Luteal Phase Deficiency

I have had the feeling for some time that luteal insufficiency as a recurring phenomenon in a given woman is often overdiagnosed. However, the definitive study has still not been performed.
Jaffe 1993, 484

Many couples sitting in their doctor's waiting room have already been initiated into one fertility ritual. Every morning, as soon as the woman wakes up, she reaches to the nightstand and places a special thermometer under her tongue for five minutes. She records this early morning temperature with a dot for each day of her menstrual cycle on graphed paper known as a basal body temperature (BBT) chart. So many women have spent so many mornings taking their temperature before doing anything else that the activity has become a not very private joke among fertility patients. The woman watches for a mid-cycle temperature rise indicating ovulation has occurred. If the temperature drops back before fourteen or so days, marking the end of that monthly cycle (and usually the start of her period), this woman is likely to hear a diagnosis of "luteal phase deficiency" or "defect" (LPD). Her doctor may then prescribe treatment with hormonal medication to correct this condition.

The luteal phase is the time between ovulation and the start of a woman's menstrual period, often thought of as the last half of her menstrual cycle. Luteal phase deficiency is a menstrual cycle abnormality generally defined as inadequate production of the hormone progesterone by the corpus luteum (the ovarian follicle from which a mature egg has just been released) following ovulation. If there is not enough progesterone and/or if production of this hormone does

not continue over enough days, the uterine lining will not receive the hormonal stimulation needed to allow implantation of an embryo. Patients diagnosed with luteal phase deficiency need to understand two basic facts about this condition: first, the diagnosis itself is uncertain, a focus of controversy among fertility specialists; and second, this uncertain diagnosis leads to treatments that are similarly controversial.

To judge by the arguments and questions among physicians, LPD might best be considered an infertility diagnosis in name only. Some specialists dispute the existence of this fertility problem altogether, placing women so labeled within the category of unexplained infertility. Although critics might grant that a condition dubbed LPD does exist in some women, they question whether this condition lowers a couple's fertility. To be defined as a factor contributing to subfertility, the condition must be consistent and repetitive, with an impact on the woman's chance for pregnancy. Instead, LPD is sporadic throughout women's reproductive life, a condition found in normally fertile women at the same rate as in the infertile, a rate expected by chance alone. As one study indicates, LPD is often observed to coincide with common events in a woman's life—including the first years of menstruation, times of stress or of very strenuous exercise, the postpartum period, the last years of menstruation.^[36] Patients need to know that critics within the profession are asking if the diagnosis and treatment of luteal phase deficiency improves the likelihood of pregnancy. So far, the answer appears to be no.

As with the elephant described by the blind men, a major problem is the absence of ways to identify accurately this entity called luteal phase deficiency. All three diagnostic tools that physicians use have serious flaws. The first and easiest tool is the basal body temperature (BBT) chart indicating whether ovulation has occurred and, if so, the length of the luteal phase. However, this daily record of a woman's morning temperature, so well known among fertility patients (see Figure 2), does not correlate well with other diagnostic techniques and does not distinguish patients ultimately thought to have a luteal deficiency.

The second diagnostic tool is a blood test measuring the woman's progesterone level during the luteal phase of her menstrual cycle in an attempt to determine whether she is producing enough of this hormone to support an embryo. Physicians do not know, however, on which day, or days, to draw a blood sample in order to gain information most useful for treating that woman. Further complicating blood tests, no matter the day, are the "frequent and rather wide fluctuations in serum [progesterone] levels over 24 hours."^[37] Because this hormone is released into the bloodstream in an intermittent pulsatile pattern,

Figure 2
Basal body temperature chart (BBT). This sample chart shows a typical
"normal" pattern of body temperature taken before rising in the morning.
The mid-cycle rise and plateau (luteal phase) indicate that ovulation occurred.
The temperature then drops if no pregnancy occurs; the next cycle begins
with the first day of menstruation. If there is no sustained temperature rise,
ovulation probably has not occurred. Fewer than 11–12 days of elevated
temperature may be interpreted as a sign of luteal phase defect (LPD).
However, basal body temperature can also be affected
by such factors as insomnia or illness.

serum levels will naturally vary at different times of day and night. The level of progesterone circulating in a woman's bloodstream, moreover, may not even reflect information actually needed about hormonal stimulation of endometrial tissue. That stimulation does not depend only on amounts of hormone produced and circulating in blood throughout her body. Hormones must also interact adequately with hormone receptors—in this instance, located in the uterine lining—to achieve their needed effect.^[38]

The third diagnostic approach, endometrial biopsy, is intended to analyze uterine tissue, in order to assess more directly the endometrium's preparation for implantation of an embryo. Though frequently performed, recent studies question the usefulness of this more invasive, painful, and costly test for predicting pregnancy success. Again, there are unresolved questions about when, during the second half of a woman's menstrual cycle, this test should be performed and about the need for testing on more than one day. The procedure itself can cause an early menstrual period, artificially reinforcing a picture that leads the doctor to a diagnosis of luteal phase deficiency.

