The abdominally guided puncture has been largely replaced by the transvaginal puncture given the improved imaging quality for gynecologic organs achieved with transvaginal ultrasound and the proximity of this probe to the targeted lesions. Procedures such as amniocentesis will always be performed abdominally, but marked changes in assisted reproductive technologies, specifically in vitro fertilization (IVF) and human egg retrieval, have paved the way for vaginally guided techniques. The aim of this chapter is to describe the various transvaginally guided puncture procedures, both those being presently performed and innovative procedures being studied experimentally, and the experience gained thus far.

Ever since Smith and Bartrum performed percutaneous aspiration of intraabdominal abscesses in 1974 and Gerzof et al used an abdominal catheter placed sonographically to drain purulent pelvic collections, ultrasound-guided puncture procedures have been used to achieve diagnostic and therapeutic goals.^1-3 The advantages of these procedures over traditional surgical means are multiple: ease of technical mastery with accurate needle or catheter placement, diminished invasiveness, avoidance of injury to adjacent organs, portability, low cost, speed of administration, and above all, patient satisfaction and comfort. Possible risks, although quite rare, include bleeding, infection, inadvertent puncture of organs, tumor seeding, and in the case of multifetal reductions, miscarriage.

Puncture procedures necessarily traverse three-dimensional(3D) space, not only the two-dimensional(2D) view of an ultrasound machine screen. This third dimension, because of the properties of ultrasound, is thinnest at the focal range of the probe and is inversely proportional to the operating frequency of the transducer crystal. This concept is called the slice thickness artifact and means that the operator must take the third dimension of the image into account: At times the tip of the needle used for puncture procedures appears to be within the structure at which it is aimed, but is actually in front of or behind the target structure.

When puncture procedures are performed abdominally, one of two techniques is employed: needle guide or free hand. Less experienced operators are more comfortable using a needle guide attached to the transabdominal ultrasound transducer to assist needle placement. With increasing experience, the free-hand approach has been successfully practiced, with greater ease of handling the needle, shorter procedure time, and better alignment of the needle within the scanning plane. The limitation of this technique is that occasionally the transverse section of the needle, excluding the tip, is imaged and the actual needle tip may not be visualized. When the puncture procedure is being performed abdominally, a quick readjustment of the scanning plane may be done to find the needle tip. Scanning along the long axis of the needle improves tip visualization. The needle is most reflective when it intersects the ultrasound beam at a 90 degree angle, producing a specular reflection. This right-angle approach may be achieved by inserted the needle at an oblique rather than perpendicular angle to the skin surface and rocking the transducer toward the needle. Third party add-on devices have been developed that enhance needle tracking by embedding an electromagnetic sensor within the needle, improving visibility (eTRAX, Civco, Coralville, Iowa).

When puncture procedures are performed transvaginally, there is limited mobility of the probe and the needle, making the free-hand approach cumbersome. A fixed needle guide attached to the probe shaft allows easier visualization of the needle tip within the scanning plane and better control for precise needle placement. The needle guide also protects the vaginal wall from inadvertent puncture during insertion of the needle. An automated spring-loaded puncture device (Labotect, Gottingen, Germany) may be used.⁴ This device when mated to the shaft of the endovaginal transducer, provides extreme accuracy and precision, and its high-velocity release makes the procedure virtually painless with no anesthesia or analgesia necessary. This technique is useful where extreme accuracy is needed for needle placement controlled and guided by the transvaginal probe.^5-10 The accuracy of the needle placement tested in vitro was found to be between 1 and 2 mm. Manual needle introduction is potentially more painful as the relatively slower forward motion of the needle frequently displaces mobile targets rather than directly penetrating them. We have found it useful to employ a sharp jabbing motion when manually advancing the needle to limit this occurrence. In most cases, where manual needle insertion is used, analgesia and sometimes local anesthesia, is used via intravenous meperidine (25-50 mg) and diazepam (5-10 mg), with local injection of 2 to 3 mL of 1% lidocaine through the needle guide into the vaginal wall at the intended puncture site. We use a 25-gauge 20 cm long Chiba biopsy needle (Cook Medical, Bloomington, IN, USA) to anesthetize the vaginal wall prior to FNA. Lidocaine jelly rather than ultrasound gel may be used as a lubricant, anesthetic, and coupling medium. When obtaining core samples with an automated biopsy gun anesthesia may not be necessary.

A general guideline of the techniques employed for the majority of the common puncture procedures performed will be described. Several procedures follow different protocols, which will be discussed separately.

The patient should be in the lithotomy position on a gynecologic table with a nondistended urinary bladder. Emptying of the bladder limits distortion of the pelvic anatomy, prevents inadvertent puncture of the bladder wall, and improves patient comfort as otherwise the patient may experience the urge to void during the procedure. The vulva and vagina are sterilely prepared. Insertion of a speculum aids in the cleansing of the vaginal walls. Transvaginal biopsy is considered a clean-contaminated procedure. There are no published recommendations concerning the use of antibiotic prophylaxis for this procedure.¹¹

Punctures are usually performed with the guidance of a 5.0 to 9.0 MHz endovaginal transducer, with a needle guide attached to the shaft of the probe. The highest frequency setting that allows adequate visualization of the target area should be utilized. Most US machine manufacturers and several third parties offer disposable needle guides and attachments specific for their transducers, along with stainless steel reusable guides that are sterilized (autoclaved) after each procedure. Separate needle guides are made for 2D versus 3D endovaginal transducers due to their differences in size. The endovaginal transducer with attached needle guide is advanced into the vaginal fornices as close to the target lesion as possible. A software-generated fixed “biopsy guide” line is displayed on the ultrasound monitor screen, which marks the path of the incoming needle (Figure 41-1).

