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. 2021 Jul 26:9:e11785.
doi: 10.7717/peerj.11785. eCollection 2021.

Clinical and perinatal outcomes of fresh single-blastocyst-transfer cycles under an early follicular phase prolonged protocol according to day of trigger estradiol levels

Yingfen Ying  1 , Xiaosheng Lu  1 , Huina Zhang  1 , Samuel Kofi Arhin  2 , Xiaohong Hou  1 , Zefan Wang  1 , Han Wu  1 , Jieqiang Lu  1 , Yunbing Tang  1
Affiliations

Clinical and perinatal outcomes of fresh single-blastocyst-transfer cycles under an early follicular phase prolonged protocol according to day of trigger estradiol levels

Yingfen Ying et al. PeerJ. .

Abstract

Backgroud: This study's objectives were to compare the clinical, perinatal, and obstetrical outcomes of patients with different estradiol (E2) levels in fresh single-blastocyst-transfer (SBT) cycles under an early follicular phase prolonged regimen on the day of trigger.

Methods: We recruited patients in fresh SBT cycles (n = 771) undergoing early follicular phase prolonged protocols with β-hCG values above 10 IU/L between June 2016 and December 2018. Patients who met the inclusion and exclusion criteria were divided into four groups according to their serum E2 level percentages on the day of trigger: <25th, 25th-50th, 51st-75th, and >75th percentile groups.

Results: Although the rates of clinical pregnancy (85.57% (166/194)), embryo implantation 86.60% (168/194), ongoing pregnancy (71.13% (138/194)), and live birth (71.13% (138/194)) were lowest in the >75th percentile group, we did not observe any significant differences (all P > 0.05). We used this information to predict the rate of severe ovarian hyperstimulation syndrome (OHSS) area under the curve (AUC) = 72.39%, P = 0.029, cut off value of E2 = 2,893 pg/ml with the 75% sensitivity and 70% specificity. The 51st-75th percentile group had the highest rates of low birth weight infants (11.73% (19/162), P = 0.0408), premature delivery (11.43% (20/175), P = 0.0269), admission to the neonatal intensive care unit (NICU) (10.49% (17/162), P = 0.0029), twin pregnancies (8.57% (15/175), P = 0.0047), and monochorionic diamniotic pregnancies (8.57% (15/175); P = 0.001). We did not observe statistical differences in obstetrics complications, including gestational diabetes mellitus (GDM), gestational hypertension, placenta previa, premature rupture of membranes (PROM), and preterm premature rupture of membranes (PPROM).

Conclusion: We concluded that serum E2 levels on the day of trigger were not good predictors of live birth rate or perinatal and obstetrical outcomes. However, we found that high E2 levels may not be conducive to persistent pregnancies. The E2 level on the day of trigger can still be used to predict the incidence of early onset severe OHSS in the fresh SBT cycle.

Keywords: Early follicular phase prolonged protocol; Estradiol level; Fresh single blastocyst transfer; Live birth; Perinatal outcome.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1. Flow chart.
A total of 1,897 cycles of prolonged protocol were collected during the period from Jun. 2016 to Dec. 2018 in our single reproductive center. Among them, 759 cycles underwent cryopreservation of all blastocysts, three cycles were cancelled for personal reasons, and 364 cycles’ β-hCG value was less than 10 IU/L on the 12th day after blastocyst transfer. Finally, 771 cycles of fresh SBT of prolonged regimen were obtained and their β-hCG value was at least 10 IU/L. PERCENTILE function of Microsoft Excel was used to get the corresponding percentile of E2 value. They were <25th percentile Group (E2 level: 212–1,677 pg/ml, n = 194), 25th–50th percentile Group (E2 level: 1,680–2,380 pg/ml, n = 195), 51st–75th percentile Group (E2 level: 2,407–3,028 pg/ml, n = 188) and >75th percentile Group (E2 level: 3,036–6,526 pg/ml, n = 194). Statistical analysis was used to compare patients’ data.
Figure 2
Figure 2. Prolonged protocol.
One single full dose 3.75 mg GnRH-a was injected during the menstrual cycle of D1–D3. Ovarian inhibition situation was evaluated 32rd to 38th day after pituitary down-regulation. Controlled ovarian hyperstimulation will begin after ovarian inhibition situation evaluation. When the average diameter of two follicles reached 18 mm, a single dose of human chorionic gonadotropin 4,000–10,000 IU was given and egg harvesting was performed after 34–36 h. Fresh SBT will be done after oocyte retrieval. β-hCG test will be done after fresh SBT 12 days later. The first transvaginal ultrasound was taken to evaluate the embryo implantation after the 26th day of fresh SBT, and the second ultrasound was on the 40th day after fresh SBT.
Figure 3
Figure 3. Logistic regression of confounding factors.
In order to observe the influence of variables with statistical differences among groups on the live birth percentage, we performed a logistic regression analysis. We found that there was no correlation between BMI, LH level, E2 level, P4 level and AFC on the first day of treatment; LH level, total E2 level, E2 level per follicle, P4 level and endometrial thickness on the day of trigger; or the initial and total FSH doses, days of stimulation and number of obtained oocytes, 2PNs, cleavage stage embryos, D3 embryos, good quality D3 embryos, D3 embryos cultured into blastocysts, blastocysts, and good quality blastocysts, rate of good quality D3 embryos, rate of blastocyst formation, rate of good quality blastocyst formation (all P > 0.05)
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Grants and funding

This research was supported by the General Projects of the Zhejiang Medical and Health Science and Technology plan (No: 2021KY211). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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