Cycle Variants : the Continuum

The time taken for the total fertile ovulatory process, that is, the beginning of the rapid growth phase of a follicle, its development, ovulation, formation of the corpus luteum and its demise (at menstruation), is always approximately 21 days. In a 28-day cycle it takes about 7 days for the FSH values to rise to threshold and for a follicle to commence its rapid growth phase. During these 7 days very little oestradiol is produced and the woman experiences several days of a BIP after cessation of bleeding. Many variants of the 28-day ovulatory cycle may occur.

Fully ovulatory cycles as short as 19 days have been observed. In these the oestrogen values were already rising on day I of the cycle showing that a follicle was developing at this time and the fertile phase had begun.

Figure 2

Alternatively, the rise in FSH production to the threshold may be delayed and this is one of the causes of lengthening of the cycle. While the FSH levels remain below the threshold no follicle begins its rapid growth phase, very little oestradiol is produced, and the cervix remains unstimulated. The woman experiences an unchanging succession of "dry" days or days with minimum vaginal discharge (BIP). However, unless the woman has reached the menopause or has permanent amenorrhoea, the FSH output eventually rises above the threshold and the ovulatory events are set in train with the same timing as in the 28-day cycle.

Figure 3

In another variant, the FSH levels rise to exceed the threshold, a follicle develops but does not progress to ovulation. The developing follicle produces oestradiol causing a corresponding change in the vaginal discharge. The FSH levels may then return to sub-threshold values, the follicle atreses, the oestradiol levels return to their baseline values with a return to the dry BIP. No LH is released, no progesterone is produced and no PC day or Peak day is identified. Depending on the amount of oestradiol produced and the sensitivity of the uterine endometrium of the individual, there may or may not be sufficient stimulation of the endometrium to result in an oestrogen withdrawal bleed. If bleeding does occur, this is anovulatory bleeding (see below). The next follicle which develops may have the same fate but eventually a follicle develops and proceeds to a full ovulatory response. In this case, the woman sees patches of mucus production when each follicle is partly developed and the oestradiol levels are correspondingly elevated with intervening return of the BIP when the follicle atreses and the oestradiol levels return to base line. However, when the follicle that eventually ovulates develops, mucus production then shows progressive development, and a progesterone change and a Peak day are recognized. Thus the woman can conclude that she has ovulated, she can calculate her entry into the post-ovulatory infertile phase and predict that menstruation will occur approximately 14 days later. Such transient attempts at follicular development before full follicular maturation and ovulation constitute another cause of long cycles.

Figure 4

In yet another variant, the rise in FSH production above the threshold may arrest before the intermediate level is exceeded and the follicles remain in a state of chronic stimulation. The amounts of oestradiol secreted stabilize at levels less than those of the pre-ovulatory peak. The vaginal discharge shows fertile characteristics corresponding to the oestradiol levels reached but these do not progress. If this situation persists the stimulated uterine endometrium may break down as oestrogen breakthrough bleeding. The FSH levels may then return to sub-threshold levels, the oestradiol levels return to base line and the vaginal discharge returns to the dry BIP.

Figure 5

However, more usually, the feed-back mechanism corrects itself, the FSH values begin to rise again, they exceed the intermediate threshold and a follicle is boosted to ovulation with the same mechanisms, timings and Peak day calculation as in the 28-day ovulatory cycle. This situation is the cause of pre-ovulatory bleeding or spotting. Indeed, it is the final rapid rise in oestradiol output to the pre-ovulatory peak which stops the bleeding and the woman should be aware that she is in a phase of high fertility during such a bleed, i.e. a bleed which has not been preceded approximately 14 days earlier by an identifiable progesterone mucus change (PC).

