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Female fertility preservation

Recent improvements in freezing techniques have made it possible to control the freezing of oocytes. This is a turning point in the field of female fertility preservation. As a result, this new field of reproductive medicine has expanded rapidly, notably for patients with cancer, the treatment of which is likely to alter their fertility, as well as for pregnant women with other chronic diseases. More recently, techniques for preserving female fertility have been proposed as a solution for physiological ovarian ageing in women who are free from any pathology. This kind of preservation of fertility for social or societal reasons is currently prohibited in France.

 

What the law says

According to the bioethics law of 6th August 2004, reviewed on 7th July 2011, with a view to subsequently providing medical support for procreation, anyone may have their gametes or germinal tissue collected and preserved with their consent, or if necessary, the consent of a parent or guardian with the relevant authority, when medical treatment is likely to alter the fertility of the person they are responsible for, or when there is a risk of their fertility being prematurely impaired.

Indications

  • Oncological (cancer)The latest anti-cancer policies assert that it is important to recommend an oncofertility consultation to any patient under 40 who has to receive cancer treatment such as chemotherapy and/or radiotherapy cancer treatment. This mainly regards breast cancers, hemopathies (acute leukemias, lymphomas), gynecological cancers (of the ovary, cervix or endometrium), colorectal cancers and solid tumors in children (neuroblastoma, nephroblastoma, sarcomas).
    Pelvic radiotherapy can lead to irreversible damage, due to its toxic effects on the ovaries (with damage to the primordial follicles), which may lead to premature ovarian failure. Unlike chemotherapy, when radiotherapy affects the uterus it can be the cause of fibrotic sequelae, possibly leading to embryo implantation failures and obstetric complications (early miscarriage, late miscarriage, intrauterine growth restriction, stillbirth and premature birth).
  • Non-oncologicalFertility preservation may also be proposed for non-oncological pathologies, the treatment or natural history/progression of which may lead to ovarian insufficiency. Thus, fertility preservation is now indicated for systemic diseases, and benign or genetic gynaecological pathologies.
    Moreover, although it is still prohibited in France, fertility preservation for social or societal reasons (without any medical grounds) is being developed in many industrialized countries.

Fertility preservation consultation

This is a multidisciplinary consultation involving doctors, reproductive biologists, and psychologists. It should be held before any treatment of ovarian function begins.
It may have several objectives:

  • To inform on the ovarian toxicity of treatment and consequences on fertility.
  • To provide information on the possibilities of fertility preservation after assessing ovarian reserve parameters (ultrasound antral follicle count, testing for levels of serum anti-Müllerian hormone).
  • To provide information on alternative techniques for attaining maternity (ovum donation, adoption, etc.)
  • To discuss pathology-specific contraceptive methods.

Due to the very low chances of success, fertility preservation is generally not offered to women over the age of 40.

Different fertility preservation techniques

    • Ovarian stimulation for oocyte or embryo vitrification

Stimulating the ovaries for mature oocyte collection and vitrification is currently the most established technique. It is intended for all women of child-bearing age who have no contraindications for ovarian stimulation and no urgent time constraints. On average, it takes 2 weeks to perform the stimulation, which is comparable to the time required for women undergoing in vitro fertilisation (IVF). The technique cannot be used when chemotherapy has already begun or when there is an urgent need to start treatment.
The principle is to stimulate the antral follicles with follicle stimulating hormone (FSH) for about ten days in order to collect mature eggs by means of a transvaginal puncture. This stimulation can be started at any time during the cycle.
Certain hormone-dependent pathologies, such as breast cancer, endometrial cancer and lupus may contraindicate conventional ovarian stimulation, due to the raise in estrogen levels. Some specific stimulation protocols have been developed, using letrozole or tamoxifen, but they are not licensed to be marketed for this therapeutic indication.

