Accepted 4 June 2019; Published 8 July 2019
Academic Editor: Alessandro Favilli
Copyright ©  Niek Exalto and Mark Hans Emanuel. is is an open access article distributed under the Creative Commons
Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is
properly cited.
Background. Tubal patency testing is an essential part of female subfertility evaluation. Traditionally, hysterosalpingography (HSG)
was the rst step to evaluate tubal patency. However, during the past decade Hysterosalpingo-Contrast Sonography (HyCoSy) was
introduced in order to avoid radiation exposure and Hysterosalpingo-Foam Sonography (HyFoSy) has been developed as a safe and
less painful alternative. Objectives and Rationale. e aim of this narrative review is to provide an overview of the currently available
HyFoSy literature and related clinical aspects. Search Methods. A literature search was conducted using PubMed and Embase from
the introduction of HyFoSy to March . Unfortunately, a meta-analysis was not possible due to a too small number of studies,
being mutually incomparable for the various subjects of clinical aspects, even for the reliability as a test for tubal patency. Outcomes.
Nine small studies concluded that the accuracy and eectiveness as a test for tubal patency of D- and D-HyFoSyare comparable
or even better than HSG or HyCoSy. With or without using Doppler techniques, D-HyFoSy does not seem to oer benets above
real-time D-HyFoSy. Five studies reported on pain and discomfort during HyFoSy, concluding that HyFoSy is a well-tolerated, less
painful procedure compared to HSG, without a need for the use of analgesics. ere are suggestions about an increased pregnancy
rate in the rst three cycles aer the procedure but in no studies pregnancy outcome aer HyFoSy was compared with other or
no intervention. Wider Im plic ations . HyFoSy is a promising and safe alternative for HSG with regard to accuracy and eectiveness.
HyFoSy lacks radiation and iodine exposure and is a well-tolerated and less painful procedure than HSG, without the need for
analgesics. However more research is needed to make clear statements regarding a therapeutic eect of HyFoSy.
1. Introduction
Tubal patency testing is an essential part of female subfertility
evaluation []. Tubal abnormalities are seen in -% of
female subfertility patients []. Laparoscopy (LSC) with
chromopertubation is considered to be the gold standard
diagnostic procedure []. LSC is an invasive test, with a risk of
intra-abdominal bleeding, visceral damage, and risks related
to general anaesthesia. Traditionally, hysterosalpingography
(HSG) is a less invasive rst-step alternative, which has been
used for decades. Considering the disadvantages of HSG
such as radiation exposure, discomfort, or even abdominal
pain, Hysterosalpingo-Contrast Sonography (HyCoSy) was
introduced as an alternative [, ] using either contrast
media or saline. e accuracy of HyCoSy is comparable to
that of HSG and LSC [, ] being reference standards for
tubal patency testing. An advantage of ultrasound is that,
in addition to tubal patency, information is also obtained
about pelvic anatomy including uterus and ovaries. Avoiding
pregnancy in the treatment cycle is extremely important in
HSG procedures.
ere are indications that the accuracy of HyCoSy may
improve by using D imaging techniques [, ]. Recently it
was claimed in a LSC controlled study [] that not only tubal
Hindawi
BioMed Research International
Volume 2019, Article ID 4827376, 12 pages
https://doi.org/10.1155/2019/4827376
BioMed Research International
patency but also peritubal adhesion could be assessed with
HyCoSy by observing a lower “spray score” at the mbrial
end. In a large systematic review with meta-analysis [] no
benet was found of commercially available contrast media
over saline and Doppler sonography was associated with a
greater sensitivity and specicity.
However, hyperechogenic contrast media such as Echo-
vist(Schering AG, Berlin) and SonoVue(Bracco, Milan)
are either no longer available or not licensed for tubal patency
testing. Hysterosalpingo-Foam Sonography (HyFoSy) was
developed as an alternative for contrast HyCoSy and was
introduced in  [] as a rst-line oce tubal patency
test. Foam is used in the HyFoSy technique to visualize
the Fallopian tubes and is created by rigorously mixing ml
ExEm-gel (containing hydroxyethyl cellulose and glycerol,
IQ Medical Ventures BV, Rotterdam, e Netherlands) with 
ml puried ExEm-water. e ExEm-foam, with a viscosity
of  cP and containing . % water, is suciently uid
to pass the Fallopian tubes and in the meantime suciently
stable to show echogenicity for at least ve minutes, which
is an advantage over saline. In a review on safety aspects
and side eects of ExEm-gel [] it was considered to be
appropriate and safe for tubal patency testing. is was
conrmed in a recently published retrospective study []
among  women undergoing HyFoSy, reporting no side
eects at the follow-up appointment.
is review on tubal patency testing is intended as an
update of the literature focusing on clinical aspects of HyFoSy
in subfertility workup, like diagnostic accuracy and side
eects, D and Doppler ow techniques, discomfort and pain,
intravasation, pelvic inammatory disease prevention, and
enhancing the chance of pregnancy.
2. Methods
A literature search wasconducted using PubMed and Embase
from the introduction of HyFoSy to  March . We
searched with terms related to the index test HyFoSy and did
not use any lter to maximize the sensitivity of the search.
Studies on the use of HyFoSy to conrm occlusion aer tubal
sterilization were excluded.
Unfortunately, a meta-analysis was not possible due to a
too small number of studies, being mutually incomparable for
the various subjects of clinical aspects, even for the reliability
as a test for tubal patency. We therefore decided to provide
a description of published ndings and facts as an update of
the literature on this subject. e results are summarized in
a table containing references per subject, type of the study,
study design, and main results (Table ).
3. Diagnostic Accuracy and Side Effects
e rst report on ecacy of HyFoSy [] was a prospective
observational cohort study in  subfertile women undergo-
ing a HyFoSy. A successful procedure was performed in 
(%) of these  women. In  women (%) tubal patency
was observed and no further examination was needed. In
 women (%) tubal occlusion was conrmed by HSG and
in another  women (%) there was a discrepancy between
HSG and HyFoSy ndings. Five patients experienced vaso-
vagal discomfort during or aer the procedure that resolved
spontaneously in time. No serious adverse eects occurred.
In the second observational cohort study [], comparing the
results of  HyFoSy procedures with LSC, there was a %
agreement between HyFoSy and LSC.
In a randomized controlled selective crossover trial
(n=) comparing HyFoSy with saline HyCoSy [], the
proportion of Fallopian tubes that were classied as patent
was higher in the HyFoSy group compared to saline HyCoSy
(,% versus ,%, p=.). On crossover testing HyFoSy
also performed better than saline HyCoSy. No major post-
procedural complications were observed.
In a randomized controlled study in  infertile women
scheduled for LSC [], the results of HyFoSy and saline
HyCoSy were compared with LSC ndings. Tubal patency
was in the HyFoSy group concordant with LSC in ,%
of cases (sensitivity ,% and specicity %) compared
to ,% in the saline HyCoSy group (sensitivity % and
specicity ,%). In a prospective observational study [ ] in
 women HyFoSy and HyFoSy with High Denition Flow
(HDF) Doppler technique was compared to saline HyCoSy
and LSC as gold standard. Saline HyCoSy and HyFoSy were
in comparison to LSC both signicantly less accurate (.%;
p<., respectively, .%; p<.) whereas HyFoSy with
HDF Doppler did not signicantly dier from LSC (,%;
p<.). Although HyFoSy with and without HDF Doppler
technique performed better, the authors conclude that saline
HyCoSy may be used as an initial test because of its high
negative predictive value on tubal occlusion (.% versus
.%, respectively; % for HyFoSy without HDF Doppler
technique).