At best, medical discussions of methods for identifying LPD describe evidence that is "suggestive," but not "diagnostic," of "rough approximations" rather than accurate or valid data. The incidence of LPD, many specialists now argue, is

considerably lower than previously claimed on the basis of the above tests. Even more important, women identified through such tests do not appear to have lowered fertility. Simply put, one review of diagnostic methods concluded: "The diagnosis of LPD in the clinical setting remains problematic and controversial primarily because there is no practical diagnostic method that has been validated."^[39] And a study of endometrial biopsy in particular found "firstly that diagnosis of LPD in both infertile and fertile women represents only a chance event; secondly, histological [from biopsy tissue analysis] endometrial adequacy or inadequacy in the cycle of conception or in previous cycles is not related to the outcome of pregnancy in infertile patients. Finally, treatment of LPD does not improve pregnancy outcome in infertile women. Thus, luteal phase evaluation [through biopsy] of the endometrium is not worthwhile."^[40]

This final conclusion points to the crucial added problem attached to the diagnosis of LPD: diagnosis does lead to treatment . Not only do women undergo unpleasant, often painful, and costly tests that are not worthwhile, but these tests then become the basis for undergoing treatments never demonstrated to be worthwhile. Doctors commonly prescribe progesterone supplements following ovulation, yet there is no evidence this treatment improves pregnancy rates. Doctors try pre-ovulation clomiphene citrate in an effort to attain a "better" ovulation that will produce greater amounts of progesterone, though some specialists advise that clomiphene should not be given to women who ovulate.^[41] After clomiphene, the doctor may prescribe the more powerful, difficult, and risky hMG; however, this treatment can itself shorten the woman's luteal phase. Confusion has come full circle—a treatment is tried on women to correct a particular condition whose very existence is a bone of contention; the treatment may cause symptoms of the diagnosed condition and must certainly obscure what is cause, what is effect, why the woman is not pregnant.

All such interventions bring risk—in these cases, with no known benefits. And, there is the further risk of initiating a self-perpetuating cycle of worthless diagnoses and futile treatments, with women and their doctors caught by the irresistible momentum of doing something. One can well imagine the following scenario: a couple has now accumulated three months of basal body temperature charts. One month the elevated dots cover thirteen days, another month ten, then thirteen again. The doctor orders a blood test for progesterone, which measures in the low-normal range. The doctor prescribes progesterone. After several months, he adds Clomid. Two months later the woman comes to the office for an endometrial biopsy, a procedure far more painful than the nurse described when she advised the woman to arrive well-dosed with Motrin. A

shorter luteal phase follows. The doctor escalates to hMG injections; the woman must schedule her days around the injections and frequent ultrasound monitoring of her ovaries to check for ovarian hyperstimulation syndrome. Still not pregnant, the couple asks, "What now?"

There is no good way for the couple or the doctor to answer this question. From the very first step, the months of BBT charts, the missing element was knowledge about the biology of this woman's fertility problem, if indeed she has one. Without such knowledge, no specialist can determine whether any treatment will help the woman conceive. As matters now stand, patients and their doctors are dealing with what the American College of Obstetricians and Gynecologists officially describes as "a term applied to a poorly understood group of subtle hormonal alterations."^[42] The diagnosis encompasses a heterogeneous group. Some women have never conceived, others miscarry very early in pregnancy. Some women ovulate regularly, others do not. Hormonal evaluations show varying patterns of various hormones. For some subgroup of women, medical intervention may improve fertility, but there is not way of knowing for whom or with what intervention.

The entity called LPD illustrates the need for more concise and discriminating diagnostic methods before applying treatments to individual women, as well as for treatments that target more specifically an identified fertility problem. In the meantime, the large, heterogeneous group of women diagnosed with LPD undergoes the same therapies when, in fact, their underlying physiological conditions call for differing medical treatment—or perhaps none at all. Indeed, this particular diagnostic label may become a historical remnant in this era of cost concerns. In the words of one specialist, LPD will be a "so what?" diagnosis. Why perform tests at all—especially flawed, often costly tests—when women will be given the same broadscale treatments anyway? Rather than improve diagnostic abilities to better determine individual patient needs, the label will fade—but interventions will continue to engulf a number of vaguely defined fertility problems.

Although physician enthusiasm for the LPD diagnosis may wane, two areas of fertility medicine attracting active and increasing attention—male factor and immunologic infertility—demonstrate how the existence of a diagnosis fuels precipitous intervention in the absence of adequate biological knowledge. These diagnoses may eventually identify well-understood physiological conditions that impair fertility and respond to treatment in some couples, affecting more definable and limited populations of women and men than does the amorphous luteal deficiency; at present, however, male factor and immunologic diagnoses

display a sense of groping in the dark and the risks such groping can bring. Patients need to be all the more cautious about new and unproven procedures on the one hand and outdated and disproven procedures on the other.