All other patients will have good control of their disease with medical treatment (1).  We would like to make it clear that surgery does not cure endometriosis, its benefit is very limited, 10% of patients have recurrence of endometriosis within a year or persistent symptoms. Furthermore, surgery for endometriomas should be considered with great caution because of its negative impact on subsequent fertility.

What are the goals of medical treatment for endometriosis?

Medical treatment will not provide a definitive cure, but it will establish a stable hormonal environment associated with the inhibition of ovulation and/or amenorrhoea/oligomenorrhoea. Its objectives are the following: 

• Symptom control.
• Prevent progression of the disease.
• Preventing relapses or recurrences.
• Preserving fertility or at least not reducing it.

What medical treatment is the most appropriate for endometriosis?

The famacological treatment (2) of endometriosis is placed in the context of a long-term therapeutic strategy.

Monophasic combined oestrogen-progestagen contraceptives in a continuous regimen (without rest) are considered the first-choice therapy, they are safe, effective and well tolerated, although when symptoms appear such as: mastalgia (breast pain), spotting (small irregular bleeding), swelling sensation… it is recommended to suspend them for 4 days, and then restart, this allows good adherence to the therapy and adequate compliance. Diu medicated with levonorgestel is also considered first-line medication and presents less thrombotic risk. In cases of continuous spotting, it can be overlapped for three months with oral gestagens.

Oral Dienogest is considered second-line therapy, it is an excellent drug in the management of endometriosis, it is not contraceptive and is now funded. It is effective especially when it induces amenorrhoea (absence of menstruation), it has an anti-androgenic effect which is an advantage over other gestagens which have androgenic effects. The latter can lead to changes in female body contours, decreased breast size and increased body hair. In the future, Dienogest may be included as a drug of first choice.

In patients at thrombotic risk, obese, smokers, etc., the use of gestagens (Diu levonorgestrel, Dienogest) is preferable to combined contraceptives. Both gestagens (norethisterone acetate, desogestrel, drosperinone, medroxyprogesterone acetate, etc.) and GnRH analogues are considered second-line therapy only when first-line treatment fails or is not well tolerated.

Should asymptomatic women be treated?

In less common cases where endometriosis patients are asymptomatic, therapy may be prescribed to prevent progression or to closely monitor the progression of endometriosis.

Therapy of choice in patients with adenomyosis

In patients with adenomyosis, therapy can be carried out with either desogestrel gestagens (mini-pill), Diu medicated with levonorgestrel or the oestrogen-progestagen pill in a continuous regimen (3). After two years, practically total regression of the radiological images characteristic of this condition was observed. 

The future

There are other drugs currently under study such as progesterone receptor modulators, GnRh antagonists, immunomodulators, etc. that may end up forming part of the therapeutic arsenal to treat endometriosis.

Nutritional supplements and antioxidants (4) are recommended for use as a complementary treatment, not as a first-line treatment. Their use is based on the fact that endometriotic lesions have high levels of oxidation, which promotes angiogenesis (development of new vascularisation) and the progression of the lesion.

A wide range of supplements and antioxidants are recommended for the complementary treatment of endometriosis: turmeric, green tea, resveratrol, myrrh, N-acetyl cysteine, alpha lipoic acid, ethanolamide palmitate, coenzyme Q 10…..

It is very likely that, in the future, treatment of the microbiota will be part of the treatment of this disease.

Endometriosis in patients who wish to become mothers in the future

 Patients who do wish to have children should not be offered medical therapy to control the disease, as it does not improve fertility, inhibits ovulation and thus delays pregnancy.

 In these cases, a correct assessment of the couple must be made, taking into account the woman’s age, her ovarian reserve, the presence of an associated male factor, or tubal involvement (hydrosalpinx). Surgery should only be indicated in the cases previously mentioned or in the case of hydrosalpinx, or technical difficulties in oocyte retrieval (5).

There are few publications that study the results after intrauterine insemination, as most patients have tubal involvement or low ovarian reserve that makes them subsidiary to in vitro fertilisation (IVF). In this case the results obtained depend on the following factors:

• Previous surgery for endometriosis
• Endometrioma surgery
• Compromised ovarian reserve with AMH less than 2ng/ml, or an antral follicle count of less than 10. 

These three factors are associated with worse prognosis (6).

There is no consensus as to the best stimulation regimen, or the benefit of pre-stimulation therapy (GnRH analogues, contraceptives), but it does seem that most of the latest publications point to better results after delayed embryo transfer rather than in the fresh IVF cycle, especially in the presence of adenomyosis.  

Due to the optimisation of endometrial receptivity, the endometrium in women with endometriosis presents alterations that influence receptivity, which is also altered by the stimulation itself.

In women with endometriosis who wish to become mothers in the future, the aim of treatment is for the patient to be asymptomatic, to slow the progression of the disease and to preserve future fertility.  

Medical treatment and the possibility of preventive vitrification of their oocytes is considered for them, especially in women at higher risk such as the presence of a bilateral endometrioma, previous surgery or a single ovary.

In this way vitrification can be offered at less advanced ages, fewer stimulations are required, IVF is avoided at older ages with worse results and we prevent these patients from having to enter an oocyte donation programme in the future.

At Clinica Fertia we provide a global approach to patients with endometriosis that allows them to maintain a good quality of life and the most satisfactory results in assisted reproduction if they wish to become mothers in the future.

Bibliography

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2. Vercellini P, Vigaro P, Somigliana E, Fedele L. Endoemtriosis: pathogenesis and treatment. Nat Rev Endocrinol.2014;10:261-275.
3. Vannucini S, Luisi S, Tosti C, Sorbi F, Petraglia F. Role of medical therapy in the management of uterine adenomyosis. Fertil Steril.2018;109:398-405.
4. Vennberg Karlsson J, Patel H, Premberg A. Experiences of health after dietary changes in endometriosis: a qualitative interview study. 2020;10:e032321.
5. De Ziegler D, Borghese B, Chapron C. Endometriosis and infertility: pathophysiology and management.The Lancet.2010;376:730-738.
6. Mignien C, Santulli P, Gayet V, Lafay-Pillet MC, Korb D, Bourdon M, Marcellin L, De Ziegler D, Chapron C. Prognostic factors for assisted reproductive technology in women with endometrioss-related infertility.Am J Of Obstet Gynecol.2017;216:1-9.
7. De Ziegler D, Pirtea P, Carbonnel M, Poulain M, Cicinelli E, Bulleti C, Kostara k, Kontopoulos G, Keefe D, Ayoubi JM. Best Prcat Res Clin Endocrinol Mteba.2019;33:47-59.