Abstract
Assisted reproductive techniques (ARTs) are the only hope for biologically own progeny for couples that fail to conceive naturally. In the developed world, up to 4.0 per cent of all children born are the result of assisted conception, be it in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). The treatment-associated interventions, though well established, are not without complications to which the couples are often oblivious, as the hope of having a child may diminish one of the most significant and basic human instincts of self-preservation.
Introduction
Assisted reproductive techniques (ARTs) are the only hope for biologically own progeny for couples that fail to conceive naturally. In the developed world, up to 4.0 per cent of all children born are the result of assisted conception, be it in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) [1,2]. The treatment-associated interventions, though well established, are not without complications to which the couples are often oblivious, as the hope of having a child may diminish one of the most significant and basic human instincts of self-preservation.
Complications in ART may arise at any stage of the process, starting at ovulation induction and concluding with obstetric complications of an achieved pregnancy. Due to under-reporting or the benign nature of some of the complications, the actual prevalence is most likely underestimated. Complication rates vary from 0.02 to 23 per cent for infectious complications and miscarriage, respectively [3,4]. When discussing the complications of ART, separation into procedure-related and pregnancy-related complications should be made, with procedure-related complications including ovarian torsion, bleeding and infection following transvaginal ultrasound-guided oocyte retrieval (TVOR) with associated co-morbidities, and ovarian hyperstimulation syndrome (OHSS). When a pregnancy is achieved, it might be in the form of an ectopic pregnancy, heterotopic pregnancy or multiple pregnancy, or it might end in a miscarriage. There is evidence to suggest that ART pregnancies that progress past the first trimester are at an increased risk of congenital anomalies, preterm birth, low birth weight, gestational diabetes and pre-eclampsia [5,6]. The exact cause of the increase in the adverse outcomes can be sought in the technology or underlying maternal factors [7].
In this chapter we cover the sonographic aspects of the procedure and pregnancy-related complications of ART.
Ovarian Hyperstimulation Syndrome
Ovarian hyperstimulation syndrome is a potentially fatal condition related to ovarian enlargement with systemic increase in vascular permeability. It may occur following any form of ovarian stimulation, including clomiphene citrate and gonadotrophins, with the latter being responsible for the majority of cases. Spontaneous – unrelated to ovulation induction – OHSS has been reported but is a rare event [8].
Varying classification systems and potential under-reporting allow for an estimate of overall incidence approximating 2–10 per cent of IVF cycles [8], with the severe form complicating 0.1–2 per cent of all IVF cycles and a mild form occurring in up to 23 per cent of IVF cycles [9]. The reported mortality rate related directly to OHSS or indirectly (due to complications) is estimated to be between 1 in 400,000 and 1 in 500,000 ovarian stimulation cycles [10].
The main pathogenic changes leading to clinical manifestations of the condition are shifts in fluid from the intravascular to the extravascular compartment. The release of vascular endothelial growth factor (VEGF) from the stimulated and punctured follicles and associated activation of the renin-angiotensin system (RAS) is the pathway responsible for the increase in global vascular permeability [8]. The exact mechanism of this process is still under debate, with various factors such as oestrogens, progestogens, interleukins, angiogenins, endothelins, prostaglandins, histamine, prolactin and kinins thought to play a role [11]. The described molecular changes lead to clinical findings of relative hypovolaemia, hypotension, tachycardia, haemoconcentration with increasing haematocrit, renal hypoperfusion with associated renal failure, and acute respiratory failure. Increased vascular permeability leads to the development of albumin-rich ascites and pleural effusions causing abdominal discomfort and distension, as well as respiratory distress. Pericardial effusions can be present in the more severe forms of the syndrome [12]. Gastrointestinal symptoms (diarrhoea and vomiting) and liver function derangements are attributed to an increase in intra-abdominal pressure, which may lead to compression of the low-pressure abdominal vessels supplying intra-abdominal organs (liver, intestines) [13]. Haemoconcentration and hyperoestrogenaemia lead to an altered thrombotic state which can cause a severe venous thrombotic event (VTE), and if undiagnosed and untreated significantly contributes to mortality.
Clinically, OHSS can have an early or late onset, be mild, moderate, severe or critical [14]. The most often quoted, older classification of OHSS was based on ultrasound findings of ovarian enlargement and ascites [9]. A newer classification combines ultrasound findings, clinical signs and symptoms and laboratory investigations [8,15,16]. The detailed description of each clinical form is shown in Table 13.1. The resolution of OHSS symptoms is expected by the sixth week of gestation.
