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22 Ultrasound Role in Embryo Transfers
Fig. 22.6 Abdominal US depicts the external coaxial catheter wedged into the endometrium in an ante­verted uterus ( lower fi gure ). Sliding a rehearsal inner catheter allows proper placement in the lower uterine segment ( upper fi gure )
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factor in obtaining high ET success rates was the actual performance of live ETs rather than prac­ticing US-guided IUIs. Thus, how training in embryo transfer should be performed remains a controversy [ 3 ].
Coaxial catheter US-guided ET approach involves initial placement of an outer catheter in the internal uterine os (Fig. 22.6 ). The outer cath- eter protects the inner catheter from mucus expo­sure and eliminates the need to renegotiate a
deviated or a branching cervical canal. In this instance, time is not a limiting factor because the embryos are loaded into the inner catheter while the outer catheter is already in place. US will then allow ET time to be less than 30 s (Fig. 22.7 ). US guidance is extremely instructive at training facilities as it can provide feedback and reassur­ance to physicians in training. Coaxial live US guided ET allows teaching ET without a decline in the center’s PR.
300
Fig. 22.7 Abdominal US demonstrates that the outer coaxial catheter is withdrawn leaving the inner soft embryo- loaded catheter at one cm from the uterine fundus ( lower fi gure ). Under live US observation, the embryo is injected and the marker bubble is observed in mid-cavity ( upper fi gure )
E. Confi no et al.
Disadvantages of Ultrasound­Guided ET
When using US for ET, there is a signifi cant increase in the time and space needed. It is obvi­ous that US equipment and trained US personnel are needed. Cross-training of the existing IVF staff to provide US guidance eliminates the need for an additional US technician. The clinical experience of the ultrasonographer assisting US-guided ET had no effect on the clinical out­come [ 28 ]. Because of the full bladder required
for transabdominal US, patients may suffer from discomfort and cramping. Emptying the bladder after ET may cause concern of losing embryos at that time. This psychological stress may be resolved with reassurance that the embryo will not “pop out” with urination.
Some physicians prefer tactile ET to minimize the need to observe the cervix and the US screen simultaneously and avoid the need for additional personnel. They also state that the use of US technique may slow the ET and require addi­tional steps. Pre-ET vaginal ultrasound may be
22 Ultrasound Role in Embryo Transfers
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performed to reassess the cervix and uterus (Fig. 22.3 ). Pre-ET US may measure the endometrial lining, detect the presence of fl uid in the endometrial cavity, and retrace on the screen the measurement of the desired depth to achieve the ideal ET. However, a recent RCT involving single physician operator confi rmed that US guidance signifi cantly increased clinical pregnancies and live birth rates compared to the clinical touch method [ 29 ].

Conclusion

Evidence-based guidelines encourage US-guided ET. This approach will result in easier ETs and better PRs. Diffi cult, long, and bloody ET should be avoided. Recommendations based on expert opin­ions include the performance of a mock ET to identify a diffi cult ET, meticulous cervical mucus removal, mid uterine cavity embryo placement, a slow catheter withdrawal to avoid embryo dragging to the cervix, and a short embryo load to unload time [ 30 , 31 ].
US has become an indispensable tool used to prepare the patient for the upcoming ET and monitor, guide, and verify proper embryo deposition in the uterus. Importantly, patients take great comfort in having the ability to visualize the fi nal step of a diffi cult process. The use of US guidance is an integral part of a perfect ET and is only expanding to improve and may include 3D and 4D ultrasound.

References

1. Tarlatzis BC, Laufer N, Decherney AH. The use of ovarian ultrasonography in monitoring ovulation induction. J In Vitro Fert Embryo Transf. 1984;1: 226–32.
2. Peluso JJ, Damien M, Nulsen JC, Luciano AA. Identifi cation of follicles with fertilizable oocytes by sequential ultrasound measurements during follicular development. J In Vitro Fert Embryo Transf. 1990;7: 304–9.
3. Bishop L, Brezina PR, Segars J. Training in embryo transfer: how should it be done? Fertil Steril. 2013; 100(2):351–2.
4. Strickler RC, Christianson C, Crane JP, Curato A, Knight AB, Yang V. Ultrasound guidance for human embryo transfer. Fertil Steril. 1985;43:54–61.