It is good to realize that it is easier to diagnose tubal
patency than tubal occlusion due to a dicult dierentiation
between true and false occlusion caused by, for example, a
mucus plug or a spasm []. Actually there is no diagnostic
test for tubal occlusion, only for tubal patency.
4. 3-Dimensional Ultrasound and Doppler
Flow Techniques
HyCoSy with saline (and air) is, in comparison to HyFoSy,
more observer-dependent due to the fact that the hyperechoic
characteristics are usually lost within a short time and the
inability to examine the whole course of the Fallopian tube
inonescanningplane[].Inattemptstoovercomethese
problems -dimensional ultrasound (D-US) and Doppler
techniques [] were introduced. As the hyperechoic char-
acteristics of HyFoSy are much more stable, there is more
time for routine D ultrasound. It is therefore questionable
whether these techniques are of additional value for HyFoSy.
In a prospective observational study [] in  subfertile
women, all women underwent HyFoSy with new automated
D coded contrast imaging (CCI) soware (GE Healthcare)
with two foam injections followed by D real-time HyFoSy.
Because the ExEm-foam was too viscous to pass through the
 French HyFoSy balloon catheter, the investigators prepared
BioMed Research International
T : A summary of the studies used, grouped per reference and subject, mentioning the type of the study, the study design, and the main results.
Subject/Reference Type of study Study design Main results
accuracy
[] Emanuel et al.  Observational First observational study (n=) Successful procedure %
[] Van Schoubroeck et
al.  Observational HyFoSy versus Laparoscopy (n=) Agreement %
[] Lim et al.  RCT HyFoSy versus saline HyCoSy (n=) HyFoSy performed better
[] Piccioni et al.  RCT LSC controlled trial HyFoSy versus HyCoSy (n=) HyFoSy ,% versus HyCoSy ,%
[] Ludwin et al.  Observational LSC controlled trial HyFoSy versus HyFoSy Doppler
and saline HyCoSy (n=)
HyFoSy (,%) and HyFoSy Doppler (,%)
performed better than saline HyCoSy (,%)
3D US and Doppler
ow techn.
[] Soliman et al.  Observational LSC versus saline HyCoSy Power Doppler ow
mapping
Power Doppler saline HyCoSy can be incorporated in
routine fertility workup
[] Exacoustos et al.
 Observational D HyFoSy compared to automated D CCI HyFoSy
(n=) D CCI HyFoSy is accurate and safe
[] Riganelli et al.  RCT LSC controlled D HyFoSy versus D HyFoSy (n=) D HyFoSy performed better (% versus %)
[] Ludwin et al.  Observational Retrospective D Doppler HyFoSy versus D HyCoSy D Doppler HyFoSy performed better
[] Lavaillant et al.  Observational Fertiliscan© including D HyFoSy Anatomy of uterus, ovaries and tubes
Discomfort and pain
[] Savelli et al.  Observational HyCoSy with paediatric balloon catheter(n=) Pain: no (,%), mild (,%) and severe (,%)
[] Tur-Kaspa  Opinion Expert opinion and review Education in gentle technique
[] Dreyer et al  RCT VAS score HyFoSy versus HSG (n=) Lower VAS score for HyFoSy (. vs .; p<.)
[] Van Schoubroeck et
al.  Cross sectional VAS score TVU and TVU + subsequent HyFoSy
(n=) Lower VAS score for TVU (. vs .)
[] Van Schoubroeck et
al.  Randomized trial VAS score HyFoSy with paediatric Foley’s catheter
versus uVue catheter (n=)
Foley’s catheter easier to insert
uVue catheter less painful
[] Ludwin et al.  Observational HyFoSy with and without analgesics (n=) VAS score higher without analgesics (. vs .;
p=.)
catheter
[] Yung et al  RTC Without balloon versus with balloon (n=) Without balloon less pain
[] Dessole et al  Obser vational Comparison of  dierent catheters (n=) No dierence observed
temperature
[] Fenzl  Observational Saline and Echovist temp 0versus 0(n=) Less pain in case of body temperature
[] Opolskiene et al.
 Observational Saline (SIS) in premenopausal versus postmenopausal
women (n=) Postmenopausal more pain (% vs %; p<.)
[] Zhu et al.  Observational HSG room versus body temperature contrast (n=) Less pain with warm contrast
BioMed Research International
T : C o n t i nu ed.
Subject/Reference Type of study Study design Main results
analgesics
[] Frishman et al.  RCT lidocaine or saline before HSG (n=) No dierences in pain score
[] Guney et al  RCT Local lidocaine before SIS (n=) Only benecial in parous women
[] Van den Bosch et al.
 Observational Local lidocaine before Hysteroscopy (n=) No dierence
[] Yung et al.  RCT SIS with and without lidocaine (n=) No dierence
[] Hindocha et al.  Systematic review Pain relief in HSG Local analgesics may be eective
[] Ahmad et al.  Systematic review Any analgesia in HSG No benet
[] Ahmad et al.  Systematic review Any analgesia in HyCoSy No benet
[] Moro et al  RTC Antispasmodic drug in HyCoSy (n=) No dierence in pain scores
[] Teran-Alonso et al.
 Observational Paracetamol and ibuprofen prior to hysteroscopy No reduction of pain scores
[]Karamanetal. RTC RectalindomethacinpriortoHSG Eectiveinpainreduction
Intravasation
[] Onwuchekwa and
Oriji  Observational HSG with WSCM (n=) Intravasation in .%
[] Wang et al.  Observational Intravasation in HyCoSy with SonoVue (n=) Intravasation in .%
[] Ludwin et al.  Case report First report on intravasation with HyFoSy
PID prevention
[] Dessole et al.  Observational Sonohysterosalpingography (n=.) Fever and peritonitis in .%
[] Pittaway et al.  Observational PID aer HSG in tubal occlusion / (%) without
and / (%) with antibiotics Antibiotics only in case of tubal occlusion
[] Simms et al.  Case control study Risk factors associated with PID in  cases compared
to  controls
Age <, early rst sex experience, low socio-economic
status and chlamydia exposure
[] Kasius et al.  RCT AB prophylaxis for hysteroscopy (n= AB vs 
contr) PID in AB .% versus contr %
[] Gregoriou et al.  RCT AB prophylaxis for hysteroscopy (n= AB vs 
contr) PID in AB .% versus contr .%
[] Nappi et al.  RCT AB prophylaxis for hysteroscopy (n= AB vs 
contr) PID in AB .% versus contr .%; p>.
[] inkamrop et al.
 Cochrane Syst Rev AB prophylaxis for transcer vical intrauterine
procedures No conclusion possible
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T : C o n t i nu ed.
Subject/Reference Type of study Study design Main results
[] Pareira et al.  Systematic review AB prophylaxis for Gynaecologic procedures. Not as routine, only in high risk cases
Enhancing chance of
pregnancy
[] Van Schoubroeck et
al.  Observational Retrospective study - months aer HyFoSy (n=) Pregnancy rate %
[] Tanaka et al.  Observational Retrospective cohort study  months aer HyFoSy
(n=) Pregnancy rate %
[] Emanuel et al.  Observational Retrospective study  months aer HyFoSy (n=) Pregnancy rate .%
[] Exacoustos et al.
 Observational Retrospective study ,  and  months aer HyFoSy
(n=) Pregnancy rates .%, .% and .%
[] Watson et al.  Meta analysis RTCsandothersonHSGwithOSCMversus
WSCM erapeutic eect of OSCM
[] Johnson et al.  Cochrane Syst Rev Systematic Review OSCM and OCSM versus WSCM erapeutic eect of OSCM
[] Johnson  Narrative review OSCM treatment of infertility erapeutic eect in endometriosis
[] Mohiyiddeen et al.
