Effects of norgestimate in combination with ethinyl estradiol on cervical mucus

The antifertility effect of norgestimate (Ng) 0.125 mg in combination with ethinyl estradiol (EE) 0.035 mg on cervical mucus of 5 apparently normal and ovulatory volunteer women was studied for 2 cycles: a control cycle followed by a study cycle in which the medication was given. Throughout both cycles, basal body temperature, cervical mucus properties, sperm penetration in cervical mucus and karyopyknotic index of vaginal cells were evaluated. Disappearance of cyclicity of these parameters in the study cycle as well as monophasic basal body temperature were suggestive of inhibition of ovulation caused by the combination pill. Deterioration of cervical mucus properties throughout the study cycle and inhibition of sperm penetration may be a reflection of anovulation. However, a direct antifertility effect of Ng on cervical mucus cannot be excluded.     

Trace metals (Cu,Mn, Zn,Fe), sulphydryl and bisulphide groups of cervical mucus

Cervical mucus was separated into an aqueous and a mucin rich fraction. The trace metals copper, manganese, zinc and iron have been measured in both fractions. The levels of sulphydryl and disulphide groups were measured in the mucin rich fraction.A comparison was made between groups of women not using any contraceptive protection and women using a Cu-7 intrauterine device (IUD) containing 200 mm² of copper wire, or a Dalkon Shield IUD.The levels of the metals studied in normal cervical mucus did not vary during the menstrual cycle. The only metal found to be associated with the mucin rich fraction was copper. Sulphydryl and disulphide groups were also present in the mucin rich fraction, and their levels remained constant throughout the menstrual cycle.Cervical mucus from women using a Cu-7 IUD was found to have decreased levels of manganese, zinc and iron. The copper content was increased at 6 months but returned to normal levels at 13 months with the Cu-7 still $\text{in situ}$. The use of the Dalkon Shield IUD resulted in a decrease in manganese levels only.The presence of the IUDs did not significantly change the levels of sulphydryl or disulphide groups in cervical mucus.     

Contraception and the cervix

In the human and subhuman primates the uterine cervix plays an important role in the reproductive process by its permissive and inhibitory action on sperm migration from the vaginal pool into the cervical canal, the uterine cavity and the fallopian tube, the site of gamete unification and fertilization. This is accomplished through physico-chemical (amount, clarity, viscosity, pH, electrolyte composition, etc.) alteration of the cervical mucus in response to the circulating sex steroids. In an ovulatory cycle, shortly prior to and at the time of ovulation the cervical mucus becomes most receptive to the spermatozoa whereas at other times, specifically following ovulation, it becomes hostile to the spermatozoa and virtually impenetrable. This unique property of the cervical mucus may, in addition to the presently available techniques (diaphragm, cervical cap and intracervical devices), allow identification of such potential contraceptive modalities as: pH modifier - changing the pH of the cervical mucus from alkaline to acid around the time of ovulation; Electrolyte modifier - changing electrolyte composition of the cervical mucus to produce a mesh impenetrable to spermatozoa. Finally, development of a temporary localized tissue-fixed immune antibody to spermatozoa in the cervical mucus is within the realm of reality and deserves the necessary attention.     

The effect of a low dose progestagen on the trace metal content and disulphide and sulphydryl groups in cervical mucus

Cervical mucus was separated into an aqueous and a mucin rich fraction. The trace metals copper, manganese, zinc and iron have been measured in both fractions. The levels of sulphydryl and disulphide groups were measured in the mucin rich fraction.A comparison was made between groups of women not using any contraceptive protection and women taking 350 μg norethisterone daily. No difference in the trace metal content of cervical mucus was found between the two groups. There was an increase in the sulphydryl group content in the cervical mucus from the women taking norethisterone.     

Effects of chelating agents on the rheological property of cervical mucus

As an ongoing effort to elucidate the mechanisms involved in the calcium-dependent fertility regulation process, the viscoelastic properties of the mucus obtained from lamb cervix and human semen, as well as their water and total protein contents after exposure to EDTA, a chelating agent, or Nonoxynol-9 (N-9), a spermicidal agent, were examined. The viscosity was measured using a Cone Plate Digital Viscometer, while the water and total protein contents were determined by the lyophilization process and the Lowry method, respectively. The significant changes in the rheological properties of mucus, such as its viscosity and the water content, upon exposure to EDTA were demonstrated. The viscosity of cervical mucus and human semen were significantly increased by EDTA treatment (as compared to the controls): lamb cervical mucus (2.9 ± 0.3 vs. 2.2 ± 0.3 cps) and human semen (5.0 ± 0.3 vs. 4.3 ± 0.3 cps), respectively. The hydration rate was decreased by EDTA treatment as compared with the control (93.6 ± 0.7 vs. 96.8 ± 0.8%). Among tested samples, the reduction in the percentage of sperm penetration through the cervical mucus was the highest in the mucus containing EDTA, which had the lowest water content (93.6 ± 0.7%), indicating that there is a positive relationship between the hydration rate of the cervical mucus and its ability to permit the penetration of spermatozoa. This result indicates that spermicidal activity exerted by high concentrations of EDTA is in part due to its effect on the rheological properties of cervical mucus or semen.     

