Conservative Management of Atypical Endometrial Hyperplasia and Early Endometrial Cancer in Childbearing Age Women

Abstract

Total hysterectomy and bilateral adnexectomy is the standard treatment for atypical endometrial hyperplasia and early-stage endometrial cancer. However, the recommended surgical treatment precludes future pregnancy when these conditions are diagnosed in women in their fertile age. In these patients, fertility-sparing treatment may be feasible if the desire for childbearing is consistent and specific conditions are present. This review summarizes the available evidence on fertility-sparing management for atypical endometrial hyperplasia and early-stage endometrial cancer. Historically, oral progestins have been the mainstay of conservative management for atypical endometrial hyperplasia and stage IA endometrioid endometrial cancer with no myometrial invasion, although there is no consensus on dosage and treatment length. Intrauterine progestin therapy has proved a valid alternative option when oral progestins are not tolerated. GnRH analogs, metformin, and hysteroscopic resection in combination with progestins appear to increase the overall efficacy of the treatment. After a complete response, conception is recommended; alternatively, maintenance therapy with strict follow-up has been proposed to decrease recurrence. The risk of disease progression is not negligible, and clinicians should not overlook the risk of hereditary forms of the disease in young patients, in particular, Lynch syndrome. Hysterectomy is performed once the desire for childbearing desire has been established. The conservative management of atypical endometrial hyperplasia and early-stage endometrial cancer is feasible, provided a strong desire for childbearing and permitting clinical–pathological conditions. However, patients must be aware of the need for a strict follow-up and the risk of progression with a possible consequent worsening of the prognosis. More homogenous and well-designed studies are necessary to standardize and identify the best treatment and follow-up protocols.

Progestin-primed ovarian stimulation for fertility preservation in women with cancer: A comparative study

“…The median [IQR] number of scans was 3 [3][4] and 3 [2][3] in the first and second period, respectively (p<0.001). The median [IQR] number of injections (including those needed for gonadotropins, GnRH antagonists, GnRH agonists, and hCG) was 12 [10][11][12][13][14] and 13 [12][13][14][15] in the first and second period, respectively (p = 0.01). The total costs of the drugs used for ovarian hyperstimulation (including those needed for gonadotropins, GnRH antagonists, GnRH agonists, hCG, and MPA) in the two study periods were 940 € [IQR: 774-1,096 €] and 520 € [IQR: 434-564 €], respectively (p<0.001).…”

“…Noteworthy, even women with early endometrial cancer are now considered for conservative management. They are treated hormonally to achieve transient cancer regression, thus allowing pregnancy seeking and postponing hysterectomy after delivery [7][8][9][10].…”

Conservative treatment of endometrial cancer in women of reproductive age (Review)

“…A meta-analysis, combining data from six studies, showed a satisfactory pregnancy and low recurrence rate ( 9 , 14 ). After one year of LNG-IUD combined with GnRH analogs, up to 57% of EC and 95% of EIN achieved a complete response, with a pregnancy rate of 85% and a recurrence rate of 20% ( 41 ).…”

“…The latest 2022 ESGO guidelines highlight the utmost importance of hysteroscopic biopsy for diagnosis and resectoscopic resection in order to maximize progestin therapy ( 41 ).…”

Fertility-Sparing Strategies for Early-Stage Endometrial Cancer: Stepping towards Precision Medicine Based on the Molecular Fingerprint

“…This is of paramount importance, as the clinical pregnancy rate in women who undergo fertilitysparing treatments is about 35-60% with hormonal treatment alone, and approximately 70% after combined treatment based on hysteroscopic and hormonal therapy [21]; moreover, hysteroscopic resection followed by progestogen use is associated with a higher complete response rate, higher live birth rate, and lower recurrence rate than using oral progestogens alone [22]. The new potential available options, using the molecular classification, may also be applied in order to stratify women with atypical endometrial hyperplasia, a condition which can progress to endometrial cancer [23], as summarized in the review by Contreras et al [24]. In addition, the molecular classification may also pave the way for increasing treatment in stage I G2 endometrioid endometrial cancer [25].…”