Anthony N. Imudia, MD

When selecting candidates for office hysteroscopy, individual patient self-assessment of pain tolerance and anxiety can help determine who would benefit most from an office-based procedure as opposed to an operating room procedure.1 Determinants of successful office-based hysteroscopy for polyp removal are polyp number, size, and location; patient characteristics such as body mass index (BMI) and other comorbidities; availability of an appropriate hysteroscopic system; and physician experience and comfort level with the procedure.Â Related:Â Endometrial polyps: In-office management

1. Ireland LD, Allen RH. Pain management for gynecologic procedures in the office. Obstet Gynecol Surv. 2016 Feb;71(2):89-98.

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When selecting candidates for office hysteroscopy, individual patient self-assessment of pain tolerance and anxiety can help determine who would benefit most from an office-based procedure

Four steps for successful office hysteroscopy

Endometrial polyps are common structural and epithelial abnormalities of the endometrium that are often encountered by gynecologists in office-based practice. These endometrial growths may be found incidentally in as many as 10% to 15% of asymptomatic women, and between 20% to 30% of women with abnormal uterine bleeding (AUB).

 Given their prevalence in patients presenting with AUB, polyps are considered as part of the FIGO classification for causes of abnormal uterine bleeding - PALM-COEIN.

 They may cause a variety of abnormal bleeding patterns, likely due to small muscular arteries found within the growths,

 but they can also be completely asymptomatic. Structural uterine pathologies often cause menstruation that is heavy or prolonged, albeit monthly,

 but polyps can also cause intermenstrual or postmenopausal bleeding.

 Endometrial polyps are usually benign but in 0.5% to 3% of cases, they are malignant.

Endometrial polyps are thought to impact fertility, and removal is recommended prior to initiating treatment, especially before proceeding with in vitro fertilization (IVF). Some proposed mechanisms by which polyps are thought to impact fertility include inhibition of implantation, endometrial inflammation, mechanical blockage of sperm from fertilization, or changes in endometrial receptivity.

 In the infertile population, prevalence of polyps is thought to be between 11% and 45%, which is higher than in the general population.

 Hysteroscopic removal of endometrial polyps found incidentally during fertility evaluation is recommended, with one study showing post-polypectomy implantation rates during IVF to be similar to those in women who do not have endometrial polyps.

True to their name, polyps may grow on a thin stalk from anywhere within the uterine cavity, or they may appear sessile: smooth and flat with a broad base. They typically measure up to about 3 cm.

 Histopathologically, polyps appear as cystic dilation of glands with mononuclear cells, often filled with mucous.

 They may contain vascular pedicles, connective tissue, and even glandular tissue.

 Their prevalence makes them an important pathology to study, so that proper diagnosis and treatment can be undertaken, with the gold standard being hysteroscopy.

Because AUB triggers further evaluation of potential etiologies, endometrial polyps are often diagnosed on ultrasound,

 as seen in Figure 1. The sonographic finding suggestive of an endometrial polyp is a bright, hyperechoic area visualized within the endometrium (Table 1).

 Using power doppler sonography may reveal a single-vessel pattern of blood flow to the polyp (sensitivity 81.2%, positive predictive value [PPV] 92.9%) compared to fibroids, which more often show an enhancing rim of vessels.

In case you missed it - Patient handout: Endometrial polyps

If further characterization is needed, office hysteroscopy is considered the gold standard for further evaluation,

 however, saline infusion sonography (SIS) is another excellent diagnostic study

 with a sensitivity of 93% and specificity of 81% in diagnosing endometrial polyps.

 Hysteroscopy and SIS are best performed during the proliferative phase of the menstrual cycle shortly after cessation of menses. Hysteroscopy allows for direct visualization of the polyps while SIS with a skillful operator can also provide specific details, such as where the polyp is attached and its size.

 If there is uncertainty about presence of a polyp on transvaginal ultrasound, SIS can be used as the next step for better visualization, with a PPV of 88.5%, compared to only 65.2% with ultrasound alone.