Effects of chelating agents on the rheological property of cervical mucus

As an ongoing effort to elucidate the mechanisms involved in the calcium-dependent fertility regulation process, the viscoelastic properties of the mucus obtained from lamb cervix and human semen, as well as their water and total protein contents after exposure to EDTA, a chelating agent, or Nonoxynol-9 (N-9), a spermicidal agent, were examined. The viscosity was measured using a Cone Plate Digital Viscometer, while the water and total protein contents were determined by the lyophilization process and the Lowry method, respectively. The significant changes in the rheological properties of mucus, such as its viscosity and the water content, upon exposure to EDTA were demonstrated. The viscosity of cervical mucus and human semen were significantly increased by EDTA treatment (as compared to the controls): lamb cervical mucus (2.9 ± 0.3 vs. 2.2 ± 0.3 cps) and human semen (5.0 ± 0.3 vs. 4.3 ± 0.3 cps), respectively. The hydration rate was decreased by EDTA treatment as compared with the control (93.6 ± 0.7 vs. 96.8 ± 0.8%). Among tested samples, the reduction in the percentage of sperm penetration through the cervical mucus was the highest in the mucus containing EDTA, which had the lowest water content (93.6 ± 0.7%), indicating that there is a positive relationship between the hydration rate of the cervical mucus and its ability to permit the penetration of spermatozoa. This result indicates that spermicidal activity exerted by high concentrations of EDTA is in part due to its effect on the rheological properties of cervical mucus or semen.     

The effect of norethisterone capsules on the pituitary-ovarian axis

An increased bioavailability of norethisterone when suspended in Polyethylene glycol 400 (PEG 400) has been previously demonstrated. This study examines the effect of norethisterone (500 mcg) over 21 days on the pituitary-ovarian axis and cervical mucus. However, this formulation failed to inhibit ovulation reliably in the eleven patients studied, despite the increased bioavailability, but exerts its major contraceptive effect on the cervical mucus. This may be due to degradation of norethisterone in polyethylene glycol.     

The influence on the pituitary-ovarian function,cervical mucus and vaginal cytology of a new progestational compound

A new progestational preparation, 17α-ethinyl-18-methyl-11-methylene-4-estren-17β-ol (Org 2969) was subjected to clinical and laboratory assessment. Five women, all with a previously regular bleeding pattern, received 60 μg daily for 21 days. The treatment entailed an appreciable change in pituitary-ovarian function. Thus, judging by daily determinations of FSH, LH, progesterone and oestrogen plasma concentrations, no volunteer ovulated. The characteristic mid-cycle FSH and LH peaks failed to appear, and progesterone was almost totally suppressed. Oestrogen showed, as during the control period, a mid-cycle peak, but it fell later, and 3 out of 5 volunteers had increased plasma levels. Changes in cervical mucus and vaginal cytology were observed. The quantity, appearance, and spinnbarkeit of the cervical mucus were approximately as in the luteal phase of the control period. No sperm penetration was observed $\text{in vitro}$. The karyopyknotic index did not reflect the increasing oestrogen values.     

A comparison of the fertile phase as determined by the Clearplan Easy Fertility Monitor and self-assessment of cervical mucus

The purpose of this study was to compare the fertile phase of the menstrual cycle as determined by the Clearplan Easy Fertility Monitor (CPEFM) with self-monitoring of cervical mucus. One-hundred women (mean age = 29.4 years) observed their cervical mucus and monitored their urine for estrogen and luteinizing hormone metabolites with the CPEFM on a daily basis for 2-6 cycles and generated 378 cycles of data; of these, 347 (92%) had a CPEFM peak. The beginning of the fertile window was, on average, day 11.8 (SD = 3.4) by the monitor and day 9.9 (SD = 3.0) by cervical mucus (r = 0.43, p < 0.001). The average first day of peak fertility by the monitor was 16.5 (SD = 3.6) and by cervical mucus 16.3 (SD = 3.7) (r = 0.85, p < 0.001). The mean length of the fertile phase by the monitor was 7.7 days (SD = 3.1) and by cervical mucus 10.9 days (SD = 3.7) (t = 12.7, p < 0.001). The peak in fertility as determined by the monitor and by self-assessment of cervical mucus is similar but the monitor tends to underestimate and self-assessment of cervical mucus tends to overestimate the actual fertile phase.     

Accuracy of the peak day of cervical mucus as a biological marker of fertility

The (PD) peak day of cervical mucus is an important biologic marker for the self-determination of the optimal time of fertility in a woman's menstrual cycle. The purpose of this article is to provide evidence (literature and empiric) for the accuracy of the PD of cervical mucus as a biologic marker of peak fertility and the estimated day of ovulation. An analysis of data from four published studies that compared the self-determination of the PD of cervical mucus with the urinary luteinizing hormone (LH) surge was conducted. The four studies yielded 108 menstrual cycle charts from 53 women participants. The 108 cycles ranged in length from 22 to 75 days (mean 29.4 SD 6.0). Ninety-three of the 108 cycles had both an identified PD and LH surge. Data charts showed that 97.8% of the PD fell within +/-4 days of the estimated day of ovulation. Use of a standardized mucus cycle scoring system indicated that the peak in cervical mucus ratings was highest on the day of the LH surge. Self-determination of the PD of cervical mucus is a very accurate means of determining peak fertility and a fairly accurate means of determining the day of ovulation and the beginning of the end of the fertile time.