Development of deep pelvic endometriosis following acute haemoperitoneum: a prospective ultrasound study.

IF 8.3 Q1 OBSTETRICS & GYNECOLOGY Human reproduction open Pub Date : 2024-05-29 eCollection Date: 2024-01-01 DOI:10.1093/hropen/hoae036
Prubpreet Chaggar, Tina Tellum, Lucrezia Viola De Braud, Sarah Annie Solangon, Thulasi Setty, Davor Jurkovic
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However, the sample size was small, and the follow-up was not standardized owing to unknown rates of clot absorption and development of endometriosis.</p><p><strong>Study design size duration: </strong>This was a prospective observational cohort study conducted at a single centre over a 31-month period. A required sample size of 30 was calculated using results from a previous study, with a minimum of 15 women each in the groups with and without significant haemoperitoneum (study and control groups, respectively). A total of 59 women were recruited to the study and eight were lost to follow-up. The final sample comprised 51 women, 15 in the study group and 36 in the control group.</p><p><strong>Participants/materials setting methods: </strong>All non-pregnant, premenopausal women aged 18-50 years who consecutively presented to our dedicated gynaecological diagnostic unit with severe acute lower abdominal pain were eligible for this study. 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A ruptured functional haemorrhagic cyst was the most common cause of haemoperitoneum, occurring in 13/15 cases (87%). The time from the initial event to sonographic evidence of endometriosis varied from 2 to 6 months. The EuroQol visual analogue scores were not significantly different at baseline between the groups that developed and did not develop endometriosis [28 (interquartile range (IQR) 15-40, n = 6) vs 56 (IQR 35-75, n = 44), <i>P </i>=<i> </i>0.09], while the EuroQol-5D values were lower in the endometriosis group [-0.01 (IQR -0.07 to 0.19, n = 6) vs 0.62 (IQR 0.24-0.73, n = 44), <i>P </i>=<i> </i>0.002]. At 6 months, the EuroQol-5D scores were improved in both groups, but remained significantly lower in the endometriosis group compared to the no endometriosis group [0.69 (IQR 0.66-0.80, n = 6) vs 0.85 (IQR 0.76-1.00, n = 44), <i>P </i>=<i> </i>0.03]. 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Abstract

Study question: Is acute haemoperitoneum that is managed conservatively a precursor of deep endometriosis?

Summary answer: Our study provides evidence to suggest that acute haemoperitoneum may lead to the development of deep endometriosis in a significant proportion of cases.

What is known already: A recent pilot study was the first to suggest that acute haemoperitoneum could be a precursor of deep endometriosis. However, the sample size was small, and the follow-up was not standardized owing to unknown rates of clot absorption and development of endometriosis.

Study design size duration: This was a prospective observational cohort study conducted at a single centre over a 31-month period. A required sample size of 30 was calculated using results from a previous study, with a minimum of 15 women each in the groups with and without significant haemoperitoneum (study and control groups, respectively). A total of 59 women were recruited to the study and eight were lost to follow-up. The final sample comprised 51 women, 15 in the study group and 36 in the control group.

Participants/materials setting methods: All non-pregnant, premenopausal women aged 18-50 years who consecutively presented to our dedicated gynaecological diagnostic unit with severe acute lower abdominal pain were eligible for this study. We only included women who were clinically stable and were suitable for conservative management. Those with prior history or evidence of endometriosis on their initial ultrasound scan, previous hysterectomy, or bilateral oophorectomy were excluded. Participants had standardized follow-up visits for 6 months, with pelvic ultrasound scans and the British Society of Gynaecological Endoscopy pelvic pain questionnaires completed at each visit. The primary outcome was the sonographically confirmed presence of newly formed endometriosis. Secondary outcomes were the presence and change of pelvic pain symptoms and health-related quality of life (HR-QOL).

Main results and the role of chance: After completion of follow-up, 7/15 (47%; 95% CI 21.3-71.4%) women presenting with acute haemoperitoneum (study group) developed sonographic evidence of deep endometriosis, compared to 0/36 (0%; 97.5% CI 0.0-9.7%) women in the control group. A ruptured functional haemorrhagic cyst was the most common cause of haemoperitoneum, occurring in 13/15 cases (87%). The time from the initial event to sonographic evidence of endometriosis varied from 2 to 6 months. The EuroQol visual analogue scores were not significantly different at baseline between the groups that developed and did not develop endometriosis [28 (interquartile range (IQR) 15-40, n = 6) vs 56 (IQR 35-75, n = 44), P =0.09], while the EuroQol-5D values were lower in the endometriosis group [-0.01 (IQR -0.07 to 0.19, n = 6) vs 0.62 (IQR 0.24-0.73, n = 44), P =0.002]. At 6 months, the EuroQol-5D scores were improved in both groups, but remained significantly lower in the endometriosis group compared to the no endometriosis group [0.69 (IQR 0.66-0.80, n = 6) vs 0.85 (IQR 0.76-1.00, n = 44), P =0.03]. There was no clinically relevant difference in the pelvic pain scores at either time point.

Limitations reasons for caution: It remains uncertain whether minimal, superficial endometriosis existed at commencement of the study and had a role in the development of deep endometriosis. Although the ultrasound findings were in keeping with deep endometriosis, this was not confirmed histologically. The pelvic pain and HR-QOL findings could have been influenced by the baseline scores being taken when the patient was admitted with acute pain. Also, the sample size was too small to draw reliable conclusions regarding the impact of newly developed endometriosis on QoL.