Most biopsy guides provide the operator with a centimeter scale with which to measure needle depth. It is important to hold the transducer firmly in a fixed position while maintaining the target within the guidelines in ensure proper needle placement. Needle gauges ranging from 14 to 25 are employed, depending on the nature of the procedure; the smallest possible needle gauge able to perform the desired task should be used. A needle with an occluding stylet is preferred to prevent contamination of the specimen by adjacent tissue or blood during passage of the needle. The length of the endovaginal transducer and needle guide necessitates a needle length of at least 20 cm. Use of a smaller depth, employing the zoom feature, lowering frame averaging, and reducing compound imaging aid in needle visualization and placement by elevating the frame rate and increasing acoustic shadowing created by the needle reflection. Removal of the stylet completely from the biopsy needle and then reinserting the stylet allows introduction of a small amount of air within the needle lumen, increasing conspicuity in difficult cases. Scoring the needle tip with a scalpel blade with care taken to prevent bending of the needle also increases reflection of the needle. Application of color Doppler while gently agitating the needle may also improve visualization.

An onsite pathologist is recommended for biopsies to insure specimen adequacy and to minimize the number of needle passes.

Transabdominal, transrectal and transperineal sonography have been found to be valuable in guiding difficult dilation and curettage (D&C), intracavitary tandem placement, and cerclage placement. The basic technique of this application is discussed at the end of this chapter, after the puncture procedures are discussed in detail individually.

Patients should be counselled before the procedure and asked to sign standard informed consent forms. Specifically designed consent forms are usually used in specialized procedures, such as multifetal reduction and puncture of ectopic pregnancies.

The procedure should be documented with still images and/or cineclips. After the final withdrawal of the needle, the pelvic structures and cul-de-sac should be observed sonographically to detect possible hemoperitoneum or other sites of hemorrhage. The patient should be informed that a small amount of postprocedure vaginal spotting may be expected. The patients may be rescanned after a 2- to 3-hour observation period, to check for internal bleeding or previously undetected complications. A detailed written report describing the procedure should be promptly completed.

A short description of the more commonly performed transvaginally directed punctures (see list) will be described, including the indications and specific attributes.

1. 
   

   Transvaginal puncture/catheterization procedures in assisted reproduction

   
   
2. 
   

   Punctures of ovarian cysts

   
   
3. 
   

   Multifetal pregnancy reductions

   
   
4. 
   

   Treatment of ectopic pregnancy

   
   
5. 
   

   Drainage of pelvic (fluid) collections

   
   
6. 
   

   Needle biopsy

   
   
7. 
   

   Ultrasound guidance for D&C

Transvaginal Puncture/Catheterization Procedures in Assisted Reproduction Oocyte Retrieval

The transvaginal approach for oocyte retrieval is now the technique of choice worldwide; the technique consists of a needle guide attached to the vaginal probe enabling guided needle placement under real-time observation (Figure 41-2).^12,13 Some programs use the automated spring-loaded puncture device that is attached to the shaft of the vaginal probe.⁴ A 16- or 17-gauge needle with a sharp tip is commonly used for this procedure.

Transabdominal aspiration is an alternative to laparoscopic retrieval in the uncommon scenario when the ovaries are not adequately approached via transvaginal sonography. This scenario may occur in patients with elevated BMI, uterine leiomyomata, adenomyosis, pelvic adhesions, congenital anomalies, and surgical transposition of the ovaries. Barton retrospectively reported 69 cases (0.4%) of transabdominal ultrasound-guided oocyte aspiration out of more than 17,000 IVF cycles over a 12-year period.¹⁴ The aspirations were performed with spinal or general anesthesia. A needle guide was attached to a 4.1 MHz transabdominal transducer, and percutaneous aspiration was performed with a standard 17-gauge retrieval needle. No serious complications were encountered in their series of transabdominal aspirations. There were slightly fewer oocytes retrieved when compared to transvaginal ultrasound guidance, but no significant difference was found in damaged oocytes, embryo number and quality, fertilization rate, or pregnancy rate.

IVF results may be improved following aspiration of a hydrosalpinx. In a study of 66 women with a hydrosalpinx, the patients were randomized to a transvaginal ultrasound-guided aspiration performed immediately following oocyte retrieval or no aspiration. Aspiration of the hydrosalpinx resulted in higher biochemical (44% vs 21%) and clinical pregnancy rates (31% vs 18%).¹⁵

Complications arising from puncture technique are rare, but have been described intermittently in the literature. Ludwig et al prospectively reviewed their experience with over 1000 oocyte retrievals, analysing their perioperative and postoperative complications.¹⁶ No complications were caused by sedation or general anesthesia. Vaginal bleeding was observed in 2.8% of procedures, with no cases of intraabdominal bleeding. A single ureteral injury occurred. No case of documented pelvic infection was noted, but one case of unexplained fever did occur. Severe ovarian hyperstimulation syndrome (OHSS) occurred in 2.7% of the cases. Although most patients tolerated the oocyte retrieval well, 3% of the patients experienced severe to very severe pain after the procedure, and 2% of patients were still suffering from severe pain 2 days after the procedure. The pain level increased with the number of oocytes retrieved.

