Ultrasonography in In Vitro FertilizationRoger A. PiersonDepartment of Obstetrics, Gynecology pptx

Recall that IVF was once done using laparoscopic retrieval of oocytes following ovarian stimulation cycles monitored only by hormonalassay of systemic estradiol levels, that embryos were

Saskatoon, Saskatchewan, Canada

Imaging has become such an integral part of clinical care in the assistedreproductive technologies that it is difficult to imagine how in vitro fertiliza-tion (IVF) was done before we had the ability to visualize the ovaries anduterus easily Recall that IVF was once done using laparoscopic retrieval

of oocytes following ovarian stimulation cycles monitored only by hormonalassay of systemic estradiol levels, that embryos were transferred back into auterus when we had no real idea about the physiologic status of the endo-metrium, and only a clinical touch was used to guide the placement of theembryo transfer catheter Easily accessible, and easy-to-use, ultrasono-graphic imaging in the hands of the individuals performing the assistedreproductive technology (ART) procedures has delivered us from thoseuncertainties The quality and quantity of the information we received fromthe ultrasonographic images that are now an essential part of every pro-cedure have been a very important aspect of the incredible increases inART success rates we have seen over the past decade It is important toremember that the integration of enhanced understanding of anatomy,physiology, endocrinology, and pathology we have gained with imaging inthe patients undergoing IVF are as important as the fantastic increase

in knowledge in the embryo laboratories The confluence of technologies

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we now used in ART care have greatly increased the probabilities of ful pregnancies for our patients.

success-The purpose of this chapter is to describe the primary uses of sound imaging in IVF and to identify some promising new areas whereimaging has the potential to enhance our understanding in assisted repro-duction The essentials of ultrasonography in IVF are in monitoring thecourse of ovarian stimulation protocols, visually guided retrieval of oocytes,assessment of the endometrium, and visually guided embryo transfer Each

ultra-of these areas also provides a springboard for new research areas which may

be incorporated into clinical care Awareness of new frontiers is essential toprogress in ART and in understanding the changes that will surely come

We rely so heavily on imaging in general gynecology, infertility workup,and early obstetrical care that it becomes challenging to narrow our focus

to only IVF; however, with the general caveat that ultrasonography hasforever changed our understanding of female reproduction, my goal is toprovide a synopsis of imaging in IVF integrated into a framework withinwhich we provide the highest quality of care for the patients who requireART to complete their families

OVARIAN ASSESSMENT

Monitoring the Course of Ovarian Stimulation

Ovarian stimulation protocols vary tremendously and have evolvedfrom fairly simplistic administration of exogenous hormones derived fromurinary sources to quite sophisticated blends of gonadotrophin-releasinghormone (GnRH) analogs, recombinant follicle-stimulating hormone(FSH), luteinizing hormone (LH), and other compounds The commondenominator in all ovarian stimulation protocols is that ultrasonography

is used to determine their effects on the ovaries of each patient All theprotocols have been designed to override the physiologic mechanism

of selection of a single dominant follicle, obviate atresia in the cohort offollicles recruited into the follicular wave, and foster and sustain the devel-opment of many follicles to an imminently pre-ovulatory state so thatproperly matured oocytes may be retrieved for IVF Ultrasonography isessential in determining the numbers and fates of individual follicles stimu-lated by exogenous gonadotrophins Toward this end, the follicularresponse of each woman to the stimulation protocol and the number ofoocytes desired and clinical assessment of the risk of ovarian hyperstimula-tion will dictate increasing or decreasing daily doses of gonadotrophins It isimportant to note that the expected linear relationship between circulatingestradiol concentrations and follicular diameter may not exist duringovulation induction Similarly, we understand that all follicles probably

do not contribute equally to the concentrations in the systemic circulation

In all the ART ovarian stimulation protocols, regardless of their nical complexity, the timing for human chorionic gonadotrophin (hCG) orrecombinant LH administration is critical to establish a time for oocyteretrieval which will yield the highest quality of oocytes in the proper stage

tech-of development with the highest probability tech-of fertilization Although dominal ultrasonography has been used, transvaginal ultrasonography(TVUS) is the best means that we have to follow the course of folliculargrowth and development (1,2) With TVUS, we have a rapid, non-invasive,and highly visual approach to following the fates of individual follicles andcohorts of follicles When we combine our knowledge of natural ovarianphysiology with concomitant assessment of circulating estradiol concentra-tions and oocyte development, we may predict the optimal timing forinduction of the final stages of folliculogenesis and oogenesis and oocyteretrieval (3–5) The relationships between follicle size and oocyte maturityremain not particularly well elucidated; however, the oocyte maturity certainlyplays a role in the ability of the resulting embryos to develop to the blastocyststage (6–8)