5. Sallam HN, Sadek SS. Ultrasound-guided embryo transfer: a meta-analysis of randomized controlled tri­als. Fertil Steril. 2003;80:1042–6.
6. Matorras R, Urquijo E, Mendoza R, Corcostegui B, Exposito A, Rodriguez-Escudero FJ. Ultrasound­guided embryo transfer improves pregnancy rates and increases the frequency of easy transfers. Hum Reprod. 2002;17:1762–6.
7. Yoldemir T, Erenus M. Does the timing of mock embryo transfer trial improve implantation in intracy­toplasmic sperm injection cycles? Gynecol Endocrinol. 2011;27:396–400.
8. Mansour R, Aboulghar M, Serour G. Dummy embryo transfer: a technique that minimizes the problems of embryo transfer and improves the pregnancy rate in human in vitro fertilization. Fertil Steril. 1990;54: 678–81.
9. Gera PS, Allemand MC, Tatpati LL, Galanits TM, Morbeck D, Coddington CC. Role of saline infusion sonography in uterine evaluation before frozen embryo transfer cycle. Fertil Steril. 2008;89:562–6.
10. Sankpal RS, Confi no E, Matzel A, Cohen LS. Investigation of the uterine cavity and fallopian tubes using three-dimensional saline sonohysterosalpingog­raphy. Int J Gynaecol Obstet. 2001;73:125–9.
11. Abou-Setta AM, Mansour RT, Al-Inany HG, Aboulghar MM, Aboulghar MA, Serour GI. Among women undergoing embryo transfer, is the probability of pregnancy and live birth improved with ultrasound guidance over clinical touch alone? A systemic review and meta-analysis of prospective randomized trials. Fertil Steril. 2007;88:333–41.
12. Brown JA, Buckingham K, Abou-Setta A, Buckett W. Ultrasound versus ‘clinical touch’ for catheter guid­ance during embryo transfer in women. Cochrane Database Syst Rev. 2007;24(1):CD006107.
13. Brown J, Buckingham K, Abou-Setta AM, Buckett W. Ultrasound versus ‘clinical touch’ for catheter guidance during embryo transfer in women. Cochrane Database Syst Rev. 2010;(1):CD006107.
14. Flisser E, Grifo JA. Is what we clearly see really so obvious? Ultrasonography and transcervical embryo transfer–a review. Fertil Steril. 2007;87:1–5.
15. Pope CS, Cook EK, Arny M, Novak A, Grow DR. Infl uence of embryo transfer depth on in vitro fertil­ization and embryo transfer outcomes. Fertil Steril. 2004;81:51–8.
16. Frankfurter D, Trimarchi JB, Silva CP, Keefe DL. Middle to lower uterine segment embryo transfer improves implantation and pregnancy rates compared with fundal embryo transfer. Fertil Steril. 2004;81: 1273–7.
17. Tiras B, Korucuoglu U, Polat M, Saltik A, Zeyneloglu HB, Yarali H. Effect of blood and mucus on the suc­cess rates of embryo transfers. Eur J Obstet, Gynecol Reprod Biol. 2012;165:239–42.
18. Allahbadia GN, Kadam K, Gandhi G, Arora S, Valliappan JB, Joshi A, et al. Embryo transfer using the SureView catheter-beacon in the womb. Fertil Steril. 2010;93:344–50.
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19. Henne MB, Milki AA. Uterine position at real embryo transfer compared with mock embryo transfer. Hum Reprod. 2004;19:570–2.
20. Kato O, Takatsuka R, Asch RH. Transvaginal­transmyometrial embryo transfer: the Towako method; experiences of 104 cases. Fertil Steril. 1993;59:51–3.
21. Groutz A, Lessing JB, Wolf Y, Azem F, Yovel I, Amit A. Comparison of transmyometrial and transcervical embryo transfer in patients with previously failed in vitro fertilization-embryo transfer cycles and/or cervi­cal stenosis. Fertil Steril. 1997;67:1073–6.
22. Porat N, Boehnlein LM, Schouweiler CM, Kang J, Lindheim SR. Interim analysis of a randomized clini­cal trial comparing abdominal versus transvaginal ultrasound-guided embryo transfer. J Obstet Gynaecol Res. 2010;36:384–92.