Aragona reported a frequency of 0.08% of severe complications resulting after more than 7000 transvaginal ultrasound-guided oocyte retrievals, with four cases of hemoperitoneum and two cases of ovarian abscess.¹⁷ In a review of the complications of transvaginal ultrasound-guided oocyte retrieval after 542 cycles, the most common complication of minor vaginal bleeding occurred in 18%.¹⁸ There was a severe complication rate of 0.72%, comprised of two cases each of anesthesia induced bronchospasm and hemoperitoneum. Lean women with polycystic ovarian syndrome have been found to have a higher risk of developing severe hemorrhage.¹⁹

Ureteral injury has been increasingly recorded after transvaginal ultrasound-guided oocyte aspiration with reports of ureteral transection, perforation, obstruction, ureterovaginal fistula, and massive ureteral hemorrhage with shock occurring.^20,21 Factors affecting ureteral injury include distortion of ureteral anatomy by either endometriosis, prior pelvic surgery, or mechanical distortion created by pressure from the endovaginal transducer.

Puncture of Ovarian Cysts

Puncturing an ovarian cyst is likely the simplest of all the puncture procedures, and it is one of the more common indications for the technique. Technically, the center of the cyst is targeted, and the needle is placed and maintained in the middle of the slowly shrinking sonolucency while direct sonographic visualization is maintained throughout the entire aspiration. The fluid may be manually aspirated with a syringe or with wall or bottle suction. Use of connecting tubing helps prevent needle dislodgement. This technique has few complications and is well tolerated. The aspirated fluid is usually submitted for cytological evaluation, although false-negative results are common with fluid cytology in ovarian malignancies.²²

Reproductive endocrinologists have employed selective follicular aspiration during the selection phase of infertile women with polycystic ovary syndrome (PCOS) under controlled ovarian hyperstimulation while undergoing IVF.²³ No cycles with moderate or severe OHSS occurred in the ultrasound-guided transvaginal follicular aspiration group, while 9 of 13 patients had OHSS in the untreated group. The oocyte maturation rate, fertilization rate, and cleavage rate in the aspirated group were all significantly higher than the untreated group. They concluded that follicular aspiration during the selection phase can significantly decrease severe and moderate OHSS prevalence in patients with PCOS undergoing controlled ovarian hyperstimulation.

Several investigators have reported series of successful punctures of ovarian cysts and symptomatic benign cystic pelvic lesions, such as parovarian cysts and peritoneal inclusion cysts, without complications.^24-27

Recurrence and persistence of ovarian cysts are another concern, although they appear to occur in approximately 30% of cases. Weinraub followed a group of 35 women with ovarian cyst puncture and performed a second aspiration for recurrence in 14 of the women.²⁸ Three parameters proved important in predicting the outcome of aspiration: patient age and the location and maximum diameter of the cyst. The older the patient and the larger the cyst, the lower the likelihood of cure with cyst aspiration, thus suggesting that aspiration of large cysts should be avoided in older women. A series of 30 transvaginal cyst aspirations achieved complete aspiration in 23 of the cases. Recurrence of the cyst was found in 12 cases (40%).²⁹ Bret published two papers using transvaginal ultrasound for aspiration of ovarian cysts and found a high recurrence rate after cyst aspiration in pre- and postmenopausal women (48% and 80%, respectively).^30,31

The recurrence rate of 107 sonographically guided aspirated ovarian cysts from 1 to 6 years after puncture was investigated.³² In 42 cases (39%), the initial cyst aspiration constituted definitive therapy. In 65 cases, the cyst recurred (complete recurrence), and in this group 35 women had subsequent surgical management. Twenty-seven women with cysts smaller than 5 cm (incomplete recurrence) were allocated to the follow-up group. In 65% of women overall, surgery was avoided, and no major complication was encountered. Twenty-four women who underwent 34 transvaginal ovarian cyst drainage procedures were studied and showed an overall recurrence rate for ovarian cysts after transvaginal drainage of 75%.³³ The mean length of follow-up was 39.5 months with a range of 1 to 85 months, significantly longer than previous studies.^34-36 Their findings imply that patients with a predisposition for ovarian cysts are likely to develop recurrence and the likelihood of demonstrating this recurrence increases with time. Unlike previous reports,²⁸ this study did not show a significant difference between patients with recurrence and those without recurrence with regard to the maximum diameter of the cyst. In the cardiovascular radiology literature, transvaginal aspiration of ovarian cysts has been utilized as a viable alternative to surgery in patients who are poor operative candidates due to their cardiovascular disease.³³

Combined ultrasound-guided puncture of cystic adnexal masses and cytologic analysis of the aspirates to prevent or at least limit surgical intervention has been studied previously.^37,38 Forty-three cystic ovarian masses were sonographically characterized using the Sassone scoring system and then aspirated if the cysts exhibited benign-appearing morphology.^38,39 All 25 cysts that were benign by TVS, histology, or both were also cytologically benign, as were an additional 11 cysts that were not resected. Seven cytologically and histologically malignant cysts, which were not aspirated but resected and evaluated postoperatively had high Sassone scores, which were suspicious for malignancy. The combination of TVS and aspiration cytology was considered valuable by the group, especially in obviating an operative procedure in the diagnosis and management of cysts having low TVS scores and benign cytology.³⁸ The concern of inadvertent ovarian cancer tumor spread has caused many gynecologic oncologists to oppose any ovarian cyst puncture procedure, creating controversy over use of the procedure.⁴⁰ In a retrospective study,⁴¹ Gupta et al studied 548 ovarian masses that underwent transabdominal fine needle aspiration and cytology (FNAC) from 1998 to 2010. The size of the lesions varied from 1 to 27 cm and included functional cysts; nonneoplastic lesions comprised 180 of 584 cases, and neoplastic lesions comprised 249 of 584 cases, of which 81 were benign and 168 malignant. The cases were then divided into concordant and discordant cases based on the histopathological and original cytological diagnoses. FNAC was 85.7% sensitive and 98.0% specific with a PPV, NPV, and accuracy of 97.7%, 87.7%, and 92%, respectively, if inconclusive cases were not computed (the accuracy was 76.0% if these were included). Similar results were found in 57 aspirates from 50 patients with a conclusion that FNAC may help avoid unnecessary interventions and facilitates the choice of the appropriate therapy since it enables a satisfactory classification of ovarian tumors.⁴² Another retrospective study evaluated the accuracy of cytological evaluation of ovarian masses in 67 ovarian cystic masses with fine needle aspiration and cytology and concurrent/subsequent cystectomy/oophorectomy. They had 100% specificity but low sensitivity (50%), the latter due to paucicellularity of the aspirate, focality of ovarian borderline tumours, and surface involvement by metastatic cancer.⁴³ Despite the lack of strong evidence, the concern of inadvertent tumour cell spillage from a malignant ovarian cyst prevents wider use of this technique.

