Keenan, J. A., Herbert, C. M., Bush, J. R., & Wentz, A. C. (1989). Diagnosis and management of out-of-phase endometrial biopsies among patients receiving clomiphene citrate for ovulation induction. Fertility and Sterility, 51(6), 964-967. https://doi.org/10.1016/s0015-0282(16)60726-4
Keenan JA, Herbert CM, Bush JR, Wentz AC. Diagnosis and management of out-of-phase endometrial biopsies among patients receiving clomiphene citrate for ovulation induction. Fertil Steril. 1989;51(6):964-967. doi:10.1016/s0015-0282(16)60726-4
Keenan, Jeffrey A., et al. "Diagnosis and management of out-of-phase endometrial biopsies among patients receiving clomiphene citrate for ovulation induction." Fertility and Sterility, vol. 51, no. 6, 1989, pp. 964-967.
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In one study, about 1 in 4 women on clomiphene had a lagging lining
A biopsy late in the cycle showed a lagging uterine lining in 21 of 87 women on clomiphene citrate, about 1 in 4. This 1989 cohort study saw it in all 5 women with hypothalamic amenorrhea. Women with a normal first biopsy conceived at 50%, and women treated for a lagging lining conceived at 41%.
About 2 in 10 women taking clomiphene citrate had a lagging lining on biopsy. Source: Keenan JA et al., 1989, PMID 2721730.Study at a glance, cohort study of 87 women taking clomiphene citrate: About 1 in 4 women on clomiphene had a lagging uterine lining. Source: Keenan JA et al., 1989, PMID 2721730.
Key Findings
Of 87 women taking clomiphene citrate who had a late secretory phase biopsy, 21 (24%) had an endometrium more than 2 days out of phase. The other 66 (76%) were in phase.
All 5 women with hypothalamic amenorrhea had an out-of-phase biopsy, the only subgroup with a statistically significant increase.
Age over 35, weight over 150 lbs, endometriosis, PCOD and clomiphene dose showed no significant difference in out-of-phase biopsies.
Conception occurred in 33 of 66 women (50%) with an in-phase biopsy and 7 of 17 (41%) treated for an out-of-phase biopsy. The difference was not significant.
Miscarriage followed 5 of 33 conceptions (15%) after an in-phase biopsy and 1 of 7 (14%) after treatment for an out-of-phase biopsy.
Interpretation
This cohort study followed 87 women taking clomiphene citrate for ovulation induction. Each woman had a late secretory phase endometrial biopsy. Doctors treated a lagging lining with a higher clomiphene dose, midcycle hCG, vaginal progesterone, or a mix of these. Hypothalamic amenorrhea was the one diagnosis linked with more lagging linings. Age, weight, endometriosis, PCOD, and clomiphene dose were not linked with it. The authors recommend a late secretory biopsy for every woman on clomiphene citrate, so a lagging lining can be found and treated. The findings support larger studies of luteal phase care in women on clomiphene citrate.
RRM Context
Ovulation and the luteal phase are two separate things. Charts showed ovulation in these women. Still, 21 had a lining that formed late. Restorative reproductive medicine addresses the whole cycle, including the luteal phase. Fertility awareness-based methods teach women to chart their cycles.
Our editorial summary of this paper, not the article's abstract.
Abstract
Eighty-seven patients who underwent a late secretory phase endometrial biopsy while taking clomiphene citrate (CC) for ovulation induction were studied. Of the endometrial biopsies, 21 (24%) showed an endometrium greater than 2 days out of phase (OOP) with respect to the subsequent menstrual cycle. All 87 patients were categorized by age, weight, CC dosage, and underlying disease entity. The patients then were evaluated by these categories in relation to the incidence of an OOP biopsy while taking CC. Patients with a diagnosis of hypothalamic amenorrhea were statistically more likely to have an OOP endometrium. No other subgroup showed an increased or decreased incidence of OOP biopsies. Conception and spontaneous abortion rates were similar among patients with in-phase biopsies and those with out-of-phase biopsies, which subsequently were corrected with further medical therapy. An aggressive approach to the diagnosis and treatment of luteal phase insufficiency in patients who receive CC for ovulation induction is recommended.
