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 | 2021 Sep

REPOSITORIES: biostudies-literature

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Publications

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

Zhang Wendy Y WY Gardner Rebecca M RM Kapphahn Kristopher I KI Ramachandran Maya K MK Murugappan Gayathree G Aghajanova Lusine L Lathi Ruth B RB

F&S reports 20210527 3

<h4>Objective</h4>To assess the impact of low estradiol (E2) levels in letrozole-stimulated frozen embryo transfer (FET) cycles on pregnancy and neonatal outcomes.<h4>Design</h4>Retrospective cohort.<h4>Setting</h4>University-affiliated fertility center.<h4>Patients</h4>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 = ...[more]

PMID: 34553158

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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.

Project description:Study questionAre there any differences in live birth rates (LBR) following fresh blastocyst transfer in natural or clomiphene-stimulated cycles, or after elective blastocyst freezing in clomiphene-stimulated cycles followed by thawing and transfer at different time-points?Summary answerClomiphene citrate (CC) administration adversely affected the LBR after single fresh blastocyst transfer (SBT) in CC cycles compared with that in natural cycles, while this adverse effect of CC is not present when a single vitrified-warmed blastocyst transfer (SVBT) is performed in subsequent natural ovulatory cycles, regardless of the duration between CC administration and the day of SVBT.What is known alreadyCC affects uterine receptivity associated with a thinning of the uterine endometrium through an antioestrogenic effect. However, the duration that this adverse effect of CC on uterine endometrium persists after initial use is still unknown.Study design size durationA retrospective cohort study of 157 natural cycle IVFs followed by SBT and 1496 minimal ovarian stimulation with CC IVF cycles followed by SBT (n = 24) or SVBT (n = 1472) from January 2010 to December 2014 was conducted. SVBT cycles were classified into two groups according to the period between the last day of CC administration and the day of SVBT (A: ≤60 d and B: ≥61 d). All groups were then compared based on pregnancy outcomes (natural-SBT group: n = 157, CC-SBT group: n = 24, SVBT-A: n = 1143, SVBT-B: n = 329).Participants/materials setting methodsWomen were aged 30-39 years at oocyte retrieval. In SVBT cycles, blastocysts were vitrified and warmed using a Cryotop safety kit. SVBT was performed in subsequent natural ovulatory cycles. The main outcomes were LBR and neonatal outcome, and both were compared among the groups.Main results and the role of chanceThe LBR in the CC-SBT group (29.2%, 7/24) was significantly lower compared with the natural-SBT (56.1%, 88/157) (P = 0.01) and SVBT-A (50.0%, 572/1143) (P = 0.04), but not SVBT-B (47.4%, 156/329), groups. Furthermore, multivariate logistic regression analysis revealed that the LBR was comparable among the natural-SBT and SVBT groups, but was significantly lower in the CC-SBT group (adjusted odds ratio: 0.324, 95% CI: 0.119-0.800, P = 0.01). No significant differences among all groups were observed for gestational age (P = 0.19), birthweight (P = 0.41) and incidence of malformation (P = 0.53).Limitations reasons for cautionIn this study we analysed a biased sample, based on clinical judgement regarding endometrial thickness, and the study was limited by its retrospective nature. The low statistical power caused by the group size disparity was also a limitation, especially in the CC-SBT group. Although the outcome showing inferiority of CC-SBT compared to natural-SBT is consistent with general findings in the literature, further large-scale clinical studies, ideally RCTs, are necessary to validate our results and clarify the prolonged effect of CC in SVBT cycles on pregnancy and neonatal outcomes.Wider implications of the findingsOur observation suggests that CC administered in minimal ovarian stimulation cycles affects adversely the pregnancy outcomes when SBT is performed. Therefore, for a CC-based minimal stimulation IVF cycle, we suggest that frozen embryo transfer should be performed in a subsequent natural ovulatory cycle to avoid the possibility of implantation failure associated with CC administration.Study funding/competing interestsThe authors have no conflicts of interest to declare. No external funding was either sought or obtained.

Dataset Information

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

Objective

Design

Setting

Patients

Interventions

Main outcome measures

Results

Conclusion

Publications

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

Similar Datasets

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