To evaluate the luteal phase in women with rigorously defined unexplained infertility.
Design
Prospective study.
Setting
National Center for Infertility Research at Michigan.
PATIENT(S): Evaluation of 1,885 women with infertility identified 12 women who met the rigorously defined criteria for unexplained infertility: [1] infertility of > or = 24 months duration, with no male factor, anatomic-functional disorders of the reproductive tract, or immunologic infertility; [2] normal body mass index (BMI); [3] ovulatory cycles ranging from 26 to 32 days; [4] normal luteal phase determined by endometrial biopsy; and [5] normal baseline hormonal profile. Controls (n = 12) were healthy, parous women with normal ovulatory cycles, normal hormonal screen, and were matched for age and BMI to patients.
MAIN OUTCOME MEASURE(S): Pattern of follicular growth rate and luteal phase hormonal profile.
RESULT(S): Women with unexplained infertility did not differ in menstrual cycle characteristics, follicular growth rate or mean preovulatory follicle diameter, or endometrial biopsy dating. The mean levels of P tended to be lower in the unexplained infertility group throughout the luteal phase, but only the midluteal interval reached statistical significance. Luteal phase mean integrated P or urinary PDG levels of unexplained infertility women did not differ from those of fertile controls. The ratio of integrated E2:P also was significantly greater in women with unexplained infertility than in fertile controls.
CONCLUSION(S): Women with rigorously defined unexplained infertility have subtle hormonal anomalies during the luteal phase when compared with fertile controls.
PMID 9091327 9091327 DOI 10.1016/s0015-0282(97)80066-0 10.1016/s0015-0282(97)80066-0 Blacker et al. 1997, Blacker 1997
Cite this article
Blacker, C. M., Ginsburg, K. A., Leach, R. E., Randolph, J., & Moghissi, K. S. (1997). Unexplained infertility: evaluation of the luteal phase; results of the National Center for Infertility Research at Michigan. Fertility and sterility, 67(3), 437-442. https://doi.org/10.1016/s0015-0282(97)80066-0
Blacker CM, Ginsburg KA, Leach RE, Randolph J, Moghissi KS. Unexplained infertility: evaluation of the luteal phase; results of the National Center for Infertility Research at Michigan. Fertil Steril. 1997;67(3):437-442. doi:10.1016/s0015-0282(97)80066-0
Blacker, Charla M., et al. "Unexplained infertility: evaluation of the luteal phase; results of the National Center for Infertility Research at Michigan." Fertility and sterility, vol. 67, no. 3, 1997, pp. 437-442.
Hormonal profiles were obtained throughout 26 conception cycles and 27 non-conception control cycles. The pregnancies followed treatment (clomiphene or bromocriptine) in 12 women but were spontaneous in the remaining 14. No sustained significant difference between the various types of conception cycle was found for LH, FSH, oestradiol or progesterone concentrations. Prolactin concentrations varied widely, suggesting that mean cycle prolactin concentrations ranging from 45 to 760 mi.u./l are compatible with conception. Although there were no significant differences in progesterone secretion within the conception cycles, there were highly significant differences between the conception cycles and the non-pregnant control cycles. Mean progesterone concentrations in the conception group were higher (P less than 0.005) than those in the control women over Days 3-8 following the LH peak. This difference could only be partly accounted for by heterogeneity within the control group (15-20% of the control cycles had low progesterone concentrations and were probably subfertile. It is suggested that the higher conception cycle progesterone concentrations during the early part of the luteal phase may constitute a preimplantation component of the maternal recognition of pregnancy in women.
