Criteria for resumption of assisted reproductive technology intervention after fertility-sparing treatment of atypical endometrial hyperplasia and endometrial cancer

Abstract

<h3>Objectives:</h3> The purpose of this study was to identify criteria for safe resumption of assisted reproductive technologies (ART) in women diagnosed with atypical endometrial hyperplasia (AH) or endometrial cancer (EC) during infertility evaluation and managed with a fertility-sparing approach. <h3>Methods:</h3> A retrospective review was performed of women diagnosed with AH or EC during infertility workup at a multi-site academic tertiary care center between 1/1/2009 and 12/1/2018. The primary outcome was the number of benign endometrial samplings required by clinicians prior to resumption of ART. Secondary outcomes included recurrence rates, type and duration of treatment, and sampling modalities. Descriptive statistics were calculated. <h3>Results:</h3> In this pragmatic sample, 22 women were treated for AH (55%) and EC (45%). Two failed medical management and proceeded with hysterectomy and five were lost to follow-up or deferred fertility. Fifteen women (68%) achieved pathologic response and were cleared to resume ART. Mean age of this subset was 34.8 (±4.0) years with mean BMI 33.9 (±10.6) kg/m². Oncologic diagnosis was AH in 87% and EC in 13%. Uterine factor (60%) and ovulatory dysfunction (47%) were the two most common infertility diagnoses. Initial treatments included oral progestins (73%), levonorgestrel intrauterine devices (13%), or a combination of these two modalities (13%). Of these fifteen women, eleven (73%) were cleared for ART after one benign endometrial sampling ("one-sample") and four (27%) were cleared after two consecutive benign endometrial samplings performed three to four months apart ("two-sample"). In the one-sample group, D&C was used for sampling in 73% and EMB in 27%. The benign sampling that cleared the patient for ART was the first sampling performed during treatment in 64%. In the two-sample group, all samplings were performed using EMB. The average treatment duration was 6.3 vs 10.9 months in the one- vs two-sample subsets. One woman from each group underwent hysterectomy despite clearance. Four of the remaining ten women in the one-sample group (40%) experienced recurrence, compared to zero in the two-sample group. All recurrences were managed with resumption of progesterone-based treatment. One woman (25%) was cleared after one subsequent benign sampling and three (75%) after two. <h3>Conclusions:</h3> Most gynecologic oncologists cleared patients to proceed with ART after a single endometrial sampling demonstrated pathologic response following progesterone-based treatment for AH/EC. Short interval recurrence was common, but with potential for salvage response. Future work should utilize prospective analyses to evaluate for differences in recurrence rates based on various clearance criteria.