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Effect of endometrial preparation protocols on the risk of ectopic pregnancy for frozen embryo transfer.

ABSTRACT: Studies have consistently reported a significantly reduced incidence of ectopic pregnancy (EP) for frozen-thawed embryo transfer (ET) cycles compared with fresh cycles. However, only a few studies reported an association between endometrial preparation protocols on EP and results were conflicting. A registry-based retrospective cohort study of 153,354 clinical pregnancies following frozen single ETs between 2014 and 2017 were conducted, of which 792 cases of EP (0.52%) were reported. Blastocyst embryo transfers accounted for 87% of the total sample and were significantly associated with a decreased risk for EP compared with early cleavage ET (0.90% vs. 0.46%, adjusted OR = 0.50, 95% CI, 0.41 to 0.60). Compared with natural cycles, hormone replacement cycles (HRC) demonstrated a similar risk for EP (0.53% vs. 0.47%, adjusted OR = 1.12, 95% CI, 0.89 to 1.42). Subgroup analysis with or without tubal factor infertility and early cleavage/blastocyst ETs demonstrated similar non-significant associations. Endometrial preparation protocols using clomiphene (CC) were associated with a significantly increased risk for EP (1.12%, adjusted OR = 2.34; 95% CI, 1.38 to 3.98). These findings suggest that HRC and natural cycles had a similar risk for EP. Endometrial preparation using CC was associated with an increased risk of EP in frozen embryo transfer cycles.

SUBMITTER: Jwa SC

PROVIDER: S-EPMC8408134 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The optimal protocol for endometrial preparation in patients with infertility remains unclear. Due to this, the current study retrospectively analyzed 1,589 patients with infertility and regular menstrual cycles to assess reproductive outcomes per embryo transferred and per embryo transfer (ET) cycle following the transfer of frozen-thawed embryos (FET) in a modified natural cycle (mNC) or hormone therapy cycle (HT) with or without gonadotropin-releasing hormone agonist (GnRHa)-induced pituitary suppression. The molecular mechanisms involved were also studied using tissues from endometrial biopsies. Patients who underwent FET were assigned to 5 groups as follows: Group A underwent a mNC (n=276); group B (n=338) received estradiol (E2) and progesterone (P4); group C received 1 cycle of GnRHa, E2 and P4 (n=323); group D received 2 cycles of GnRHa, E2 and P4 (n=329); and group E received 3 cycles of GnRHa, E2 and P4 (n=323). Tissues from endometrial biopsies of 91 patients performed on the day of ET were tested for endometrial receptivity marker mRNA expression and microRNA (miR)-223-3p mRNA. Furthermore, endometrial stromal cells (ESCs) were used for an in-depth study of the molecular mechanisms involved. Among the 5 groups of patients, implantation rates, clinical pregnancy rates and live birth rates were not significantly different. However, endometrial receptivity was enhanced in group E when compared with groups A-D, which was associated with endometrial leukemia inhibitory factor (LIF), osteopontin, vascular endothelial growth factor, integrin ?3 and homeobox gene 10 and 11 mRNA upregulation, and miR-223-3p miRNA downregulation. Transfection of ESCs with an miR-223-3p mimic significantly reduced levels of LIF mRNA and protein. In addition, pre-treating ESCs with GnRHa upregulated mRNA and protein expression of the decidualization markers prolactin and insulin-like growth factor binding protein-1 in a time-dependent manner. In conclusion, these results indicated that HT with GnRHa may be a potential endometrial preparation protocol for FET.

Project description:Background: Endometrial preparation is essential in frozen-thawed embryo transfer (FET) cycles. Recent studies suggested that different endometrial preparation methods may influence obstetrical complications. However, the association between hormone replacement therapy (HRT) and ovarian stimulation (OS) FET endometrial preparation and obstetrical complications remains unknown. Methods: This retrospective cohort study included a total of 79,662 confirmed embryo transfer cycles during the period from January 2003 to December 2019. After exclusion, the remaining cases were categorized into an ovarian stimulation FET group (OS FET group, n = 29,121) and a hormone replacement therapy FET group (HRT FET group, n = 26,776) and subjected to the analyses. The primary outcome was the rate of obstetrical complications included placenta previa, placenta abruption, hypertensive disorders of pregnancy (HDP), placenta accreta, gestational diabetes mellitus (GDM), preterm premature rupture of the membrane (pPROM). The secondary outcome was pregnancy outcomes such as live birth rate, birth weight, pre-term and post-term delivery and cesarean sections. In order to minimize the bias, 10 pregnancy-related factors were adjusted in multiple logistic regression analysis. Results: Placenta previa (0.6 vs. 1.2%, P < 0.001) and HDP (3.5 vs. 5.3%, P < 0.001) were found lower in the OS FET than HRT FET group. Cesarean section was observed lower in the OS than HRT group (76.3 vs. 84.3%, P < 0.001). After adjustment for 10 important pregnancy-related confounding factors, we found that the risk of placenta previa (aOR 0.54, 95% CI 0.39-0.73) and HDP (aOR 0.65, 95% CI 0.57-0.75) and cesarean section (aOR 0.61, 95% CI 0.57-0.66) were still significantly reduced in the OS than HRT group. Furthermore, live birth rates were higher (80.0 vs. 76.0%, P < 0.001), and the miscarriage rate was lower (17.7 vs. 21.3%, P < 0.001) for pregnancies conceived with OS FET than with HRT FET. And the average birth weight was lower in the OS group compared to HRT group (2982.3 ± 636.4 vs. 3025.0 ± 659.0, P < 0.001), as well as the small-for-gestational age (SGA) was higher (8.7 vs. 7.2%, P < 0.001) and the large-for-gestational age (LGA) was lower (7.2 vs. 8.6%, P < 0.001) in the OS group than in the HRT group. Conclusions: The risks of placenta previa and HDP were lower in patients conceiving after OS FET than in those after HRT FET. Further prospective studies are required to further clarify the mechanism underlying the association between endometrium preparation and obstetrical complications.

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Effect of endometrial preparation protocols on the risk of ectopic pregnancy for frozen embryo transfer.

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