Appraising cervical mucus: a new approach to evaluating contraceptives

Abstract

Purpose: Timing of sample collection represents a major source of variability in studies evaluating the effects of administered agents on cervical mucus in naturally-cycling women. We sought to create and validate an artificial model of the cervical mucus cycle using exogenous E2 and P4 replacement in ovarian suppressed women.

Materials and methods: We conducted a prospective experiment (clinicaltrials.gov, NCT02969590) examining cervical mucus changes in six women during natural and artificial menstrual cycles [leuprolide acetate, estradiol transdermal patch (0.05–0.3 mg/day) and progesterone 200 mg/day]. We collected serum and mucus samples at each visit corresponding to early, mid and late follicular, ovulation and mid-luteal time points in the natural and artificial cycles. We evaluated mucus according to the modified Insler score described in the WHO laboratory Manual for the Examination and Processing of Human Semen.

Results: We enrolled healthy women between 27 and 40 years of age. All of the subjects achieved a mucus score of ≥10 both in the natural cycle and during peak estradiol replacement levels (0.3 mg/day) in the artificial cycle. During the simulated luteal phase, all mucus scores were ≤5 (median 3.5; range 1–5), similar to scores seen in the luteal phase of natural cycles (median 1; range 1–3).

Conclusions: Our artificial cycle model (leuprolide acetate suppression) and dose escalation with estradiol patches produced favourable cervical mucus with mucus scores similar to those in the periovulatory phase of natural menstrual cycles. Additional studies are needed to validate the model for evaluation of mucus effects of contraceptive agents.

摘要

目的：在研究中, 评价药物对自然月经周期妇女宫颈粘液的影响时, 样本的采集时间是表现变异性的主要方面。我们试图在卵巢抑制妇女中使用外源性E2和P4替代治疗来创建和验证宫颈粘液循环的人工模型。材料和方法：我们进行了一项前瞻性的试验（政府临床试验：NCT02969590）检测6名女性在自然和人工月经周期中宫颈粘液的变化（醋酸亮丙瑞林、雌二醇皮贴（0.05-0.3 mg/天）和孕酮200 mg/天）。我们收集了每位参加者在自然月经周期和人工周期中相应的卵泡早期、中期和晚期、排卵期和黄体中期的血清和宫颈黏液样本。我们根据世卫组织检测和处理人类精液实验室手册中描述的改良的Insler评分对宫颈黏液进行了评估。结果：我们招募了27到40岁的健康女性。所有受试者在自然周期和人工周期雌激素替代高峰水平(0.3 mg/d)时, 宫颈粘液评分均≥10分。在模拟黄体期, 所有宫颈黏液评分≥5分(中位数3.5分；范围1-5分), 与自然周期黄体期评分相当(中位数1；范围1-3)。结论：我们的人工周期模型(醋酸亮丙瑞林抑制)和增加雌二醇贴片剂量能产生良好的宫颈黏液, 黏液评分与自然月经周期的排卵期相似。避孕药物对宫颈黏液效果还需要进一步的研究来验证。

Keywords:

• Cervical mucus
• contraception
• insler
• model

Acknowledgements

The authors would like to acknowledge the tremendous support of the OHSU Women’s Health Research Unit and especially Marci Messerle Forbes FNP and Andrea O’Donnell FNP for aiding in study coordination and sample collection.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Additional information

Funding

This project is supported by The Society of Family Planning. The Endocrine Technologies Support Core (ETSC) at the Oregon National Primate Research Center (ONPRC) is supported by NIH Grant [P51 OD011092] awarded to ONPRC.