Downs, K. A., & Gibson, M. (1983). Clomiphene citrate therapy for luteal phase defect. Fertility and Sterility, 39(1), 34-38. https://doi.org/10.1016/s0015-0282(16)46754-3
Downs KA, Gibson M. Clomiphene citrate therapy for luteal phase defect. Fertil Steril. 1983;39(1):34-38. doi:10.1016/s0015-0282(16)46754-3
Downs, Kevin A., and Mark Gibson. "Clomiphene citrate therapy for luteal phase defect." Fertility and Sterility, vol. 39, no. 1, 1983, pp. 34-38.
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Severe luteal phase defect linked to more pregnancies on clomiphene
In a 1983 case series of 41 women treated with clomiphene for luteal phase defect, those whose uterine lining lagged five or more days conceived more often. Among women with no other fertility problem found, three in four with a large lag conceived, against fewer than one in ten with a smaller lag. The series came from one Vermont clinic.
Key Findings
The clinic diagnosed luteal phase defect in 47 of 366 women screened for infertility (12.7%), using a late-luteal biopsy confirmed by a second biopsy or serial progesterone tests.
Of 41 treated women, 16 (39%) conceived. The 44 courses of therapy produced 18 pregnancies, a crude conception rate of 40.9%.
Seven pregnancies came in the first cycle, five in the second and five in the third. No others followed except one ectopic pregnancy in the 11th cycle.
Among 25 women with no other fertility factor found, biopsy lag averaged 6.28 days in those who conceived and 4.32 days in those who did not (P < 0.02).
In that group, 9 of 12 women with a lag of 5 or more days conceived (75%). Only 1 of the 13 with a smaller lag conceived (P < 0.001).
Interpretation
The report is a case series from one clinic with no comparison group. Without untreated women for comparison, the data cannot separate clomiphene's effect from other reasons for pregnancy. The lag difference reached significance only in the 25 women with no other fertility factor found. Across all treated women, mean lag was 5.7 days in those who conceived and 4.9 in those who did not, which the authors call not significant. Couples with abnormal semen, cervical mucus or tubal findings were set aside for the smaller analysis. Group sizes are small, and the authors looked for group differences within their own data.
RRM Context
Unexplained infertility is undiagnosed, and a luteal phase problem is one diagnosable cause a workup can find. The authors graded each defect by days of biopsy lag. Grading the cause first fits the evaluation-first principle of Restorative Reproductive Medicine (RRM). The authors suggest reviewing the rest of the evaluation in women who do not respond.
Our editorial summary of this paper, not the article's abstract.
Abstract
The incidence of luteal phase defects in 366 infertility patients was 12.7%. Life-table analysis was used for determination of the conception rate with clomiphene citrate therapy, and with this method, evidence was found for the presence of two subgroups with respect to response. The crude conception rate was 40.9%. In a group of patients with a luteal phase defect and no other infertility factors, those that conceived had a significantly larger mean biopsy delay than those who did not (6.28 days versus 4.32; P less than 0.02). In a group with a histologic delay of 5 days or more, the conception rate was 79%, while the rate was only 8.9% in those with a less severe deficit (P less than 0.001). Theoretic considerations for clomiphene citrate therapy are discussed.
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