Another combination approach in the management of ovarian cysts includes both sonographically guided drainage and subsequent laparoscopic excision.⁴⁴ This technique is particularly useful in very large, unilocular cysts, which would be contraindicated for the laparoscopic approach alone. The authors employed this combined technique in a patient with a 24 × 10 × 20 cm unilocular cyst. Transabdominally guided insertion of a Veress needle into the center of the cyst through the patient’s umbilicus was performed, and the needle was attached to a suction pump: 3100 cc of fluid was drained off. As the cyst had shrunk to one-third its original size, standard laparoscopic techniques were then employed, and the cyst wall was removed without incident.

Several recent authors have used combined transvaginal aspiration and instillation of a sclerosing agent in the hopes of decreasing the known high recurrence rate.^45,46 Although most sclerosing agents were used in the setting of endometriomas and endometriosis, Kukura described a similar technique for use in simple-type cysts.⁴⁵ After complete emptying of the cyst, they injected an amount of sterile 96% alcohol equalling 50% of the volume of the cyst. The alcohol was left within the cyst lumen for 5 minutes and then aspirated completely. They treated 152 patients in this manner with a cyst volume of between 40 and 140 cc. After 3 months, recurrence occurred in eight patients (5%), mostly in cysts with volumes of greater than 100 cc. The technique of TVS-guided aspiration with methotrexate injection in the management of 162 female patients with simple or endometriotic ovarian cysts was studied, with 148 patients available for follow-up.⁴⁶ The cysts had disappeared in 124 patients (83.8%) and persisted in 16.2% at follow-up ultrasound. Cyst diameter proved to be a significant prognostic factor for cyst resolution (P = .01), and no major complications were observed.

A randomized study in 96 women with nonneoplastic ovarian cysts compared two groups of patients: one group treated with cyst aspiration only, and the other group underwent cyst aspiration with tetracycline sclerotherapy.⁴⁷ There was no difference in the two groups regarding demographic data and tumor markers, which were all within normal limits. The recurrence rates were 14.6% for the sclerotherapy group and 50% for the cyst aspiration-only group. They subdivided the groups based on the size of the cysts. The recurrence rate for sclerotherapy and small cysts (<7 cm) was 12%, whereas the sclerotherapy large cyst (>7 cm) group had a recurrence rate of 17.4%. The recurrence rate for small cyst aspiration-only group was 51.9% and 47.6% for the large cyst aspiration-only group. Cytological examination of aspirated cyst fluid revealed no malignant cells in any of the cases. Patients who had recurrent cysts (31 patients) were treated via laparoscopic approach. Twenty cystectomies and 11 salpingo-oophorectomies were performed. The histopathological diagnoses in these patients were 24 serous cystadenomas, 6 mucinous cystadenomas, and 1 endometriotic cyst. They concluded that transvaginal aspiration with tetracycline sclerotherapy should be preferred over cyst aspiration alone considering the lower recurrence rates of the former.