transab-hCG is usually administered to trigger the final phases of follicularmaturation when the largest follicle first attains a predetermined diameter(e.g., 18–20 mm) The time of hCG administrations varies in many programsbased upon the individual clinician’s feel for the stimulation cycle and lab-oratory logistics Most commonly, 5000 or 10,000 IU hCG is administered.Oocyte retrieval for IVF is then typically scheduled for 30–34 hr thereafter.Many programs use only ultrasonographic monitoring to determine thecourse of ovarian stimulation and it has been demonstrated that includingestradiol monitoring during the stimulation protocol seldom changed thetiming of hCG administration and did not affect pregnancy rates or the risks

of ovarian hyperstimulation syndrome (OHSS) (9)

The characteristics and appropriate sizes of follicles which producemature oocytes ready for fertilization remain the subject of much contro-versy and research Although we know that mature oocytes yield the highestfertilization rates (Fig 1), through recent developments in the embryo lab-oratory, we know that in vitro maturation and fertilization are quite viableideas in ART practice (10,11) The role of ultrasonography in vitro matu-ration (VM)–IVF protocols will very definitely revolve around the optimaltiming of oocyte retrieval for optimal fertilization and cleavage rates (11–14) Ovulation has been reported from follicles as small as 14 mm andoocytes collected from small follicles may indeed fertilize In a recent study,oocytes from follicles less than 10 mm in diameter and in vitro maturationwere used to increase the number of transferable embryos (15) Throughresearch in animal models, we know that there appears to be a correlationbetween computer-assisted ultrasound image attributes of follicles and theability of the oocyte to fertilize; however, similar studies in humans haveapparently not yet been completed (16)

Examination of growth rates for individual follicles may be a usefulcharacteristic with which to predict the number of follicles which maydevelop during ovarian stimulation protocols This information is equallyimportant when assessing the risks of ovarian hyperstimulation In the past,follicular growth rates during induced cycles were observed to be faster thanthose of natural cycles (17) However, a mathematical equation developed toequate follicular growth rate to follicular age was used to conclude that thegrowth rates of individual follicles in spontaneous cycles were similar tothose recruited by human menopausal gonadotrophin therapy (18).Reduced growth rates of follicles in cycles where a pregnancy was estab-lished led to the conclusion that growth rate was a more useful characteristicfor prediction of ovulation than follicular diameter (19) Follow-up workdoes not appear to have been done It will be logistically challenging tocombine daily detailed ultrasound measurements of individually mappedfollicles with per follicle outcomes from the embryo laboratory and finalpregnancy outcomes However, the rationale that follicular growth ratesmay be more accurate in predicting the actual maturity of the ova isintriguing Recent detailed studies on follicular growth have shown thatfollicles grow at approximately 1.5 mm per day regardless of whether theydeveloped during natural menstrual cycles, oral contraceptive cycles, or dur-ing ovarian stimulation (20,21) These data fit well with a new mathematicalmodel developed to predict the ovarian response to superstimulation

Figure 1 Image of an ovary with three dominant follicles visible in the plane of tion The image was acquired 24 hours prior to oocyte retrieval The thick walls ofthe follicles are consistent with collection of oocytes with a high probability offertilization

sec-protocols and based upon daily data on follicular growth rates (22,23) It isevident that new imaging-based studies are required.

Assessment of Ovarian Follicular Reserve

Changes in demographic trends in the age at first pregnancy in our times havecombined to yield more and more women seeking pregnancy when they areolder and less fertile Numerous studies in recent years have demonstratedthat fertility declines progressively as age advances In IVF, the main focus

of attention is on assessment of what is termed the ovarian reserve nography is now being used to investigate follicular dynamics in aging women

Ultraso-as are detailed endocrine-bUltraso-ased tests (24) A decreUltraso-ase in the ovarian reserve,

or number of follicles capable of being stimulated, is a primary reason fordeclining fertility Similarly, the ovarian response to exogenous gonado-trophin stimulation also decreases, but the range of individual variation isextremely wide and it is well known that age is only a rough guesstimate ofthe ovarian reserve and hence the ovarian stimulation response

