Method and Apparatus for Detecting the Onset of Ovulation

The invention relates to a method and apparatus for detecting the onset of ovulation for the purpose of ascertaining when sexual intercourse is most likely to result in conception. This method and apparatus can therefore be used both as a means of promoting and avoiding conception.

Nowadays, contraceptive techniques may be divided into two groups: invasive methods and non-invasive methods.

Whereas invasive methods, such as the oral administration of various hormone combinations, in the form of contraceptive pills, and intra-uterine devices, have a high degree of efficiency, the use of contraceptive pills inhibits LH (luteinizing hormone) surge and induces a multitude of metabolic, hormonal and other bodily changes during their intake. In addition, the use of contraceptive pills may give rise to long-lasting effects after cessation of their use. Although the relationship between the use of contraceptive pills and genital malignancy has not been definitely established and appears to be unlikely, the sequential type of contraceptive pill may in some cases produce proliferative changes in the uterus. The list of serious complications following the use of contraceptive pills is considerable and includes the following: thromboembolism, hepatomata, and pseudo-tumor cerebri. Intrauterine devices are produced in more than twenty forms and each of these forms, with its different constituents, such as copper impregnated elements and progesterone carrying elements are known to be responsible for heavy blood loss, abdominal pain, infection and discharge. Thus, although both of these invasive methods of contraception are effective to 95-97%, they are not without serious dangers to a woman's wellbeing. On the other hand, the non-invasive methods of contraception in use today, like the use of pre-coital tablets, creams, foams, diaphragms, and condoms and the reliance on "safe periods" as determined by basal body temperature tests, all carry a considerably high rate of failure and require a very high degree of motivation for successful use.

There is therefore an urgent need for a non-invasive method of contraception that can attain a reasonably low rate of failure.

Any method to determine the day of ovulation could be based on detection of one of the three following endocrine events associated with ovulation: the rapid rise of estradiol, the LH surge or the rise in 17-hydroxy progesterone and progesterone. Any endeavor to predict ovulation must involve the direct determination of serum E.sub.2 or T.E. in urine of the metabolic effects of the rapid E.sub.2 rise. The daily laboratory determination of E.sub.2 in blood or estrogens in urine cannot serve as a popular method of family planning.

One of the parameters of follicular maturation and the rise in estrogen production is the quantity and rheological properties of the cervical mucus. The quantity of cervical mucus increases markedly from 60mg/day, on days 8-9 of the menstrual cycle to a peak of 200-700mg/day at ovulation. This is due mainly to the water content of the cervical mucus. One other important characteristic is the change in cervial mucus viscosity which is at its lowest at ovulation.

It is therefore an object of the present invention to provide a method and apparatus that will give a rapid reading of water content in the vaginal cavity. According to the invention, there is provided a plurality of identical pellets of hydrophilic material which swell on the uptake of aqueous liquid and a gauge comprising an apertured plate.

In use of the method and apparatus according to the invention, during the woman's menstrual cycle, or at least the portion thereof which extends from several days before up to about or after the onset of ovulation, a pellet of hydrophilic material is placed inside the vaginal cavity for a fixed time period during each twenty hours four hours. Conveniently, this is done by inserting the pellet into the vaginal cavity each night and leaving it there for a period of eight hours. It is possible that longer or shorter time periods can be used with satisfactory results, provided that the time period is sufficiently long to cause the size of the pellet to swell to a value indicative of the water content and volume of the vaginal mucus. At the end of this period, the pellet is removed from the vaginal cavity and measured with the apertured gauge. If the pellet is able to pass through the aperture, this indicates that the water content of the cervical mucus has not risen sufficiently to indicate the onset of ovulation.

The process is repeated each day with a fresh pellet until it is found that the pellet has expanded sufficiently in size, as a result of the increase in the water content of the cervical mucus, that it will not pass through the aperture in the gauge. It may then be predicted that ovulation wil take place within a given number of days.

Thus, it has been found by experimentation that the peak variation in the size of the pellets, as a result of the absorption of water from cervical mucus, is closely related to the LH surge and the variation in basal body temperature.

The hydrophilic material of the pellets must be capable of swelling markedly as a result of the variation in the water content of cervical mucus which takes place during each menstrual cycle and must also be a material which is compatible with human tissue.

