Background:Endometriosis is an oestrogen-dependent disease that can cause subfertility
in women who may require assisted reproductive technology (ART) to achieve
their pregnancy goals.Objectives:The aim of this study was to compare ART outcomes in women with endometriosis
following the long GnRH-agonist controlled ovarian stimulation (COS)
protocol with those taking the GnRH-antagonist COS protocol.Data Sources and Methods:MEDLINE, Embase and Web of Science were systematically searched in June 2022.
Randomized controlled trials (RCTs) and observational studies comparing the
long GnRH-agonist COS protocol and the GnRH-antagonist COS protocol in women
with all stages/subtypes of endometriosis were included. Data were
synthesized into comprehensive tables for systematic review. The Scottish
Intercollegiate Guidelines Network (SIGN) checklists were used for the risk
of bias assessment of non-randomized studies and randomized studies, and all
the included studies were deemed to have acceptable quality.Main Results:Eight studies (one RCT and seven observational) with 2695 patients (2761
cycles) were included. Most studies generally reported non-significant
differences in clinical pregnancy or live birth rates regardless of the COS
protocol used. However, the GnRH-agonist protocol may yield a higher total
number of oocytes retrieved, especially mature oocytes. Conversely, the
GnRH-antagonist protocol required a shorter COS duration and lower
gonadotrophin dose. Adverse outcomes, such as rates of cycle cancellation
and miscarriage, were similar between both COS protocols.Conclusion:Both the long GnRH-agonist and GnRH-antagonist COS protocols generally yield
similar pregnancy outcomes. However, the long GnRH-agonist protocol may be
associated with a higher cumulative pregnancy rate due to the higher number
of retrieved oocytes available for cryopreservation. The underlying
mechanisms of the two COS protocols on the female reproductive tract remain
unclear. Clinicians should consider treatment costs, stage/subtype of
endometriosis and pregnancy goals of their patients when selecting a GnRH
analogue for COS. A well-powered RCT is needed to minimize the risk of bias
and compare the risk for ovarian hyperstimulation syndrome.Registration:This review was prospectively registered at PROSPERO under Registration No.
CRD42022327604.