O-191 Endometriosis is associated with a lowered cumulative live birth rate by alters the macrophage polarization and the cytokine concentrations in follicular fluid
Authors: Zhou L , Mo M , Xu S , Zhang H , Geng Q , Zeng Y 
Published: June 2022

Study question

The impact of endometriosis on the outcomes of ART is still ambiguous and the mechanism by which endometriosis impacts fertility has not been fully elucidated

Summary answer

Endometriosis was associated with low CLBR in IVF, which might be due to the change of follicular microenvironment and compromising the quality of embryos.

What is known already

Despite the great advantages of IVF treatment in endometriosis-linked infertility, the impact of endometriosis on outcomes of infertility management with ART is controversial and few studies focused on the association between endometriosis and CLBR. Numerous mechanisms have been proposed in an effort to delineate the multifaceted pathophysiology that induces impairment of reproductive dynamics in patients with endometriosis. Reactive oxygen species, dysregulation of the immune system and cellular architectural disruption constitute the crucial mechanisms that detrimentally affect oocyte and embryo developmental potential. 

Study design, size, duration

This study retrospectively included 433 patients with endometriosis and 1299 patients with tuber factor infertility to evaluate the impact of endometriosis on IVF pregnancy outcome between January 2016 and December 2018.The basic study prospectively recruited 30 patients with ovarian endometriosis and 35 controls with tubal factor infertility to analyze polarization stage of macrophages in their follicular fluid, and another 20 females with ovarian endometriosis and 30 controls to detect cytokines in their FF. 

Participants/materials, setting, methods

Data on all women undergoing fresh or frozen IVF treatment cycles were analysed to compare the CLBR between endometriosis and tuber factor infertility patients. A cytometry panel of 4 antibodies (CD45, CD3, CD80, CD163) was designed to enumerate the numbers of MI and MII macrophages from the cell sediment from FF samples. Quantibody® array was utilized to determine the concentration of 10 cytokines in FF, including IFN-γ, IL-1α, IL-1β, IL-10,IL-13,IL-4, IL-6, IL-8, MCP-1 and TNF-α. 

Main results and the role of chance

The results showed that patients with endometriosis were associated with noticeably fewer retrievable oocytes, a lower oocyte maturity rate, decreased numbers of available and high-quality embryos (all p &lt; 0.001) in comparison with the control group. The clinical pregnancy and live birth rate of the endometriosis group were lower in the frozen-thawed embryo transfer cycles (p = 0.028 and p = 0.008, respectively), which leading to a declined cumulative live birth rate (CLBR) (p = 0.001). Logistic regression analysis indicated a close association between endometriosis and low CLBR (p = 0.002). Furthermore, the numbers of type I and type II macrophages in follicular fluid (FF) of patients with ovarian endometriosis were significantly increased compared with the control group (p &lt; 0.001). The expressions of IL-1α, IL-1β, TNF-α, IL-6, IL-13, and IL-10 in FF were higher in endometrioma group(p &lt; 0.05). The increased expression of cytokines was negatively correlated with embryo outcomes, including the numbers of total oocytes retrieved, mature oocytes, and fertilized oocytes, and the numbers of high-quality blastocysts and embryos. Additionally, IL-6 and IL-8 were positively correlated with AMH, rate of available blastocysts, number of blastocysts formed and available blastocysts, but were negatively associated with rate of MII oocytes. 

Limitations, reasons for caution

The present study being of a retrospective and monocentric study, may not come to a very convincing conclusion, and some unknown biases might still exist due to possible underestimation of some confounders.

Wider implications of the findings

Collectively, our results indicate that endometriosis does adversely affect pregnancy outcomes of ART, as women with endometriosis produce a lower quantity of oocytes and embryos. Moreover, endometriosis might play a role in oocyte or embryo outcomes via regulating the production of cytokines or the number of immune cells in FF. 

Trial registration number

no