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无已知生育力低下的女性的宫颈粘液模式和易孕期:三个队列的汇总分析。

Cervical mucus patterns and the fertile window in women without known subfertility: a pooled analysis of three cohorts.

机构信息

Office of Cooperative Reproductive Health, Division of Public Health, Department of Family and Preventive Medicine, University of Utah, Salt Lake City, UT 84108, USA.

College of Nursing, University of Utah, Salt Lake City, UT 84108, USA.

出版信息

Hum Reprod. 2021 Jun 18;36(7):1784-1795. doi: 10.1093/humrep/deab049.


DOI:10.1093/humrep/deab049
PMID:33990841
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8487651/
Abstract

STUDY QUESTION: What is the normal range of cervical mucus patterns and number of days with high or moderate day-specific probability of pregnancy (if intercourse occurs on a specific day) based on cervical mucus secretion, in women without known subfertility, and how are these patterns related to parity and age? SUMMARY ANSWER: The mean days of peak type (estrogenic) mucus per cycle was 6.4, the mean number of potentially fertile days was 12.1; parous versus nulliparous, and younger nulliparous (<30 years) versus older nulliparous women had more days of peak type mucus, and more potentially fertile days in each cycle. WHAT IS KNOWN ALREADY: The rise in estrogen prior to ovulation supports the secretion of increasing quantity and estrogenic quality of cervical mucus, and the subsequent rise in progesterone after ovulation causes an abrupt decrease in mucus secretion. Cervical mucus secretion on each day correlates highly with the probability of pregnancy if intercourse occurs on that day, and overall cervical mucus quality for the cycle correlates with cycle fecundability. No prior studies have described parity and age jointly in relation to cervical mucus patterns. STUDY DESIGN, SIZE, DURATION: This study is a secondary data analysis, combining data from three cohorts of women: 'Creighton Model MultiCenter Fecundability Study' (CMFS: retrospective cohort, 1990-1996), 'Time to Pregnancy in Normal Fertility' (TTP: randomized trial, 2003-2006), and 'Creighton Model Effectiveness, Intentions, and Behaviors Assessment' (CEIBA: prospective cohort, 2009-2013). We evaluated cervical mucus patterns and estimated fertile window in 2488 ovulatory cycles of 528 women, followed for up to 1 year. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were US or Canadian women age 18-40 years, not pregnant, and without any known subfertility. Women were trained to use a standardized protocol (the Creighton Model) for daily vulvar observation, description, and recording of cervical mucus. The mucus peak day (the last day of estrogenic quality mucus) was used as the estimated day of ovulation. We conducted dichotomous stratified analyses for cervical mucus patterns by age, parity, race, recent oral contraceptive use (within 60 days), partial breast feeding, alcohol, and smoking. Focusing on the clinical characteristics most correlated to cervical mucus patterns, linear mixed models were used to assess continuous cervical mucus parameters and generalized linear models using Poisson regression with robust variance were used to assess dichotomous outcomes, stratifying by women's parity and age, while adjusting for recent oral contraceptive use and breast feeding. MAIN RESULTS AND THE ROLE OF CHANCE: The majority of women were <30 years of age (75.4%) (median 27; IQR 24-29), non-Hispanic white (88.1%), with high socioeconomic indicators, and nulliparous (70.8%). The mean (SD) days of estrogenic (peak type) mucus per cycle (a conservative indicator of the fertile window) was 6.4 (4.2) days (median 6; IQR 4-8). The mean (SD) number of any potentially fertile days (a broader clinical indicator of the fertile window) was 12.1 (5.4) days (median 11; IQR 9-14). Taking into account recent oral contraceptive use and breastfeeding, nulliparous women age ≥30 years compared to nulliparous women age <30 years had fewer mean days of peak type mucus per cycle (5.3 versus 6.4 days, P = 0.02), and fewer potentially fertile days (11.8 versus 13.9 days, P < 0.01). Compared to nulliparous women age <30 years, the likelihood of cycles with peak type mucus ≤2 days, potentially fertile days ≤9, and cervical mucus cycle score (for estrogenic quality of mucus) ≤5.0 were significantly higher among nulliparous women age ≥30 years, 1.90 (95% confidence interval (CI) 1.18, 3.06); 1.46 (95% CI 1.12, 1.91); and 1.45 (95% CI 1.03, 2.05), respectively. Between parous women, there was little difference in mucus parameters by age. Thresholds set a priori for within-woman variability of cervical mucus parameters by cycle were examined as follows: most minus fewest days of peak type mucus >3 days (exceeded by 72% of women), most minus fewest days of non-peak type mucus >4 days (exceeded by 54% of women), greatest minus least cervical mucus cycle score >4.0 (exceeded by 73% of women), and most minus fewest potentially fertile days >8 days (found in 50% of women). Race did not have any association with cervical mucus parameters. Recent oral contraceptive use was associated with reduced cervical mucus cycle score and partial breast feeding was associated with a higher number of days of mucus (both peak type and non-peak type), consistent with prior research. Among the women for whom data were available (CEIBA and TTP), alcohol and tobacco use had minimal impact on cervical mucus parameters. LIMITATIONS, REASONS FOR CAUTION: We did not have data on some factors that may impact ovulation, hormone levels, and mucus secretion, such as physical activity and body mass index. We cannot exclude the possibility that some women had unknown subfertility or undiagnosed gynecologic disorders. Only 27 women were age 35 or older. Our study participants were geographically dispersed but relatively homogeneous with regard to race, ethnicity, income, and educational level, which may limit the generalizability of the findings. WIDER IMPLICATIONS OF THE FINDINGS: Patterns of cervical mucus secretion observed by women are an indicator of fecundity and the fertile window that are consistent with the known associations of age and parity with fecundity. The number of potentially fertile days (12 days) is likely greater than commonly assumed, while the number of days of highly estrogenic mucus (and higher probability of pregnancy) correlates with prior identifications of the fertile window (6 days). There may be substantial variability in fecundability between cycles for the same woman. Future work can use cervical mucus secretion as an indicator of fecundity and should investigate the distribution of similar cycle parameters in women with various reproductive or gynecologic pathologies. STUDY FUNDING/COMPETING INTEREST(S): Funding for the three cohorts analyzed was provided by the Robert Wood Johnson Foundation (CMFS), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (TTP), and the Office of Family Planning, Office of Population Affairs, Health and Human Services (CEIBA). The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