 Cochrane Syst Rev e eect of tubal ushing on life birth and pregnancy
rates
Higher life birth rate for OSCM versus WSCM (OR
. versus .)
[] Dreyer et al.  Multicentre RCT Pregnancy  months aer OSCM versus WSCM
(n=) Higher pregnancy rate aer OSCM (% vs %)
[] Lindborg et al.  RCT HyCoSy with WSCM (n=) No enhanced pregnancy rate
[] Giugliano et al  Observational Saline HyCoSy (n=) % pregnancy rate in the rst  days
[] Ahinko-Hakamaa et
al.  Observational Pregnancy rates aer (mean) . cycles with IUI. Pregnancy rates aer LSC %, HyCoSy % and HSG
%.
[] Dreyer et al.  Post-hoc analysis Prospective multicentre cohort study (n= ) HSG increased pregnancy rate compared to no HSG
regardless of WSCM or OSCM
[] Chunyan et al.  Observational Pregnancy within  days aer HyCoSy (n=) Higher pregnancy rates if both tubes are open
[] Salehpour et al.  RCT Saline infusion prior to IVF (n=) versus controls
(n=) Pregnancy / versus / (p=.)
[] Reilly et al.  RCT OSCM endometrial bathing prior to IVF (n=) vs
controls (n=) in women with endometriosis
Pregnancy within  months / (%) versus /
(%)
BioMed Research International
F : An example of D HyFoSy. e clear white line is sucient
evidenceforanopenFallopiantube.
a dierent and unusual o-label ExEm-gel dilution. e
concordance rate between the rst and second D volume
reconstruction and the nal D real-time evaluation was
.% and .%, respectively. Vasovagal reactions were
observed in two patients and no other adverse eects were
noted.
Riganelli et al. [] described in a pilot study the
results of a randomized controlled trial in  women who
were previously subjected to LSC and randomly assigned
to D-HyFoSy or D-HyFoSy. e D-HyFoSy was in %
of the cases concordant with the LSC, with a sensitivity
of % and a specicity of %. e D-HyFoSy was in
% concordant with LSC, with a sensitivity of % and
a specicity of .%. Statistical analysis of this dierence
is lacking in this study. e D-HyFoSy procedures were
found to be less painful and faster (P<.). In the dis-
cussion the authors state that D-HyFoSy is less operator-
dependent and more reproducible and it allows postproce-
dural reconstruction of images. ey conclude that, in low
risk patients, if the tubes appear obstructed in D-HyFoSy,
D-HyFoSy seems advisable before submitting patients to
LSC.
Ludwin et al. [] concluded from their retrospec-
tive study in  women that the interobserver reliability
and agreement on the diagnosis of tubal patency using
stored videos improved when HyFoSy combined with power
Doppler technique was used in comparison to D-HyCoSy.
e relatively small number of patients in this retrospective
study and the lack of real-time D information are limita-
tions.
With or without using Doppler techniques, D-HyFoSy
does not seem to oer benets above real-time D-HyFoSy
performed by an ultrasonographer who is familiar with pelvic
anatomy (Figure ). e clear white line indicating foam
passage through the proximal part of the tube is sucient evi-
dence for the absence of a distal occlusion as is known from
studies using hysteroscopy and air bubbles []. Anyway,
from the nine clinical studies [–], it can be concluded
that HyFoSy appears to be accurate and well-tolerated rst-
line diagnostic procedure and the D-HyFoSy technique is
helpful for a less experienced operator. Furthermore, D
scanning oers standardization of pelvic scanning and its use
is superb for educational purposes. Recently a novel concept
named Fertilityscan© was described [] using D-HyFoSy
as a women-friendly and cheap assessment for both anatomy
and function of the uterus, ovaries, and tubes.
5. Discomfort and Pain
Intrauterine application of contrast media may cause discom-
fort and pain. is may be due to the dilatation of the cervix,
application of a catheter, lling of the cavity under pressure,
the composition of the contrast medium, or a combination
of factors. In an observational study [] on  patients
undergoing saline HyCoSy via a paediatric balloon catheter
no pain was observed in .%, mild pain in .%,moderate
pain in .%, and severe pain in .% and vasovagal reactions
were seen in .%.
In general, a gynaecological examination is for the major-
ity of patients embarrassing and stressful, enhanced by fear
or pain []. It is important to explain the procedure before
starting the examination, to insert the speculum slowly, and,
most importantly, to inject the medium very slowly to avoid
high intrauterine pressure.
Five studies have been published regarding pain expe-
rience during HyFoSy. e rst [] was a randomized
controlled trial including  women, comparing visual ana-
logue scale (VAS) pain score during tubal patency testing
using HyFoSy and serial HSG. For HyFoSy, a small cervical
balloonless catheter was placed. For HSG, a hysterophore
with one tenaculum on the anterior cervical lip was used.
All media were injected in the uterine cavity with the use
of an electrical pump with a standardized ow and pressure.
is trial showed a lower VAS score in the HyFoSy group
compared to the HSG group (median VAS score . cm;
interquartile range (IQR) . versus median VAS score . cm;
IQR .; P<.).
In a cross-sectional study [] on  patients the median
VAS score for pain during transvaginal ultrasound (TVU)
and subsequent HyFoSy was . cm (% CI, .-.) and
. cm (% CI, .-.), respectively. To instil the foam, a
balloon catheter was placed. One in three women reported
the same level of discomfort or pain during TVU as for
HyFoSy; % of the women reported the HyFoSy to be
neutral/unpleasant, but not painful. ere was an inverse
association between both patient’s age and parity and expe-
rienced pain [].
In a randomized controlled trial [ ] including  women,
HyFoSy was performed using two dierent balloon catheters,
uVue HSGcatheter or a paediatric Foley’s catheter. It was
concluded that a paediatric Foley catheter was easier to insert
and the HyFoSy was less painful compared to HyFoSy using
uVue HSGcatheter.
One study has been published [] concerning the use of
analgesics during D/D Doppler HyFoSy. In a prospective
observational study  women were subjected to uterine
cavity and tubal patency ultrasound assessment and asked to
report VAS pain scores. From October  until March 
the procedure was performed without any analgesics in 
women. From March until the end of the study  women
received approximately  hour before the procedure a tablet
containing paracetamol mg and codeine phosphate mg.
BioMed Research International
During D/D-Doppler-HyFoSy, the median VAS pain score
was signicantly higher for women not using analgesics
(median VAS score . cm; IQR .-. versus a median VAS
score . cm; IQR .-.; p= .).
ere are no other studies concerning pain and the
placement of the catheter, lling of the uterus, and local or
systemic anaesthesia during HyFoSy. We therefore will report
on these aspects in relation to gel instillation sonography
(GIS), saline infusing sonography (SIS), HSG, and HyCoSy.
5.1. e Use of Catheter. It has been suggested [] that SIS
performed with an infant feeding tube without a balloon
is associated with very low pain levels in comparison to
catheters with a balloon (median pain score , on a scale of
-). at is consistent with the theory that most sensory
receptors are located in the area of the cervical internal
ostium. On the other hand, Dessole et al. [] compared
six dierent catheters, used in  sonohysterograms. e
diameter of the catheters varied from Charrier  to Charrier ,
ve had a balloon at the tip with a capacity of -mL, and one
was equipped with a movable stopper, which is xed to the
external os of the uterus. e authors did not nd signicant
dierences with regard to reliability, the physicians ease of
use, the insertion time, the volume of contrast medium, and
pain.
