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Elevated estradiol levels in frozen embryo transfer have different effects on pregnancy outcomes depending on the stage of transferred embryos.

ABSTRACT: Supplementation with estradiol (E₂) is routinely used in frozen embryo transfer (FET) cycles and embryo age plays an important role in conceiving. This study was to compare the effects of serum E₂ levels on pregnancy outcomes between cleavage- and blastocyst-stage FET cycles using hormone replacement therapy. A total of 776 FET cycles (669 couples) performed from January 2016 to December 2019 were included in the present retrospective cohort study. Regarding cleavage-stage embryo transfers, E₂ levels on progesterone initiation day were significantly lower in the ongoing pregnancy/live birth (OP/LB) group than in the non-OP/LB group (214.75 ± 173.47 vs. 253.20 ± 203.30 pg/ml; P = 0.023). In addition, there were downward trends in implantation, clinical pregnancy and OP/LB rates with increasing E₂ levels. However, in blastocyst-stage embryo transfers, such trends were not observed, and E₂ levels were not significant difference between the OP/LB group and the non-OP/LB group (201.66 ± 182.14 vs. 197.89 ± 212.83 pg/ml; P = 0.884). The results suggests that elevated progesterone-initiation-day E₂ levels may negatively affect pregnancy outcomes during artificial cleavage-stage embryo transfers. However, it is not necessary to monitor E₂ levels when transferring blastocysts in artificial FET cycles.

SUBMITTER: Li Q

PROVIDER: S-EPMC8980097 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Elevated estradiol levels in frozen embryo transfer have different effects on pregnancy outcomes depending on the stage of transferred embryos.

Li Qing Q Ruan Liming L Zhu Lingling L Yang Zengyu Z Zhu Maoling M Luo Yudi Y

Scientific reports 20220404 1

Supplementation with estradiol (E<sub>2</sub>) is routinely used in frozen embryo transfer (FET) cycles and embryo age plays an important role in conceiving. This study was to compare the effects of serum E<sub>2</sub> levels on pregnancy outcomes between cleavage- and blastocyst-stage FET cycles using hormone replacement therapy. A total of 776 FET cycles (669 couples) performed from January 2016 to December 2019 were included in the present retrospective cohort study. Regarding cleavage-stage ...[more]

PMID: 35379862

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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:ImportanceThe optimal interpregnancy interval (IPI) after a clinical pregnancy loss (CPL) remains controversial. Few studies have addressed the role of the IPI after a preceding CPL during in vitro fertilization (IVF) treatment.ObjectiveTo evaluate the association between different IPI lengths after a preceding CPL and pregnancy outcomes of the next frozen embryo transfer (FET).Design, setting, and participantsThis retrospective cohort study was conducted using data from the Center for Reproductive Medicine of Shandong University in China. The study included women who underwent frozen-thawed blastocyst transfer between July 1, 2017, and June 30, 2022, within 1 year after a preceding CPL during IVF treatment. Follow-up for pregnancy outcomes was completed for all participants on March 31, 2023. Data analysis was performed from April to May 2023.ExposuresInterpregnancy interval length was classified as less than 3 months, 3 to less than 6 months, or 6 to 12 months.Main outcomes and measuresOutcomes included live birth, conception, clinical pregnancy, pregnancy loss, preterm birth, small or large for gestational age, and low birth weight. Multivariable logistic regression analysis was conducted to evaluate the association between IPI and pregnancy outcomes by adjusted odds ratios (AORs).ResultsThis study included 2433 women (mean [SD] age, 31.8 [4.6] years) who received IVF treatment. There were 338 women (13.9%) with an IPI of less than 3 months, 1347 (55.4%) with an IPI of 3 to less than 6 months, and 748 (30.7%) with an IPI of 6 to 12 months. The median (IQR) IPI lengths for the 3 groups were 77 (65-85), 128 (109-152), and 234 (202-288) days, respectively. Compared with an IPI of 6 to 12 months, shorter IPIs (<3 and 3 to <6 months) were associated with decreased odds of clinical pregnancy (AOR, 0.70 [95% CI, 0.53-0.92] and 0.79 [0.65-0.95]), live birth (AOR, 0.64 [95% CI, 0.48-0.85] and 0.74 [0.61-0.90]), and healthy live birth (AOR, 0.63 [95% CI, 0.46-0.87] and 0.79 [0.64-0.98]). Compared with women with an IPI of 6 to 12 months, women with shorter IPIs (<3 and 3 to <6 months) had a higher risk of total pregnancy loss (AOR, 1.87 [95% CI, 1.31-2.67] and 1.29 [1.00-1.66], respectively).Conclusions and relevanceThe results of this study suggest that delaying the next FET for at least 6 months after a preceding CPL was associated with beneficial pregnancy outcomes, considering that a decreased likelihood of achieving clinical pregnancy and live birth was observed among women with shorter IPIs. Further prospective studies are needed to confirm these findings.

Project description:Background: Nowadays, frozen-thawed embryo transfer (FET) cycles represent a high proportion of fertility treatments worldwide. Recent studies suggest differences in pregnancy outcomes depending on the FET treatment protocol used. The reason for this is still unclear, but the number of corpora lutea (CL) at conception is discussed as a possible factor. This study aims to investigate whether maternal and neonatal outcomes for pregnancies following FET lacking a CL differ from FET with one or more CL in order to explore a potential link between CL absence and adverse pregnancy outcomes. Methods: The study was designed as a retrospective, multi-center observational study with two cohorts after singleton live birth [0 CL cohort (FET in a programmed cycle, n = 114) and ≥ 1 CL cohort (FET in a natural or stimulated cycle, n = 68)]. Participants completed a questionnaire on the outcome of pregnancy and birth records were analyzed in a descriptive way. Multivariable logistic and linear regressions were performed in order to explore associations between CL absence and pregnancy outcomes. The strength of the agreement between the information in the survey and the diagnoses extracted from the files was assessed by Cohen's Kappa. Results: The risk of hypertensive disorders of pregnancy was higher after FET in the absence of a CL compared to FET with CL presence (aOR 5.56, 95% CI 1.12 - 27.72). Birthweights and birthweight percentiles were significantly higher in the 0 CL group. CL absence was a predictor of higher birthweight (adjusted coefficient B 179.74, 95% CI 13.03 - 346.44) and higher birthweight percentiles (adjusted coefficient B 10.23, 95%, 95% CI 2.28 - 18.40) particularly in female newborns of the 0 CL cohort. While the strength of the agreement between the reported information in the survey and the actual diagnoses extracted from the files was good for the majority of outcomes of interest it was fair in terms of hypertension (κ = 0.38). Conclusion: This study supports observations suggesting a potential link between a lack of CL at conception and adverse maternal and neonatal outcomes. Further investigations on causes and pathophysiological relationships are yet to be conducted.

Dataset Information

Elevated estradiol levels in frozen embryo transfer have different effects on pregnancy outcomes depending on the stage of transferred embryos.

Publications

Elevated estradiol levels in frozen embryo transfer have different effects on pregnancy outcomes depending on the stage of transferred embryos.

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