Comparison of five clomiphene citrate dosage regimens: follicular recruitment and distribution in the human ovary

Josef Shalev; Mordechai Goldenberg; Ehud Kukia; Dan Lewinthal; Ron Tepper; Shlomo Mashiach; Josef Blankstein

doi:10.1016/s0015-0282(16)60963-9

Therapeutics Ovulation Agents

Comparison of five clomiphene citrate dosage regimens: follicular recruitment and distribution in the human ovary

Shalev J, Goldenberg M, Kukia E, Lewinthal D, Tepper R, Mashiach S, Blankstein J

Published October 1989 Fertility and Sterility, 52(4), 560-563

DOI 10.1016/s0015-0282(16)60963-9 PMID 2680615

RRM Academy Synopsis

Higher clomiphene doses link to more follicles in both ovaries

Women given higher clomiphene citrate doses had more ovarian follicles on the day of ovulation. The 1989 dose-comparison study enrolled 156 women with absent or infrequent ovulation, each treated in one cycle at one of five doses. Follicles appeared in both ovaries more often with higher doses.

Key Findings

The average number of follicles on the day of assumed ovulation rose from 1.1 at the lowest dose to 4.4 at the highest dose, a statistically significant increase.
Mature follicles (larger than 15 mm) averaged 1.0 at the lowest dose and 2.4 at the highest dose, an increase the authors did not find statistically significant.
With three follicles in a cycle, 62.5% showed follicles in both ovaries. The share was 83.3% with four, 87.0% with five and 100% with six to eleven follicles.
Follicles in both ovaries appeared in 30% of cycles at the lowest dose and 70% at the highest dose.
Pregnancy rates ranged from 12.5% to 26.3% across the five dose groups, with no significant difference.

Interpretation

The study compares five dose groups made up of different women, each studied in a single cycle, using ultrasound on the assumed day of ovulation. The 156 women had absent or infrequent ovulation or luteal phase deficiency (World Health Organization group II). The authors report that follicle number rises with dose and that follicles spread to both ovaries as numbers climb.

RRM Context

The authors note that IVF programs use clomiphene to start the growth of multiple follicles in patients with normal spontaneous cycles. The dose-dependent rise in follicle number shows what the drug does to follicle recruitment. Restorative reproductive medicine asks a separate question first: why ovulation is absent or the luteal phase is deficient in a given woman.

Our editorial summary of this paper, not the article's abstract.

Abstract

One hundred fifty-six women with cycle disorders presenting as absence or infrequency of ovulation and with luteal phase deficiency (group II, according to the World Health Organization classification) received clomiphene citrate (CC) for ovulation induction. The administered dosage ranged from 50 to 250 mg/d. The follicular development in terms of numbers of small (less than 8 mm), intermediate (9 to 15 mm), and large (greater than 15 mm) follicles and their distribution in either one or both ovaries on the day of assumed ovulation was related to the dosage of CC. A statistically significant increase was found in the total number of follicles in relation to the dosage of CC (P less than 0.003). In view of the development of the mature follicles, the gradual increase in CC daily dosage was thought to be associated with additional mature follicles before ovulation. However, this increased follicular recruitment was not regarded as statistically significant. Treatment with low doses of CC resulted in follicular development in only one ovary, whereas increased follicular recruitment after high CC dosage was found in association with follicular development in both ovaries.

Topics

Therapeutics › Ovulation Agents › Selective Estrogen Receptor Modulators · Reproductive Endocrinology › Ovulation Physiology › Follicular Development · Menstrual Cycle › Cycle Disorders › Ovulatory Disturbances

Josef Shalev, Mordechai Goldenberg, Ehud Kukia, Dan Lewinthal, Ron Tepper, Shlomo Mashiach, Josef Blankstein

J Shalev, M Goldenberg, E Kukia, Daniel Lewinthal, D Lewinthal, Ronald Tepper, R Tepper, S Mashiach, J Blankstein

PMID 2680615 2680615 DOI 10.1016/s0015-0282(16)60963-9 10.1016/s0015-0282(16)60963-9 Shalev et al. 1989, Shalev 1989

Keywords

Clomiphene/administration & Dosage/therapeutic Use, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Humans, Ovarian Follicle/anatomy & Histology/drug Effects/physiology, Ovary/anatomy & Histology/drug Effects, Ovulation Induction, Ultrasonography, Clomiphene

Comparison of five clomiphene citrate dosage regimens: follicular recruitment and distribution in the human ovary

Higher clomiphene doses link to more follicles in both ovaries

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

Related research

Keywords