5.2. Type and Temperature of Contrast. e inuence of the
contrast medium (Echovistversus saline) and the tempera-
ture (Cversus
C) was investigated in a prospective ran-
domized HyCoSy study [] including  patients. Echovist
induced signicantly less pain in comparison to saline at the
same temperature (p=. and p=.). Between the two
groups there was also a signicant dierence in pain during
the introduction of the same contrast at dierent temperature
(p<.). e most tolerable one for the patient is body
temperature. is applies for both contrast media. ese
results may indicate that Echovistis more “patient-friendly”
than saline. In another study [] on pain experience during
SIS (n=) it was observed that postmenopausal women
experiencedpainmoreoenthanpremenopausalwomen
(% versus %; p<.). Also the character of the pain
in relation to saline was dierent: postmenopausal women
more oen felt a sharp pain (%), whereas premenopausal
womenmoreoenfeltgnawingand/orcrampingpain(%).
is may be related to the thin atrophic endometrium
in postmenopausal women. Furthermore, in a randomized
study on  HSG procedures [] it was observed that
warming the contrast to body temperature is associated with
less pain and fewer vasovagal episodes.
5.3. Analgesics. In a randomized double-blinded placebo-
controlled trial []  women received  mL % lidocaine
solution or .% normal saline before undergoing a HSG.
As there were no dierences with respect to pain scores
between both groups, intrauterine lidocaine did not appear
to be eective. In a smaller study of  women [], a
benecial eect of intrauterine lidocaine was only seen in
parouswomenundergoingSIS.Inastudyonpatients
[] undergoing GIS with and without lidocaine containing
gel prior to a hysteroscopy no dierences were seen either.
From another randomized double-blind placebo-controlled
trial [] on  patients undergoing SIS it could be concluded
that topical or local intrauterine application of lidocaine was
not eective in reducing pain.
FromasystematicreviewonpainreliefinHSG[]
it was concluded that topical analgesics applied before the
procedure may be eective, although the available evidence
was of low quality. Also, intravenous opioids may be eective
though this must be weighed against their side eects. In
other systematic reviews and meta-analysis [, ] it was
concluded that there is no evidence of signicant benet in
using any analgesia before HyCoSy or HSG compared to
placebo.
Mechanical distension of the uterine walls may cause
a release of prostaglandins, resulting in uterine cramps.
However in a large randomized double-blind clinical trial
[] (n=) there was no dierence in pain scores between
a group receiving an antispasmodic drug (hyoscine-N-
butylbromide) during HyCoSy or a placebo. In another study
[] administration of  mg paracetamol and  mg
ibuprofen one hour prior to oce hysteroscopy did not
reduce pain scores. Rectal indomethacin, however, reduced
the pain signicantly during HSG in a randomized placebo-
controlled trial [].
With regard to discomfort and pain it can be concluded
from all available literature that HyFoSy is a well-tolerated
procedure, less painful than HSG. ere is no role for local
and general analgesia. Prophylactic analgesia is not necessary
and, in case it is nevertheless considered, rectal application of
Indomethacin or codeine tablets seems to be eective.
6. Intravasation
Venous intravasation is a well-known complication of HSG,
occurring in about .% of cases []. Rarely cerebral and
pulmonary oil embolism aer oil-soluble contrast media
(OSCM), like Lipiodol, has been described in case reports
and aer water-soluble contrast media WSCM complications
like fever, infection, and pain have been described. In a study
on HyCoSy with SonVueintravasation occurred in .%
of  patients []. e incidence of intravasation was high
in case of thin endometrium and high pressure and low on
days - aer ending of the menstrual period. Recently a
rst case on intravasation during HyFoSy has been published
[]. As hydroxyethyl cellulose and glycerol are safe, even
in case of intravenous application [], no clinical signs or
complications occurred.
7. Pelvic Inflammatory Disease Prevention
As described in the rst paragraph, no major postprocedural
complications aer HyFoSy were observed in nine obser-
vational studies [–]. Glycerol, one of the components
of ExEm-gel, is known to have antimicrobial and virucidal
eects []. Fever and peritonitis occurred in only .%
of . patients undergoing sonohysterosalpingography [].
BioMed Research International
From HSG studies [] it is known that only patients with
an existing hydrosalpinx are at risk of PID and may benet
from prophylactic antibiotics. Age under  years, rst sex
at an early age, lower socioeconomic status, and exposure to
chlamydia trachomatis are risk factors for PID [].
Routine antibiotic prophylaxis is not benecial and is
not recommended in diagnostic hysteroscopy, because of the
very low risk of infection [–]. In a Cochrane Review
on antibiotics for transcervical intrauterine procedures []
it was concluded that no trials were eligible for inclusion
and it is therefore not possible to draw any conclusion.
In a large systematic review on antibiotic prophylaxis for
gynaecological procedures prior to and during the utilization
of assisted reproductive technologies [] it is also concluded
that routine antibiotic prophylaxis is generally not recom-
mended for these procedures. However, patients at risk of
pelvic infections should be screened and treated prior to
procedures such as HSG, SIS, HyCoSy, HyFoSy, hysteroscopy,
embryo transfer, and chromopertubation.
8. Enhancing the Chance of Pregnancy?
Up until now, only observational studies are available con-
cerning the chance of subsequent pregnancy aer HyFoSy.
A retrospective study [] reported on a % pregnancy
rate in  women aer HyFoSy during a variable follow-
up period of  to  months. In this study the number of
pregnancies was the highest in the cycle of the HyFoSy and
the rst two cycles aer the procedure. In a retrospective
cohort study [], among  subfertile women,  (.%)
women conceived within  months aer HyFoSy, of whom
 women conceived naturally. Emanuel et al. [] reported a
natural conception rate of .% with a median of  months
aer the HyFoSy procedure. In a retrospective observational
study [] regarding  subfertile women who underwent
HyFoSy,  women provided information by phone on their
fertility aer  months. e authors observed a cumula-
tive spontaneous pregnancy rate of .% within  month
aer HyFoSy, .% within  months, and .% within 
months.
More is known about the fertility enhancing eect of
tubal ushing at HSG []. Tubal ushing with (OSCM) is
increasing the odds of pregnancy and live birth in comparison
to no intervention or WSCM []. It is uncertain whether
this is a “tubal ushing” phenomenon, an eect on the
intraperitoneal environment, or an implantation enhancing
eect on the endometrium. Flushing with an OSCM has been
proven to be eective in endometriosis-related infertility
[]. In a recent Cochrane Review [] the ecacy of tubal
ushing with OSCM or WSCM was evaluated. In comparison
to no intervention the OSCM group had a higher rate of life
birth (OR ., % CI ,–.) compared to the WSCM
group (OR ., % CI .–.). Recently a multicentre
RCT on  patients [] showed signicantly more ongoing
pregnancies in the rst  months following HSG with OSCM
as compared to HSG with WSCM (% versus %, RR
.; % CI, . to .; P<.). e increased number
of pregnancies in this study was found to be based on pain
experienced during the procedure []. e use of OSCM
in HSG procedures is associated with the occurrence of
peritoneal granulomata [], neonatal hypothyroidism [],
and immunological eects [].
e clinical impression of enhanced pregnancy rates aer
HyCoSy with WSCM (Echovist) could not be conrmed
in a prospective randomized study [] (n=). In an
observational study on  patients aer saline HyCoSy []
a possible benecial eect of HyCoSy was observed directly
aer the procedure. e pregnancy rate was signicantly
higher in the rst  days aer HyCoSy (%) compared
to other months of observation aer HyCoSy (p<.).
