LUNA Explains: Endometriosis and Medically Assisted Reproduction (MAP)

Infertility is defined as the absence of conception after one year of unprotected intercourse without contraception for a couple who want to conceive. In patients with endometriosis, this waiting period can be reviewed or even shortened, especially if the patient is older, has reduced ovarian reserves or severely painful symptoms.

To provide the best possible guidance to patients, a double assessment is necessary:

A complete infertility assessment of the couple (including notably an evaluation of the ovarian reserve and tubal permeability, and a male assessment).

Accurate mapping of endometriosis lesions and the documentation of any associated adenomyosis are important elements to consider.

In fact, when a patient with endometriosis consults for infertility, there are two options: surgery followed by MAP in the absence of pregnancy, or medically assisted procreation without prior intervention.

Surgical intervention consists of the most comprehensive removal of endometriosis lesions possible. It may be considered for a young patient, who presents pain, has never had surgery for her endometriosis, has a good ovarian reserve and has been infertile for a short time, without any associated infertility factor, neither endometrioma nor adenomyosis.

All patients can be considered for immediate MAP treatment. However, priority should be given to patients who are older, have little or no pain, have an altered ovarian reserve and have been infertile for a long time. This is especially true if there is a history of endometrioma surgery, associated infertility factors (tubal or male anomalies), endometriomas and/or adenomyosis. Patients should be central to this treatment choice. It is therefore important to provide as much information as possible about these two treatment options.

This involves depositing sperm in the bottom of the uterine cavity. An IUI is often combined with mild ovarian stimulation to promote the development of one or two follicles. In cases of endometriosis, the use of intrauterine insemination (IUI) has not been proved useful, either before or after surgical treatment. In fact, this technique does not make it possible to avoid the consequences of inflammation that can alter the different stages of fertilisation.

In most cases, IVF with or without intracytoplasmic sperm injection (ICSI) is the preferred initial technique in cases of endometriosis. This technique makes it possible to avoid the harmful effects of inflammation on the stages of natural fertilisation in the peritoneal cavity.

The birth rate achieved with IVF/ICSI is comparable in cases of endometriosis to that of other MAP indications (tubal, male, unexplained infertility).

In patients with endometriosis, the number of eggs collected appears lower than in other causes of infertility. Nevertheless, the outcome of IVF/ICSI in terms of pregnancy and birth chances does not seem to be affected. The main predictive factors are age and the quality of the ovarian reserve, which should be respected and preserved as much as possible.

Furthermore, the endometriosis phenotype does not appear to affect pregnancy and live birth outcomes in MAP. However, a history of endometriosis surgery (including or excluding endometrioma surgery) is associated with poorer IVF/ICSI outcomes in terms of pregnancies.

Adenomyosis, which is frequently associated with endometriosis, is a factor in poor MAP outcomes, leading to lower pregnancy and live birth rates, and requires appropriate treatment protocols.

There is no difference in terms of cumulative pregnancies between IVF and ICSI.

The use of pre-treatment with molecules that block ovulation and therefore endometrial growth, such as the oestro-progestin pill or gonadotropin-releasing hormone (GnRH) agonists, prior to ovarian stimulation with a view to IVF/ICSI, could make it possible to improve pregnancy rates by correcting the endometrial abnormalities, which are essentially inflammatory, characteristic of endometriosis.

There is no specific recommendation on which ovarian stimulation protocol for IVF/ICSI should be favoured in endometriosis. To date, no differences have been shown between agonist and antagonist protocols in patients with endometriosis. Stimulation monitoring procedures are the same as for a patient without endometriosis.

Preliminary results suggest that embryonic freezing with delayed transfer (embryo transfer at a distance from stimulation) could improve the chances of pregnancy. From a physiological point of view, these results probably reflect better receptivity of the eutopic endometrium outside ovarian stimulation. However, the superiority of delayed transfer in cases of endometriosis has yet to be confirmed.

Embryo quality does not seem to be affected by the presence of endometriosis. The studies do not show any difference in the percentage of embryos of “good morphological quality” when comparing patients with endometriosis and “control” patients. Furthermore, the rates of aneuploidy (embryonic genetic abnormalities) are equivalent when comparing blastocysts (embryos at day 5-6 of development) whether the patients have endometriosis or not.

There are few side effects or complications with IVF/ICSI, and they do not appear to be significantly more common in cases of endometriosis.

One of the main complications is the risk of ovarian hyperstimulation syndrome. However, today, the use of adapted protocols makes it possible to reduce this risk, notably by triggering ovulation with the GnRH agonist when using an antagonist protocol associated with delayed embryo transfer.

The other notable complications are related to the technical procedure of transvaginal oocyte puncture with rare risks of haemorrhage (0.1%) or infection (0.1-0.5%). Antibiotic therapy during puncture is recommended in the case of endometriomas.

Post puncture tubo-ovarian abscesses are rare and do not appear to be more frequent in patients who have undergone oocyte puncture than in those with endometriosis not undergoing MAP. The presence of endometriomas, particularly if they are large, may hinder oocyte puncture. Transvaginal drainage (or in some cases laparoscopy if the cyst is very large) may be recommended.

Data from international publications is all reassuring. There does not seem to be any risk of aggravating lesions, exacerbating painful symptoms or altering the quality of life during ovarian stimulation in patients with endometriosis, compared with other infertile patients receiving MAP treatment.