Copolymers of N-vinyl pyrrolidone and methyl methacrylate, made with or without small amounts (up to 2%) of cross-linking agents, which polymers may have weight percentage water uptakes of up to 100%, or even higher, have been found to be especially suitable for this application. These polymers are in an anhydrous (nonswollen) or substantially anhydrous condition when inserted into the vaginal cavity and they swell as a consequence of contact with the vaginal mucus and uptake of water therefrom. The polymers may be made by a known process of polymerization initiated by a chemical initiator, for example, a peroxide (as in British patent specification No. 1 391,438 and U.S. Ser. No. 530,570, now U.S. Pat. No. 4,032,599, the entire contents of which are incorporated herein by reference, for their description of the compositions and polymerization processes for preparing the hydrophilic polymer). However, polymers made by polymerization initiated by ultraviolet or gamma ray irradiation, as described in British patent specification No. 1,439,132 and U.S. Pat. No. 3,943,043, are of special significance. Polymers produced by the irradiation process are free from the impurities present as a result of the use of initiation additives, and are thus less liable to promote allergic reaction when in contact with human tissue.

In general the invention contemplates the use of physiologically harmless, hydrophilic polymers which will swell by absorption of water, when in contact with the cervical mucus, to a degree indicative of the water content of the cervical mucus. The polymer is anhydrous or substantially anhydrous when it is placed in the vaginal cavity so that the increase in size that occurs will reliably indicate the water content and water volume of the cervical mucus.

One such material which is particularly suitable for this purpose is vinyl pyrrolidone/methyl methacrylate copolymer which is sold under the registered trademark Sauflon 85. In this polymer the volume of the anhydrous polymer is about 17.1% of the volume when the polymer is fully swollen in physiological saline solution.

It has been found that cylindrical pellets of this material, having a diameter of 8mm and a length of 8mm swell to a diameter of up to 12.9mm when the water content of the cervical mucus reaches its peak. Thus, if a gauge is provided with an aperture having a diameter of 11mm, it may be assumed that whenever a pellet has swelled until it can no longer be received in the aperture, then ovulation is imminent and the fertile period has begun.

In certain people a more positive sign of the approach of ovulation may be a sudden rise in vaginal water content. This water content may be monitored by measuring daily the size of the swollen pellet, using a gauge such as the one described hereafter with reference to FIGS. 3 and 4; or by setting a pointer (such as the one described hereafter with reference to FIGS. 5 and 6) to a particular day's pellet diameter and thereby highlighting any large increase in the subsequent day's measurement.

With hydrophilic pellets as described, it is possible to attach a short cord to each pellet for ease of removal of the pellet from the vaginal cavity.

Embodiments of the invention are hereinafter described, by way of example only, with reference to the accompanying drawings:

FIG. 1 is a cross-section view through the central axis of a swollen hydrated cylindrical pellet;

FIG. 2 is an elevation of a non-swollen pellet prior to hydration;

FIG. 3 is a plan view of a gauge provided with a plurality of circular apertures of varying sizes;

FIG. 4 is an elevation of the gauge in FIG. 3;

FIG. 5 is a plan view of alternative gauge provided with a graduated tapering aperture and a pointer slideable along the scale;

FIG. 6 is a view of the elevation of the gauge in FIG. 5;

FIG. 7 is a perspective view of a test kit comprising a gauge and a supply of non-hydrated pellets;

FIG. 8 is a graph showing the relation between size of the pellets, LH readings and basal body temperature, for three typical female humans.

The swollen cylindrical pellet 16, shown in FIG. 1, is provided with a cord 13 which is embedded in a cap 15. The cord 13 passes through an aperture along the central axis of the cylindrical pellet and into the cap 15 so as to retain the swollen pellet 16 on the cord 13 and facilitate removal of the swollen pellet 16 from the vaginal cavity by pulling the cord 13.

The cylindrical pellet 10, shown in FIG. 2, is in a non-hydrated state. The diameter of the cap 15 and the pellet 10 are substantially equal and the central axes of the cap 15 and the pellet 10 are aligned by the cord 13 so as to facilitate insertion of the assembly 17 into the vaginal cavity. Insertion is further facilitated by the formation of the cap as a dome-shape.

The diameter of the swollen cylindrical pellet 16 is measured, in the embodiment shown in FIG. 3, by inserting the swollen pellet into an aperture 19 in the gauge 18, choosing the hole so that a close-fit is achieved and reading the appropriate diameter marked adjacent the aperture. The test of a close-fit in any particular aperture is that the swollen pellet 16 will not fit into the aperture which is next smallest in diameter. The diameter of each of the apertures 19 is indicated by raised numerals formed on the surface of the gauge 18 adjacent their respective apertures. As FIG. 4 shows, the gauge 18 in the embodiment of FIG. 3 is substantially planar. The gauge 18 is conveniently made by injection molding polymethylpentane or polymethylmethacrylate, or a similar transparent plastics material.

