Is there any correlation between Estradiol supplementation, as luteal phase support, and clinical pregnancy in ART cycles? A cross-sectional study.

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This cross-sectional study found that adding estradiol supplementation to progesterone for luteal phase support in IVF cycles did not significantly improve clinical pregnancy rates compared to progesterone alone.

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This cross-sectional study evaluated whether adding estradiol to progesterone for luteal phase support improves clinical pregnancy rates in women undergoing ICSI-ET cycles with an antagonist protocol. The researchers analyzed 200 patients, excluding those with a history of endometriosis, and found no statistically significant difference in pregnancy or implantation rates between the group receiving progesterone alone and the group receiving combined hormone supplementation. While endometrial thickness was slightly higher in the estradiol group, the authors concluded that adding estradiol did not provide a beneficial effect on overall ART outcomes in this population. Relevance to endometriosis: the paper explicitly excludes patients with a history of endometriosis from its study population, indicating it is not centrally about the condition but rather focuses on general assisted reproductive technology outcomes in women without this diagnosis.

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Abstract

BackgroundEndometrial receptivity is one of the important factors in assisted reproductive technology (ART) success. In the luteal phase of an ART cycle, serum estradiol (E2) and progesterone are often placed in low levels. Supporting the luteal phase with progesterone is a usual method.ObjectiveTo evaluate the effects of E2 supplementation plus progesterone on the luteal phase support in the antagonist protocol who have undergone intracytoplasmic sperm injection-embryo transfer cycles.Materials and methodsIn this cross-sectional study, 200 patients with antagonist stimulation protocol, who had undergone intracytoplasmic sperm injection treatment, were divided into two groups based on the use of E2 supplementation. In both groups, 400 mg progesterone suppositories (CyclogestⓇ), twice a day/vaginally, was administered starting from the day of oocyte collection until the fetal heart activity. However, in the E2 group, in addition to progesterone, 4 mg tablet of E2 was received daily. Beta hCG was checked 14 days after the embryo transfer, and the clinical pregnancy rate was the main endpoint.ResultsThe patients' characteristics were matched, and insignificant differences were observed, except for endometrial thickness. The clinical outcomes showed the rate of pregnancy was higher in the E2 group compared to the control group; nonetheless, statistically, there was no noticeable difference.ConclusionE2 supplementation had no beneficial effect in the luteal phase support of IVF cycles. Nevertheless, more studies are required to confirm the supportive role of E2 supplementation for embryo implantation and to improve the outcomes in ART cycles.
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In conclusion, the supportive role of E2 in improving embryo implantation and pregnancy is unclear and needs further studies. Although the results of this study exhibited no useful effect of E2 supplementation in the luteal phase of IVF cycles, estrogen supplementation may be useful in some subgroups of the patients. Therefore, a large RCT study is needed to further clear up the role of luteal E2 supplementation in IVF cycles, as well as the optimal regimen (dose and route), not well defined to the date.

Coi Statement

The authors have no conflict of interest to declare.

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europepmc
last seen: 2026-09-13T09:25:22.628771+00:00
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