There are several tests of ‘‘ovarian reserve’’ that include clomiphenecitrate challenge and the GnRH agonist stimulation tests (24–27) Ovarianbiopsy is available, although it remains controversial (24,28) The endocrinetests offer prognostic information valuable in the counseling of aging infer-tile women However, there is much recent evidence to suggest that ultraso-nography may be used to estimate the number of antral follicles at specifictimes of the menstrual cycle and provide additional useful information ofclinical relevance (29–32) Ultrasound assessments take place using antralfollicle counts or measurement of ovarian volume Early follicular-phaseantral follicle counts, typically done on days 3 to 7 post-menstruation,may be used to predict the number of follicles likely to develop during ovar-ian stimulation with exogenous gonadotrophins (31,33–36) Women havingfewer than five follicles under 10 mm in diameter before ovarian stimulationbegins have a relatively poor prognosis for success (35) Studies to determinethe extent to which antral follicle counts correlate with endocrinologic mea-sures of ovarian reserve (e.g., cycle day 3 FSH and estradiol concentrations)remain to be widely confirmed (30) Ovarian volume assessments are based

on the presumption that there is a significant correlation between the lation of primordial follicles remaining in the ovary and the volume of theovary, measured using either two- or three-dimensional ultrasonography(27,29,33,37) A very clear relationship between decreased ovarian volumeand antral follicle counts and advancing age combined with increasedFSH has been demonstrated (26,30) Although there remains a good deal

popu-of work yet to do in order to standardize the imaging based assessments,ultrasonography remains an important aspect of ovarian reserve estima-tion and prediction of the probability of a successful ovarian stimulationcycle (35)

Ovarian Hyperstimulation Syndrome

OHSS is a potentially serious complication of ovarian stimulation withexogenous gonadotrophins The risk of serious disease is much higher whenexogenous gonadotrophins are employed In women with the disorder,transvaginal or transabdominal ultrasonography often demonstrates grosslyenlarged ovaries containing numerous large follicular cysts with thin, highlyechogenic borders, and dramatically increased local blood flow (38) Theovaries may enlarge to diameters in excess of 10 cm, and echotexture inter-preted as intrafollicular hemorrhage in some of the large cysts frequentlymay be observed Serial TVUS during ovarian stimulation cycles and carefultailoring of the dose of exogenous gonadotrophins has helped to limit therisk of OHSS (38,39) Clinicians take an active role in the prevention ofOHSS by aborting the treatment cycle and cryopreserving the embryosfor later, or replacement of a single embryo when excessive numbers of pre-ovulatory follicles develop in association with markedly elevated serumestradiol concentrations and the risk of OHSS is high (40) When OHSSdoes occur, torsion of an enlarged ovary is a complication that must be kept

in mind When torsion is suspected, color flow Doppler imaging can help toestablish an early and accurate diagnosis (41,42)

Computer-Assisted Ultrasonographic Imaging of Follicular

Development

New work in application of computer-assisted image analysis is ing that ultrasound images have the potential to aid in the identification ofhealthy versus atretic follicles in natural and ovarian stimulation cycles(22,43,44) (Fig 2) Physiologically dominant ovarian follicles are identifiable

demonstrat-by ultrasonography at approximately day 7 post-menstruation in lated cycles (22), and ovulatory and non-ovulatory follicles are identifiable

unstimu-in ovulation unstimu-induction cycles (43) The image attributes of ultrasonographicimages of normal preovulatory follicles include thick, low-amplitude wallsand a gradual transformation zone at the fluid–follicle interface Thewalls of preovulatory follicles are characterized by increased heterogeneity,increased wall breadth, and a more gradual transformation at the fluid–follicle wall interface Atresia is characterized by thin walls, high numericalpixel value (bright) signals, and highly variable signals from the follicularfluid Evaluation of the acoustic characteristics indicative of viability andatresia is an active area of research that has profound implications fordevelopment of safer and more effective ovarian stimulation protocols

ULTRASOUND-GUIDED OOCYTE RETRIEVAL

The most visible use of ultrasound imaging in IVF has been the tremendousadvance facilitated by transvaginal retrieval of oocytes (45–55) Oocyte

retrieval was a procedure-limiting step when IVF was first done Retrievalswere done laparoscopically or using ultrasound guidance from transure-thral, transvesicular, or transabdominal approaches (48,51,55–58) Theadvent of transvaginal transducers and concerted efforts to develop effec-tive, accurate tracking of the needles used for follicle aspiration wasprobably the single most important step in making IVF as safe and effective

as it is today (Fig 3) (45,53–55,59–63)

