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.
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Women with unexplained infertility had lower midluteal progesterone
Women with unexplained infertility had lower progesterone in the middle of the luteal phase than fertile women. The comparison used 12 women in each group. Endometrial biopsy dating and ultrasound follicle growth did not differ between the groups.
Key Findings
Researchers in Michigan screened 1,885 women with infertility and found 12 who met every criterion for unexplained infertility. Controls were 12 healthy, parous women matched for age and BMI.
Midluteal progesterone (days +5 to +7) was lower in the unexplained infertility group (P = 0.0006 by ANOVA; P = 0.0142 after Greenhouse-Geisser correction).
The ratio of integrated estradiol to progesterone was significantly greater in unexplained infertility than in controls (P = 0.023 after a log transformation).
Integrated progesterone and integrated urinary PDG tended to be lower in unexplained infertility without reaching statistical significance. Follicular growth rate and preovulatory follicle diameter did not differ.
Using ultrasound to date ovulation, 2 of 12 control women (17%) and 2 of 12 women with unexplained infertility (17%) had out-of-phase biopsies.
Interpretation
This case-control study compared 12 women with unexplained infertility to 12 fertile women. The groups were matched for age and weight. Each woman was studied for one cycle. Midluteal progesterone was lower in the unexplained infertility group. The ratio of estradiol to progesterone was higher. The authors note that whether these differences affect fertility or the ability to sustain a pregnancy remains to be determined. The findings support larger studies of luteal hormone patterns in unexplained infertility.
RRM Context
Unexplained infertility means the cause has not been found. These 12 women had normal results on the traditional luteal tests. Still, their hormone pattern differed from fertile women. Restorative reproductive medicine examines the whole cycle, including the luteal phase, because one normal test can leave the cause undiagnosed.
Our editorial summary of this paper, not the article's abstract.
Abstract
Objective
To evaluate the luteal phase in women with rigorously defined unexplained infertility.
Design
Prospective study.
Setting
National Center for Infertility Research at Michigan.
Patients
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 Measures
Pattern of follicular growth rate and luteal phase hormonal profile.
Results
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.
Conclusions
Women with rigorously defined unexplained infertility have subtle hormonal anomalies during the luteal phase when compared with fertile controls.
