Maternal and Neonatal Complications After Natural vs. Hormone Replacement Therapy Cycle Regimen for Frozen Single Blastocyst Transfer

Abstract

Objective: To evaluate the maternal and neonatal complications after frozen-thawed blastocyst transfer cycles utilizing different endometrial preparation regimens. Design: This is a retrospective cohort study and a secondary analysis of a multicenter, randomized, controlled trial comparing live birth rate after fresh vs. frozen single blastocyst transfer (Frefro-blastocyst). Setting: Reproductive medicine centers. Patient(s): A total of 800 women with regular menstrual cycles undergoing their first cycle of in-vitro fertilization after frozen-thawed single blastocyst transfer. Intervention(s): Endometrium preparation was performed with a natural cycle regimen or hormone replacement therapy (HRT) cycle regimen, at the discretion of local investigators. All pregnancies were followed up until delivery. Main Outcome Measure(s): Maternal and neonatal complications. Result(s): 513 infertile patients who underwent natural cycles regimen and 287 who underwent HRT cycles regimen were analyzed. The incidences of maternal and neonatal complications were comparable between the natural cycle and HRT cycle regimen. Regarding the risk of gestational diabetes, gestational hypertension, pre-eclampsia, preterm delivery, small for gestational age and large for gestational age, the HRT cycle was still not a significant risk factor after adjusting for potential confounders. The natural cycle regimen yielded an insignificant higher total live birth rate [59.45 vs. 50.17%, P = 0.001, adjusted odds ratio (AOR) 1.366, 95% confidence interval (CI) 0.975–1.913], clinical pregnancy rate (68.23 vs. 58.89%, P = 0.008, AOR 1.406, 95% CI 0.992–1.991) and ongoing pregnancy rate (62.18 vs. 52.61%, P = 0.008, AOR 1.387, 95% CI 0.988–1.948) than did the HRT cycle regimen. However, compared to natural cycles, HRT cycles were associated with a significantly higher risk of biochemical miscarriage (6.86 vs. 18.18%, P < 0.001, AOR 0.328, 95% CI, 0.176–0.611). Conclusion(s): The incidence of maternal and neonatal complications in natural cycle and HRT cycle regimens after frozen single blastocyst transfer were comparable. Frozen-thawed single blastocyst transfer in a natural cycle was associated with lower biomedical miscarriage than the use of the HRT cycle. Clinical Trial Registration Number: Frefro-blastocyst was registered at Chinese Clinical Trial Registry, ChiCTR-IOR-14005405.

Lower risk of adverse perinatal outcomes in natural versus artificial frozen–thawed embryo transfer cycles: a systematic review and meta-analysis

“…However, studies evaluating the perinatal and maternal outcomes are scarce and reported dissimilar results. While some observational data have suggested higher rates of HDP, LGA and macrosomia after programmed FET cycles compared with NC-FET (Ginstrom Ernstad et al, 2019;Saito et al, 2019;Zong et al, 2020), other studies have not confirmed these findings (Lin et al, 2020;Pan et al, 2020;Wang et al, 2020b).…”

Pregnancy Outcomes After Frozen-Thawed Embryo Transfer in the Absence of a Corpus Luteum

“…However, more recent studies suggest better outcomes with regards to clinical (19,(33)(34)(35)(36)(37), ongoing (19,33,(38)(39)(40), and live birth (18,19,33,34,(36)(37)(38)(40)(41)(42)(43) rates in (modified) natural or stimulated FET cycles compared to cycles performed in an artificial setting. Nevertheless, these data are from different populations and quality and mainly from retrospective observational studies which prompts caution when drawing conclusions for clinical practice.…”

“…However, the reasons behind this are still unknown. Recent studies imply a link between CL absence and specific maternal and neonatal outcomes, such as macrosomia (15), postterm birth (16), HDP (2), postpartum hemorrhage (15)(16)(17), and Cesarean section rate (15,16,(18)(19)(20).…”

Assessing obstetric outcomes: A systematic review and meta‐analysis comparing fresh, artificial, and natural thaw embryo transfer cycles

“…Fifteen studies evaluated PTB as an outcome -the results of these studies are summarised in Figure S40. [6][7]10,[12][13][16][17][19][20][21][22][23][26][27][28] The pooled analysis of PTB comparing ArtThawET and NatThawET included 47 585 artificial cycles and 50 970 natural cycles. The pooled estimate of PTB showed a significant result, with a higher rate of PTB in ArtThawET (OR 1.18, 95% CI 1.13, 1.23).…”

“…Eight studies, the results of which are summarised in Figure 4, considered PPH as an outcome. [7][8][13][14]19,21,[25][26] The analysis of PPH comparing ArtThawET and NatThawET included 6562 artificial cycles and 20 049 natural cycles. The pooled result was statically significant for increased PPH in ArtThawET (OR 2.61, 95% CI 2.30, 2.97).…”