Plasma progesterone concentrations drawn at the time of endometrial biopsy in 26 infertility patients with histologically documented luteal phase inadequacy were compared with those of 26 infertility patients with normal biopsies. Although as a group the former patients had lower progesterone values and shorter cycles, there was considerable overlap. Therefore, although plasma progesterone determinations and temperature charts are useful in the detection of ovulation and in the interpretation of the biopsy results, a properly obtained endometrial biopsy is essential for the diagnosis of luteal phase inadequacy.
In order to clarify the relationship between endometrial histology and progesterone (P4), plasma P4 and estradiol levels in the luteal phase were measured in 126 cases of unexplained infertility. Endometrial biopsies were performed in the midluteal period of menstrual cycles. Forty-three of the 126 cases showed retarded endometrium. Of these 43 cases, 23 exhibited three different types of abnormal P4 secretion. Type A showed low P4 levels throughout the luteal period. Type B showed low P4 levels only in the early luteal period. Type C showed normal P4 levels in the early luteal period followed by a prompt decline. These findings indicated that P4 determination during the early, mid- and late luteal phases is necessary to assess P4 secretion. However, 20 of the 43 cases had normal P4 levels through the entire luteal phase, demonstrating an insufficient response of the endometrium to P4. Consequently, histological examination of the endometrium is required to investigate the luteal phase defect.
Menstrual CycleLuteal Phase Defect EtiologyNormal Follicular DevelopmentLuteal Phase Dating
Luteal phase defect (LPD) accounts for a significant proportion of reproductive disorders, however its etiology is still debated. A prospective study was performed on 37 ovulatory women to determine whether LPD can occur in cycles characterized by completely normal folliculogenesis. Criteria for normal a gradual rise of serum estradiol, a luteinizing hormone (LH) surge, the presence of a dominant follicle that disappeared, an increase of serum progesterone, and normal serum levels of prolactin, testosterone, dehydroepiandrosterone sulfate, follicle-stimulating hormone, and LH. Thirty of 37 women fulfilled the above mentioned strict criteria and underwent endometrial biopsy in the late luteal phase. Seven of 30 (23%) demonstrated a delay in endometrial development and all had normal hormonal and ultrasonographic parameters of folliculogenesis and ovulation. Women with delayed endometrial development demonstrated slightly longer follicular phases (17.0 +/- 1.1 versus 14.5 +/- 0.3 days). Perfectly normal follicular and periovulatory events may be followed by deficient luteal phases.
InfertilityDiagnostic EvaluationLuteal Phase ProfilesLuteal Phase Dating
The authors have further analyzed women diagnosed as having luteal phase insufficiency in hope of determining the value of specific screening tests as well as determining the degree of heterogeneity of pathophysiologic mechanisms involved in the disorder. Twelve women with the disorder were identified, 6 with two consecutive midluteal serum progesterone (P) levels less than 10 ng/ml (group 1) and 6 with two consecutive late luteal phase endometrial biopsies out of phase (group 2); 4 infertile women with normal serum P and late luteal biopsies also were studied (group 3). All underwent serum sampling for P and luteinizing hormone (LH) at 20-minute intervals for 24 hours, beginning at 9:00 A.M. of day 7 post-LH surge. No significant differences were noted among the three groups for LH area under the curve, pulse frequency, or pulse amplitude. Furthermore, no differences were ascertained for P area under the curve. However, individuals were identified who had one or more hormonal abnormalities but no abnormal biopsy, as well as patients with normal hormonal profiles but having abnormal endometrial development. Receiver Operating Characteristic curves demonstrated that pooled morning serum P levels provided optimal predictive ability of biopsy results. The authors conclude that luteal phase insufficiency is a heterogeneous disorder, and that neither endometrial biopsy nor serum hormonal analysis obviates the need for the other.
Three hundred and ninety-six patients were evaluated for primary and secondary infertility between December 1976 and May 1979 at a large referral center. Timed late luteal endometrial biopsies were routinely obtained as part of the work-up and were repeated for confirmation if subsequent menses did not occur within 2 days of the expected date. If both biopsies were abnormal, a diagnosis of luteal phase defect (LPD) was made and patients were treated with vaginal progesterone suppositories for a minimum of 6 months. LPD was discovered in 32 of 396 patients (8.1%); among those patients whose infertility was not complicated by other abnormalities, 9 of 13 conceived (70%) and 7 of 13 carried to term (54%). These data suggest an incidence higher than generally recognized and a very encouraging response to replacement therapy.