Because endometrial polyps are often the culprit in AUB, treatment is warranted to decrease a patient’s symptoms and confirm the diagnosis, especially because benign and malignant polyps cannot be reliably distinguished with imaging alone.

 Hysteroscopy with polypectomy is the treatment of choice, serving both as a diagnostic and therapeutic procedure.

 With office hysteroscopy now widely available, it is much easier to address polyps than in the past.

Narrow-caliber hysteroscopes with diameters ranging from 2 to 3 mm and flexible hysteroscopes allow for these office procedures to be performed with minimal pain for patients.

 Office hysteroscopy can be used for both diagnosis and treatment and it has the ability to immediately confirm successful polyp removal; therefore, it serves as the gold standard for management of endometrial polyps (Figures 2a and 2b).

 When a polyp is visualized during office hysteroscopy, directed removal or biopsy should be performed, even if it is suspected to be benign.

Office hysteroscopy as opposed to hysteroscopy performed in the operating room is the preferred method for management of endometrial polyps for a variety of reasons.

 Benefits for patients include reduced cost of medical services and time off from work, greater convenience, and more flexibility in scheduling the surgery.

A recent study evaluating the effectiveness of office hysteroscopic removal of endometrial polyps showed that office hysteroscopy was successful in removing endometrial polyps 95.7% of the time, and while hysteroscopy in the operating room resulted in fewer residual polyps (98.1% successful), office hysteroscopy is still preferred due to the aforementioned benefits.

 Because of the convenience and cost savings associated with office hysteroscopy, many women are amenable to it, but special consideration has to be paid to patients’ pain and comfort during the procedure. Patients’ reported pain has been shown to be reasonable and tolerable, with an average reported pain score of 5 on the visual analogue scale, the classic pain scale ranging from 0 to 10.

 When selecting candidates for office hysteroscopy, individual patient self-assessment of pain tolerance and anxiety can help determine who would benefit most from an office-based procedure as opposed to an operating room procedure (Table 2).

 Determinants of successful office-based hysteroscopy for polyp removal are polyp number, size, and location; patient characteristics such as body mass index (BMI) and other comorbidities; availability of an appropriate hysteroscopic system; and physician experience and comfort level with the procedure. 

Traditional mechanical instruments such as polyp scissors or grasping forceps introduced down the operative channel of a hysteroscopy as well as more modern tissue-extracting devices are both excellent ways of resecting polyps under direct visualization.

 The appeal of modern tissue removal systems such as TRUCLEAR, MyoSure, and the Integrated Bigatti Shaver is that they allow for mechanical cutting of tissue and suction extraction, ensuring full removal of the polyp and easy collection of tissue for further histopathologic evaluation and diagnosis.

 Blind, sharp dilation and curettage previously may have been performed for polypectomy, but it is no longer recommended because of its lack of targeted effect.

Treatment of all visible endometrial polyps is recommended, but some patients decline removal, perhaps because they are asymptomatic. In those cases, data on the natural history of polyps may help guide clinical management. One retrospective study estimated that 6.3% of polyps may spontaneously resolve after 6 months in premenopausal women, however, 15% of these patients may develop AUB in that same time period.

 Hysteroscopic polypectomy should be recommended and advocated, especially in patients with higher risk factors for malignant transformation. 

Although in polyps, risk of underlying malignancy is not very high, careful clinical evaluation to rule it out is critical.

 In postmenopausal women who have AUB, risk of finding precancerous pathology in polyps may be as high as 6%.

 Risk factors that increase concerns about cancer include: postmenopausal status (OR 8.274)

, obesity, AUB, polyp size, and even diabetes and hypertension.

One study suggests that BMI > 32 or endometrial thickness > 10 mm increases risk of hyperplasia or malignancy.

 Use of tamoxifen, a common maintenance medication taken by women with a history of estrogen receptor-positive breast cancer or who are at risk of breast cancer, has been shown to increase risk not only of endometrial polyps, but of endometrial hyperplasia and cancer. It is thought that while tamoxifen has an anti-estrogenic effect on breast tissue, it may selectively promote proliferation in the endometrium (Table 3).