One has to keep in mind however that this is comparable
to a % natural conception rate observed [] in the rst
cycle of the normal population. In a retrospective study
[] on  patients treated with intrauterine insemination
(IUI) it was observed that the cumulative pregnancy rates
(mean , cycles) aer LSC, saline HyCoSy, and HSG were
%, %, and %, respectively. In a recent post hoc
analysis of a prospective multicentre cohort study [] among
 couples with unexplained infertility HSG increased
the ongoing pregnancy rate compared to no HSG (adjusted
hazard ratio ., % CI .-.) regardless of WSCM
or OSCM was used. Furthermore, in a large study on 
infertile patients patency of both Fallopian tubes and the
absence of injective resistance turned out to be independent
factors associated with the ability to conceive aer HyCoSy
[]. is is consistent with the one-half reduction of clinical
pregnancies in a large study on the eect of unilateral tubal
abnormalities on the results of intrauterine inseminations
[].
In a prospective randomized controlled trial on intrauter-
ine saline infusion as a form of pregnancy enhancing
endometrial injury during IVF cycles in  patients with
recurrent implantation failure [] a possible negative eect
of saline on reproductive outcomes was observed. In this
study a clinical pregnancy occurred in  out of the 
women undergoing intrauterine saline infusion on days -
 in the stimulation phase as opposed to  out of 
women without an infusion (p<.). In a randomized study
[] comparing uterine bathing with OSCM prior to IVF
with IVF alone, no evidence was found of any benecial
eect.
ExEm-foam is safe and even passed the mouse-embryo-
test []. Although in observational studies we could not nd
any negative eect on fertility aer the HyFoSy procedure, we
have to conclude that no studies on postprocedure pregnancy
rates are available comparing HyFoSy with other or no
intervention.
9. Conclusion and Discussion
Although most of the studies presented in this review are
small with an observational design, it can be concluded
that HyFoSy is a promising alternative for HSG with regard
to accuracy and eectiveness. HyFoSy lacks radiation and
iodine exposure, which is a benet in comparison to HSG.
With or without using Doppler techniques, D-HyFoSy
BioMed Research International
does not seem to oer benets above real-time D-HyFoSy.
However, D scanning oers standardization of pelvic scan-
ning and may be performed by a less experienced opera-
tor. HyFoSy is a well-tolerated and less painful procedure
than HSG without a need for the use of analgesics. No
serious or severe complications have been reported aer
more than . procedures. Routine antibiotic prophy-
laxis is generally not recommended; however patients at
risk at pelvic infections should be screened and treated
accordingly prior to the HyFoSy procedure. Moreover, there
appears to be no detrimental eect of HyFoSy on fertility
and there might even be a benecial eect in the rst
three menstrual cycles aer the procedure on enhancing
pregnancies.
10. Future Perspectives
As HyFoSy is still a relatively new tubal patency test, only
observational data are available. erefore, robust random-
ized controlled trials are needed to draw rm conclusion
on the degree of accuracy and eectiveness of HyFoSy and
the fertility enhancing eect. As ExEm-foam is not yet
FDA-approved, large trials and clinical use of HyFoSy in
the US are lacking. In the Netherlands a large randomized
controlled study, the so-called FOAM trial, comparing the
eectiveness and costs of HyFoSy with HSG, is currently
ongoing []. In this study subfertile patients (N=), who
are scheduled for tubal patency testing during their fertility
workup, undergo both HSG and HyFoSy in a random order.
If the results of both tubal tests are discordant, women will be
randomly allocated to either a management strategy based on
HyFoSy or a management strategy based on HSG, implicating
either a LSC or a strategy that assumes tubal patency. e
primary outcome of this trial is an ongoing pregnancy
leading to live birth within  months aer randomization.
Recruitment for this trial is expected to be completed in the
fall of . erefore, the results will be available around
.
With regard to the fertility enhancing eect randomized
controlled trials comparing HyFoSy with other or no inter-
vention are urgently needed.
Disclosure
is research was not funded or nancially supported by any
grant; that is, no external funding was requested or provided
for this study.
Conflicts of Interest
Niek Exalto and Mark Hans Emanuel are the inventors of GIS
and HyFoSy with ExEm-gel. ey are shareholders in Giskit
B. V., the manufacturer of GIS-Kit and ExEm-Foam Kit,
and receive royalties from this company. is survey of the
clinical aspects of this new technique is a cons equence of their
involvement.
Acknowledgments
We are very grateful to Joukje van Rijswijk, Dr. Velja Mija-
tovic, and Prof. Dr. Nils Lambalk for their critical contribu-
tions from the rst manuscript onwards, their additions, and
suggestions for improvements.
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[] J. van Rijswijk, N. van Welie, K. Dreyer et al., “e FOAM study:
is Hysterosalpingo foam sonography (HyFoSy) a cost-eective
alternative for hysterosalpingography (HSG) in assessing tubal
patency in subfertile women? study protocol for a randomized
controlled trialfor a randomized controlled trial,BMC Womens
Health,vol.,no.,.
... Several studies have demonstrated diagnostic efficacy and benefits of HyFoSy (11,16,17) compared to HSG and laparoscopy with dye test. ...
... Distribution of the pain score with VAS agreed with the patient's feeling, confirming good tolerance of the examination for our population, with 80.3% of HyFoSy patients reporting a VAS pain score ≤ 3. In agreement with the literature, no side effects were reported (16,17). Of interest, non-visualisation of tubal patency was more frequently accompanied by poor tolerance of the examination (30% versus 17.5%). ...
... In patients with tubal obstruction (real or due to spasm), intrauterine pressure during the test leads to increased uterine contractility. However, no benefit of analgesia before the procedure has been demonstrated (16,28). ...
Article
Objective : Investigate potential factors associated with non-visualisation of tubal patency during Hysterosalpingo-Foam-Sonography (HyFoSy). Study design : This retrospective study was carried out at the medically assisted procreation centre of the University Hospital Centre in Reunion Island and focuses on HyFoSy performed between 01/01/2018 and 31/12/2020. We aimed to compare HyFoSy with bilateral tubal patency and those with a passage defect. Factors associated with non-visualisation of the contrast medium were investigated using comparison tests and logistic regression. Explanatory variables were patient history and ultrasound characteristics. Results : 137 eligible HyFoSy were included, of which 70.8% could be established for bilateral tubal patency. The assessment of tubal patency decreased in cases of overweight/obesity (62.5% versus 47.4%), previous pelvic surgery (17.5% versus 10.3%) and deep endometriosis (12.5% versus 5.2%), without significant difference. In the logistic regression model, a trend towards significance was observed for body mass index ≥ 25 kg/m² (OR 2.01 [95% CI 0.93-4.35], p = 0.07). Conclusion : HyFoSy as a first-line infertility test should be discussed in certain circumstances, due to risk of non-visualisation of tubal patency. In case of poor echogenicity, it should be performed by a trained ultrasonographer or a hysterosalpingography should be preferred. For tubo-pelvic pathologies, a laparoscopy should be discussed for diagnostic and therapeutic purposes. Discipline : gynaecology, infertility
... Compared with saline, foam has a higher viscosity, which provides longer contrast material stability (at least 5 minutes) and better fallopian tube visualization (35). The fertilityenhancing effect of HyFoSy has been reported, but randomized controlled trials are necessary to establish the efficacy of the method (36). Intravasation occurs less frequently with foam than with microbubble contrast material (36). ...
... The fertilityenhancing effect of HyFoSy has been reported, but randomized controlled trials are necessary to establish the efficacy of the method (36). Intravasation occurs less frequently with foam than with microbubble contrast material (36). Advantages of air-saline HyCoSy include virtually no risk of allergy, lower cost, and shorter procedural times (37). ...
