The true natural cycle frozen embryo transfer - impact of patient and follicular phase characteristics on serum progesterone levels one day prior to warmed blastocyst transfer

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MÜMÜŞOĞLU S., Erden M., Ozbek I. Y., İNCE O., Esteves S. C., Humaidan P., ...More

Reproductive Biology and Endocrinology, vol.21, no.1, 2023 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 21 Issue: 1
  • Publication Date: 2023
  • Doi Number: 10.1186/s12958-023-01136-z
  • Journal Name: Reproductive Biology and Endocrinology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Animal Behavior Abstracts, BIOSIS, CAB Abstracts, MEDLINE, Veterinary Science Database, Directory of Open Access Journals
  • Keywords: Follicular phase, Frozen embryo transfer, Luteal phase support, Luteinized unruptured follicle, Natural cycle, Progesterone
  • Kütahya Health Sciences University Affiliated: Yes


Background: In a true-natural cycle (t-NC), optimal progesterone (P4) output from the corpus luteum is crucial for establishing and maintaining an intrauterine pregnancy. In a previous retrospective study, low P4 levels (< 10 ng/mL) measured one day before warmed blastocyst transfer in t-NC were associated with significantly lower live-birth rates. In the current study, we aim to examine the relationship between patient, follicular-phase endocrine and ultrasonographic characteristics, and serum P4 levels one day prior to warmed blastocyst transfer in t-NC. Method: 178 consecutive women undergoing their first t-NC frozen embryo transfer (FET) between July 2017-August 2022 were included. Following serial ultrasonographic and endocrine monitoring, ovulation was documented by follicular collapse. Luteinized unruptured follicle (LUF) was diagnosed when there was no follicular collapse despite luteinizing-hormone surge (> 17 IU/L) and increased serum P4 (> 1.5 ng/mL). FET was scheduled on follicular collapse + 5 or LH surge + 6 in LUF cycles. Primary outcome was serum P4 on FET − 1. Results: Among the 178 patients, 86% (n = 153) experienced follicular collapse, while 14% (n = 25) had LUF. On FET-1, the median serum luteal P4 level was 12.9 ng/mL (IQR: 9.3–17.2), ranging from 1.8 to 34.4 ng/mL. Linear stepwise regression revealed a negative correlation between body mass index (BMI) and LUF, and a positive correlation between follicular phase peak-E2 and peak-P4 levels with P4 levels on FET-1. The ROC curve analyses to predict < 9.3 ng/mL (< 25th percentile) P4 levels on FET-1 day showed AUC of 0.70 (95%CI 0.61–0.79) for BMI (cut-off: 23.85 kg/m2), 0.71 (95%CI 0.61–0.80) for follicular phase peak-P4 levels (cut-off: 0.87 ng/mL), and 0.68 (95%CI 0.59–0.77) for follicular phase peak-E2 levels (cut-off: 290.5 pg/mL). Combining all four independent parameters yielded an AUC of 0.80 (95%CI 0.72–0.88). The adjusted-odds ratio for having < 9.3 ng/mL P4 levels on FET-1 day for patients with LUF compared to those with follicle collapse was 4.97 (95%CI 1.66–14.94). Conclusion: The BMI, LUF, peak-E2, and peak-P4 levels are independent predictors of low serum P4 levels on FET-1 (< 25th percentile; <9.3 ng/ml) in t-NC FET cycles. Recognition of risk factors for low serum P4 on FET-1 may permit a personalized approach for LPS in t-NC FET to maximize reproductive outcomes.