Endometrial polyps, whether found on ultrasound during a workup for AUB or suspected to be the etiology of a patient’s infertility, are commonly encountered and easily managed with office-based hysteroscopic procedures. Given the underlying risk of malignancy in endometrial polyps, which may be as low as 0.5% to 3% in all women diagnosed with polyps

 or up to 6% in postmenopausal women presenting with bleeding,

 removal is strongly recommended with hysteroscopic polypectomy for eventual histopathologic diagnosis.

The authors report no potential conflicts of interest with regard to this article.

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Vroom AJ, Timmermans A, Bongers MY. Diagnostic accuracy of saline contrast sonohysterography to detect endometrial polyps in women with postmenopausal bleeding: a systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2019 Jan 28.

Articles

Practical tips on how to spot these common growths on ultrasound and how to remove them.

Endometrial polyps: In-office management

Adenomyosis is a common gynecologic disorder, yet its etiology and association with infertility remains unclear. It is a benign disorder previously associated with multiparity. Recently, however, an association with infertility has emerged. Adenomyosis can be asymptomatic or present with menorrhagia, dysmenorrhea, and metrorrhagia with these symptoms usually occurring in patients aged 35 to 50. 

Approximately 20% of cases of adenomyosis involve women younger than 40 and 80% are aged 40 to 50. On histological analysis, adenomyosis is defined by ectopic location of endometrial and stromal tissue distal to the endometrial-myometrial junction with associated myometrial smooth muscle hypertrophy.

Histologic diagnostic criteria for adenomyosis have been debated and inconsistently applied, making studies unreliable and often incompatible. 

The most accepted hypothesis for the etiology of adenomyosis stems from the invagination of the endometrial basalis layer into the myometrium.

Adenomyosis can have a diffuse, haphazard distribution or more focal regions known as adenomyomas. Women with the condition, therefore, present with enlarged, boggy uteri. 

Traditionally, the diagnosis was made by means of histopathologic examination, usually on a hysterectomy specimen as the treatment of choice for the disease was hysterectomy.

With the evolution of magnetic resonance imaging (MRI) and high-quality transvaginal ultrasound (TVS), today the diagnosis can be made with a level of accuracy of 80% to 90% without the need for excisional surgery (Figures 1a and 1b).

Criteria used to define adenomyosis on ultrasound include focal areas with diffuse hyperechogeneity and loss of a normal endo-myometrial interface; increased or decreased areas of echogenicity; or cystic structures within myometrium with increased color Doppler flow. On MRI, assessment of the thickness of the junctional zone (the subendometrial myometrium) is the mainstay of diagnosis. The consensus for diagnosis of adenomyosis is when the junctional zone is greater than 12 mm but the disorder can be suspected when the thickness is between 8 and 12 mm.

The advantage of MRI over TVS is that MRI has a greater specificity and can differentiate adenomyomata from leiomyoma.

When noninvasive diagnosis with MRI and TVS imaging became available, the role of adenomyosis in infertility and early pregnancy was better recognized.

How is the condition linked with infertility?

Most evidence that links adenomyosis to infertility is limited to case reports and small case series. There is also the potential for confounding in these studies as adenomyosis commonly coexists along with other pathologic processes linked to infertility, such as endometriosis, polyps, or leiomyoma.

There is a significant association between pelvic endometriosis and adenomyosis, with estimates indicating that it occurs in 54% to 90% of cases.

Because endometriosis is well-known to cause infertility, there is concern that findings of infertility were due to concurrent endometriosis rather than adenomyosis.

However, a study in baboons showed a strong association between histological adenomyosis and lifelong infertility (20-fold increased odds) even in cases where coexisting endometriosis was excluded.

In a study of women who received embryos created through oocyte donation rates of miscarriage were significantly higher in those who had adenomyosis alone versus those with co-existing endometriosis or controls.

A recent meta-analysis concluded that adenomyosis has a detrimental effect on clinical outcomes of in vitro fertilization (IVF). In women undergoing IVF, rates of implantation, clinical pregnancy per cycle, clinical pregnancy per embryo transfer, ongoing pregnancy, and live birth among women with adenomyosis were significantly lower than in those without adenomyosis.