    • Oocyte or embryo vitrification without stimulation: in vitro maturation (IVM) of oocytes

IVM consists in collecting partially immature oocytes by means of an ultrasound-guided transvaginal puncture. The oocytes are cultured for 24 to 48 hours, in order to obtain mature eggs. Only oocytes which have matured in vitro are suitable for vitrification or freezing after fertilisation. One of the limitations of this technique is the unpredictable success of immature egg collection. In addition, once the IVM process is complete, only half of the oocytes will reach maturity. Finally, the potential of vitrified oocyes and embryos after IVM is not as good as when they have been obtained after ovarian stimulation.

    • GnRH analogues

The purpose of administering gonadotropin-releasing hormone (GnRH) agonists during chemotherapy is to “let the ovaries rest”, in order to protect the stock of primordial follicles. Their efficacy is however very controversial and considering the limited or even inexistent levels of their effectiveness, injections of GnRH analogue may be proposed but they should ideally be combined with another fertility preservation method.

Surgical techniques for preserving fertility

    • Cryopreservation of ovarian tissue (cortex)

The aim of this procedure is to preserve ovarian tissue and its reserve of immature eggs (within primordial follicles). It entails the surgical removal of all or part of an ovary, by laparoscopy under general anesthesia. Fragments of the ovarian cortex (the outer portion of the ovary containing the eggs) are then frozen. They can be thawed and orthotopically transplanted later (into its normal place in the pelvic cavity) by means of laparoscopy, or into heterotopic sites (such as the abdominal wall or the forearm). The fragments may lead to a resumption of transient ovarian activity, with endocrine production (of hormones) and exocrine production (of oocytes). Pregnancies can then be achieved naturally or following Assisted Reproductive Technology. The transplantation technique is still considered experimental.

    • Ovarian transposition

This surgical technique initially seeks to preserve endocrine ovarian function (hormone production) in women under the age of 40 who have to undergo pelvic radiotherapy. The principle is to reposition, through laparoscopy, one or both ovaries outside the boundary of the field of radiation.
However, it is difficult to assess the efficacy of ovarian transposition. In fact, although hormone production is usually resumed, the quality and quantity of the oocytes after transposition is altered. Pregnancy can be achieved naturally or after in vitro fertilisation without repositioning the ovaries (by trans-abdominal oocyte retrieval). Exposing the uterus to radiotherapy makes it more difficult to achieve pregnancy, and certain complications are specifically associated with ovarian transposition, especially the detachment of the ovary from its new position, chronic pelvic pain and ovarian cysts (in 30-40% of cases).

 

 

Table

 

Advantages and disadvantages of the different techniques for preserving female fertility.

Advantages Disadvantages
Ovarian stimulation Technique of choice (best results)
Feasible at any phase of the cycle
Minimally invasive oocyte retrieval
No risk of reintroducing cancer cells
Patients of child-bearing age
Sufficient ovarian reserve
Risk of poor response
Duration of stimulation (2 to 3 weeks)
Induced hyperestradiolaemia (hormone peak)
Limited number of frozen oocytes
In vitro maturation Feasible at any phase of the cycle
Achievable in an emergency
No induced hyperestradiolaemia (hormone peak)
Minimally invasive oocyte retrieval
Possibility of association with cryopreservation of ovarian tissue
No risk of reintroducing cancer cells
Experimental
Patients of child-bearing age
Random oocyte collection
Limited number of frozen oocytes
Lower oocyte potential than for oocytes collected after stimulation
Cryopreservation of ovarian tissue The only technique which may be used before puberty
Achievable in an emergency
Possibility of association with IVM of oocytes
Restoration of endocrine ovarian function
Possibility of natural pregnancy after transplant
Large number of cryopreserved follicles
Experimental
Surgical sampling
GnRH analogues Minimally invasive
Contraceptive
Efficacy not proven

 

Find out more at: http://www.fertiellp-onco.com

BOOK YOUR CONSULTATION

Public consultations (sector 1, without exceeding fees): contact the appointment office of Antoine Béclère Hospital: 01 41 07 95 95

BOOK YOUR PRIVATE CONSULTATION

Private consultations (sector 2, with overruns): contact Ms. Céline Delattre at 01.45.37.40.53. or celine.delattre@aphp.fr