Article
Impaired tubal patency accounts for up to 35% of cases of subfertility and infertility. Hysterosalpingography (HSG) or hysterosalpingo-contrast sonography (HyCoSy) represents a first-line test in evaluating fallopian tube patency. Despite the association of HSG with ionizing radiation, HSG is a reference standard in assessing fallopian tube patency and tubal conditions such as tubal occlusion, salpingitis isthmica nodosa, and hydrosalpinx. HSG is widely available and utilizes either a water-soluble contrast medium (WSCM) or an oil-soluble contrast medium (OSCM). Compared with WSCM, HSG with OSCM results in a higher incidence of non-in vitro fertilization pregnancies and, therefore, may be preferred in women younger than 38 years with unexplained subfertility. HSG may also be helpful in assessment after sterilization or before fallopian tube recanalization. US-based tubal tests are free of ionizing radiation and include HyCoSy, with either air-saline or microbubble US contrast material, and hysterosalpingo-foam sonography (HyFoSy), a tubal patency test that utilizes a gel foam. A comprehensive US infertility evaluation of the pelvis and fallopian tubes can be achieved in one setting by adding coronal three-dimensional imaging of the uterus, saline infusion sonohysterography, and HyCoSy or HyFoSy to routine pelvic US. MR HSG and virtual CT HSG also depict tubal patency and uterine and adnexal pathologic conditions and may be considered in select patients. While laparoscopic chromopertubation remains the standard for tubal patency evaluation, its disadvantages are its invasiveness and cost. Knowledge of the different fallopian tube tests and radiologic appearance of normal and abnormal fallopian tubes results in fewer pitfalls, accurate interpretation, and optimal patient care. Online supplemental material is available for this article. ©RSNA, 2021.
... In 2007, a non-embryotoxic gel known as ExEm ® gel (GynaecologIQ, Delft, The Netherlands) was developed. Because ultrasound scans (US) of good-quality at an acceptable price were obtained, hysterosalpingo-foam sonography (HyFoSy) has been established as a safe and less painful alternative and has become widely adopted in infertility clinics and outpatient settings, shortening waiting times for treatment initiation [10]; moreover, its feasibility, tolerability and safety have been already demonstrated [11][12][13]. ...
... Lastly, we confirmed that the clinical pregnancy rates from intrauterine inseminations carried out after performing HyFoSy were not affected by an incorrect diagnosis since our outcomes were like those observed in daily clinical practice, when HyFoSy was previously used to diagnose tubal patency. In addition, the studies published to date have reported a spontaneous pregnancy rate that ranges between 19-30% for a period of approximately 6 months [10,23]. ...
Article
Full-text available
Introduction: Simplified ultrasound-based infertility protocols that appear to provide enough information to plan effective management have been described. Thus, the objective of this study is to compare the diagnostic accuracy of the hysterosalpingo-foam sonography (HyFoSy) in tubal patency testing with the traditional hysterosalpngography (HSG) for establishing a new diagnostic strategy in infertility. Material and methods: Prospective observational diagnostic accuracy was performed in a private fertility clinic in which 106 women undergoing a preconceptionally visit were recruited. All of them had low risk for tubal disease, had performed an HSG and were negative for Chlamydia trachomatis antibody. Main outcome measures were tubal patency and pain grade. Results: Evaluation of tubal patency by HyFoSy showed a total concordance with the results of the previous HSG in 72.6% (n = 77), and a total discordance for 4.7% (n = 6), with the inter-test agreement Kappa equal to 0.57, which means moderate concordance. Among the patients, 59.1% did not report pain during the procedure, while the remaining 48.1% indicated pain in different degrees; patients usually report less pain and only 6.6% described more pain with HyFoSy than with HSG (OR 6.57 (CI 95% 3.11-13.89)). Clinical outcomes after performing HyFoSy were not affected. Conclusions: HyFoSy is in concordance with HSG regarding tubal patency results and it is a less painful technique than HSG. HyFoSy is more economical and can be performed in an exam room only equipped with an ultrasound scanner. Based on these results, HyFoSy could be the first-choice diagnostic option to assess tubal patency in patients with low risk of tubal disease.
Article
The high efficacy of modern assisted reproductive technology (ART) and increase in the number of noninfertile patients who are using ART for family building in the United States call into question the relevance of the standard, one-size-fits-all infertility evaluation. Here, we explore whether all patients presenting for ART need uterine cavity and tubal assessment and what tests are most appropriate, efficient, and cost-effective in current times.
Article
Objective To determine the clinical pregnancy rate following sequential hydrosonography and hysterosalpingo-foam sonography (HyFoSy) in tubal patency assessment among women undergoing infertility work-up. Study design Prospective follow-up of women referred to our department between July 2019 and October 2020. Sequential hydrosonography and HyFoSy were carried out. Results Out of 250 having the procedure, 100 women were excluded from study due to limited infertility, semen abnormal or not examined, evaluation for social egg freezing or they were single. Of the remaining 150 women, 48 (32%) conceived during a 10–24 months follow-up period: 17 (11%) conceived naturally and 7 (4.7%) by IUI. The mean time to conception was 5.5±5.4 months and the pregnancy rate was 52% within 6 months. Among the spontaneous pregnancies 47% occurred within a month and 76% within 3 months. Conclusion Sequential hydrosonography and HyFoSy is a promising method for assessing the uterine cavity and tubal patency in women undergoing infertility workup. The findings suggest that the procedure may increase the chance of a spontaneous pregnancy following the procedure. Given the other known advantages of sequential hydrosonography and HyFoSy, this test is worth including in the initial workup for infertile patients.
Article
Introduction : The aim of our study was to carry out a national survey of French practitioners to evaluate (i) their diagnostic criteria for making a diagnosis of unexplained infertility (UEI) and (ii) their management strategy when facing UEI. Materials and Method : An online questionnaire comprising ten multiple-choice questions was sent by mail to French reproductive practitioners in 80 fertility centres. Results : The response rate was 59.6% (195/327). Post coital testing was always or often prescribed by 14.8% of respondents (n=36). Chlamydia trachomatis testing was never prescribed by 31.7% (n=59) of them, 30.2% prescribed a pelvic MRI in cases of UEI and 18.4% (n=33) always or often performed laparoscopy. For 87.6% (n=169), advanced maternal age was always or often an indication of first-line IVF, with an average threshold of 37.4 years. For 68.6% (n=129), diminished AMH was an indication for first-line IVF, with an average AMH threshold of 1.2 ng/ml. With respect to the management of UEI, we did not observe a consensus between the strategies of 2 to 6 intrauterine insemination cycles before IVF or IVF as the first-line treatment. Conclusion : There is no consensus in France on what tests should or should not be carried out to conclude UEI, and there is also no consensus on the management of UEI. UEI is one of the top 10 priorities for future infertility research. The diagnostic criteria must be standardized to enable the comparison of studies on this topic as well as to improve the translation of research into clinical practice.