The aspiration of endometriotic cysts is also an area of controversy and is considered relatively contraindicated, although recently more work has been undertaken in the subset of patients undergoing assisted reproductive technologies. De Crespigny aspirated 6 endometriomas among 28 punctured ovarian cysts without incidence.⁴⁸ Twenty-one ovarian and endometriotic cysts were aspirated using a transvaginally guided puncture technique, and a low incidence of recurrence with improvement in symptoms was found.⁴⁹ Technically, the procedure is simple, although patient selection is particularly important. Indications for the aspiration of endometriotic ovarian cysts include avoiding impairment of folliculogenesis,⁵⁰ following sequential follicle growth, improving follicular retrieval techniques,⁵¹ and the improvement of symptoms associated with large endometriotic cysts and adhesions. The recurrence rate within 3 months is high, between 66% and 83%, although often these recurrences do not occur until after the IVF program has been completed. Hsieh et al studied 108 consecutive patients treated for recurrent endometriomas.⁵² Ultrasound-guided transvaginal cyst aspiration was performed followed by ethanol sclerosis, and patients were followed for a minimum of 1 year. There were 29 recurrences (26.9%), which needed surgical intervention, and there was no significant difference between the recurrent rates and ethanol instillation time (ethanol instilled and immediately removed, instilled for ≤10 minutes). They did report a difference between the ethanol irrigation and ethanol retention groups: the recurrence-free rate for the ethanol irrigation group was significantly lower than that of the ethanol retention group at month 12. The antral follicles increased in both groups. They concluded that treatment by aspiration and sclerotherapy of endometriomas with ethanol in situ is a simple and effective therapy with a relatively low recurrence rate of 13.3% and additional advantages of a shorter treatment period, avoidance of general anesthesia, and absence of serious complications. Sclerotherapy with 5% tetracycline has been found to be a simple alternative to potentially complex surgical treatment of ovarian endometriomas before IVF.⁵³ Sclerotherapy rather than laparoscopy was performed for 32 women in their infertility practice. Five to 10 mL of tetracycline 5% was instilled into and then removed from the cyst after the endometriotic contents were completely aspirated. Ultrasound was performed 6 weeks later to assess the efficacy of treatment. They used resolution of the endometrioma and subsequent IVF pregnancy rate as their main outcome measures. Complete resolution was observed in 75% (24 of 32) patients at follow-up exam. Repeat aspiration was required in eight patients, and repeat treatment with tetracycline was required in two patients. Only one patient in the group did not ultimately respond. IVF was then performed in 28 of these patients; ongoing gestation occurred in 16 (57%) at the next cycle. These authors concluded that sclerotherapy with 5% tetracycline is a simple, effective, and in their limited series, safe alternative to surgical intervention for treatment of endometriomas before IVF. Endometriotic cysts were sclerosed with methotrexate after aspiration, with a 28.6% recurrence rate found.⁵⁴ A retrospective study in a small number of patients suggested that US-guided transvaginal ethanol sclerotherapy does not affect the reproductive outcome of these women after IVF.⁵⁵ Ethanol sclerotherapy has been used prospectively for the treatment of recurrent endometriotic cysts before IVF attempt. The recurrence rate was 12.9% of cases at a mean of 10 months after treatment without harmful side effects to ovarian reserve and ovarian response stimulation. They showed a higher cumulative and clinical pregnancy rates compared to laparoscopic cystectomy and suggested ethanol sclerotherapy as a good alternative to surgical management of recurrent endometriotic cysts before assisted reproductive treatment.⁵⁶

Combination modalities have also been recently employed for the treatment of endometriosis. A double-blind randomized controlled trial was performed to evaluate the results of ultrasound-guided aspiration of endometriomas under the effect of gonadotropin-releasing hormone (GnRH) analogues and a possible additional beneficial effect by leaving recombinant interleukin-2 (rIL-2) in the cysts.⁵⁷ Twenty-four women with endometriosis-related symptoms and TVS evidence of endometriomas greater than 3 cm who were initially sent to this group for laparotomy and conservative surgery were included. They found moderate clinical results after treatment with drainage plus GnRH analogues and significantly improved results in women having received rIL-2 intracystically. Although the rates of recurrence were similar in the two groups, the time until recurrence was significantly greater when rIL-2 was used. Although a subset of patients in both groups did need definitive surgery during the following 30 ± 12.7 months, this group did conclude that transvaginal ultrasound-guided puncture and aspiration of endometriomas under suppressive therapy with GnRH analogues has value for endometriosis treatment, and that rIL-2 instillation significantly increased the beneficial effects.

The pregnancy rates among 236 patients with a history of endometriotic cysts undergoing IVF associated with the use of a GnRH analog who also underwent US-guided aspiration were compared to patients who did not undergo aspiration.⁵⁸ The patients were separated into an experimental group who underwent aspiration and a control group who did not undergo aspiration. Both groups received two doses of a GnRH analog before IVF was performed, the first dose on the second day of the menstrual cycle and the second dose 28 days later. Patients younger than 35 years of age, with unilateral and bilateral endometriotic cysts, FSH hormone level of less than 10 mIU/mL, fewer than two cycles of IVF, and no history of uterine or ovarian surgery were included. They excluded patients who had a male partner with fertility issues and functional cysts. The aspirations of recurrent cysts were performed up to three times, and no complications occurred after aspiration. The diagnosis of endometriotic cyst was confirmed by cytology in all patients. The recurrence rate for the aspiration group was 28.9% after the first aspiration, and all cysts disappeared after the third aspiration. The number of implanted oocytes, the embryo quality, and the clinical pregnancy rate were higher in the cyst aspiration group. The conclusion reached is that aspiration should be considered as an alternative that would minimize further impairment of ovarian function in women with fertility issues due to endometriosis. They also showed that repeated aspirations could be performed and seemed to progressively reduce recurrence of endometriotic cysts.

Another area of controversy is the clinical benefit of aspirating “simple” ovarian and adnexal cysts. Ovarian simple cysts have a sonographic appearance that includes thin smooth walls with no septa or irregularities along the inner surface and are filled with anechoic fluid. The natural history of these cysts has been studied extensively in both pre- and postmenopausal women. There is also clinical evidence that a significant percentage of simple ovarian cysts resolve spontaneously and require no treatment. In a randomized trial, 278 women with simple cysts either underwent needle aspiration or observation for a 6-month follow-up period.⁵⁹ The main outcome measures were resolution of the cyst or the development of a malignancy. The rate of resolution was 46% with aspiration and 44.6% with observation alone; only the diameter of the cyst was a significant independent prognostic factor for resolution. Of the patients followed, no adverse sequelae or evidence of malignant transformation was noted from 10 to 58 months after initial diagnosis of the cyst. The authors concluded that a short period of expectant management is of very low risk.