23. Bodri D, Colodron M, Garcia D, Obradors A, Vernaeve V, Coll O. Transvaginal versus transabdomi­nal ultrasound guidance for embryo transfer in donor oocyte recipients: a randomized clinical trial. Fertil Steril. 2011;95:2263–8, 8e1.
24. Karande VC, Morris R, Chapman C, Rinehart J, Gleicher N. Impact of the “physician factor” on preg­nancy rates in a large assisted reproductive technol­ogy program: do too many cooks spoil the broth? Fertil Steril. 1999;71:1001–9.
25. Woolcott R, Stanger J. Ultrasound tracking of the movement of embryo-associated air bubbles on stand­ing after transfer. Hum Reprod. 1998;13:2107–9.
26. Confi no E, Zhang J, Risquez F. Air bubble migration is a random event post embryo transfer. J Assist Reprod Genet. 2007;24:223–6.
27. Shah DK, Missmer SA, Correia KF, Racowsky C, Ginsburg E. Effi cacy of intrauterine inseminations as a training modality for performing embryo transfer in reproductive endocrinology and infertility fellowship programs. Fertil Steril. 2013;100:386–91.
28. Harris ID, Styer AK, Petrozza JC. Ultrasonographer experience does not impact outcomes following ultrasound- guided embryo transfer. Fertil Steril. 2009;92:918–22.
29. Eskandar M, Abou-Setta AM, Almushait MA, El-Amin M, Mohmad SE. Ultrasound guidance during embryo transfer: a prospective, single­operator, randomized, controlled trial. Fertil Steril. 2008;90:1187–90.
30. Ebner T, Yaman C, Moser M, Sommergruber M, Polz W, Tews G. The ineffective loading process of the embryo transfer catheter alters implantation and preg­nancy rates. Fertil Steril. 2001;76:630–2.
31. Mains L, Van Voorhis BJ. Optimizing the technique of embryo transfer. Fertil Steril. 2010;94:785–90.

Ultrasound and Ovarian Hyperstimulation Syndrome

Laura Proud Smith
2 3

Ultrasound in the Prediction of Ovarian Hyperstimulation Syndrome

Because ovarian hyperstimulation syndrome (OHSS) is one of the most severe iatrogenic com­plications of in vitro fertilization (IVF), there have been many attempts to predict which patients are most at risk. Unfortunately, there are no perfectly reliable tests which universally predict the devel­opment of OHSS. Ultrasound determination of antral follicle count, counting the number of fol­licles developing in response to controlled ovar­ian hyperstimulation, sonographic evidence of polycystic ovarian syndrome, assessment of ovar­ian volume, and Doppler fl ow studies of ovarian vasculature have all been evaluated as markers to identify a higher likelihood of developing OHSS.
Among the sonographic tools used in the predic­tion of OHSS, quantitation of the antral follicle count (AFC) is one of the most accurate tests. Antral follicles are 2–10 mm follicles which can be identifi ed by ultrasound in the early follicular phase. Antral follicles appear as round, sonolucent struc­tures scattered throughout the ovary when viewed by 2D transvaginal ultrasound (Fig. 23.1 ). The size
L. P. Smith , MD Department of Reproductive Endocrinology and Infertility, Reproductive Medicine and Surgery Center of Virginia, P.L.C , 595 Martha Jefferson Drive, Suite 390 , Charlottesville , VA 22902 , USA e-mail: laura.smith@rmscva.com
of the antral follicle pool is considered to refl ect the total number of remaining follicles [ 1 ]. Generally, a low antral follicle count suggests a poor response to ovarian stimulation and a high antral follicle count suggests better ovarian response to gonadotropin stimulation and higher oocyte yield.