To examine the role of steroid hormone receptor compartmentalization in infertile women with "in-phase" or "out-of-phase" endometrium. Nonrandomized prospective clinical study. A university clinic. Twenty-nine infertile patients without evidence of endometriosis, tubal factor, male factor, galactorrhea, or hyperandrogenism were enrolled. Sixteen patients had in-phase endometrium and a P level > or = 10 ng/mL (conversion factor to SI unit, 3.18) (group A). Four patients had out-of-phase endometrium and a P level > 10 ng/mL (group B). Four patients had in-phase endometrium and a P level < 10 ng/mL (group C), and five patients had out-of-phase endometrium and a P level < 10 ng/mL (group D). Each patient underwent determination of serum P and endometrial sampling on postovulatory days 6 to 9 based on serum LH measurement. Dating according to endometrial histology and biochemical assessment of estrogen receptor (ER) and P receptor (PR) were performed on each sample. The level of cytosol ER was significantly lower in out-of-phase endometrium regardless of serum P level. There were no significant differences in the levels of cytosol PR and nuclear ER and PR among groups. In a long-term follow-up study, 6 of 29 patients became pregnant. The cytosol ER:PR ratio in these patients was found to fit a single straight regression line (y = 0.34x - 2.2). Out-of-phase endometrium probably depends on inadequate cytosol ER. An appropriate cytosol ER:PR ratio may be important to become pregnant.
To assess the sensitivity and specificity of common clinical tests used for the diagnosis of luteal phase defect (LPD). The sensitivity and specificity of these tests for predicting low integrated P levels over the luteal phase were calculated. Outpatient reproductive endocrinology and infertility clinic at a university medical center. Fifty-eight strictly defined normal women were used to determine normal integrated luteal phase P levels. The study population was a separate 34 women who either were normal (n = 15) or were being evaluated for infertility or recurrent abortion (n = 19). These 34 study subjects all had the following tests performed in the same menstrual cycle: daily reproductive hormone levels, daily assessment of preovulatory follicle size, late luteal endometrial biopsies, and BBT charts. Basal body temperature, maximum preovulatory follicle size, dated endometrial biopsies, and serum P levels (single and multiple) were used in an attempt to predict which patients had low integrated P levels. Unacceptably low sensitivity and/or specificity levels were found for the following tests: appearance of BBT charts, luteal phase length, and preovulatory follicle diameter. Timed endometrial biopsy was found to have marginally acceptable sensitivity and specificity levels whether dated by next menstrual period or midcycle events. The best test for the prediction of low integrated P was a single serum P level from the midluteal phase that was < 10 ng/mL (31.8 nmol/L) or a sum of three random serum P measurements that was < 30 ng/mL (95.4 nmol/L) (also obtained in the midluteal phase). Luteal phase defect is a relatively uncommon but important cause of infertility and/or habitual abortion. The recommended test for the determination of LPD is a midluteal phase single serum P level < 10 ng/mL or the sum of three serum P levels that is < 30 ng/mL. The endometrial biopsy is a second line test that is only recommended when LPD needs to be evaluated in a treated cycle (ovulation induction or supplemental P).
Luteal phase abnormalities are known to complicate ovulation induction with gonadotropins. This study was performed to test the effect of a modified human chorionic gonadotropin (hCG) regimen on the luteal phase during gonadotropin treatment. Fifteen women from a private practice setting volunteered to be studied during each of two nonconception, gonadotropin-stimulated cycles. After ovarian stimulation with human menopausal gonadotropins (hMG), hCG was administered either as a single dose of 10,000 IU (single dose) or in two divided doses of 5,000 IU given 1 week apart (split dose). Early, midluteal, and late luteal estradiol (E2) and progesterone (P) levels and luteal phase lengths were measured, and their median values and intraquartile ranges (IQR) compared using nonparametric analysis. Early and midluteal E2 and P levels were similar regardless of which hCG regimen was administered. The median late luteal E2 level was 1,146.0 pg/mL (the IQR ranged from 633 to 1,650, IQR = 1,017) with the split-dose regimen and 240.0 pg/mL (the IQR ranged from 150 to 460, IQR = 310) with the single-dose regimen. The median late luteal P level was 108.0 ng/mL (the IQR ranged from 58.5 to 129, IQR = 70.5) with the split-dose regimen and 4.2 ng/mL (the IQR ranged from 1.9 to 11.7, IQR = 9.8) with the single-dose regimen. Median luteal phase lengths were 16 days (the IQR ranged from 15 to 17, IQR = 2) for the split-dose regimen and 11 days (the IQR ranged from 10 to 12, IQR = 2) for the single-dose regimen. In hMG-stimulated cycles, a second dose of hCG given during the midluteal phase significantly increases late luteal E2 and P levels and consistently lengthens the luteal phase.