The miscarriage rate in women with adenomyosis was also higher than in those without adenomyosis.

One of the confounding variables in this study was age, given that women with adenomyosis were older; however, even after controlling for these confounders using regression analysis, the significant difference still existed.

Proposed mechanisms of infertility in patients with adenomyosis focus on derangements of three putative pathways: uterotubal transport, endometrial receptivity, and implantation.

In patients with adenomyosis, uterotubal transport is impaired due to intrauterine anatomical distortion that blocks the tubal ostia and potentially blocks sperm migration and embryo transport.

Uterine hyperperistalsis has been seen on ultrasound in patients with adenomyosis due to destruction of normal myometrial architecture.

These abnormal myometrial contraction waves lead to abnormal sperm transport through the uterine cavity and may also lead to increased intrauterine pressure.

Endometrial receptivity and function becomes altered via increased production of estrogens from aromatization of androgens and altered estrogen receptor/progesterone receptor expression.

The inflammatory response in women with adenomyosis has also been shown to be increased.

Patients with severe adenomyosis in whom implantation failed were found to have higher density of macrophages.

This increased macrophage density subsequently increases intrauterine inflammatory response and release of reactive oxygen species that are thought to be embryotoxic.

Lastly, impaired implantation results from a lack of adequate expression of adhesion molecules, reduced expression of implantation markers, and altered function of the gene for embryonic development (HOXA10).

In contrast to women with endometriosis, adenomyosis has not yet been shown to have an adverse influence on oocyte function or folliculogenesis.

In patients with endometriosis, levels of activated macrophages, prostaglandins, interleukin (IL)-1Î², tumor necrosis factor (TNF)Î±, and proteases were increased in peritoneal fluid and their high concentrations may adversely affect oocyte function.

As of yet, there no association has been found between adenomyosis and oocyte quality or function. 

Possible treatments for adenomyosis in infertility

Based on limited available evidence, patients with adenomyosis could be treated with medical and/or surgical therapies to improve pregnancy and live birth outcomes. Treatment with gonadotrophin-releasing hormone agonist (GnRH-a) serves to down-regulate the pituitary, exert an anti-proliferative effect, promote apoptosis, and reduce the anti-inflammatory and angiogenesis effect.

Multiple case reports show conception and live birth in women with infertility and adenomyosis after pretreatment with GnRH-a for 3 to 5 months.

In other retrospective studies, pretreatment with GnRH-a prior to fresh- or frozen-embryo transfer appears to increase pregnancy rates.

Further prospective studies with larger sample size are needed to validate these findings.

In retrospective studies, conservative surgery or combination surgery with GnRH-a has shown to be more effective in controlling symptoms and also in increasing pregnancy and live birth rates when compared with GnRH-a alone in patients with extensive adenomyosis.

In case reports and case series, multiple methods of fertility-sparing surgery for adenomyosis have been performed, with subsequent pregnancies. These techniques include classical adenomyomectomy, H-incision, triple-flap method, and laparoscopic cytoreductive surgery.

No evidence as of yet points to superiority of one technique over another (Video). Surgical management of adenomyomas and adenomyosis can present an operative challenge, especially compared with myomectomy.

Adenomyomas are less distinct given absence of well-defined borders and given protrusion into the myometrium. During dissection, the plane is identified mainly by recognizing healthy myometrium rather than simple enucleation as in myomectomies. This can lead to increased risk of intraoperative bleeding and weakening of the myometrium, which can increase risk of uterine rupture or abnormal placentation in future pregnancies. Uterine-preserving surgeries have shown benefit for women who have previously experienced IVF treatment failures, especially patients ≤ 39 years old.

A large prospective study showed that combination conservative surgery and medical treatment with GnRH-a for patients with severe symptomatic adenomyoma lowers symptom relapse rates and yields a trend toward improved reproductive outcomes.

