Treatment of endometriosis-associated infertility

Medical and surgical treatment

The role of hormonal therapy (i.e. ovarian suppression) in the treat­ment of endometriosis-associated infertility has been evaluated in a Cochrane review (92).

There is agreement among international guidelines that laparo­scopic surgery is beneficial for infertility associated with endomet­riosis (2, 60). In a Cochrane review in 2010, the role of laparoscopic surgery for endometriosis-related infertility was addressed (93). The authors conclude that in women with stage I-II endometriosis operative laparoscopy is effective in increasing live birth rate (93). In women with stage III-IV endometriosis there are no controlled studies comparing reproductive outcome after surgery and after ex­pectant management. Observational studies suggest that surgery in patients with stage III-IV disease may increase spontaneous preg­nancy rates; however, the significant complication rates of this com­plex surgery needs to be taken into account (2, 94). Therefore, both the ASRM and ESHRE guidelines recommend surgical treatment for stage I-II endometriosis and in women with stage III-IV endo­metriosis, operative laparoscopy can be considered to increase spon­taneous pregnancy rates (2, 60).

Furness and colleagues assessed the role of pre- and postopera­tive hormonal therapy in endometriosis (95).

Medically assisted reproduction

Medically assisted reproduction is defined is ‘Reproduction brought about through ovulation induction, controlled ovarian stimulation, ovulation triggering, assisted reproductive technology procedures and intrauterine, intracervical and intravaginal insemination with semen of husband/partner or donor' (96). Assisted reproductive technology (ART) is defined as ‘all treatments or procedures that include the in vitro handling of both human oocytes and sperm or of embryos for the purpose of establishing a pregnancy' (96).

Intrauterine insemination in women with endometriosis

Ovulation induction with intrauterine insemination (IUI) has been used in the treatment of couples with infertility associated with endometriosis, especially of minimal or mild stage. This is sup­ported by limited data from observational studies and small ran­domized controlled trials (2). The ESHRE guideline states that in women with minimal to mild endometriosis, IUI with controlled ovarian stimulation may be effective in increasing live birth rate when compared with expectant management (2). Several studies on IUI in endometriosis-associated infertility have included women whose endometriosis was treated. One case-control study showed that pregnancy rates following controlled ovarian stimulation plus IUI were not different between women with unexplained infertility and women with surgically treated minimal or mild endometri­osis (97). Therefore both the ASRM and ESHRE guidelines recom­mend controlled ovarian stimulation plus IUI as a viable option for women who have had a surgical diagnosis and treatment of stage I/ II endometriosis (60).

Assisted reproductive technology in women with endometriosis

Data on the impact of endometriosis on ART success rates are incon­sistent. A review of observational studies reported lower pregnancy rates in patients with endometriosis when compared to patients with tubal factor infertility (98). However, these data were not supported by the observed pregnancy rates in large databases monitoring ART outcomes (2, 60). While endometriosis may or may not affect ART results, IVF likely maximizes cycle fecundity for patients with endo­metriosis (60). All studies that evaluated the risk of endometriosis recurrence after ovarian stimulation for ART found no increased risk of recurrence (99-102).

A potential role of medical treatment of endometriosis prior to ART has been proposed. GnRH agonists have been studied most extensively for this indication and were reviewed by Sallam and col­leagues (103). Although the quality of the studies was poor the re­sults concurred, showing a beneficial effect. The authors concluded that 3-6 months of GnRH agonist treatment before ART increases the odds of clinical pregnancy by more than fourfold (103).

Since surgical treatment of endometriosis is considered to be beneficial for endometriosis-associated infertility, it might also improve ART outcomes. In line with the finding that operative laparoscopy increases (spontaneous) live birth rates in stage I/II endometriosis, Opoien and colleagues showed that complete re­moval of endometriosis in women with stage I/ II disease before ART significantly increased the live birth rate (104). For women who are found to have an (asymptomatic) endometrioma and who are plan­ning to undergo IVF/intracytoplasmic sperm injection, there is in­sufficient evidence to suggest that removal of the endometrioma will improve IVF success rates (2, 60). However, if the endometrioma is large (>4 cm), surgery should be considered to confirm the diag­nosis histologically, to improve access to follicles during oocyte re­trieval, and possibly to improve ovarian response (60). However, the patient should be counselled that extensive ovarian surgery could compromise ovarian function and diminish the response to ovarian stimulation (2). In the literature, there is no good evidence for sur­gical excision of deep endometriosis prior to ART to improve repro­ductive outcomes. However, the majority of these patients will have pain symptoms, and these symptoms represent a valid indication for endometriosis surgery in addition to or before ART treatment for which surgical treatment is considered the treatment of choice.