Article
Research question To evaluate the efficacy of sequential 2D transvaginal ultrasound (US) and hysterosalpingo-foam sonography (HyFoSy) after methotrexate (MTX) treatment for tubal pregnancy among patients who desire a future pregnancy. Design A prospective trial was conducted between May 2019 and November 2020. Only patients who had a suspected tubal ectopic pregnancy diagnosed by US and treated by MTX were included. These patients underwent sequential transvaginal 2D-US assessment of the pelvic organs and a complementary HyFoSy for tubal patency. The primary outcome was tubal obstruction in the affected side. Results During a study period, a total of 360 women underwent sequential transvaginal 2D-US assessment of the pelvic organs and a complementary HyFoSy for tubal patency. Of them, 40 (11.1%) women fulfilling the inclusion criteria were enrolled. In 6/40 (15%), hydrosalpinx of the affected tube was found during the initial transvaginal US examination and were excluded from further investigation. In the remaining 34/40 (85%) patients, HyFoSy was performed. Tubal block was found in 10/34 (29.4%) the patients. Of these, 8/34 (23.5%) and 2/34 (5.9%) had a proximal block of the affected tube and bilateral proximal obstruction, respectively. HSG confirmed the tubal obstruction in all the affected cases. No procedure-related complications were documented. Conclusions In this preliminary study, almost every second woman who was treated by MTX for tubal pregnancy was diagnosed as having a tubal obstruction. We suggest that sequential transvaginal US and HyFoSy be part of the routine follow-up for these women, thus offering them timely referral to the appropriate specialist. This approach should be considered in clinical guidance addressing the follow-up of women with tubal pregnancy treated with MTX.
Article
Hysterosalpingo-foam sonography (HyFoSy) is considered an acceptable alternative for hysterosalpingography (HSG). By combining HyFoSy with two and three-dimensional (2D and 3D) ultrasound and hysterosonography, a complete fertility work-up can be done. We aimed to evaluate the value of a combined ultrasound examination for fertility work-up. During the study period 113 women were examined. Five of 113 (4.4%) examinations were abandoned due to intra-uterine adhesions that were detected by hysterosonography, and five (4.4%) were abandoned due to technical difficulties. Of 103 women who had completed the examination, 2D ultrasound revealed six patients with hydrosalpinx (5.8%) and sonographic signs of adenomyosis in 13 (12.6%) patients. By combining 2D ultrasound with hysterosonography, two (1.9%) fibroids that were penetrating the uterine cavity and seven (6.8%) endometrial polyps were detected. HyFoSy showed bilateral patent tubes in 58 patients (56.3%), unilateral tubal occlusion in 29 (28.1%) and bilateral tubal occlusion in 16 (15.5%). This study shows that the ‘one-stop shop’ examination is feasible. The combined examination had detected 16 pathological findings that would have not been detected by HyFoSy alone. Hence, it should be offered to couples undergoing routine infertility work-up. • IMPACT STATEMENT • What is already known on this subject? The accuracy of the HyFoSy alone has been evaluated in different studies, but this presented ultrasound scan is integrating 4 different modalities in one exam (2D scanning of the pelvis, 3D scanning of the uterus, hysterosonography and HyFoSy) and we were able to evaluate the female pelvic organs, including the uterine cavity, the tubes and the ovaries, in order to expand the range of diagnosed pathologies. • What do the results of this study add? The concept of ‘one-stop shop’ for the evaluation of female pelvis in couples suffering from infertility is feasible, has comparable accuracy as HSG for tubal occlusion, and higher detection rate for uterine malformations. • What are the implications of these findings for clinical practice and/or further research? We suggest to incorporate this examination in routine fertility work-up.
Article
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Objective Our objective was to explore whether the pregnancy rate (PR) was higher than usual after hysterosalpingo-contrast sonography (HyCoSy). Methods We conducted a prospective observational study of 1,008 infertility patients, all of whom were examined by HyCoSy. The expected time for spontaneous pregnancy was at least 180 days after the HyCoSy exams. There were three types of HyCoSy results: type I, defined as both fallopian tubes patent; type II, defined as one fallopian tube patent with obstruction in the other; and type III, defined as both fallopian tubes obstructed. During the HyCoSy examinations, we recorded the mobility of the ovaries, injective resistance, and contrast agent venous intravasation. Before the examinations, we recorded each patient's medical history, including maternal age, infertility type, median duration of menstrual cycle, dysmenorrhea, and parity number. Results The PR was 19.44% within 180 days after HyCoSy and it was significantly higher in the first 30 days (6.35%) (P <.01). The PR of type I was highest, with a rate of 32.01%, followed by the PR of type II (25.51%) and type III (15.04%) (P <.01). Univariate analysis showed that younger age, patency of both fallopian tubes, good ovarian mobility, and absence of injective resistance were positively related to the initiation of pregnancy (P <.01). Infertility type, median duration of menstrual cycle, dysmenorrhea, parity number, contrast agent venous intravasation, and identity of the sonographer were unrelated to pregnancy (P >.05). However, multivariate analysis showed that patency of both fallopian tubes and the absence of injective resistance were independently associated with pregnancy. Conclusion Some infertility patients conceived successfully and naturally not long after HyCoSy, most often in the first month after the examination. Multivariate analysis showed that patency of both fallopian tubes and the absence of injective resistance were independently factors associated with the ability to conceive after HyCoSy examination.
Article
Full-text available
Background Tubal pathology is a causative factor in 20% of subfertile couples. Traditionally, tubal testing during fertility work-up is performed by hysterosalpingography (HSG). Hysterosalpingo-foam sonography (HyFoSy) is a new technique that is thought to have comparable accuracy as HSG, while it is less expensive and more patient friendly. HyFoSy would be an acceptable alternative for HSG, provided it has similar effectiveness in terms of patient outcomes. Methods/design We aim to compare the effectiveness and costs of management guided by HyFoSy or by HSG. Consenting women will undergo tubal testing by both HyFoSy and HSG in a randomized order during fertility work-up. The study group will consist of 1163 subfertile women between 18 and 41 years old who are scheduled for tubal patency testing during their fertility work-up. Women with anovulatory cycles not responding to ovulation induction, endometriosis, severe male subfertility or a known contrast (iodine) allergy will be excluded. We anticipate that 7 % (N = 82) of the participants will have discordant test results for HyFoSy and HSG. These participants will be randomly allocated to either a management strategy based on HyFoSy or a management strategy based on HSG, resulting in either a diagnostic laparoscopy with chromopertubation or a strategy that assumes tubal patency (intrauterine insemination or expectant management). The primary outcome is ongoing pregnancy leading to live birth within 12 months after randomization. Secondary outcomes are patient pain scores, time to pregnancy, clinical pregnancy, miscarriage rate, multiple pregnancy rate, preterm birth rate and number of additional treatments. Costs will be estimated by counting resource use and calculating unit prices. Discussion This trial will compare the effectiveness and costs of HyFoSy versus HSG in assessing tubal patency in subfertile women. Trial registration Dutch Trial Register (NTR 4746, http://www.trialregister.nl). Date of registration: 19 August 2014.
Article
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Background Infertility is a complex disorder with significant medical, psychological and economic problems. Aims The aim of the study is to evaluate the structural abnormalities of the uterus and fallopian tubes in infertile women as elucidated by hysterosalpingography. Setting and Design A retrospective study, conducted at the Radiology and Obstetric and Gynaecologic Departments of a tertiary health care institution. Materials and Methods Evaluation of all consecutive patients in whom hysterosalpingographic (HSG) was performed for infertility between July 2013 and June 2015 in the Department of Radiology. For the biodata, indications for the investigation and the HSG findings were obtained. Statistical Analysis The data were analyzed using IBM Statistical Package for the Social Sciences (SPSS Inc., Chicago, IL, USA) for Windows, version 20 software. Results A total of 299 patients were evaluated. Of these, 250 were for infertility with primary and secondary infertility constituting 18.4 and 81.6%, respectively. Seventy percent of the cases for infertility had abnormalities on the HSG. Normal uterine cavity was found in 123 (49.2%) cases. Uterine filling defects were the most common uterine abnormality. Fallopian tube occlusion, loculated contrast material spillage and hydrosalpinx were more common on the right, and bilateral tubal occlusion was seen only in 11.2%. All cases of intravasation were associated with either unilateral or bilateral fallopian tube blockage or irregularity of the uterus. Conclusion There was a high incidence of tubal disease in the women presenting with infertility. This was commonly as a result of infection and inflammatory process. This study showed that HSG is very vital in detecting birth canal pathologies; hence, the facility for this important procedure, especially fluoroscopy, should be made available in the health centres for adequate assessment of the women with infertility.
