Yagel, S., Ben-Chetrit, A., Anteby, E., Zacut, D., Hochner-Celnikier, D., & Ron, M. (1992). The effect of ethinyl estradiol on endometrial thickness and uterine volume during ovulation induction by clomiphene citrate. Fertility and Sterility, 57(1), 33-36. https://doi.org/10.1016/s0015-0282(16)54772-4
Yagel S, Ben-Chetrit A, Anteby E, Zacut D, Hochner-Celnikier D, Ron M. The effect of ethinyl estradiol on endometrial thickness and uterine volume during ovulation induction by clomiphene citrate. Fertil Steril. 1992;57(1):33-36. doi:10.1016/s0015-0282(16)54772-4
Yagel, Simcha, et al. "The effect of ethinyl estradiol on endometrial thickness and uterine volume during ovulation induction by clomiphene citrate." Fertility and Sterility, vol. 57, no. 1, 1992, pp. 33-36.
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Ethinyl estradiol may reverse clomiphene's thinner uterine lining
Adding ethinyl estradiol may reverse the thinner uterine lining seen with clomiphene alone. In a 1992 ultrasound study of 35 women with infertility and 10 untreated women, lining growth with combined treatment did not differ from untreated cycles. Clomiphene alone gave less growth in lining thickness and uterine volume than untreated or menotropin cycles. Every cycle included ovulation.
Key Findings
With clomiphene alone, the endometrium (uterine lining) was thinner than in untreated cycles all through the follicular phase except 7 days before ovulation.
With clomiphene alone, uterine volume was significantly lower than in untreated and menotropin cycles 5, 3 and 1 days before ovulation.
With clomiphene plus ethinyl estradiol (12 women), endometrial thickness and uterine volume rose through the follicular phase and did not differ from the untreated or menotropin groups.
The groups held 10 untreated women, 11 on menotropin, 12 on clomiphene and 12 on clomiphene plus ethinyl estradiol. Every woman ovulated by ultrasound and hormonal criteria.
Blood estradiol was significantly higher with menotropin and with clomiphene than in untreated cycles. Clomiphene alone and clomiphene plus ethinyl estradiol showed no difference in levels.
Interpretation
This study compared four groups of women over one ovulatory cycle at a hospital in Jerusalem, tracking endometrial growth by ultrasound. Three subgroups were randomized among women attending an infertility clinic, and ten untreated women monitored for donor insemination formed the comparison group. The sonographer did not know each woman's group assignment. The authors conclude that ethinyl estradiol may reverse the effect of clomiphene on endometrial development. They add that the combination may help in some cases and describe additional patients who grew normally on it as data not shown. The findings support further study of this combination, including its effect on pregnancy outcomes.
RRM Context
The authors cite ovulation after clomiphene in 57% to 91% of cases but pregnancy in only 27% to 40%, and place part of that gap at the endometrium. Restorative reproductive medicine starts from the cause of a missing ovulation and follows the whole cycle. The endometrium and the luteal phase get the same attention as ovulation.
Our editorial summary of this paper, not the article's abstract.
Abstract
Objective
To assess the deleterious effect of clomiphene citrate (CC) on the development of the endometrium and its improvement by the addition of ethinyl estradiol (E2).
PARTICIPATING
Patients
Infertility-treated patients, monitored for induction of ovulation or timing of insemination (control group).
Design
We studied four groups of women during an ovulatory cycle with various treatment schedules. Group 1: untreated patients; group 2: patients treated by CC; group 3: patients treated by CC + ethinyl E2; group 4: patients treated by human menopausal gonadotropin. Follow-up of the patients was done by vaginal ultrasonography and measurements of blood E2.
Results
In the group treated by CC, both endometrial thickness and uterine volume growth during the follicular phase were lower as compared with untreated controls and menotropin-treated patients. The addition of ethinyl E2 to these patients reversed this deleterious effect of CC without interfering with ovulation.
Conclusion
Ethinyl E2 may reverse the deleterious effect of CC on endometrial development during the follicular phase.
