There are numerous pathologies that can affect the reproductive function of women: systemic diseases (genetic, inflammatory, autoimmune, neoplasms) and pathologies that specifically affect the genital system: uterine myomas, ovarian cysts, pelvic infections, adherential syndromes or chronic inflammatory diseases such as endometriosis. This pathology affects more than 10% of women of reproductive age and about 30% are affected by infertility. Conversely, 50% of women who go to an Assisted Reproduction Centre are affected by endometriosis.

Endometriosis causes inflammation, tubo-ovarian or entero-genital adhesions, it can potentially develop in any part of the body, but the organs most affected are the ovaries (50% of cases) where it forms cysts of the most varied sizes. Endometriosis is a chronic relapsing disease: causing pain, it interferes with the life of a couple and may require multiple surgeries over the course of a lifetime. What does this entail? Women with endometriosis know this well, in fact those who need surgical treatment for mono or bilateral endometriotic cysts are informed of the potential risk of undergoing a Premature Ovarian Failure (estimated in the order of 2% in women with disease of both ovaries).

In recent years, cases of preservation of fertility in young women have multiplied, especially before exposure to gonadotoxic therapies typical of antineoplastic treatments. The growing successes of fertility preservation techniques, through the freezing of ovarian tissue or mature oocytes, have promoted the preservation strategy also in other categories of patients at risk of impaired ovarian function due to benign pathology or iatrogenic damage.

Among these patients are women with endometriosis.

In fact, endometriosis involves infertility and premature loss of the ovarian reserve in a substantial percentage of affected women. Relapses after surgical treatments are also common as a chronic pathology. Young women with endometriosis are therefore potentially eligible for fertility preservation programs. Considering, however, the high incidence of the disease among all women of reproductive age (10-15%), it is necessary to limit the indication to any subgroups of women who could really benefit from the program, evaluating the pros and cons of each individual case.

Let us go into detail about why the ovarian reserve is depleted in women with endometriosis:

The premature depletion of the follicular reserve linked to endometriosis is mainly due to the surgical techniques of excision of endometriotic cysts in the ovary. Although it has long been the subject of debate, it is now established that the removal of ovarian cysts by laparoscopic stripping also leads to the loss of healthy tissue, causing a reduction in the number of primordial ovarian follicles and resulting in a drop in anti-Müllerian hormone levels (AMH). There is some evidence to this effect: in the case of hormonal stimulation of follicular growth by in vitro fertilisation, a reduced number of follicles generally grows on the ovary operated for endometriotic cysts compared to the non-operated contralateral ovary. Although not yet fully demonstrated, in addition to the surgical damage, the presence of endometriomas would in itself represent a factor in reducing the quality / quantity of oocytes available on the affected ovary. This could be due both to the mechanical effect of stretching the healthy tissue due to the volume of the endometriotic cyst, and to the release of potentially toxic substances by the cyst towards the surrounding oocytes. In addition, bilaterally operated women show a significantly lower age at menopause than that of controls.

Unfortunately, however, even without the need for surgical resolution, endometriosis in itself can cause a reduction in reproductive potential due to possible qualitative alterations of the same. It should be borne in mind that the earlier the eggs are stored, the greater the chances of success.

The experience of preserving fertility in women with endometriosis, despite the presence of an interesting rationale, is still very limited. Both main available strategies were used, i.e. both the freezing of mature oocytes after ovarian stimulation, and the freezing of ovarian tissue, but the number of patients treated and the follow-up (control) period is still too short to allow collection of sufficient data on the effectiveness of the methods in this particular group of patients.

However, it has now been demonstrated that the effectiveness of a fertility preservation program depends on the number of gametes available and the patient’s age at the time of cryopreservation.

In this specific case, the clinical conditions of the individual subjects will determine the appropriateness of resorting to the fertility preservation program. It is useful to identify categories that are particularly at risk of infertility and who are therefore more likely to benefit from cryopreserved gametes; these are patients suffering from bilateral ovarian endometriosis or possibly already operated on with relapse. In fact, the loss of oocytes due to surgery is highly verifiable in these women. Conversely, women with endometriosis, but with at least one intact ovary and not affected by endometriotic cysts, are more likely to maintain adequate reproductive potential, making the cryopreservation program less useful. Intermediate situations must be evaluated considering the risk of loss of healthy ovarian tissue and the possibility of actually using cryopreserved material.

In conclusion, there is still insufficient evidence to support the application of fertility preservation techniques to all women of reproductive age suffering from endometriosis.
Reference bibliography
1. Donnez J, Dolmans MM. Cryopreservation and Transplantation of Ovarian Tissue. Clin Obstet Gynecol 2010 Dec; 53 (4): 787-96.

2. Practice Committees of American Society for Reproductive Medicine, American Society for Assisted Reproductive Technology. Mature Oocyte Cryopreservation: a Guideline. Fertil Steril 2013 Jan; 99 (1): 37-43.

3. Somigliana E, Viganò P, Filippi F, et al. Fertility preservation in women with endometriosis: for all, for some, for none? Hum Reprod 2015; 30 (6): 1280-6.