The fertility-sparing treatment in patients with endometrial atypical hyperplasia and early endometrial cancer: A debated therapeutic option

Abstract

Fertility-sparing treatment may represent a realist option for accurately selected young patients with endometrial atypical hyperplasia or well differentiated, early endometrial cancer. Oral progestins, and especially medroxyprogesterone acetate (MPA) and megestrol acetate with different doses and schedules, represent the most commonly used hormone agents in this clinical setting. Approximately three fourths of the women achieve a histologically documented complete response, with an mean response time of 12 weeks, but about one third of these subsequently developed a recurrence after a mean time of 20 months. The expression of receptor for progesterone receptor (PR), PTEN gene, DNA mismatch repair gene MLH1 and phospho-AKT on tissue specimens may be useful for selecting patients fit for a conservative management. Several successful pregnancies have occurred after a fertility-sparing treatment of endometrial atypical hyperplasia or endometrial cancer, more frequently with assisted reproductive technologies. The implementation of in vitro fertilisation techniques not only increases the chance of conception, but it may also decrease the interval to conception. The opportunity of a demolitive surgery after delivery or after childbearing being no longer required is a still debated issue. Large multicenter trials are strongly warranted to better define the selection criteria for a conservative treatment, endocrine regimen of choice, the optimal dosing, the duration of treatment and follow-up protocols. In any case, the patient should be accurately informed about the relatively high recurrence rates after complete response to hormone treatment and expectations for pregnancy.

Fertility-sparing treatment in a young patient with complex atypical hyperplasia of the endometrium

“…oestrogen and progesterone receptors or phosphatase and tensin homolog gene expression, may serve as predictors to treatment response, but prospective data are lacking. 1,9 Fertility-sparing management of CAH aims to completely reverse the pathology to normal endometrial function and prevent progression to endometrial cancer. Progesterone counterbalances the mitogenic effects of oestrogen and induces secretory differentiation of the endometrium.…”

“…11 These relapses can be successfully re-treated, but require adequate followup and resampling. 1 An alternative to progestin therapy is gonadotropin-releasing hormone agonist treatment, which has a success rate of 85%. Systemic side-effects, e.g.…”

“…It affects postmenopausal women predominantly, but 25% of cases occur in premenopausal women, 5% of whom are younger than 40 years of age. 1 Complex atypical hyperplasia (CAH) of the endometrium is a precursor to endometrial carcinoma, with a progression rate to carcinoma of 10%. Women with stage I, grade 1 endometrial carcinoma treated by hysterectomy, have a 99.2% five-year survival.…”

Fertility outcomes in infertile women with complex hyperplasia or complex atypical hyperplasia who received progestin therapy and in vitro fertilization

“…Based on our analysis of the outcomes of IVF, including fresh and frozen cycles, the cumulative live birth rate did not differ significantly between the two groups, including 3 patients in the CAH group and 16 patients in the CH group. MPA is the most commonly used agent to treat CAH and CH, but megestrol acetate and levonorgestrelreleasing intrauterine system have both been reported to be effective (Gadducci et al, 2009;Orbo et al, 2014).…”

“…Introduction of IVF soon after achieving tumor disappearance by MPA would therefore be beneficial for patients with disease recurrence, thin endometrium, or a higher age of pregnancy permission (Inoue et al, 2016). The implementation of IVF techniques not only increases the chance of conception, but it may also decrease the interval to conception (Gadducci et al, 2009). A multivariate analysis suggested that patients who accepted assisted reproductive technology (ART) were more likely to become pregnant (Zhou et al, 2015).…”