An important 4 year prospective study in a large cohort of women from the intervention arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial utilized TV-US screening to assess postmenopausal ovarian cysts.⁶⁰ Women were eligible if they were between 55 and 74 years old and had no previous lung, colon, or ovarian cancer diagnosis. TV-US screening was performed at baseline and for 3 additional years using a 5 to 7.5 MHz TV probe to measure each ovary and describe any observed abnormalities. Enrolled into the screening were 39,115 women, and of these, 4895 were not eligible for TV-US. A total of 15,735 of these women had both ovaries visualized more than once during the study. In addition, 2217 women (14.1%) of 15,735 women had more than 1 simple cyst detected at their first US screening. Among women without a cyst of any kind on their first study, the rate of having a new simple cyst at the second screen 1 year later was 8.3%. The calculated incidence rate for each individual screening year of the trial was 8.3% at year 1 after baseline, 7.4% from years 1 to 2, and 7.3% from years 2 to 3. In this analysis, it was determined that postmenopausal simple ovarian cysts are a common incidental finding on pelvic ultrasound. An increase over time in the number or complexity of the cysts was infrequent, and many cysts resolved between annual examinations, reinforcing the belief that simple cysts are not likely cancer precursors or markers of increased risk and can be followed conservatively in postmenopausal women. A similar study done previously showed that only 10 ovarian cancers were detected among 2700 women with simple cysts after an average follow-up of 6 months, and no cancers developed among women with isolated simple cysts.⁶¹

In conclusion, ultrasound-guided aspiration of ovarian cysts offers a simple outpatient strategy for immediate pain relief and effective treatment in a majority of cases. In our practice, we limit ovarian cyst aspiration to patients with simple or slightly complex cysts who are symptomatic or are poor surgical candidates. The important criteria for selection include size and location of the cyst, morphologic characterization by sonography, and the patient’s age.

Multifetal Pregnancy Reduction

The increasing use of ovulation-induction medications and the increasing number of assisted reproductive technology programs over the years have resulted in a recent dramatic increase in multifetal pregnancies. It is known that the risk of pregnancy complication is proportional to the number of fetuses and conversely that the probability of achieving a term pregnancy is inversely proportional to the number of fetuses.^62-67 Fetal and maternal complication rates for multifetal gestations are high; mothers of triplets have a 35% risk of postpartum hemorrhage and at least a 20% rate of preeclampsia.⁶⁴ An extensive study from the Oxford Perinatal Epidemiological Unit compared mortality rates among infants born of multifetal pregnancies between 1975 and 1983, and it may be concluded that the risk increases dramatically in all orders after twins.⁶⁵ In addition to decreasing gestational age with increasing fetuses, the concomitant decrease in birth weight among multifetal pregnancies is striking; the mean gestational duration for twins is 260 days (37 weeks), for triplets is 247 days (35 weeks), and for singletons is 281 days (40 weeks).⁶⁶ The mean gestational age for quadruplets was only 29 weeks in a series where both the time of ovulation and time of delivery were accurately known.⁶³

The puncture procedure known as multifetal pregnancy reduction (MFPR) was developed to reduce the number of fetuses in utero to a lower, more desirable number, and it was first performed as a transcervical ultrasound-guided suction aspiration.⁶⁸ The transabdominal ultrasound-guided technique was first developed by French physicians in the early 1980s⁶⁹ and was soon adopted by many others.^70-78 Once the widespread use of transvaginally guided ovum aspiration for IVF and embryo transfer was in place, these techniques were successfully modified and applied for multifetal reduction procedures.^6,7,10,79-83

This technique of first-trimester MFPR performed for reduction of fetal number must be contrasted to second trimester selective fetal reduction, which is uniquely performed for anomalous fetuses, usually as one of a set of twins or, less commonly, triplets. The second-trimester selective technique is almost always performed with transabdominal ultrasound guidance, often after a second-trimester ultrasound anatomic survey reveals a fetal structural defect, or second-trimester genetic amniocentesis reveals a chromosomal or biochemical abnormality. The scope of this section focuses only on first-trimester transvaginal and transabdominal MFPR performed for fetal number.

Technically, the transabdominal or transvaginal MFPR is accomplished in the following manner. The patient first undergoes an extensive counselling session and a “baseline” mapping scan to evaluate the viability and chorionicity of each of the fetuses. The counselling session includes information given to the patient regarding the technique, the complication and pregnancy loss rates, and outcome measures, such as final gestational age and route of delivery. In either of the approaches (transabdominal or transvaginal), the area of the fetal heart is sought; once the desired location has been chosen, the needle tip is placed, either manually or using the automated device. In the transvaginal approach, a fixed biopsy guide is visible on the ultrasound monitor screen to assist in accurate needle placement. Approximately 0.5 to 1 mL of 2 mEq/mL potassium chloride (KCl) solution is injected slowly through a 20- or 21-gauge needle for cessation of fetal heart activity; the heartbeat of each injected fetus is then observed sonographically for 5 to 10 minutes to ensure complete cessation. If the desired technique is aspiration of early 6- to 7-week embryos, 17- to 18-gauge needles are preferred.⁸⁴ The patient is then observed in the ultrasound unit for several hours and rescanned before discharge and rescanned after the procedure according to the protocol of the program. The resolution of the reduced fetus and chorionic sac is monitored intermittently throughout the first two trimesters or for as long as it is visualized. Occasionally, a subchorionic hematoma is seen along the line of needle penetration, but it is self-limiting; Complication of the remaining fetuses may occur if their placental sites are compromised.

