Effects of different doses of estrogen on ER expression and ovarian function in patients with unexplained recurrent abortion

Abstract

Study design: Randomized trial. Objective: This study was designed to investigate the effects of different doses of estrogen on the expression of estrogen receptor (ER) in endometrial tissue and ovarian function in patients with unexplained recurrent spontaneous abortion (URSA). Methods: Eighty-eight patients with URSA in our outpatient department were randomly divided into three groups. They were treated with estradiol valerate (EV); standard dose of 4 mg/d (31 cases), high dose of 6 mg/d (27 cases) and 9 mg/d (30 cases). Progesterone was detected in the luteal phase, ovarian ovulation during follow-up treatment and the next month after drug withdrawal. ER expression in intima of EV 4 mg group, EV 6 mg group, and EV 9 mg group was detected by immunohistochemistry and PCR was performed before and 3 months after the treatment. Results: Anovulation of 88 URSA patients during hormone treatment was found as follows: 5 cases in the EV 4 mg group, 18 cases in the EV 6 mg group, 25 cases in the EV 9 mg group; Anovulation in the next month after drug withdrawal: 1 case in EV 4 mg group, 8 cases in EV 6 mg group, and 16 cases in EV 9 mg group. After stratified and grouped analysis, the expression of intimal ER in the EV 4 mg group, EV 6 mg, and EV 9 mg groups was significantly increased compared to before treatment in the 3 groups after treatment compared to before treatment (p < .05). There was no significant difference in ER expression between the three groups before and after treatment (p > .05). Conclusion: The higher the therapeutic dose of estrogen, the stronger the inhibition of ovarian ovulation, and the standard dose of estrogen has obvious advantages in increasing the expression of ER in intima. Limitation: 1) Insufficient sample size; 2) We need to increase the sampling time point to further observe the difference of estrogen in time effect, so as to obtain a more accurate action time of estrogen; 3) The longer-term effects of different doses of estrogen on intima were not studied, such as whether there are adverse pregnancy outcomes such as preterm birth, placental implantation, or premature exfoliation.

摘要

研究设计

随机试验。

目的

探讨不同剂量雌激素对不明原因反复自然流产患者子宫内膜组织雌激素受体(ER)表达及卵巢功能的影响。

方法

将我院门诊的88例URSA患者随机分为3组。用戊酸雌二醇(EV)治疗； 标准剂量4 mg/d（31例）,高剂量6 mg/d（27例）,9 mg/d（30例）。 黄体期、随访治疗期间卵巢排卵及停药次月检测孕酮。分别于治疗前和治疗后3个月用免疫组化和PCR方法检测EV4mg组、EV6mg组和EV9mg组内膜ER的表达。

结果

88例Ursa患者在激素治疗期间无排卵情况如下：EV4mg组5例,EV6mg组18例,EV9mg组25例；停药后次月无排卵EV4mg组1例,EV6mg组8例,EV9mg16例。经分层分组分析EV4mg组、EV6 m组和EV9mg组治疗后, 3组内膜ER表达较治疗前明显增加(P<.05)。三组ER治疗前与治疗后表达均无明显差异(P>.05)。

结论

治疗剂量越高的雌激素对卵巢排卵的抑制作用越强, 标准剂量雌激素在增加内膜ER表达方面具有明显优势。

局限性

1）样本量不足；2）我们需要增加采样时间点, 进一步观察雌激素在时间效应上的差异, 从而获得更准确的雌激素作用时间；3）未研究不同剂量雌激素对内膜的长期影响, 如是否存在早产、胎盘植入或过早脱落等不良妊娠结局。

Keywords:

• URSA
• estradiol valerate
• estrogen receptor
• ovulation inhibition

关键词:

• 反复自然流产
• 戊酸雌二醇
• 雌激素受体
• 排卵抑制

Data statement

The patients’ data were authorized to our research.

Disclosure statement

No potential conflict of interest was reported by the authors.

Ethical statement

This work was approved by ethical committee of Department of Obstetrics and Gynecology Zigong Maternity and Child Care Hospital and informed consent was taken from individuals

Additional information

Funding

This study was supported by Zigong Science and Technology Bureau of China (No. 2019YLSF15).