Endometriosis is a medical condition in which tissue resembling the one that usually lines the uterus grows elsewhere in the body forming lesions. Because these lesions cannot exit the body through menstrual bleeding, they cause inflammation, pain, and infertility in more severe cases.

Some women with endometriosis can only become pregnant with the help of assisted reproduction technologies, which includes a procedure called intra-cytoplasmic sperm injection (ICSI).

What is intra-cytoplasmic sperm injection?

ICSI is similar to in vitro fertilization (IVF). Both methods involve fertility medications that stimulate the ovaries to cause several eggs to mature. The eggs are then harvested under light anesthesia using a needle guided by ultrasound imaging. In IVF, the eggs are then combined with the sperm, which penetrates the egg without further assistance. In ICSI, the sperm is injected into the egg to force fertilization. A few days after fertilization, one or several embryos are placed inside the uterus.

ICSI is usually used when the male partner’s sperm count, or motility, is too low for IVF. Studies suggest that compared with IVF, ICSI increases the chances of a woman with endometriosis becoming pregnant, independent of the male’s sperm quality.

Studies assessing the effects of ICSI in women with endometriosis

An observational clinical trial (NCT02762461) evaluated whether the ovarian stimulation required for assisted reproductive technologies affects endometriosis symptoms.

Ovarian stimulation causes high levels of estrogen. Because the growth of endometrial lesions depends on estrogen, the researchers suspected that the process of ovarian stimulation might worsen endometriosis symptoms.

The study included 154 participants, 52 women with endometriosis and a control group of 50 women without endometriosis, both undergoing controlled ovarian stimulation for IVF or ICSI. A second control group consisted of 52 women with endometriosis who did not attempt to get pregnant and therefore did not undergo ovarian stimulation.

Pain and quality of life were assessed with questionnaires. The two groups undergoing ovarian stimulation received the questionnaire before undergoing ovarian stimulation and 10 days after egg retrieval, before knowing the results of the pregnancy test. The group that included women with endometriosis who did not undergo ovarian stimulation received the first questionnaire after a medical consultation and the second one four weeks later.

Both groups undergoing ovarian stimulation experienced an increase in non-menstrual pelvic pain. The worsening in pain symptoms was, however, similar, and women with endometriosis did not experience a greater worsening of pain symptoms than those without endometriosis.

The two groups of women with endometriosis reported a small increase in quality of life, while the group that included women without endometriosis reported a decrease.

Another study retrospectively analyzed data to assess whether laparoscopic removal of endometriotic lesions affects the success of ICSI. The study included 150 participants, 48 women with minimal endometriosis, 25 women with endometriosis who had undergone laparoscopy, 53 women with endometriosis who did not undergo laparoscopy, and 24 women without endometriosis who underwent ICSI because of tubal factors. In tubal factor infertility, damage in the fallopian tubes, or the tubes that connect the ovaries to the uterus, prevents sperm from reaching the ovary to fertilize the egg or prevents the fertilized embryo from reaching the uterus.

The number of retrieved eggs and the fertilization rate was lower in women with endometriosis who had undergone laparoscopy than in other groups. The pregnancy rate per ICSI cycle and embryo transfer were significantly lower in women who underwent laparoscopy than in women who did not. Even though these factors are thought to be important for the outcome, there was no statistically significant difference in live birth rate per ICSI cycle and embryo transfer between the groups.

A retrospective study assessed whether the long-term use of gonadotropin-releasing hormone (GnRH) receptor agonists affects the efficacy and safety of IVF and ICSI in women with endometriosis. GnRH receptor agonists inhibit the growth of endometriotic lesions by lowering estrogen levels. Some small studies suggest that the use of GnRH receptor agonists for three to six months before IVF or ICSI increase pregnancy rates in endometriosis patients. On the other hand, the long-term use of GnRH receptor agonists may lower the ovarian response to stimulation.

The study included 113 women with endometriosis stage 3 or 4. A total of 68 women were treated with a GnRH receptor agonist for at least three months, while the remaining 45 did not receive the treatment before IVF or ICSI.

Around one-fifth, (19.1%) of patients in the GnRH receptor agonist group became pregnant through the transfer of freshly fertilized embryos, compared with 20% in the group who did not receive GnRH receptor agonist treatment.

Some patients had cryopreserved (frozen) embryos that had been fertilized in the past. In the GnRH receptor agonist group, 27 patients underwent embryo transfer using cryopreserved embryos, and 11 of them (40.7%) became pregnant. In the group without GnRH receptor agonist treatment, 15 patients used cryopreserved embryos, and one (6.6 %) became pregnant.

Overall, 35.3% of patients in the GnRH receptor agonist group became pregnant, compared with 22.2% in the group without GnRH treatment. After adjusting for body mass index (BMI), age, and dose of fertility medications that stimulate the ovaries, the difference was not statistically significant.

A retrospective study analyzed whether ICSI increases the pregnancy success rate compared with IVF in endometriosis patients. The study included 221 women with endometriosis. A total of 124 patients tried to become pregnant with IVF and 97 with ICSI. The control group included 150 participants with unexplained infertility.

Women with endometriosis who underwent ICSI had the same pregnancy and live birth rates as women in the control group who underwent ICSI. The endometriosis group that used ICSI had a higher pregnancy and live birth rate than the endometriosis group that used IVF.

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