Several investigators have evaluated AFC to predict the development of OHSS. Kwee et al. evaluated 110 patients with unexplained infertil­ity, male factor, or cervical factor infertility, counted antral follicles in all patients, and corre­lated the number of antral follicles with level of ovarian response to IVF [ 2 ]. They categorized ovarian response as poor, normal, and high and then calculated the AFC cutoff which most accu­rately identifi ed each group. The AFC value of >14 identifi ed hyper-responders with a sensitiv­ity of 82 % and a specifi city of 89 %. Oncal et al. also evaluated the predictive role of AFC in OHSS in 41 women identifi ed to have moderate to severe OHSS and 41 age-matched controls who did not develop OHSS [ 3 ]. They found that AFC had a moderate accuracy to predict the development of OHSS. Using an AFC cutoff of eight, much lower than the AFC cutoff used by Kwee et al., they calculated 78 % sensitivity and 65 % specifi city. In a meta-analysis done by Broer et al. investigating AFC as a predictor of ovarian hyperstimulation, fi ve studies were iden­tifi ed which met criteria for inclusion [ 4 ]. Two reported on AFC alone, three reported on both anti-Mullerian hormone (AMH) and AFC, and all fi ve were prospective cohort studies. Among the included studies, the defi nition of excessive
L.A. Stadtmauer, I. Tur-Kaspa (eds.), Ultrasound Imaging in Reproductive Medicine, DOI 10.1007/978-1-4614-9182-8_23, © Springer Science+Business Media New York 2014
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Fig. 23.1 Ovary with normal antral follicle count
ovarian response to IVF varied between ≥15 and ≥20 oocytes. Importantly, the number of oocytes retrieved was used as a surrogate for risk of OHSS; no study specifi cally identifi ed the patients who met diagnostic criteria for OHSS. When these fi ve studies of AFC were evaluated together, the sensitivity of AFC to predict ovarian hyper-response was seen to vary between 20 and 94 % depending on the AFC cutoff used, and the specifi city varied between 33 and 98 %. From these values, the authors calculated a sum esti­mate of the sensitivity to be 82 % and a sum esti­mate of the specifi city to be 80 %. Considering this evidence, there is a clear association between increased AFC and increased risk of OHSS. Given the sensitivity and specifi city estimates of AFC in the studies to date, if the AFC is found to be greater than 14–16, caution should be exe­cuted in the initial gonadotropin dosing and choice of stimulation protocol since there is clearly increased risk of ovarian hyper-response in such patients.
When proposing the use of AFC to predict OHSS, it is important to be aware of the variabil­ity both in defi nition of antral follicle and opera­tor technique in follicle counting [ 5 ]. Interestingly, some authors adhere to the defi nition of antral follicle as those follicles which are measured to be 2–10 mm in the early follicular phase, as above; but other authors limit that defi nition to only those follicles which measure 2–5 mm. The precise menstrual timing of the measurement of AFC is also important. AFC should be performed either between cycle day 2 and 4 or while on oral contraceptive pills for greatest accuracy and reproducibility.
The number of growing follicles in response to gonadotropin stimulation during ART is another sonographic test which has been pro­posed to predict the development of OHSS. Clearly, there is a connection between the ovarian response to stimulation and AFC, as patients with higher baseline AFC would be expected to have a more robust ovarian response to treatment. Papanikolaou et al. sought to correlate the num­ber of follicles ≥11 mm growing in response to gonadotropin treatment during IVF with the like­lihood of developing moderate or severe ovarian hyperstimulation syndrome [ 6 ]. They evaluated 1,801 patients undergoing IVF treatment over a 2-year period. Factors such as peak estradiol level and number of follicles ≥11 mm were cor­related with the development of OHSS. In this cohort, 53 patients were hospitalized because of OHSS. They found that a threshold of ≥13 folli­cles measuring ≥11 mm was predictive of the development of OHSS with a sensitivity of
85.5 % and a specifi city of 69 %. Interestingly, the number of follicles ≥11 mm was a much bet­ter predictor of OHSS than the peak serum estra­diol level, which had only a 53 % sensitivity and 77 % specifi city. Therefore, if it becomes appar­ent during an IVF cycle that there are 13 or more follicles measuring ≥11 mm, the patient and phy­sician should both be cognizant of the increased risk of developing OHSS regardless of the serum estradiol level.
