Norwegian Resource Centre for Women's Health, Department of Gynaecology, Oslo University Hospital Rikshospitalet, Box 4950 Nydalen, 0424 Oslo, Norway.
Hum Reprod. 2013 Jul;28(7):1837-45. doi: 10.1093/humrep/det087. Epub 2013 Mar 29.
Do endometriomas induce an inflammatory reaction with increased cytokine concentrations in nearby follicles and thereby affect follicular development during controlled ovarian stimulation for in vitro fertilization (IVF)?
With most endometriomas, there is no evidence of increased cytokine concentrations in the ipsilateral leading follicle. Infrequently, the concentration of inflammatory cytokines is increased in the follicular fluid (FF) and associated with diminished ovarian response.
The link between peritoneal endometriosis, inflammation and infertility is well established; however, the association between intraovarian inflammation and endometrioma is unknown.
STUDY DESIGN, SIZE, DURATION: This prospective cohort study included 117 infertile women undergoing IVF in a tertiary infertility clinic at Oslo University Hospital Rikshospitalet, Norway, during the period May 2009 to September 2011.
PARTICIPANTS, SETTING, METHODS: There were 47 patients with unilateral endometrioma and 17 patients with bilateral endometrioma, while the 53 control patients had unexplained or male factor infertility. Concentrations of IL-1β, IL-6, IL-8, IL-10, IL-12 and TNF-α were measured in serum and in the fluid of the largest pre-ovulatory follicles from each ovary of each participant.
Cytokine levels in the follicular fluid from the two ovaries in women with unilateral endometriomas were comparable, and were not significantly altered compared with that of control groups with male factor infertility, unexplained infertility or bilateral endometriomas. Compared with serum levels, the follicular fluid levels of IL-8 and IL-6 were higher, suggesting a local production or recruitment. The follicular fluid IL-8 level varied considerably and showed an inverse relationship with IL-12, IL-10 and TNF-∝, suggesting a complex interaction between various immune cells. A small group of patients (n = 3) had increased levels of all follicular fluid cytokines combined with moderately to slightly elevated serum levels and these patients had a significantly lower ovarian response.
LIMITATIONS, REASONS FOR CAUTION: For ethical reasons, the endometriomas were diagnosed indirectly by ultrasound rather than by histology.
This paper reveals that endometriomas seldom induce inflammation in nearby follicles during IVF; therefore, routine cystectomy prior to IVF may not be necessary. Cytokine levels in the follicular fluid, nonetheless, show distinctive patterns and increased levels may be linked to reduced ovarian response independent of the cause of infertility.
内异症是否会引起炎症反应,导致同侧优势卵泡中细胞因子浓度增加,从而影响体外受精(IVF)控制性卵巢刺激过程中的卵泡发育?
大多数情况下,同侧优势卵泡中并没有证据表明细胞因子浓度增加。偶尔,卵泡液(FF)中的炎症细胞因子浓度增加,并与卵巢反应减弱相关。
腹膜内异症、炎症和不孕之间的联系已得到充分证实;然而,卵巢内炎症与内异症之间的关联尚不清楚。
研究设计、规模、持续时间:本前瞻性队列研究纳入了 2009 年 5 月至 2011 年 9 月期间在挪威奥斯陆大学医院 Rikshospitalet 接受 IVF 的 117 名不孕女性。其中 47 名患者为单侧内异症,17 名患者为双侧内异症,而 53 名对照组患者为不明原因或男性因素不孕。测量每位参与者每侧卵巢中最大的预排卵卵泡的血清和卵泡液中的 IL-1β、IL-6、IL-8、IL-10、IL-12 和 TNF-α浓度。
单侧内异症患者两侧卵巢的卵泡液中细胞因子水平相似,与不明原因不孕、男性因素不孕或双侧内异症对照组相比,并无显著差异。与血清水平相比,卵泡液中 IL-8 和 IL-6 水平较高,提示局部产生或募集。卵泡液中 IL-8 水平变化较大,与 IL-12、IL-10 和 TNF-α呈负相关,提示各种免疫细胞之间存在复杂的相互作用。一小部分患者(n=3)所有卵泡液细胞因子水平升高,同时血清水平中度至轻度升高,这些患者卵巢反应明显降低。
局限性、谨慎的原因:出于伦理原因,内异症是通过超声间接诊断的,而不是通过组织学诊断。
本研究表明,IVF 期间内异症很少引起附近卵泡炎症;因此,在进行 IVF 之前常规进行囊肿切除术可能没有必要。然而,卵泡液中的细胞因子水平显示出独特的模式,升高的水平可能与卵巢反应减弱有关,而与不孕的原因无关。