Figure 6

In other variants of the ovarian cycle a follicle is boosted towards ovulation but the release of LH is faulty. Sometimes the release mechanism may not operate at all, there is no LH surge resulting from the raised oestradiol levels, the boosted follicle has a limited life span, it atreses and the resulting fall in oestradiol output signalling the end of the follicle's rapid growth phase results in oestrogen withdrawal bleeding. The raised oestradiol levels cause mucus to be produced but no PC day (or Peak day) can be identified because there is no rise in progesterone production. This is one form of anovulatory ovarian activity.

Figure 7

In another form, some LH is released but not in sufficient amount to cause rupture (ovulation) of the boosted follicle but sufficient to cause a small amount of luteinization of the follicle which in turn causes a small amount of progesterone to be produced for a short period of time. This is known as the luteinized unruptured follicle (LUF). No clear PC day (or Peak day) can be identified (the symptoms are "fuzzy") .

Figure 8

An LUF may or may not be followed by a bleed and, as in the previous variant, the next episode of ovarian activity may be a fully fertile ovulatory cycle or a repeat of a variant.

Figure 9

Another variation is seen when the LH surge is sufficient to cause ovulation but is insufficient to produce a fully formed corpus luteum capable of supporting a pregnancy. The progesterone levels rise above those seen in an LUF, usually sufficient to cause a PC. However, either they do not reach the levels seen in a fully formed corpus luteum, or they reach normal post-ovulatory values and fall prematurely so that bleeding occurs 10 days or less after ovulation. The first is known as the "deficient luteal phase" and the second as the "short luteal phase". Both cycles are ovulatory but infertile, both are followed by menstruation and the Peak rule applies.

Figure 10

Figure 11

The deficient luteal phase may be associated with some difficulty in recognizing a PC and calculating the Peak day or of diagnosis by hormone assays, and the short luteal phase can be recognized by the shortened interval between the Peak day and menstruation. A cycle which results in a continuing pregnancy must ipso facto be a normal fertile cycle. However, when the luteal phase progesterone levels of such a cycle are in the lower range of normal it is difficult to distinguish that cycle from an infertile cycle with a deficient luteal phase. The distinction is unimportant for pregnancy avoidance but it is important for pregnancy achievement where persistently low luteal phase progesterone levels can be enhanced by giving clomiphene and this is an important means of increasing pregnancy rates in these cases.

These cycle variants have been described as if they were separate entities. Actually, one merges into the next so that there is a continuous gradation from no follicular activity (amenorrhoea) through follicular activity without an LH surge (anovulatory ovarian activity), through increasing maturation of the LH mechanism up to the fully fertile ovulatory cycle. We term this the "continuum" of ovarian activity.

Figure 12

At menarche, the first bleeding cycle is usually anovulatory and it may take several years for the full LH response to mature and fertile ovulatory cycles to commence. The reverse occurs as menopause approaches. Return of fertility after childbirth and during breast-feeding is similar to the mechanism at menarche but the time intervals between the variants are shorter. In athletes, a woman with regular ovulatory cycles frequently shows changes during times of intensive training, first to deficient luteal phases, then to LUFs, anovulation and finally amenorrhoea and then reverts back within a few months of ceasing training to fully fertile ovulatory cycles.

Figure 13

The cycle variants do not necessarily repeat themselves from cycle to cycle. For example, with approach of menopause or during stress, the woman may experience periods of amenorrhoea or a series of anovulatory cycles or LUFs interspersed with fully fertile ovulatory cycles. As pregnancy can result from only the fully developed ovulatory cycle, one would expect that all the days that the other cycle variants were in progress would be available for intercourse if the aim is pregnancy avoidance. The problem is that the build-up to these infertile cycle variants is the same as for the ovulatory cycle and the fact that they were actually infertile is seen only in retrospect by the absence of a distinct PC or a shortening of the luteal phase. Thus vigilance is required at all times and the Early Day Rules of the BOM are applied until a distinct PC is felt. The cycle variants should not be considered as abnormal, they are normal responses to the environment to ensure that pregnancy does not occur under very unfavourable conditions for the mother and fetus. Being able to identify an infertile cycle variant while it is still in progress is the aim of future research.

Figure 14

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