Therefore, for patients with presumed severe adenomyosis who want to retain fertility, surgical cytoreduction and GnRH-a combined may be desirable.

Other methods of fertility-sparing treatment for adenomyosis have recently generated interest. High-intensity focused ultrasound ablation (HIFU) has been used for leiomyoma and is now being used for patients with adenomyosis who want fertility.

HIFU is a noninvasive thermal ablation technique in which high-intensity ultrasound energy is focused on a small focal region to increase tissue temperature sufficient to cause irreparable cell damage in the target at a certain depth within the body.

Selection criteria for using HIFU ablation for adenomyosis vary depending on the center, but very strict selection criteria are required to improve efficacy and decrease risk of thermal injury.

Patients typically must be age 18 or older, premenopausal, have no history of pelvic inflammatory disease or severe pelvic endometriosis, and have symptomatic adenomyosis with junctional zone thickness > 3 cm for diffuse adenomyosis or a lesion diameter between 3 and 10 cm for focal adenomyosis.

A recent retrospective study showed high rates of conception and live birth in HIFU-treated patients with adenomyosis, suggesting that it is a promising noninvasive fertility-sparing treatment option.

In another study, pregnancies after HIFU resulted in 2 miscarriages and delivery of 4 healthy babies. One delivery was complicated by a major placenta previa and hemorrhage.

Although adenomyosis is a common gynecologic disorder, its role in infertility is unclear. It previously was believed to be a symptomatic disease in older women but it is now being seen in an asymptomatic and younger population undergoing evaluation for infertility. Limited studies have found an association between adenomyosis and poor reproductive outcomes. However, other coexisting pathologies, such as endometriosis, may be 
significant confounders. 

Proposed mechanisms of adenomyosis and infertility point toward derangements in uterotubal transport, endometrial receptivity, and intrauterine inflammation impairing implantation. No association with oocyte function has yet to be identified. Women with severe adenomyosis and in whom IVF previously failed who want fertility can be treated with GnRH-a and/or surgical resection. The strategy has produced promising outcomes in pregnancy and live birth along with symptom improvement. While definitive treatment with hysterectomy was previously the gold standard for adenomyosis, emerging conservative surgical interventions are gaining momentum. Alternatively, HIFU thermal ablation has been presented as another potential noninvasive option for fertility preservation. Large prospective trials are needed to confirm the clinical efficacy of these new fertility-sparing treatment modalities and to better understand their risk and safety profiles.  

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Comorbidities such as endometriosis can confound the picture in patients with adenomyosis, a condition that may lead to poor IVF outcomes.

Adenomyosis and its impact on fertility

COMMITTEE ON PRACTICE BULLETINS-GYNECOLOGY 

Practice Bulletin #193: Tubal Ectopic Pregnancy. American College of Obstetricians and Gynecologists. Obstet Gynecol 2018; 131:e91–103. Full text of Practice Bulletin #193 is available to ACOG members at 

http://www.acog.org/Resources-and-Publications/Practice-Bulletins/Committee-on-Practice-Bulletins-Gynecology/Tubal-Ectopic-Pregnancy


Ectopic pregnancy is defined as a pregnancy that occurs outside of the uterine cavity. The most common site of ectopic pregnancy is the fallopian tube. Most cases of tubal ectopic pregnancy that are detected early can be treated successfully either with minimally invasive surgery or with medical management using methotrexate. However, tubal ectopic pregnancy in an unstable patient is a medical emergency that requires prompt surgical intervention. The purpose of this document is to review information on the current understanding of tubal ectopic pregnancy and to provide guidelines for timely diagnosis and management that are consistent with the best available scientific evidence.

The interim update of the ACOG Practice Bulletin on Tubal Ectopic Pregnancy

provides a review of information on the current understanding of tubal ectopic pregnancy and offers comprehensive guidelines for timely diagnosis and management options. Compared to the previous publication, the current bulletin provides comprehensive management options for ectopic pregnancy by incorporating new guidance on pregnancy of unknown location and on surgical management of ectopic pregnancy, as well as revised guidance on use of hCG levels for diagnosis.