Wider implications of the findings: Our study provides further evidence showing that significant haemoperitoneum may be a precursor of deep endometriosis. Haemodynamically stable women presenting with acute pelvic pain and significant haemoperitoneum should be counselled about the risk of developing deep endometriosis. Interventional studies should be carried out in the future to see whether laparoscopy and pelvic washout could prevent development of deep endometriosis. Preventative strategies, including treatment to suppress ovulation and formation of functional cysts, should be further investigated. This includes the combined and progesterone-only contraceptive pills. Larger future studies are also required to assess women over a longer period of time, with adjustment for confounding factors, to evaluate a possible effect on HR-QOL and pain symptoms.

Study funding/competing interests: Funding was obtained from The Gynaecology Ultrasound Centre, London, UK. TT received personal fees from GE, Samsung, Medtronic, and Merck for lectures on ultrasound. TT also received a postdoctoral grant from the South-Eastern Norwegian Health Authority (grant number 2020083).

Trial registration number: researchregistry6472.

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急性腹腔积血后盆腔深部子宫内膜异位症的发展:一项前瞻性超声波研究。
研究问题:保守治疗的急性腹腔积血是否是深部子宫内膜异位症的前兆?我们的研究提供的证据表明,在相当一部分病例中,急性腹腔积血可能会导致深部子宫内膜异位症的发生:最近的一项试验性研究首次表明,急性腹腔积血可能是深部子宫内膜异位症的前兆。然而,由于血块吸收率和子宫内膜异位症的发生率未知,因此样本量较小,随访也没有标准化:这是一项前瞻性观察性队列研究,在一个中心进行,为期 31 个月。根据之前一项研究的结果计算出所需样本量为 30 人,其中有明显腹腔积血组和无明显腹腔积血组(研究组和对照组)各至少有 15 名妇女。研究共招募了 59 名妇女,其中 8 人失去了随访机会。最终样本包括 51 名妇女,其中研究组 15 人,对照组 36 人:所有年龄在 18-50 岁之间、未怀孕、绝经前、因严重急性下腹痛连续到我们的专门妇科诊断室就诊的女性都有资格参与这项研究。我们只纳入临床病情稳定、适合保守治疗的女性。那些曾有过子宫内膜异位症病史或在初次超声波扫描中有子宫内膜异位症证据、曾进行过子宫切除术或双侧输卵管切除术的妇女被排除在外。参与者接受了为期 6 个月的标准化随访,每次随访都要完成盆腔超声扫描和英国妇科内镜学会盆腔疼痛问卷调查。主要结果是声像图证实是否存在新形成的子宫内膜异位症。次要结果是盆腔疼痛症状和健康相关生活质量(HR-QOL)的存在和变化:随访结束后,7/15(47%;95% CI 21.3-71.4%)名出现急性腹腔积血的妇女(研究组)出现了声像图显示的深部子宫内膜异位症,而对照组妇女为 0/36(0%;97.5% CI 0.0-9.7%)。功能性出血性囊肿破裂是导致腹腔积血的最常见原因,有 13/15 例(87%)。从初始事件到声像图显示子宫内膜异位症的时间从 2 个月到 6 个月不等。发生和未发生子宫内膜异位症组的EuroQol视觉模拟评分在基线时无明显差异[28(四分位距(IQR)15-40,n = 6) vs 56(IQR 35-75,n = 44),P = 0.09],而子宫内膜异位症组的EuroQol-5D值较低[-0.01(IQR -0.07至0.19,n = 6) vs 0.62(IQR 0.24-0.73,n = 44),P = 0.002]。6个月后,两组患者的EuroQol-5D评分均有所改善,但与无子宫内膜异位症组相比,子宫内膜异位症组的评分仍明显较低[0.69(IQR 0.66-0.80,n = 6) vs 0.85(IQR 0.76-1.00,n = 44),P = 0.03]。两个时间点的盆腔疼痛评分均无临床相关性差异:尚不确定在研究开始时是否存在微小的浅表子宫内膜异位症,是否对深部子宫内膜异位症的发展有影响。虽然超声波检查结果与深部子宫内膜异位症相符,但组织学上并未证实。盆腔疼痛和 HR-QOL 结果可能会受到基线评分的影响,因为基线评分是在患者因急性疼痛入院时得出的。此外,由于样本量太少,无法就新发子宫内膜异位症对 QoL 的影响得出可靠的结论:我们的研究提供了进一步的证据,表明大量腹腔积血可能是深部子宫内膜异位症的前兆。应向血流动力学稳定、伴有急性盆腔疼痛和明显腹腔积血的妇女提供有关罹患深部子宫内膜异位症风险的咨询。今后应开展介入性研究,探讨腹腔镜检查和盆腔冲洗能否预防深部子宫内膜异位症的发生。应进一步研究预防策略,包括抑制排卵和功能性囊肿形成的治疗。这包括联合避孕药和纯黄体酮避孕药。今后还需要进行更大规模的研究,对妇女进行更长时间的评估,并对混杂因素进行调整,以评估对心率-QOL和疼痛症状可能产生的影响:经费由英国伦敦妇科超声中心提供。TT从通用电气、三星、美敦力和默克公司获得了个人超声讲座费用。TT还获得了挪威东南部卫生局的博士后基金(基金号:2020083)。试验注册号:researchregistry6472。
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Membrane-bound receptor for advanced glycation end products (RAGE) is a stable biomarker of low-quality sperm. Women may not benefit from repeated frozen embryo transfers: a retrospective analysis of the cumulative live birth rate of 43 972 women. Sperm and leukocyte telomere length are related to sperm quality parameters in healthy men from the Led-Fertyl study. Reply: Emerging evidence of endometrial compaction in predicting ART outcomes. Emerging evidence of endometrial compaction in predicting ART outcomes.
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