Restoration of normal endometrium

Medical therapy

In order to restore basal endometrium and rebuild the normal endometrial layer inside the uterine cavity many authors have proposed hormonal treatment.

Many different treatments have been suggested and there is no shared consensus about the time of the administration (preoperative and/or postoperative) and the type of regimen (oestradiol or combined oestradiol and progesterone). The general idea is to encourage fast growth of any residual endometrium immediately after surgery with the dual purpose of preventing new scar formation and restoring a normal uterine environment. It is supposed that this goal can only be achieved with supraphysiological hormonal levels.

Myers et al. proposed a prolonged preoperative and a postoperative treatment with estrogens in 12 subjects with severe amenorrhea. All women resumed a normal menstrual pattern and six of them become pregnant.

March et al. suggested a treatment with micronized oestradiol, 2 mg twice daily for 30–60 days and medroxyprogesterone acetate 10 mg per day at last 5 days of oestrogen therapy.

Other authors prescribed estradiolvalerate 4 mg per day for 4 weeks and medroxyprogesterone acetate, 10 mg per day at last two week of treatment. There is evidence that oestrogen-progestin treatment after curettage for post-partum haemorrhage or incomplete abortion increases endometrial thickness. Specifically, 60 women were randomized to receive estradiolvalerate 2 mg for 21 days and norgestrel 0.5 mg in the last 10 days of oestrogen treatment. 21–26 days after curettage all women underwent a transvaginal ultrasound. The endometrial thickness, width and volume were reported significantly elevated in the treated group.

The use of sildenafil citrate intravaginally was documented as possible pharmacological treatment to restore endometrial thickness. This drug is a type 5 specific phosphodiesterase inhibitor that enhances vasodilator effect of nitric oxide (NO) whose synthase isoforms were also found in the uterus. In a prospective observational study, sildenafil citrate improved endometrial thickness in 92% of cases who presented thin endometrium (endometrial thickness <8 mm). Other encouraging results came from IVF where the combination of oestradiol and sildenafil citrate improved endometrial blood flow and endometrial thickness in 4 women with prior failed assisted reproductive cycles due to poor endometrial response. There are only two case reports concerning the use of sildenafil in AS. Endometrial thickness significantly improved with treatment, and both women become pregnant after the first treatment cycle.

Stem cells and endometrial regeneration

Endometrial tissue had an intrinsic capacity of regeneration. Endometrial regeneration normally occurs after menstruation and delivery. There is substantial evidence in literature that adult endometrial tissue contains epithelial progenitor cells and mesenchymal/stromal (MSC) cells. These cells could be the target of a specific therapy in order to regenerate the endometrial tissue in cases of dysfunctional or atrophic endometrium. Recently, a case report of a severe AS treated with autologous stem cells isolated from the women’s own bone marrow has been described [83]. The woman had a history of infertility and hypomenorrhea following a D&C in 2005. She was treated hysteroscopically for severe intrauterine adhesions, and a T-shaped IUD was placed inside the uterus for six months. During this time, she also received therapy with combined oestrogen and progesterone (ethinylestradiol 0.05 mg from fifth to 25th day of the cycle and medroxyprogesterone acetate 10 mg from 20th to 25th day). Finally, after failure of hormonal therapy in restoring endometrium, endometrial stem cells were implanted inside the uterus after curettage on the second day of menstrual cycle. A clinical pregnancy was obtained after a heterologous embryo transfer. These pioneering discoveries could open a new scenario in the management of AS, although more evidences are mandatory.

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