摘要

研究问题:在没有已知生育力低下的情况下,非妊娠妇女的宫颈粘液分泌的正常宫颈粘液模式和具有较高或中度特定天受孕概率(如果在特定天发生性交)的天数范围是多少,以及这些模式与产次和年龄有何关系?

摘要答案:每个周期中雌激素型粘液的平均高峰天数为 6.4,潜在可育天数为 12.1;经产与未产妇,年轻未产妇(<30 岁)与年长未产妇相比,具有更多的高峰型粘液天数,并且每个周期中具有更多的潜在可育天数。

已知情况:排卵前雌激素的增加支持宫颈粘液分泌量和雌激素质量的增加,排卵后孕激素的增加导致粘液分泌突然减少。如果在当天发生性交,当天的宫颈粘液分泌与怀孕的可能性高度相关,并且整个周期的宫颈粘液质量与周期生育能力相关。之前的研究没有联合描述产次和年龄与宫颈粘液模式的关系。

研究设计、大小、持续时间:本研究是对三个女性队列数据的二次数据分析:“Creighton 模型多中心生育力研究”(CMFS:回顾性队列,1990-1996 年)、“正常生育力的时间”(TTP:随机试验,2003-2006 年)和“Creighton 模型有效性、意图和行为评估”(CEIBA:前瞻性队列,2009-2013 年)。我们评估了 528 名女性的 2488 个排卵周期的宫颈粘液模式,并对其进行了长达 1 年的随访。