First-trimester sonography before MFPR allows for a basic preliminary early anatomic fetal survey, which can pick up a wide variety of major and minor structural fetal defects that also may aid in selection of the fetus to reduce.⁸⁵

We expect that the prematurity rates of these reduced pregnancies would approach those of nontreated singletons, twins, and triplets,^67,68 although there is a continuous debate regarding the risk-to-benefit ratio of reducing twins or triplets. Although a variety of intervention methods are available, multifetal pregnancies are still a challenge to be faced in all aspects of infertility treatments. There is very little doubt that MFPR is beneficial in cases of four or more fetuses, and some studies support a lack of causative relationship between fetal reduction and pregnancy endpoint. Multiple well-designed studies have examined the outcomes of reduced triplets and twins as opposed to nonreduced triplets and nonreduced twins.^86,87

Lipitz et al compared the outcome of triplet pregnancies managed expectantly or reduced to twins by MFPR.⁸⁷ There were lower incidences of prematurity, low and very low birth weight infants, pregnancy complications, and neonatal morbidity and mortality in the reduced group. Raval et al compared the perinatal outcome of triplet pregnancies reduced to twins with that of continuing twin and triplet pregnancies.⁸⁸ According to the results, MFPR reducing triplets to twins yielded an improved outcome compared with nonreduced triplets, and a similar outcome when compared with nonreduced twins. They also found a significant difference in gestational age at delivery. Reduced triplets had higher gestational ages overall with more reaching full term than nonreduced triplet pregnancies. Similarly, for patients who had MFPR, there was a shorter hospitalization time, which is a surrogate for maternal morbidity.⁸⁷ More recently, a study compared the outcome of 78 nonreduced twin pregnancies versus that of 55 twin pregnancies following early transvaginal MFPR. The rates of preterm delivery before 32 weeks of gestation were 1.9% versus 1.4% and before 34 weeks of gestation were 15.1% versus 19.2%, similar between both groups. There was no significant difference in the incidence of gestational diabetes and IUGR between the two groups. Although the incidence of gestational hypertension was higher in the triplets reduced to twins group than in the nonreduced group (24.5% vs 9%), this was not associated with an increased risk for IUGR or prematurity. They concluded that the outcome of twin pregnancies after early TV multiple fetal reduction from triplet to twin seems to be comparable to the outcome of nonreduced twin pregnancies.⁸⁹

A study by Haas compared the perinatal outcome in multifetal pregnancies containing a monochorionic twin pair, managed either expectantly or by fetal reduction.⁹⁰ The data on 47 triplet and 10 quadruplet pregnancies recruited between 10 and 14 weeks of gestation were retrospectively reviewed. The miscarriage rates before 24 weeks were 6.3% after reduction and 20.0% for expectant management. Those with expectant management had a 25% rate of severe preterm delivery before 30 weeks, while no cases of severe preterm delivery occurred in the reduction group. Similarly, mean gestational age and birth weight were significantly higher after fetal reduction than for the conservative approach. The expectant management of triplets was complicated by twin-twin transfusion syndrome and intrauterine fetal death in 18.8% and 8.3% of cases, respectively. The survival rates were 100% in the reduction group versus 58.3% in the expectant management group. They concluded that fetal reduction in triplets and quadruplets including a monochorionic pair is associated with decreased early prematurity and complications of monochorionicity. The overall survival in quadruplets is higher after reduction, although there was no difference for dichorionic triplets with reduction or conservative management.

The two major technical approaches in MFPR that have been developed are the transabdominal route and the transvaginal route, where the injection of KCl solution is performed through a needle guide or using an automated device. Occasionally, centers use a transcervical approach in much the same manner. The major difference in approach is gestational age at time of procedure: transabdominal MFPR is usually performed at a gestational age that is 1¹/₂ to 2 weeks more advanced than that at which the transvaginal approach is used for both visualization and technical reasons. The technique most commonly used has been transabdominal needle insertion of KCl solution into the fetal thorax, but intraabdominal and intracranial injections may be used when intrathoracic injections are not feasible.⁹¹ In a collaborative study evaluating the cumulative database among the world’s largest centers, the differences in efficacy and complication rates by transabdominal, transcervical, and transvaginal MFPR were analyzed.^92,93 Data had shown that the transvaginal and transcervical routes appeared to have a higher loss and complication rate than that using transabdominal sonography (TAS); thereafter, utilization of the transvaginal technique has decreased except for specific cases on an individualized basis.^93,94

In a retrospective study between 2005 and 2012, Haas et al evaluated the rates of pregnancy loss, preterm delivery, gestational diabetes, and hypertensive disorders in 83 pregnancies that underwent early (6-8 weeks) transvaginal MPR versus 125 pregnancies that underwent late (11-14 weeks) transabdominal MPR and showed that the perinatal outcomes of twin pregnancies after early and late MPR seem to be grossly similar.⁹⁵ The conclusion reached was that optimal timing for multifetal reduction depends on other factors such as selectivity of the procedure and the preference of the patient.

Timor-Tritsch et al reported on 290 consecutive cases of MFPR and compared the TA versus the TV approach in 2004.⁹⁶ Two hundred and three cases (70%) were performed transabdominally, 75 cases (25.9%) were performed transvaginally, and 12 cases (4.1%) used both routes. The indications for the transvaginal route were extreme obesity, abdominal scars, or if the target area of the fetus could not be reached transabdominally. As previously noted in other studies, the MFPR success rate was higher with the transabdominal route compared with the transvaginal route. Total pregnancy loss rates of MFPR were 3.5% (7 of 203 reductions) for the transabdominal route and 13.3% (10 of 75 reductions) for the transvaginal route (P = .004).

