Dataset Information

The impact of estradiol on pregnancy outcomes in letrozole-stimulated frozen embryo transfer cycles.

ABSTRACT:

Objective

To assess the impact of low estradiol (E2) levels in letrozole-stimulated frozen embryo transfer (FET) cycles on pregnancy and neonatal outcomes.

Design

Retrospective cohort.

Setting

University-affiliated fertility center.

Patients

All patients who underwent letrozole-stimulated FET cycles from January 2017 to April 2020 (n = 217). The "Low E2" group was defined as those with E2 serum levels on the day of trigger <10th percentile level (E2 <91.16 pg/mL, n = 22) and the "Normal E2" group was defined as those with E2 serum levels ≥10th percentile level (E2 ≥91.16 pg/mL, n = 195).

Interventions

None.

Main outcome measures

Pregnancy outcomes including rates of clinical pregnancy, clinical miscarriage, and live birth. Neonatal outcomes including gestational age at delivery, birth weight, and Apgar score.

Results

The mean ± SD estradiol level was 66.8 ± 14.8 pg/mL for the "Low E2" group compared with 366.3 ± 322.1 pg/mL for the "Normal E2" group. There were otherwise no substantial differences in cycle characteristics such as endometrial thickness on the day of ovulation trigger and progesterone levels in early pregnancy. The "Low E2" group had a significantly higher clinical miscarriage rate (36.4% vs. 8.8%, adjusted odds ratio 8.06) and lower live birth rate (31.8% vs. 57.9%, adjusted odds ratio 0.28). Neonatal outcomes such as gestational age at delivery, mean birth weight, Apgar scores, and incidence of newborn complications were not clinically different between the groups.

Conclusion

Low E2 levels were associated with a significantly higher miscarriage rate and lower live birth rate, suggesting that E2 levels in the follicular phase may have an effect on cycle outcomes. Given the rise in use of FET, further studies are needed to confirm our findings and understand the mechanisms.

SUBMITTER: Zhang WY

PROVIDER: S-EPMC8441577 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Introduction Frozen embryo transfer is being increasingly used for assisted reproductive therapy and offers similar pregnancy rates as treatment with fresh embryo transfer. In women with regular menstrual cycles, transfer of a frozen thawed blastocyst can be performed in either natural cycle or substituted cycle. Anovulatory women can only be offered a substituted or a stimulated cycle. Knowledge on fetal exposure to estradiol in early pregnancy is very limited, but studies on mice and rats have shown hormonal and metabolic disturbances in cubs born from estradiol-exposed mothers. We aim to investigate serum estradiol and progesterone levels in women who conceived after natural, estradiol and progesterone, or gonadotrophin stimulated frozen embryo transfer. Methods and analysis The study is an open-label, randomised controlled trial with normo-ovulatory women being randomised to natural cycle or estradiol and progesterone substitution and anovulatory women being randomised to estradiol and progesterone substitution or gonadotrophin stimulation. Serum estradiol and progesterone will be measured every 2 weeks from cycle days 2–3 until gestational age 9+6. Serum levels will be compared according to treatment regimens and cycle length. Furthermore, obstetric outcomes (live birth rates, birth weight, gestational age at birth, complications and malformations) and a possible association with serum estradiol and progesterone levels will be evaluated. Ethics and dissemination The three treatment regimens are all standard treatments and are comparable with regard to pregnancy rates. Patients will be following routine treatments and thus discomforts are limited to routine transvaginal ultrasound scans and additional blood testing. The study is approved by the Scientific Ethical Committee of the Capital Region of Denmark and the Danish Medicines Agency. The study will be carried out in accordance with the Declaration of Helsinki and monitored by a good clinical practice unit. Positive, negative and inconclusive findings will be published in international peer-reviewed journals. Trial registration number NCT04997525, 2020-001218-39.

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