Because patients who have higher baseline AFC and higher functional ovarian response to stimulation have been found to have a greater likelihood of developing OHSS, it is important to identify such patients early in clinical care. It is well known that patients with polycystic ovarian syndrome (PCOS) have by defi nition a high antral follicle count and magnifi ed response to IVF. Ultrasound assessment of ovarian morphology serves as one of the key criteria for the diagnosis of PCOS by the Rotterdam criteria [ 7 ]. The sono- graphic fi ndings which meet Rotterdam diagnostic criteria are either 12 or more follicles in each ovary measuring 2–9 mm in diameter and/or increased ovarian volume >10 mL [ 8 ] (Fig. 23.2 ). In com- bination with either anovulation/oligo- ovulation or clinical/biochemical hyperandrogenism and
23 Ultrasound and Ovarian Hyperstimulation Syndrome
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Fig. 23.2 AFC of PCOS ovary in 2D ultrasound
having excluded other endocrine conditions such as Cushing’s syndrome and congenital adrenal hyperplasia, a patient could be diagnosed as hav­ing PCOS. Interestingly, even women who do not technically meet criteria for PCOS but have iso­lated polycystic-appearing ovaries on ultrasound have been found to have a higher risk of devel­oping OHSS [ 7 ]. Therefore, clinical management including gonadotropin dosing and choice of stimulation protocol should incorporate knowl­edge of PCOS or polycystic-appearing ovaries on ultrasound in an attempt to minimize the develop­ment of OHSS in these patients.
Using patients with PCOS as a model for other patients at risk for OHSS, researchers have inves­tigated ultrasound calculation of baseline ovarian volume alone as a predictive marker. Danninger et al. studied 101 patients undergoing IVF, all of whom had 3D volumetric assessment of ovarian volume starting on stimulation day 1 [ 9 ]. The authors then remeasured ovarian volume on the day of human chorionic gonadotropin (hCG) and correlated those fi ndings with the development of OHSS. They found a signifi cant correlation between the baseline ovarian volume and OHSS ( p = 0.03) with a greater baseline ovarian volume in women who subsequently developed OHSS compared to those who did not. The authors esti­mated an ovarian volume cutoff of 10 mL as pre­dictive of OHSS. Importantly, this sonographic fi nding was not as robust as some of the other markers already discussed. Even in the 34 patients identifi ed to have an ovarian volume >10 mL, only 23.5 % ultimately developed
OHSS. Although it is logical in the context of PCOS and the PCOS-associated risk of OHSS, the measurement of ovarian volume is not con­sidered to be a standard marker at this time to predict OHSS.
The fi nal ultrasound characteristics which have been used to attempt to predict the develop­ment of OHSS are Doppler fl ow studies of ovar­ian vasculature. The concept behind the assessment of ovarian vascular resistance and fl ow is that because OHSS involves third spacing of fl uid secondary to increased vascular permea­bility, one might expect changes in ovarian vas­cular fl ow which may occur prior to clinical signs or symptoms of OHSS and therefore could be used to predict the development of OHSS [ 10 ]. Coupled with increased vascular permeability, there is also abnormal intraovarian angiogenesis in OHSS leading to low vascular impedance. Multiple authors have investigated sonographic characterization of ovarian vascular fl ow, resis­tance, peak systolic velocity, and pulse-wave power Doppler to try to correlate vascular chances with the likelihood of developing OHSS. In 1997, Moohan et al. evaluated 30 patients who were diagnosed with mild or severe OHSS within 2–15 days of oocyte retrieval [ 10 ]. All patients underwent transabdominal ultrasound at the time of diagnosis of OHSS with color Doppler done on low-fl ow setting to characterize the fl ow velocity waveforms within the ovarian vessels. Vascular pulsatility index, resistance index, S-D ratio, and maximal peak systolic velocity were calculated. The authors found that in patients with severe OHSS, there was markedly reduced vascular impedance with a statistically signifi ­cantly higher resistance index in patients with mild OHSS compared to severe (0.49 vs. 0.41, p < 0.005). Surprisingly, there was no difference in maximal peak systolic velocity, but pulsatility index and S-D ratio also differed signifi cantly between patients with mild and severe OHSS. Of importance, this study evaluated only patients diagnosed with OHSS. There was no comparison with patients who did not develop OHSS, so it is impossible to know if these differences in vascu­lar fl ow could have been used to predict the development of OHSS. Other authors including
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Agrawal et al. did compare patients with OHSS to controls and found a difference in ovarian stro­mal peak systolic velocity and time-averaged maximal velocity between patients with and without OHSS [ 11 ]. In the study by Agrawal et al. published in 1998, ovarian Doppler fl ow velocity was statistically signifi cantly higher in patients with OHSS than controls, but pulsatility index and resistance index did not differ between the groups. The authors concluded that the changes in fl ow velocity correlated with changes in vascular endothelial growth factor (VEGF) serum and follicular fl uid concentrations. More recently, Jayaprakasan et al. used three­dimensional (3D) power Doppler angiography to attempt to predict OHSS [ 12 ]. In 118 patients, of whom 18 developed moderate or severe OHSS, ovarian vascular fl ow indices were quantifi ed by 3D ultrasound. Unexpectedly, there was no difference in vascularization index, fl ow index, or vascularization fl ow index between either patients with OHSS vs. controls or the subgroups of patients with moderate vs. severe OHSS. Therefore, although the pathophysiology of OHSS involves known changes in vascular per­meability which logically suggest a connection between Doppler measurements of ovarian vas­cular fl ow and the development of OHSS, unfor­tunately no studies to date have convincingly shown that ultrasound measurement of ovarian vascular parameters can be used to predict the risk of OHSS.