Significant differences in favor of the transabdominal route were observed for pregnancies originating with triplets or finishing with a single fetus, and concluded the transvaginal route should be performed only when the transabdominal approach was difficult or impossible.⁹⁶

Evans previously published data on improvement in outcomes of MFPR with increased experience.⁹⁴ More than 3500 cases from 11 centers with extensive experience in this procedure were analyzed. Increasing experience was correlated with considerable improvement in outcomes, with decreases in rates of pregnancy loss and prematurity. Overall loss rates correlated strongly with starting and finishing numbers of fetuses, with improvement of outcome for smaller starting and finishing numbers. Birth weight discordance between surviving twins was increased with greater starting number, and overall the proportion of cases with a starting number greater than or equal to 5 decreased significantly from 23% to 12% over two decades. This study confirms that the technique is a safe and effective option for multifetal pregnancies, and that the outcome has improved significantly with experience. Reductions from triplets to twins and recently from quadruplets to twins carry outcomes as good as those of unreduced twin gestations.⁹⁴ Pregnancy of very high order uses a special technique that is not often required. Monteagudo et al reported on a 12-to-2 MFPR that was successfully carried out in three steps over 2 weeks.⁹⁷ The concern of impaired coagulation in the presence of large volumes of nonviable fetal tissue was addressed in a study that found no significant clinical or laboratory expression of coagulopathy after MFPR.⁹⁸

Selection of the final number of fetuses is complex, and many factors must be included in the decision, including the potential for reasonable perinatal outcome. Based on the improved perinatal outcome for twins, the suggestion that two fetuses remain after the MFPR in quadruplet or triplet pregnancies seems reasonable. For these same reasons, twin pregnancies should not as a rule be offered selective reduction to singletons, although there will always be the rare case of twins where, for physical or emotional reasons, a reduction may be offered.

Many patients undergoing MFPR are candidates for genetic counselling and testing. Maternal serum α-fetoprotein levels are not useful in these patients.^99,100 Amniocentesis following MFPR has been studied in several articles in the literature. A cohort study performed on 127 patients who underwent amniocentesis after MFPR compared their pregnancy loss rate to 167 patients who did not have amniocentesis after MFPR.¹⁰¹ This group found a pregnancy loss rate of 3.1% (4 of 127) in the amniocentesis group compared with 7.2% (12 of 167) in the control group. They concluded that amniocentesis after MFPR does not increase the risk of pregnancy loss, a conclusion that has been corroborated by other studies.^102,103 Amniocentesis in multifetal pregnancies usually involves sampling each sac with an estimated attributable loss rate of 1.6% with amniocentesis performed in twin pregnancies. Chorionic villous sampling (CVS) has the advantage that it can be performed earlier in pregnancy, and some studies have shown no increased risk of procedure-related loss in twin pregnancies compared with second-trimester amniocentesis. A retrospective review of 470 patients referred for fetal reduction between 2007 and 2011 showed 3.1% of patients with normal-appearing fetuses undergoing first trimester fetal reduction had a fetal karyotypic abnormality, reflecting the fact that the infertility population is on average older than the general pregnant population.^104-106 They showed that CVS prior to fetal reduction adds significant information that can guide reduction decisions despite a normal fetal sonogram. The coupling of fetal genetic and structural assessment proximate to FR provides an optimal approach to maximizing the likelihood of a good outcome. A recent systematic review compared the rates of pregnancy loss following first-trimester CVS and midtrimester genetic amniocentesis in twins. The rate of pregnancy loss before 20 weeks was 2.75% after CVS in twins, and before 28 weeks it was 3.44%. For amniocentesis, the rates of pregnancy loss were 2.25% and 1.7%, before 20 and 28 weeks, respectively. Although there was no significant difference in pregnancy loss between any of these approaches, this study shows a higher risk of pregnancy loss before 24 weeks after amniocentesis than CVS.¹⁰⁷

Recently, Evans analyzed 25 years’ experience in fetal reduction, observed further improvement in outcomes of pregnancy reduction secondary to continued enhancements of ultrasound techniques, a smaller percentage of very high-order multiples that have worse outcomes with reduction, and further improvement in the experience of physicians over the last two decades.¹⁰⁸ In this analysis, a strong trend of increasing age at which women gave birth to their first child was noted. Their data show that pregnancy outcomes are vastly improved by reducing the number of fetuses in multifetal pregnancies, including the of reduction of twins to singletons.

Comment should be made on the ethical issues raised by this procedure, which range from duty of preservation of life all the way down to less complex issues, such as nomenclature. Berkowitz and Lynch suggested the term reduction of multifetal pregnancy, because this term illustrates the nature of the procedure and does not emphasize the “selective” aspect of the process.¹⁰⁹ The extent to which ethical issues are discussed with patients may be individualized, although common aspects that should be addressed include the preservation of the pregnancy and the duty not to destroy human life unless necessary to maintain that preservation. There are several treatises addressing these moral issues that should be consulted, written by leaders in the field: Evans¹⁰⁸ and Berkowitz and Lynch.¹⁰⁹ The consensus among these groups concludes that this procedure should be offered to patients as a modality to preserve a desired, potentially viable pregnancy and that the physician must support the management that results in the least harm and most good for both mother and fetus.

Treatment of Ectopic Pregnancy

The introduction of TVS, with a high-frequency high-resolution transducer, has greatly improved diagnostic accuracy of ectopic pregnancy, enabling both the sonographer and the clinician several different approaches to the problem that were not available previously. Due to improvement in ultrasound equipment as well as the availability of quantitative beta-human gonadotropin, the diagnosis of ectopic pregnancy can be made before the patient becomes symptomatic. Historically, the classic approach to treatment of ectopic tubal pregnancy has been salpingectomy. Conservative and nonsurgical approaches have gained popularity, usually involving systemic methotrexate, a chemotherapeutic agent.¹¹⁰ However, due to the high failure rate of systemic treatment in live, ectopic pregnancies, local treatment by injection of the ectopic pregnancies under ultrasound guidance may minimize the use of systemic chemotherapeutic agents. This approach may be more effective than methotrexate in more advanced ectopic gestations, particularly in live embryos.¹¹¹