Table 13.1 Leuven University Fertility Centre classification system of OHSS
| Grade of OHSS | Symptoms | Management |
|---|---|---|
| Mild OHSS |
|
|
| Moderate OHSS |
| Conservative, outpatient based |
| Severe OHSS |
| Hospital based |
| Critical OHSS |
| Admission to critical care unit |
Ultrasound assessment should be performed via the abdominal and transvaginal route when assessing women with suspected OHSS. This approach allows visualization of the pelvic organs, often-enlarged ovaries that have moved out of the pelvis, and the upper abdomen with quantification of ascites. Ovarian size >12 cm may preclude complete ovarian assessment due to ultrasound attenuation, and bleeding into the ovarian follicles may be missed. In such cases, clinical judgement or computed tomography (CT) in the absence of pregnancy may be carried out.
Following oocyte collection, the ovaries change their appearance dramatically. There is a significant enlargement, with the follicles refilling with fluid and blood. The vascularity significantly increases and multiple corpora lutea are formed. These range in size and appearance, with some being filled with clear fluid, some appearing solid and some having a mixed content of blood, blood clot and clear fluid (Figure 13.1). Greyscale ultrasound shows these to be isoechoic with the ovarian stroma. The dominant feature is the presence of strong peripheral Doppler signal signifying rapid neo-angiogenesis.
(c) Transvaginal ultrasound scan of bilaterally enlarged ovaries following ART. Both ovaries are displaced superiorly above the uterus and meet in the midline (‘kissing ovaries’). Some of the follicles contain blood clots (arrow).
(d) Transvaginal ultrasound scan of post-oocyte retrieval ovary with significantly increased vascularity as demonstrated by power Doppler modality.
The abdominal scan should be performed first, with the vaginal scan to follow. In the assessment, the standard description of the pelvic organs should be undertaken as described in Chapter 2. Special focus should be placed on assessment of any points of tenderness, the presence of large haemorrhagic cysts within the enlarged ovaries (signifying bleeding into the ovaries), absence of vascularity within one or both ovaries, the deepest vertical pool of fluid in the pouch of Douglas and pouch of Morrison (upper abdomen), presence of intra-abdominal blood clots, and appearance of the fluid (clear or particulate, with the latter representing blood or pus) (Figure 13.2).
(a) In cases of severe OHSS, free fluid can be seen in the pouch of Morrison (arrow). The left upper quadrant can also be filled with free fluid in severe cases of OHSS.
(b) Note free-floating loops of bowel (arrow).
According to the Royal College of Obstetricians and Gynaecologists (RCOG), clinical assessment of women with mild to moderate OHSS should include body weight recording, abdominal girth measurement and pelvic ultrasound, and should be carried out every 2–3 days in order to determine deterioration of condition [16]. In more severe cases, with tense ascites causing severe discomfort or impeding respiration, ultrasound-guided paracentesis should be considered [17,18]. Similarly, women with inadequate urine output, despite appropriate rehydration, and ascites could benefit from decreased intra-abdominal pressure, as this might improve renal circulation and restore urine production [19]. Gradual drainage of ascites and the use of pigtail catheters should be encouraged to prevent cardiovascular collapse due to rapid fluid shifts [20].
Oocyte Retrieval-Related Complications
Transvaginal ultrasound-guided oocyte retrieval is currently the procedure of choice for oocyte collection in most IVF centres worldwide [21]. Though the procedure is safe overall, associated risks exist, such as bleeding, intra-abdominal sepsis and injury to pelvic organs.
Bleeding
Visible vaginal bleeding can be limited by minimizing the number of vaginal punctures, which are the most common form of haemorrhagic complications, occurring in 0.5–8.6 per cent of oocyte retrievals, with significant vaginal bleeding exceeding >100 ml reported to occur in 0.8 per cent of cases [22]. Occult haemorrhage into the ovary or peritoneal cavity is a more severe complication, with an incidence of 0–0.35 per cent. This complication is related to direct injury to the ovary, bleeding from the ruptured follicle or injury to large pelvic vessels [23]. Coagulation disorders, inherited or iatrogenic, increase the risk of haemorrhagic complications.
Careful visualization of the follicle and neighbouring iliac vessels and application of power Doppler if there is doubt as to the nature of the structure allows for unequivocal identification of follicles and avoidance of puncturing the neighbouring blood vessels. A more detailed description of oocyte collection can be found in Chapter 12.
In the event of an uncomplicated TVOR, the expected blood loss should not exceed 250 ml, with a haematocrit drop of approximately 5 per cent. Larger visible loss, unexpectedly low haemoglobin values following TVOR, or symptomatic hypovolaemia should warrant further investigations [24]. Abdominal and transvaginal ultrasound scan should be performed and should suffice to identify and quantify presence of free fluid in the abdomen (Figure 13.2). Organized blood collections localized above the pelvic brim, retroperitoneal and broad ligament haematomas might not be immediately visible and may necessitate employment of other imaging modalities such as computed tomography (CT).
As in the case of OHSS, thorough and systematic assessment of the pelvis and abdomen should be undertaken, with abdominal scan carried out first. The appearance of the ovaries should be described, with identification and size quantification of haemorrhagic cysts – fresh with liquid blood, as well as old where blood has organized to produce a blood clot (Figure 13.3).