In summary, ultrasound has been investigated as a tool to predict the development of OHSS through assessment of AFC, quantitation of fol­licular development during IVF, identifi cation of polycystic-appearing ovaries or PCOS, determi­nation of ovarian volume, and Doppler fl ow stud­ies of ovarian vasculature. Of these potential sonographic markers, AFC is the most signifi cant predictor of the development of OHSS and should be used to guide management. There is also evidence linking the number of developing follicles and the diagnosis of PCOS with the risk of OHSS. To date, the other ultrasound tools including ovarian volume and vascular fl ow anal­ysis do not have clinical utility in the prediction of OHSS.
Fig. 23.3 Hyperstimulated ovary after gonadotropin therapy

Ultrasound in the Diagnosis of Ovarian Hyperstimulation Syndrome

Once OHSS is suspected on clinical grounds, the diagnosis is aided by ultrasound fi ndings. OHSS is categorized into mild, moderate, and severe dis­ease. The differentiation involves sonographic fea­tures including the degree of ovarian enlargement, presence and volume of abdominal ascites, pres­ence or absence of pleural effusions, and Doppler studies showing venous thromboembolism [ 13 ].
The clinical fi ndings of OHSS encompass a spectrum ranging from mild disease, unpleasant for the patient but not considered to be danger­ous, to severe OHSS with signifi cant conse­quences and risk of death. Mild OHSS is common and involves symptoms such as lower abdominal or pelvic discomfort, gastrointestinal complaints including nausea, emesis, and diarrhea, and some degree of abdominal distention [ 14 ]. The process of superovulation frequently leads to these mild manifestations of OHSS, and up to a third of IVF cycles may involve these complaints. The only sonographic characteristic of mild OHSS may be enlarged ovaries (5–12 cm) [ 15 ] (Fig. 23.3 ).
Moderate OHSS consists of intensifi ed pain, nausea or emesis, enlarged ovaries seen on ultrasound, and sonographic identifi cation of abdominal or pelvic ascites with normal serum
23 Ultrasound and Ovarian Hyperstimulation Syndrome
Fig. 23.4 ( a ) Ultrasound of moderate OHSS with ascites. ( b ) Ultrasound of ascites in the cul-de-sac with severe OHSS
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a
laboratory parameters (Fig. 23.4a ). Some authors have described OHSS as an abdominal compart­ment syndrome because the rapid accumulation of ascites can lead to increased intra-abdominal pressure [ 16 ]. Increased intra-abdominal pres- sure can become acute and lead to organ dysfunc­tion. In severe forms, abdominal compartment syndrome affects respiratory function, as in the case of severe OHSS.
