Department of Obstetrics and Gynecology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Department of Obstetrics and Gynecology, Hyvinkää Hospital, Hyvinkää, Finland.
Hum Reprod. 2023 Aug 1;38(8):1520-1528. doi: 10.1093/humrep/dead120.
Do women with endometriosis have lower first live birth rate before surgical diagnosis than women without verified endometriosis?
Compared to reference women, the incidence of first live birth was lower in women prior to surgical verification of endometriosis irrespective of the type of endometriosis.
Endometriosis is associated with pain and reduced fertility. The mechanism of infertility is partly explained by anatomical, endocrinological, and immunological changes. Over the past decades, the treatment of both endometriosis and infertility has evolved. Knowledge of fertility far before surgical diagnosis of endometriosis in large cohorts and of different types of endometriosis has been lacking. The diagnostic delay of endometriosis is long, 6-7 years.
STUDY DESIGN, SIZE, DURATION: Retrospective population-based cohort study focused on the time period before the surgical verification of endometriosis. All women with surgical verification of endometriosis in 1998-2012 were identified from the Finnish Hospital Discharge Register and the reference cohort from the Central Population Register. Data on deliveries, gynecological care, and sociodemographic factors before the surgical diagnosis were gathered from Finnish national registers maintained by the Finnish Institute for Health and Welfare, the Digital and Population Data Services Agency, and Statistics Finland.
PARTICIPANTS/MATERIALS, SETTING, METHODS: All women aged 15-49 years at the time of surgical verification of endometriosis (ICD-10: N80.1-N80.9) in Finland during 1998-2012 were identified (n = 21 620). Of them, we excluded women born in 1980-1999 due to the proximity of the surgical diagnosis (n = 3286) and women left without reference (n = 10) for the final endometriosis cohort of 18 324 women. From the final cohort, we selected sub-cohorts of women with isolated diagnosis of ovarian (n = 6384), peritoneal (n = 5789), and deep (n = 1267) endometriosis. Reference women were matched by age and residence and lacked registered clinical or surgical diagnosis of endometriosis (n = 35 793). The follow-up started at the age of 15 years and ended at the first birth, sterilization, bilateral oophorectomy, hysterectomy, or until the surgical diagnosis of endometriosis or corresponding index day-whichever came first. Incidence rate (IR) and the incidence rate ratio (IRR) of first live birth before the surgical verification of endometriosis with corresponding CIs were calculated. In addition, we reported the fertility rate of parous women (the number of all children divided by the number of parous women in the cohort) until the surgical verification of endometriosis. The trends in first births were analysed according to the women's birth cohort, type of endometriosis, and age.
Surgical diagnosis of endometriosis was set at the median age of 35.0 years (IQR 30.0-41.4). Altogether 7363 women (40.2%) with endometriosis and 23 718 (66.3%) women without endometriosis delivered a live born infant before the index day (surgery). The IRs of the first live birth per 100 person-years were 2.64 (95% CI 2.58-2.70) in the endometriosis cohort and 5.21 (95% CI 5.15-5.28) in the reference cohort. Between the endometriosis sub-cohorts, the IRs were similar. The IRR of the first live birth was 0.51 (95% CI 0.49-0.52) between the endometriosis and reference cohorts. Fertility rate per parous woman before the surgical diagnosis was 1.93 (SD 1.00) and 2.16 (SD 1.15) in the endometriosis and reference cohorts (P < 0.01). The median age at the first live birth was 25.5 (IQR 22.3-28.9) and 25.5 (IQR 22.3-28.6) years (P = 0.01), respectively. Between the endometriosis sub-cohorts, women in the ovarian sub-cohort were the oldest at the time of surgical diagnosis with the median age of 37.2 years (IQR 31.4-43.3), (P < 0.001). Altogether 44.1% (2814) of the women with ovarian, 39.4% (2282) with peritoneal, and 40.8% (517) with deep endometriosis delivered a live born infant before the diagnosis. IRRs between the endometriosis sub-cohorts did not differ. Fertility rate per parous woman was lowest, 1.88 (SD 0.95), in the ovarian sub-cohort compared to 1.98 (SD 1.07) in the peritoneal and 2.04 (SD 0.96) in deep endometriosis (P < 0.001). Women with ovarian endometriosis were oldest at first live birth compared to women in other sub-cohorts with a median age of 25.8 years (IQR 22.6-29.1) (P < 0.001). Cumulative distributions of first live birth were presented according to age at first live birth and birth cohorts of the participants.
LIMITATIONS, REASONS FOR CAUTION: The increasing age at first live birth, increasing practice of clinical diagnostics, conservative treatment of endometriosis, a possible effect of coexisting adenomyosis, and use of artificial reproductive treatments should be considered when assessing the results. In addition, the study is limited due to possible confounding effects of socioeconomic factors, such as level of education. It should be noted that, in this study, we assessed parity only during the years preceding the surgical verification of endometriosis.
The need for early diagnosis and relevant treatment of endometriosis appears clear given the impairment of fertility prior to its surgical verification.
STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the Hospital District of Helsinki and Uusimaa and by Finska Läkaresällskapet. The authors report no conflicts of interest. All authors have completed the ICMJE Disclosure form.
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与经证实患有子宫内膜异位症的女性相比，手术诊断前患有子宫内膜异位症的女性首次活产率是否较低？
与参照女性相比，无论子宫内膜异位症的类型如何，在手术证实子宫内膜异位症之前，首次活产的发生率都较低。
子宫内膜异位症与疼痛和生育能力降低有关。不孕的部分机制可归因于解剖学、内分泌和免疫学变化。在过去几十年中，子宫内膜异位症和不孕症的治疗都有了发展。在大型队列中以及不同类型的子宫内膜异位症中，缺乏对手术诊断前生育能力的了解。子宫内膜异位症的诊断延迟很长，为 6-7 年。
研究设计、规模、持续时间：这是一项针对手术诊断前时间的基于人群的回顾性队列研究。所有在 1998-2012 年接受手术证实的子宫内膜异位症的女性均从芬兰医院出院登记处和中央人口登记处确定，并从芬兰卫生福利研究所、数字和人口数据服务机构以及芬兰统计中心维护的芬兰国家登记处收集了关于分娩、妇科护理和社会人口因素的数据。
参与者/材料、设置、方法：在 1998-2012 年期间，芬兰所有年龄在 15-49 岁的经手术证实的子宫内膜异位症（ICD-10：N80.1-N80.9）的女性（n=21620）都被纳入了研究。其中，由于手术诊断的临近（n=3286）和女性离开（n=10）而未纳入 1990-1999 年出生的女性，最终的子宫内膜异位症队列包括 18324 名女性。在最终队列中，我们选择了孤立性卵巢（n=6384）、腹膜（n=5789）和深部（n=1267）子宫内膜异位症的女性亚组。参照女性通过年龄和居住地进行匹配，且缺乏登记的临床或手术诊断的子宫内膜异位症（n=35793）。随访从 15 岁开始，直到首次分娩、绝育、双侧卵巢切除术、子宫切除术或手术诊断子宫内膜异位症或相应的索引日-以先发生者为准。计算了手术诊断前子宫内膜异位症的首次活产率（IR）和相应的发病率比（IRR）及其置信区间。此外，我们报告了在手术诊断子宫内膜异位症之前，已生育女性（队列中所有儿童人数除以生育过的女性人数）的生育力。根据女性的出生队列、子宫内膜异位症的类型和年龄分析了首次分娩的趋势。
手术诊断的子宫内膜异位症中位数为 35.0 岁（IQR 30.0-41.4）。总共 7363 名（40.2%）子宫内膜异位症女性和 23718 名（66.3%）无子宫内膜异位症的女性在索引日（手术）前分娩了活产婴儿。每 100 人年的首次活产率分别为子宫内膜异位症队列中的 2.64（95%CI 2.58-2.70）和参照队列中的 5.21（95%CI 5.15-5.28）。在子宫内膜异位症亚组之间，发病率相似。首次活产的发病率比为 0.51（95%CI 0.49-0.52），子宫内膜异位症组与参照组之间。手术诊断前生育过的女性的生育率为 1.93（SD 1.00）和 2.16（SD 1.15）在子宫内膜异位症和参照队列中（P<0.01）。首次活产的中位年龄分别为 25.5（IQR 22.3-28.9）和 25.5（IQR 22.3-28.6）岁（P=0.01）。在子宫内膜异位症亚组中，卵巢亚组的女性在手术诊断时年龄最大，中位数为 37.2 岁（IQR 31.4-43.3）（P<0.001）。总共 44.1%（2814）的卵巢、39.4%（2282）的腹膜和 40.8%（517）的深部子宫内膜异位症女性在诊断前分娩了活产婴儿。子宫内膜异位症亚组之间的发病率比没有差异。与卵巢亚组的 1.88（SD 0.95）相比，腹膜和深部子宫内膜异位症的生育力分别为 1.98（SD 1.07）和 2.04（SD 0.96）（P<0.001）。与其他亚组相比，卵巢子宫内膜异位症的女性首次活产年龄最大，中位数为 25.8 岁（IQR 22.6-29.1）（P<0.001）。根据首次活产年龄和参与者的出生队列，呈现了首次活产的累积分布。
局限性、谨慎的原因：随着首次活产年龄的增加、临床诊断的增加、子宫内膜异位症的保守治疗、共存的腺肌症的可能影响以及辅助生殖治疗的使用，应在评估结果时考虑这些因素。此外，由于社会经济因素（如教育水平）的可能混杂效应，该研究受到限制。应当指出，在本研究中，我们仅在手术诊断子宫内膜异位症之前的几年内评估了生育力。
鉴于其手术诊断前生育能力受损，明确需要早期诊断和相关治疗子宫内膜异位症。
研究资金/利益冲突：该研究由赫尔辛基和乌西玛地区医院和芬兰医师学会资助。作者报告没有利益冲突。所有作者均已完成 ICMJE 披露表。
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