Retrieval of oocytes in IVF cycles is now routinely performed underTVUS guidance (49) An aspirating needle is introduced through a guideattached to a transvaginal probe and is inserted into first one ovary, thenthe other, via the vaginal fornices Almost all aspiration needles now in com-mon use have a small band of highly reflective surface near the tip of theneedle to facilitate ease of visualization as the needle enters the ovary andonce it is in the follicles The path of the needle as it is guided into each ovar-ian follicle may be accurately defined by a biopsy guideline imposed on theultrasound screen, although, the highly reflective walls of the needle makeidentifying its path quite easy in most cases The needle tip can be observeddirectly as it is maneuvered within the ovaries and into each follicle The fol-licular fluid containing the oocyte/cumulus complex is then aspirated byapplication of gentle suction The walls of the follicle collapse as the fluid

is aspirated and the needle moved within the follicle to ensure that all thefollicular fluid is withdrawn

There are two main types of aspiration needles used for oocyteretrieval, single and double lumen needles Single lumen needles typically

Figure 2 Power-flow Doppler image of a dominant preovulatory follicle showingthe perifollicular vascularization consistent with follicular maturity

have a smaller diameter and tend to cause less discomfort (49) In many, ifnot most, IVF centers follicle aspirations are done using single lumen needlesand no follicle flushing The double lumen needles were developed for atechnique involving constant infusion of oocyte collection media into the fol-licle at the same time as the follicular fluid is being removed The doublelumen flushing technique is thought to increase the turbulence within the fol-licle, assist in dislodging the oocyte–cumulus complex from the follicle wall,and increase the chances of oocyte collection A single lumen needle flushingtechnique may also be used In this technique, all the follicular fluid is firstaspirated from the follicle and the follicle is then refilled with collectionmedium and re-aspirated A back-and-forth motion on the plunger of theinfusion syringe may be used to increase the turbulence of flow which may

be easily visualized on the ultrasound screen No significant differences werefound in the number of oocytes collected in either a prospective, randomizedtrial or a retrospective examination of 2378 cases and the time required forretrieval in women whose follicles were flushed was increased (49,64,65).Unsuccessful oocyte retrieval following apparently normal ovarianstimulation reportedly occurs in 1–7% of cycles—the so-called ‘‘empty fol-licle syndrome.’’ The etiology appears to be multifactorial and may involveboth technical and biological mechanisms (49,66)

The complication rates of oocyte retrieval are reportedly extremelylow and almost all procedures are performed under conscious sedation on

an outpatient basis (52,60,61,67–72)

ASSESSMENT OF THE ENDOMETRIUM AT EMBRYO TRANSFER

Endometrial Thickness and Pattern for Assessing Endometrial

Receptivity

Ultrasonography has been used, with varying degrees of success, to correlatethe probability of pregnancy in ovarian stimulation–ovulation inductioncycles and IVF cycles (73–77) Most imaging studies have been attempting

to predict the probability of implantation A thicker endometrium wasobserved on the day of oocyte retrieval in women who conceived during thatcycle (74) The IVF pregnancy rate increased in cycles when the endo-metrium was > 9 mm but <14 mm (75) In another study, no correlationwas observed among endometrial pattern or thickness and estradiol levels,number of oocytes retrieved, or progesterone level on the day of embryotransfer; however, the authors appeared to appreciate the pattern of theendometrium on the day of hCG administration, but stated that patternassessment was of no value (78) In another IVF study, the endometrium

on the day before embryo transfer was nearly 2 mm thicker in womenwho conceived (10.2 mm) than in those who did not (8.6 mm) (79) Onlytwo pregnancies were reported when the endometrial thickness was less than