Given that abdominal ascites is a key char­acteristic of the diagnosis of moderate OHSS, it is critical that the ultrasound fi ndings be inter­preted correctly in the context of the clinical presentation. Gunabushanam et al. reported the case of a 22-year-old woman who had received
b
fertility treatments and presented to the emer­gency department complaining of a 12 h his­tory of severe lower abdominal pain [ 17 ]. Transabdominal ultrasound showed enlarged ovaries bilaterally (7 × 5 × 5 cm) with signifi cant anechoic peritoneal free fl uid felt consistent with ascites. She was diagnosed with OHSS. She then began to clinically decompensate with the development of pallor and peritoneal signs and underwent diagnostic paracentesis notable for non-clotting blood. Ultimately she was taken to the operating room for emergent laparotomy and a bleeding ovarian cyst was identifi ed and treated. This case demonstrates the dangers of assuming the diagnosis of OHSS in all patients undergoing
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fertility treatments, as other pelvic pathology can clearly lead to the accumulation of pelvic fl uid. Cyst rupture can certainly lead to signifi cant intraperitoneal bleeding with risk of death, and accurate communication between the sonogra­pher, Radiologist, Emergency Department physi­cian, and Reproductive Endocrinologist is critical to appropriate and timely diagnosis.
Severe OHSS is one of the most serious complications of ovarian hyperstimulation (Fig. 23.4b ). The incidence of severe OHSS is estimated between 0.5 and 5 % per IVF cycle. Severe OHSS has been reported to be fatal, so the prompt diagnosis and treatment is paramount [ 18 ]. Patients with severe OHSS describe rapid weight gain, signifi cant abdominal distention with inability to fi t into usual clothes, shortness of breath, pain which can be refractory to oral medications, oliguria, and severe and unrelent­ing nausea or emesis with inability to tolerate oral intake. Clinical fi ndings include all of the features of moderate OHSS plus clinical ascites, sonographic ascites, ultrasound evidence of pleu­ral effusions, and serum laboratory abnormalities such as hemoconcentration, coagulopathy, elec­trolyte imbalance, and renal and hepatic dysfunc­tion or failure [ 19 ].
Current research indicates that the fl uid shifts which occur in OHSS are directly caused by increased VEGF. VEGF leads to increased vas­cular permeability, reduced colloid osmotic gra­dient, and spillage of fl uid out of the vascular compartment and into the extravascular spaces [ 20 ]. These fl uid shifts can be identifi ed sono- graphically, and it is recommended that in the evaluation of the patient suspected to have mod­erate or severe OHSS, ultrasound should be used to check for abdominal ascites or pleural effu­sions. Generally, the volume of accumulated fl uid is not subtle and can easily be identifi ed either through abdominal or vaginal ultrasound or ultra­sound of the lung bases. The third spacing of fl uid into the peritoneal and pleural cavities leads to respiratory compromise, hypotension, increased intra-abdominal pressure, and renal compromise related to decreased perfusion [ 21 ].
The hemoconcentration and resultant hyper­coagulability of severe OHSS can lead to venous
and arterial thromboembolism both in the typi­cal locations such as lower extremities and lungs and in sites which seem more specifi c to OHSS such as the subclavian and internal jugular ves­sels. It is unclear why thrombosis may be local­ized to the neck rather than the lower extremities; some have hypothesized that increased perito­neal fl uid containing infl ammatory mediators drains into the thoracic duct and directly into the subclavian veins, possibly locally increasing coagulation at those sites [ 22 ]. Rova et al. evalu- ated the risk of venous thromboembolism in all IVF cycles and particularly in the subset com­plicated by OHSS [ 21 ]. They found that the incidence of venous thromboembolism from the time of the IVF cycle into the fi rst trimester of pregnancy was 0.17 % (32 out of 19,194 patients), which was a 10-fold increase over the background risk in spontaneous conceptions. Furthermore, in patients diagnosed with OHSS, the risk of venous thromboembolism was 1.4 % (19/1,272), a 100-fold increase. Given this markedly increased risk, Doppler studies to evaluate for thromboembolism are a critical part of the evaluation of the patient with suspected moderate or severe OHSS. Even if thrombosis is not identifi ed, it is generally recommended to initiate prophylactic anticoagulation in hemo­concentrated patients with heparin or low molecular weight heparin when the hematocrit is found to be 45–50 % in order to mediate this risk [ 23 ].

Ultrasound in the Management and Treatment of Ovarian Hyperstimulation Syndrome

Timely and accurate diagnosis of OHSS facili­tates proactive management and treatment. The management strategy varies in the literature, from some authors recommending immediate hospitalization upon the diagnosis of moderate or severe OHSS to others advocating active outpa­tient treatment. Regardless of the location, ultra­sound is critical in the management and treatment of OHSS. Sonographic monitoring can determine decrease in volume of abdominal ascites which