Detailed inform­a­tion and a list of ref­er­ences can be found in Chapter 2.7 of the Fer­ti­PRO­TEKT book, “Indic­a­tions and fertility pre­ser­va­tion methods for onco­lo­gic­al and non-onco­lo­gic­al disorders”, which can be down­loaded free of charge.

PROGNOSis

Autoim­mune diseases often affect young women of child­bear­ing age. Despite great advances in treatment, general rheumatic diseases such as con­nect­ive tissue disease and vas­cu­lit­is are still often the reason for chemo­ther­apy. Cyc­lo­phos­ph­am­ide (CYC) is almost exclus­ively used here and also in stem cell transplants.

With early diagnosis and ini­ti­ation of appro­pri­ate therapy, most patients can now be given effective and permanent treatment.   Since the life expect­ancy of a treated patient is drawing closer to that of a healthy woman, the subject of fertility and pre­ser­va­tion of fertility plays an increas­ingly important role.

damage to the ovaries caused by chemotherapy

The ovarian reserve, determ­ined by the con­cen­tra­tion of Anti-Müllerian hormone (AMH), is already often limited by the illness itself in autoim­mune disease. A con­sulta­tion on fertility pre­ser­va­tion should therefore be carried our before CYC treatment in patients with autoim­mune disease.

CYC sig­ni­fic­antly increases the risk of premature failure of ovarian function (= premature ovarian insuf­fi­ciency, POI) in autoim­mune disease. The stated prob­ab­il­it­ies are between 12% and 54% and are mainly influ­enced by the age of the patients at the time of treatment and the total dose of CYC.

Risks of fertility preservation

GNRH-AGONISTs (GNRHA)

The risk of GnRHa therapy is be con­sidered to be low in patients with rheumatic disease. The effect­ive­ness is con­sidered to be con­tro­ver­sial; however several studies have shown a detect­able pro­tec­tion of ovarian function through the use of GnRHa for CYC treatment.

Hormonal Stim­u­la­tion of the ovaries

Stim­u­la­tion therapy for freezing fer­til­ized or unfer­til­ized eggs should be decided on an indi­vidu­al basis.

Basically, there are two possible risks:

  1. The risk of stim­u­la­tion worsening the disease 
    • Stim­u­la­tion can lead to an increase in disease activity, par­tic­u­larly in con­nect­ive tissue disease and espe­cially in SLE. However, few studies are available.
  2. Risik of thrombosis 
    • The risk of throm­bos­is is generally increased in autoim­mune disease. There are limited studies on throm­bos­is risk under hormonal stimulation.

freezing of ovarian tissue

In young women up to the age of 35 years (to a maximum of. ca.38 years), freezing of ovarian tissue is a sensible method. Since autoim­mune disease is a chronic condition, this method also offers fertility pre­ser­va­tion if CYC therapy needs to be repeated. Due to the often dimin­ished ovarian reserve, however, the AMH value should be measured and the number of small follicles (AFC) should be evaluated using ultra­sound to assess whether cryo­p­reser­va­tion is reasonable.

practical approach

The choice of fertility pre­ser­va­tion method is an indi­vidu­al decision which should be made after con­sulta­tion with the patient, the respons­ible gyn­ae­co­lo­gists and rheumatologists.

Patients should be referred to a repro­duct­ive medical centre as soon as possible to allow a suf­fi­cient time frame for the imple­ment­a­tion of fertility pre­ser­va­tion measures. The figure opposite illus­trates the possible practical approach.