7.5 mm, and no pregnancies were observed when the endometrial thickness

on the day of embryo transfer was less than 5 mm However, no differenceswere observed in endometrial thickness among women who conceivedcompared to those who did not in a similar study (80) Subsequently, a morefavorable outcome has been suggested when embryos were transferred whenthe endometrial thickness was greater than 9 mm and a ‘‘triple-line’’ patternwas observed (81) This observation was supported by a retrospective analy-sis in which the pregnancy rate was significantly higher in women whoexhibited a triple-line pattern than in those with other endometrial patterns(Fig 4) (82) These contradictory reports and the apparent lack of corre-lation between ultrasonographic endpoints and histologic staging of theendometrium in women undergoing IVF can be interpreted to suggest thatultrasonography using simple measurements is simply not yet sensitiveenough to be useful in predicting endometrial receptivity and the probability

of implantation with the exception of a strong negative correlation when theendometrium is thin (81,83,84) It is also possible that inconsistencies inthe day on which measurements were done among the many studies andmeasurement techniques have played a role in our seeming inability to inter-pret the data Consensus among studies is that implantation may occur aslong as the endometrial thickness is greater than 6 mm, although there is

a single case report of a pregnancy established when the endometriummeasured 4 mm (74,85–87)

Figure 3 Ultrasound image taken during oocyte retrieval The highly echogenicband around the distal end of the needle and the tip of the follicle aspiration needleare visualized in the superior-most follicle The needle is maneuvered within theovary to aspirate all follicles Source: Image courtesy of Dr Roger Stronell

Collections of fluid are sometimes found within the uterine lumen onthe day of embryo transfer (88) (Fig 5) In a retrospective analysis of caserecords, approximately 5% of cycles were compromised by the presence oflumen fluid accumulation at some time during the IVF cycle procedures,and in 2% of the cases the fluid accumulations persisted until the day ofembryo transfer The pregnancy rate among women with fluid accumula-tions was markedly lower than those who did not exhibit intralumenal fluid.Interestingly, fluid accumulations were found in almost three times as manywomen with tubal factor infertility compared with other causes (88).Although lumenal fluid collection does not appear to be a common problem

in IVF cycles, it does appear to have a negative impact on implantation andpregnancy rates

Spectral Doppler and Color Flow Doppler Ultrasonography

The history of Doppler ultrasonography of the uterine arteries in the ture is confusing because many reports failed to differentiate between spec-tral Doppler and color flow Doppler imaging Early studies tend to be based

litera-on spectral Doppler examinatilitera-ons, which are a means of evaluating theresistance to blood flow using calculations of the pulsatility index (PI), resis-tance index (RI), Vmax, or the systolic-to-diastolic ratio (S/D ratio) Colorflow Doppler and power flow Doppler imaging are means of turningmotion, either toward or away from the transducer in the case of color flow

Figure 4 Midsagittal view of the uterus The cervix is to the right of the image andthe fundus is to the left The endometrium is well demarcated and shows apronounced, thick ‘‘triple-line’’ pattern associated with a higher probability ofimplantation following embryo transfer

Doppler, or motion in any direction in the case of power flow Doppler, into

a visually detectable color overlay on the two-dimensional ultrasound image(Fig 2) (89)

Initially, attempts to determine if evaluation of blood flow in the uterinearteries could be useful were based on RI calculations to look for differences

in uterine receptivity, where in a small series of women, no differences werefound between women who conceived and those who did not (90) Whenthe PI of uterine arteries was examined and data were grouped into low,medium, and high categories, no differences were found between cycles wherewomen either conceived or did not; however, no pregnancies were established

in the women with high PI values (91) Elevated PI, as a measure of dance to vascular flow in the uterine artery, was associated with a significantlylower pregnancy rate (92) However, no differences in uterine artery PI wereobserved between conception and non-conception cycles (93) A study asses-sing RI of the uterine arteries was inconclusive, except that absent or lowdiastolic flow was associated with failure to conceive (93) Uterine arteryvascular impedance measured by RI was not found to be useful for predictingthe probability of pregnancy, but if the PI values were found to be greaterthan 0.79 before hCG administration, poor uterine vascular perfusion wasassumed (94) A subsequent study reported the PI and RI in the uterinearteries to be lower in conception cycles, and the authors suggested that a

impe-PI greater than 3.3 and an RI greater than 0.95 before embryo transfer wereassociated with a low probability of conception (95) Furthermore, a study ofwomen undergoing cycles in which embryos were produced using ICSIreported no demonstrable differences in PI on the day of embryo transferbetween conception and non-conception cycles (96)