FIGS. 5 and 6 are views of an alternative embodiment of a gauge for measuring the size of the swollen pellet 16. The gauge allows measurement of both the diameter and length of the swollen pellet 16 so as to assess more completely the amount of swelling of the pellet 16. The swollen pellet 16 is inserted into the wider end of the tapered aperture 20 in the molding 21 in a direction perpendicular to the plan view in FIG. 5 and is moved towards the narrow end of the tapered aperture 20 until binding between the wall 22 and the swollen pellet 16 prevents further movement in this direction. The width of the tapered aperture 20 at any given point along its length is indicated by graduations and raised numerals on a scale 23 alongside the tapered aperture 20. The number next to the graduation closest to the mean position of the swollen pellet 16 in the tapered aperture 20, indicates the approximate diameter of the swollen pellet 16.

The wall 22 of the tapered aperture 20 also tapers so that its height (measured from the top edge 25 of the wall 22 to the far side of the base plate 26) is equal at all points along its length to the width of the tapered slot at this point. The side of the wall 22 also carries the same gradations as the base plate 26. The swollen cylinder may be moved along the tapered aperture 20 until its length most closely equals the height of the wall 22. The length of the swollen cylinder may then be read from the scale 23.

The pointer 24, which slides along the scale 23, may be set to provide a record of the mean measured length and diameter of the swollen pellet 16 on that day. This may be compared to the next day's measurement and any significantly large increase from day to day may, depending on the particular pattern of vaginal water content changes in any particular person, indicate the onset of ovulation.

In FIG. 7, twelve cylindrical pellets 10 of vinyl pyrrolidone/acrylic copolymer are mounted in a tray 11 which also contains a gauge 12. The pellets 12 are cylindrical in shape having a diameter of 8mm and a length of 8mm. Each pellet 10 is provided with a removal cord 13 which is threaded through a diametral aperture formed in the pellet 10. As shown, the gauge 12 is formed with a circular aperture 14 having a diameter of 11mm.

In use, one of the pellets 10 is placed inside the vaginal cavity each night, for a period of eight hours. Each morning, the pellet 10 is removed, by means of the cord 13, and measured with the gauge 12. If the pellet 10 is small enough to be received within the aperture 14, then it can be said that the fertile period has not yet started and that ovulation is not imminent. When it is found that the swelling of the pellet 10 is such that it cannot be received within the aperture 14 of the gauge 12, it may, in a particular person, indicate that the fertile period has commenced and that ovulation is about to take place.

It has been observed that water content of bovine cervical mucus is maximal at ovulation and similar pattern was found in human cervical mucus, Blair, et al, Nature (Lond) 147:453 (1946); Bommerenke, Am. J. Obst. Gynec. 52:1028 (1946); and Kopito et al, Fertil. and Steril. 24:499 (1973). The utilization of the timing of change in vaginal mucus to a clear slippery discharge, at ovulation, was proposed as a method of family planning, Billings, Lancet 11, 1193 (1972).

The correlations between water content of the vaginal mucus, serum LH titers and basal body temperature in 12 women, with regular ovulatory cycles, were studied.

The water content of the vaginal mucus was determined by the degree of expansion due to hydration of cylinders of hydrophilic polymers that were left in the vagina for about 8 hours. These cylinders were made of vinyl pyrrolidone/methyl methacrylate copolymer (Sauflon 85) that were 8mm long with a diameter of 8mm. A perforation in the cylinder allowed threading, for easy handling.

The women were asked to place the hydrophilic cylinders in the vagina at night. The next morning, these cylinders were removed. The degree of hydration was determined by checking the new diameter of the cylinder, in a suitable perforated plate. In all cases, blood for serum LH (RIA) was taken on the morning when the cylinder was removed.

The results showed a close correlation between the serum LH surge and the peak expansion of the cylinder, expressed as ".DELTA. Diameter" (.DELTA..sub.D), which is the difference between the initial character of the cylinder and that found after 8 hours in the vagina. The peak in .DELTA..sub.D coincided with the LH surge in 6 cases, preceded the LH surge by 24 to 48 hours in 4 cases, and followed the LH surge by 24 hours in 2 cases. There was a similar good correlation with the shift in basal body temperature. The data is shown in FIG. 8.

The maximal .DELTA..sub.D reached was 4.6mm. Assuming a .DELTA..sub.D limit of 3.2mm, as the beginning of the fertile period, there is defined a relatively short period, between 48 hours before and up to 24 hours after the LH surge. Since the serum LH surge preceeds ovulation by 24h, the .DELTA..sub.D may serve as an indication of impending ovulation.