Article
The investigation of the probable cause of infertility is mandatory to propose an accurate therapeutic option to the infertile couple i.e. good chance of pregnancy. Usually, this investigation in woman includes at least hormonal dosages to estimate the ovarian function and reserve, a pelvic ultrasound scan and a hystero-salpingography to determine tubal patency. We introduce a unique investigation based on the realization of a high quality 3D ultrasound scan that involves the assessment of tubal patency. It is called Fertiliscan as opposed to the standard pelvic scan. The Fertiliscan assesses both the anatomy and the function of the uterus, the ovaries as well as the tubes. It includes a hystero-sonography for the analysis of the uterine cavity and with respect to tubal patency, a hysterosalpingo-foam-sonogography (Hyfosy). The investigation is woman-friendly, cheaper and shorter. It allows a fast track to a treatment if needed and shortens “time to pregnancy” for the couple.
Article
Research question: Does pre-IVF Lipiodol® increase the success of IVF treatment in women with endometriosis or repeat implantation failure (RIF) compared with IVF alone? Design: Lipiodol is known to enhance natural fertility, especially amongst women with endometriosis. The effect of Lipiodol may accrue through an impact on the endometrium that enhances receptivity to implantation. A randomized controlled trial (RCT) was carried out on 70 women due to undergo IVF. Women with endometriosis or RIF in previous IVF treatments, recruited from IVF clinics in New Zealand and in Pune, India, received either Lipiodol by hysterosalpingogram or no intervention prior to IVF treatment. Results: Between May 2009 and January 2014, 33 women were randomized to Lipiodol plus IVF and 37 to IVF alone. When pregnancies resulting from fresh embryo transfer from the IVF cycle under study were considered, live birth rates were 8/33 (24%) in the pre-IVF Lipiodol group and 11/37 (30%) in the IVF only group (relative risk [RR] 0.81; 95% confidence interval [CI] 0.37 to 1.8). Live birth rates from pregnancies within 6 months were 11/33 (33%) and 12/37 (32%) in these respective groups (RR 1.03; 95% CI, 0.53 to 2.0). The trial was underpowered to detect smaller differences between treatment and control groups. Conclusions: No evidence was found of benefit of Lipiodol prior to fresh embryo transfer in women with endometriosis or RIF. It is suggested that this treatment should not be undertaken purely as an adjuvant in IVF other than in the context of a further well-designed RCT.
Article
Research question: Hysterosalpingography (HSG) with an oil-based contrast has been shown to increase ongoing pregnancy rates compared with HSG with water-based contrast, but it remains unclear if an effect of HSG occurs compared with no HSG. Design: A secondary data-analysis of a prospective cohort study among 4556 couples that presented with unexplained subfertility in 38 clinics in the Netherlands between January 2002 and December 2004. A time-varying Cox regression with inverse probability of treatment weighing was used to analyse ongoing pregnancy rates in women after undergoing the HSG procedure (with the use of either water- or oil-based contrast media) compared with women who did not undergo HSG. Results: The probability of natural conception within 24 months after first presentation at the fertility clinic was increased after HSG, regardless of the type of contrast medium used, compared with no HSG (adjusted hazard ratio 1.48, 95% CI 1.26 to 1.73, corresponding to an absolute increase in 6-month pregnancy rate of +6%). When this analysis was limited to HSGs that were made with water-contrast, the treatment effect remained (adjusted hazard ratio 1.40, 95% CI 1.16 to 1.70). Conclusions: HSG increases the ongoing pregnancy rate of couples with unexplained subfertility compared with no HSG, regardless of the contrast medium used. Results need to be validated in future, preferably randomized, studies.
Article
Objectives To explore the risk factors on contrast agent venous intravasation during transvaginal 4‐dimensional hysterosalpingo‐contrast sonography (TVS 4D‐HyCoSy). Methods The TVS 4D‐HyCoSy imaging data were collected from 276 female infertile patients. The correlation between endometrial thickness, days after menstruation, intrauterine intervention history, fallopian tubal patency degree, and contrast agent venous intravasation, respectively, was analyzed. Results In our study, the incidence of contrast agent venous intravasation was 13.04%. Endometrial thickness and days after menstruation were significantly associated with venous intravasation (P < .05). However, there was no significance for intrauterine intervention history and fallopian tube patency degree. Conclusions Contrast agent intravasation during TVS 4D‐HyCoSy is not infrequent. Performing TVS 4D‐HyCoSy according to endometrial thickness and menstrual period could reduce intravasation incidence to some extent.
Article
Purpose To estimate the inter-observer reliability and agreement of offline analyses of three different ultrasound techniques for assessing tubal patency. Methods 100 tubes (n = 100) in 50 women were evaluated for tubal patency between November 2013 and July 2015 using ultrasound as index tests and laparoscopy as the reference standard. Three different ultrasound techniques were applied: two-dimensional grayscale ultrasound using air + saline as the contrast media (2D-HyCoSy); two- and three-dimensional grayscale ultrasound using foam as the contrast media (2 D/3D-HyFoSy); and the same technique but adding bi-directional power Doppler (2 D/3D-Doppler-HyFoSy). The videos containing full standardized exams using these three techniques were split into three parts, anonymized, encoded, randomized and reassessed in Nov. 2015 by two observers who assessed tubal patency using standardized criteria. These observers were blinded to any clinical information and each other’s results. Proportions of observed agreement (po) and Cohen's Kappa (κ) including the 95 % confidence intervals (CI) were calculated. Results The inter-observer reliability/agreement in 2 D/3D-Doppler-HyFoSy (po = 0.99, κ = 0.95, 95 % CI: 0.93 – 0.97) was higher compared to 2D-air/saline-HyCoSy (po = 0.83, κ = 0.55, 95 % CI: 0.40 – 0.68) and 2 D/3D-HyFoSy (po = 0.92, κ = 0.67, 95 % CI: 0.54 – 0.76). Conclusion The inter-observer reliability and agreement of the diagnosis of tubal patency evaluating stored videos are improved when foam and power Doppler are used during acquisition. Therefore, this technique may be preferred to minimize misclassification and misdiagnosis.
Article
Background: The aim of this study was to compare 2D and 3D-sonohysterosalpingography (2D - 3D- HyFoSy) with previous diagnostic laparoscopy in the diagnosis of tubal patency, and compare each procedure in terms of procedure's time, perceived pain and complication rate. Methods: We prospectively recruited infertile women, previously submitted to laparoscopy and randomly allocated into 2D-HyFoSy (group I) and 3D-HyFoSy (group II). We analyzed the results in term of sensitivity, specificity, positive predictive value and negative predictive value in tubal patency evaluation of both procedures in comparison with laparoscopy. Results: We enrolled 50 women, 25 in group I and 25 in group II. 2D-HyFoSy findings obtained in group I, were concordant with laparoscopy in 81 % of cases, with a sensitivity of 80 % and a specificity of 92 %. In group II, a correspondence was present in 88 % of examinations, with a sensitivity and specificity of 98% and 91.4% respectively. 3D-HyFoSy was found to be faster and less painful than 2D (p < 0.001). Conclusions: In the diagnosis of tubal occlusion, in the high-risk population, it seems advisable to us using the 3D-HyFoSy as the first-level examination, while, in low-risk patients, if the tubes appear obstructed in 2D-HyFoSy, the 3D-HyFoSy should be indicated before submitting patients to operative laparoscopy.