Clinical Advantages of Performing Concomitant Office Hysteroscopy and Endometrial Biopsy in Patients With Oligomenorrhea Seeking Infertility Treatment as Compared to Only Endometrial Biopsy: A Prospective Randomized Study

Patients with subfertility due to hormonal disorders are at increased risk of endometrial cancer and hyperplasia . Such conditions are associated with chronic anovulation, obesity and/or hyperinsulinemia. Presumably, the mechanism relates to constant, unrelenting estrogen stimulation of the endometrium, predisposing to abnormal patterns of growth. Hence, patients with long standing anovulation presenting for infertility evaluation, are often subjected to endometrial biopsy to rule out any underlying hyperplasia or malignancy.

The polycystic ovary syndrome (PCOS) is the most obvious and common condition associated with chronic anovulation. It is characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphologic features. Based on National Institutes of Health (i.e. hyperandrogenism plus ovulatory dysfunction), "classic" polycystic ovary syndrome affects 10% of women of reproductive age but the prevalence may be twice under the broader Rotterdam criteria . Women with PCOS are at increased risk of infertility, endometrial hyperplasia and cancer. The risk of endometrial cancer in a woman with PCOS is reported to be 2.7 times higher than someone without this syndrome. Other uncommon conditions associated with chronic anovulation are Cushing's syndrome, congenital adrenal hyperplasia secondary to 21 hydroxylase deficiency, thyroid or liver disorder leading to decreased clearance of estrogen from the body. Similarly, obese postmenopausal women are also at increased risk for developing endometrial cancer.

In these patients, elevated plasma levels of androgen precursors increase estrogen level through aromatization of androgens in adipose tissue. In addition, it has been seen that non cycling patients with grossly increased endometrial thickness (greater than 12 mm) are also at high risk of endometrial hyperplasia. So these are the indications, which warrants patients to undergo endometrial biopsy. Literature shows that the prevalence of minor intrauterine abnormalities identified at hysteroscopy in cases with a normal transvaginal sonography (TVS) can be as high as 20-40%. Similarly, the prevalence of unsuspected uterine cavity abnormalities, diagnosed in an unselected group of patients undergoing IVF can be 11%. In this study, they identified endometrial polyps in 6% women, submucous myomas in 1%, intrauterine adhesions (2%), and septa (2%) . Another study also reports 16% intracavitary lesion in patients with infertility. It has been seen that in an IVF population, obesity (BMI >30) is also an independent risk factor for developing endometrial polyps. The prevalence of polyps in patients with BMI > 30 is 52% as compared to 15% among patients with BMI <30. Similarly, PCOS patients also show a higher incidence of endometrial polyp (29%) diagnosed by hysteroscopy as compared to the nonPCOS population and the presence of 2 or more such polyps is associated with significant premalignant or malignant condition. So, missing the diagnosis of polyps in PCOS patients renders them to higher risk of developing malignancy in future. With this background, an important clinical question is if it is clinically justified to combine office hysteroscopy and endometrial biopsy as part of the comprehensive evaluation of these patients? It is possible that prompt diagnosis and treatment of these unsuspected uterine abnormalities could optimize the condition of the uterine environment and thereby the outcome of treatment.

In spite of all the advantages office hysteroscopy offers, one of the reasons for avoiding office hysteroscopy has been the apprehension that adding office hysteroscopy will lead to higher pain score. But based on our literature review we propose that adding flexible office hysteroscopy to endometrial biopsy will not lead to any increase in pain score. In routine practice, endometrial biopsy is usually performed with "Pipelle" and is a simple office procedure. It is an excellent tool for evaluating the histopathology of the endometrium. The mean pain score during endometrial biopsy is 3 in a VAS scale of 1-10 with only 6.7% patients reporting severe pain . In a more recent study, the pain score during endometrial biopsy has been reported to be 6.2, which is higher than the previous reports. Similarly, office hysteroscopy is also a simple procedure with high patient acceptability and safety. The pain score reported during office hysteroscopy using flexible scope range from 2.3 -3. During traditional hysteroscopy where speculum and tenaculum is used, the pain score has been reported to be as high as 5.3. In fact, a comparative study of endometrial biopsy and office hysteroscopy showed that the pain score is higher during endometrial biopsy (5.1) as compared to diagnostic hysteroscopy (2.7). Hence, it seems very reasonable to add office hysteroscopy to endometrial biopsy for patients undergoing endometrial evaluation. This combined approach will have better diagnostic yield without increasing the pain perception.