In a critical review of the literature prior to 1996, some cally detectable criteria were observed to be associated with negative pregnancyoutcomes; however, no prognostic value was observed in any measurement ofvascular perfusion (97) A more recent study appears to confirm the results thatwomen who conceived exhibited lower PI than those who did not (98).Studies that evaluated endometrial perfusion on the day of hCGadministration consistently reported that values for PI and Vmax were notdifferent, irrespective of whether or not conception was established(95,97,99–101) However, when only the color flow data were examined,absence of detectable subendometrial vascular flow, indicative of poor vas-cular penetration, was associated with failure of implantation (99) Powerflow Doppler ultrasonography was subsequently used to examine womenwhose endometrial thickness was >10 mm Intra-endometrial flow calcula-tions of the maximal area that showed evidence of motion indicative ofvascular flow of < 5 mm2 were associated with a lower pregnancy rate(100) Subsequently, a high degree of endometrial perfusion visualized usingthree-dimensional ultrasonography was thought to indicate a more favor-able endometrium (102) The most recent study in this line of inquiry

ultrasonographi-concluded that spiral arterial flow and uterine artery flows were not differentbetween pregnant and non-pregnant women; however, if spiral arterial flowcould not be detected, there was no probability of conception (101).Imaging-Based Uterine Scoring System

An imaging-based scoring system to predict uterine sensitivity has been posed which appears to be based on an earlier uterine biophysical profilesystem (103,104) The scoring system was designed by assigning ‘‘points’’for various criteria and then adding the cumulative columns Comparisons

pro-of uterine scores in conception with non-conception cycles demonstrated

no differences in any criteria measured, including endometrial thickness,endometrial pattern, PI, RI, color Doppler, and other vascular indices.Development of the scoring system appears to have ceased

Three-Dimensional Imaging of the Endometrium

Three-dimensional (3D) ultrasonography first became available in the late1990s and 3D is now a part of almost all high-end imaging systems Thereare several methods used to provide 3D information and there are no studiescomparing the same endpoints with different imaging systems (105) Theprospects for predicting the probability of implantation in IVF programshave now extended into 3D exploration of endometrial receptivity (106).When endometrial volumes were compared among women whoconceived and those who did not, pregnancy and implantation rates weresignificantly lower in women with volumes of less than 2 mL, and nopregnancies were established when endometrial volumes were less than

1 mL A contemporary study found no relationship between 3D volume

of the endometrium and conception (106,107) Nor was a correlation foundamong estradiol levels, endometrial thickness, or endometrial volume, lead-ing the authors to conclude that there was no predictive value for conception

in assessing endometrial volume Endometrial thickness and endometrialvolumes were not correlated with probability of pregnancy; however, 3Dpower flow Doppler indices used to measure endometrial perfusion mayhave some predictive value (101,102,108,109) Spiral artery blood flow mea-surements in 3D had positive predictive value when performed on the firstday of ovarian stimulation, whereas women who became pregnant hadlower RI and a higher 3D flow index than those that did not (101,102).Taken together, these observations provide rationale for further investi-gation, although it is clear that a predictive index is beyond the limits ofour current technology

Motion Analysis

Motion analysis, or direct measurement of subendometrial contractions, is amethod of evaluating the endometrium based on the observation that the

uterus and endometrium are in constant motion (110–117) Objective ment of these contractions has now been applied to assisted reproductioncycles (118–120) A computer is interfaced with an ultrasound instrument,digital frames are acquired, and the pixels comprising the endometrial imagealong a single line are isolated (Fig 6) A line is serially acquired fromimages taken one or two times per second over a 5–10-min period, the pixeldata from the line are concatenated, and the result is displayed as a graph ofthe velocity and amplitude of endometrial contractions.

assess-Endometrial contractions may have a predictive effect on the ability of pregnancy in IVF cycles (114,121) Women with a higher frequency

prob-of uterine contractions were found to have lower pregnancy rates (119).However, contradictory evidence has been reported (122) Exogenousprogesterone has demonstrably reduced uterine contractility on the day ofembryo transfer and it has been hypothesized that progesterone supple-mentation before embryo transfer may improve endometrial receptivity bylowering the possibility that embryos might be expelled from the uterus

by contractions (123–125) Uterine contractility at the time of blastocysttransfer was lower and reached a nadir 7 days after hCG administration

in IVF cycles The low amplitude and frequency of contractions arehypothesized to facilitate blastocyst implantation (126) The effects of pro-gesterone on uterine contractions have been demonstrated by the obser-vation that higher progesterone concentrations correlated with loweramplitude and frequency uterine contractions (115,125) It was suggested

Figure 5 Midsagittal view of a uterus with a pronounced intraluminal fluid tion The cervix is visualized to the left of the image and the fundus to the right Fluidcollections on the day of embryo transfer are associated with a very low probability

collec-of pregnancy