A pilot study to prevent a thin endometrium in patients undergoing clomiphene citrate treatment

Akihisa Takasaki; Hiroshi Tamura; Toshiaki Taketani; Katsunori Shimamura; Hitoshi Morioka; Norihiro Sugino

doi:10.1186/1757-2215-6-94

Reproductive Endocrinology Ovarian Hormones

A pilot study to prevent a thin endometrium in patients undergoing clomiphene citrate treatment

Takasaki A, Tamura H, Taketani T, Shimamura K, Morioka H, Sugino N

Published December 27, 2013 Journal of ovarian research, 6(1), 94

DOI 10.1186/1757-2215-6-94 PMID 24369731 PMC PMC3880974

RRM Academy Synopsis

Half-dose or early clomiphene thickened a previously thin lining

Clomiphene at half the usual amount or earlier in the cycle thickened a previously thin uterine lining in a trial. The randomized trial included 61 infertile women whose lining had been thin on the standard regimen. About 7 out of 10 and 9 out of 10 reached a normal thickness, against fewer than 2 out of 10 on standard treatment.

Key Findings

Endometrial thickness reached 8 mm or more in 14 of 20 women (70%) on half-dose clomiphene, 19 of 21 (90%) on early administration, and 3 of 20 (15%) on the standard regimen.
Mean endometrial thickness was 8.6 ± 1.5 mm with half dose and 9.4 ± 1.5 mm with early administration, compared with 6.7 ± 1.8 mm in the control group (p < 0.05).
Follicles took longer to mature in the half-dose group: 13.6 ± 2.7 days, against 12.0 ± 1.5 days in the control group and 11.6 ± 2.3 days with early administration.
The number of growing and mature follicles and the mid-luteal serum progesterone levels did not differ significantly among the three groups.
One woman in the half-dose group and two in the early administration group conceived in the study cycle. The authors observed no side effects.

Interpretation

The study is a prospective randomized controlled pilot trial from one Japanese hospital, run over four months. Sixty-six women aged 20 to 42 were randomized. Sixty-one were analyzed, after four were lost to follow-up and one stopped because she was not ovulating. Every woman had a thin lining on standard treatment and a normal lining in spontaneous cycles. The primary endpoint was lining thickness on the day of the ovulation trigger. The authors state that a large randomized trial is needed to evaluate pregnancy and live birth.

RRM Context

Clomiphene blocks estrogen receptors. The authors attribute the thinner lining seen with the drug to that action, and the lining is where an embryo implants. Restorative reproductive medicine evaluates what a fertility drug does to the whole cycle and asks why ovulation or the lining falls short. The trial measured the lining by ultrasound and checked progesterone after ovulation.

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

Abstract

Background

Clomiphene citrate (CC) is most commonly used as a first-line treatment of infertility. However, a disturbance of endometrial growth by the adverse effects of the CC has been recognized. Since a thin endometrium is recognized as a critical factor of implantation failure, preventing CC-induced thinning of the endometrium is important. This study was undertaken to investigate whether the modified CC treatments are useful to prevent a thin endometrium in patients undergoing CC treatments.

Methods

This study is a prospective, randomized controlled study. The study was performed at the Saiseikai Shimonoseki General Hospital during a 4-month period (May 2012 to September 2012). Sixty-six infertile women who had a thin endometrium (< 8 mm) during the standard CC treatment (50 mg/day on days 5-9 of the menstrual cycle) were enrolled. The patients were randomly divided into three groups: 22 patients were given 25 mg/day CC on days 5-9 (half-dose group), 22 patients were given 50 mg/day CC on days 1-5 (early administration group) and 22 patients received a standard CC treatment again (control group). Endometrial thickness at the induction of ovulation was assessed by ultrasonography. The primary endpoint of this study was an endometrial thickness.

Results

Half dose administration and early administration improved the endometrial thickness (≥ 8 mm) in 14 patients (70%) and in 19 patients (90%) respectively, while only 3 patients (15%) improved in endometrial thickness in the control group. The mean endometrial thickness was also significantly higher in the half dose group (8.6 ± 1.5 mm) and early administration group (9.4 ± 1.5 mm) compared to the control group (6.7 ± 1.8 mm). No side effect was observed in this study.

Conclusions

The modified treatment with a half-dose or early administration of CC significantly increased endometrial thickness in patients with a history of thin endometrium caused by the standard CC regimen. The modified CC treatments in this study can be beneficial for patients with a thin endometrium as a result of standard CC treatment.

Trial Registration

UMIN000007959.

Topics

Reproductive Endocrinology › Ovarian Hormones › Estrogen · Therapeutics › Ovulation Agents › Selective Estrogen Receptor Modulators · Infertility › Uterine Factor › Endometrial Receptivity

Akihisa Takasaki, Hiroshi Tamura, Toshiaki Taketani, Katsunori Shimamura, Hitoshi Morioka, Norihiro Sugino

A Takasaki, H Tamura, T Taketani, K Shimamura, H Morioka, N Sugino

PMID 24369731 24369731 DOI 10.1186/1757-2215-6-94 10.1186/1757-2215-6-94 Takasaki et al. 2013, Takasaki 2013

A pilot study to prevent a thin endometrium in patients undergoing clomiphene citrate treatment

Half-dose or early clomiphene thickened a previously thin lining

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

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