参与者/材料、设置、方法:参与者为年龄在 18-40 岁之间的美国或加拿大女性,未怀孕且无任何已知生育力低下。女性接受了使用标准化方案(Creighton 模型)进行每日外阴观察、描述和记录宫颈粘液的培训。粘液高峰日(雌激素质量粘液的最后一天)被用作估计排卵日。我们对年龄、产次、种族、近期口服避孕药使用(<60 天)、部分母乳喂养、酒精和吸烟的宫颈粘液模式进行了二项分层分析。重点关注与宫颈粘液模式最相关的临床特征,使用线性混合模型评估宫颈粘液的连续参数,并使用泊松回归的广义线性模型评估二项结果,同时调整了近期口服避孕药使用和母乳喂养,分层考虑了女性的产次和年龄。

主要结果和机会的作用:大多数女性年龄<30 岁(75.4%)(中位数 27;IQR 24-29),非西班牙裔白人(88.1%),社会经济指标较高,且未产妇(70.8%)。每个周期的雌激素(高峰型)粘液天数(生育窗口的保守指标)为 6.4(4.2)天(中位数 6;IQR 4-8)。任何潜在可育天数(生育窗口的更广泛临床指标)的平均(SD)天数为 12.1(5.4)天(中位数 11;IQR 9-14)。考虑到近期口服避孕药使用和母乳喂养,与年龄<30 岁的未产妇相比,年龄≥30 岁的未产妇每个周期的高峰型粘液天数(5.3 比 6.4 天,P=0.02)和潜在可育天数(11.8 比 13.9 天,P<0.01)较少。与年龄<30 岁的未产妇相比,年龄≥30 岁的未产妇的高峰型粘液天数≤2 天、潜在可育天数≤9 天和粘液周期评分(用于粘液雌激素质量)≤5.0 的周期的可能性明显更高,分别为 1.90(95%置信区间[CI]1.18,3.06);1.46(95% CI 1.12,1.91);和 1.45(95% CI 1.03,2.05)。在经产妇中,年龄对粘液参数的影响很小。我们设定了用于检查女性内周期宫颈粘液参数变异性的预先设定的阈值如下:高峰型粘液天数最多减去最少>3 天(72%的女性超过),非高峰型粘液天数最多减去最少>4 天(54%的女性超过),宫颈粘液周期评分最大减去最小>4.0(73%的女性超过),潜在可育天数最多减去最少>8 天(50%的女性发现)。种族与宫颈粘液参数没有任何关联。近期口服避孕药的使用与宫颈粘液周期评分降低有关,部分母乳喂养与粘液(高峰型和非高峰型)天数增加有关,这与先前的研究一致。在 CEIBA 和 TTP 中有数据的女性中,酒精和烟草使用对宫颈粘液参数的影响最小。

局限性、谨慎的原因:我们没有关于可能影响排卵、激素水平和粘液分泌的一些因素的数据,例如体力活动和体重指数。我们不能排除某些女性有未知的生育力低下或未确诊的妇科疾病。只有 27 名女性年龄在 35 岁或以上。我们的研究参与者在地理位置上分布广泛,但在种族、民族、收入和教育水平方面相对同质,这可能限制了研究结果的普遍性。

研究结果的更广泛影响:女性观察到的宫颈粘液分泌模式是生育力和可育窗口的指标,与年龄和产次与生育力的已知关联一致。潜在可育天数(12 天)可能大于通常认为的,而高度雌激素型粘液(和更高的怀孕概率)的天数与先前确定的可育窗口(6 天)相关。同一妇女的周期之间可能存在较大的生育能力差异。未来的研究可以使用宫颈粘液分泌作为生育力的指标,并应研究具有不同生殖或妇科病理的妇女中类似周期参数的分布。

研究资金/利益冲突:对分析的三个队列的资助由罗伯特伍德约翰逊基金会(CMFS)、美国国立儿童健康与人类发展研究所(TTP)和人口事务办公室、家庭计划办公室、卫生和人类服务部(CEIBA)提供。作者声明他们没有利益冲突。

试验注册编号:无。

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