ACOG recommends not using serum hCG values alone to diagnose an ectopic pregnancy and that they be correlated with the patient’s history, symptoms, and ultrasound findings. If the concept of the hCG discriminatory level is to be used as a diagnostic aid in women at risk of ectopic pregnancy, the value should be conservatively high (eg, as high as 3500 mIU/mL) to avoid the potential for misdiagnosis and possible interruption of an intrauterine pregnancy that a woman hopes to continue.

 Overall, in this Practice Bulletin, ACOG is advocating use of a comprehensive approach and more conservative guidelines to avoid the potential for misdiagnosis, possible interruption of an intrauterine pregnancy or unnecessary medical treatment that could lead to teratogenicity in surviving pregnancies. 

While this Practice Bulletin specifically and clearly emphasizes the importance of discussion of risks versus benefits with patients in determining treatment method, there are also other logistical issues that may arise and affect decisions about treatment. Most ectopic pregnancies are managed in the outpatient setting and with minimal variation in the team involved. However, depending on individual hospital and office setup, if different laboratories and/or hCG assays are used for trending hCG levels, it is possible that these inter-assay/laboratory variabilities in hCG values could significantly affect the clinical decision-making process. In addition, the issue concerning insured and uninsured patients deserves special consideration. It has been shown that there exists substantial insurance-related variation in treatment.

Uninsured women and Medicaid recipients were less likely to receive treatment with methotrexate and were less likely to undergo salpingostomy. In the same article

, the authors also discuss the disparity in that black and Hispanic women were less likely to receive tube-conserving surgery.

Some of the recent changes that have facilitated a more conservative approach in treatment of tubal ectopic pregnancy include wider availability of methotrexate, use of early sonography and management of pregnancy of unknown location with uterine aspiration to distinguish between early intrauterine pregnancy loss and ectopic pregnancy. These factors are leading to earlier diagnosis of the disease and subsequent growth in medical management in the outpatient setting. When indicated, surgical management with minimally invasive surgical techniques is preferable to laparotomy. It is important to note that ACOG recommends that the decision to perform a salpingostomy or salpingectomy for treatment of ectopic pregnancy be guided by the patient’s clinical status, her desire for future fertility, and the extent of damage to the fallopian tube. 

There has been a decline in rates of salpingostomy compared to salpingectomy.

Although cumulative rates of intrauterine pregnancy and recurrence of ectopic pregnancy in patients who had salpingostomy versus salpingectomy are not statistically significantly different in randomized controlled trials, the move towards salpingectomy is increasing.

This is likely due to a combination of many factors, including patient history, intraoperative findings, physician preference and comfort with the procedure as well as increased availability of in vitro fertilization. As the number of salpingostomies being performed nationwide continues to decrease,

it is possible that over time, younger physicians will become unskilled in performing the procedure and the frequency could drop even more drastically. Furthermore, recent publications favoring opportunistic salpingectomy for risk reduction of ovarian cancer may be leading physicians towards complete tubal removal whenever feasible.

The author reports no potential conflicts of interest with regard to this article.

Tubal ectopic pregnancy. ACOG Practice Bulletin No. 193. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2018;131:e91-103.

Hsu JY, Chen L, Gumer AR, Tergas AI, et al. Disparities in management of ectopic pregnancy. Am J Obstet Gynecol. 2017 July;217(1):49.e1-49.

Mikhail E, Salemi JL, Schickler R, Salihu HM, Plosker S, Imudia AN. National rates, trends and determinants of inpatient surgical management of tubal ectopic pregnancy in the United States, 1998-2011. J Obstet Gynaecol Res. 2018 Apr;44(4):730-738.

Yoon SH, Kim SN, Shim SH, Kang SB, Lee SJ. Bilateral salpingectomy can reduce the risk of ovarian cancer in the general population: A meta-analysis. Eur J Cancer. 2016 Mar;55:38-46.

Expert commentary on ACOG's interim update, which focuses on a comprehensive approach and more conservative guidelines to avoid the potential for misdiagnosis. 

Anthony N. Imudia, MD

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