Routine assessment of ovulation is unlikely to be medically necessary among eumenorrheic women

Because ovulation induction is generally the first-line treatment target for couples with difficulty conceiving, existing recommendations regarding the role of ovulation testing among regularly menstruating women should be clear and evidence based. The American Society for Reproductive Medicine (ASRM) recommends ovulatory function assessment as part of the female subfertility workup without specification to menstrual history regularity, and the U.K.-based National Institute for Health and Clinical Excellence (NICE) recommends midluteal progesterone testing for confirming ovulation, even among regularly menstruating women.

Because ovulatory disorders are cited to account for up to 40% of subfertility, and subsequent clinical course relies on accurate assessment of ovulatory dysfunction, their identification during the subfertility workup is indeed consequential. However, all three types of ovulation disorders classified by the World Health Organization (1) (i.e., hypothalamic pituitary failure, hypothalamic pituitary dysfunction, and ovarian failure) occur in the setting of menstrual cycle disturbances (e.g., amenorrhea and oligomenorrhea). We are unaware of reliable evidence documenting the presence of consistent ovulatory dysfunction among regularly menstruating women. Indeed, as Chinta et al. (2) note in this issue of Fertility and Sterility, cycle disturbances are often a sufficient criterion for diagnosis of ovulatory dysfunction in clinical practice (2). Accordingly, we agree with the authors’ perspective that menstrual history may be sufficient to “determine ovulatory status in most cases” (2). Although ovulatory disorders are characterized by high anovulation prevalence, we reason that incident ovulatory status is not clinically relevant among eumenorrheic women, because sporadic anovulation is only likely to occur up to two cycles per year among this population, with minimal potential impact on pregnancy. But do the available data support this?

In their manuscript, “Revisiting the role of serum progesterone as a test of ovulation in eumenorrheic subfertile women: a prospective diagnostic accuracy study,” Chinta et al. (2) report a 0.5% and a 7.1% prevalence of anovulatory cycles in eumenorrheic subfertile women, based on ultrasound and midluteal serum progesterone assessment, respectively. These findings are in line with previously reported incidences of sporadic anovulation of 1% (3) to 14.5% (4) based on urinary hormone assessment among other cohorts of regularly menstruating women attempting to conceive. This wide reported range is affected by normal variation in the strength of endocrine signals coupled with the specific algorithm or cutoff point applied to define anovulation. Although Chinta et al. (2) conclude that serum progesterone testing may not be needed when a single well timed ultrasound is available to confirm ovulation, the question remains as to whether routine ovulation testing among eumenorrheic women is even necessary. Though the rates of sporadic anovulation in eumenorrheic women seem to be quite low, it is still crucial to determine whether this albeit low prevalence of sporadic anovulation may meaningfully influence fertility and pregnancy rates.

Our recent work used clinical data to design a simulation study to evaluate the impact of sporadic anovulation on fecundability and cumulative pregnancy rates among regularly menstruating women (5). We found that sporadic anovulation reported among eumenorrheic women across the range of 1%–14.5% produced differences in median time to pregnancy by only a single menstrual cycle and in cumulative pregnancy rate of only 4.0% over 12 consecutive menstrual cycles. To put this into context, we also observed that varying mean intercourse patterns from weekly to every other day resulted in a five-cycle median reduction in time to pregnancy and a nearly 29% increase in cumulative pregnancy rates over 12 cycles. This work importantly highlights that pregnancy rates do not seem to be meaningfully affected by sporadic anovulation, even across the full range of reported prevalence of anovulation among eumenorrheic women. Taken together with the new evidence from Chinta et al. (2) that a separate timed serum test appears to be unfounded in eumenorrheic women, this suggests that routine ovulation testing among eumenorrheic women is a practice unsupported by existing evidence and should be reserved for women with irregular menstrual history.

These findings call into question current ASRM and NICE recommendations on ovulation testing among eumenorrheic women and highlight the need for evidence in clinical diagnostic testing. Furthermore, from a resource perspective, ovulation assessment requires correct timing, laboratory support, and clinic visits (2). Relieving eumenorrheic women and their providers of this seemingly unnecessary but routine step of the infertility workup will conserve time and financial resources for these patients and the health care system alike, particularly when, if medically warranted, ultrasound conducted for other clinical purposes in the infertility workup can suffice in lieu of an additional serum test, as shown by Chinta et al. (2). We expect that recommending routine ovulation testing only to women with irregular menstrual histories would streamline clinical care, ethically reduce the emotional burden of excessive testing that does not improve clinical outcomes, and reserve these clinical resources for women who will benefit from this testing. Of note, although this includes the use of at-home “ovulation predictor kits” to confirm ovulation, couples may find value in using ovulation prediction for timing intercourse to the fertile window, because that practice has been shown to increase fecundability.

Because existing evidence does not support routine ovulation testing as part of the female subfertility workup among women having regular menstrual cycles, the next step is to determine whether ovulation induction is an appropriate first-line treatment target for eumenorrheic women experiencing difficulty conceiving, as we seek to direct all populations toward their appropriate clinical course sooner and more efficiently.